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Sample records for familial mediterranean fever

  1. Familial Mediterranean Fever.

    PubMed

    Kucuk, Adem; Gezer, Ilknur Albayrak; Ucar, Ramazan; Karahan, Ali Yavuz

    2014-01-01

    Familial Mediterranean Fever is an autosomal recessive inherited disease with a course of autoinflammation, which is characterized by the episodes of fever and serositis. It affects the populations from Mediterranean basin. Genetic mutation of the disease is on MEFV gene located on short arm of Chromosome 16. The disease is diagnosed based on clinical evaluation. Amyloidosis is the most important complication. The only agent that decreases the development of amyloidosis and the frequency and severity of the episodes is colchicine, which has been used for about 40 years. In this review, we aimed to discuss especially the most recent advances about Familial Mediterranean Fever which is commonly seen in our population.

  2. Familial Mediterranean Fever

    MedlinePlus

    ... don't use genetic tests as the sole method of diagnosing familial Mediterranean fever. There's no cure ... may be options, though these treatments are considered experimental. Other medications include rilonacept (Arcalyst) and anakinra (Kineret). ...

  3. Familial Mediterranean Fever

    PubMed Central

    Migita, Kiyoshi; Agematsu, Kazunaga; Yazaki, Masahide; Nonaka, Fumiaki; Nakamura, Akinori; Toma, Tomoko; Kishida, Dai; Uehara, Ritei; Nakamura, Yoshikazu; Jiuchi, Yuka; Masumoto, Junya; Furukawa, Hiroshi; Ida, Hiroaki; Terai, Chihiro; Nakashima, Yoshikazu; Kawakami, Atsushi; Nakamura, Tadashi; Eguchi, Katsumi; Yasunami, Michio; Yachie, Akihiro

    2014-01-01

    Abstract Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by MEditerranean FeVer gene (MEFV) mutations. In Japan, patients with FMF have been previously reported, including a mild or incomplete form. Several factors are presumed to contribute to the variable penetrance and to the phenotypic variability of FMF. We conducted the current study to investigate the correlation of variable clinical presentations and MEFV genotypic distributions in Japanese FMF patients. We analyzed demographic, clinical, and genetic data for 311 FMF patients enrolled in the study. Clinically, we classified FMF into 2 phenotypes: 1) the “typical” form of FMF, and 2) the “atypical” form of FMF according to the Tel Hashomer criteria. Patients with the typical FMF phenotype had a higher frequency of febrile episodes, a shorter duration of febrile attacks, more frequent thoracic pain, abdominal pain, a family history of FMF, and MEFV exon 10 mutations. Conversely, patients with the atypical FMF phenotype had a lower frequency of fever episodes and more frequent arthritis in atypical distribution, myalgia, and MEFV exon 3 mutations. Multivariate analysis showed that the variable associated with typical FMF presentation was the presence of MEFV exon 10 mutations. Typical FMF phenotype frequencies were decreased in patients carrying 2 or a single low-penetrance mutations compared with those carrying 2 or a single high-penetrance mutations (M694I), with an opposite trend for the atypical FMF phenotype. In addition, patients having more than 2 MEFV mutations had a younger disease onset and a higher prevalence of thoracic pain than those carrying a single or no mutations. Thus, MEFV exon 10 mutations are associated with the more typical FMF phenotype. In contrast, more than half of the Japanese FMF patients without MEFV exon 10 mutations presented with an atypical FMF phenotype, indicating that Japanese FMF patients tend to be divided into 2 phenotypes by a variation

  4. Familial Mediterranean fever.

    PubMed

    Padeh, Shai; Berkun, Yackov

    2016-09-01

    Familial Mediterranean fever (FMF) is the oldest and most common of the hereditary autoinflammatory diseases (AIDs). A large body of information has been accumulated over recent years on the pathophysiology, diagnosis and treatment of these diseases. The purpose of this review is to bring an up-to-date summary of the clinic manifestations, diagnostic criteria and treatment of FMF. An overview of the pathophysiologic basis of FMF as part of the AID is discussed. Over the last year, attempts to establish new criteria for childhood FMF, new guidelines for treatment and follow-up of disease and novel treatment for FMF were made. A comparison of the different disease severity scores for research purposes suggests that a new score is needed. New evidence for antiinterleukin-1 blockade as a new treatment modality is described. New diagnostic criteria, disease severity score, treatment and follow-up guidelines have been proposed, and need validation in the next several years.

  5. [Amyloidosis and familial Mediterranean fever].

    PubMed

    Pras, M

    1986-01-01

    Familial Mediterranean Fever (F. M. F.) is an autosomal recessive disorder occurring most commonly in Sepharadi Jews and Armenians. Two phenotypic features characterize the disease: brief episodic febrile attacks of peritonitis, pleuritis or synovitis recurring from childhood or adolescence and the development of systemic amyloidosis. Attacks are accompanied by striking elevations of acute phase proteins, including serum amyloid A protein. The amyloidosis of Familial Mediterranean Fever is of the AA type, and manifest clinically as a nephropathy that passes through proteinuria, nephrotic and uremic stages to renal death. Although there is ethnic variation in the incidence of amyloidosis of F. M. F. in our patient population--predominantly Sepharadi Jews of North African extraction--an amyloidotic death at an early age is their genetic destiny. Since the introduction in 1972 of colchicine to prevent the febrile attacks, the drug has been proven and become the main stay of therapy. Today, colchicine has been shown to be effective in preventing amyloidosis as well as the febrile attacks in Familial Mediterranean Fever. End stage renal disease is not the end of the road for patients with F.M.F. because of improving outlook for dialysis and renal transplantation in these patients.

  6. Familial Mediterranean Fever and Hypercoagulability

    PubMed Central

    Tayer-Shifman, Oshrat E.; Ben-Chetrit, Eldad

    2011-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease which is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease. As such, FMF is a prototype of autoinflammatory diseases where genetic changes lead to acute inflammatory episodes. Systemic inflammation – in general - may increase procoagulant factors, and decrease natural anticoagulants and fibrinolytic activity. Therefore, it is anticipated to see more thrombotic events among FMF patients compared with healthy subjects. However, reviewing the current available literature and based upon our personal experience, thrombotic events related purely to FMF are very rare. Possible explanation for this discrepancy is that along with the procoagulant activity during FMF acute attacks, anticoagulant and fibrinolytic changes are also taking place. Colchicine which is the treatment of choice in FMF may also play a role in reducing inflammation thereby decreasing hypercoagulability. PMID:21713077

  7. Familial Mediterranean fever: current perspectives

    PubMed Central

    Sönmez, Hafize Emine; Batu, Ezgi Deniz; Özen, Seza

    2016-01-01

    Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease, and it is characterized by recurrent attacks of fever and polyserositis. The disease is associated with mutations in the MEFV gene encoding pyrin, which causes exaggerated inflammatory response through uncontrolled production of interleukin 1. The major long-term complication of FMF is amyloidosis. Colchicine remains the principle therapy, and the aim of treatment is to prevent acute attacks and the consequences of chronic inflammation. With the evolution in the concepts about the etiopathogenesis and genetics of the disease, we have understood that FMF is more complicated than an ordinary autosomal recessive monogenic disorder. Recently, recommendation sets have been generated for interpretation of genetic testing and genetic diagnosis of FMF. Here, we have reviewed the current perspectives in FMF in light of recent recommendations. PMID:27051312

  8. [Sacroiliitis in familial Mediterranean fever].

    PubMed

    Connemann, B J; Steinhoff, J; Benstein, R; Sack, K

    1991-11-22

    A 15-year-old girl of Turkish descent had for one year complained of severe recurrent fever-associated deep back pains. Since she was three years of age she had suffered from repeated attacks of fever and severe abdominal pain which ceased spontaneously in 1-3 days. On physical examination the sacrum and iliosacral joints were very painful to percussion, and she limped. Radiography revealed symmetric destructive sacroiliitis. Despite the unusual location of the arthritis, the triad of fever, abdominal pain and arthritis, as well as her belonging to an ethnic "at risk" group, pointed to the diagnosis of familial mediterranean fever (FML) or recurrent hereditary polyserositis. This diagnosis was confirmed by a positive metaraminol provocation test in that infusion of metaraminol reproduced the typical pains. Collagen diseases, rheumatic disease, acute porphyria and chronic infectious processes were excluded. The sacroiliitis quickly responded to long-term administration of colchicine, 0.5 mg twice daily. The patient also has Hageman factor deficiency whose significance remains unclear.

  9. Familial Mediterranean fever in siblings.

    PubMed

    Özçakar, Z Birsin; Erdogan, Beyza Doganay; Elhan, Atilla H; Yalçinkaya, Fatoş

    2012-11-01

    Genetic and environmental factors have been implicated in disease severity and development of amyloidosis in familial Mediterranean fever (FMF). We investigated similarities in clinical characteristics, disease severity, and treatment response within siblings with FMF. The study group consisted of 2 or more siblings who were followed in our center with the diagnosis of FMF. Siblings were evaluated for demographic data, clinical and laboratory disease features, genetic analysis of MEFV mutations, and disease severity score. The intraclass correlation coefficient (ICC), which can be interpreted as the expected correlation between 2 siblings, was used to reflect within-family similarity. The study included 67 pediatric patients from 31 different families. When we investigated the similarity of siblings after adjusting for genetic effects, we found very low ICC with p > 0.05 in the majority of clinical features, disease severity, and colchicine dosages. However, age at disease onset, age at onset of therapy, attack-free acute-phase reactant levels, and presence of amyloidosis were found to be similar within siblings (relatively high ICC with p < 0.05). Siblings with FMF had different clinical findings and disease severity. They had similar amyloidogenic potential, proven by both similar presence of amyloid and increased levels of acute-phase reactants between attacks. Our findings strongly support that genetic factors may be more dominant in the development of amyloidosis.

  10. Genetics Home Reference: familial Mediterranean fever

    MedlinePlus

    ... Epub 2013 Sep 9. Review. Citation on PubMed Lidar M, Kedem R, Berkun Y, Langevitz P, Livneh ... 090401. Epub 2009 Dec 15. Citation on PubMed Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular ...

  11. Familial Mediterranean fever--a review.

    PubMed

    Shohat, Mordechai; Halpern, Gabrielle J

    2011-06-01

    Familial Mediterranean fever is inherited in an autosomal recessive manner. There are two phenotypes: types 1 and 2. Familial Mediterranean fever type 1 is characterized by recurrent short episodes of inflammation and serositis, including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to renal failure, is the most severe complication. Familial Mediterranean fever type 2 is characterized by amyloidosis as the first clinical manifestation of familial Mediterranean fever in an otherwise asymptomatic individual. Routine treatment of end-stage renal disease, including renal transplantation, is advised. Lifelong treatment with colchicine is required for homozygotes for the p.Met694Val mutation or compound heterozygotes for p.Met694Val and another disease-causing allele; this prevents the inflammatory attacks and the deposition of amyloid. Individuals who do not have the p.Met694Val mutation and who are only mildly affected should be either treated with colchicine or monitored every 6 months for the presence of proteinuria. Molecular genetic testing of the MEFV gene, the only gene currently known to be associated with familial Mediterranean fever, can be offered to family members, especially when the p.Met694Val allele is present, because renal amyloidosis can be prevented by colchicine.

  12. Familial Mediterranean Fever: An Unusual Case Presentation.

    PubMed

    Soora, Raksha; Nicandri, Katrina

    2015-12-01

    Familial Mediterranean Fever is a heritable illness typically characterized by recurrent fevers and serositis. Triggers of this illness include many things, such as cold or stress. This case describes a teenager who initially presented to the gynecologist office because of recurrent fevers with menses. Because she only had symptoms with menses, was healthy between attacks, and met the Livneh criteria, treatment with colchicine and combined oral contraceptive pills was initiated, with improvement of her symptoms. There are multiple etiologies for febrile illness during menses, and one should consider familial Mediterranean fever as a possible cause of cyclic fevers. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  13. Familial Mediterranean fever: An updated review

    PubMed Central

    Sarı, İsmail; Birlik, Merih; Kasifoğlu, Timuçin

    2014-01-01

    Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder characterised by acute attacks of fever and serosal inflammation. FMF primarily affects Jewish, Armenian, Turkish, and Arab populations. The disease is accompanied by a marked decrease in quality of life due to the effects of attacks and subclinical inflammation in the attack-free periods. Untreated or inadequately treated patients run the risk of amyloidosis, which is an important cause of morbidity and mortality. In this review, the current information available on FMF is summarised. PMID:27708867

  14. Diagnostic criteria of familial Mediterranean fever.

    PubMed

    Berkun, Yackov; Eisenstein, Eli M

    2014-01-01

    Familial Mediterranean fever (FMF) is the most prevalent monogenic autoinflammatory disease, mainly affecting ethnic groups living at Mediterranean basin. FMF is characterized by recurrent, self-limited episodes of fever and serositis. The diagnosis is difficult in the presence of atypical signs, which may result in significant delay in initiating treatment. As autoinflammatory diseases may have overlapping symptoms, strict diagnostic criteria are essential. Since the discovery that mutations in the gene MEFV underlie FMF, molecular genetic testing has been used as a diagnostic adjunct, especially in atypical cases. However, despite progress in the understanding of FMF disease mechanisms during the past 15 years; the diagnosis is still based on clinical criteria. Several sets of diagnostic criteria have been proposed and used. Existing diagnostic criteria should be modified to include genetic data, and need to be more widely validated. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. [Mesothelioma and familial Mediterranean fever: A relationship?].

    PubMed

    Challita, S; Guerder, A; Charpentier, M-C; Daher, M; Giraud, F; Roche, N

    2015-03-01

    The majority of pleural and peritoneal mesotheliomas are linked to asbestos exposure but, in around 20% of cases, no history of such exposure is found. Periodic disease is associated with recurrent serositis, which could favor the development of mesothelioma. We report a case of pleural mesothelioma in a 50-year-old Lebanese woman, with no detectable exposure to asbestos but suffering from periodic disease (familial Mediterranean fever) with recurrent episodes of serositis. Many cases of peritoneal mesothelioma in patients with FMF are reported in the literature. This is the second reported case of pleural mesothelioma associated with periodic disease. Because of the low incidence of both diseases, further publications are required to support the hypothesis of a causal link. It is important, therefore, that all cases of an association of periodic disease and mesothelioma are reported. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  16. Biologic therapy in familial Mediterranean fever.

    PubMed

    Koga, Tomohiro; Migita, Kiyoshi; Kawakami, Atsushi

    2016-09-01

    Familial Mediterranean fever (FMF) is the most common autoinflammatory hereditary disease characterized by self-limited attacks of fever and serositis. Although colchicine is the gold standard treatment for the attacks ∼10% of cases of FMF are resistant or intolerant to effective doses of colchicine. In such cases, however, there are increasing numbers of case reports or clinical trials treated by biologic agents which directly target the proinflammatory cytokines. Anti-interleukin-1 (IL-1) treatment has proven beneficial in improving the inflammation in terms of clinical manifestations and laboratory findings in clinical trials. Furthermore, anti-tumor necrosis factor treatment has also revealed the efficacy and safety in patients with colchicine-resistant FMF. More recently, cases of successful treatment with IL-6 inhibitor, tocilizumab (TCZ), has been reported from Japan and Turkey. Of note, TCZ may be preferable in the treatment as well as the prevention of secondary amyloidosis of FMF patients since it significantly suppresses acute inflammatory response. In the present review, we summarize the literatures regarding the efficacy of biologic therapy in colchicine-resistant or -intolerant patients with FMF.

  17. A rare cause of massive ascites: familial Mediterranean fever.

    PubMed

    Aslan, Mehmet; Demir, Güner; Esen, Ramazan; Dülger, Ahmet Cumhur; Beğenik, Hüseyin; Çelik, Yılmaz; Küçükoğlu, Mehmet Emin; Bahar, Kadir

    2012-06-01

    Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent fever and peritoneal and pleural inflammation. It is an inherited disorder commonly found in Armenians, Turks, Arabs, Balkans, and Jews originating from North African countries. A small amount of peritoneal fluid collection can be observed during peritoneal attacks in patients with Familial Mediterranean fever, but chronic ascites has been described rarely in these patients. A 42-year-old female patient was admitted to our clinic in June 2010 with fever, severe abdominal pain and abdominal distention that had continued for one month. There was no family history of periodic fevers or abdominal pain. We could not find any cause for ascites, including tuberculosis. A diagnosis of Familial Mediterranean fever was suspected based on the clinical findings and her family history. She was screened for mutations causing Familial Mediterranean fever, and when found to be homozygous for M694V, treatment with colchicine was initiated. After treatment, the amount of ascites decreased, and relief of symptoms was confirmed during a follow-up. In conclusion, because Familial Mediterranean fever is common in our country, it should be considered in the differential diagnosis of patients with ascites of unknown etiology in populations where hereditary inflammatory disease is endemic.

  18. Familial Mediterranean fever and membranous glomerulonephritis: report of a case.

    PubMed

    Ceri, Mevlut; Unverdi, Selman; Altay, Mustafa; Unverdi, Hatice; Ensari, Arzu; Duranay, Murat

    2010-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive genetic disease characterized by recurrent attacks of fever and painful episodes of sterile polyserositis. Kidney involvement may occur as a result of secondary amyloidosis during the course of FMF. Previously, different types of glomerulopathies such as IgM and IgA nephropathy, crescentic glomerulonephritis, diffuse proliferative glomerulonephritis, minimal change disease, and membranoproliferative glomerulonephritis were rarely reported. We herein represent a first case of membranous glomerulonephritis who had complete remission with colchicine treatment in the course of familial Mediterranean fever.

  19. Liver involvement in children with Familial Mediterranean fever.

    PubMed

    Unal, Fatih; Cakir, Murat; Baran, Masallah; Arıkan, Cigdem; Yuksekkaya, Hasan Ali; Aydoğdu, Sema

    2012-08-01

    Familial Mediterranean fever is characterised by recurrent, febrile, inflammatory attacks of the serosal membranes. Prolonged inflammatory response is triggered secondary to cytokine stimulation due to reduced activity of pyrin. Inflammatory cytokines play major role in the pathogenesis of acute liver injury; and chronic, recurrent cytokine production may cause chronic hepatitis/cirrhosis. We aimed to analyse liver involvement in children with Familial Mediterranean fever. The study included 58 patients with Familial Mediterranean fever. Patients with liver involvement were examined in detail. Liver involvement was seen in 11 of 58 patients (18.9%). Two patients (3.4%) had abnormal liver enzymes during the diagnostic evaluation, whilst 9 patients (15.5%) were admitted with the features of liver diseases, and had final diagnosis of Familial Mediterranean fever (2 had Budd-Chiari syndrome, 5 had chronic hepatitis/cirrhosis, 2 had acute hepatitis). None of the demographic factors or laboratory findings was different between the patients with or without liver involvement M694V allele was more common in patients with liver involvement but did not reach significant difference (50% vs. 33.6%, p=0.21). All the patients showed clinical and laboratory improvement after colchicine. Paediatric hepatologists must keep Familial Mediterranean fever in mind in the patients with cryptogenic hepatitis/cirrhosis especially in regions where hereditary inflammatory diseases are common. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  20. Determination of hearing levels in patients with Familial Mediterranean Fever.

    PubMed

    Cevik, Cengiz; Silfeler, Ibrahim; Arica, Vefik; Yengil, Erhan; Akbay, Ercan; Sarac, Tuba; Basarslan, Fatmagul; Akoglu, Ertap

    2013-12-01

    Familial Mediterranean Fever is the most common congenital, periodic fever condition that affects over 100,000 people worldwide. In the literature, there is limited number of studies about hearing levels in children with Familial Mediterranean Fever. In the present study, we aimed to investigate hearing levels and cochlear functions by using Distortion product Otoacoustic Emission and High Frequency Audiometry (250-20,000 Hz) in pediatric patients with Familial Mediterranean Fever. The study included 62 children with Familial Mediterranean Fever and 27 healthy children with similar age and gender. After otoscopic examination, both groups underwent audiological evaluation including High Frequency Audiometry (250-20,000 Hz) and Distortion product Otoacoustic Emissions. The results obtained were assessed among groups. In addition, these results were compared regarding colchicine use, age at the onset of disease and duration of the diseases in the Familial Mediterranean Fever group. Of the Familial Mediterranean Fever patients, 93.5% were on colchicine therapy and mean duration of colchicine use was 19.9 ± 13.9 months. The mean age at diagnosis was 6.57 ± 2.86 years (min-max: 2-14) and mean duration of disease was 23 ± 17 months (min-max: 6-84). Pure tone audiometry values, and hearing levels between 9000 and 20,000 Hz were similar and within normal range in both groups. The Distortion product Otoacoustic Emissions responses at the frequencies of 1020, 2040, 3000, 4080 and 5040 Hz were similar for both groups. To the best of our knowledge, this is the first study evaluating hearing levels at the frequencies of 18k Hz and 20k Hz in children with Familial Mediterranean Fever in the literature. In children with Familial Mediterranean Fever, Pure tone audiometry values, hearing values obtained at all frequencies from 250 to 20,000 Hz, and Distortion product Otoacoustic Emissions levels were within normal range. Furthermore, hearing levels were found to be similar to

  1. A Case of Eosinophilic Esophagitis Accompanying Familial Mediterranean Fever

    PubMed Central

    Rohani, Pejman; Najafi Sani, Mehri; Ahmadi, Mitra

    2017-01-01

    Background. Eosinophilic esophagitis is an inflammatory condition where there is a dense infiltration of eosinophils typically exceeding fifteen cells per high power field. Familial Mediterranean fever is an autosomal recessive disorder characterized by brief, acute, and self-limited episodes of fever and polyserositis that recur at irregular intervals. Case Presentation. A three-year-and-nine-month-old Iranian girl was admitted to our center. The patient's parents complained of a history of abdominal pain, poor appetite, and poor weight gain from 1.5 years ago and episodes of food impaction after starting solid foods. Eosinophilic esophagitis was diagnosed based on histology. Because of continuing abdominal pain after treatment of eosinophilic esophagitis, the episodic nature of disease, and the presence of fever with pain, screening for familial Mediterranean fever mutation was performed and the patient was found to be heterozygote for Mediterranean fever. Conclusion. We have reported a case of eosinophilic esophagitis coexisting with familial Mediterranean fever which has not been described previously. PMID:28255474

  2. A Case of Eosinophilic Esophagitis Accompanying Familial Mediterranean Fever.

    PubMed

    Rohani, Pejman; Najafi Sani, Mehri; Ahmadi, Mitra; Ziaee, Vahid

    2017-01-01

    Background. Eosinophilic esophagitis is an inflammatory condition where there is a dense infiltration of eosinophils typically exceeding fifteen cells per high power field. Familial Mediterranean fever is an autosomal recessive disorder characterized by brief, acute, and self-limited episodes of fever and polyserositis that recur at irregular intervals. Case Presentation. A three-year-and-nine-month-old Iranian girl was admitted to our center. The patient's parents complained of a history of abdominal pain, poor appetite, and poor weight gain from 1.5 years ago and episodes of food impaction after starting solid foods. Eosinophilic esophagitis was diagnosed based on histology. Because of continuing abdominal pain after treatment of eosinophilic esophagitis, the episodic nature of disease, and the presence of fever with pain, screening for familial Mediterranean fever mutation was performed and the patient was found to be heterozygote for Mediterranean fever. Conclusion. We have reported a case of eosinophilic esophagitis coexisting with familial Mediterranean fever which has not been described previously.

  3. Familial mediterranean fever in an Iranian patient with behcet disease.

    PubMed

    Mobini, Maryam

    2011-01-01

    Familial Mediterranean fever (FMF) is the most prevalent disorder among the hereditary autoinflammatory syndromes. This disorder is characterized by fever and some painful attacks such as abdominal, chest or joint pain and potentially development of AA amyloidosis. Several vasculitis are more common in FMF than general population. There are some reports about association of FMF with Behcet Disease (BD). In this study, we describe a 27 year old patient with BD who suffered from attacks of fever, arthralgia, abdominal pain and genetic study confirmed the diagnosis of FMF. FMF should be considered in a patient with Behcet disease who is suffering from attacks of fever, arthralgia and abdominal pain.

  4. Unilateral lymphocytic pleuritis as a manifestation of familial Mediterranean fever.

    PubMed

    Katsenos, Stamatis; Mermigkis, Charalampos; Psathakis, Kostas; Tsintiris, Kostas; Polychronopoulos, Vlassios; Panagou, Panagiotis; Ritis, Kostas; Light, Richard W

    2008-04-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease affecting predominantly populations surrounding the Mediterranean basin. It is the most prevalent hereditary periodic fever syndrome characterized mainly by recurrent and short attacks of fever and serositis (pleuritis, arthritis, peritonitis). Unilateral polymorphonuclear exudative pleuritis associated with fever has been reported as the solitary manifestation of the first FMF attack, in < 10% of patients. This case study describes a 30-year-old Greek man with recurrent episodes of lymphocytic exudative pleuritis associated with fever. After a thorough workup (clinical criteria and molecular genetic testing identifying homozygosity polymorphisms of the FMF gene), the diagnosis of FMF was established. Treatment with colchicine, 2 mg/d, eliminated FMF attacks. To our knowledge, this is the first well-documented case report of a patient with FMF presenting with a lymphocytic exudative pleural effusion.

  5. Malignant nephrosclerosis in a patient with familial Mediterranean fever.

    PubMed

    Yamanouchi, Masayuki; Ubara, Yoshifumi; Imafuku, Aya; Kawada, Masahiro; Koki, Mise; Sumida, Keiichi; Hiramatsu, Rikako; Hasegawa, Eiko; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Ohashi, Kenichi; Fujii, Takeshi; Matsuda, Masayuki; Takaichi, Kenmei

    2015-01-01

    A 37-year-old man was admitted to our hospital for an evaluation of renal dysfunction and hypertension. The C-reactive protein level was 6.0 mg/dL, and the serum renin activity was extremely high. A renal biopsy showed malignant nephrosclerosis-like lesions with an onion skin pattern. He had a history of recurrent abdominal pain associated with periodic fevers above 38 degrees that resolved within three days. A MEditerranean FeVer (MEFV) gene analysis revealed that he was homozygous for the E148Q polymorphism (exon 2) and heterozygous for the L110P polymorphism (exon 2). The present case demonstrates that persistent subclinical inflammation can lead to malignant nephrosclerosis in familial Mediterranean fever patients with this genotype.

  6. A retrospective analysis of 7 cases of familial mediterranean fever.

    PubMed

    Ogita, Chie; Matsui, Kiyoshi; Kisida, Dai; Yazaki, Masahide; Nakamura, Akinori; Kaku, Satosi; Makino, Hidehiko; Tadokoro, Rei; Azuma, Kouta; Tsuboi, Kazuyuki; Tani, Mei; Tamura, Masao; Yoshikawa, Takahiro; Morimoto, Mai; Nishioka, Aki; Sekiguchi, Masahiro; Azuma, Naoto; Kitano, Masayasu; Tsunoda, Shinichiro; Sawai, Hideaki; Sano, Hajime

    2017-01-01

    Familial mediterranean fever (FMF) is a single inherited autoinflammatory disease characterized by periodic fever with relatively short duration of 1 to 3 days and sterile serositis. Although the prevalence rate is highest in the Mediterranean coastal area, a large number of cases have been reported recently by genetic analysis by identification of MEFV (Mediterranean fever) which is responsible gene in Japan too. In outpatient department of rheumatology, diagnosis and treatment of FMF is performed in cases where fever and abdominal pain attack are repeated for a short period of time. We examined cases in which symptoms considered periodic seizures were repeated, excluding autoimmune diseases, infectious diseases, and malignant tumors. In both cases, genetic analysis is performed as auxiliary diagnosis. Seven cases satisfied the Tel-Hashomer criteria criteria and MEFV gene mutation was detected. Everyone was a female, and half had seizure symptoms at menstruation. Even though there is a difference in the amount of colchicine to be used, either one is effective. In cases of periodic symptoms or cases called periodic fever, exclusion diagnosis is carried out, there is a need to suspect FMF, determine the effect of colchicine, and perform genetic analysis.

  7. Familial Mediterranean fever: the first adult case in Korea.

    PubMed

    Lim, Ah Leum; Jang, Hyun Joo; Han, Jung Wan; Song, Yong Keun; Song, Won Jun; Woo, Heung Jung; Jung, Young Ok; Kae, Sea Hyub; Lee, Jin

    2012-11-01

    Familial Mediterranean fever (FMF) is known to be a genetic disorder that prevalent among populations surrounding the Mediterranean Sea. Since Mediterranean fever gene (MEFV) was discovered at 1997, some cases have been reported in countries not related or close to this area like Japan. In addition it has been generally accepted that the clinical onset of FMF begins before 20 yr of age in most patients. Onset of the disease at an older age may occur but is rare. Adult-onset FMF may be a form of disease with distinct clinical, demographic and molecular characteristics. We describe a case of adult-onset FMF confirmed by DNA analysis of the MEFV gene in a Korean patient. A 32-yr-old man, who has no family history of FMF, presented with periodic fever, abdominal pain and vomiting. Though several various tests were thoroughly performed to evaluate the cause of his symptoms, there was no evidence of infectious, autoimmune or neoplastic diseases. Several gene analysis of periodic fever syndrome was finally performed and two point mutations (p.Leu110Pro, p.Glu148Gln) were identified. We confirmed the first adult case of FMF through detection of MEFV gene mutations in Korea and describe his clinical characteristics.

  8. Familial Mediterranean Fever: The First Adult Case in Korea

    PubMed Central

    Lim, Ah Leum; Han, Jung Wan; Song, Yong Keun; Song, Won Jun; Woo, Heung Jung; Jung, Young Ok; Kae, Sea Hyub; Lee, Jin

    2012-01-01

    Familial Mediterranean fever (FMF) is known to be a genetic disorder that prevalent among populations surrounding the Mediterranean Sea. Since Mediterranean fever gene (MEFV) was discovered at 1997, some cases have been reported in countries not related or close to this area like Japan. In addition it has been generally accepted that the clinical onset of FMF begins before 20 yr of age in most patients. Onset of the disease at an older age may occur but is rare. Adult-onset FMF may be a form of disease with distinct clinical, demographic and molecular characteristics. We describe a case of adult-onset FMF confirmed by DNA analysis of the MEFV gene in a Korean patient. A 32-yr-old man, who has no family history of FMF, presented with periodic fever, abdominal pain and vomiting. Though several various tests were thoroughly performed to evaluate the cause of his symptoms, there was no evidence of infectious, autoimmune or neoplastic diseases. Several gene analysis of periodic fever syndrome was finally performed and two point mutations (p.Leu110Pro, p.Glu148Gln) were identified. We confirmed the first adult case of FMF through detection of MEFV gene mutations in Korea and describe his clinical characteristics. PMID:23166428

  9. Isolated recurrent pleuritis revealing familial mediterranean Fever in adulthood.

    PubMed

    Lega, J C; Khouatra, C; Cottin, V; Cordier, J F

    2010-01-01

    Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease especially affecting populations of Mediterranean origin with an autosomal recessive inheritance. The cardinal manifestations consist of short febrile and painful attacks of peritonitis, arthritis and pleuritis developing during childhood. We report the case of a 26-year-old man of Tunisian descent who had febrile episodes of right-sided pleuritis without any extrathoracic complaints. Disappearance of attacks with one dose of colchicine (1 mg/day) strengthened the presumptive diagnosis of atypical FMF, which was further confirmed by genetic testing identifying the homozygous mutation M694I/M694I of the MEFV gene.

  10. Familial Mediterranean fever variant with repeated atypical skin eruptions.

    PubMed

    Takahashi, Tomoko; Fujisawa, Tomomi; Kimura, Masaki; Ohnishi, Hidenori; Seishima, Mariko

    2015-09-01

    Familial Mediterranean fever (FMF) is characterized by self-limited bouts of fever and polyserositis. Skin involvement is not common in FMF, and erysipelas-like erythema is found to be the most frequent skin eruption which is often accompanied by arthritis and fever, and disappears within 12-72 h. We report a 40-year-old Japanese woman who presented with a 2-year history of recurrent fever with general fatigue, polyarthralgia and transient maculopapular eruptions on her lower extremities and trunk. The histological findings of the maculopapular eruption showed lymphocyte infiltration around the capillaries in the entire dermis. Mutation analysis showed a heterozygous E148Q-P369S mutation of MEFV. These findings suggested a diagnosis of late-onset FMF variant with atypical skin eruptions. The patient was successfully treated with colchicine. Thus, we should pay attention to repeated atypical skin eruptions for the early detection of atypical FMF. © 2015 Japanese Dermatological Association.

  11. Familial Mediterranean Fever with Rheumatoid Arthritis Complicated by Pulmonary Paragonimiasis.

    PubMed

    Nureki, Shin-Ichi; Ishii, Koji; Fujisaki, Hideaki; Torigoe, Masataka; Maeshima, Keisuke; Shibata, Hirotaka; Miyazaki, Eishi; Kadota, Jun-Ichi

    A 42-year-old woman presented with an intermittent fever and chest and back pain, and an abnormal chest shadow was detected. She was diagnosed with paragonimiasis caused by Paragonimus westermani. Praziquantel therapy improved the abnormal chest shadow, but did not relieve her symptoms. She was also diagnosed with familial Mediterranean fever (FMF), and colchicine therapy resolved her symptoms. She subsequently developed arthralgia and morning stiffness in her hands. We also diagnosed the patient with rheumatoid arthritis (RA), and corticosteroid and salazosulfapyridine therapy improved her symptoms. The existence of paragonimiasis complicated the diagnosis of FMF. The coexistence of FMF and RA is very rare, but does exist.

  12. Familial Mediterranean Fever with Rheumatoid Arthritis Complicated by Pulmonary Paragonimiasis

    PubMed Central

    Nureki, Shin-ichi; Ishii, Koji; Fujisaki, Hideaki; Torigoe, Masataka; Maeshima, Keisuke; Shibata, Hirotaka; Miyazaki, Eishi; Kadota, Jun-ichi

    2016-01-01

    A 42-year-old woman presented with an intermittent fever and chest and back pain, and an abnormal chest shadow was detected. She was diagnosed with paragonimiasis caused by Paragonimus westermani. Praziquantel therapy improved the abnormal chest shadow, but did not relieve her symptoms. She was also diagnosed with familial Mediterranean fever (FMF), and colchicine therapy resolved her symptoms. She subsequently developed arthralgia and morning stiffness in her hands. We also diagnosed the patient with rheumatoid arthritis (RA), and corticosteroid and salazosulfapyridine therapy improved her symptoms. The existence of paragonimiasis complicated the diagnosis of FMF. The coexistence of FMF and RA is very rare, but does exist. PMID:27725555

  13. The impact of familial Mediterranean fever on women's health.

    PubMed

    Dotters-Katz, Sarah; Kuller, Jeffrey; Price, Thomas

    2012-06-01

    Familial Mediterranean fever (FMF) is the most common hereditary recurrent febrile disorder, characterized by the sudden onset of high fever and severe abdominal pain. The implications of this disorder on a woman's health are significant and not well known among obstetrician/gynecologists. The goal of this review is to familiarize providers caring for women on the ramifications of FMF on different aspects of a woman's life, including puberty, fertility, pregnancy, and menopause, as well as to help them to diagnose and manage FMF when these patients become pregnant.

  14. Familial Mediterranean fever presenting as fever of unknown origin in Korea.

    PubMed

    Lee, Jun Hee; Kim, Jong Hyun; Shim, Jung Ok; Lee, Kwang Chul; Lee, Joo Won; Lee, Jung Hwa; Chae, Jae Jin

    2016-11-01

    Familial Mediterranean fever (FMF) is the most common Mendelian autoinflammatory disease, characterized by uncontrolled activation of the innate immune system that manifests as recurrent brief fever and polyserositis (e.g., peritonitis, pleuritic, and arthritis). FMF is caused by autosomal recessive mutations of the Mediterranean fever gene, MEFV which encodes the pyrin protein. Although FMF predominantly affects people from Mediterranean and Middle Eastern ethnic origins, 3 cases of FMF have been reported in Korea since 2012. We report another case of FMF in Korea in which the patient presented with a month-long fever without serositis. After treatment with colchicine was initiated, the patient's symptoms quickly subsided. The response to colchicine was helpful for diagnosis. We compare the FMF genotypes in Korea with in other countries. Studying FMF cases in Korea will help establish the best MEFV exons to use for screening and diagnosis of Korean FMF.

  15. Familial Mediterranean fever presenting as fever of unknown origin in Korea

    PubMed Central

    Lee, Jun Hee; Kim, Jong Hyun; Shim, Jung Ok; Lee, Kwang Chul; Lee, Joo Won; Chae, Jae Jin

    2016-01-01

    Familial Mediterranean fever (FMF) is the most common Mendelian autoinflammatory disease, characterized by uncontrolled activation of the innate immune system that manifests as recurrent brief fever and polyserositis (e.g., peritonitis, pleuritic, and arthritis). FMF is caused by autosomal recessive mutations of the Mediterranean fever gene, MEFV which encodes the pyrin protein. Although FMF predominantly affects people from Mediterranean and Middle Eastern ethnic origins, 3 cases of FMF have been reported in Korea since 2012. We report another case of FMF in Korea in which the patient presented with a month-long fever without serositis. After treatment with colchicine was initiated, the patient’s symptoms quickly subsided. The response to colchicine was helpful for diagnosis. We compare the FMF genotypes in Korea with in other countries. Studying FMF cases in Korea will help establish the best MEFV exons to use for screening and diagnosis of Korean FMF. PMID:28018446

  16. Cutaneous necrotizing vasculitis as a manifestation of familial Mediterranean fever.

    PubMed

    Komatsu, Shigetsuna; Honma, Masaru; Igawa, Satomi; Tsuji, Hitomi; Ishida-Yamamoto, Akemi; Migita, Kiyoshi; Ida, Hiroaki; Iizuka, Hajime

    2014-09-01

    Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease, which is characterized by recurrent and paroxysmal fever, peritonitis, arthritis, myalgia, and skin rashes. Although various skin lesions such as "erysipelas-like erythema", urticaria, nonspecific purpura, and subcutaneous nodules have been described, cutaneous vasculitis is rare. We report a Japanese case of sporadic FMF accompanied by cutaneous arteritis at the time of febrile attacks of FMF. Gene analysis revealed M694I mutation in a single allele of the MEFV gene, and oral colchicine successfully controlled both periodic fever and subcutaneous nodules of arteritis. Cutaneous necrotizing vasculitis repeatedly emerging with febrile attacks should be included among the skin manifestations of FMF. © 2014 Japanese Dermatological Association.

  17. Polyarteritis nodosa in a case of familial Mediterranean fever.

    PubMed

    Bakkaloğlu, Sevcan A; Muzaç, Sule; Akpek, Sergin; Söylemezoğlu, Oğuz; Buyan, Necla; Hasanoğlu, Enver

    2004-05-01

    We describe a 7-year-old boy with familial Mediterranean fever (FMF) complicated by polyarteritis nodosa (PAN) with distinct angiographic findings. On admission, he had abdominal pain, arthralgia, and severe fibromyalgia. During hospitalization, he displayed maculopapular eruptions, high blood pressure, gastrointestinal bleeding, and persistent constitutional symptoms mimicking a vasculitic process, most probably PAN. Renal angiography showed a perfusion defect compatible with a renal infarction secondary to a vasculitic process. He responded well to pulse methylprednisolone therapy with colchicine. We emphasize the rare association of FMF and PAN and the non-aneurysmal angiographic signs of PAN.

  18. Pulmonary Necrotizing Granulomas in a patient with familial mediterranean fever.

    PubMed

    Kushima, Hisako; Ishii, Hiroshi; Ishii, Koji; Kadota, Jun-ichi

    2015-09-01

    We herein report a case of familial Mediterranean fever (FMF) presenting with granulomatous lung lesions with neuronal apoptosis inhibitory protein (NAIP), MHC class II transcription activator (CIITA), incompatibility locus protein from Podospora anserina (HET-E), and telomerase-associated protein (TP1) (NACHT) leucine-rich-repeat 1-positive inflammatory cell infiltrates. FMF is an autoinflammatory disorder characterized by recurrent and self-limited attacks of pyrexia, arthritis and erysipelas-like skin lesions. Lung disorders associated with FMF are extremely rare. This is the first report of an immunologically-confirmed case of pulmonary manifestations of this disease.

  19. Clinical Review: Familial Mediterranean Fever-An Overview of Pathogenesis, Symptoms, Ocular Manifestations, and Treatment.

    PubMed

    Petrushkin, Harry; Stanford, Miles; Fortune, Farida; Jawad, Ali S

    2016-08-01

    Familial Mediterranean fever is an autoinflammatory multisystem disease, which most commonly affects patients from the Mediterranean basin. This review discusses the common polymorphisms in the MEFV gene as well as the role of pyrin in disease pathogenesis. Patients with familial Mediterranean fever typically develop peritonitis, pleuritis, arthritis, and fever. In addition, a number of authors have reported ophthalmic features. These case reports and series are further explored in this review. Colchicine has transformed the prognosis for patients with familial Mediterranean fever. The rationale for the use of colchicine, as well as the evidence for newer biologic agents is also covered.

  20. [Familial Mediterranean fever - clinical picture, diagnosis and treatment].

    PubMed

    Dallos, Tomáš; Ilenčíková, Denisa; Kovács, László

    2014-01-01

    Familial mediterranean fever (FMF) is the most prevalent genetically determined autoinflammatory disease. FMF significantly decreases the quality of life and limits life expectancy due to the development of amyloidosis in affected individuals. Prevalence of FMF is highest in the south-eastern Mediterraneans. In other parts of the world, its occurance is often restricted to high-risk ethnic goups. In Central Europe, experience with FMF is scarse. As for Slovakia, we have reported the first cases of FMF in ethnic Slovaks only recently. Along with their complicated fates, this has lead us to compile a comprehensive overview of the clinical picture, diagnosis and treatment of this elusive disease. Hereby we hope to be able to promote the awareness about this disease and possibly aid the diagnosis in new patients.

  1. Interventions for reducing inflammation in familial Mediterranean fever.

    PubMed

    Wu, Bin; Xu, Ting; Li, Youping; Yin, Xi

    2015-03-20

    Familial Mediterranean fever, a hereditary auto-inflammatory disease, mainly affects ethnic groups living in the Mediterranean region. Early studies reported colchicine as a potential drug for preventing attacks of familial Mediterranean fever. For those people who are colchicine-resistant or intolerant, drugs such as rilonacept, anakinra, etanercept, infliximab, thalidomide and interferon-alpha might be beneficial. To evaluate the efficacy and safety of interventions for reducing inflammation in people with familial Mediterranean fever. We used detailed search strategies to search the following databases: CENTRAL; MEDLINE; Embase; Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure Database (CNKI); Wan Fang; and VIP. In addition, we also searched the clinical trials registries including ClinicalTrials.gov, the International Standard Randomized Controlled Trial Number Register, the WHO International Clinical Trials Registry Platform and the Chinese Clinical Trial Registry, as well as references listed in relevant reports.Date of last search: 21 May 2014. Randomized controlled studies of people with diagnosis of familial Mediterranean fever, comparing active interventions (including colchicine, anakinra, rilonacept, etanercept, infliximab, thalidomide, interferon-alpha, ImmunoGuard™ (a herbal dietary supplement) and non-steroidal anti-inflammatory drugs) with placebo or no treatment, or comparing active drugs to each other. The authors independently selected studies, extracted data and assessed risk of bias. We pooled data to present the risk ratio or mean difference with their 95% confidence intervals. We assessed overall evidence quality according to the GRADE approach. We included four randomized placebo-controlled studies with a total of 75 participants (aged three to 53 years); three were of cross-over and one of parallel design. Two studies used the active intervention of oral colchicine (0.6 mg three times daily or 0.5 mg

  2. Effect of familial Mediterranean fever on sexual and reproductive health in women.

    PubMed

    Karakaş Uğurlu, Görkem; Uğurlu, Mustafa; Erten, Şükran; Can, Serdar Süleyman; Ulusoy Kaymak, Semra; Çayköylü, Ali

    2017-04-18

    The aim of this study was to investigate the relationship between familial Mediterranean fever and female sexual dysfunction and premenstrual syndrome. This study included 36 patients with familial Mediterranean fever and 33 healthy volunteers. Familial Mediterranean fever was diagnosed according to the Tel Hashomer criteria and familial Mediterranean fever mutations were identified in all of the patients. The patients and healthy volunteers were compared in terms of anxiety, depression, sexual dysfunction, and premenstrual syndrome, and a model was created that describes the relationships among these variables. We found statistically significant differences between the groups in terms of anxiety, premenstrual syndrome, and Golombok Rust Inventory of Sexual Satisfaction frequency and vaginismus subscale scores. There was no difference in depression scores between the groups. Familial Mediterranean fever is a rheumatic disease that predisposes patients to sexual dysfunction and premenstrual syndrome, which emerges as direct and indirect psychological factors.

  3. Adjuvant chemotherapy with 5-fluorouracil in a patient with colorectal cancer and Familial Mediterranean Fever.

    PubMed

    Purim, Ofer; Sulkes, Aaron; Brenner, Baruch

    2007-07-01

    Colorectal cancer is a common malignancy often requiring adjuvant chemotherapy. Familial Mediterranean Fever is a chronic hereditary disease which is relatively prevalent in the Middle East and is associated with recurrent episodes of serosal, synovial or cutaneous inflammations. The aim of this paper was to describe a patient with Familial Mediterranean Fever who received fluorouracil-based adjuvant chemotherapy for colorectal cancer. A 56-year-old man with Familial Mediterranean Fever and amyloidosis was referred for evaluation and treatment following surgery for colorectal cancer. In light of his relatively young age, good general state of health and apparently well-controlled Familial Mediterranean Fever, he was treated with chemotherapy consisting of four cycles of 5-fluorouracil and leucovorin. The patient's clinical course during chemotherapy was unremarkable except for one minor attack of Familial Mediterranean Fever. The patient's follow-up was notable for periodic fluctuations in serum carcinoembryonic antigen levels, up to 4-fold of normal. The Familial Mediterranean Fever remained stable. Although our patient showed a good tolerability of treatment, the administration of chemotherapy to patients with Familial Mediterranean Fever raises several concerns. These include a potential deterioration in the Familial Mediterranean Fever status owing to chemotherapy-induced stress, the potential effect of Familial Mediterranean Fever or its treatment on the tolerability of chemotherapy and an overlapping toxicity of the drugs used to treat the two diseases. An increase in serum carcinoembryonic antigen in this setting may be related to the underlying pathophysiologic mechanism of Familial Mediterranean Fever but does not necessarily indicate disease recurrence. Clinicians should be aware of these issues considering the recent worldwide increase in colorectal cancer.

  4. Genetic Analysis of Southwestern Iranian Patients with Familial Mediterranean Fever

    PubMed Central

    Haghighat, Mahmoud; Moghtaderi, Mozhgan; Farjadian, Shirin

    2017-01-01

    Background: Familial Mediterranean fever (FMF) is an autosomal recessive genetic disorder characterized by recurrent episodes of self-limited fever and serosal tissues inflammation. Methods: To evaluate clinical symptoms and common genetic mutations in southwestern Iranian patients with FMF, 20 unrelated patients were enrolled in this study based on clinical criteria. A panel of 12 common MEFV gene mutations was tested Results: The most frequent clinical presentations of the patients were fever, colicky abdominal pain and arthritis. Eighteen patients responded completely to colchicine therapy. MEFV gene mutations were detected in only 40% of the patients. The most common mutation was E148Q, detected in five patients (25%). The V726A, M694V and P369S mutations were each observed in one patient. Conclusions: Although none of the 12 mutations we included in our test panel was detected in 60% of our patients, all of them had FMF symptoms and responded well to colchicine. MEFV full gene sequencing analysis in these patients may lead to finding new mutations in southwestern Iranian FMF patients which would be helpful in designing a local diagnostic kit. PMID:28367474

  5. Protracted febrile myalgia in a patient with Familial Mediterranean Fever and Ankylosing Spondylitis.

    PubMed

    Ekşioğlu, Emel; Kesikburun, Bilge; Çakçı, Aytül

    2016-06-03

    Protracted Febrile Myalgia is a rare form of vasculitis that is diagnosed in patients with Familial Mediterranean Fever. To present a case with Familial Mediterranean and Anklosing Spondylitis on anti-TNF therapy for three years, who developed protracted febrile myalgia syndrome. Case report. A 35-year-old woman with known Familial Mediterranean Fever and Anklosing Spondylitis for 3 years presented with fever, diarrhea, intermittent abdominal pain and severe diffuse muscular pain lasting for two weeks. The patient was investigated for any infection focus. The patient was diagnosed as having Protracted Febrile Myalgia four weeks after the onset of the symptoms. Prednisolone 1 mg/kg per day was applied. Her fever and muscle pain resolved within 48 hours. The coexisting Ankylosing Spondylitis disease and the use of anti-TNF treatment in patients with Familial Mediterranean Fever could be a confounding factor for the investigation of fever. Steroid therapy has a dramatic response.

  6. IL-1β biological treatment of familial Mediterranean fever.

    PubMed

    Soriano, Alessandra; Verecchia, Elena; Afeltra, Antonella; Landolfi, Raffaele; Manna, Raffaele

    2013-08-01

    Familial Mediterranean fever (FMF) is a recessive, autosomal, auto-inflammatory disorder characterised by brief, recurring, self-limited episodes of fever and serositis resulting in abdominal, chest, joint and muscular pain; it is the most common of the periodic hereditary fevers and mostly affects Mediterranean populations. Daily administration of colchicine, a tricyclic alkaloid with anti-microtubule and anti-inflammatory properties, prevents the recurrence of FMF attacks and the development of secondary (AA) amyloidosis, the major long-tem complication of FMF. Colchicine is generally safe and well-tolerated; nevertheless, 5-10 % of FMF patients do not respond to conventional treatment, while another 2-5 % of patients are colchicine-intolerant because of toxicity issues, leading physicians to search for alternative therapeutic strategies. Recent new insights into the mechanisms of auto-inflammation add further proof to the efficacy of IL-1 targeting drugs in colchicine non-responder/intolerant FMF patients. A systematic study of relevant literature through PubMed/Medline was performed in order to identify publications reporting IL-1β biological treatment of FMF. Treatment methods, comorbidities, clinical response and side effects in literature case reports were analysed, as well as recent advances in the pathogenesis of auto-inflammation mechanisms in FMF and the causes of colchicine resistance or toxicity in common clinical practice. The paradigmatic experience of an FMF patient with severe FMF mutations (M694V/M694V) suffering from colchicine toxicity and successfully treated with anakinra is also reported. The present data show that anti-IL-1β biological treatment is actually a therapeutic option for FMF patients unresponsive or intolerant to colchicine or in FMF patients with concomitant vasculitis.

  7. Renal, gastric and thyroidal amyloidosis due to familial Mediterranean fever.

    PubMed

    Kavukçu, S; Türkmen, M; Eroğlu, Y; Canda, T; Yörükoğlu, K; Iğci, E; Büyükgebiz, A

    1997-04-01

    Chronic renal failure developed in a 10-year-old girl due to renal amyloidosis secondary to familial Mediterranean fever (FMF). During management of the chronic renal failure by hemodialysis and of FMF with colchicine, goiter and hypothroidism were observed. Thyroid fine-needle aspiration and gastric endoscopical biopsies, performed when recurrent abdominal pain could not be controlled, revealed amyloid deposits in both thyroid and gastric tissues. After 6 months' therapy with colchicine and levothyroxine, there was no significant change in the thyroid volume. This is the first case in which gastric amyloidosis secondary to FMF in childhood has been demonstrated. Patients with amyloidosis secondary to FMF who have thyroid enlargement and unexplained gastrointestinal symptoms despite adequate therapy should be evaluated with imaging studies and biopsy examinations.

  8. Increased enthesopathy in patients with familial Mediterranean fever: evaluation with a new sonographic enthesitis index.

    PubMed

    Ozkan, Fuat; Cetin, Gozde Yildirim; Inci, Mehmet Fatih; Bakan, Betul; Yuksel, Murvet; Ekerbicer, Hasan Cetin; Sayarlioglu, Mehmet

    2013-02-01

    The aim of this study was to determine the frequency of enthesopathy in familial Mediterranean fever by using a newly developed sonographic method, the Madrid Sonographic Enthesitis Index (MASEI). The study included 50 consecutive patients with familial Mediterranean fever and 57 healthy sex- and age-matched control participants. Six entheseal sites (olecranon tuberosity, superior and inferior poles of the patella, tibial tuberosity, and superior and inferior poles of the calcaneus) on both lower limbs were evaluated. All sonographic findings were identified according to MASEI. Validity was analyzed by receiver operating characteristic curves. P < .05 was considered significant. Mean total enthesitis scores ± SD were 7.54 ± 4.99 for patients and 3.63 ± 3.03 for controls (P < .001). No statistically significant correlation was found between the MASEI score and familial Mediterranean fever duration or colchicine treatment duration. There was no difference between the MASEI score and the presence or absence of arthritic involvement among the patients. The area under the receiver operating characteristic curve was 0.74 (95% confidence interval, 0.649-0.839). When analyzed by sex, men with familial Mediterranean fever had significantly higher MASEI scores than women (P < .05). This study showed significant enthesopathy in patients with familial Mediterranean fever. The findings support the hypothesis that familial Mediterranean fever and spondyloarthropathy may have common inflammatory mechanisms and suggest that the MASEI scoring system can be incorporated into clinical protocols for studying patients with familial Mediterranean fever in daily practice.

  9. Patient management and the association of less common familial Mediterranean fever symptoms with other disorders.

    PubMed

    Moradian, Mike M; Sarkisian, Tamara; Amaryan, Gayane; Hayrapetyan, Hasmik; Yeghiazaryan, Anna; Davidian, Nairi; Avanesian, Nare

    2014-03-01

    In this study, we present clinical data from 16,000 familial Mediterranean fever patients. We also discuss the clinical manifestation of a subset of these patients and their potential symptom associations with other disorders. Familial Mediterranean fever patients were confirmed using Tel-Hashomer criteria and were tested for the 12 most common mutations using the familial Mediterranean fever StripAssay. A total of 100 samples were selected, and their MEFV gene exons and intron junctions were completely sequenced. We observed that in children severe phenotypes with polyserositis, erysipelas-like erythema, splenomegaly, and vasculitis are associated with high penetrance of exon 10 mutations, particularly M694V. Several forms of arthritis were associated with familial Mediterranean fever, including acute mono/oligoarthritis in the lower extremities, destructive arthritis, ankylosing spondylitis, sacroiliitis, arthritis of the hip joint, and juvenile chronic arthritis. Severe life-threatening complications, such as adhesive intestinal obstruction, renal amyloidosis, and uncommon/rare symptoms were sometimes the only form of familial Mediterranean fever manifestation. We suggest performing familial Mediterranean fever genetic testing for patients presenting with rare/uncommon symptoms also common in other disorders, to prevent misdiagnosis or delayed diagnosis. In our experience, the most effective patient management for familial Mediterranean fever was its rapid diagnosis through genetic testing, initiation of colchicine therapy, and promotion of attack prevention through counseling.

  10. Assessment of cardiac functions using tissue Doppler imaging in children with familial Mediterranean fever.

    PubMed

    Ozdemir, Osman; Agras, Pinar Isik; Aydin, Yusuf; Abaci, Ayhan; Hizli, Samil; Akkus, Halil Ibrahim; Fidan, Cihan

    2012-04-01

    Familial Mediterranean fever may carry a potential for cardiovascular disorders because of sustained inflammation during its course; however, there has been a limited number of studies investigating the cardiac functions in children. The aim of this study was to assess both ventricular diastolic functions using conventional echocardiography and tissue Doppler imaging in children with familial Mediterranean fever. The study population included 25 patients with familial Mediterranean fever - mean age was 11.8 plus or minus 5.30 years - and 23 healthy patients as controls - mean age was 9.88 plus or minus 3.69 years. Both ventricular functions were measured using echocardiography comprising standard M-mode and conventional Doppler and tissue Doppler imaging during an attack-free period. The conventional echocardiographic parameters with myocardial performance index were in normal ranges and similar in patients with familial Mediterranean fever and controls, with a p-value more than 0.05. However, right ventricular diastolic dysfunction was observed in patients with familial Mediterranean fever documented by tissue Doppler imaging, with a p-value less than 0.05 for E't and A't wave ratio. Using tissue Doppler imaging, we have demonstrated that although left ventricular functions were comparable in the patients and healthy children, right ventricular diastolic function indices were impaired in patients with familial Mediterranean fever during childhood. Impaired right ventricular diastolic function may be an early manifestation of cardiac involvement in children with familial Mediterranean fever.

  11. Update on Pyrin Functions and Mechanisms of Familial Mediterranean Fever

    PubMed Central

    Manukyan, Gayane; Aminov, Rustam

    2016-01-01

    Mutations in the MEFV gene, which encodes the protein named pyrin (also called marenostrin or TRIM20), are associated with the autoinflammatory disease familial Mediterranean fever (FMF). Recent genetic and immunologic studies uncovered novel functions of pyrin and raised several new questions in relation to FMF pathogenesis. The disease is clinically heterogeneous reflecting the complexity and multiplicity of pyrin functions. The main functions uncovered so far include its involvement in innate immune response such as the inflammasome assemblage and, as a part of the inflammasome, sensing intracellular danger signals, activation of mediators of inflammation, and resolution of inflammation by the autophagy of regulators of innate immunity. Based on these functions, the FMF-associated versions of pyrin confer a heightened sensitivity to a variety of intracellular danger signals and postpone the resolution of innate immune responses. It remains to be demonstrated, however, what kind of selective advantage the heterozygous carriage conferred in the past to be positively selected and maintained in populations from the Mediterranean basin. PMID:27066000

  12. Efficacy and safety of biologic treatments in Familial Mediterranean Fever.

    PubMed

    Akgul, Ozgur; Kilic, Erkan; Kilic, Gamze; Ozgocmen, Salih

    2013-08-01

    Colchicine is the mainstay treatment for Familial Mediterranean Fever (FMF). However 5% to 10% of the patients with FMF are unresponsive or intolerant to colchicine. Biologics are efficient in many rheumatic diseases, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, cryopyrin-associated periodic syndromes. We performed a systematic review to analyze patients with FMF, including juvenile patients who received treatment with biologics. A MEDLINE search, including articles published in English language between 1990 and May 2012, was performed. Patients who had Mediterranean fever variants but could not be classified as FMF according to Tel-Hashomer criteria were excluded. There is no controlled trial on the efficacy and safety of biologics in FMF. Fifty-nine (32 female and 27 male) patients with FMF who had been treated with biologics (infliximab, etanercept, adalimumab, anakinra, and canakinumab) were reported in 24 single reports and 7 case series. There were 16 children and 43 adults (7- to 68-year olds). Five patients were reported to have colchicine intolerance or had adverse events related to colchicine use, and the rest 54 were unresponsive to colchicine treatment. The current data are limited to case reports, and it is difficult to obtain a quantitative evaluation of response to biologic treatments. However, on the basis of reported cases, biologic agents seem to be an alternative treatment for patients with FMF who are unresponsive or intolerant to colchicine therapy and seem to be safe. Controlled studies are needed to better evaluate the safety and efficacy of biologics in the treatment of patients with FMF.

  13. Familial Mediterranean fever-associated diseases in children.

    PubMed

    Özçakar, Z B; Çakar, N; Uncu, N; Çelikel, B A; Yalçinkaya, F

    2017-05-01

    MEditerranean FeVer (MEFV) gene encodes for the pyrin protein and a mutated pyrin is associated with a prolonged or augmented inflammation. Hence, various diseases were reported to be associated with familial Mediterranean fever (FMF) or carriers of MEFV mutations. However, systematic evaluation of all associated diseases in children with FMF has not been done previously. The aim of this study was to investigate the frequency and type of FMF-associated diseases in children. Files of FMF patients who had been seen in two reference hospitals in Ankara, in the last two years, were retrospectively evaluated. Patients with FMF and concomitant diseases were included to the study. Among 600 FMF patients, 77 were found to have a concomitant disease (12.8%). Thirty patients (5%) had vasculitis; 21 (3.5%) had juvenile idiopathic artritis (JIA); 7 (1.16%) had inflammatory bowel disease (IBD) and 19 had other diseases including 5 patients with isolated sacroiliitis. Overall, 13 (2.17%) patients had sacroiliitis in our cohort. The most frequent mutation was M694V/M694V (44%) and 81% of the patients had at least one M694V mutation. Majority of the patients (74%) developed associated diseases while they were not receiving colchicine therapy. Certain inflammatory diseases including vasculitis, chronic arthritis and IBD were more frequently detected in patients with FMF during childhood. M694V mutation is a susceptibility factor for associated diseases. In countries where FMF is prevalent, clinicians dealing with FMF and other inflammatory diseases should be aware of these associations.

  14. Association Between Keratoconus and Familial Mediterranean Fever in Turkey.

    PubMed

    Kosker, Mustafa; Arslan, Nese; Alp, Muhammed Yunus; Ozisler, Cem; Acar, Mutlu; Dogan, Aysun Sanal; Yesilyurt, Ahmet; Gurdal, Canan

    2016-01-01

    To evaluate the association between familial Mediterranean fever (FMF) and keratoconus (KC). This retrospective case-control study was performed to compare the prevalence of KC in patients with FMF with the corresponding prevalence in control patients without FMF referred to Genetic Diagnostic Center at Diskapi Yildirim Beyazit Training and Research Hospital from June 2012 to June 2015. We included all 100 patients with FMF. Each FMF-affected patient was matched to 3 controls. None of the patients in the control group (0%, 0/300) had KC, whereas 4 of 100 patients with FMF (4%) had KC (P < 0.004). Three of 33 patients with a homozygous mutation (9.1%) (M694V/M694V in 2 cases and M680I/M680I in 1 case) and 1 of the 46 patients with a compound heterozygous mutation (2.2%) (M694V/M680I) had KC, whereas none of the 21 patients with a heterozygous mutation (0%) had KC. All patients with KC were women, and mean age was 40.8 years (range, 30-51). Although 1 of the 4 patients with KC had hypertension and type 2 diabetes mellitus, the other 3 patients did not have any systemic illness except FMF. When we compared the prevalence of KC in patients with FMF (4%) with the highest prevalence of KC reported in the literature (0.2%), FMF was a predisposing factor to develop KC [odds ratio: 18.1 (95% CI: 11.9-27.5)] especially in patients with a homozygous mutation [odds ratio: 43.4 (95% CI: 28.6-65.7)]. Mediterranean fever (MEFV) gene mutations, particularly in homozygous mutations of the MEFV gene, may be a predisposing factor in the development of KC.

  15. Familial Mediterranean Fever -- an increasingly important childhood disease in Sweden.

    PubMed

    Wekell, P; Friman, V; Balci-Peynircioglu, B; Yilmaz, E; Fasth, A; Berg, S

    2013-02-01

    To characterize Familial Mediterranean Fever (FMF) in western Sweden, focusing on genotype, clinical picture, prevalence and age of onset as well as time to diagnosis. Patients with autoinflammatory diseases are continuously registered at the five main hospitals in Western Sweden. Case records of patients with FMF were analysed retrospectively. Population data on immigration was retrieved from Statistics Sweden. Until 2008, 37 patients with FMF were identified. The prevalence among inhabitants of Turkish, Lebanese, Syrian and Iranian origin was 173, 124, 86 and 17/100 000, respectively. Median age at first symptoms was 4 years (range 3 month-37 years) and at diagnosis 10 years (range 2-44 years). Median time from first symptoms to diagnosis was 4 years (range <1 year-34 years). Among 32 patients screened for twelve common mutations, 75% were homozygotes or compound heterozygotes, 16% were heterozygotes and in 9% no mutation was found. In our cohort the frequencies of symptoms were fever 100%, peritonitis 92%, pleuritis 22% and arthritis 11%. The majority of patients with FMF present during childhood. The prevalence among immigrants in western Sweden is in the same range as in their country of origin. Time to diagnosis needs to be shortened by means of increased awareness of the disease. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.

  16. Canakinumab for the treatment of familial Mediterranean fever.

    PubMed

    Ozdogan, Huri; Ugurlu, Serdal

    2017-05-01

    Familial Mediterranean fever (FMF) is the most frequent of all hereditary autoinflammatory syndromes. It is characterized by recurrent attacks of fever and serositis. If not treated it may be complicated with AA amyloidosis. It is caused by mutations in the MEFV gene that encodes pyrin which is involved in the regulation of IL-1β. The mainstay of treatment is colchicine, however a subset of patients requires an alternative treatment either due to inadequate response or intolerance. The accumulating data indicates that anti IL-1 drugs are effective in treating colchicine resistant FMF cases and improving their quality of life. Areas covered: This review focuses on canakinumab, a fully human anti IL-1β antibody, treatment in FMF. The data obtained from case reports, case series, two Phase II studies and an ongoing double-blind, randomized, placebo controlled Phase III trial are analyzed. Efficacy and safety profiles of canakinumab are discussed. Expert commentary: Canakinumab became the first approved therapy by the Food and Drug Administration for FMF very recently, which highlights its importance as the alternative treatment in FMF.

  17. Recurrent peripheral facial palsy in a child with familial Mediterranean fever.

    PubMed

    Yılmaz, Unsal; Gülez, Nesrin; Cubukçu, Duygu; Güzel, Orkide; Akinci, Gülçin; Oztürk, Aysel

    2013-10-01

    Recurrent peripheral facial palsy is uncommon in children. It mostly occurs as an idiopathic disorder and to a lesser extent in the setting of some infectious, genetic, or systemic disorders. However, its association with familial Mediterranean fever has not been reported before. We present a 14-year-old girl who experienced three episodes of right-sided peripheral facial palsy during a 9-month interval. She had a diagnosis of familial Mediterranean fever (homozygous with M694V mutation) and she had been receiving colchicine for 8 years. Recurrent peripheral facial palsy could be a neurological manifestation of vasculitis in familial Mediterranean fever. Recurrent peripheral facial palsy may be a manifestation of familial Mediterranean fever in children. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. The prevalence of celiac disease among patients with familial mediterranean Fever.

    PubMed

    Işikay, Sedat; Işikay, Nurgül; Kocamaz, Halil

    2015-01-01

    Familial Mediterranean Fever and celiac disease are both related to auto-inflammation and/or auto-immunity and they share some common clinical features such as abdominal pain, diarrhea, bloating and flatulence. Objectives We aimed to determine the association of these two diseases, if present. Totally 112 patients diagnosed with Familial Mediterranean Fever and 32 cases as healthy control were included in the study. All participants were examined for the evidence of celiac disease, with serum tissue transglutaminase IgA levels (tTG IgA). Totally 144 cases, 112 with Familial Mediterranean Fever and 32 healthy control cases were included in the study. tTG IgA positivity was determined in three cases with Familial Mediterranean Fever and in one case in control group. In that aspect there was no significant difference regarding the tTG IgA positivity between groups (P=0.81). Duodenum biopsy was performed to the tTG IgA positive cases and revealed Marsh Type 3b in two Familial Mediterranean Fever cases and Marsh Type 3c in the other one while the biopsy results were of the only tTG IgA positive case in control group was Marsh Type 3b. In HLA evaluation of the celiac cases; HLA DQ2 was present in two celiac cases of the Familial Mediterranean Fever group and in the only celiac case of the control group while HLA DQ8 was present in one celiac case of the Familial Mediterranean Fever group. We did not determine an association of Familial Mediterranean Fever with celiac disease. Larger studies with subgroup analysis are warranted to determine the relationship of these two diseases.

  19. Familial Mediterranean fever in which Crohn's disease was suspected: a case report.

    PubMed

    Matsumoto, Satohiro; Urayoshi, Shunsuke; Yoshida, Yukio

    2014-09-27

    Familial Mediterranean fever is a hereditary autoinflammatory disease, mainly characterized by periodic fever and serositis. The level of awareness about familial Mediterranean fever is far from sufficient, and it is assumed that there may be many patients with this disease who are under observation without an accurate diagnosis. A 30-year-old Japanese man presented to us with a few years' history of recurrent episodes of fever, abdominal pain and diarrhea. He often visited a hospital when the attacks occurred; however, acute enteritis was diagnosed each time, and the symptoms resolved spontaneously within a few days. When he noticed a shortening of the interval between the attacks, he visited the hospital again. Upper endoscopy and colonoscopy performed at this hospital revealed no significant abnormal findings. He was then referred to our hospital under the suspicion of a small intestinal disease. Abdominal computed tomography revealed wall thickening and increased density of the mesenteric adipose tissue in the jejunum, which led us to suspect Crohn's disease. Oral double-balloon enteroscopy was performed; because this revealed only mild mucosal edema in the jejunum, Crohn's disease was considered to be highly improbable. Based on the patient's clinical course, we suspected familial Mediterranean fever. As the Livneh criteria for familial Mediterranean fever were satisfied, the patient was started on oral colchicine for the purpose of diagnostic treatment. A definitive diagnosis of familial Mediterranean fever was then made based on the detection of a mutation of the Mediterranean fever gene. A marked reduction in the frequency of attacks was observed in response to colchicine treatment. Although Crohn's disease may be considered first in the differential diagnosis of young patients presenting with periodic fever, abdominal pain and diarrhea, the possibility of familial Mediterranean fever should also be borne in mind.

  20. EULAR recommendations for the management of familial Mediterranean fever.

    PubMed

    Ozen, Seza; Demirkaya, Erkan; Erer, Burak; Livneh, Avi; Ben-Chetrit, Eldad; Giancane, Gabriella; Ozdogan, Huri; Abu, Illana; Gattorno, Marco; Hawkins, Philip N; Yuce, Sezin; Kallinich, Tilmann; Bilginer, Yelda; Kastner, Daniel; Carmona, Loreto

    2016-04-01

    Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, but many rheumatologists are not well acquainted with its management. The objective of this report is to produce evidence-based recommendations to guide rheumatologists and other health professionals in the treatment and follow-up of patients with FMF. A multidisciplinary panel, including rheumatologists, internists, paediatricians, a nurse, a methodologist and a patient representative, was assembled. Panellists came from the Eastern Mediterranean area, Europe and North America. A preliminary systematic literature search on the pharmacological treatment of FMF was performed following which the expert group convened to define aims, scope and users of the guidelines and established the need for additional reviews on controversial topics. In a second meeting, recommendations were discussed and refined in light of available evidence. Finally, agreement with the recommendations was obtained from a larger group of experts through a Delphi survey. The level of evidence (LoE) and grade of recommendation (GR) were then incorporated. The final document comprises 18 recommendations, each presented with its degree of agreement (0-10), LoE, GR and rationale. The degree of agreement was greater than 7/10 in all instances. The more controversial statements were those related to follow-up and dose change, for which supporting evidence is limited. A set of widely accepted recommendations for the treatment and monitoring of FMF is presented, supported by the best available evidence and expert opinion. It is believed that these recommendations will be useful in guiding physicians in the care of patients with FMF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Familial Mediterranean fever and its implications for fertility and pregnancy.

    PubMed

    Mijatovic, Velja; Hompes, Peter G A; Wouters, Maurice G A J

    2003-06-10

    Familial Mediterranean fever (FMF) is a recessively inherited disease of episodic fever in combination with severe abdominal pain, pleurisy, arthritis or erysipelas-like skin rashes. The disease is mainly prevalent in Sephardic Jews, Armenians, Turks and Arabs. The gene responsible for FMF was cloned in 1997. The gene expresses a protein called pyrin which is believed to play a role in the downregulation of mediators of inflammation. Several mutations have been identified of which the homozygous form of the M694V mutation is associated with a more severe expression of FMF. Prophylactic administration of colchicine is effective in relieving most patients from their attacks and preventing the development of amyloidosis, which usually leads to end-stage renal disease. Unfortunately, there is little awareness of the disease in gynaecological practice although a FMF full blown episode may mimic an acute abdominal calamity suggesting several possible gynaecological diagnoses. FMF is also associated with subfertility. In females, infertility was mainly related to oligomenorrhea although the causes remain unclear. In male FMF patients, progression of the disease may induce testicular impairment, consequently affecting spermatogenesis. Some controversy exists as to the adverse effects of colchicine on sperm production and function although the impression is that the occurrence of sperm pathology in FMF patients, using the recommended dosage of colchicine, is very low. In pregnant FMF patients, an increased occurrence of miscarriage has been found. However, the mechanisms involved remain unclear. Although colchicine is a mitotic inhibitor and transplacental crossing of colchicine has been demonstrated, no increased risk of foetal abnormalities in colchicine-treated pregnant FMF patients has been found. Therefore, amniocentesis should not be done for reassurance alone.

  2. Crohn disease in patients with familial Mediterranean fever.

    PubMed

    Fidder, Herma H; Chowers, Yehuda; Lidar, Merav; Sternberg, Matan; Langevitz, Pnina; Livneh, Avi

    2002-11-01

    Crohn disease and familial Mediterranean fever (FMF) are inflammatory diseases characterized by abdominal pain and fever. The concurrence of the 2 diseases (FMF-CD) may pose a challenge to diagnosis and treatment. We undertook the present study to determine the prevalence of Crohn disease in FMF and to characterize FMF-CD patients clinically and genetically. Using a computerized search, the patients of our FMF clinic were screened for a concomitant diagnosis of Crohn disease. Patients and their medical records were thoroughly examined, and their DNA was genotyped for mutations in the MEFV gene. Control groups of ethnically and sex-matched patients suffering from each of the diseases alone, either Crohn disease or FMF, were used for comparison. We identified 7 patients with concomitant Crohn disease and FMF, which is more than the expected prevalence in the general population (p = 0.03). Crohn disease presented at a significantly later age in the FMF-CD group (40.6 +/- 10.0 yr versus 26.2 +/- 11.4 yr; p < 0.004). Disease severity and other characteristics of Crohn disease were comparable to the Crohn disease control group. Contrary to the FMF control group patients, FMF in FMF-CD patients was characterized by a higher attack frequency (p < 0.05) and increased prevalence of amyloidosis (p < 0.02). The overall severity score was similar in both groups. In conclusion, Crohn disease appears to be more prevalent in FMF and presents later than in patients without FMF. FMF in this group of patients shows a higher attack frequency and is more often complicated by amyloidosis.

  3. [Familial Mediterranean Fever (FMF): from diagnosis to treatment].

    PubMed

    Medlej-Hashim, Myrna; Loiselet, Jacques; Lefranc, Gérard; Mégarbané, André

    2004-01-01

    Familial Mediterranean Fever (FMF), also known as paroxysmal polyserositis, is an autosomal recessive disease affecting mainly Mediterranean populations (Jews, Armenians, Arabs, Turks). It is characterised by recurrent crises of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Erysipela-like erythema affecting mainly feet and legs and effort-induced myalgia are less frequently encountered symptoms. The major complication of FMF is the development of renal amyloidosis. Standard laboratory tests of FMF patients are non-informative, except for the high sedimentation rate and white blood cell count, but during and immediately after crises, diminished albumin concentrations and elevated fibrinogen, C-reactive protein, beta2 and alpha2 M globulins, haptoglobin and lipoprotein concentrations are noted. Studies have measured immunoglobulin (Ig) levels in the sera of FMF patients and found elevated levels of IgA, IgM, IgG, and IgD in 23%, 13%, 17% and 13%, respectively. FMF crises are characterised by a massive influx of polymorphonuclear leukocytes into the inflamed regions. Moreover, the peritoneal fluid of FMF patients contains abnormally low levels of the inhibitor of complement fragment C5a and interleukin 8. Failure to suppress inflammatory response to C5a may explain the typical inflammatory FMF crises. The MEFV (for MEditerranean FeVer) gene responsible for the disease has been identified on 16p13.3. It is composed of 10 exons and spans approximately 14 Kb of genomic DNA. More than 35 mutations have so far been identified. The most frequent are M694V, M694I, M680I, V726A and E148Q. The M694V mutation is the most frequent mutation in the various ethnic groups considered, although its frequency varies from group to group. The V726A mutation is observed mainly among Ashkenazi and Iraqi Jews, Druzes and Armenians, and the M680I among Armenians and Turks. M694I and A744S seem specific to Arab populations, and R761H is frequently found in

  4. The spectrum of Familial Mediterranean Fever (FMF) mutations.

    PubMed

    Touitou, I

    2001-07-01

    Familial Mediterranean Fever (FMF) is the prototype of a group of inherited inflammatory disorders. The gene (MEFV) responsible for this disease, comprises 10 exons and 781 codons. Twenty-nine mutations, most located in the last exon, have been identified so far. It is unclear whether all are true disease-causing mutations. Five founder mutations, V726A, M694V, M694I, M680I and E148Q account for 74% of FMF chromosomes from typical cases (Armenians, Arabs, Jews, and Turks). Rare mutations are preferentially found in populations not usually affected by FMF (eg Europeans not from the above ancestries). The various combinations of MEFV mutations define severe to mild genotypes. The trend is that genotypes including two mutations located within mutational 'hot-spots' (codons 680 or 694) of the gene are associated with severe phenotypes, whereas mild phenotypes are associated with some other mutations, E148Q being the mildest and least penetrant. Understanding the correlation between the FMF phenotype and genotype is further obscured by the existence of complex alleles, modifier loci, genetic heterogeneity and possible epigenetic factors. Additionally, mutations in the MEFV gene are thought to be involved in non FMF disorders. Carrier rates for FMF mutations may be as high as 1:3 in some populations, suggesting that the disease is underdiagnosed. This review update emphasises that both clinical and genetic features are to be taken into account for patient diagnosis, colchicine treatment and prognosis.

  5. Pyrin gene and mutants thereof, which cause familial Mediterranean fever

    DOEpatents

    Kastner, Daniel L [Bethesda, MD; Aksentijevichh, Ivona [Bethesda, MD; Centola, Michael [Tacoma Park, MD; Deng, Zuoming [Gaithersburg, MD; Sood, Ramen [Rockville, MD; Collins, Francis S [Rockville, MD; Blake, Trevor [Laytonsville, MD; Liu, P Paul [Ellicott City, MD; Fischel-Ghodsian, Nathan [Los Angeles, CA; Gumucio, Deborah L [Ann Arbor, MI; Richards, Robert I [North Adelaide, AU; Ricke, Darrell O [San Diego, CA; Doggett, Norman A [Santa Cruz, NM; Pras, Mordechai [Tel-Hashomer, IL

    2003-09-30

    The invention provides the nucleic acid sequence encoding the protein associated with familial Mediterranean fever (FMF). The cDNA sequence is designated as MEFV. The invention is also directed towards fragments of the DNA sequence, as well as the corresponding sequence for the RNA transcript and fragments thereof. Another aspect of the invention provides the amino acid sequence for a protein (pyrin) associated with FMF. The invention is directed towards both the full length amino acid sequence, fusion proteins containing the amino acid sequence and fragments thereof. The invention is also directed towards mutants of the nucleic acid and amino acid sequences associated with FMF. In particular, the invention discloses three missense mutations, clustered in within about 40 to 50 amino acids, in the highly conserved rfp (B30.2) domain at the C-terminal of the protein. These mutants include M6801, M694V, K695R, and V726A. Additionally, the invention includes methods for diagnosing a patient at risk for having FMF and kits therefor.

  6. The evaluation of cochlear functions in Familial Mediterranean Fever.

    PubMed

    Eryilmaz, Mehmet Akif; Yucel, Abitter; Cure, Erkan; Sakiz, Davut; Koder, Ahmet; Kucuk, Adem; Tunc, Recep

    2016-12-01

    Familial Mediterranean Fever (FMF) is a progressive disease characterized by chronic inflammation, which also has negative effects on cochlear functions and hearing levels. We investigated whether the cochlear functions and hearing levels of FMF patients were different than healthy controls and also evaluated the relationship of hearing levels with the age at diagnosis, duration without treatment, and inflammation and lipid parameters in this study. A total of 60 patients diagnosed with FMF and 48 age, gender and body mass index (BMI)-matched healthy controls were included in the study. The hemogram, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lipid parameters of the subjects were studied and they all underwent pure tone audiometry and Transient evoked otoacoustic emission tests after an otologic examination. The hearing levels of the FMF group were significantly higher than those of the control group. The TEOAE signal/noise (S/N) ratios were similar in both groups. A positive relationship was present between the audiometric test results and the age, BMI, low-density lipoprotein and triglyceride levels and a negative relationship with the high-density lipoprotein levels. A negative relationship was present between the TEOAE S/N ratios and the age of the patients, duration without treatment, lipid parameters, inflammation markers and the creatinine level. FMF patients are exposed to chronic inflammation and this can influence their hearing levels. The age at diagnosis, duration without treatment, chronic inflammation, unfavorable lipid parameters, and obesity can affect hearing tests negatively.

  7. Vitamin D levels in children with familial Mediterranean fever.

    PubMed

    Onur, Hatice; Aral, Hale; Arica, Vefik; Bercem, Gamze Atalay; Kasapcopur, Ozgur

    2016-04-27

    This study aimed to determine whether vitamin D deficiency is more common in children with familial Mediterranean fever (FMF) than in healthy individuals. The study group consisted of 100 patients diagnosed with FMF and 50 healthy children. Serum baseline 25-hydroxyvitamin D levels and other related parameters were evaluated. The mean (standard deviation [SD]) vitamin D levels in patients with FMF and healthy controls were 24.78 (8.35) and 28.70 (11.70) ng/mL, respectively. Patients with FMF had significantly decreased vitamin D levels compared with those in healthy controls (P = 0.039). Vitamin D levels were similar in patients with FMF with different MEFV mutations (P = 0.633). Age was significantly correlated with vitamin D levels (r = -0.235, P = 0.019). In addition, a negative correlation between parathyroid hormone and vitamin D levels was detected (rs = -0.382, P < 0.0001). This study demonstrated that vitamin D levels are lower in children with FMF than in healthy controls. We speculate that vitamin D levels should be carefully examined, and nutritional supplementation may be required in patients with FMF. Further studies with larger patient populations are needed to confirm the frequency of vitamin D deficiency in patients with FMF.

  8. Compound heterozygosity for three common MEFV mutations in a highly consanguineous family with familial Mediterranean fever.

    PubMed

    Seidel, H; Steinlein, O K

    2008-07-01

    Consanguinity is not the only factor influencing the occurrence of autosomal recessive disorders such as familial Mediterranean fever (FMF). The extended, multiple consanguineous Turkish pedigree presented here demonstrates that the population frequency of certain mutations (so-called "ancient" mutations) can be at least equally important. In high-risk populations different combinations of mutations can occur within the same family, increasing not only the intrafamilial clinical variability, but also causing considerable recurrence risks even in marriages with unrelated spouses.

  9. Familial Mediterranean fever without cardinal symptoms and role of genetic screening.

    PubMed

    Ulas, T; Buyukhatipoglu, H; Bes, C; Dal, M S; Hacıbekiroglu, I; Apucu, H G; Borlu, F

    2012-07-19

    Familial Mediterranean fever is an autosomal recessive disorder characterized by paroxysmal episodes of fever and serosal inflammation. The classical presentation is fever and severe recurrent abdominal pain due to serositis that lasts for one to three days and the resolves spontaneously. Between the episodes patients are asymptomatic. Ninety-five percent of patients with familial mediterranean fever have painful episodes localized to the abdomen, which is usually the dominant manifestation of the disease. Herein, we present a case of 34-year-old man with incomplete abdominal pain episode of familial mediterranean fever limited to the epigastrum and had no cardinals symptoms of this disease. The diagnosis was made by genetic screening. Successful treatment response was achieved by colchicine.

  10. Diagnosis and management of familial Mediterranean fever: integrating medical genetics in a dedicated interdisciplinary clinic.

    PubMed

    Zadeh, Neda; Getzug, Terri; Grody, Wayne W

    2011-03-01

    Familial Mediterranean fever is an autosomal recessive genetic disorder characterized by recurrent febrile polyserositis, especially prevalent in individuals of Mediterranean descent. Familial Mediterranean fever can have nonspecific manifestations that mimic many common acquired disorders such as infections, acute appendicitis, cholecystitis, and arthritis, which can delay diagnosis for many years and subject patients to extensive evaluations and even unnecessary surgery. Untreated familial Mediterranean fever can result in serious complications such as end-stage renal disease and malabsorption secondary to amyloid deposition in the kidneys and digestive tract, male and female infertility, and growth retardation in children. These significant sequelae, along with the episodic acute attacks, are readily preventable by treatment with oral colchicine and underscore the necessity of early detection and treatment from a medical, psychosocial, and economic standpoint. We describe our comprehensive approach to the accurate diagnosis and effective management of this disorder by means of a dedicated familial Mediterranean fever clinic that incorporates medical genetics on equal footing with general medicine. In addition to providing the clinician with the presenting features of familial Mediterranean fever, methods of diagnosis including molecular testing, and current management based on our extensive experience with hundreds of affected individuals, we also advance this approach as a model for the incorporation of medical genetics practice into the more traditional domains of general medicine.

  11. Canakinumab as rescue therapy in familial Mediterranean fever refractory to conventional treatment.

    PubMed

    Alpa, Mirella; Roccatello, Dario

    2015-01-01

    Familial Mediterranean fever is an autosomal recessive autoinflammatory disorder mainly affecting Mediterranean populations, which is associated with mutations of the MEFV gene that encodes pyrin. Functional studies suggest that pyrin is implicated in the maturation and secretion of interleukin-1 (IL-1). The IL-1 receptor antagonist or anti-IL-1 monoclonal antibody may therefore represent a rational approach for the treatment of the rare patients who are refractory to conventional therapy. We report the case of a young female affected by familial Mediterranean fever who proved to be resistant to colchicine and was successfully treated with canakinumab.

  12. Evaluation of circulating endothelial biomarkers in familial Mediterranean fever.

    PubMed

    Pamuk, Baris Onder; Sari, Ismail; Selcuk, Sema; Gokce, Goksel; Kozaci, Didem Leyla

    2013-08-01

    The aim of this was to evaluate some of the vascular biomarkers and cytokines related with atherosclerosis in regularly treated and attack-free familial Mediterranean fever (FMF) patients. Forty (21 males [M] and 19 females [F], 31 [15-58] years) FMF patients and eighteen healthy controls (11 M and 7 F, 35.5 [19-46] years) with no known cardiovascular (CV) risk factors were included. All patients were receiving regular colchicine treatment, and examinations were performed during attack-free periods. Serum samples were used for the determination of high-sensitive C-reactive protein (hs-CRP), tissue factor (TF), tissue plasminogen activator (t-PA), osteoprotegerin (OPG), interleukin-6 (IL-6), IL-17, and IL-23. Plasma samples were used for the determination of asymmetric dimethylarginine (ADMA) and thrombomodulin (TM). Age, sex distribution, waist circumference, body mass index, smoking status, and serum lipids were similar between the patients and controls (P > 0.05). The concentrations of (hs-CRP) and IL-17 were significantly higher in FMF patients compared with controls (P < 0.05). On the other hand, IL-6 and IL-23 levels were not different between the groups (P > 0.05). ADMA, OPG, and TM concentrations were significantly lower in the patients' group compared to those of controls (P < 0.05). However, vWF, TF, and t-PA levels were similar between the groups (P > 0.05). FMF patients receiving regular colchicine therapy during inactive disease state had significantly lower levels of vascular injury parameters.

  13. Current trends in colchicine treatment in familial Mediterranean fever.

    PubMed

    La Regina, Micaela; Ben-Chetrit, Eldad; Gasparyan, Armen Yuri; Livneh, Avi; Ozdogan, Huri; Manna, Raffaele

    2013-01-01

    Since the publication of the first reports on the efficiency of colchicine in familial Mediterranean fever (FMF), very few randomised studies have investigated issues related to its long-term use. Thus, different approaches taken by physicians involved in FMF care, are exclusively empiric, emulative, and based on case-reports or case-series. Problems such as colchicine intolerance and colchicine resistance have not been solved yet. This paper aims to evaluate trends in colchicine therapy among physicians taking care of FMF patients around the world. We conducted a survey by sending questionnaires to FMF research and treatment centres in Europe and Asia. Many issues (such as dosages, schedules, side effects, interactions, efficacy and toxicity monitoring, definition of colchicine intolerance, colchicine resistance and responsiveness, etc) have been investigated. When more than 70% of physicians responded giving similar answers to an item, the response was considered as a 'trend'. A comparison between answers of physicians from FMF-prevalent and non-prevalent countries was also made. Thirty-five physicians from 11 countries filled the questionnaires, taking care of a total of more than 15000 FMF patients (pts). Different approaches were evident among the various physicians. Statistically significant different approaches between physicians from FMF-prevalent countries with respect to those from non-prevalent countries were found in items like colchicine during pregnancy, severity score and blood tests for disease monitoring. No consensus was found regarding the definition of colchicine resistance. The current study demonstrated significant variations in the strategy of colchicine therapy for FMF around the world and re-emphasised the need for standardised definitions of colchicine resistance and colchicine intolerance.

  14. Can colchicine response be predicted in familial Mediterranean fever patients?

    PubMed

    Özçakar, Zeynep Birsin; Elhan, Atilla H; Yalçınkaya, Fatoş

    2014-10-01

    The aims of this study were to explore whether the demographic and clinical features of paediatric familial Mediterranean fever (FMF) patients with different colchicine response vary or not and to determine whether colchicine response can be predicted in FMF patients. Files of patients who have been on colchicine therapy for at least 6 months were retrospectively evaluated. Patients were divided into two groups: group I included patients with no attacks after colchicine and group II comprised patients with ongoing attacks. Thereafter group II was further divided into two groups according to the reduction rate of attack frequency: group IIA (>50%) and group IIB (≤50%). The study group comprised 221 FMF patients (116 females, 105 males). There were 131 patients in group I and 90 patients in group II (54 in group IIA and 36 in group IIB). Leg pain and M694V homozygosity were more frequent in group II (P < 0.05). Final colchicine doses, disease severity scores and number of patients with elevated acute phase reactant levels (attack-free period) were significantly higher and colchicine compliance was lower in group II when compared with group I (P < 0.05). Erysipelas-like erythema (ELE), leg pain and protracted arthritis/protracted febrile myalgia/vasculitis were more frequently detected in group IIB (P < 0.05). Colchicine response is excellent in the majority of FMF patients, however, colchicine unresponsiveness cannot be predicted easily at onset. More rarely encountered clinical findings such as ELE, leg pain and protracted complaints and M694V homozygosity may be a clue for less colchicine response. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Decreased vitamin D levels in children with familial Mediterranean fever.

    PubMed

    Anık, Ahmet; Catlı, Gönül; Makay, Balahan; Abacı, Ayhan; Küme, Tuncay; Unsal, Erbil; Böber, Ece

    2014-03-01

    To determine the frequency of vitamin D deficiency in children with familial Mediterranean fever (FMF) and to investigate the factors associated with low vitamin D status. Forty-four patients with FMF and 39 age- and sex-matched healthy controls were enrolled in this study. Demographic data, FMF symptoms, disease duration, time to delay for diagnosis, duration of follow-up, disease severity score, MEFV gene mutation, cumulative colchicine dose, compliance to treatment and serum C-reactive protein levels were recorded for each patient. Serum 25-hydroxyvitamin D levels were measured by an original commercial kit based on chemiluminescent microparticle immunoassay (CMIA). The serum 25-hydroxyvitamin D levels were significantly lower in FMF patients than the healthy controls (12.9 ± 3.6 and 16.3 ± 5.5 ng/mL, respectively, P = 0.001). Vitamin D levels were similar in patients homozygous for M694V and other genotypes (11.8 ± 3.7 and 13.2 ± 3.6 ng/mL, respectively, P = 0.21). Stepwise multiple linear regression analysis confirmed that the cumulative colchicine dose was the strongest independent variable correlating with vitamin D levels (r(2) = 0.194, P = 0.001). Our results suggest that serum 25-hydroxyvitamin D levels are decreased in children with FMF. Cumulative colchicine dose appears to negatively affect vitamin D levels. The role of colchicine on vitamin D metabolism needs to be elicited. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  16. Does breast-feeding affect severity of familial Mediterranean fever?

    PubMed

    Makay, Balahan; Unsal, Erbil

    2009-12-01

    Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease, which is caused by an inborn error in innate immune system. It was shown that disease severity of patients of the same ethnic origin differed according to different country of residence, suggesting an influence of environment on phenotype of FMF. Different microbial milieus of the countries were accused. Breast-feeding has an important role on innate immunity and protects the infant from infections. The aim of this study is to investigate whether being breast-fed and duration of breast-feeding has an impact on disease severity of FMF. The mothers of patients were asked to fill a questionnaire about the feeding type in infancy. Mode of delivery, gestational age, and age at onset of FMF symptoms were also asked. The disease severity score of each patient was calculated according to the scoring system suggested by Pras et al. (Am J Med Genet 75:216-219, 1998). MEFV mutations were noted. The mothers of 81 FMF patients completed the questionnaire. Fifteen patients (18.5%) had mild, 49 (60.5%) had moderate, and 17 (21%) had severe disease. All the patients except four were breast-fed for some period. The duration of breast-feeding was similar between three severity groups. Time to introduce cow's milk and complementary foods also did not differ between groups. Longer duration of breast-feeding did not delay the onset of FMF symptoms. Mode of delivery and gestational age had no effect on disease severity. Patients homozygous for M694V had higher severity scores. This preliminary study suggests that breast-feeding is not an exogenous factor having an influence on phenotype of FMF. M694V genotype seems to cause more severe disease.

  17. Evaluation of cochlear functions in children with Familial Mediterranean Fever.

    PubMed

    Lordoglu, Begüm; Acar, Baran; Yazilitas, Fatma; Ozlu, Sare Gulfem; Senel, Saliha

    2016-08-01

    To evaluate cochlear functions in patients with Familial Mediterranean Fever in relation to the disease severity score and treatment duration. 50 patients (4-18 years) who had been followed-up with the diagnosis of FMF and regularly receiving appropriate colchicine treatment and 39 healthy controls were included in the study. All the patients and controls were evaluated by audiologic evaluation, including high-frequency pure-tone audiometry and distortion product otoacoustic emission tests (DPOAE). The disease severity was determined by scoring system developed by Pras et al. Fifty patients (52% female, 48% male; mean age12.2 ± 4.1 years) and 39 controls (58.9% female, 41.1% male, mean age 11.1 ± 3.4 years) were enrolled the study. The pure tone average of FMF patients was significantly higher than that of the control group at 500, 4000, and 8000 Hz frequencies. The patients' DPOAE signal values at 6 kHz, 8 kHz frequencies and SNR values at 8 kHz were significantly higher than control group. The patients' audiometry and DPOAE results were compared with the disease severity scores. Pure tone average was significantly higher in severe and moderate patient groups compared to the mild patient group at 2000 Hz frequency. DPOAE signal values showed statistically significant differences between the patient severity scores at 1.4 and 2.8 kHz frequencies. The mean colchicine treatment duration was found to be 5.1 ± 3.7 years. There were significant differences at 250 and 500 Hz frequencies when patients' audiometry results were compared with the treatment periods. FMF affects cochlear functions particularly at high frequencies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Cardiac autonomic functions in children with familial Mediterranean fever.

    PubMed

    Şahin, Murat; Kır, Mustafa; Makay, Balahan; Keskinoğlu, Pembe; Bora, Elçin; Ünsal, Erbil; Ünal, Nurettin

    2016-05-01

    Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. The long-term effects of subclinical inflammation in FMF are not well recognized. Some studies have suggested that FMF is associated with cardiac autonomic dysfunction in adult FMF patients. The objective of this study was to investigate the cardiac autonomic functions in pediatric FMF patients by using several autonomic tests. Thirty-five patients with FMF and 35 healthy controls were enrolled in this cross-sectional study. Demographic data, disease-specific data, and orthostatic symptoms were recorded. In all participants, 12-lead electrocardiography (ECG), 24 h ambulatory electrocardiographic monitoring, transthoracic echocardiography, treadmill exercise test, and head upright tilt-table (HUTT) test were performed. The heart rate recovery (HRR) indices of the two groups were similar. Also, chronotropic response was similar in both groups. The time-domain parameters of heart rate variability (HRV) were similar in both groups, except mean RR (p = 0.024). Frequencies of ventricular and supraventricular ectopic stimuli were similar in both groups. There were no statistically significant differences between the groups in average QT and average corrected QT interval length, average QT interval dispersion, and average QT corrected dispersion. There was no significant difference between the two groups regarding the ratio of clinical dysautonomic reactions on HUTT. However, we observed a significantly higher rate of dysautonomic reactions on HUTT in patients with exertional leg pain than that in patients without (p = 0.013). When the fractal dimension of time curves were compared, FMF patients exhibited significantly lower diastolic blood pressure parameters than controls in response to HUTT. Cardiovascular autonomic dysfunction in children with FMF is not prominent. Particularly, patients with exertional leg pain are more prone to have dysautonomic features

  19. Decreased Chitotriosidase Activity and Levels in Familial Mediterranean Fever.

    PubMed

    Doğan, Halef Okan; Omma, Ahmet; Turhan, Turan; Boğdaycıoğlu, Nihal; Karaaslan, Yaşar; Yavuz, Hayrettin; Demirpençe, Özlem; Aydın, Hüseyin; Bakır, Sevtap

    2016-12-01

    Different studies have demonstrated changes in chitotriosidase (ChT) activity and concentrations in multiple diseases. However, changes in ChT activity and concentrations have not been concurrently evaluated in patients with Familial Mediterranean Fever (FMF). In this study, we analyzed the changes in serum ChT activity and concentrations in patients with FMF. The study included a total of 80 patients with FMF and 80 healthy controls. ChT enzyme activity and concentrations were measured and then compared between the groups. ChT activity was measured by using fluorometric ELISA and ChT concentrations were measured by using colorimetric ELISA methods. The median ChT activity was 10.00 (6.00-15.00) nmol/mL/hr in the patients and 14.00 (6.25-20.75) nmol/mL/hr in the controls. There was a statistically significant difference in the ChT activity between the controls and patients (P = 0.027). The median ChT concentrations were 65.40 (46.20-84.92) pg/mL and 125.00 (75.72-143.95) pg/mL in the patients and controls, respectively (P < 0.001), which were expressed as median percentiles (25th-75th). Additionally, we found no correlation between C-reactive protein and ChT activity (P = 0.978, r = 0.003) and concentrations (P = 0.446, r = -0.87). Serum ChT enzyme activity and concentrations may not be considered as a biomarker in FMF patients taking colchicine. New studies are needed to evaluate the changes of enzyme activity and concentration in colchicine-negative patients.

  20. Neutrophil-lymphocyte ratio in patients with familial Mediterranean fever.

    PubMed

    Celikbilek, Mehmet; Dogan, Serkan; Akyol, Lutfi; Borekci, Elif; Zararsiz, Gokmen; Kozan, Mustafa; Gunaydin, Ilhan

    2015-01-01

    Blood neutrophil-to-lymphocyte (N/L) ratio is an indicator of the overall inflammatory status of the body, and an alteration in N/L ratio may be found in patients with familial Mediterranean fever (FMF). The aim of this study was to investigate the interrelationship between N/L ratio and FMF. One hundred and fifteen patients and controls were enrolled in the study. The cases in the study were categorized as FMF with attack, FMF with attack-free period, and controls. The neutrophil and lymphocyte counts were recorded, and the N/L ratio was calculated from these parameters. All patients were diagnosed according to Tel Hashomer criteria. A total of 79 FMF patients were included in the study and all subjects were receiving colchicine treatment at the time. The serum N/L ratios of active patients were significantly higher than those of attack-free FMF patients and controls (P < 0.001). The optimum N/L ratio cut-off point for active FMF was 2.63 with sensitivity, specificity, positive predictive value, and negative predictive value of 0.62 (0.41-0.80), 0.85 (0.72-0.93), 0.67 (0.44-0.85), and 0.82 (0.69-0.91), respectively. The overall accuracy of the N/L ratio in determination of FMF patients during attack was 71%. Our results demonstrate that N/L ratio is higher in patients with active FMF compared with FMF patients in remission and controls, and a cut-off value of 2.63 can be used to identify patients with active FMF. © 2014 Wiley Periodicals, Inc.

  1. Familial Mediterranean fever in childhood: a single-center experience.

    PubMed

    Barut, Kenan; Sahin, Sezgin; Adrovic, Amra; Sinoplu, Ada Bulut; Yucel, Gozde; Pamuk, Gizem; Aydın, Aslı Kirectepe; Dasdemir, Selcuk; Turanlı, Eda Tahir; Buyru, Nur; Kasapcopur, Ozgur

    2017-08-21

    The aim of this study is to present demographic and clinical features, MEFV mutation variations, and treatment response of a large number of pediatric familial Mediterranean fever (FMF) patients from a single tertiary centre. Moreover, we aimed to investigate the current outcome of FMF, namely frequency of amyloidosis in children with FMF. We evaluated 708 FMF patients who were followed up in our clinic and who were under colchicine treatment for at least 6 months. The data were recorded from patient records and also verified by negotiations with patients and parents. The male/female proportion of the cohort was 1.05/1 (n = 362/346). Abdominal pain (89.5%, n = 634) was the most common manifestation of FMF episodes, followed by fever (88.8%, n = 629) and arthritis (40.7%, n = 288). However, arthritis in 23 (8%) of the 288 cases was not self-limited; and they subsequently diagnosed with juvenile idiopathic arthritis in addition to FMF. Homozygote or heterozygote M694V mutation was more frequent in patients with arthritis (63.2%) and chronic arthritis (69.6%) than the whole cohort (53.8%). Erythrocyte sedimentation rate and CRP level were in high levels even during attack-free period in 13.9% (n = 97/697) and 11% (n = 78/670) of the patients, respectively. Proteinuria was found in ten patients (1.4%). Amyloidosis was confirmed by renal biopsy in only two of these cases who were homozygous for M694V and compound heterozygous for M694V/M680I. 47 (6.6%) subjects were considered as colchicine resistant. Homozygote M694V mutation was the most frequent mutation in those resistant cases (63.8%, n = 30), followed by compound heterozygote mutation of M694V/M680I (6.3%, n = 3). Homozygous M694V mutation are still the most frequent mutation and associated with the most severe clinical picture and the worst outcome in Turkish children. M694V genotype seems to be more frequently associated with arthritis as well as with chronic arthritis than other genotypes

  2. Plasma ghrelin levels in patients with Familial Mediterranean Fever.

    PubMed

    Keskin, Göksal; Inal, Ali; Ilikçi, Rahşan; Baysal, Ozan

    2009-01-01

    Familial mediterranean fever (FMF) is a familial disease characterized by recurrent episodes of febrile serositis, peritonitis, arthritis and pleuritis. Many studies have been performed is an attempt to understand the basis of the inflammatory attacts in FMF. Ghrelin, a recently described orexigene peptide is predominantly produced by stomach. Ghrelin also exerts multiple regulatory effects on immune system. It has reported that grelin has anti-inflammatory effects. There is currently no published evidence demonstrating a role for anti-inflammatory effects of ghrelin in FMF. For this reason, we investigated the role of plasma ghrelin levels in patients with FMF. Thirty seven patients with FMF and 10 healthy controls (5 female, 5 male; mean age 35.4 +/- 5.6 years) were enrolled in this study. Twenty-one patients were in active stage (10 female, 11 male, mean age; 31.0 +/- 5.4 years, mean disease duration 7.2 +/- 3.3 years) and 16 patients were in inactive stage (7 female,9 male, mean age; 33.0 +/- 6.0 years, mean disease duration; 8.7 +/- 3.2 years). Plasma ghrelin levels were determined by EIA. The mean plasma ghrelin levels were 158.4 +/- 52.9 pg/ml in patients with FMF and 56.7 +/- 7.5 pg/ml in healthy controls. The mean plasma ghrelin levels were 190.5 +/- 49.4 pg/ml in the active patients and 116.2 +/- 11.7 pg/ml in the inactive patients. Plasma ghrelin levels were significantly high in patients with FMF compared to healthy controls (p<0.001). Plasma ghrelin levels were significantly high in the active patients compared to in the inactive patients and healthy controls (p<0.001 and p<0.001 respectively). There was significantly difference between in active and inactive patients with FMF (p<0.001). As a results; Plasma ghrelin levels were high both in active and inactive patients with FMF. It is showed that ghrelin may play significant role of the pathogenesis of FMF.

  3. The myths we believed in familial Mediterranean fever: what have we learned in the past years?

    PubMed

    Ozen, Seza; Batu, Ezgi Deniz

    2015-07-01

    Familial Mediterranean fever is the most common monogenic periodic fever syndrome over the world especially in the eastern Mediterranean. It presents with recurrent and self-limited inflammatory attacks of fever and polyserositis along with high acute-phase reactants. The disease is associated with mutations in the MEFV gene that encodes pyrin, a component of inflammasome, which leads to exaggerated inflammatory response through uncontrolled production of interleukin 1. With the identification of the gene associated with the disease, we believed that everything was solved and that this was an ordinary monogenic disease with autosomal recessive inheritance. However, through the breathtaking progress in the basic research field as well as the clinical care of these patients, we have understood that the picture for this monogenic disorder was more complicated than we had anticipated. In this review, we have discussed the myths we believed in familial Mediterranean fever and how they have evolved during the past years.

  4. Protracted febrile myalgia syndrome in a kidney transplant recipient with familial Mediterranean fever.

    PubMed

    Abdel Halim, Medhat M; Al-Otaibi, Torki; Donia, Farouk; Gheith, Osama; Asif, Ponnambath; Nawas, Moideen; Rashad, Rashad H; Said, Tarek; Nair, Prasad; Nampoory, Narayanan

    2015-04-01

    Drug-induced toxic myopathy is a complication of familial Mediterranean fever in patients who receive colchicine, especially when combined with cyclosporine. Protracted febrile myalgia syndrome is a severe form of familial Mediterranean fever. A 34-year-old man who had familial Mediterranean fever for > 15 years developed kidney failure because of secondary amyloidosis. He received living-unrelated-donor kidney transplant that functioned normally. He was on colchicine prophylaxis that was continued after transplant, and he received immuno-suppression induction with antithymocyte globulin and maintenance with prednisolone, mycophenolate mofetil, and cyclosporine. After 2 months, he presented with severe myopathy and elevated creatine kinase. Muscle biopsy showed evidence of drug-induced toxic myopathy, most likely caused by cyclosporine in combination with colchicine. Cyclosporine was replaced with sirolimus and colchicine was stopped. Symptoms partially improved and creatine kinase decreased to normal. The prednisolone dosage was reduced gradually to 5 mg daily. At 8 months after transplant, he was readmitted because of severe arthralgia, prolonged fever, pleuritic chest pain, diffuse abdominal pain, purpuric rash, macroscopic hematuria, proteinuria, and diarrhea. The C-reactive protein and erythrocyte sedimentation rate were elevated. The clinical diagnosis was recurrent familial Mediterranean fever presenting as protracted febrile myalgia syndrome. Despite the history of toxic myopathy, he was restarted on colchicine (0.5 mg, twice daily), and colchicine was well tolerated. There was marked improvement of most symptoms within several days. Follow-up 5 years later showed normal kidney graft function and no familial Mediterranean fever activity on colchicine prophylaxis. In summary, familial Mediterranean fever reactivation and protracted febrile myalgia syndrome after kidney transplant may be treated with colchicine and modulation of immunosuppressive therapy.

  5. Sacroiliitis and Polyarteritis Nodosa in a Patient with Familial Mediterranean Fever

    PubMed Central

    Ugan, Yunus; Doğru, Atalay; Şencan, Hüseyin; Şahin, Mehmet; Ercan Tunç, Şevket

    2016-01-01

    Familial Mediterranean fever (FMF) is an autoinflammatory disorder with autosomal recessive inheritance, characterized by recurrent fever and episodes of serositis. The condition is known to be caused by mutations in the MEFV (Mediterranean FeVer) gene, located in the short arm of chromosome 16. While more than 310 sequence variants in the MEFV gene have been described to date, the diagnosis is still established clinically. FMF may be accompanied by sacroiliitis and various forms of vasculitis. The most common forms of associated vasculitis are Henoch-Schonlein purpura and polyarteritis nodosa (PAN). We have presented here a fairly rare case of FMF, accompanied by both sacroiliitis and PAN. PMID:27143975

  6. Bone mineral density in children with familial Mediterranean fever.

    PubMed

    Duzova, Ali; Ozaltin, Fatih; Ozon, Alev; Besbas, Nesrin; Topaloglu, Rezan; Ozen, S; Bakkaloglu, A

    2004-06-01

    The aim of this study was to evaluate bone mineral content (BMC), serum and urinary bone turnover parameters in patients with familial Mediterranean fever (FMF), an autosomal recessive disease characterized by recurrent episodes of inflammation of serous membranes. Demographic characteristics and MEFV mutations were defined in 48 children diagnosed with FMF (23 F, 25 M; median age 7.0 years (3.0-10.0)). We evaluated the blood counts, acute-phase proteins and serum and urinary bone turnover parameters during attack-free periods. The BMC and BA (bone area) of vertebrae L1-L4 were measured by DEXA. Thirty-eight age-, sex- and ethnicity-matched healthy children constituted the control group. Mean L1-L4 BMC in Group I (patients with two mutations) and II (patients with no or single mutations) were 15.49+/-5.99 g and 15.68+/-4.89 g, respectively, both significantly lower than the mean L1-L4 BMC of control patients, which was 19.59+/-6.7 g (p<0.05). Mean L1-L4 BMD in Group I, Group II and the control group were 0.466+/-0.066 g/cm(2), 0.487+/-0.085 g/cm(2 )and 0.513+/-0.079 g/cm(2), respectively. Mean z-scores in Group I, Group II and the control group were -1.87+/-0.74, -1.55+/-0.92 and -1.39+/-0.84, respectively. Mean L1-L4 BMD and z-score of Group I were lower than in the control group (p<0.05). ESR and SAA (serum amyloid A) levels were higher in Group I patients: 28.3+/-14.5 mm/h and 350+/-62 mg/l in Group I; and 20.5+/-11.7 mm/h and 190+/-68 mg/l in Group II, respectively. In conclusion, FMF patients had lower BMC, BMD and z-scores than a control group. We suggest that decreased BMD, BMC and z-score in FMF patients may be secondary to subclinical inflammation.

  7. Cochlear involvement in Familial Mediterranean Fever: a new feature of an old disease.

    PubMed

    Koybasi, Serap; Atasoy, Halil İbrahim; Bicer, Yusuf Ozgur; Tug, Esra

    2012-02-01

    In this study we first aimed to assess the cochlear functions in children with Familial Mediterranean Fever. The second aim was to investigate the correlation between the hearing levels and some clinical features of Familial Mediterranean Fever including the duration of the disease, age at onset, genetic analysis and colchicine use. Thirty-four children with Familial Mediterranean Fever and 27 age matched children were included in the study. Following otologic examination, all children underwent audiometric evaluation, including Pure Tone Average measurements and Distortion Product Otoaoustic Emission testing. Audiological results of the two groups were compared and correlation between the audiologic status and clinical parameters of the disease like the duration of disease, age at onset, mutations and colchicine treatment were studied. Pure tone audiometry hearing levels were within normal levels in both groups. Hearing thresholds of Familial Mediterranean Fever patients were found to be increased at frequencies 8000, 10,000, 12,500 and 16,000 (p<0.05). In otoacoustic emission evaluation, distortion products and signal-noise ratio of FMF children were lower in the tested frequencies, from 1400 Hz to 4000 Hz (p<0.05). Interaction of the disease duration and age of disease onset was found to predict hearing levels, distortion products and signal-noise ratios of children with Familial Mediterranean Fever (F value=2.034; p=0.033). To our knowledge this is the first study demonstrating cochlear involvement in children with Familial Mediterranean Fever which showed increased hearing thresholds at higher frequencies in audiometry together with decreased distortion products and signal-noise ratios demonstrated by distortion product otoacoustic emission testing. Similar studies must be carried out on adult patients to see if a clinical hearing impairment develops. The possible mechanisms that cause cochlear involvement and the effect of colchicine treatment on cochlear

  8. Infections After Renal Transplant in Recipients With Familial Mediterranean Fever: A Life-Threatening Issue.

    PubMed

    Tatar, Erhan; Karatas, Murat; Aykas, Ahmet; Okut, Gokalp; Bozkaya, Giray; Uslu, Adam

    2017-02-01

    We evaluated long-term results and infections requiring hospitalization in kidney transplant patients with Familial Mediterranean Fever (associated amyloidosis-type). We retrospectively reviewed medical records of patients with familial Mediterranean fever with at least 1-year posttransplant follow-up. Kidney transplant recipients with primary glomerulonephritis and equivalent demography, immunity status, and follow-up comprised the control group. In 32 patients with familial Mediterranean fever versus 25 control patients (mean follow-up 82 ± 57 vs 79 ± 54 mo; P = .82), average serum creatinine values were 1.7 ± 0.9 versus 1.5 ± 1.0 mg/dL (P = .41) at discharge, 1.4 ± 0.4 versus 1.3 ± 0.5 mg/dL (P = .44) at 1 year, 1.4 ± 0.6 versus 1.3 ± 0.5 mg/dL (P = .63) at 3 years, and 2.0 ± 1.5 versus 2.1 ± 1.5 mg/dL (P = .92) at last follow-up. Groups were not statistically different regarding average inpatient and number of hospitalizations due to infections at 1 year; however, at last follow-up, 26 patients with familial Mediterranean fever (81%) had 8.6 average admissions and 13 control patients (52%) had 2.8 average admissions (P = .02, P < .01). Early posttransplant, both groups were taking a triple drug immunosuppression regimen. However, at 1 and 3 years posttransplant, withdrawal and/or minimization occurred in 40.6% and 83.3% of patients with familial Mediterranean fever and 28% and 55.5% of control patients (P < .05, P < .05). During follow-up, 6 familial Mediterranean fever patients (18.7%) and 2 control patients (8%) died (P = .23). Although renal transplant patients with associated amyloidosis-type familial Mediterranean fever and those with glomerulonephritis have similar rejection and/or graft loss rates, hospital admissions due to infection and increased mortality are more common in the familial Mediterranean fever group, with immunosuppression drug withdrawal.

  9. Anakinra use during pregnancy: Report of a case with Familial Mediterranean Fever and infertility

    PubMed Central

    İlgen, Ufuk; Küçükşahin, Orhan

    2017-01-01

    Familial Mediterranean fever (FMF), affecting people of Mediterranean origin, is an endemic and sometimes problematic disease because of colchicine resistance/intolerance, with relative lack of treatment alternatives, and disease- or treatment-related issues, such as subfertility. Anakinra, being a rational and effective treatment alternative, has no conclusive human pregnancy data. Here we report a case of FMF with infertility who became pregnant with in vitro fertilization (IVF) under treatment with anakinra, along with the pregnancy outcome. PMID:28293457

  10. Canakinumab treatment in four children with colchicine resistant familial mediterranean fever.

    PubMed

    Ozkan, Solmaz; Atas, Bulent

    2017-06-01

    Familial Mediterranean Fever (FMF) is an autosomal recessive and autoinflammatory disease, characterized with inflammation of serous membranes such as peritoneum, pleura, synovium with fever and pain. Colchicine is the main treatment of FMF, but 5-10 % of patients are unresponsive to colchicine. We report using anti-interleukin-1 agents anakinra and canakinumab in four colchicine-resistant patients who were successfully treated. Three of the patients were siblings.

  11. [Familial Mediterranean fever in Mexico City. A 20-year follow-up].

    PubMed

    Halabe-Cherem, José; Pérez-Jiménez, Carolina; Nellen-Hummel, Haiko; Mercado-Atri, Moisés; Sigala-Rodríguez, Carolina; Castañón-González, Jorge

    2004-01-01

    Familial Mediterranean fever (MFF) is an autosomic recessive, inherited inflammatory disease principally seen in persons from the Mediterranean area. Clinical findings include fever, abdominal pain, and pleuritis. The most severe complication of MFF is renal amyloidosis, manifested as nephrotic syndrome, which evolves into chronic renal failure. In this study, we described clinical findings, evolution, and response to treatment in 52 patients diagnosed with MFF living in Mexico City in whom the most important clinical features were fever and abdominal pain. Differing from previous reported series of patients from the Mediterranean area, patient developed renal amyloidosis during the 20-year follow-up, which suggests that an environmental factor might have a significant influence in development of renal amyloidosis.

  12. Colchicine treatment in children with familial Mediterranean fever: is it a risk factor for neuromyopathy?

    PubMed

    Işıkay, Sedat; Yılmaz, Kutluhan; Yiğiter, Remzi; Balat, Ayşe; Büyükçelik, Mithat

    2013-12-01

    We cared for a 17-year-old adolescent with familial Mediterranean fever under colchicine treatment. Because of the increased creatinine kinase level (3937 U/L) observed in this individual, we planned to assess all pediatric patients with familial Mediterranean fever under colchicine treatment to detect any resultant neuromyopathy. The study included 88 children with familial Mediterranean fever who were receiving colchicine. The patient with myopathy was not included in the study. Serum creatinine kinase levels were measured and nerve conduction studies were carried out in all patients. The study included 88 patients (47 female, 53.4%) with an average age of 10.1 ± 3.35 years. The average period of colchicine use was 28.25 ± 17.66 months. Side effects of colchicine were detected in 10 patients (11%)--as diarrhea in eight patients, leukopenia in one patient, and hair loss in one patient. Nerve conduction studies determined incidental carpal tunnel syndrome in only one patient. Our study did not suggest an elevated risk of neuromyopathy associated with the use of colchicine for familial Mediterranean fever. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  13. Goats, germs, and fever: Are the pyrin mutations responsible for familial Mediterranean fever protective against Brucellosis?

    PubMed

    Ross, John J

    2007-01-01

    Mutations in the MEFV gene are highly prevalent in the Middle East and Mediterranean basin, with carrier rates of up to 1:3 in some populations. More than 50 mutations in the MEFV gene have been described. The high prevalence, multiple mutations, and geographic localization to the Middle East suggest a positive selection advantage for the abnormal gene operating in this area over the last several thousand years. To date, no satisfactory explanation of this phenomenon has been made. Rather, many harmful effects of these mutations have been described. MEFV gene mutations cause familial Mediterranean fever in homozygotes, a disease associated with recurrent febrile inflammatory episodes, and death from renal failure and amyloidosis. Heterozygotes with MEFV mutations are predisposed to premature coronary disease, and rheumatologic conditions such as Behçet's disease. MEFV mutations do not appear to protect against tuberculosis. Brucellosis is still highly endemic in the Middle East because of the traditional reliance for meat and dairy production on goats and sheep, the major vectors for this zoonosis. Brucellosis causes a prolonged febrile illness lasting for months and even years, and it may have exacted a major toll among Bronze Age peasant populations in the Middle East. The gene product for MEFV, pyrin, normally inhibits interleukin-1beta production. Mutations in MEFV result in a pro-inflammatory state, with a Th1 polarization and high levels of interferon-gamma. This may actually be protective against intracellular pathogens such as brucellosis. The possible heterozygote advantage of MEFV mutations against brucellosis may therefore be a balanced polymorphism, analogous to the protective effect against malaria that maintains high levels of sickle cell trait in sub-Saharan Africa.

  14. Myositis in a patient with familial Mediterranean fever and spondyloarthritis successfully treated with anakinra.

    PubMed

    Estublier, Charline; Stankovic Stojanovic, Katia; Bergerot, Jean-François; Broussolle, Christiane; Sève, Pascal

    2013-12-01

    Familial Mediterranean fever is an autosomal-recessive autoinflammatory disorder more commonly observed in Mediterranean populations and characterized by recurrent episodes of fever, serositis, myalgia and arthritis. There is rarely any association with spondyloarthritis. The most important long-term complication is progressive systemic type AA amyloidosis. Treatment with colchicine is effective in reducing the frequency of attacks and prevents the development of amyloidosis. However, 5% of cases are considered resistant to colchicine. We here describe the case of a 39-year-old man, with a history of arthritis, arthralgias, and sacroiliitis in the course of a familial Mediterranean fever. He is homozygous for the M694I mutation in the MEFV gene. He subsequently developed myositis of the right quadriceps muscle confirmed by magnetic resonance imaging, electromyography and histology. He had frequent and severe arthralgias, despite colchicine, then etanercept and adalimumab, impairing his quality of life. The patient was successfully treated with the IL-1 receptor antagonist anakinra with a dramatic improvement of muscular and articular symptoms. To our knowledge, our patient is the first patient with coexisting FMF, spondyloarthritis and myositis responding to anakinra treatment. Moreover this is the second case in the literature of myositis associated with familial Mediterranean fever. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  15. Guidelines for the management and treatment of periodic fever syndromes familial Mediterranean fever.

    PubMed

    Terreri, Maria Teresa R A; Bernardo, Wanderley Marques; Len, Claudio Arnaldo; da Silva, Clovis Artur Almeida; de Magalhães, Cristina Medeiros Ribeiro; Sacchetti, Silvana B; Ferriani, Virgínia Paes Leme; Piotto, Daniela Gerent Petry; de Souza Cavalcanti, André; de Moraes, Ana Júlia Pantoja; Sztajnbok, Flavio Roberto; de Oliveira, Sheila Knupp Feitosa; Campos, Lucia Maria Arruda; Bandeira, Marcia; Santos, Flávia Patricia Sena Teixeira; Magalhães, Claudia Saad

    2016-01-01

    To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints. 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene. 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment. 4. The therapy of choice is colchicine; this drug has proven its effectiveness in preventing acute inflammatory episodes and progression toward amyloidosis in adults. 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  16. Familial Mediterranean fever gene as a possible modifier of Sweet syndrome with chronic myelogenous leukemia.

    PubMed

    Miyoshi, Takashi; Yamashita, Kouhei; Ohno, Tatsuharu; Izumi, Taisuke; Takaori-Kondo, Akifumi; Sasada, Masataka; Uchiyama, Takashi

    2008-01-01

    Sweet syndrome is a multisystem inflammatory disorder characterized by acute fever, as well as painful erythematous plaques infiltrated with mature neutrophils in the absence of vasculitis. The pathogenesis of the disease has not yet been clarified, although several proinflammatory cytokines have been reported to be involved in the disease process. We describe here a patient clinically diagnosed with Sweet syndrome with chronic myelogenous leukemia. The mutational analysis of the patient revealed a compound heterozygous E148Q/R202Q mutation in exon 2 of MEFV gene, which is a causative gene for familial Mediterranean fever. This is the first report to describe MEFV gene mutations in Sweet syndrome. Our results suggest that Sweet syndrome may be mediated though similar inflammatory mechanisms to those of familial Mediterranean fever. Copyright 2008 S. Karger AG, Basel.

  17. [Heterozygote forms of familial Mediterranean fever can be manifested in adults as myofacial pain syndrome].

    PubMed

    Meilinger, A; Burger, M; Peter, H-H

    2015-08-01

    Familial Mediterranean fever (FMF) is a disease characterized by recurrent fever, serositis, arthritis and unspecific myalgia. It is prevalent among Mediterranean people and has been shown to be associated with mutations in the Mediterranean fever (MEFV) gene which, encodes pyrin a regulatory protein of the inflammasome. As heterozygous mutations in MEFV can be associated with only mild inflammatory symptoms, such as arthralgia or chronic fibromyalgic pain, FMF may be underdiagnosed in the current diagnostic work-up of musculoskeletal diseases. The selection of patients was carried out according to the following criteria: myofacial pain syndrome, seronegative oligoarthralgia, a slight inflammatory constellation and ethnic origin from the Mediterranean area. When these criteria were fulfilled a molecular genetic investigation was carried out This article presents evidence that 9 out of 12 Mediterranean patients with recurrent myofascial pain syndrome and mild inflammation revealed heterozygote mutations in the MEFV gene and 7 of these patients benefitted from treatment with colchicine. As colchicine treatment not only improved the myofascial pain but also prevented FMF-associated amyloidosis and nephropathy, differential diagnosis of fibromyalgia in patients of Mediterranean origin should include FMF and a genetic screening of the MEFV locus.

  18. Familial Mediterranean fever in two Bedouin families: mutation analysis and disease severity.

    PubMed

    Press, J; Shinar, Y; Langevitz, P; Livneh, A; Pras, M; Buskila, D

    2000-06-05

    Familial Mediterranean fever (FMF) is an autosomal recessive disease prevalent among non-Ashkenazi Jews, Armenians, Arabs, and Turks. The Bedouin are nomad Arab tribes residing in desert margins of the Middle East and Arabia. FMF is quite rare in Bedouins, and here we report on two Bedouin families from southern Israel suffering from this disorder. The MEFV mutations found in the Bedouin patients M694I, V726A, and E148Q are consistent with their Arab origin. The disease severity score showed a mild to moderate severity disease in six patients. The Bedouins, leading a unique nomadic life, may prove instrumental in unraveling the role of environmental factors in the course and severity of FMF.

  19. A case of familial Mediterranean fever who complained of periodic fever and abdominal pain diagnosed by MEFV gene analysis.

    PubMed

    Ogita, Chie; Matsui, Kiyoshi; Kisida, Dai; Kakudou, Mariko; Yazaki, Masahide; Nakamura, Akinori; Azuma, Kouta; Tsuboi, Kazuyuki; Abe, Takeo; Yokoyama, Yuichi; Furukawa, Tetsuya; Maruoka, Momo; Tamura, Masao; Yoshikawa, Takahiro; Saito, Atsushi; Nishioka, Aki; Sekiguchi, Masahiro; Azuma, Naoto; Kitano, Masayasu; Tsunoda, Shinichiro; Hashimoto-Tamaoki, Tomoko; Sano, Hajime

    2016-01-01

      Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease caused by Mediterranean FeVergene (MEFV) mutations on Chromosome 16, and characterized by periodic fever of and serositis. FMF is the result of gain-of-function mutations in pyrin that lead to interleukin-1β activation. FMF can be classified as "typical" and "atypical" types based on clinical finding and genetic screening. Although MEFV genotyping has enabled FMF to be confirmed in some cases, the diagnosis remains predominantly clinical since genotyping has shown that the disease is characterized by variable manifestations in Japanese. In 1976, the first report performed on the case of Japanese FMF with periodic fever of and serositis. Since 2002, genetic analyses are performed on Japanese FMF patients by K. Shiozaki et al. and N. Tomiyama et al. In our case, she was a 25-year-old Japanese woman with at periodic fever and abdominal pain. MEFV gene analysis demonstrated a heterozygous mutation of variant M694I, leading to a diagnosis of FMF. After the increase dose (up to 3 mg/day) of colchicine, periodic fever and abdominal pain disappeared. It is the important candidate of FMF for differential diagnosis with unexplained periodic fever and serositis, such as our case.

  20. Fever of unknown origin in the outpatient setting: A retrospective analysis of 30 cases of familial Mediterranean fever.

    PubMed

    Kunimatsu, Junwa; Maeda, Junko; Watanabe, Riri; Kato, On; Kishida, Dai; Yazaki, Masahide; Nakamura, Akinori

    2016-01-01

    In Japan, familial Mediterranean fever (FMF) is a rare cause of fever of unknown origin (FUO). However, we experienced an extraordinary number of FMF cases over 3 years. This suggests that many patients with FMF remain misdiagnosed in Japan. This study examines the clinical picture of FMF to assist Japanese clinicians in daily practice dealing with FUO. Three years of medical records were reviewed, and 38 patients with FMF or suspected FMF were collected from our patient database. We applied the Tel-Hashomer criteria to those patients. Of the 38 patients, 30 were classified as having FMF in this investigation. The mean patient age was 27.8 years. MEFV gene mutations were detected in 14 patients. Three cases were colchicine-resistant. Clinicians should recognize the pattern of short, spontaneously resolving attacks of fever with fever-free intervals, especially when they see patients with recurrent FUO in the outpatient setting.

  1. Living kidney transplantation between brothers with unrecognized renal amyloidosis as the first manifestation of familial Mediterranean fever: a case report.

    PubMed

    Peces, Ramón; Afonso, Sara; Peces, Carlos; Nevado, Julián; Selgas, Rafael

    2017-08-31

    Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent episodes of fever and polyserositis and by the onset of reactive amyloid-associated amyloidosis. Amyloidosis due to familial Mediterranean fever can lead to end-stage renal disease, culminating in kidney transplantation for some patients. In this study, we report the clinical outcome of two brothers with familial Mediterranean fever who were the inadvertent donor and recipient, respectively, of a kidney. Subsequently, they were diagnosed with renal amyloidosis secondary to familial Mediterranean fever and were successfully treated with anakinra and colchicine. Two brothers with familial Mediterranean fever and renal amyloidosis were the inadvertent donor and recipient, respectively, of a kidney. The recipient had presented recurrent acute febrile episodes of familial Mediterranean fever, developed nephrotic syndrome secondary to amyloidosis and needed bilateral nephrectomy and chronic dialysis. His elder brother, in apparent good health, donated his left kidney to his brother. Immediately after the kidney transplantation, both the donor and recipient presented massive proteinuria, impaired renal function and elevated serum amyloid A levels. Biopsies of the brothers' kidneys showed amyloidosis. Genetic studies thereafter revealed a homozygous variant for the MEFV gene (NM_000243.2.c.2082G > A; p.M694I) in both brothers. At this point, both the donor and recipient were treated with colchicine and anakinra, resulting in improved renal function, decreased proteinuria, undetectable serum amyloid A levels and stable renal function at 62 months of follow-up and no major adverse effects. In familial Mediterranean fever, analyses of the MEFV gene should be performed in potential live kidney donors from a direct family member (either between siblings or between parents and children). In addition, genetic studies are required when consanguinity is suspected between members involved in

  2. Diffuse and multifocal nephrogenic adenoma with Familial Mediterranean Fever: a case report with molecular study.

    PubMed

    Ishikawa, Noriyoshi; Amano, Chika; Taketani, Takeshi; Kumori, Koji; Harada, Yuji; Hiraiwa, Hisayuki; Itamura, Kayoko; Maruyama, Riruke

    2015-07-16

    Nephrogenic adenoma, also referred to nephrogenic metaplasia, is a benign proliferative lesion of urothelium, usually associated with chronic physical stimuli or inflammation. Familial Mediterranean fever is an inherited autosomal recessive disease characterized by recurrent short episodes of fever. The site of mutation is found in MEFV gene which controls inflammatory responses. We have experienced a case of nephrogenic adenoma in a 16-year-old girl with Familial Mediterranean Fever, showing proliferative lesions diffusely in the urinary bladder and multifocally in the other parts of urinary tract. These lesions disappeared after colchicine treatment. We searched for MEFV gene mutation using the specimen from the resected urinary bladder and detected heterozygous mutation of E148Q. There is a possibility that control of inflammation caused by the surgery for vesicoureteral reflux in the local site didn't work well on the background of heterozygous mutation of MEFV gene, and as a result, nephrogenic adenoma appeared. This is the first report of a combination of two rare diseases. We have to be aware that nephrogenic adenoma can occur in association with Familial Mediterranean Fever, and the former condition should be taken into consideration when rendering a correct pathological diagnosis.

  3. PFAPA syndrome mimicking familial Mediterranean fever: report of a Turkish child.

    PubMed

    Ataş, Bülent; Caksen, Hüseyin; Arslan, Sükrü; Tuncer, Oğuz; Kirimi, Ercan; Odabaş, Dursun

    2003-11-01

    The PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitidis) syndrome is characterized by periodic fever, adenitis, pharyngitis, and aphthous stomatitis. Herein, we present a Turkish child with PFAPA syndrome mimicking familial Mediterranean fever because of a rare presentation. A 9-year-old boy was admitted with recurrent fever, aphthous stomatitis, sore throat, headache, and general body pains, lasting 2 to 3 days since 3.5 years of age. He was completely symptom-free between the attacks. He was diagnosed as having familial Mediterranean fever according to the clinical findings when he was 6 years of age and Colchicum tablet was administrated. Despite colchicines therapy for 8 months, his attacks did not subside; therefore, the drug was discontinued. He had high fever, a painful cervical lymphadenopathy, aphthous stomatitis, and tonsillo-pharyngitis. The patient was then diagnosed as having PFAPA syndrome. He was given a single dose of prednisolone (0.35 mg/kg/dose). His complaints dramatically and completely disappeared 3 h after administration of the drug. During the 8th month of follow-up, a similar febrile attack lasting only 1 day was noted and it was controlled with a single dose of prednisolone (0.5 mg/kg/day). At this writing the patient is in the 12th month of follow-up, and there have been no symptoms after the second attack. In conclusion, our patient shows that PFAPA syndrome can be confused with familial Mediterranean fever. We also would like to emphasize that the typical PFAPA syndrome can be easily diagnosed by detailed history-taking and physical findings.

  4. Brain stem infarction associated with familial Mediterranean fever and central nervous system vasculitis.

    PubMed

    Luger, Sebastian; Harter, Patrick N; Mittelbronn, Michel; Wagner, Marlies; Foerch, Christian

    2013-01-01

    Familial Mediterranean fever (FMF) is an autoinflammatory autosomal recessive disease caused by mutations of the Mediterranean fever (MEFV) gene on chromosome 16p. Clinically, it is characterized by recurrent episodes of fever and painful polyserositis. An association of FMF with systemic vasculitis, namely Henoch-Schönlein purpura, polyarteritis nodosa and Behçet's disease has been described. Neurological manifestations of FMF occur rarely and include demyelinating (MS-like) lesions, posterior reversible encephalopathy syndrome, and pseudotumour cerebri. Hitherto hardly known, we herein present a young patient with a genetically proven FMF who suffered a brain stem infarction during a typical FMF attack. After a careful diagnostic workup including cerebrospinal fluid analysis, intra-arterial angiography and leptomeningeal biopsy, a FMF-associated central nervous system vasculitis was identified as the cause of stroke. The pathophysiological background and potential therapeutic strategies are discussed.

  5. Pregnancy outcome of five patients with renal amyloidosis regarding familial Mediterranean fever.

    PubMed

    Turgal, Mert; Selcuk, Ilker; Ozyuncu, Ozgur

    2014-03-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease affecting mainly patients of the Mediterranean basin and its major complication is the development of renal AA amyloidosis. On the other hand pregnancy with amyloidosis is not common; nevertheless, amyloidosis will complicate pregnancies also with the underlying disease and may cause terrible perinatal morbidities and mortalities. We report here the cases of five pregnant women and their pregnancy outcomes, who have been diagnosed with FMF complicated by renal amyloidosis. In the five cases, we observed that increased pregnancy complication such as small for gestational age, intrauterine growth restriction, preeclampsia and preterm birth.

  6. Rheumatoid Arthritis and Familial Mediterranean Fever or Sacroiliitis Accompanied by FMF.

    PubMed

    Sahin, Ali; Yetişgin, Alparslan; Sahin, Mehtap

    2013-01-01

    The coexistence of rheumatoid arthritis (RA) and familial Mediterranean fever (FMF) has been rarely seen in case reports in the literature. Herein, we wanted to present a patient who had been followed up and treated as RA, but on investigation we concluded that he really had FMF and its joint complaints associated with sacroiliitis. Recovery was achieved by etanercept administered as if he was an RA patient.

  7. Efficacy of anakinra treatment in a patient with colchicine-resistant familial Mediterranean fever.

    PubMed

    Alpay, Nilüfer; Sumnu, Abdullah; Calışkan, Yaşar; Yazıcı, Halil; Türkmen, Aydın; Gül, Ahmet

    2012-10-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limited recurrent attacks of fever and serositis. The serious complication of FMF is AA-type amyloidosis, which can result in end-stage renal disease. Although colchicine is effective in the majority of patients, there is no established treatment for those who are resistant or intolerant to colchicine. We herein report the efficacy of anakinra in a 52-year-old Turkish patient with FMF, secondary amyloidosis and renal transplant, who was resistant to colchicine treatment.

  8. Novel therapeutics for the treatment of familial Mediterranean fever: from colchicine to biologics.

    PubMed

    Grattagliano, I; Bonfrate, L; Ruggiero, V; Scaccianoce, G; Palasciano, G; Portincasa, P

    2014-01-01

    Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is characterized by sporadic, paroxysmal attacks of fever and serosal inflammation, lasting 1-3 days. Patients may develop renal amyloidosis, arthritis, serositis, and skin and oral lesions. Diagnosis is based on clinical features, response to treatment with colchicine, and genetic analysis. Colchicine prevents attacks and renal amyloidosis, in addition to reversing proteinuria. Nonresponders may receive novel therapy, including interleukin (IL)-1 receptor antagonists and IL-1 decoy receptor. Recently, new options have been considered.

  9. Psoriasis-like lesions in a patient with familial Mediterranean fever.

    PubMed

    Ashida, Miwa; Koike, Yuta; Kuwatsuka, Sayaka; Ichinose, Kunihiro; Migita, Kiyoshi; Sano, Shigetoshi; Utani, Atsushi

    2016-03-01

    Familial Mediterranean fever (FMF) is a rare hereditary autoinflammatory disorder that is caused by pyrin gene mutation associated with aberrance of the interleukin (IL)-1β pathway and characterized by recurrent, self-limiting attacks of fever and other inflammatory symptoms. We report a case of FMF with annular erythema and psoriasis-like lesions, the latter of which demonstrated parakeratosis with neutrophil microabscesses and mild inflammatory mononuclear cell infiltration in the upper dermis. Immunofluorescence staining showed IL-17-positive T-cells. Skin eruption with neutrophil migration in the epidermis may be provoked by T-helper 17 cell activation through the abnormal IL-1β cascade in FMF.

  10. Serum lipid changes and insulin resistance in familial Mediterranean fever

    PubMed Central

    Candan, Zehra; Akdoğan, Ali; Karadağ, Ömer; Kalyoncu, Umut; Şahin, Abdurrahman; Bilgen, Şule; Çalgüneri, Meral; Kiraz, Sedat; Ertenli, Ali

    2014-01-01

    Objective Inflammation is known to alter lipid profiles and to induce insulin resistance. This study was planned to test the hypothesis that familial Mediterranean ferver (FMF) patients and their first-degree asymptomatic relatives may have lipid profile changes and/or insulin resistance, similar to other inflammatory diseases. Material and Methods We studied 72 FMF patients, 30 asymptomatic first-degree relatives, and 75 healthy controls. Fasting and 2-hour postprandial glucose, insulin, apolipoprotein (Apo) A1, Apo B, acute phase reactants, and lipid profiles of all subjects were studied. Insulin resistance was determined by the HOMA (Homeostasis Model Assessment) index. Results There was no difference between the groups with regard to sex, mean systolic and diastolic blood pressure, body mass index, smoking status, fasting and postprandial 2-hour glucose, insulin, acute phase reactants, and HOMA index levels. High-density lipoprotein cholesterol (HDL-C) levels were similar between FMF patients and FMF relatives (48.9±12.4 mg/dL vs 49.3±13.8 mg/dL; p=NS), and both were lower than controls (48.9±12.4 mg/dL vs 59.6±15.1 mg/dL; p<0.001 and 49.3±13.8 mg/dL vs 59.8±15.1 mg/dL; p=0.001, respectively). Apo A1 levels in FMF patients and asymptomatic first-degree FMF relatives were both lower than in controls, similar to the HDL-C levels (126.1±25.7 mg/dL vs 151.2±31.4 mg/dL; p<0.001 and 129.5±29.0 mg/dL vs 151.2±31.4 mg/dL; p=0.002, respectively). TG levels were significantly higher in FMF relatives as compared to controls (113.4±53.6 mg/dL vs 97.1± 54.9 mg/dL; p=0.025). Conclusion Low HDL-C and low Apo A1 levels are found in FMF patients and their first-degree asymptomatic relatives. Low-grade inflammation caused by MEFV mutations may be responsible for these lipid profile changes. PMID:27708899

  11. Serum lipid changes and insulin resistance in familial Mediterranean fever.

    PubMed

    Candan, Zehra; Akdoğan, Ali; Karadağ, Ömer; Kalyoncu, Umut; Şahin, Abdurrahman; Bilgen, Şule; Çalgüneri, Meral; Kiraz, Sedat; Ertenli, Ali

    2014-12-01

    Inflammation is known to alter lipid profiles and to induce insulin resistance. This study was planned to test the hypothesis that familial Mediterranean ferver (FMF) patients and their first-degree asymptomatic relatives may have lipid profile changes and/or insulin resistance, similar to other inflammatory diseases. We studied 72 FMF patients, 30 asymptomatic first-degree relatives, and 75 healthy controls. Fasting and 2-hour postprandial glucose, insulin, apolipoprotein (Apo) A1, Apo B, acute phase reactants, and lipid profiles of all subjects were studied. Insulin resistance was determined by the HOMA (Homeostasis Model Assessment) index. There was no difference between the groups with regard to sex, mean systolic and diastolic blood pressure, body mass index, smoking status, fasting and postprandial 2-hour glucose, insulin, acute phase reactants, and HOMA index levels. High-density lipoprotein cholesterol (HDL-C) levels were similar between FMF patients and FMF relatives (48.9±12.4 mg/dL vs 49.3±13.8 mg/dL; p=NS), and both were lower than controls (48.9±12.4 mg/dL vs 59.6±15.1 mg/dL; p<0.001 and 49.3±13.8 mg/dL vs 59.8±15.1 mg/dL; p=0.001, respectively). Apo A1 levels in FMF patients and asymptomatic first-degree FMF relatives were both lower than in controls, similar to the HDL-C levels (126.1±25.7 mg/dL vs 151.2±31.4 mg/dL; p<0.001 and 129.5±29.0 mg/dL vs 151.2±31.4 mg/dL; p=0.002, respectively). TG levels were significantly higher in FMF relatives as compared to controls (113.4±53.6 mg/dL vs 97.1± 54.9 mg/dL; p=0.025). Low HDL-C and low Apo A1 levels are found in FMF patients and their first-degree asymptomatic relatives. Low-grade inflammation caused by MEFV mutations may be responsible for these lipid profile changes.

  12. Familial Mediterranean fever (FMF) and renal AA amyloidosis--phenotype-genotype correlation, treatment and prognosis.

    PubMed

    Ben-Chetrit, Eldad

    2003-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease, which primarily affects the population surrounding the Mediterranean basin. It is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis or erysipelas-like erythema. Amyloidosis, causing renal failure, is one of the most severe complications of the disease. The gene associated with FMF (MEFV) has been recently isolated. Phenotype-genotype correlation studies revealed that amyloidosis was more common in FMF patients originating from North-Africa who were homozygous for the M694V mutation. Such a correlation was not found in Turkish patients. The risk of amyloidosis is increased in male FMF patients and in patients bearing polymorphism a/a in the SAA1 gene. Colchicine is the chosen drug for the treatment of FMF and can prevent amyloidosis.

  13. Mutational analysis of the PRYSPRY domain of pyrin and implications for familial mediterranean fever (FMF).

    PubMed

    Goulielmos, G N; Fragouli, E; Aksentijevich, I; Sidiropoulos, P; Boumpas, D T; Eliopoulos, E

    2006-07-14

    Familial Mediterranean fever (FMF) is an autosomal, recessively inherited disease, characterized by recurrent fever and serositis that affects mainly patients of the Mediterranean basin. The gene responsible for FMF, named MEFV, was cloned and several missense mutations were found to be responsible for the disease. Based on a recent molecular analysis of MEFV gene mutations in 43 patients from Crete aiming to correlate specific genotypes and clinical manifestations of FMF, we were prompted to construct a three-dimensional model (3-D model) of the PRYSPRY domain of pyrin. The majority of the known MEFV mutations located on this domain have been classified, according to disease severity, and localized on this 3-D model. The functional consequences of these mutations and their implications on disease severity are discussed. Moreover, we report a putative novel missense mutation, S702C, which we identified in exon 10 of the MEFV gene and localized on the constructed 3-D model.

  14. Late Diagnosis of E148Q Mutation-Positive Familial Mediterranean Fever in a Kidney Transplant Patient With Fever of Unknown Origin: A Case Report.

    PubMed

    Tatar, Erhan; Uslu, Adam; Simsek, Cenk; Aykas, Ahmet; Bozkaya, Giray; Imamoglu, Cetin

    2017-02-01

    Fever of unknown origin is a rare condition after solid organ transplant and is generally associated with atypical infections (eg, tuberculosis, fungal infections) and/or lymphoproliferative disorders. Here, we present a kidney transplant patient with a late diagnosis of E148Q mutation-positive familial Mediterranean fever as the cause of fever of unknown origin. A 22-year-old female patient with a previous history of 4 years of hemodialysis and unknown primary renal disease received a deceased-donor kidney transplant at our center 5 years previously. She had an uneventful course in the first 3 years following transplant. After this period, she was hospitalized 3 times during a 4-month period with fever, nausea, vomiting, and atypical abdominal pain. At that time, hemogram results were unremarkable, except for mild leukocytosis and slightly elevated acute-phase reactants; blood, urine, and throat cultures were negative, and there were no remarkable findings on imaging tests. Fever was controlled within 48 hours by administering empiric ampicillin-sulbactam therapy and discontinuing immunosuppressive treatment except steroids. Three successive hospital admissions owing to similar complaints suggested periodic fever syndrome, and therapy with 1 g/day colchicine led to an excellent clinical response with no recurrence of fever or other symptoms. An FMF gene mutation analysis revealed heterozygous E148Q mutation positivity. Continuing the current treatment regimen, the patient did well during at approximately 1.5 years of follow-up. In the Mediterranean region population, familial Mediterranean fever should be considered in the diagnosis of fever of unknown origin in patients who have undergone renal transplant. E148Q mutation-positive familial Mediterranean fever has a subclinical course and renal manifestations that differ from AA amyloidosis during childhood and may be responsible for de novo familial Mediterranean fever after renal transplantation.

  15. Is neutrophil/lymphocyte ratio associated with subclinical inflammation and amyloidosis in patients with familial Mediterranean fever?

    PubMed

    Uslu, Ali Ugur; Deveci, Koksal; Korkmaz, Serdal; Aydin, Bahattin; Senel, Soner; Sancakdar, Enver; Sencan, Mehmet

    2013-01-01

    The purpose of the present study is to determine the association between neutrophil/lymphocyte ratio and both subclinical inflammation and amyloidosis in familial Mediterranean fever. Ninety-four patients with familial Mediterranean fever and 60 healthy volunteers were included in the study. Of the patients, 12 had familial Mediterranean fever related amyloidosis. The neutrophil/lymphocyte ratio of the patients was obtained from the hematology laboratory archive. The neutrophil/lymphocyte ratio was significantly higher among persons with familial Mediterranean fever compared to healthy individuals (P < 0.0001). Also, neutrophil/lymphocyte ratio was significantly higher in patients with amyloidosis than in amyloidosis-free patients (P < 0.0001). Since NLR was evaluated in nonamyloid and amyloid stages of the same patient population (type 1 phenotype), we obtained significant statistical differences (1.95 ± 0.30 versus 2.64 ± 0.48, P < 0.05, resp.). With the cutoff value of neutrophil/lymphocyte ratio >2.21 and AUC = 0.734 (P = 0.009), it was a reliable marker in predicting the development of amyloidosis. The neutrophil/lymphocyte ratio, an emerging marker of inflammation, is higher in patients with familial Mediterranean fever in attack-free periods. The neutrophil/lymphocyte ratio may be a useful marker in predicting the development of amyloidosis.

  16. Anakinra induces complete remission of nephrotic syndrome in a patient with familial mediterranean fever and amyloidosis.

    PubMed

    Sevillano, Ángel M; Hernandez, Eduardo; Gonzalez, Esther; Mateo, Isabel; Gutierrez, Eduardo; Morales, Enrique; Praga, Manuel

    2016-01-01

    Renal amyloidosis is one of the most severe complications of familial Mediterranean fever (FMF). Colchicine has reduced the incidence of this complication, which now only appears in untreated, under-treated and resistant patients, but it is usually ineffective in patients with advanced amyloidosis. Here we report a patient with FMF and biopsy-proven amyloidosis who presented with nephrotic syndrome despite colchicine treatment. Anakinra (an interleukin-1β inhibitor) was started and a dramatic complete remission of nephrotic syndrome was observed in the following months. Anakinra can be an effective treatment for FMF patients with severe secondary amyloidosis.

  17. Performance of Different Diagnostic Criteria for Familial Mediterranean Fever in Children with Periodic Fevers: Results from a Multicenter International Registry.

    PubMed

    Demirkaya, Erkan; Saglam, Celal; Turker, Turker; Koné-Paut, Isabelle; Woo, Pat; Doglio, Matteo; Amaryan, Gayane; Frenkel, Joost; Uziel, Yosef; Insalaco, Antonella; Cantarini, Luca; Hofer, Michael; Boiu, Sorina; Duzova, Ali; Modesto, Consuelo; Bryant, Annette; Rigante, Donato; Papadopoulou-Alataki, Efimia; Guillaume-Czitrom, Severine; Kuemmerle-Deschner, Jasmine; Neven, Bénédicte; Lachmann, Helen; Martini, Alberto; Ruperto, Nicolino; Gattorno, Marco; Ozen, Seza

    2016-01-01

    Our aims were to validate the pediatric diagnostic criteria in a large international registry and to compare them with the performance of previous criteria for the diagnosis of familial Mediterranean fever (FMF). Pediatric patients with FMF from the Eurofever registry were used for the validation of the existing criteria. The other periodic fevers served as controls: mevalonate kinase deficiency (MKD), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), aphthous stomatitis, pharyngitis, adenitis syndrome (PFAPA), and undefined periodic fever from the same registry. The performances of Tel Hashomer, Livneh, and the Yalcinkaya-Ozen criteria were assessed. The FMF group included 339 patients. The control group consisted of 377 patients (53 TRAPS, 45 MKD, 32 CAPS, 160 PFAPA, 87 undefined periodic fevers). Patients with FMF were correctly diagnosed using the Yalcinkaya-Ozen criteria with a sensitivity rate of 87.4% and a specificity rate of 40.7%. On the other hand, Tel Hashomer and Livneh criteria displayed a sensitivity of 45.0 and 77.3%, respectively. Both of the latter criteria displayed a better specificity than the Yalcinkaya-Ozen criteria: 97.2 and 41.1% for the Tel Hashomer and Livneh criteria, respectively. The overall accuracy for the Yalcinkaya-Ozen criteria was 65 and 69.6% (using 2 and 3 criteria), respectively. Ethnicity and residence had no effect on the performance of the Yalcinkaya-Ozen criteria. The Yalcinkaya-Ozen criteria yielded a better sensitivity than the other criteria in this international cohort of patients and thus can be used as a tool for FMF diagnosis in pediatric patients from either the European or eastern Mediterranean region. However, the specificity was lower than the previously suggested adult criteria.

  18. [Amyloidosis of familial Mediterranean fever (FMF)--insights to FMF phenotype II].

    PubMed

    Livneh, Avi

    2006-10-01

    Amyloidosis is the most grievous manifestation of Familial Mediterranean Fever (FMF), occurring in a high proportion of untreated patients. Continuously elevated serum amyloid A (SAA) levels during remissions, rather than a pulsatile rise during FMF attacks, underlies the development of amyloidosis. FMF phenotype II is one extreme of AA amyloidosis, evolving despite a complete absence of FMF attacks. FMF phenotype II is diagnosed in patients with AA amyloidosis in the context of a family history of FMF. In these patients and in patients with AA amyloidosis without family history of FMF and with unknown precipitating disease, MEFV gene analysis is mandatory. Moreover, since FMF phenotype II is an actual hazard, a cost-benefit analysis suggests that MEFV mutation determination in all first-degree family members of FMF patients is warranted, as it will significantly reduce future patient treatment costs.

  19. Febrile seizures in children with familial Mediterranean fever: Coincidence or association?

    PubMed

    Çomak, Elif; Tüfekçi, Özlem; Kılıçbay, Fatih; Isıyel, Emel; Sever, Ali Haydar; Aslanger, Ayça; Ekici, Barış

    2015-09-01

    Familial Mediterranean fever (FMF) is an inherited disease characterized by recurrent bouts of fever and polyserositis and caused by MEditerranean FeVer gene (MEFV) mutations. Given the febrile characteristics of the disease one would expect higher frequency of febrile seizure in this group of pediatric patients. To evaluate the frequency of febrile seizure and related factors in patients with FMF. The children with the diagnosis of FMF were enrolled in the study. Information including clinical features, type of mutation and the history of febrile seizure were all noted. A total of 97 patients, 43 (44.3%) girls with a median age of 7.93 ± 4.05 years (2-16) and a median follow-up period of 20.65 ± 24.33 months (6-135) were included in the study. The frequency of febrile seizure in children with FMF was found as 13.4%, which is higher than the general population [p = 0.04, OR: 2.9 (95% CI: 1.0-8.5)]. The allele frequency of exon 2 mutations in MEFV genes was higher in the patients with febrile seizure (p = 0.03). Frequency of FMF related clinical findings (fever, abdominal pain, arthralgia/myalgia, arthritis, chest pain and erysipelas-like erythema) was similar between the two groups. However, frequency of headache was higher in the patients with febrile seizure (p = 0.014). The frequency of febrile seizure in children with FMF was found to be higher than the general population. Although this finding may be related to high fever during FMF attacks in individuals with genetic propensity of febrile seizure, it may also be a neurologic complication of FMF. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  20. Intrauterine device may trigger typical attacks of familial Mediterranean fever: a case report.

    PubMed

    Kurultak, Ilhan; Kinalp, Can; Ceri, Mevlut; Evrenkaya, Tevfik Rıfkı

    2015-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by episodic, recurrent, self-limited attacks of fever and serositis (sterile peritonitis, pleuritis, arthritis, etc). The insufficiency in restriction of mild inflammation contributes this consequence in FMF.Intrauterine devices (IUDs) have been widely used in the world for contraception by gynecologists as an effective and safe method. Herein, we present a woman with FMF as the first case, whose attacks were triggered by copper-containing IUD. Our hypothesis in the present case was that sterile mild inflammation in the uterus caused by copper-containing IUD may be the initial source of systemic inflammatory response.In our opinion, clinicians should consider that the copper-containing IUDs may be another cause of FMF attacks in women using this contraceptive method.

  1. Familial Mediterranean fever occurring in an elderly Japanese woman with recent-onset rheumatoid arthritis.

    PubMed

    Mori, Shunsuke; Yonemura, Kensuke; Migita, Kiyoshi

    2013-01-01

    A 60-year-old woman with a two-year history of rheumatoid arthritis (RA) developed recurrent two- to three-day attacks of fever (>38 °C) accompanied by monoarthritis of the right hip joint. The first attack occurred two months after beginning anti-tumor necrosis factor-α therapy. Since a diagnosis of infectious arthritis was suspected, the therapy was discontinued. Thereafter, the patient repeated similar episodes; however, oral colchicine effectively controlled the attacks. The patient was diagnosed to have familial Mediterranean fever (FMF). The clinical manifestations of FMF mimic infectious complications during anti-RA therapy. Clinicians should therefore consider the possibility of FMF development in RA patients exhibiting recurrent febrile attacks.

  2. Familial Mediterranean fever associated with optic neuritis, successfully treated with anti-interleukin 1 agents.

    PubMed

    Başaran, Özge; Kavuncu, Sevim; Güven, Alev; Uncu, Nermin; Acar-Çelikel, Banu; Çakar, Nilgün

    2016-01-01

    Familial Mediterranean fever (FMF) is an inherited periodic auto-inflammatory disease characterized by recurrent attacks of fever, synovitis and serositis. Ophthalmological manifestations of FMF are extremely rare. Here we described a boy who has been followed-up for FMF and attended with a loss of vision during the course of the disease. He was diagnosed with optic neuritis. As the other etiologies were excluded his optic neuritis was attributed to the underlying auto inflammatory process. After pulse steroid therapy, his symptoms improved and a complete remission occurred. Afterwards he had two more optic neuritis attacks. Thereafter anti-interleukin 1 (IL-1) drugs were introduced and he did not develop further attacks of both optic neuritis and FMF. This case presentation highlights the possible association between FMF and optic nerve involvement.

  3. [Three cases with familial Mediterranean fever misdiagnosed as juvenile idiopathic arthritis].

    PubMed

    Li, J; Zhang, Y; Wang, W; Zhong, L Q; Song, H M

    2017-05-04

    Objective: To explore the key points of diagnosis and treatment of familial Mediterranean fever(FMF). Method: The clinical data of 3 cases with FMF misdiagnosed as Juvenile idiopathic arthritis(JIA)seen from January 2014 to June 2016 in Peking Union Medical College Hospital were retrospectively collected. The clinical manifestations, gene mutation characteristics, treatment and prognosis were also evaluated. Result: Two cases were male and 1 was female. The mean age of onset was 17 months (3 months to 36 months), while the average age of diagnosis was 6 years and 8 months (24 months to 11 years). All the 3 cases presented with periodic fever, red rash and arthritis.Two of them suffered from anemia, 2 of them showed lymphadenopathy, and 1 of them presented with hepatosplenomegaly. All of the 3 cases were diagnosed as JIA by excluding infectious diseases and neoplastic diseases and respondiug poorly to anti-infection treatment, but they benefitted little from glucocorticoids and a variety of immunosuppressive therapy. The mutations of MEFV gene were found in 3 cases by gene detection, and all of them were complex heterozygous mutations. Four reported pathogenic mutations were found: R202Q, E148Q, L110P, P369S. All the 3 cases are currently receiving oral colchicine (in accordance with the initial dose of children under the age of 5 recommended ≤ 0.5 mg/d, 5 to 10 years old children 0.5-1.0 mg/d, 10 years old children and older children 1.0-1.5 mg / d) , and the symptoms were significantly improved. Conclusion: The familial Mediterranean fever can be characterized by repeated remittent fever, red rash, arthritis, and is easy to be confused with JIA in clinical manifestation.In this paper, 3 cases were diagnosed as complex heterozygous MEFV gene mutation by gene analysis.During the 6 months follow-up, all of the 3 patients responded well to colchicine.

  4. Familial mediterranean fever (FMF) in Moroccan Jews: Demonstration of a founder effect by extended haplotype analysis

    PubMed Central

    Aksentijevich, Ivona; Pras, Elon; Gruberg, Luis; Shen, Yang; Holman, Katherine; Helling, Sharon; Prosen, Leandrea; Sutherland, Grant R.; Richards, Robert I.; Dean, Michael; Pras, Mordechai; Kastner, Daniel L.

    1993-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The FMF gene (designated “MEF”) is on 16p, with the gene order 16cen–D16S80–MEF–D16S94–D16S283–D16S291–16pter. Here we report the association of FMF susceptibility with alleles at D16S94, D16S283, and D16S291 among 31 non-Ashkenazi Jewish families (14 Moroccan, 17 non-Moroccan). We observed highly significant associations at D16S283 and D16S291 among the Moroccan families. For the non-Moroccans, only the allelic association at D16S94 approached statistical significance. Haplotype analysis showed that 18/25 Moroccan FMF chromosomes, versus 0/21 noncarrier chromosomes, bore a specific haplotype for D16S94–D16S283–D16S291. Among non-Moroccans this haplotype was present in 6/26 FMF chromosomes versus 1/28 controls. Both groups of families are largely descended from Jews who fled the Spanish Inquisition. The strong haplotype association seen among the Moroccans is most likely a founder effect, given the recent origin and genetic isolation of the Moroccan Jewish community. The lower haplotype frequency among non-Moroccan carriers may reflect differences both in history and in population genetics. PMID:8102507

  5. Familial Mediterranean Fever (FMF) in Moroccan Jews: Demonstration of a founder effect by extened haplotype analysis

    SciTech Connect

    Aksentijevich, I.; Pras, E.; Helling, S.; Prosen, L.; Kastner, D.L.; Gruberg, L.; Pras, M. )

    1993-09-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The FMF gene (designated MEF') is on 16p, with the gene order 16 cen-D16S80-MEF-D16S94-D16S283-D16S291-16pter. Here the authors report the association of FMF susceptibility with alleles at D16S94, D16S283, and D16S291 among 31 non-Ashkenazi Jewish families 14 Moroccan families. For the non-Moroccans, only the allelic association at D16S94 approached statistical significance. Haplotype analysis showed that 18/25 Moroccan FMF chromosomes, versus 0/21 noncarrier chromosomes, bore a specific haplotype for D16S94-D16S283-D16S291. Among non-Moroccans this haplotype was present in 6/26 FMF chromosomes versus 1/28 controls. Both groups of families are largely descended from Jews who fled the Spanish Inquisition. The strong haplotype association seen among the Moroccans is most likely a founder effect, given the recent origin and genetic isolation of the Moroccan Jewish community. The lowest haplotype frequency among non-Moroccan carriers may reflect differences both in history and in population genetics. 28 refs., 1 fig., 3 tabs.

  6. Expression of the familial Mediterranean fever gene is regulated by nonsense-mediated decay.

    PubMed

    Grandemange, Sylvie; Soler, Stephan; Touitou, Isabelle

    2009-12-15

    Mutations in the MEditerranean FeVer (MEFV) gene are responsible for familial Mediterranean fever (FMF), a recessively inherited auto-inflammatory disease. Cases of dominant inheritance and phenotype-genotype heterogeneity have been reported; however, the underlying molecular mechanism is not currently understood. The FMF protein named pyrin or marenostrin (P/M) is thought to be involved in regulating innate immunity but its function remains subject to controversy. Recent studies postulate that a defect in MEFV expression regulation may play a role in FMF physiopathology. Our group, along with others, has identified several alternatively spliced MEFV transcripts in leukocytes. Since alternative splicing and nonsense-mediated decay (NMD) pathways are usually coupled in the post-transcriptional regulation of gene expression, we hypothesized that NMD could contribute to the regulation of the MEFV gene. To address this issue, we examined the effect of indirect and direct inhibition of NMD on expression of the MEFV transcripts in THP1, monocyte and neutrophil cells. We showed that MEFV is the first auto-inflammatory gene regulated by NMD in both a cell- and transcript-specific manner. These results and preliminary western-blot analyses suggest the possible translation of alternatively spliced MEFV transcripts into several P/M variants according to cell type and inflammatory state. Our results introduce the novel hypothesis that variation of NMD efficiency could play an important role in FMF physiopathology as a potent phenotypic modifier.

  7. Interleukin-1 targeting treatment in familial Mediterranean fever: an experience of pediatric patients.

    PubMed

    Başaran, Özge; Uncu, Nermin; Çelikel, Banu Acar; Taktak, Aysel; Gür, Gökçe; Cakar, Nilgun

    2015-07-01

    The aim of this report was to evaluate and discuss treatment of pediatric familial Mediterranean fever (FMF) patients with anti-interleukin1 (IL-1) agents. Refractory or colchicine unresponsive FMF was described as severe and frequent attacks and/or having high acute phase reactance levels despite having a maximum dose of colchicine (2 mg/day). Disease course, adverse effects, duration of follow-up, treatment protocols, responses to the therapies were discussed. Eight patients (6 male, 2 female) having refractory FMF were identified. Mediterranean fever (MEFV) gene analyses revealed homozygous M694V mutations in six patients and heterozygote M694V mutations in one patient and no mutation in one patient. They were all treated with anakinra and/or canakinumab. The use of anti-IL-1 drugs was beneficial to all patients. None of them had any severe adverse effects due to the therapy. Anakinra and canakinumab were effective in patient refractory to colchicine treatment as shown both in our series and in the literature. Therefore, controlled trials are needed to evaluate the safety and long-term efficacy of IL-1 targeting agents in colchicine resistant patients.

  8. The Risk of Familial Mediterranean Fever in MEFV Heterozygotes: A Statistical Approach

    PubMed Central

    Jéru, Isabelle; Hentgen, Véronique; Cochet, Emmanuelle; Duquesnoy, Philippe; Le Borgne, Gaëlle; Grimprel, Emmanuel; Stojanovic, Katia Stankovic; Karabina, Sonia; Grateau, Gilles; Amselem, Serge

    2013-01-01

    Background Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder due to MEFV mutations and one of the most frequent Mediterranean genetic diseases. The observation of many heterozygous patients in whom a second mutated allele was excluded led to the proposal that heterozygosity could be causal. However, heterozygosity might be coincidental in many patients due to the very high rate of mutations in Mediterranean populations. Objective To better delineate the pathogenicity of heterozygosity in order to improve genetic counselling and disease management. Methods Complementary statistical approaches were used: estimation of FMF prevalence at population levels, genotype comparison in siblings from 63 familial forms, and genotype study in 557 patients from four Mediterranean populations. Results At the population level, we did not observe any contribution of heterozygosity to disease prevalence. In affected siblings of patients carrying two MEFV mutations, 92% carry two mutated alleles, whereas 4% are heterozygous with typical FMF diagnosis. We demonstrated statistically that patients are more likely to be heterozygous than healthy individuals, as shown by the higher ratio heterozygous carriers/non carriers in patients (p<10−7–p<0.003). The risk for heterozygotes to develop FMF was estimated between 2.1×10−3 and 5.8×10−3 and the relative risk, as compared to non carriers, between 6.3 and 8.1. Conclusions This is the first statistical demonstration that heterozygosity is not responsible for classical Mendelian FMF per se, but constitutes a susceptibility factor for clinically-similar multifactorial forms of the disease. We also provide a first estimate of the risk for heterozygotes to develop FMF. PMID:23844200

  9. Could familial Mediterranean fever gene mutations be related to PFAPA syndrome?

    PubMed

    Celiksoy, Mehmet H; Ogur, Gonul; Yaman, Elif; Abur, Ummet; Fazla, Semanur; Sancak, Recep; Yildiran, Alisan

    2016-02-01

    The cause and pathophysiology of PFAPA syndrome is unknown. The aim of this study was to determine all MEFV gene variants relevant to familial Mediterranean fever in children with PFAPA syndrome. All MEFV gene variants were analyzed in patients with PFAPA syndrome. All patients were evaluated using the Gaslini scoring system. Serum immunoglobulin levels were also determined upon admission. We evaluated 64 patients with PFAPA syndrome. The median age at diagnosis was 37.5 (min-max: 6-96) months, and the percentage of male patients was 55.0%. The Gaslini diagnostic score for periodic fever was high in 81.0% of the patients. An MEFV gene mutation was found in 42 (66.0%) children. Mostly, heterozygous or compound heterozygous variants of the MEFV gene were found. Two patients were homozygous for R202Q. MEFV gene mutations were not detected in 22 (34.0%) patients. No significant differences in clinical or laboratory findings were observed between the two groups (p > 0.05), and there were no significant differences in period and duration of the fever episodes (p > 0.05). The fever of all 47 patients (100.0%) who received prednisolone during the episodes decreased within hours and did not recur. Eighteen of the patients using prednisolone underwent prophylaxis with colchicine, and the fever episodes of 9/18 (50.0%) patients using colchicine decreased within months. Most patients presenting with PFAPA syndrome have heterozygous MEFV gene mutations. Whether carrying a heterozygous MEFV gene is the primary cause of this syndrome requires further investigation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes

    PubMed Central

    Erman, Burak; Gül, Ahmet

    2015-01-01

    Familial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations in MEFV and NLRP3 genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1β. Overproduction of IL-1β by Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations. PMID:26161132

  11. The MEFV mutations and their clinical correlations in children with familial Mediterranean fever in southeast Turkey.

    PubMed

    Ece, Aydın; Çakmak, Erdal; Uluca, Ünal; Kelekçi, Selvi; Yolbaş, İlyas; Güneş, Ali; Yel, Servet; Tan, İlhan; Şen, Velat

    2014-02-01

    The aim of this study was to determine the Mediterranean fever (MEFV) gene mutations and their clinical correlations in children with familial Mediterranean fever (FMF) in southeast Turkey. Clinical and laboratory characteristics of 147 (65 males, 82 females) consecutive children with FMF having a positive MEFV gene mutation were prospectively investigated. Patients with negative MEFV gene mutations or atypical FMF presentations and those from other regions of the country were excluded. Clinical manifestations and disease severity scores were recorded. The six most frequent MEFV mutations including M694V, V726A, R726H, P369S, E148Q and P369S were investigated by a reverse hybridization test method. The median age of study group was 9.0 years, median age at diagnosis was 7.8 years, median age at disease onset was 5.0 years, and median follow-up duration was 4.0 years. A positive family history of FMF and parent-to-offspring transmission was found in 58.5 and 42.2 % of families, respectively. The frequencies of independent alleles, with decreasing order, were E148Q (30.7 %), M694V (26.0 %), R761H (13.5 %), V726A (13.0 %), P369S (10.5 %) and M680I (6.3 %) in FMF patients. The M694V subgroup had higher mean disease severity score and longer attack duration compared with E148Q and other mutations subgroups (p < 0.05). Two patients with amyloidosis had the M694V homozygote genotype. In conclusion contrast to other regions and many other ethnicities of the world, the most frequent MEFV gene mutation was E148Q in southeast Turkey. The M694V mutation frequency was lower, and disease severity was relatively mild in FMF children of this region.

  12. Normal QT dispersion in colchicine-resistant familial Mediterranean fever (FMF).

    PubMed

    Nussinovitch, Udi; Livneh, Avi; Volovitz, Benjamin; Nussinovitch, Moshe; Ben-Zvi, Ilan; Lidar, Merav; Nussinovitch, Naomi

    2012-07-01

    The association between familial Mediterranean fever (FMF) and subclinical cardiac disease remains controversial. The aim of the current study was to evaluate whether FMF patients, who do not respond to colchicine treatment, and thereby endure persistent inflammation, have increased QT dispersion (QTd) values. Twenty-two FMF patients and 22 age- and sex-matched control subjects were included in the study. Repolarization and QT dispersion parameters were computed from 12-lead ECG recording using designated computer software, and results of five beats were subsequently averaged. Both FMF patients and controls had similar comorbidities, similar values of average QT, average corrected QT interval length, average QTd interval, average QT corrected dispersion, QT dispersion ratio, JT dispersion (JTd), and JT corrected dispersion. In conclusion, FMF patients who were unresponsive to colchicine treatment and did not develop amyloidosis had normal QTd and JTd parameters, indicating a non-increased risk for repolarization-associated ventricular arrhythmias.

  13. Treatment of Crohn's disease and familial Mediterranean fever by leukopheresis: single shot for two targets.

    PubMed

    Yuksel, Mahmut; Saygili, Fatih; Coskun, Orhan; Suna, Nuretdin; Kaplan, Mustafa; Kuzu, Ufuk Baris; Kilic, Zeki Mesut Yalin; Ozin, Yasemin Ozderin; Kayacetin, Ertugrul

    2015-04-07

    Coexistence of Crohn's disease (CD) and familial Mediterranean fever (FMF) is a rare condition and knowledge about this clinical situation is limited with a few case reports in the literature. The treatment of both diseases depends on their individual therapies. However, it is very hard to deal with this coexistence when CD is refractory to standard therapies. Ongoing activity of CD triggers the clinical attacks of FMF and the symptoms like abdominal pain interfere with both disease presentations which can cause problems about diagnostic and therapeutic approach. The main therapeutic agent for FMF is colchicine and diarrhea is the most common side effect of this drug. This side effect also causes problems about management of these diseases when both of them are clinically active. Here we report probably the first case in the literature with coexisting CD and FMF who was successfully treated by leukopheresis since he was refractory to conventional therapies for CD.

  14. Coexistence of hereditary angioedema in a case of familial Mediterranean fever with partial response to colchicine

    PubMed Central

    Bahceci, Semiha Erdem; Genel, Ferah; Gulez, Nesrin

    2015-01-01

    Hereditary angioedema (HAE) is a very rare and potentially life-threatening genetic disease characterised by episodes of edema in various parts of the body, including the extremities, face, and airway. The disease is usually associated with attacks of abdominal pain. On the other hand, familial Mediterranean fever (FMF) is an inherited condition characterised by recurrent episodes of painful inflammation in the abdomen, chest, or joints. In this report, we present a child with FMF and undiagnosed HAE, which made him a partial responder to colchicine treatment. Consequently, HAE must be considered in differential diagnosis of cases in which a partial response is obtained from FMF treatment, particularly in countries where FMF is frequently encountered, because early diagnosis of HAE can facilitate prevention of life-threatening complications, such as upper airway obstruction. To our knowledge, our patient is the first patient reported in the literature with the diagnosis of HAE and FMF together. PMID:26155193

  15. [INTERLEUKIN 1 INHIBITORS--A NEW HORIZON IN THE TREATMENT OF FAMILIAL MEDITERRANEAN FEVER].

    PubMed

    Shouval, Roni; Livneh, Avi; Ben-Zvi, Ilan

    2015-11-01

    Familial Mediterranean Fever (FMF) is a common genetic auto-inflammatory disease in the Middle Eastern population. Colchicine is the only proven treatment for the prevention of FMF attacks and reactive amyloidosis. However, 5-10% of FMF patients do not respond to colchicine, and an additional 5% are intolerant to it. Progress in the understanding of FMF and the recognition of the central role of IL-1 in its pathophysiology has led to the introduction of IL-1 inhibitors in FMF patients who are unresponsive to colchicine. In this paperwe review the clinical experience gained with IL-1 inhibitors in FMF. Overall, it appears that IL-1 inhibitors are safe and may serve as an alternative in FMF patients resistant to colchicine.

  16. Assessment of left ventricular functions with tissue Doppler, strain, and strain rate echocardiography in patients with familial Mediterranean fever.

    PubMed

    Ceylan, Özben; Özgür, Senem; Örün, Utku Arman; Doğan, Vehbi; Yılmaz, Osman; Keskin, Mahmut; Arı, Mehmet Emre; Erdoğan, Özlem; Karademir, Selmin

    2015-08-01

    This study assessed the early changes in regional and global systolic and diastolic myocardial functions in patients with familial Mediterranean fever without any cardiovascular symptoms using tissue Doppler and strain and strain rate echocardiography and compared them to the results of a control group. This study has a cross-sectional and observational design. FMF patients with normal left ventricular function were included in the study. We excluded patients who had arrhythmia, acquired/congenital heart disease, pericarditis, or acute attack. We compared 45 children with familial Mediterranean fever on colchicine therapy and 45 age- and sex-matched healthy children. The 45 patients with familial Mediterranean fever included 24 (55.3%) girls and 21 (46.7%) boys with a mean age of 11.3 ± 3.7 (range 2-18) years. The mean disease duration was 4.6 ± 2.4 (range 0.5-10) years. In the patient group, the homozygous M694V mutation was the most common (64.4%) mutation. The patients with familial Mediterranean fever had statistically lower longitudinal global strain, radial global strain, and strain rates (-14.44 ± 4.77%, 14.80 ± 6.29%, and 0.59 ± 0.24 s, respectively) than the controls (-17.40 ± 1.79%, 17.53 ± 4.63%, and 0.83 ± 0.51 s) (p < 0.05). The circumferential global strain did not differ significantly between the groups. Patients with familial Mediterranean fever who are subclinical from a cardiac aspect might have normal left ventricular function as measured by conventional echocardiography. However, the disease affects their myocardial tissue, and these patients should be followed with conventional, strain, and strain rate echocardiography techniques regularly.

  17. Assessment of left ventricular functions with tissue Doppler, strain, and strain rate echocardiography in patients with familial Mediterranean fever

    PubMed Central

    Ceylan, Özben; Özgür, Senem; Örün, Utku Arman; Doğan, Vehbi; Yılmaz, Osman; Keskin, Mahmut; Arı, Mehmet Emre; Erdoğan, Özlem; Karademir, Selmin

    2016-01-01

    Objective: This study assessed the early changes in regional and global systolic and diastolic myocardial functions in patients with familial Mediterranean fever without any cardiovascular symptoms using tissue Doppler and strain and strain rate echocardiography and compared them to the results of a control group. Methods: This study has a cross-sectional and observational design. FMF patients with normal left ventricular function were included in the study. We excluded patients who had arrhythmia, acquired/congenital heart disease, pericarditis, or acute attack. We compared 45 children with familial Mediterranean fever on colchicine therapy and 45 age- and sex-matched healthy children. Results: The 45 patients with familial Mediterranean fever included 24 (55.3%) girls and 21 (46.7%) boys with a mean age of 11.3±3.7 (range 2-18) years. The mean disease duration was 4.6±2.4 (range 0.5-10) years. In the patient group, the homozygous M694V mutation was the most common (64.4%) mutation. The patients with familial Mediterranean fever had statistically lower longitudinal global strain, radial global strain, and strain rates (-14.44±4.77%, 14.80±6.29%, and 0.59±0.24 s, respectively) than the controls (-17.40±1.79%, 17.53±4.63%, and 0.83±0.51 s) (p<0.05). The circumferential global strain did not differ significantly between the groups. Conclusion: Patients with familial Mediterranean fever who are subclinical from a cardiac aspect might have normal left ventricular function as measured by conventional echocardiography. However, the disease affects their myocardial tissue, and these patients should be followed with conventional, strain, and strain rate echocardiography techniques regularly. PMID:25550179

  18. Neutrophil-lymphocyte ratio in children with familial Mediterranean fever: Original article

    PubMed Central

    Duksal, Fatma; Alaygut, Demet; Güven, Ahmet Sami; Ekici, Mahmut; Oflaz, Mehmet Burhan; Tuncer, Rukiye; Cevit, Ömer

    2015-01-01

    Objective The aim of present study was (a) to evaluate the relationship between the neutrophil/lymphocyte (N/L) ratio and mutation types of familial Mediterranean fever (FMF) in children and (b) to evaluate the relationship between the N/L ratio and age. Material and Methods Three hundred forty-three children with familial Mediterranean fever in the attack-free period and 283 healthy control children were included in the study. Patients were divided into subgroups according to mutation types. Neutrophil and lymphocyte counts were retrieved from medical records of patients and the N/L ratio was calculated from these parameters. Results The N/L ratio of patients was found to be significantly higher than that of controls (p<0.001). Among 343 patients, homozygous, heterozygous, and compound mutations were observed in 39, 253, and 51 patients, respectively. The differences in the N/L ratio among patients with homozygous, heterozygous, and compound mutations were not statistically significant. The most common mutations were M694V (n=126), E148Q (n=70), M680I, (n=33), and V726A (n=28). Significant differences were not observed among these mutations in terms of the N/L ratio (p>0.05). In all subjects, there was a weak but significant relationship between age and the N/L ratio (r: 0.215, p<0.001). Conclusion The N/L ratio, which can be determined by simple methods in routine blood tests, may be used for the follow-up monitoring of chronic inflammation in patients. In addition, the N/L ratio may give an idea to clinicians regarding the early initiation of treatment in patients with typical clinical findings of FMF. PMID:27708915

  19. Familial Mediterranean Fever in Iran: A Report from FMF Registration Center.

    PubMed

    Salehzadeh, Farhad

    2015-01-01

    Background. Familial Mediterranean fever (FMF) is a periodic AR autoinflammatory disorder. This comprehensive study describes FMF in Iran as a country near Mediterranean area. Materials and Methods. From the country FMF registration center 403 patients according to Tel-Hashomer criteria enrolled this study, 239 patients had MEFV gene mutations analyses. Data, if needed, was analyzed by SPSS v20. Results. 175 patients (43.4%) were female and 228 patients (56.6%) were male. The mean age was 21.3 years. Abdominal pain was in 93.3% patients and 88.1% had fever. Abdominal pain was the main complaint of patients in (49.6%). The mean interval between attacks was 36.5 ± 29.6 days and the mean duration of every episodes was 43.3 ± 34.5 hours. 15.1% of patients had positive family history and 12.7% had previous surgery; in 52.3% of patients delay in diagnosis was more than three years. 12 common MEFV gene mutations were analyzed, 21.33% were without mutations, 39.7% had compound heterozygote, 25.52% showed heterozygous, and 13.38% showed homozygous results. The most common compound genotype was M694V-V726A (% 10.46) and in alleles M694V (% 20.9) and V726A (% 12.7) were the most frequent mutations, respectively. Conclusion. M694V was the most common mutation, and the most common compound genotype was M694V-V726A. Our genotype results are similar to Arabs and in some way to Armenians, erysipelas-like skin lesions are not common in this area, and clinical criteria are the preferred methods in diagnosis of FMF.

  20. Familial Mediterranean Fever in Iran: A Report from FMF Registration Center

    PubMed Central

    Salehzadeh, Farhad

    2015-01-01

    Background. Familial Mediterranean fever (FMF) is a periodic AR autoinflammatory disorder. This comprehensive study describes FMF in Iran as a country near Mediterranean area. Materials and Methods. From the country FMF registration center 403 patients according to Tel-Hashomer criteria enrolled this study, 239 patients had MEFV gene mutations analyses. Data, if needed, was analyzed by SPSS v20. Results. 175 patients (43.4%) were female and 228 patients (56.6%) were male. The mean age was 21.3 years. Abdominal pain was in 93.3% patients and 88.1% had fever. Abdominal pain was the main complaint of patients in (49.6%). The mean interval between attacks was 36.5 ± 29.6 days and the mean duration of every episodes was 43.3 ± 34.5 hours. 15.1% of patients had positive family history and 12.7% had previous surgery; in 52.3% of patients delay in diagnosis was more than three years. 12 common MEFV gene mutations were analyzed, 21.33% were without mutations, 39.7% had compound heterozygote, 25.52% showed heterozygous, and 13.38% showed homozygous results. The most common compound genotype was M694V-V726A (% 10.46) and in alleles M694V (% 20.9) and V726A (% 12.7) were the most frequent mutations, respectively. Conclusion. M694V was the most common mutation, and the most common compound genotype was M694V-V726A. Our genotype results are similar to Arabs and in some way to Armenians, erysipelas-like skin lesions are not common in this area, and clinical criteria are the preferred methods in diagnosis of FMF. PMID:26413094

  1. A novel cluster of patients with Familial Mediterranean Fever (FMF) in southern Italy.

    PubMed

    Bonfrate, Leonilde; Scaccianoce, Giuseppe; Palasciano, Giuseppe; Ben-Chetrit, Eldad; Portincasa, Piero

    2017-09-01

    Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterised by recurrent attacks of fever and serositis (peritonitis, pleuritic or synovitis) affecting mainly populations of Mediterranean origin. To describe a relatively new cluster of FMF subjects from Apulia and Basilicata regions (southern Italy). Subjects were screened for FMF using the Tel-Hashomer criteria and genetic analysis. Demographic data were taken from patients' files and direct interviews. Patients were investigated about attack duration, intensity and site, body temperature, skin manifestations and overall quality of life before and after treatment with colchicine. Inflammatory parameters were also measured between these periods. Forty-nine subjects had FMF (M : F = 26 : 23, age 38 years ± 2 SE) and followed-up up to 8 years. The age at disease onset was 22·1 years ± 1·2SE and the diagnostic delay was 15·5 years ± 1·9SE. The majority of patients (82%) suffered from abdominal pain, and 35% had undergone prior abdominal surgery or laparotomy. Severity score (ISSF) was mild in 43% of patients and intermediate in 57% of patients. Serum amyloid A (SAA) was increased in 20% of patients (16·9 ± 3·7, normal range < 6·4 mg/dL). In over 95% of patients, inflammation markers, duration and intensity of febrile painful attacks, quality of life and ISSF score improved dramatically following colchicine treatment. The Apulia region represents a new endemic area for FMF. Clinical presentation of FMF can be misleading and requires a complete and early workup to recognise the disease and avoid unjustified surgery. Colchicine remains the gold standard therapy to prevent FMF attacks and fatal long-term complications. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  2. The relative contribution of environmental and genetic factors to phenotypic variation in familial Mediterranean fever (FMF).

    PubMed

    Ben-Zvi, Ilan; Brandt, Benny; Berkun, Yackov; Lidar, Merav; Livneh, Avi

    2012-01-10

    Familial Mediterranean fever (FMF) is an autosomal recessive disease, caused by mutations in the FMF gene MEFV (MEditerranean FeVer). It has a large phenotypic diversity even in patients with similar genotypes. Despite evidence that environmental factors (EFs) and genetic factors, including MEFV mutations (such as M694V, E148Q) and background modifier genes (MGs), affect the clinical manifestations of FMF, the relative contribution of each remains unknown. To investigate the relative contribution of environmental and genetic factors to the phenotype of FMF, we compared the intra-pair clinical concordance of 10 mono and 7 dizygotic twins with FMF. The part played by EFs was determined by the phenotypic discordance of the monozygous twins, and the MGs effect was determined by deducing the environmental effect, computed for MZ twins, from the phenotypic discordance of the dizygous twins. The mean±SD of intra-pair concordance was higher in the MZ than in DZ twin group (88.1±13.2 vs. 70.7±14.1 respectively, P value<0.05). Based on the concordance in clinical manifestations in MZ and DZ twins, the environmental effect on the phenotype of FMF is estimated as 11.9%±6.6% and the MGs effect as 17.4%±15.5% in average. In FMF the phenotype is affected by MEFV mutations, MGs and EFs in an estimated ratio of about 6:1.5:1 respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. The role of MEFV mutations in the concurrent disorders observed in patients with familial Mediterranean fever

    PubMed Central

    Güncan, Sabri; Bilge, N. Şule Y.; Cansu, Döndü Üsküdar; Kaşifoğlu, Timuçin; Korkmaz, Cengiz

    2016-01-01

    Objective This study aimed to investigate the frequency in which familial Mediterranean fever (FMF) coexists with other diseases and determine whether Mediterranean fever (MEFV) gene mutations are involved in such coexistence. Material and Methods In total, 142 consecutive patients with FMF investigated for MEFV mutation were enrolled in this study [Female: 87; Male: 55, mean age 32±12 years (11–62)]. All the patients were questioned for the presence of concurrent disorders, and the medical records of these patients were revised retrospectively. A previous diagnosis of inflammatory disorder other than FMF was considered true if it met the relevant criteria. MEFV mutations were divided into 2 groups, namely M694V and its subgroup (homozygous or heterozygous) (Group I) and others (Group II). Compound heterozygosity for M694V mutation was included in Group II to form a homogeneous group for Group I. Group I and Group II were compared according to phenotypical features. The presence of MEFV mutation was investigated in exons 2, 3, 5, and 10 by the multiplex-PCR reverse hybridization method. Results Concomitant disorders were found in 17 of 73 patients with FMF (23%) in Group I and 5 of 56 patients (8.9%) in Group II (p=0.04). Concomitant disorders in Group I were as follows: 7 cases of amyloidosis, 2 cases of Behcet’s disease (BD), 4 cases of ankylosing spondylitis (AS), 1 case of antiphospholipid syndrome, 1 case of Henoch–Schonlein purpura (HSP), 1 case of combination of psoriatic arthritis, HSP, and membranoproliferative glomerulonephritis, and 1 case of AS and amyloidosis. In Group II, the following disorders were found: 1 case of amyloidosis, 1 case of BD, 1 case of AS, 1 case of ulcerative colitis, and 1 case of vitiligo. Conclusion The presence of M694V mutation may predispose patients with FMF to developing other inflammatory disorders. PMID:27733942

  4. A survey of resistance to colchicine treatment for French patients with familial Mediterranean fever.

    PubMed

    Corsia, Alice; Georgin-Lavialle, Sophie; Hentgen, Véronique; Hachulla, Eric; Grateau, Gilles; Faye, Albert; Quartier, Pierre; Rossi-Semerano, Linda; Koné-Paut, Isabelle

    2017-03-16

    Colchicine is the standard treatment for familial Mediterranean fever (FMF), preventing attacks and inflammatory complications. True resistance is rare and yet not clearly defined. We evaluated physicians' definition of colchicine resistance and report how they manage it. We recruited patients with a clinical diagnosis of FMF, one exon-10 Mediterranean fever (MEFV) gene mutation and considered resistant to colchicine, via networks of expert physicians. Clinical, biological characteristics and information about colchicine treatment (dose adjustment, compliance) were collected. The severity of FMF was assessed by the Tel Hashomer criteria. We included 51 patients, most females (55%), mean age 34 ± 23.1 years years (range 4.7-86.3). Overall, 58% (27/47) patients had homozygous M694 MEFV gene mutations. Seventeen of 42 patients (40%) declared full adherence to colchicine treatment, greater for children (48%) than adults (22%). Physicians considered colchicine resistance with > 6 attacks/year (n = 21/51, 42%), > 4 attacks in the last 6 months (n = 13/51, 26%), persistent inflammation (n = 23/51, 45%), renal amyloidosis in (n = 6/28, 22%) of adult patients and intolerance to an increase in colchicine dose (n = 10/51, 19%), and other reasons (n = 13/51, 23%), including chronic arthralgia (n = 6/51, 12%). Interleukin 1-targeting drugs represented the only alternative treatments in addition to daily colchicine. Resistance to colchicine is rare (<10% of patients) and mostly observed in severe MEFV genotypes. The main reasons for physicians assessing resistance were severe clinical symptoms, persistent subclinical inflammation, and secondary amyloidosis. Low adherence to colchicine treatment is a key component of resistance.

  5. Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management

    PubMed Central

    Özen, Seza; Batu, Ezgi Deniz; Demir, Selcan

    2017-01-01

    Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β). Recent studies have shown that pyrin recognizes bacterial modifications in Rho GTPases, which results in inflammasome activation and increase in IL-1β. Pyrin does not directly recognize Rho modification but probably affected by Rho effector kinase, which is a downstream event in the actin cytoskeleton pathway. Recently, an international group of experts has published the recommendations for the management of FMF. Colchicine is the mainstay of FMF treatment, and its regular use prevents attacks and controls subclinical inflammation in the majority of patients. Furthermore, it decreases the long-term risk of amyloidosis. However, a minority of FMF patients fail to response or tolerate colchicine treatment. Anti-interleukin-1 drugs could be considered in these patients. One should keep in mind the possibility of non-compliance in colchicine-non-responders. Although FMF is a relatively well-described AID and almost 20 years has passed since the discovery of the MEFV gene, there are still a number of unsolved problems about it such as the exact mechanism of the disease, symptomatic heterozygotes and their treatment, and the optimal management of colchicine resistance. PMID:28386255

  6. Small bowel mucosal damage in familial Mediterranean fever: results of capsule endoscopy screening.

    PubMed

    Demir, Abdurrahman; Akyüz, Filiz; Göktürk, Suut; Evirgen, Sami; Akyüz, Umit; Örmeci, Aslı; Soyer, Özlem; Karaca, Cetin; Demir, Kadir; Gundogdu, Gökcen; Güllüoğlu, Mine; Erer, Burak; Kamalı, Sevil; Kaymakoglu, Sabahattin; Besisik, Fatih; Gül, Ahmet

    2014-12-01

    Familial Mediterranean fever (FMF) is the most common form of autoinflammatory diseases. We aimed to evaluate the small bowel mucosa by capsule endoscopy (CE) in FMF patients for investigation of other possible causes of abdominal pain. The study group consisted of 41 patients with FMF. A standard questionnaire was used to record the gastrointestinal symptoms, other clinical findings, Mediterranean fever gene (MEFV) mutations, and history of medications including non-steroidal anti-inflammatory drugs (NSAIDs). Gastroscopy, colonoscopy and small bowel CE were performed in all patients, and biopsies were taken from terminal ileum and duodenum. The mean age of the patients was 34 ± 11 years, 63% of them were female, and 76.5% of them were carrying MEFV exon 10 mutations. Only one patient used NSAIDs in addition to colchicine. In endoscopic investigations, gastric erosion was detected in only one patient, and no significant findings were detected in colonoscopy. CE showed small bowel mucosal defects in 44% (erosions in 26.8%, ulcer in 17.1%) and edema in 29.3% of the patients. Most (64%) of the ulcer and erosions were localized to jejunum, and only 24% were in ileum. Mitotic changes as an indirect finding of colchicine toxicity were not different from the changes observed in samples of independent group of patients with irritable bowel syndrome. Mucosal defect was observed in half of the FMF patients, which may be associated with underlying inflammation or chronic colchicine exposure. Detection of nonspecific chronic inflammation without mitotic changes supports that mucosal defects may be associated with the autoinflammatory process.

  7. Is familial Mediterranean fever (FMF) common in patients with negative appendectomy?

    PubMed

    Kisacik, Bunyamin; Karabicak, Ilhan; Erol, Mehmet Fatih; Ozer, Saadet; Pehlivan, Yavuz; Onat, Ahmet Mesut; Tirpanci, Berna; Ertenli, Ihsan

    2013-03-01

    Familial Mediterranean fever (FMF) is an autosomal-recessive disease characterized by recurrent attacks of fever with serositis. Differential diagnosis of a FMF abdominal attack with acute abdomen is difficult. Acute appendicitis is the most common cause of acute abdominal pain that requires surgical treatment. The aim of this study was to investigate frequency of FMF in patients with negative appendectomy. We assessed 278 patients (female/male 127/151) who were operated with preoperative diagnosis of acute appendicitis. In 250 of the patients, definitive diagnosis of acute appendicitis was established by histo-pathological examination. Patients with negative appendectomy were assessed for FMF by rheumatologist. Negative appendectomy was detected in 28 patients (M/F 5/23, mean age 25.3 ± 8.4 years). Negative appendectomy ratio was 10.1 %. Among 28 patients two had FMF (7.7 %). FMF were established in 7.7 % of patients with negative appendectomy. Our study suggests patients having negative appendectomy should be evaluated for FMF. Further large sample studies are needed to define the real prevalence of FMF among negative appendectomy patients.

  8. Colchicine failure in familial Mediterranean fever and potential alternatives: embarking on the anakinra trial.

    PubMed

    Ben-Zvi, Ilan; Livneh, Avi

    2014-05-01

    Familial Mediterranean fever (FMF) is a genetic auto-inflammatory disease characterized by spontaneous short attacks of fever, elevated acute-phase reactants, and serositis. Approximately 5%-10% of FMF patients do not respond to colchicine treatment and another 5% are intolerant to colchicine because of side effects. Recently, following the discovery of the inflammasome and recognition of the importance of interleukin-1beta (IL-1beta) as the major cytokine involved in the pathogenesis of FMF, IL-1beta blockade has been suggested and tried sporadically to treat FMF, with good results. To date, case reports and small case series involving colchicine-resistant FMF patients and showing high efficacy of IL-1beta blockade have been reported. At the Israel Center for FMF at the Sheba Medical Centerthe first double-blind randomized placebo-controlled trial of anakinra in FMF patients who are resistant or intolerant to colchicines is underway. In this report we discuss the mechanism of colchicine resistance in FMF patients, the data in the literature on IL1beta blockade in these patients, and the anakinra trial inclusion criteria and study protocol.

  9. Is recurrent aseptic meningitis a manifestation of familial Mediterranean fever? A systematic review.

    PubMed

    Capron, Jean; Grateau, Gilles; Steichen, Olivier

    2013-01-01

    Familial Mediterranean fever (FMF) causes recurrent episodes of fever and painful serositis. It has been suggested that FMF can cause recurrent aseptic meningitis (RAM). Due to the rarity of both diseases, this claim cannot be assessed with epidemiological methods. We therefore decided to perform a systematic review of the literature to assess the number and validity of published case reports. Medline, Embase, Pascal, Web of Science and the proceedings of relevant conferences were searched. Two independent investigators selected reports asserting RAM in FMF patients, abstracted data and rated the strength of evidence with a custom tool designed to assess: (a) the diagnosis of FMF; (b) the diagnosis of RAM; and (c) the link between FMF and RAM. A causal link was supported by (i) evidence of inflammation and/or clinical FMF features during episodes of RAM; (ii) effectiveness of colchicine to prevent further bouts of meningitis; and (iii) the exclusion of other causes of RAM. Among 944 retrieved references, 917 were rejected by title and abstract screening and 15 after full text review. The strength of evidence of 12 alleged cases of RAM due to FMF was assessed. FMF was unsupported in 4 cases and RAM in 3 further cases. Four of the 5 remaining cases did not provide adequate evidence to support a causal relationship between FMF and RAM. The possibility of RAM due to FMF is poorly supported by a single fairly documented case report that does not, however, meet current diagnostic standards.

  10. Refined mapping of the gene causing Familial Mediterranean fever, by linkage and homozygosity studies

    SciTech Connect

    Aksentijevich, I.; Pras, E.; Gruberg, L.; Helling, S.; Prosen, L.; Pras, M.; Kastner, D.L. ); Shen, Y.; Holman, K.; Sutherland, G.R.; Richards, R.I. ); Ramsburg, M.; Dean, M. ); Amos, C.I. )

    1993-08-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. The authors recently reported linkage of the gene causing FMF (designated [open quotes]MEF[close quotes]) to two markers on chromosome 16p. To map MEF more precisely, they have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. They also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location. 30 refs., 6 figs., 2 tabs.

  11. Coexistence of two rare genetic disorders: Kartagener syndrome and familial Mediterranean fever.

    PubMed

    Çetin, Deniz; Genç Çetin, Beyza; Şentürk, Taşkın; Şahin Çildağ, Songül; Yılmaz Akdam, İkbal

    2015-03-01

    Primary ciliary dyskinesia (PCD) is a rare disease, predominantly inherited as an autosomal recessive, with ciliary dysfunction leading to impaired mucociliary clearance, chronic airway infection and inflammation. Situs inversus totalis occurs in ~50 % of PCD patients and it is known as Kartagener syndome. Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease. FMF is caused by mutations in the MEFV gene which is located on chromosome 16p13.3. p.M680I, p.M694 V, p.M694I, p.V726A on exon 10 and p.E148Q on exon 2 are the most common mutations among FMF patients and these constitute 85 % of all. Homozygosity of R202Q polymorphism is strongly associated with FMF. We would like to present a case of Kartagener syndrome accompanied by FMF with R202Q polymorphism. Our case is the first in the literature indicating the accidental coexistence of FMF and Kartagener syndrome.

  12. Low plasma vitamin D levels in patients with familial Mediterranean fever.

    PubMed

    Erten, Sükran; Altunoğlu, Alpaslan; Ceylan, Gülay Güleç; Maraş, Yüksel; Koca, Cemile; Yüksel, Aydan

    2012-12-01

    Familial Mediterranean fever (FMF) is an autosomal recessive, inherited autoinflammatory disease characterized by recurrent, self-limited attacks of fever and inflammation of serosal surfaces. There is an explosion of the data regarding inflammatory markers in FMF and clinical effects of chronic inflammation on the disease presentation. Vitamin D (vit D) is the common denomination of a group of sterols with a crucial role in phospho-calcium metabolism. There are some data about the importance of vit D in the initiation and propogation of a range of autoimmune diseases. The aim of the present study was to determine whether vit D deficiency is present in patients with FMF compared with healthy individuals. The study group included 99 patients with diagnosis of FMF attended to our outpatient Rheumatology and Nephrology Clinics of Atatürk Education and Research Hospital. The control group comprised 51 age- and sex-matched healthy people selected from hospital staff. Serum baseline 25-hydroxy vit D levels were measured by HPLC method using an Agilent 1100 Liquid Chromatograph. We found significantly lower serum 25-hydroxy vit D levels among FMF patients compared with matched controls and a high prevalence of vit D deficiency. This study demonstrated that vit D deficiency is frequent in patients with FMF than the healthy controls. It is convenient to look for vit D deficiency and to correct vit D nutritional status in FMF patients.

  13. Genetic and physical localization of the gene causing familial Mediterranean fever

    SciTech Connect

    Aksentijevich, I.; Chen, X.; Levy, E.

    1994-09-01

    Familial Mediterranean fever (FMF) is a recessively inherited disease characterized by acute attacks of fever and serositis. The gene causing FMF, designated MEF, is located on chromosome 16p13. We have genotyped a panel of 65 families (non-Ashkenazi Jewish, Armenian, and Arab) for 15 polymorphic markers from distal chromosome 16p. FMF families from all three populations show linkage to chromosome 16. Analysis of recombinants, as well as multipoint linkage data, place MEF in the interval between D16S246 (p218EP6) and D16S138 (N2), a genetic distance of 1-2 cM. We observed a total of 3 recombinants at the telomeric flanking marker D16S246, and 5 at the centromeric flanking marker D16S138. We have previously shown that a haplotype extending from D16S291 to D16S94 on the telomeric side of MEF is strongly associated with FMF among the Moroccan Jewish population, probably representing a founder effect. Here we report that the 2.5 kb allele of the closest telomeric flanking marker D16S246 (p218EP6) was associated with FMF in both Moroccan and non-Moroccan Jews, although not in Armenians and Arabs. Allelic associations for the centromeric flanking markers were much weaker in the Jewish population, suggesting that MEF may be closer to the telomeric end of the D16S246-D16S318 interval. Physical mapping indicates that this interval covers less than 1 Mb of genomic DNA. We will present data on a YAC contig covering this region.

  14. Late-onset disease is associated with a mild phenotype in children with familial Mediterranean fever.

    PubMed

    Özdel, Semanur; Özçakar, Z Birsin; Kunt, Seda Şahin; Elhan, Atilla H; Yalçınkaya, Fatoş

    2016-07-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease, characterised by recurrent, self-limited attacks of fever with serositis. Recently, it was shown that patients with early disease onset during childhood period had more severe disease. The aim of this study was to describe the demographic, clinical and genetic features of FMF patients who had late-onset disease during childhood period and to compare them to those with earlier onset patients. Files of patients who had been seen in our department between January 2013 and January 2014 were retrospectively evaluated. Patients were divided into two groups according to age of disease onset (group I, ≤8 years; group II, >8 years), and clinical findings were compared between the two groups. The study group comprised 317 FMF patients. There were 267 patients in group I and 50 patients in Group II. Median attack frequency was 24/year in group I and 12/year in group II (p < 0.05). Fever and M694V homozygosity were less frequently detected in group II (p = 0.003 and p = 0.022). Median delay in diagnosis was 24 months in group I and 12 months in group II (p = 0.002). Disease severity scores and final colchicine dosages were lower in group II (p < 0.001 and p = 0.003). Only a small number of FMF patients had disease onset at older ages in childhood period. It seems that FMF patients with late-onset disease have milder illness. However, more readily expression of their clinical findings in older ages yields earlier diagnosis in this group.

  15. MEFV mutations and their relation to major clinical symptoms of Familial Mediterranean Fever.

    PubMed

    Cekin, Nilgun; Akyurek, Murat Eser; Pinarbasi, Ergun; Ozen, Filiz

    2017-08-30

    Familial Mediterranean fever is a common hereditary disease in Turkey. To date, different mutational spectrum of MEFV gene was observed in studies carried out in different regions of Turkey but in most of these studies association of clinical symptoms of FMF to mutant genotypes have not been investigated in details. Here we report the MEFV gene variations in exons 2, 3, 5 and 10 and their relations to major clinical symptoms of FMF in 514 unrelated (245 males and 269 females) Turkish patients. MEFV mutations were found in 45% (n=230) of patients and 55% (n=284) of patients did not have any mutations. One hundred and thirty-seven (60%) patients were heterozygous, 57 (24.7%) patients were compound heterozygous, 33 (14%) patients were homozygous and 3 (1.3%) patients were having a complex genotype. Allele frequencies of MEFV mutations were M694V (48%), E148Q (18%), M680I (15%), V726A (12.5%), P369S (3.3%), R761H (0.9), K695R (0.9), E148V (0.9) and A744S (0.5%). Abdominal pain (76%) and fever (58%) were two most seen complications among patients followed by arthritis (28%) and chest pain (19%). Almost all major clinical symptoms of FMF were higher in patients with one or more M694V or M680I mutant allele. In contrast, patients having E148Q or V726A mutant allele showed fewer clinical FMF symptoms. Patients with P369S have higher abdominal pain, chest pain and fever than expected. Arthritis was high in K695R heterozygous genotype. One hundred and eighteen patients were carrying more than one polymorphic allele. The most common polymorphism was R202Q (13%). In addition, a novel heterozygous polymorphism at 564th nucleotide (C>T) of exon2 were found in 2 patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246

    SciTech Connect

    Levy, E. N.; Aksentijevich, I.; Pras, E.

    1996-03-01

    This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbruck formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM). 41 refs., 3 figs., 5 tabs.

  17. Relationship between clinical findings and genetic mutations in patients with familial Mediterranean fever.

    PubMed

    Kilic, Ayse; Varkal, Muhammet Ali; Durmus, Mehmet Sait; Yildiz, Ismail; Yıldırım, Zeynep Nagihan Yürük; Turunc, Gorkem; Oguz, Fatma; Sidal, Mujgan; Omeroglu, Rukiye Eker; Emre, Sevinc; Yilmaz, Yasin; Kelesoglu, Fatih Mehmet; Gencay, Genco Ali; Temurhan, Sonay; Aydin, Filiz; Unuvar, Emin

    2015-12-12

    Familial Mediterranean fever (FMF) is one of the most frequent genetic diseases encountered in the Mediterranean region. We aimed to investigate the correlation between genetic mutations and the clinical findings in 562 patients with FMF. In this retrospective cross-sectional study conducted with patients' files between 2006, and 2013, reverse hybridization assay for MEFV gene mutations was used and the 12 most frequent mutations were screened. Mutation types and clinical findings were compared with variance analysis. The mean age was 6.9 ± 3.4 years (range, 1.8-11.6 years). The most common symptom was fever (97.3%). Thirty-four of the patients (6.04%) were admitted with periodic fever only. Of these patients, M694V was the most common mutation type (73.5%). The percentage of the patients predominantly presenting with recurrent abdominal pain was 77.78% and the most frequent mutations were M694V and E148Q. The rate of arthritis and arthralgia was significantly higher in patients with M694V and E148Q mutations. Chest pain was reported more often in patients homozygous for M694V (61.4%). Pericardial effusion was documented in the echocardiography of 10.9% of the 229 children with chest pain. Some patients had both FMF and Henoch Schönlein purpura (HSP), and were more likely to harbor either homozygote M694V or E148Q mutations. The frequency of episodes was higher in patients with homozygous M694V mutations (number of attacks = 4.4 ± 1.6/month). Proteinuria was detected in 106 patients of cases (29.2%), at an average of 854 ± 145 mg/L. Most of the patients with proteinuria and elevated serum amyloid-A had homozygous M694V mutation. The most common mutation in children in Turkey with FMF is the M694V mutation. Recurrent abdominal pain, arthritis or arthralgia, chest pain, and pericarditis were commonly seen in patients with M694V and E148Q mutations.

  18. Diagnosis delay in familial Mediterranean fever (FMF): social and gender gaps disclosed.

    PubMed

    Lidar, M; Tokov, I; Chetrit, A; Zaks, N; Langevitz, P; Livneh, A

    2005-01-01

    To characterize the factors contributing to a greater than 10 year delay in the diagnosis of familial Mediterranean fever (FMF). 50 patients, in whom diagnosis of FMF was delayed by more than 10 years, comprised the study population. The clinical, demographic and molecular genetic characteristics were compared to a control group of 50 FMF patients, in whom the diagnosis was made within a reasonable time period (less than 5 years from onset). Additional factors contributing to a delayed diagnosis in the study group, including physician-related factors, patient-related factors, disease-factors and other factors, were studied as well. Overall, attack sites, duration and severity were comparable among study and control groups. No differences in ethnic origin or family history of FMF were noted between the groups. There were significantly more females (p = 0.009), newly-arrived immigrants (p = 0.005) and carriers of unidentified MEFV mutations (p = 0.04) in the study group. Delayed diagnosis of FMF stemmed from misdiagnosis and physician negligence (70%), as well as from patient negligence (70%). The diagnosis was ultimately made mainly due to a change in disease pattern and other causes, such as diagnosis of FMF in a relative. The study unveils unexpected causes behind a prolonged delay in the diagnosis of FMF such as social status (immigrant), female gender, physician negligence and lack of patient awareness. The possibility that the delay stems from a milder disease pattern was dismissed.

  19. Does familial Mediterranean fever affect cognitive function in children? Electrophysiological preliminary study.

    PubMed

    Keskindemirci, Gonca; Eskikurt, Gökçer; Ayaz, Nuray Aktay; Çakan, Mustafa; Ermutlu, Numan; İşoğlu Alkaç, Ümmühan

    2017-06-22

    Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease with subclinical inflammation occurring between attacks. The aim of the study was to prospectively evaluate the cognitive function of children diagnosed with FMF that were under colchicine therapy and compare them with healthy controls through electrophysiologically event-related potentials (ERPs) study. Twelve children with FMF and 12 healthy controls were included in the study. During the electroencephalography recordings, all participants were instructed to discriminate rare stimuli (target stimuli) from frequent stimuli (standard stimuli) by pressing a botton on a mouse immediately following the target stimulus. P300, the cognitive component of ERP, was obtained in response to target stimuli and its amplitude and latency were measured. The amplitude of the P300 of the FMF patients was higher and the latencies of the P300 of the FMF patients were shorter than the amplitudes and latencies of control patients, respectively. The difference between the groups was statistically significant for amplitude but not for latency. Cognitive processing reflecting allocation of attention and visual processing speed seems not to be negatively affected in FMF patients with homozygous M694V mutations undergoing colchicine treatment. As this study is unique in its evaluation of the cognitive function of children with FMF, these findings may be helpful for counseling families and patients affected by the condition.

  20. Familial Mediterranean fever in Ashkenazi Jews: the mild end of the clinical spectrum.

    PubMed

    Lidar, Merav; Kedem, Ron; Berkun, Yaacov; Langevitz, Pnina; Livneh, Avi

    2010-02-01

    To characterize familial Mediterranean fever (FMF) in Ashkenazi patients, a Jewish subgroup in which FMF has rarely been described before. A retrospective analysis, comparing demographic, clinical, and genetic measures of the cohort of Ashkenazi Jewish patients with FMF (n = 57), followed at the National Center for FMF in Israel, to age and sex matched patients of Iraqi Jewish (n = 62) and North African Jewish (NAJ; n = 61) origin. Age at disease onset and diagnosis was earlier in NAJ than among Ashkenazi and Iraqi patients. Family history of FMF was described by only 30% of Ashkenazi patients as opposed to the majority of Iraqi and NAJ patients (p = 0.001). The frequency of abdominal and febrile attacks was similar among the 3 groups, while chest and joint attacks were far less common in Ashkenazi and Iraqi compared to NAJ patients. A good response to colchicine was noted in a similar proportion of Ashkenazi and Iraqi patients (82-84%) as opposed to only 56% of NAJ patients (p = 0.0001). Proteinuria, renal failure, and amyloidosis were most frequent among the NAJ patients (18, 6.6, and 9.8% compared to 5.3, 0, and 3.5% and 1.6, 0, and 0% in Ashkenazi and Iraqi patients, respectively). Ashkenazi patients with FMF stand at the mildest end of the clinical spectrum of FMF. This is notwithstanding the tendency for amyloidosis, the frequency of which is not trivial and which deserves particular awareness.

  1. Morvan's syndrome and myasthenia gravis related to familial Mediterranean fever gene mutations.

    PubMed

    Koge, Junpei; Hayashi, Shintaro; Murai, Hiroyuki; Yokoyama, Jun; Mizuno, Yuri; Uehara, Taira; Ueda, Naoyasu; Watanabe, Osamu; Takashima, Hiroshi; Kira, Jun-ichi

    2016-03-29

    We present the first case of Morvan's syndrome (MoS) and myasthenia gravis (MG) related to familial Mediterranean fever (FMF) gene mutations. A 40-year-old woman with a 1-year history of bilateral ptosis and limb muscle weakness presented to our hospital. She also had memory impairment, insomnia, hyperhidrosis, and muscle twitches. Electromyography confirmed widespread myokymia, and there was evidence of temporal region dysfunction on electroencephalography. Anti-voltage-gated potassium channel complex antibodies and anti-acetylcholine receptor antibodies were both positive. Edrophonium administration was effective for bilateral ptosis and muscle weakness. She and her family experienced self-limiting febrile attacks with arthralgia, which led us to suspect FMF. Genetic analyses revealed compound heterozygous mutations in exon 2 of the MEFV gene (L110P/E148Q). From these findings, a diagnosis of MoS and MG complicated with MEFV gene mutations was made. Intravenous high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin resulted in only transient, limited improvement, and frequent relapses, especially in the myasthenic symptoms. Interleukin (IL)-6, IL-1β, and tumor necrosis factor-α were markedly elevated in the serum, which was considered to be derived from the MEFV mutations and responsible for the resistance to immunotherapy. The present case illustrates a possible link between auto-inflammation and auto-antibody-mediated neurological diseases.

  2. The Contribution of SAA1 Polymorphisms to Familial Mediterranean Fever Susceptibility in the Japanese Population

    PubMed Central

    Migita, Kiyoshi; Agematsu, Kazunaga; Masumoto, Junya; Ida, Hiroaki; Honda, Seiyo; Jiuchi, Yuka; Izumi, Yasumori; Maeda, Yumi; Uehara, Ritei; Nakamura, Yoshikazu; Koga, Tomohiro; Kawakami, Atsushi; Nakashima, Munetoshi; Fujieda, Yuichiro; Nonaka, Fumiaki; Eguchi, Katsumi; Furukawa, Hiroshi; Nakamura, Tadashi; Nakamura, Minoru; Yasunami, Michio

    2013-01-01

    Background/Aims Familial Mediterranean Fever (FMF) has traditionally been considered to be an autosomal-recessive disease, however, it has been observed that substantial numbers of patients with FMF possess only 1 demonstrable MEFV mutation. The clinical profile of familial Mediterranean fever (FMF) may be influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. Methodology/Principal Findings In view of the inflammatory nature of FMF, we investigated whether serum amyloid A (SAA) and interleukin-1 beta (IL-1β) gene polymorphisms may affect the susceptibility of Japanese patients with FMF. The genotypes of the -13C/T SNP in the 5′-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 83 Japanese patients with FMF and 200 healthy controls. The same samples were genotyped for IL-1β-511 (C/T) and IL-1 receptor antagonist (IL-1Ra) variable number of tandem repeat (VNTR) polymorphisms. There were no significant differences between FMF patients and healthy subjects in the genotypic distribution of IL-1β -511 (C/T), IL-1Ra VNTR and SAA2 polymorphisms. The frequencies of SAA1.1 allele were significantly lower (21.7% versus 34.0%), and inversely the frequencies of SAA1.3 allele were higher (48.8% versus 37.5%) in FMF patients compared with healthy subjects. The frequency of -13T alleles, associated with the SAA1.3 allele in the Japanese population, was significantly higher (56.0% versus 41.0%, p = 0.001) in FMF patients compared with healthy subjects. Conclusions/Significance Our data indicate that SAA1 gene polymorphisms, consisting of -13T/C SNP in the 5′-flanking region and SNPs within exon 3 (2995C/T and 3010C/T polymorphisms) of SAA1 gene, are associated with susceptibility to FMF in the Japanese population. PMID:23437051

  3. Sonographic assessment of spleen size in Turkish migrants with Familial Mediterranean fever in Germany.

    PubMed

    Ornek, Ahmet; Kurucay, Mustafa; Henning, Bernhard F; Pagonas, Nikolaos; Schlottmann, Renate; Schmidt, Wolfgang E; Giese, Arnd

    2014-11-01

    Familial Mediterranean fever (FMF) can be associated with splenomegaly. Prospective quantitative data are lacking. We performed a sonographic assessment of spleen size in patients with FMF and healthy control participants to assess its diagnostic value. Patients with FMF according to the criteria of Livneh et al (Arthritis Rheum 1997; 40:1879-1885) who were in an asymptomatic interval and control participants were prospectively included in this study in Germany and underwent sonographic measurement of the spleen as well as a structured interview and a physical examination. Patients and controls were Turkish migrants. Thirty-six patients and 27 controls were included. Patients and controls did not differ significantly in age (mean ± SD, 34.8 ± 9.7 versus 33.3 ± 10.0 years, respectively; P = .56), sex, height, weight, or body mass index (26.7 ± 4.7 versus 26.1 ± 4.3 kg/m(2); P = .63). Spleen size was greater in patients than controls in width (4.3 ± 1.0 versus 3.7 ± 0.7 cm; P = .008) and also length (12.1 ± 1.9 versus 10.5 ± 1.4 cm; P = .001). Twenty-six of 36 patients (72.2%) had a history of appendectomy compared to 3 of 27 controls (11.1%; P < .001). The combination of an enlarged spleen (length >11 cm and/or width >4 cm) gave specificity of 100% (95% confidence interval, 87%-100%) and a positive predictive value of 100% (95% confidence interval, 78%-100%) for the diagnosis of FMF in our study. Spleen size as evaluated by sonography is larger in patients with FMF compared to healthy controls. Most patients with FMF included in this study had undergone appendectomy. Familial Mediterranean fever should be considered as a differential diagnosis in Turkish migrants in Germany if the spleen is enlarged and a history of appendectomy is reported. © 2014 by the American Institute of Ultrasound in Medicine.

  4. Sweet's syndrome in familial Mediterranean fever: possible continuum of the neutrophilic reaction as a new cutaneous feature of FMF.

    PubMed

    Oskay, Tugba; Anadolu, Rana

    2009-08-01

    Sweet's syndrome (SS) or acute febrile neutrophilic dermatosis is an uncommon disorder that often occurs in association with other systemic diseases. In its systemic manifestation, SS resembles familial Mediterranean fever (FMF) in many aspects. Although the exact pathogenesis of SS and FMF is not yet clear, their clinical similarities and simultaneous occurrence suggest a possible common underlying mechanism and may represent a continuum of a reactive neutrophilic condition.

  5. Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype Distribution in Familial Mediterranean Fever (FMF) Patients.

    PubMed

    Erken, Ertugrul; Goruroglu Ozturk, Ozlem; Kudas, Ozlem; Arslan Tas, Didem; Demirtas, Ahmet; Kibar, Filiz; Dinkci, Suzan; Erken, Eren

    2015-11-17

    BACKGROUND Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease predominantly affecting Mediterranean populations. The gene associated with FMF is the MEFV gene, which encodes for a protein called pyrin. Mutations of pyrin lead to uncontrolled attacks of inflammation, and subclinical inflammation continues during attack-free intervals. Killer cell immunoglobulin-like receptor (KIR) genes encode HLA class I receptors expressed by NK cells. The aim this study was to look for immunogenetic determinants in the pathogenesis of FMF and find out if KIR are related to susceptibility to disease or complications like renal amyloidosis. MATERIAL AND METHODS One hundred and five patients with FMF and 100 healthy individuals were involved in the study. Isolated DNA from peripheral blood was amplified by sequence specific PCR probes and analyzed by Luminex for KIR genotypes. Fisher Exact test was used to evaluate the variation of KIR gene distribution. RESULTS All patients and healthy controls expressed the framework genes. An activator KIR gene, KIR2DS2, was significantly more frequent in FMF patients (p=0.036). Renal amyloidosis and presence of arthritis were not associated with KIR genes and genotype. KIR3DL1 gene was more common in patients with high serum CRP (p=0.016). CONCLUSIONS According to our findings, we suggest that presence of KIR2DS2, which is an activator gene for NK cell functions, might be related to the autoinflammation in FMF. The potential effect of KIR genes on amyloidosis and other clinical features requires studies with larger sample sizes.

  6. Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype Distribution in Familial Mediterranean Fever (FMF) Patients

    PubMed Central

    Erken, Ertugrul; Ozturk, Ozlem Goruroglu; Kudas, Ozlem; Tas, Didem Arslan; Demirtas, Ahmet; Kibar, Filiz; Dinkci, Suzan; Erken, Eren

    2015-01-01

    Background Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease predominantly affecting Mediterranean populations. The gene associated with FMF is the MEFV gene, which encodes for a protein called pyrin. Mutations of pyrin lead to uncontrolled attacks of inflammation, and subclinical inflammation continues during attack-free intervals. Killer cell immunoglobulin-like receptor (KIR) genes encode HLA class I receptors expressed by NK cells. The aim this study was to look for immunogenetic determinants in the pathogenesis of FMF and find out if KIR are related to susceptibility to disease or complications like renal amyloidosis. Material/Methods One hundred and five patients with FMF and 100 healthy individuals were involved in the study. Isolated DNA from peripheral blood was amplified by sequence specific PCR probes and analyzed by Luminex for KIR genotypes. Fisher Exact test was used to evaluate the variation of KIR gene distribution. Results All patients and healthy controls expressed the framework genes. An activator KIR gene, KIR2DS2, was significantly more frequent in FMF patients (p=0.036). Renal amyloidosis and presence of arthritis were not associated with KIR genes and genotype. KIR3DL1 gene was more common in patients with high serum CRP (p=0.016). Conclusions According to our findings, we suggest that presence of KIR2DS2, which is an activator gene for NK cell functions, might be related to the autoinflammation in FMF. The potential effect of KIR genes on amyloidosis and other clinical features requires studies with larger sample sizes. PMID:26574972

  7. Evaluation of various cardiac autonomic indices in patients with familial Mediterranean fever on colchicine treatment.

    PubMed

    Canpolat, Uğur; Dural, Muhammed; Aytemir, Kudret; Akdoğan, Ali; Kaya, Ergün Barış; Sahiner, Levent; Yalçin, Ulvi; Canpolat, Asena Gökçay; Calgüneri, Meral; Kabakçi, Giray; Tokgözoğlu, Lale; Oto, Ali

    2012-04-03

    Familial Mediterranean fever (FMF) is characterized by sporadic, acute attacks of fever and serositis. Cardiovascular involvement is one of the leading cause of morbidity and mortality among FMF patients. Herein, we aimed to evaluate cardiac autonomic functions in FMF patients without overt cardiac symptoms. We enrolled 38 patients (20 female; mean age 34.4 ± 10.2 years) with FMF and 34 healthy subjects (18 female; mean age 33.2 ± 9.3 years). All participants underwent 24-hour Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting first, second, and third minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV), heart rate turbulance (HRT) and QT dispersion analysis. The mean FMF duration was 9.8 ± 4.2 years. Both groups were similar with regard to baseline characteristics. Mean HRR1 (p=0.001), HRR2 (p=0.003) and HRR3 (p<0.001) were significantly lower in FMF group. SDNN (standard deviation of all NN intervals), SDANN (SD of the 5 min mean RR intervals), RMSSD (root square of successive differences in RR interval), and PNN50 (proportion of differences in successive NN intervals >50 ms) and high-frequency (HF) components were significantly decreased, but low frequency (LF) and LF/HF were significantly higher in FMF patients. HRT onset and slope were significantly less negative in FMF patients. Also, QTd was significantly higher in FMF patients (p<0.001). Patients with FMF showed delayed recovery of heart rate and abnormal HRV and HRT parameters with respect to normal subjects. Cardiac autonomic functions might be involved in FMF patients even in patients without cardiac symptoms. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Familial Mediterranean fever (FMF)-associated amyloidosis in childhood. Clinical features, course and outcome.

    PubMed

    Cakar, N; Yalçinkaya, F; Ozkaya, N; Tekin, M; Akar, N; Koçak, H; Misirlioğlu, M; Akar, E; Tümer, N

    2001-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disorder of childhood characterized by attacks of fever and serositis. Renal amyloidosis is the most important complication of the disease that determines the prognosis. Forty-eight Turkish FMF patients with amyloidosis who have been followed at the two hospitals in Ankara were included in this study. All patients with amyloidosis had been symptomatic for FMF at the time of the diagnosis (Phenotype I), none had received regular colchicine therapy and all presented with proteinuria. Ten of them had asymptomatic proteinuria; 38 had nephrotic syndrome and 8 of them had renal insufficiency (CRI) as well, at the time of the diagnosis. Regular colchicine therapy was commenced to all of the patients. At the end of observation period of 4.5 +/- 2.23 years (range 2-12 yrs) on treatment, nephrotic syndrome resolved in 13 patients and proteinuria was lost in 5 of them. None but 2 of the patients who were diagnosed at proteinuric stage progressed to end stage renal failure (ESRF). Seven MEFV mutations (M694V, M680I, V726A, M694I, K695R, R761H, E148Q) were systematically investigated in 32 patients. Six of the seven studied mutations were found in these patients and clinical diagnosis was confirmed by mutation analysis in 24 patients. Eight patients were found to have mutations on one of the alleles. Amyloidosis is the most serious complication of FMF. Colchicine treatment ameliorates the progression of renal disease in the patients who presented with proteinuria and even with nephrotic syndrome. No correlation between the outcome of the patients with nephrotic syndrome and the degree of proteinuria and/or serum albumin levels at the initiation of treatment were noted. Progression to ESRF seems inevitable despite colchicine therapy after the development of CRI in patients with FMF associated amyloidosis.

  9. Expression of CD64 on polymorphonuclear neutrophils in patients with familial Mediterranean fever

    PubMed Central

    Migita, K; Agematsu, K; Yamazaki, K; Suzuki, A; Yazaki, M; Jiuchi, Y; Miyashita, T; Izumi, Y; Koga, T; Kawakami, A; Eguchi, K

    2011-01-01

    Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever and serosal or synovial inflammation. We examined the utility of CD64 (FcγRI) expression in polymorphonuclear neutrophils (PMNs) as clinical and biological parameters in patients with FMF. We studied 12 Japanese FMF patients (mean age; 22·8 ± 15·5 years, male/female: 2/10), along with rheumatoid arthritis patients (RA, n = 38 male/female: 6/32, mean age; 52·2 ± 15·3 years), systemic lupus erythematosus (SLE, n = 15 male/female: 0/15, mean age; 38·5 ± 15·9 years) and 12 healthy subjects (male/female: 3/9, mean age; 37·9 ± 17·2 years). CD64 expression on PMNs was determined using flow cytometry. The quantitative expression of CD64 in patients with FMF (2439·6 ± 2215·8 molecules per PMN) was significantly higher than in healthy subjects (547·8 ± 229·5, P = 0·003) or in patients with RA (606·5 ± 228·2, P < 0·0001) and SLE (681·3 ± 281·1, P = 0·004). The increased CD64 expression on PMNs isolated from untreated FMF patients was down-regulated by colchicine treatment. NACHT-LRR-PYD-containing protein 3 (NLRP3) activation using MurNAc-L-Ala-D-isoGln (MDP) resulted in increased CD64 expression on PMNs from healthy subjects. Our results suggest that quantitative measurement of CD64 expression on PMNs can be a valuable tool to discriminate between FMF and autoimmune diseases. PMID:21438869

  10. Familial Mediterranean fever in the "Chuetas" of Mallorca--origin in inquisition?

    PubMed

    Buades, J; Ben-Chetrit, E; Levy, M

    1995-08-01

    The aim of our study was to compare the features of familial Mediterranean fever (FMF) in Mallorcan "Chuetas" with those in non-Ashkenazi Jews in Israel. The clinical and laboratory data of FMF were evaluated in a recently identified cluster of 50 FMF patients from Mallorca (the Chuetas) and 45 patients from Israel. We found that the prevalence and clinical manifestations of FMF were similar among the Chuetas and the Israeli group. Furthermore, in contrast to other ethnic groups with FMF, joint involvement was quite common in both the Chuetas (70%) and the Israeli group (75%). The Chuetas are descendants of Mallorcan Jews who emigrated from Spain to the island in the 12th century. The non-Ashkenazi Jews originated mainly in North Africa and are descendants of refugees who escaped from Spain as a result of the Inquisition in the 15th century. We suggest that the non-Ashkenazi Jews and the Chuetas may have a common gene defect for FMF.

  11. Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation

    PubMed Central

    Van Gorp, Hanne; Saavedra, Pedro H. V.; de Vasconcelos, Nathalia M.; Van Opdenbosch, Nina; Vande Walle, Lieselotte; Matusiak, Magdalena; Prencipe, Giusi; Insalaco, Antonella; Van Hauwermeiren, Filip; Demon, Dieter; Bogaert, Delfien J.; Dullaers, Melissa; De Baere, Elfride; Hochepied, Tino; Dehoorne, Joke; Vermaelen, Karim Y.; Haerynck, Filomeen; De Benedetti, Fabrizio; Lamkanfi, Mohamed

    2016-01-01

    Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type and FMF Pyrin are differentially controlled by microtubules. Diverse microtubule assembly inhibitors prevented Pyrin-mediated caspase-1 activation and secretion of IL-1β and IL-18 from mouse macrophages and human peripheral blood mononuclear cells (PBMCs). Remarkably, Pyrin inflammasome activation persisted upon microtubule disassembly in PBMCs of FMF patients but not in cells of patients afflicted with other autoinflammatory diseases. We further demonstrate that microtubules control Pyrin activation downstream of Pyrin dephosphorylation and that FMF mutations enable microtubule-independent assembly of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) micrometer-sized perinuclear structures (specks). The discovery that Pyrin mutations remove the obligatory requirement for microtubules in inflammasome activation provides a conceptual framework for understanding FMF and enables immunological screening of FMF mutations. PMID:27911804

  12. Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation.

    PubMed

    Van Gorp, Hanne; Saavedra, Pedro H V; de Vasconcelos, Nathalia M; Van Opdenbosch, Nina; Vande Walle, Lieselotte; Matusiak, Magdalena; Prencipe, Giusi; Insalaco, Antonella; Van Hauwermeiren, Filip; Demon, Dieter; Bogaert, Delfien J; Dullaers, Melissa; De Baere, Elfride; Hochepied, Tino; Dehoorne, Joke; Vermaelen, Karim Y; Haerynck, Filomeen; De Benedetti, Fabrizio; Lamkanfi, Mohamed

    2016-12-13

    Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type and FMF Pyrin are differentially controlled by microtubules. Diverse microtubule assembly inhibitors prevented Pyrin-mediated caspase-1 activation and secretion of IL-1β and IL-18 from mouse macrophages and human peripheral blood mononuclear cells (PBMCs). Remarkably, Pyrin inflammasome activation persisted upon microtubule disassembly in PBMCs of FMF patients but not in cells of patients afflicted with other autoinflammatory diseases. We further demonstrate that microtubules control Pyrin activation downstream of Pyrin dephosphorylation and that FMF mutations enable microtubule-independent assembly of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) micrometer-sized perinuclear structures (specks). The discovery that Pyrin mutations remove the obligatory requirement for microtubules in inflammasome activation provides a conceptual framework for understanding FMF and enables immunological screening of FMF mutations.

  13. Changes in Cerebral Blood Flow in Patients with Familial Mediterranean Fever.

    PubMed

    Çetin, Gözde; Utku, Uygar; Atilla, Nurhan; Gişi, Kadir; Sayarlioğlu, Mehmet

    2017-06-01

    It is known that there is a relationship between systemic inflammation and atherosclerosis. Atherosclerosis is one of the best-known causes of cerebrovascular diseases. The aim of this study was to assess cerebral blood flow velocity using transcranial Doppler (TCD) ultrasonography in patients with familial Mediterranean fever (FMF). A total of 30 patients aged from 20 to 50 years with FMF were enrolled in the FMF group consecutively. The control group (non-FMF group) consisted of 30 age- and sex-matched randomly selected patients without FMF who had other diagnoses such as fibromyalgia and did not have risk factors for atherosclerosis. Bilateral peak-systolic, end-diastolic, and mean blood flow velocities in the middle cerebral artery (MCA), values of Gosling's pulsatility index, and values of Pourcelot's resistance index were recorded using TCD ultrasonography by a neurosonologist blinded to the FMF and control groups. There were 30 participants in the FMF group in remission (male/female: 4/26, mean age: 34.7±5.9 years) and 30 participants in the control group (male/female: 4/26, mean age: 32.3±4.7 years). C-reactive protein levels and bilateral blood flow velocities in the MCA were significantly higher in the FMF group than in the control group. This study suggests that persistent clinical and subclinical inflammation in patients with FMF causes an increase in cerebral blood flow velocities. Our findings provide an insight into this association between FMF and cerebrovascular diseases.

  14. Inflammatory/demyelinating central nervous system involvement in familial Mediterranean fever (FMF): coincidence or association?

    PubMed

    Akman-Demir, G; Gul, A; Gurol, E; Ozdogan, H; Bahar, S; Oge, A E; Gurvit, H; Saruhan-Direskeneli, G; Yazici, H; Eraksoy, M

    2006-07-01

    Familial Mediterranean fever (FMF) is an inherited inflammatory disease characterized by recurrent febrile polyserositis. Central nervous system (CNS) involvement in FMF is uncommon, but recently cases with multiple sclerosis (MS) and FMF have been reported. Here we assess patients with both FMF and MS, in order to clarify any relationship between FMF and MS, and to evaluate disease characteristics. Our MS database between 1986-2005 was screened retrospectively, and patients with both FMF and inflammatory/demyelinating CNS disease were evaluated among a total of 2800 patients including definite MS (n = 2268) and other demyelinating disorders. There were 12 patients with FMF, who developed a CNS disorder with multifocal white matter lesions. Median age at onset of FMF was 7 years, and median age at neurological onset was 26.8 years. Nine patients (including two siblings) had definite MS according to clinical and MRI findings, whereas 3 patients had atypical features suggesting other demyelinating disorders. Disease severity varied among the patients between very mild to a fatal course. All 8 patients evaluated for oligoclonal IgG bands in CSF were positive. The rate of FMF among our patients with definite MS is almost 4 times the expected prevalence in Turkey. Our series including a sibling pair concordant for FMF and MS may suggest that similar genetic susceptibility and environmental factors might be responsible, although coincidence still remains a possibility. A prospective study on a larger sample seems to be justified.

  15. Risk factors for amyloidosis and impact of kidney transplantation on the course of familial Mediterranean fever.

    PubMed

    Ben-Zvi, Ilan; Danilesko, Iveta; Yahalom, Gilad; Kukuy, Olesya; Rahamimov, Ruth; Livneh, Avi; Kivity, Shaye

    2012-04-01

    Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation in some patients. To assess demographic, clinical and genetic risk factors for the development of FMF amyloidosis in a subset of kidney-transplanted patients and to evaluate the impact of transplantation on the FMF course. Demographic, clinical and genetic data were abstracted from the files, interviews and examinations of 16 kidney-transplanted FMF amyloidosis patients and compared with the data of 18 FMF patients without amyloidosis. Age at disease onset and clinical severity of the FMF amyloidosis patients prior to transplantation were similar to FMF patients without amyloidosis. Compliance with colchicine treatment, however, was much lower (50% vs. 98%). Posttransplantation, FMF amyloidosis patients experienced fewer of the typical serosal attacks than did their counterparts (mean 2214 days since last attack vs. 143 days). Patients with FMF amyloidosis carried only M694V mutations in the FMF gene, while FMF without amyloidosis featured other mutations as well. Compliance with treatment and genetic makeup but not severity of FMF constitutes major risk factors for the development of amyloidosis in FMF. Transplantation seems to prevent FMF attacks. The protective role of immunosuppressive therapy cannot be excluded.

  16. Normal arterial stiffness in familial Mediterranean fever: evidence for a possible cardiovascular protective role of colchicine.

    PubMed

    Kukuy, Olga; Livneh, Avi; Mendel, Liran; Benor, Ariel; Giat, Eitan; Perski, Oleg; Feld, Olga; Kassel, Yonatan; Ben-Zvi, Ilan; Lidar, Merav; Holtzman, Eliezer J; Leiba, Adi

    2017-02-09

    Familial Mediterranean fever (FMF) is an autoinflammatory disorder with episodic and persistent inflammation, which is only partially suppressed by continuous colchicine treatment. While chronic inflammation is considered an important cardiovascular risk factor in many inflammatory disorders, its impact in FMF is still disputed. We measured arterial stiffness, a marker of atherosclerotic cardiovascular disease, in a group of FMF patients, in order to evaluate the cardiovascular consequences of inflammation in FMF and the role of colchicine in their development. Eighty colchicine treated FMF patients, without known traditional cardiovascular risk factors, were randomly enrolled in the study. Demographic, genetic, clinical and laboratory data were retrieved from patient files and examinations. Arterial stiffness was measured using pulse wave velocity (PWV). The recorded values of PWV were compared with those of an age and blood pressure adjusted normal population, using internationally endorsed values. FMF patients displayed normal PWV values, with an even smaller than expected proportion of patients deviating from the 90th percentile of the reference population (5% vs. 10%, p=0.02). The lowest PWV values were recorded in patients receiving the highest dose of colchicine (≥2 mg vs. 0-1 mg, p=0.038), and in patients of North African Jewish origin, whose disease was typically more severe than that of patients of other ethnicities; both observations supporting an ameliorating colchicine effect (p=0.043). Though subjected to chronic inflammation, colchicine treated FMF patients have normal PWV. Our findings provide direct evidence for a cardiovascular protective role of colchicine in FMF.

  17. Familial Mediterranean fever without MEFV mutations: a case-control study.

    PubMed

    Ben-Zvi, Ilan; Herskovizh, Corinne; Kukuy, Olga; Kassel, Yonatan; Grossman, Chagai; Livneh, Avi

    2015-03-25

    Although familial Mediterranean fever (FMF) was originally defined as an autosomal recessive disorder, approximately 10-20% of FMF patients do not carry any FMF gene (MEFV) mutations. Fine phenotype characterization may facilitate the elucidation of the genetic background of the so called "FMF without MEFV mutations". In this study we clinically and demographically characterize this subset. MEFV mutation-negative FMF and control patients were recruited randomly from a cohort followed in a dedicated FMF clinic. The control subjects comprised 2 groups: 1. typical population of FMF, consisting of genetically heterogeneous patients manifesting the classical spectrum of FMF phenotype and 2. a severe phenotype of FMF, consisting of FMF patients homozygous for the p.M694V mutation. Forty-seven genetic-negative, 60 genetically heterogeneous and 57 p.M694V homozygous FMF patients were enrolled to the study. MEFV-mutation negative FMF patients showed a phenotype closely resembling that of the other 2 populations. It differed however from the p.M694V homozygous subset by its milder severity (using Mor et al. scoring method), as determined by the lower proportion of patients with chest and erysipelas like attacks, lower frequency of some of the chronic manifestations, lower colchicine dose and older age of disease onset. MEFV mutation-negative FMF by virtue of its classical FMF phenotype is probably associated with a genetic defect upstream or downstream to MEFV related metabolic pathway.

  18. Nutcracker syndrome in a child with familial Mediterranean fever (FMF) disease: renal ultrastructural features.

    PubMed

    Ozcan, Ayhan; Gonul, Ipek Isik; Sakallioglu, Onur; Oztas, Emin

    2009-12-01

    Renal nutcracker syndrome is an uncommon clinical condition caused by compression of the left renal vein. It is usually accompanied by hematuria and/or orthostatic proteinuria. To date, the pathogenic mechanism of proteinuria and its ultrastructural features have not been clearly identified. Here, we present the glomerular ultrastructural features of nutcracker syndrome and our attempt to analyze the relationship between proteinuria and ultrastructural features. Two months prior to admission, a 11-year-old girl with familial Mediterranean fever who was treated with colchicine was found to have proteinuria. Accompanying hematuria was not identified, and laboratory findings were otherwise normal. Doppler ultrasonography and computerized tomography angiography revealed an entrapment of the left renal vein. A kidney biopsy was performed due to the persistent proteinuria. Light microscopy revealed segmental, minimal increases in the mesangial cells and matrix. No amyloid deposition was present. Neither immunofluorescence nor electron microscopy showed immunoglobulin deposition. Increased thickness of the glomerular basement membrane due to the unequivocal radiolucent widening of the lamina rara interna was the most striking ultrastructural finding. At high magnification, there were no amyloidal fibrils. It has been proposed that hemodynamic alterations and structural changes in glomerular basement membrane glycosaminoglycans may play a role in the pathogenesis of proteinuria. Radiolucent expansion of the lamina rara interna of the glomerular basement membrane in the presenting case would seem to support these data.

  19. Association of hidradenitis suppurativa and familial Mediterranean fever: A case series of 6 patients.

    PubMed

    Abbara, Salam; Georgin-Lavialle, Sophie; Stankovic Stojanovic, Katia; Bachmeyer, Claude; Senet, Patricia; Buob, David; Audia, Sylvain; Delcey, Véronique; Fellahi, Soraya; Bastard, Jean-Philippe; Awad, Fawaz; Legendre, Marie; Amselem, Serge; Grateau, Gilles

    2017-03-01

    Familial mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. Hidradenitis suppurativa (HS) is an inflammatory cutaneous disease. Those diseases can occur simultaneously among the same individual. Our objective was to describe the features of patients displaying both FMF and HS. We screened the French adult FMF reference center for FMF patients with HS. Six patients out of 151 (4%) with a median age of 36 years old were concerned. Among them, FMF was symptomatic at a median age of 11.5years old and colchicine was introduced at a median age of 20.5years old. HS was diagnosed at a median age of 31.5years old. An elderly patient displayed AA amyloidosis in the outcome of FMF, with a late diagnosis of HS, with response to anakinra. There was no temporal relation between FMF and HS attacks. Some patients had a persistent inflammatory syndrome under treatment. FMF and HS are both inflammatory diseases involving young patients, with HS possibly being an autoinflammatory disease. Although their association seems to be fortuitous, both can induce an important inflammation state that could lead to AA amyloidosis and require a close monitoring of clinical signs and acute-phase reactants. Anakinra was successful in treating the only patient with both HS, FMF and amyloidosis. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  20. Assessment of aortic wall stiffness in patients with Familial Mediterranean Fever.

    PubMed

    Tavil, Yusuf; Oztürk, Mehmet Akif; Ureten, Kemal; Sen, Nihat; Kaya, Mehmet Güngör; Cemri, Mustafa; Cengel, Atiye

    2008-05-01

    To evaluate aortic wall stiffness and its relation between the aortic stiffness and the left ventricular function in patients with Familial Mediterranean Fever (FMF). The study population was composed of 31 patients with FMF in attack-free period (12 men, 19 women; mean age: 36+/-7 years) and 27 healthy subjects (10 men, 17 women; mean age: 34+/-7 years) who had volunteered to participate. Aortic stiffness indices, aortic strain and distensibility, were calculated from the aortic diameters measured by echocardiography and blood pressure obtained by sphygmomanometry. There were significant differences between the control and the patient group in aortic strain (mean (SD), 7.23+/-2.14 versus 4.91+/-1.66%, p=0.01) and distensibility (4.02+/-1.42 versus 2.84+/-1.46, 10(-6)cm(2)dyn(-1), p=0.001). Although there was no correlation between the aortic stiffness parameters and the left ventricular function parameters, there were significant negative correlations between the disease duration and aortic strain index (r=-0.29, p<0.001), and between the disease duration and distensibility (r=-0.32, p<0.001). Aortic stiffness measurements were found abnormal in patients with FMF. We have also demonstrated that there were significant correlations between aortic stiffness parameters and disease duration.

  1. Triggers for attacks in familial Mediterranean fever: application of the case-crossover design.

    PubMed

    Yenokyan, Gayane; Armenian, Haroutune K

    2012-05-15

    The etiology of recurrent attacks of serositis in familial Mediterranean fever (FMF) is not completely understood. Uncontrolled clinical case series have reported that factors associated with emotional, physiological, or physical stress precede and might trigger the attacks. This case-crossover study, conducted between July 2007 and May 2008, aimed to estimate the role of precipitating factors in attacks in a sample of Armenian FMF patients in Yerevan, Armenia, where 104 patients contributed 55 case and 189 control time periods. The authors used conditional logistic regression to compare frequency of exposure to stressful events, strenuous physical activity, menstrual periods, and high-fat food consumption prior to FMF attacks and on attack-free random days. Multiple stressful life events predicted FMF attacks 2 days following the event. After adjustment for treatment, an additional stressful event was associated with an estimated 70% increase in the odds of having an FMF attack on the second day (95% confidence interval: 1.04, 2.79). High levels of perceived stress were also associated with FMF attacks. Physical exertion and high-fat diet did not increase the likelihood of FMF attacks. The possibility of prevention of attacks in FMF needs to be tested through stress-reduction interventions.

  2. Frosted Branch Angiitis Secondary to Familial Mediterranean Fever Resembling Central Retinal Vein Occlusion

    PubMed Central

    Ozdal, Pınar Çakar; Teke, Mehmet Yasin

    2016-01-01

    Purpose. To report a case of unilateral frosted branch angiitis (FBA) resembling central retinal vein occlusion associated with Familial Mediterranean Fever (FMF). Case Report. A 32-year-old woman presented with progressive, painless vision loss in her left eye lasting for 2 days. She was clinically diagnosed with FMF 2 months ago. The best-corrected visual acuity (BCVA) was 20/20 in her right eye and there was light perception in the left. Ophthalmologic examination revealed severe retinal vasculitis showing clinical features of FBA in the left eye. 64 mg/day oral methylprednisolone was started. A significant improvement in retinal vasculitis was observed in two weeks. However, BCVA did not increase significantly due to subhyaloid premacular hemorrhage. Argon laser posterior hyaloidotomy was performed. One week after hyaloidotomy, visual acuity improved to 20/20 and intravitreal hemorrhage disappeared. Four months after the first attack, FBA recurred. Oral methylprednisolone dosage was increased to 64 mg/day and combined with azathioprine 150 mg. At the end of 12-month follow-up, the BCVA was 20/25 and development of epiretinal membrane was observed in the left eye. Conclusions. Frosted branch angiitis may occur with gene abnormalities as an underlying condition. Our case showed that FMF might be a causative disease. PMID:28044118

  3. Serum Amyloid A Level in Egyptian Children with Familial Mediterranean Fever

    PubMed Central

    Lofty, Hala M.; Marzouk, Huda; Nabih, Mohammad; Mostafa, Noha; Salah, Ahmed; Rashed, Laila

    2016-01-01

    Background and Objectives. SAA is an acute-phase reactant detected during an FMF attack or other inflammatory conditions. High SAA levels may increase the risk of amyloidosis. The aim of the study is to measure the serum amyloid A (SAA) level in a group of Egyptian children with familial Mediterranean fever (FMF) and study its various correlates, if any. Methods. The study enrolled seventy-one children with FMF. Results. SAA level was high in 78.9% of the studied patients with a mean of 81.62 ± 31.6 mg/L, and CRP was positive in 31% of patients. There was no significant releation between SAA level and any demographic or clinical manifestation. High SAA was more frequent in V726A allele (16.9%) followed by M694V allele (12.3%). Elevated SAA levels were more frequent in patients on low colchicine doses. Forty-five percent (45%) of patients have low adherence to colchicine therapy. Interpretation and Conclusion. High SAA levels were detected two weeks after last FMF attack in a large percentage of Egyptian FMF children. This indicates that subclinical inflammation continues during attack-free periods, and SAA could be used as a marker of it. PMID:28070191

  4. Evaluation of Ovarian Reserve with Anti-Müllerian Hormone in Familial Mediterranean Fever.

    PubMed

    Şahin, Ali; Karakuş, Savaş; Durmaz, Yunus; Yıldız, Çağlar; Aydın, Hüseyin; Cengiz, Ahmet Kıvanç; Güler, Duygu

    2015-01-01

    Objective. To investigate ovarian reserves in attack-free familial Mediterranean fever (AF-FMF) patients at the reproductive age by anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, and hormonal parameters. Methods. Thirty-three AF-FMF patients aging 18-45 years and 34 healthy women were enrolled and FSH, LH, E2, PRL, and AMH levels were measured in the morning blood samples at 2nd-4th days of menstruation by ELISA. Concomitant pelvic ultrasonography was performed to calculate AFC and ovarian volumes. Results. In FMF patient group, median AMH levels were statistically significantly lower in the M69V mutation positive group than in the negative ones (P = 0.018). There was no statistically significant difference in median AMH levels between E148Q mutation positive patients and the negative ones (P = 0.920). There was also no statistically significant difference in median AMH levels between M680I mutation positive patients and the negative ones (P = 0.868). No statistically significant difference was observed in median AMH levels between patients who had at least one mutation and those with no mutations (P = 0.868). We realized that there was no difference in comparisons between ovarian volumes, number of follicles, and AMH levels ovarian reserves when compared with FMF patients and healthy individuals. Conclusions. Ovarian reserves of FMF pateints were similar to those of healthy subjects according to AMH. However, AMH levels were lower in FMF patients with M694V mutation.

  5. Does enthesopathy relate to M694V gene mutation in patients with Familial Mediterranean fever?

    PubMed

    Yilmaz, Ömer; Kısacık, Bünyamin; Ozkan, Fuat; Güven, Gülçimen; Unlü, Elif Nisa; Pehlivan, Yavuz; Onat, Ahmet Mesut

    2013-11-01

    Familial Mediterranean fever (FMF) is a systemic hereditary autoinflammatory disorder. The present study aimed to investigate the relationship of enthesitis to FMF and to search the potential association between enthesitis and MEFV gene missense variations in patients with FMF. The study consisted of 72 FMF patients (mean age 29.12 ± 11.47 years, 32 females), 29 patients with ankylosing spondylitis (AS) (mean age 34.14 ± 11.73 years, 16 females), and 34 healthy volunteers (mean age 23.06 ± 6.41 years, 8 females). FMF patients were classified according to the kind of MEFV gene mutation. Doppler ultrasound was used to determine enthesitis based on the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) scoring system. OMERACT score was significantly different between FMF patients and control group (p < 0.001 in all patients, p = 0.009 in men, and p = 0.002 in women). However, it was not significantly different between FMF and AS patients in both sexes. OMERACT score did not differ between FMF patients with and without M694V gene mutation. The best cutoff point of OMERACT score to predict enthesitis was found as ≥0.5 with sensitivity of 29 %, specificity of 100 %, positive predictive value of 100 %, and negative predictive value of 40 %.

  6. Colchicine-clarithromycin-induced rhabdomyolysis in Familial Mediterranean Fever patients under treatment for Helicobacter pylori.

    PubMed

    Cohen, Oren; Locketz, Garrett; Hershko, Alon Y; Gorshtein, Alexander; Levy, Yair

    2015-11-01

    Chronic administration of colchicine remains a mainstay of therapy for patients with Familial Mediterranean Fever (FMF). As this medication is a strong CYP3A4 inhibitor, it has the potential to interact with many routinely used medications. One such medication is clarithromycin, itself a strong inhibitor of the same enzyme, and a typical choice for triple therapy eradication of H. pylori. Various sequelae of colchicine-clarithromycin interaction have been documented and can be expected by prescribing physicians, with rhabdomyolysis, though rare, being among the most serious. Review of cases from a tertiary academic medical center and full PubMed/MEDLINE literature review. Despite the prevalence of diseases treated with clarithromycin and the expected drug interaction with colchicine, only two cases in the literature document clinical rhabdomyolysis due to colchicine-clarithromycin interaction. In neither case, however, were patients undergoing treatment for FMF. Herein, we describe the first two cases in the literature of clinical rhabdomyolysis in FMF patients under colchicine therapy after administration of clarithromycin as part of therapy treating H. pylori infection.

  7. Risk factors for subclinical inflammation in children with Familial Mediterranean fever.

    PubMed

    Bayram, Meral Torun; Çankaya, Tufan; Bora, Elçin; Kavukçu, Salih; Ülgenalp, Ayfer; Soylu, Alper; Türkmen, Mehmet

    2015-08-01

    Familial Mediterranean fever (FMF) is the most common autosomal recessive inherited inflammatory disease characterized by attacks of painful inflammation. Some patients with FMF have subclinical inflammation persisting between the attacks. We aimed to identify the demographic, clinical and genetic risk factors for subclinical inflammation in children with FMF. The medical records of the children with FMF were evaluated retrospectively for acute-phase response along with gender, age at the onset of symptoms and at the time of diagnosis, clinical signs and symptoms, the presence of amyloidosis and MEFV genotype. Patients with persistently elevated acute-phase response between the attacks were considered to have subclinical inflammation. Patients with or without subclinical inflammation (Group 1 and Group 2, respectively) were compared for the parameters defined above. Independent risk factors for subclinical inflammation were identified by multivariate logistic regression analysis. There were 105 children (male/female: 52/53) who were compliant on colchicine treatment. Subclinical inflammation was detected in 22 (20 %) patients. Group 1 had significantly higher rate of myalgia, arthritis/arthralgia, erysipelas like erythema, amyloidosis, protracted febrile myalgia and M694V mutation compared with Group 2. However, only the presence of myalgia and erysipelas like erythema were found to be independent risk factors for subclinical inflammation (OR 9.8 and 5.9, respectively). Children with FMF who have myalgia and erysipelas like erythema during the attacks are particularly at risk of ongoing inflammation and should be closely monitored for subclinical inflammation even during attack-free periods.

  8. Normal Heart Rate Variability in Colchicine-Resistant Familial Mediterranean Fever Patients.

    PubMed

    Nussinovitch, Naomi; Esev, Konstantin; Lidar, Merav; Nussinovitch, Udi; Livneh, Avi

    2015-05-01

    The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF. To evaluate ANS function in colchicine non-responders by using the HRV tool. The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls. No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters. Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults.

  9. Anti-IL-1 treatment in familial Mediterranean fever and related amyloidosis.

    PubMed

    Özçakar, Z Birsin; Özdel, Semanur; Yılmaz, Songül; Kurt-Şükür, E Didem; Ekim, Mesiha; Yalçınkaya, Fatoş

    2016-02-01

    Colchicine is the standard treatment in familial Mediterranean fever (FMF) patients. New treatment strategies are needed in FMF patients who were unresponsive to colchicine therapy or who had developed amyloidosis. The aim of this study was to present clinical-laboratory features and treatment responses of pediatric FMF patients that were treated with anti-IL-1 therapies. Files of patients who had been followed in our department with diagnosis of FMF were retrospectively evaluated. Patients that have been receiving anti-IL-1 therapies (anakinra or canakinumab) were included to the study. All patients were interpreted with respect to the demographic data, clinical and laboratory features of the disease, genetic analysis of MEFV mutations and treatment responses. Among 330 currently registered FMF patients, 13 patients were included to the study. Seven of them received anti-IL-1 therapy due to colchicine resistance and 6 due to FMF-related amyloidosis (1 of them with nephrotic syndrome, 2 with chronic kidney disease, 3 with renal transplantation). In all treated patients, attacks completely disappeared or decreased in frequency; partial remission occured in nephrotic syndrome patient; and their life quality improved. Anti-IL-1 therapies can be successfully used in colchicine-resistant FMF patients and patients with amyloidosis during childhood and adolescent period without major side effects.

  10. Evaluation of the mean platelet volume in children with familial Mediterranean fever.

    PubMed

    Arıca, Seçil; Ozer, Cahit; Arıca, Vefik; Karakuş, Ali; Celik, Tanju; Güneşaçar, Ramazan

    2012-11-01

    To evaluate the Mean Platelet Volume (MPV) levels in children diagnosed with familial Mediterranean fever (FMF), during attack and attack-free periods. The records of a total of 117 children with FMF, diagnosed using the Tel-Hashomer criteria, have been scanned. The study consisted of 53 patients during an attack (group 1), 64 patients in attack-free period (group 2), and 57 healthy controls (group 3). Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded. The MPV and platelet values in FMF patients during attack (group 1) and FMF patients during attack-free periods (group 2) have been found to be significantly higher than those of the health control group (group 3). Positive correlation has been found between the MPV and platelet values in Group 1 and the disease's severity score (r = 0.224, and r = 0.268, respectively). Positive correlation (r = 0.528, and r = 0.485, respectively) has been also identified between MPV and blood platelet count in patients in Group 1 and 2. No correlation was found between the Colchicine treatment period and MPV (r = -0.005). The MPV values in the complete group of FMF diagnosed children have been found to be much higher compared to those in healthy children. As a consequence, we consider the MPV value as a useful marker that demonstrates the risk of early stage atherosclerosis in children with FMF.

  11. Association between colchicine resistance and vitamin D in familial Mediterranean fever.

    PubMed

    Ozer, Ismail; Mete, Turkan; Turkeli Sezer, Ozlem; Kolbasi Ozgen, Guyem; Kucuk, Gultekin Ozan; Kaya, Coskun; Kilic Kan, Elif; Duman, Gulhan; Ozturk Kurt, Hacer Pinar

    2015-08-01

    Although colchicines are the only effective treatment of familial Mediterranean fever (FMF), resistance to colchicines (CR) which is observed in up to 30% of the patients is still a problem. Clinically, resistance to colchicine is defined as three or more attacks within the last 6 months period while using ≥2 mg/day colchicine. Previous studies have shown decreased vitamin D levels in FMF patients compared with healthy controls. The aim of this study is to evaluate whether vitamin D levels differ between CR and non-CR FMF patients. This study included 64 FMF patients who were being followed in Nephrology Clinic of Samsun Research and Education Hospital for at least 1 year. FMF was diagnosed according to the criteria defined by Livneh et al. Serum 25-hydroxy vitamin D (25-OHD) concentration (ng/mL) was detected in all FMF patients who were not in an acute attack period. From 64 patients 29 were accepted as CR. Mean 25-OHD level was 9.39 ± 1.00 ng/mL in CR patients and 18.48 ± 1.09 ng/mL in colchicine responsive patients (p < 0.001). Plasma vitamin D levels were significantly lower in colchicine resistant patients. Vitamin D deficiency may be a factor in etiopathogenesis of CR. Studies in larger patient samples that particularly evaluate the response to vitamin D replacement in CR FMF patients are needed.

  12. Relationship between periodontal destruction and gene mutations in patients with familial Mediterranean fever.

    PubMed

    Sezer, Ufuk; Şenyurt, Süleyman Ziya; Özdemir, Eda Çetin; Zengin, Orhan; Üstün, Kemal; Erciyas, Kamile; Kısacık, Bünyamin; Onat, Ahmet Mesut

    2016-07-01

    Recent studies have shown that genetic factors involved in the host responses might determine the disease severity for both familial Mediterranean fever (FMF) and periodontitis. The present study aimed to investigate the relationship of FMF with periodontitis and to search for the potential association between periodontitis and MEFV gene missense variations in patients with FMF. The study consisted of 97 FMF patients and 34 healthy volunteers. FMF patients were classified according to the kind of MEFV gene mutation: (1) patients with homozygous M694V gene mutation, (2) patients with heterozygous M694V gene mutation, and (3) patients with MEFV gene different mutations. Gingival Index (GI), Plaque Index (PI), probing pocket depth (PD), and clinical attachment level (CAL) were measured in all participants. The results of multivariate logistic regression showed a highly significant association between homozygous M694V gene mutation and periodontitis in FMF patients (p < 0.05). After adjusting for potential confounders (smoking, body weight, age, and gender), FMF patients with homozygous M694V gene mutation were 3.51 (1.08-11.45) times more likely to present periodontitis than the other FMF patients. These results indicate that the presence of homozygous M694V gene mutation seems to increase the risk for periodontitis in FMF patients.

  13. Semaphorin 3A, a potential immune regulator in familial Mediterranean fever.

    PubMed

    Rimar, Doron; Rosner, Itzhak; Slobodin, Gleb; Rozenbaum, Michael; Halasz, Katy; Jiries, Nizar; Kaly, Lisa; Boulman, Nina; Vadasz, Zahava

    2016-01-01

    Semaphorin 3A (sema3A) plays a regulatory role in immune responses with effects on both T and B regulatory cells. Familial Mediterranean fever (FMF) is an autoinflammatory disease, yet a possible role for regulatory T and B cells has been described. 17 FMF patients during attack and then in remission, 8 FMF patients with smoldering disease and 12 healthy controls were enrolled. Sema3A in serum and its expression on regulatory T and B cells was evaluated. Clinical parameters of FMF patients were assessed. Semaphorin 3A serum level was lower in FMF patients during attack, smoldering disease or remission than healthy controls, (242.3±9.8 ng/ ml vs. 258.9±11.5 ng/ml vs. 232.5±22.7 ng/ml vs. 323.3±160.2 ng/ml, respectively p<0.05). This decrease was specifically noted on regulatory B and T cells in FMF patients during attack and in smoldering disease and normalized in remission. Sema3A expression on T and B regulatory lymphocytes is low in FMF patients during attack and in smoldering disease compared to the expression in remission and healthy controls. These results are in line with previous descriptions suggesting a possible role of regulatory T cells in termination of FMF attacks. Further studies are needed to verify these preliminary findings.

  14. Ischemia-Modified Albumin and Atherosclerosis in Patients With Familial Mediterranean Fever.

    PubMed

    Kucuk, Adem; Uslu, Ali Ugur; Arslan, Sevket; Balta, Sevket; Ozturk, Cengiz; Uysal, Saliha; Yılmaz, Ramazan; Sakız, Davut; Kayrak, Mehmet

    2016-05-01

    The constriction of vessels due to atherosclerotic lesions causes hypoxia/ischemia and oxidative changes resulting in transformation of free albumin to ischemia-modified albumin (IMA) in the circulation and increased carotid intima-media thickness (cIMT). We investigated the reliability of IMA increase in evaluating atherosclerosis in patients with familial Mediterranean fever (FMF) compared with cIMT. Patients with FMF (n = 58) diagnosed by the Tel-Hashomer criteria in attack-free period and 38 healthy people were included in the study. Patient demographics as well as the clinical and laboratory characteristics of the healthy controls and patients with FMF were noted. The IMA levels and cIMT in patients with FMF were 0.30 ± 0.09 absorbance units (ABSUs) and 1.12 ± 0.27 mm, respectively, and in the control group, IMA levels and cIMT were 0.25 ± 0.07 ABSU and 0.74 ± 0.26 mm, respectively. The IMA levels and cIMT were significantly higher in patients with FMF than in controls (P= .020 andP< .0001, respectively). The IMA values showed positive correlation with cIMT in patients with FMF(r= .302,P= .041). Our results reveal that IMA--an oxidative stress marker--may be an indicator of atherosclerosis in patients with FMF. This finding deserves further investigation. © The Author(s) 2015.

  15. Assessment of renal involvement in patients with familial Mediterranean fever: a clinical study from Ardabil, Iran.

    PubMed

    Bashardoust, B; Maleki, N

    2014-11-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent episodes of painful inflammation in the abdomen, chest or joints. The association between FMF and non-amyloid glomerulopathies are unusual. In this study, we describe our experiences and observations about renal involvement in patients with FMF. A total of 108 patients with FMF was enrolled in the study. Twelve patients with FMF were referred to the Nephrology Service, for evaluation and assessment of the degree of renal involvement. All the 12 patients underwent percutaneous ultrasound-guided renal biopsies and genetic analysis. On microscopic examination of the kidney specimens, six patients were found to have amyloidosis, five focal segmental glomerulosclerosis and one patient membranoproliferative glomerulonephritis. It seems that in patients with FMF and renal amyloidosis, the response to treatment with colchicine is excellent, but in patients with FMF and focal segmental glomerulosclerosis, the response to treatment with colchicine is poor. We present an evidence-based algorithm, constructed based on literature review, to aid decision making in management of renal involvement in patients with FMF. The results of our study suggest that in patients with FMF and renal involvement, non-amyloid renal lesions should be considered in the differential diagnosis in addition to amyloidosis. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  16. Efficacy of interleukin-1 targeting treatments in patients with familial mediterranean Fever.

    PubMed

    Cetin, Pinar; Sari, Ismail; Sozeri, Betul; Cam, Ozlem; Birlik, Merih; Akkoc, Nurullah; Onen, Fatos; Akar, Servet

    2015-02-01

    Herein, we reported our experience in colchicine-resistant familial Mediterranean fever (FMF) patients who are treated with anti-interleukin-1 (IL-1) drugs. A retrospective review of medical records of anti-IL-1 recipients was performed. The main clinical characteristics of these patients and the evolution after anti-IL-1 were recorded. There were 20 patients (11 male [M] and 9 female [F]). Despite regular colchicine treatment, median number of attacks per month and per year was 1 (1-4) and 12 (4-50), respectively. Twelve patients were receiving anakinra, and eight patients were treated with canakinumab. The number of monthly and yearly attacks after IL-1 treatment was significantly decreased after the biologic agent (p < 0.05). One patient did not respond to the treatment, and one patient developed serious infection during anti-IL-1. We also observed a significant decrease in proteinuria in the amyloidosis complicated FMF patients. Anti-IL-1 targeting drugs seem safe and effective therapies in colchicine-resistant FMF.

  17. Fas and Fas ligand gene polymorphisms in Turkish patients with Familial Mediterranean Fever.

    PubMed

    Ozel, Emine Gulce; Duran, Gulay Gulbol; Celik, Muhammet Murat; Duran, Nizami; Gunesacar, Ramazan

    2017-08-05

    Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent fever, serositis, abdominal pain, arthritis, arthralgia and erysipelas like erythema. Fas and Fas ligand molecules play a central role in the apoptosis signaling of various cell types including neutrophils. Neutrophils are the major cell population involved in acute inflammation in patients with FMF and the role of Fas and Fas ligand molecules in this cells of FMF patients may be crucial. Therefore, in the present study, we aimed to investigate whether the Fas cell surface receptor gene (FAS); NM_000043.5: c.-671A>G (rs1800682, MvaI) and Fas ligand gene (FASLG), NM_000639.2: c.-844C>T (rs763110, BsrD1) functional polymorphisms in patients with FMF and their relation to the main clinical features of the disease. The polymorphisms in the promoter regions of FAS c.-671A>G and FASLG c.-844C>T were investigated in 97 non-related FMF patients and 70 non-related healthy controls by using PCR-RFLP technique. The frequencies of FAS c-671AG genotype and G allele were not significantly different between FMF patients and healthy subjects. The frequency of FASLG -844TC genotype was found significantly different between the patients with FMF and healthy controls whereas T or C allele frequency was not significantly different between the groups. Haplotype frequencies of the studied polymorphisms were also not significantly different between FMF patients and controls. There were no correlations between the studied FAS c.-671A>G and FASLG c.-844C>T polymorphisms and the main clinical features of FMF such as fever, arthritis, abdominal and chest pain, arthralgia and erysipelas-like erythema. Our findings suggest that FAS c.-671AG genotype or G allele and FASLG c.-844 allele are not to be a risk factor, whereas FASLG c.-844TC genotype may be protective in the studied Turkish population. According to our results we may suggest that although not statistically significant

  18. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study.

    PubMed

    Tunca, Mehmet; Akar, Servet; Onen, Fatos; Ozdogan, Huri; Kasapcopur, Ozgur; Yalcinkaya, Fatos; Tutar, Ercan; Ozen, Seza; Topaloglu, Rezan; Yilmaz, Engin; Arici, Mustafa; Bakkaloglu, Aysin; Besbas, Nesrin; Akpolat, Tekin; Dinc, Ayhan; Erken, Eren

    2005-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease that is prevalent among eastern Mediterranean populations, mainly non-Ashkenazi Jews, Armenians, Turks, and Arabs. Since a large proportion of all the FMF patients in the world live in Turkey, the Turkish FMF Study Group (FMF-TR) was founded to develop a patient registry database and analyze demographic, clinical, and genetic features. The cohort was composed of 2838 patients (mean age, 23.0 +/- 13.33 yr; range, 2-87 yr), with a male:female ratio of 1.2:1. There was a mean period of 6.9 +/- 7.65 years from disease onset to diagnosis; the period was about 2 years shorter for each decade since 1981. Ninety-four percent of patients were living in the central-western parts of the country; however, their familial origins (70% from the central-eastern and Black Sea regions) reflected not only the ongoing east to west migration, but also the historical roots of FMF in Turkey. Patients' clinical features included peritonitis (93.7%), fever (92.5%), arthritis (47.4%), pleuritis (31.2%), myalgia (39.6%), and erysipelas-like erythema (20.9%). Arthritis, arthralgia, myalgia, and erysipelas-like erythema were significantly more frequent (p < 0.001) among patients with disease onset before the age of 18 years. Genetic analysis of 1090 patients revealed that M694V was the most frequent mutation (51.4%), followed by M680I (14.4%) and V726A (8.6%). Patients with the M694V/M694V genotype were found to have an earlier age of onset and higher frequencies of arthritis and arthralgia compared with the other groups (both p < 0.001). In contrast to other reported studies, there was no correlation between amyloidosis and M694V homozygosity in this cohort. However, amyloidosis was still remarkably frequent in our patients (12.9%), and it was prevalent (27.8%) even among the 18 patients with a disease onset after age 40 years. Twenty-two patients (0.8%) had nonamyloid glomerular diseases. The high prevalence of vasculitides

  19. The association of endoplasmic reticulum aminopeptidase-1 (ERAP-1) with Familial Mediterranean Fever (FMF).

    PubMed

    Sezgin, Gülbüz; Dabak, Reşat; Kaya, Fatih Oner; Kotevoglu, Nurdan; Uygur-Bayramiçli, Oya; Nalbant, Selim

    2016-02-01

    The ERAP1 gene cleaves the receptors and reduces their ability to transmit chemical signals to the cell that affect the process of inflammation and, secondly, it cleaves many types of proteins into small peptides that are recognized by the immune system. ERAP-1 gene mutations may create a sensitivity for Familial Mediterranean Fever (FMF). We included 15 FMF patients with the M694 (+) mutation in the study in order to exclude patients without pyrin gene mutations and create a homogeneous study group. Fifteen patients with ulcerative colitis formed the control group. There wasn't any case without ERAP-1 gene mutations. At least one mutation at exon 3 or exon 10 was found in all cases in both groups. There were 14 ERAP-1 gene mutations at exon 10 and 11 at exon 3 in patients with FMF. Interestingly, if there were ERAP-1 gene mutations at exon 3, a p.Arg127 Pro (c.380 G>C) mutation always existed for three FMF patients with polymorphic mutations at this exon. There were 11 ERAP-1 gene mutations at exon 10 and 12 gene mutations at exon 3 in patients with ulcerative colitis. Exon 3 mutations were usually single p.Arg127 Pro (c.380 G>C) mutations for 12 patients with ulcerative colitis as seen in the patients with FMF. The single mutation was always p.Ser453 Ser (c.1359T>C) for patients with ulcerative colitis at exon 10. There are more ERAP-1 mutations in the FMF group in comparison to the ulcerative colitis group. So, there may be a strong susceptibility to ERAP-1 gene mutations in FMF patients according to our results. However, further studies with larger study and control groups are needed.

  20. The role of regulatory T cells in familial Mediterranean fever (FMF).

    PubMed

    Rimar, D; Rosner, I; Slobodin, G; Boulman, N; Toubi, E; Kessel, A; Peri, R; Rozenbaum, M

    2012-05-01

    The role of regulatory T cells (T-regs) in familial Mediterranean fever (FMF) was never evaluated. Preliminary studies that we have conducted suggested a rise in the number of regulatory T cells after FMF attacks reaching a maximal level at 7 days. The aim of this study was to evaluate the percentage and activity of regulatory T cells in FMF. Six patients with refractory FMF and six healthy controls were evaluated. The percentage of T-reg cells and forkhead box protein 3 (Foxp3) expression was evaluated and compared between four states: FMF in remission, FMF at the first day of an attack, FMF 7 days after the start of the attack, and healthy controls. Four females and two males were included. All patients had FMF with high severity score, 2.8 ± 0.4 (0-3). The mean age was 31.6 ± 6.2. The mean age at onset was 9.3 ± 9.3. The mean colchicine dose was 2.6 mg ± 0.4. The expression of Foxp3 7 days after the attacks was significantly higher than in FMF at the first day of the attack, FMF in remission, and healthy controls 10.08 ± 2.36 vs. 7.005 ± 0.3 vs. 5.3 ± 1.06 vs. 4.44 ± 1.8; p < 0.05 (Fig.1). The percentage of T-regs in peripheral blood was not statistically different between the four groups. Theexpression of Foxp3 by T-regs increases 7 days after attacks of FMF. Anti-inflammatory cytokines interleukin-10 and TGF-β are known to activate T-regs and have been reported to increase in FMF attacks in line with the present findings. It is suggested that T-regs may have a role in terminating FMF attacks.

  1. Acute phase response and oxidative stress status in familial Mediterranean fever (FMF).

    PubMed

    Guzel, Savas; Andican, Gulnur; Seven, Arzu; Aslan, Mahmure; Bolayirli, Murat; Guzel, Eda Celik; Hamuryudan, Vedat

    2012-06-01

    We aimed to determine acute phase response (APR) and oxidative stress in patients with familial Mediterranean fever (FMF) and compare these characteristics with those in healthy controls; 20 patients with FMF and 15 healthy controls were enrolled in the study. The erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), fibrinogen, and leukocyte levels were determined as markers of APR. Thiobarbituric acid reactive substances (TBARS), conjugated diene, and lipid hydroperoxide levels were measured as markers of lipid peroxidation. Carbonyl group and thiol (T-SH) levels were analyzed to determine the oxidative damage to proteins, and 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to reflect DNA oxidation. The erythrocyte glutathione (GSH) level, and glutathione peroxidase (GSH-Px), CuZn superoxide dismutase (CuZn SOD), and catalase activities were measured as markers of antioxidant status. Conjugated diene (p < 0.001) and carbonyl group (p < 0.05) levels were significantly higher and GSH-Px activity (p < 0.01) was significantly lower in FMF patients compared with controls. FMF patients in the attack period (n = 8) had significantly higher CRP, ESR, fibrinogen, and leukocyte levels (p < 0.001) than patients in the attack-free period (n = 12). The T-SH level (p < 0.05) was significantly higher and CuZn SOD activity was significantly lower (p < 0.05) in FMF patients in the attack period. The findings revealed upregulated APR during the attack period in FMF patients and enhanced oxidative stress in the FMF patients as compared to controls.

  2. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF).

    PubMed

    Demirkaya, Erkan; Acikel, Cengizhan; Hashkes, Philip; Gattorno, Marco; Gul, Ahmet; Ozdogan, Huri; Turker, Turker; Karadag, Omer; Livneh, Avi; Ben-Chetrit, Eldad; Ozen, Seza

    2016-06-01

    To develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice. Candidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi survey, the candidate criteria, defined by the survey, were discussed by experts in a consensus meeting. Each expert brought data of clinical manifestations, laboratory findings and physician's global assessments (PGAs) of minimum 20 patients from their centres. We used the PGAs for disease severity as a gold standard. Logistic regression analysis was used to evaluate the predicting value of each item, and receiver operating characteristic curve analysis was performed to demonstrate the success of the criteria set. A total of 281 patients consist of 162 children and 119 adults with FMF were enrolled and available for validity analysis: Nine domains were included in the final core set of variables for the evaluation of disease severity in FMF. The International Severity Score for FMF (ISSF) may reach a maximum of 10 if all items are maximally scored. The threshold values to determine: severe disease ≥6, intermediate disease 3-5, mild disease ≤2. Area under the curve was calculated as 0.825 for this set in the whole group. The initial validity of ISSF both in children and adult with FMF was demonstrated. We anticipate that it will provide a robust tool to objectively define disease severity for clinical trials, future research as well as for therapeutic decisions in managing patients with FMF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Anti-cyclic citrullinated peptides positivity rate in patients with familial Mediterranean fever.

    PubMed

    Ceri, Mevlut; Unverdi, Selman; Altay, Mustafa; Ureten, Kemal; Oztürk, M Akif; Gönen, Namik; Duranay, Murat

    2010-01-01

    To investigate the prevalence and levels of anti-cyclic citrullinated peptide antibodies (anti-CCP) in patients with familial Mediterranean fever (FMF) with and without arthritis. Eighty-three patients with FMF and 43 healthy controls were included in the study. Thirty seven FMF patients had a history of arthritis, and 46 patients did not. Serum antibodies directed to the anti-CCP were assessed with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Values <20U were considered negative, between 20 and 39U low, 40-99U moderate, and >100U high positive. Positivity rate of anti-CCP in the whole FMF group (14.5%) was three-fold higher than the control group (4.7%). However, the difference failed to achieve a statistically significant level (p=0.09). Anti-CCP levels were 21±30.1 in patients with arthritis and 13.1±10.3 in the non arthritic group (p<0.05). Anti-CCP positivity rates were 10/37 (27%) in patients with arthritis and 2/46 (4.3%) in patients without arthritis (p<0.005). Five FMF patients with arthritis (13.5%) had moderate-high anti-CCP levels (>40U/ml). Anti-CCP levels were between 20-39U/ ml in 2FMF patients without arthritis and in 2 healthy controls. Anti-CCP positivity rate is higher in FMF patients with arthritis (27%) than healthy controls (4.7%) (p<0.005). Anti-CCP prevalence is higher in FMF patients with arthritis than without arthritis, and that a significant proportion of FMF patients with arthritis (13.5%) had moderate-high titers of anti-CCP. Therefore, anti-CCP antibodies may not be a reliable indicator to differentiate between FMF arthritis and rheumatoid arthritis.

  4. Higher Pentraxin-3 Levels are Associated With Inflammation in Familial Mediterranean Fever.

    PubMed

    Bulut, Mesudiye; Ceri, Mevlut; Unverdi, Selman; Altay, Mustafa; Senes, Mehmet; Ecemis, Zafer Aydın; Duranay, Murat

    2016-11-01

    Circulating levels of Pentraxin-3 (PTX3) have been shown to increase in several inflammatory conditions. However, there is no information about the levels of PTX3 in patients with familial Mediterranean fever (FMF). This study was designed to evaluate the serum PTX3 levels in patients with FMF during attack and free-attack periods. Twenty FMF patients in attack and free-attack period, and 20 age-, sex-, and body mass index-matched healthy controls were included in the study. Blood samples were obtained within the first 24 h of the attack period and between attacks, and levels of white blood cell, erythrocyte sedimentation rate, Fibrinogen, high sensitive CRP, and PTX3 were determined. PTX3 levels during the attack period were not significantly different from those in free-attack patients (4.9 ± 4.6 ng/ml vs. 2.8 ± 1.4 ng/ml, P > 0.05). However, both attack and free-attack patients had significantly higher PTX3 levels than healthy controls (4.9 ± 4.6 ng/ml vs. 1.8 ± 0.8 ng/ml, P < 0.001; 2.8 ± 1.4 ng/ml vs. 1.8 ± 0.8 ng/ml, P < 0.025, respectively). PTX3 levels were not markedly affected from FMF attacks, but high level of PTX3 in free-attack period of FMF patients shows ongoing subclinical inflammation. However, further studies are needed to determine its usefulness as a marker in clinical practice. © 2016 Wiley Periodicals, Inc.

  5. Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever

    PubMed Central

    Koga, Tomohiro; Migita, Kiyoshi; Sato, Shuntaro; Umeda, Masataka; Nonaka, Fumiaki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Masumoto, Junya; Agematsu, Kazunaga; Yachie, Akihiro; Yoshiura, Koh-Ichiro; Eguchi, Katsumi; Kawakami, Atsushi

    2016-01-01

    Abstract The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients. We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in “attack” or “remission” was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines’ serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%). Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks. PMID:27100444

  6. Evaluation of Ovarian Reserve with Anti-Müllerian Hormone in Familial Mediterranean Fever

    PubMed Central

    Şahin, Ali; Karakuş, Savaş; Durmaz, Yunus; Yıldız, Çağlar; Aydın, Hüseyin; Cengiz, Ahmet Kıvanç; Güler, Duygu

    2015-01-01

    Objective. To investigate ovarian reserves in attack-free familial Mediterranean fever (AF-FMF) patients at the reproductive age by anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, and hormonal parameters. Methods. Thirty-three AF-FMF patients aging 18–45 years and 34 healthy women were enrolled and FSH, LH, E2, PRL, and AMH levels were measured in the morning blood samples at 2nd–4th days of menstruation by ELISA. Concomitant pelvic ultrasonography was performed to calculate AFC and ovarian volumes. Results. In FMF patient group, median AMH levels were statistically significantly lower in the M69V mutation positive group than in the negative ones (P = 0.018). There was no statistically significant difference in median AMH levels between E148Q mutation positive patients and the negative ones (P = 0.920). There was also no statistically significant difference in median AMH levels between M680I mutation positive patients and the negative ones (P = 0.868). No statistically significant difference was observed in median AMH levels between patients who had at least one mutation and those with no mutations (P = 0.868). We realized that there was no difference in comparisons between ovarian volumes, number of follicles, and AMH levels ovarian reserves when compared with FMF patients and healthy individuals. Conclusions. Ovarian reserves of FMF pateints were similar to those of healthy subjects according to AMH. However, AMH levels were lower in FMF patients with M694V mutation. PMID:26064124

  7. Relationship between response to colchicine treatment and MDR1 polymorphism in familial Mediterranean fever patients.

    PubMed

    Uludag, Ahmet; Silan, Coskun; Atik, Sinem; Akurut, Cisem; Uludag, Aysegul; Silan, Fatma; Ozdemir, Ozturk

    2014-02-01

    Investigate the relationship between MDR1 C3435T polymorphism and colchicine response in Familial Mediterranean fever (FMF) patients. Patients (n=50) who received colchicine regularly, were willing to participate in the study, and attended control visits were included in the study. MDR1 C3435T genotype was defined by the real-time polymerase chain reaction method. Patients were divided into three groups. Patients, who recovered from episodes with standard colchicine treatment, and had no attack in the last 1 year were accepted as complete; patients whose episode number and intensity were decreased with the ongoing standard treatment as partial; and patients whose episodes were not decreased despite the standard treatment as nonresponders. MDR1 C and T allele frequencies of FMF patients with colchicine responses of complete, partial, and nonresponders were C=0.75 and T=0.25; C=0.56 and T=0.44; and C=0.50 and T=0.50, respectively. When complete responding patients were compared with the partial responding patients, subjects with CT genotype had 6.18 times more increased risk than with CC genotype (OR=6.18; p=0.015). Poor response risk of subjects with the T allele was increased 2.45 times more when compared with the C allele (p=0.03). MDR1 gene C3435T polymorphism enacts an important role on colchicine response in FMF; good response to colchicine treatment was related to the C allele, whereas poor response was related to the T allele in FMF.

  8. The effect of colchicine and disease severity on physical growth in children with familial Mediterranean fever.

    PubMed

    Yoldaş, Tuba Çelen; Çakar, Nilgün; Başaran, Özge; Acar, Banu; Uncu, Nermin; Çaycı, F Şemsa

    2016-06-01

    This study aimed to investigate the effects of colchicine on growth parameters in familial Mediterranean fever (FMF) patients. Fifty-one (29 girls, 22 boys) FMF patients were enrolled in the study. All of the patients were in the prepubertal stage and had not received colchicine treatment before the study. Anthropometric measurements, demographic features, clinical findings at diagnosis and during periods of attacks of FMF, disease activity, frequency of exacerbations, colchicine dosage, and weight and height measurements were recorded at an interval of 6 months. Height, weight, and body mass index standard deviation scores and Z-scores were calculated. The mean height standard deviation score (HSDS) was significantly increased from -0.64 ± 1.20 to -0.26 ± 1.07 (p < 0.001), the mean weight standard deviation score (WSDS) was significantly increased from -0.60 ± 1.03 to -0.45 ± 0.98 (p = 0.008), and the mean body mass index standard deviation score was decreased from -0.33 ± 1.06 to -0.47 ± 0.98 (p = 0.128) at 1 year after colchicine treatment compared with before initiation of treatment. In patients who had no FMF attacks during colchicine treatment, height and weight were significantly increased at 1 year (HSDS: p < 0.001 WSDS: p = 0.002), but in patients who had recurrent attacks, height and weight did not change (HSDS: p = 0.051, WSDS: p = 0.816). Even when subclinical inflammation is present, preventing attacks of FMF with colchicine allows growth to continue. However, suppression of subclinical inflammation and control of attacks of FMF are required for weight gain.

  9. Uniparental disomy of chromosome 16 in offsprings of Familial Mediterranean Fever (FMF) patients treated with colchicine

    SciTech Connect

    Korenstein, A.; Avivi, L.; Ravia, Y.

    1994-09-01

    Uniparental disomy (UPD), an altered mode of Mendelian inheritance, may reveal expression of recessive alleles due to the loss of heterozygosity, as well as imprinted genes. The mechanism causing UPD can be best elucidated in offsprings of individuals at high risk for chromosomal non-disjunction. Such individuals are Familial Mediterranean Fever (FMF) patients, who are routinely treated with the antimitotic agent colchicine, and, therefore, are expected to be at an increased risk for aneuploidy. A dominant mode of inheritance was observed in four FMF offsprings having one parent exhibiting the FMF phenotype (homozygote recessive) while the other was free of the mutant allele (as assumed from his ethnic background). Out of these, two exhibited UPD of chromosome 16, which carries the FMF gene, as judged from four different RFLP markers along this chromosome. Since in both case the UPD was of maternal origin, it is suggested that the colchicine-treated FMF mothers contributed two doses of chromosome 16, presumably due to meiotic non-disjunction, followed by a somatic loss of the paternal chromosome 16 in the embryo. The somatic chromosome loss is also assumed to be caused by the antimitotic drug since the mother continued to receive it during pregnancy. Whether the UPD arises from the colchicine treatment, from the high tendency of chromosome 16 to maternal non-disjunction or from both remains to be elucidated. Our results highlighted the importance of taking UPD into account when counseling individuals who are either treated with antimitotic agents or are carriers of recessive mutant alleles which are mapped to chromosomes prone to aneuploidy.

  10. Efficacy and safety of canakinumab in adolescents and adults with colchicine-resistant familial Mediterranean fever.

    PubMed

    Gül, Ahmet; Ozdogan, Huri; Erer, Burak; Ugurlu, Serdal; Kasapcopur, Ozgur; Davis, Nicole; Sevgi, Serhan

    2015-09-04

    This open-label pilot study aimed to investigate the efficacy of canakinumab in colchicine-resistant familial Mediterranean fever (FMF) patients. Patients with one or more attacks in a month in the preceding 3 months despite colchicine were eligible to enter a 30-day run-in period. Patients who had an attack during the first run-in period advanced to a second 30-day period. At the first attack, patients started to receive three canakinumab 150 mg subcutaneous injections at 4-week intervals, and were then followed for an additional 2 months. Primary efficacy outcome measure was the proportion of patients with 50 % or more reduction in attack frequency. Secondary outcome measures included time to next attack following last canakinumab dose and changes in quality of life assessed by SF-36. Thirteen patients were enrolled in the run-in period and 9 advanced to the treatment period. All 9 patients achieved a 50 % or more reduction in attack frequency, and only one patient had an attack during the treatment period. C-reactive protein and serum amyloid A protein levels remained low throughout the treatment period. Significant improvement was observed in both physical and mental component scores of the Short Form-36 at Day 8. Five patients had an attack during the 2-month follow-up, occurring median 71 (range, 31 to 78) days after the last dose. Adverse events were similar to those observed in the previous canakinumab trials. Canakinumab was effective at controlling the attack recurrence in patients with FMF resistant to colchicine. Further investigations are warranted to explore canakinumab's potential in the treatment of patients with colchicine resistant FMF. ClinicalTrials.gov NCT01088880 . Registered 16 March 2010.

  11. Thiol/disulphide homeostasis in pregnant women with Familial Mediterranean fever.

    PubMed

    Yucel, Aykan; Sanhal, Cem Yasar; Daglar, Korkut; Kara, Ozgur; Uygur, Dilek; Erel, Ozcan

    2016-11-01

    To investigate the presence of oxidative stress (OS) in pregnant women with Familial Mediterranean fever (FMF) in the first trimester by evaluating thiol/disulphide homeostasis. A total of 31 pregnant women with a diagnosis of FMF, between 11(0) and 13(6) weeks of gestation, were compared with 51 healthy pregnant controls at the same gestational weeks. A recently defined method was used to measure plasma native thiol, total thiol and disulphide levels. There were no differences between groups in terms of maternal age, body mass index and numbers of gravida and parity. Antenatal complications (45.2% vs. 9.8%, P = 0.001) and primary caesarean section (22.6% vs. 5.9%, P = 0.037) were higher in the FMF group. Pregnant women with FMF had significantly lower first trimester serum levels of native thiol (297.5 μmol/l (153.2-441.8) vs. 366.1 μmol/l (288.7-432.4), P = 0.000), total thiol (327.2 μmol/l (171.0-471.0) vs. 389.9 μmol/l (317.1-449.8), P = 0.000) and higher levels of disulphide (14.2 ± 4.5 μmol/l vs. 12.4 ± 3.4 μmol/l, P = 0.045). No differences were found in these parameters among FMF patients with and without antenatal complications. The main outcome demonstrates a relation between OS and pregnant women with FMF in the first trimester of gestation. OS in the first trimester may be a major aetiological factor of unfavourable pregancy outcomes in this group of patients.

  12. The association of endoplasmic reticulum aminopeptidase-1 (ERAP-1) with Familial Mediterranean Fever (FMF)

    PubMed Central

    Sezgin, Gülbüz; Dabak, Reşat; Kaya, Fatih Oner; Kotevoglu, Nurdan; Uygur-Bayramiçli, Oya

    2015-01-01

    Background The ERAP1 gene cleaves the receptors and reduces their ability to transmit chemical signals to the cell that affect the process of inflammation and, secondly, it cleaves many types of proteins into small peptides that are recognized by the immune system. Objective ERAP-1 gene mutations may create a sensitivity for Familial Mediterranean Fever (FMF). Method We included 15 FMF patients with the M694 (+) mutation in the study in order to exclude patients without pyrin gene mutations and create a homogeneous study group. Fifteen patients with ulcerative colitis formed the control group. Results There wasn’t any case without ERAP-1 gene mutations. At least one mutation at exon 3 or exon 10 was found in all cases in both groups. There were 14 ERAP-1 gene mutations at exon 10 and 11 at exon 3 in patients with FMF. Interestingly, if there were ERAP-1 gene mutations at exon 3, a p.Arg127 Pro (c.380 G>C) mutation always existed for three FMF patients with polymorphic mutations at this exon. There were 11 ERAP-1 gene mutations at exon 10 and 12 gene mutations at exon 3 in patients with ulcerative colitis. Exon 3 mutations were usually single p.Arg127 Pro (c.380 G>C) mutations for 12 patients with ulcerative colitis as seen in the patients with FMF. The single mutation was always p.Ser453 Ser (c.1359T>C) for patients with ulcerative colitis at exon 10. Conclusion There are more ERAP-1 mutations in the FMF group in comparison to the ulcerative colitis group. So, there may be a strong susceptibility to ERAP-1 gene mutations in FMF patients according to our results. However, further studies with larger study and control groups are needed. PMID:26966528

  13. Efficacy and safety of treatments in Familial Mediterranean fever: a systematic review.

    PubMed

    Demirkaya, Erkan; Erer, Burak; Ozen, Seza; Ben-Chetrit, Eldad

    2016-03-01

    Familial Mediterranean fever (FMF) is an autoinflammatory disease, which can be well controlled with lifelong use of colchicine. Since studies dealing with the efficacy and safety of colchicine were conducted mainly in the sixties and seventies of the previous century, it seems that this topic needs to be updated. Recently, an international expert panel was undertaken for the establishment of recommendations on how to manage FMF. We aimed to summarize the efficacy and safety of the current treatments available to prevent FMF attacks and to avert the appearance of amyloidosis secondary to FMF. A systematic review was performed. Two reviewers and methodologist established the protocol of the review and the epidemiological questions in PICO terms. MEDLINE through PubMed, Embase, and Cochrane Central Trials Register all up to May 31, 2014, were searched, and only randomized controlled trials or quasicontrolled trials were accepted. For each study, a judgment on risk of bias was then rated as high, moderate, or low. Of 1222 initially captured publications, 153 articles were studied in detail. Finally, only seven studies met all criteria and were included. Among these seven studies, four were randomized crossover clinical trials of colchicine including a total of 57 patients, one RCT of Andrographis paniculata Herba Nees extract employed in 24 patients, one randomized crossover clinical trial of Rilonacept used in 12 patients, and one RCT of interferon treating 34 acute abdominal attacks in 22 patients. The quality of the colchicine trials was low compared with the other drugs trials. Safety was not clearly mentioned in the trials. Colchicine is an effective treatment in FMF.

  14. Red cell distribution width is associated with albuminuria in adults with familial Mediterranean fever.

    PubMed

    Uslu, Ali Ugur; Yonem, Ozlem; Aydin, Bahattin; Uncu, Tunahan; Seven, Dogan; Balta, Sevket; Cicekli, Emre

    2016-04-01

    Systematic inflammation, enhanced oxidative stress, and endothelial dysfunction are important for evolution and progression of renal damage, and they cause an increase in red cell distribution width (RDW). Familial Mediterranean fever (FMF) patients who are in the attack-free period and its relation with albuminuria and performance on assessment of microalbuminuria. One hundred and seventy-seven patients who had been diagnosed in accordance with Tel-hoshmer criteria and were in the attack-free period, and 143 age- and sex-matched healthy individuals were enrolled in our study. RDW values of FMF patients were higher compared with those of the controls (13.85 ± 1.07 and 13.15 ± 0.91, respectively; p < 0.0001). RDW values of FMF patients with microalbuminuria were higher compared with those of FMF patients with normoalbuminuria and the control group (p = 0.002 and p < 0.0001, respectively). RDW values of FMF patients with normoalbuminuria were higher compared with those of the control group (p < 0.0001). We have showed RDW levels are positively correlated with albuminuria (r = 0.185, p = 0.014). When assessing microalbuminuria with RDW in the patients, a cutoff value of 13.85 with sensitivity of 60%, specificity of 62%, and p = 0.002 (area under curve: 0.651, 95% confidence interval 0.563-0.738), was observed according to receiver-operating characteristic curve analysis. Among the various variables associated with albuminuria in multivariate logistic regression analyses, RDW remained an independent predictor of albuminuria (95% confidence interval 0.479-0.942, p = 0.021). RDW may be associated with albuminuria in FMF patients and it can be a predictor of microalbuminuria. Copyright © 2016. Published by Elsevier Taiwan.

  15. Non-response to colchicine in familial Mediterranean fever should be identified accurately.

    PubMed

    Melikoglu, Meltem A; Senel, Kazim

    2014-04-07

    Colchicine prophylaxis is the single most important factor in ameliorating familial Mediterranean fever (FMF) for the prevention of both attacks and secondary amyloidosis. The aim of the present study was to evaluate the exact proportion of those patients who do not respond to colchicine and to characterize their demographic, sociodemographic and clinical aspects. One hundred and eight patients with FMF were included in our study. The demographic (age, gender), socioeconomic (education level, employment status, economic income level) and clinical features (age at onset of FMF, age at FMF diagnosis, family history of FMF, mean duration of colchicine use and mean daily colchicine dose) of the patients were evaluated. The patients unresponsive to colchicine therapy, according to their statements, were recorded. Also with another question, patients' routine colchicine-consuming habits were elucidated in a self-answering format. 'Non-responders' were defined as patients who experienced FMF attacks at a frequency greater than once every 3 months despite treatment with 2 mg colchicine daily. Data were analyzed with the chi-square test and Fisher's exact test. There were 50 female and 58 male patients with a mean age of 42.4 ± 11.3 years. The mean age at FMF onset and at FMF diagnosis were 14.3 ± 10.5 and 19.1 ± 12.9 years, respectively. Sixteen percent of the patients defined themselves as 'suffering from attacks in spite of regular colchicine'. Irregular colchicine usage was determined in 11% of the patients who were considered as 'unresponsive to colchicine therapy' according to their statements. In spite of regular colchicine regimen, attacks were present in 5% of the patients in our study. Although there was no difference in demographic and clinical aspects, patients with irregular colchicine usage were found to be from lower socioeconomic backgrounds, had less education and more unemployment (P < 0.001). Regular colchicine usage anamnesis may be

  16. MEFV gene mutations and cardiac phenotype in children with familial Mediterranean fever: a cohort study

    PubMed Central

    2014-01-01

    Background Familial Mediterranean fever (FMF) is the most common autoinflammatory disorder in the world. It is characterized by recurrent febrile inflammatory attacks of serosal and synovial membranes. MEFV gene mutations are responsible for the disease and its protein product, pyrin or marenostrin, plays an essential role in the regulation of the inflammatory reactions. Although the disease may carry a potential for cardiovascular disorders because of sustained inflammation during its course, the spectrum of cardiac involvement in children with FMF has not been well studied. We aimed at defining the frequency and spectrum of cardiac affection in children with FMF. The correlation between these affections and MEFV gene mutations was searched for to establish the relationship between cardiac phenotype and the patient's genotype in FMF. Methods The present work is a cohort study including 55 patients with the clinical diagnosis of FMF based on the Tel-Hashomere criteria, confirmed by genetic analysis showing homozygous or compound heterozygous mutation of MEFV genes. Fifty age- and sex-matched normal children were included as controls. The entire study group underwent detailed cardiac examination, 12-lead ECG and echocardiography. All data was statistically analysed using SPSS version-15. Results Patients had an average age of 8.5+/−4.2 years; with an average disease duration of 2.1+/−2.2 years; 28 were males. All controls showed no MEVF gene mutations. The most frequent gene mutation of the studied cases was E148Q mutation seen in 34% of cases and the most frequent compound mutation was E148Q/V726A seen in 16.6% of cases. Echocardiographic examination revealed pericardial effusion in nine patients. Twelve had aortic regurgitation; nine had mitral regurgitation and six had pulmonary regurgitation. The most common mutation associated with pericardial effusion was E148Q/V726A in 5/9 of cases. Valvular involvement were significantly more common in FMF patients

  17. Long chain fatty acid (Lcfa) abnormalities in hyper Igd syndrome (Hids) and Familial Mediterranean Fever (Fmf): new insight into heritable periodic fevers.

    PubMed

    Simon, Anna; Drenth, Joost P H; Matern, Dietrich; Goetzman, Eric S; Hager, Elizabeth J; Gibson, K Michael

    2013-03-01

    To examine essential fatty acids (EFAs) in hyper-IgD syndrome (HIDS) and Familial Mediterranean Fever (FMF). EFAs were determined in sera derived from an archival, cross-sectional group of HIDS/FMF patients, stratified for presence and absence of fever. Control populations included healthy afebrile adults, and individuals with non-periodic fever (septic shock). EFAs were quantified using isotope dilution gas chromatography-mass spectrometry and data analyzed employing a Kruskal-Wallis non-parametric ANOVA with Dunn's post-hoc test. Sera samples derived from HIDS patients showed significantly decreased C20, C26, phytanic and pristanic acids during febrile crises that normalized in the afebrile state, and a significantly increased afebrile C22_4ω6 level that normalized with fever. Samples derived from FMF patients revealed increased ω-oxidized LCFAs as compared to controls, and the trend was for these same species to be increased in comparison to febrile, but not afebrile, HIDS patients. Individuals with non-periodic fever demonstrated global decreases in C10-C24 fatty acids, both saturated and unsaturated, accompanied by an elevated triene/tetraene ratio. Our results suggest that different mechanisms are active in hereditary periodic fever syndromes that appear unrelated to fever, including depletion of very long chain fatty acids (VLCFAs) in febrile HIDS patients and increased ω-oxidized LCFAs in patients with FMF. These findings underscore new roles for EFAs in the potential production of inflammatory species in patients with hereditary periodic fever. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Generation of integration-free induced pluripotent stem cells from a patient with Familial Mediterranean Fever (FMF).

    PubMed

    Fidan, Kerem; Kavaklıoğlu, Gülnihal; Ebrahimi, Ayyub; Özlü, Can; Ay, Nur Zeynep; Ruacan, Arzu; Gül, Ahmet; Önder, Tamer T

    2015-11-01

    Fibroblasts from a Familial Mediterranean Fever (FMF) patient were reprogrammed with episomal vectors by using the Neon Transfection System for the generation of integration-free induced pluripotent stem cells (iPSCs). The resulting iPSC line was characterized to determine the expression of pluripotency markers, proper differentiation into three germ layers, the presence of normal chromosomal structures as well as the lack of genomic integration. A homozygous missense mutation in the MEFV gene (p.Met694Val), which lead to typical FMF phenotype, was shown to be present in the generated iPSC line. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Overlap syndrome between Familial Mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome in a lupus patient.

    PubMed

    Nonaka, Fumiaki; Migita, Kiyoshi; Iwasaki, Keisuke; Shimizu, Toshimasa; Kawakami, Atsushi; Yasunami, Michio; Eguchi, Katsumi

    2014-06-01

    Autoinflammatory diseases represent an expanding spectrum of genetic and non-genetic inflammatory diseases characterized by recurrent episodes of fever and systemic inflammation, affecting joints, skin and serosal surfaces. Familial Mediterranean fever (FMF) is the most common autosomal recessive hereditary autoinflammatory disease. Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant hereditary autoinflammatory disease. They share some clinical manifestations such as a periodic fever and skin rash. We present here the association of FMF with TRAPS in a systemic lupus erythematosus (SLE) patient. A 54-year-old SLE patient with recurrent attacks of fever, arthritis, and skin rashes was referred to our hospital. She had been diagnosed with lupus nephritis at 19 years old. Her lupus nephritis was controlled by steroid treatments; however, since childhood she has suffered from recurrent episodes of periodic fever, abdominal pain, arthritis, and erythematous skin rashes. An initial diagnosis of FMF was suspected based on the genetic analysis, showing the compound heterozygous L110P/E148Q mutations in the MEFV gene that is responsible for FMF. Her symptoms responded to colchicine, but the febrile attacks were not completely resolved. Therefore, genetic testing for TRAPS was performed. The results revealed a heterozygous T61I mutation in the TNFRSF1A gene that encodes tumor necrosis factor-α receptor and is responsible for TRAPS. The patient was diagnosed with overlapping FMF and TRAPS, in addition to SLE. This is the first report of SLE associated with both FMF and TRAPS.

  20. Secondary bladder amyloidosis with familial Mediterranean fever in a living donor kidney transplant recipient: a case report.

    PubMed

    Imamura, Sentaro; Narita, Shintaro; Nishikomori, Ryuta; Tsuruta, Hiroshi; Numakura, Kazuyuki; Maeno, Atsushi; Saito, Mitsuru; Inoue, Takamitsu; Tsuchiya, Norihiko; Nanjo, Hiroshi; Heike, Toshio; Satoh, Shigeru; Habuchi, Tomonori

    2016-10-19

    Secondary bladder amyloidosis is an extremely rare disease, resulting from a chronic systematic inflammatory disorder associated with amyloid deposits. Although uncommon in Japan, familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent episodes of fever of short duration and serositis and is frequently associated with systemic amyloidosis. Here, we present a case of a Japanese patient complaining of fever and macroscopic hematuria after a living donor renal transplantation. Consequently, he was diagnosed with secondary bladder amyloidosis with FMF. A 64-year-old Japanese male received a living ABO-incompatible kidney transplant from his wife. The postoperative clinical course was normal, and the patient was discharged 21 days after the transplantation with a serum creatinine level of 0.78 mg/dl. The patient frequently complained of general fatigue and fever of unknown origin. Six months later, the patient presented with continuous general fatigue, macroscopic hematuria, and fever. Cystoscopic examination of the bladder showed an edematous region with bleeding, and a transurethral biopsy revealed amyloid deposits. His wife stated that the patient had a recurrent high fever since the age of 40 years and that his younger brother was suspected to have a familial autoinflammatory syndrome; thus, the patient was also suspected to have a familial autoinflammatory syndrome. Based on his brother's medical history and the genetic tests, which showed a homozygous mutation (M694V/M694V) for the Mediterranean fever protein, he was diagnosed with FMF. Although colchicine treatment for FMF was planned, the patient had an untimely death due to heart failure. We re-evaluated the pathological findings of the various tissue biopsies obtained during the treatment after the renal transplantation. Immunohistochemistry revealed amyloid deposits in the bladder region, renal allograft, and myocardium and the condition was diagnosed as AA

  1. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial.

    PubMed

    Hashkes, Philip J; Spalding, Steven J; Giannini, Edward H; Huang, Bin; Johnson, Anne; Park, Grace; Barron, Karyl S; Weisman, Michael H; Pashinian, Noune; Reiff, Andreas O; Samuels, Jonathan; Wright, Dowain A; Kastner, Daniel L; Lovell, Daniel J

    2012-10-16

    Currently, there is no proven alternative therapy for patients with familial Mediterranean fever (FMF) that is resistant to or intolerant of colchicine. Interleukin-1 is a key proinflammatory cytokine in FMF. To assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF. Randomized, double-blind, single-participant alternating treatment study. (ClinicalTrials.gov number: NCT00582907). 6 U.S. sites. Patients with FMF aged 4 years or older with 1 or more attacks per month. One of 4 treatment sequences that each included two 3-month courses of rilonacept, 2.2 mg/kg (maximum, 160 mg) by weekly subcutaneous injection, and two 3-month courses of placebo. Differences in the frequency of FMF attacks and adverse events between rilonacept and placebo. 8 males and 6 females with a mean age of 24.4 years (SD, 11.8) were randomly assigned. Among 12 participants who completed 2 or more treatment courses, the rilonacept-placebo attack risk ratio was 0.59 (SD, 0.12) (equal-tail 95% credible interval, 0.39 to 0.85). The median number of attacks per month was 0.77 (0.18 and 1.20 attacks in the first and third quartiles, respectively) with rilonacept versus 2.00 (0.90 and 2.40, respectively) with placebo (median difference, -1.74 [95% CI, -3.4 to -0.1]; P = 0.027). There were more treatment courses of rilonacept without attacks (29% vs. 0%; P = 0.004) and with a decrease in attacks of greater than 50% compared with the baseline rate during screening (75% vs. 35%; P = 0.006) than with placebo. However, the duration of attacks did not differ between placebo and rilonacept (median difference, 1.2 days [-0.5 and 2.4 days in the first and third quartiles, respectively]; P = 0.32). Injection site reactions were more frequent with rilonacept (median difference, 0 events per patient treatment month [medians of -4 and 0 in the first and third quartiles, respectively]; P = 0.047), but no differences were seen

  2. Investigation of the arterial stiffness and associated factors in patients with familial Mediterranean fever

    PubMed Central

    Çakar, Mustafa; Akhan, Muharrem; Doğan, Tolga; Taşkın, Gürhan; Öztürk, Kadir; Çınar, Muhammet; Arslan, Erol; Yılmaz, Sedat

    2017-01-01

    Objective: Because of the ongoing and recurring inflammatory state in familial Mediterranean fever (FMF), patients may experience a high risk of cardiovascular events. Our aim was to investigate the arterial stiffness and associated factors in patients with FMF. Methods: Sixty-nine consecutive FMF patients (including 11 females) and 35 controls (including 5 females) were enrolled in the study. The demographical, clinical, and laboratory data and genetic mutations of the patients were recorded. In the study, FMF patients according to the Tel-Hashomer criteria were included, whereas patients with other known inflammatory rheumatologic disease, atherosclerotic cardiovascular disease, hypertension, diabetes, those under the age of 18 years, or those refusing to participate in the study were excluded. Arterial stiffness measurements were performed using the TensioMed device (TensoMed Ltd, Budapest, Hungary). Results: The patient and control groups were similar in terms of the mean ages, BMIs, gender, systolic blood pressures, and smoking. FMF patients had a higher pulse wave velocity (PWV) (7.73±1.3 and 7.18±1.1 m/s; p=0.03) and lower brachial and aortic augmentation indexes (–64.6±14.6% and –54.6±25.9%, p=0.041 and 4.9±7.4% and 14.0±11.5%, p=0.025, respectively) compared with the controls. Thirty-one (45%) patients were in the “during-attack” state and had higher PWV (8.17±1.6 and 7.38±0.9 m/s; p=0.027) compared with the asymptomatic patients. PWV was correlated to serum CRP, WBC, ESR, fibrinogen, and neutrophil/lymphocyte ratios (r=0.666, 0.429, 0.441, 0.388, and 0.460, respectively). The genetic mutation and predominant attack type had no effect on arterial stiffness. Conclusion: FMF patients have increased arterial stiffness during attacks compared with asymptomatic patients and controls. The impaired arterial stiffness is correlated to the severity of the inflammatory state rather than to the attack type or genetic mutations. PMID:27488756

  3. Association of familial Mediterranean fever in Turkish children with inflammatory bowel disease.

    PubMed

    Beşer, Ömer Faruk; Çokuğraş, Fügen Çullu; Kutlu, Tufan; Erginöz, Ethem; Gülcü, Didem; Kasapçopur, Özgür; Erkan, Tülay

    2014-09-01

    Familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD) carry similar clinical and biological properties. Both are characterized with chronic inflammation attacks and neutrophil migration and impaired apoptosis mechanism are present in the areas of damage in both conditions. In our study, we aimed to determine the frequency of association of FMF in patients with IBD, to compare the demographic, clinical, laboratory and treatment response properties in these patients with the ones in other IBD patients and to determine association of FMF especially in treatment-resistant patients. Fifty-three patients who were being followed up with a diagnosis of IBD aged between 0 and 18 years were included in the study. The patient group included the patients who were diagnosed with IBD according to clinical, serological, endoscopic and histopathological criteria, who were being followed up and whose therapies were continuing. Genetic analysis in terms of MEFV gene mutations was performed in all patients with a diagnosis of IBD. Acute phase reactants, complete blood count, immunoglobulin levels, stool analysis, "perinuclear anti-neutrophil cytoplasmic antibodies" (pANCA) and "anti-Saccharomyces cerevisiae antibodies" (ASCA) were studied at the time of diagnosis. The diagnosis of FMF was made according to detailed history, physical examination findings, laboratory tests and the results of genetic analyses in terms of MEFV gene mutations in accordance with the criteria defined in 2009. We found that FMF accompanied in 14 (26.4%) of the patients who had a diagnosis of IBD. 3 of these 14 patients in whom FMF accompanied were being followed up with a diagnosis of Crohn disease and 11 were being followed up with a diagnosis of ulcerative colitis. All of these patients had MEFV gene mutation. These mutations included M694V (50%), K695R (21.4%), M680I (14.3%) and R202Q (14.3%) in order of frequency. When the laboratory data were compared between the patients who had a

  4. Treatment of colchicine-resistant Familial Mediterranean fever in children and adolescents.

    PubMed

    Eroglu, Fehime Kara; Beşbaş, Nesrin; Topaloglu, Rezan; Ozen, Seza

    2015-10-01

    Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. Approximately 5-10 % of patients are unresponsive to colchicine. Aim of this study was to determine the short- and long-term efficacy and safety of anti-interleukin 1 (anti-IL1) and anti-tumor necrosis factor agents in colchicine-resistant FMF cases in Turkish children and adolescents. This is a single-center retrospective case series of colchicine-resistant FMF patients. The included patients were treated with biologics for either colchicine resistance or because of one of the following: (1) amyloidosis, (2) recurrent prolonged febrile myalgia and frequent need of steroid and (3) persistent arthritis. Colchicine resistance was defined as at least one attack per month for three consecutive months and elevated erythrocyte sedimentation rate or C-reactive protein or serum amyloid A in-between attacks despite taking adequate dose of colchicine. Response to biologicals was evaluated by the Autoinflammatory Diseases Activity Index (AIDAI) score sheet, patients/parents'/physicians' global assessment of disease severity and laboratory parameters every 3-6 months. Fourteen patients were included in the study. Three patients were treated with etanercept for median 7 months (range 3-11 months), and all patients had to be switched to anti-IL1 treatment because of adverse effects and/or partial response. Eleven patients were treated with anakinra with a median duration of 8 months (4-60 months). Nine patients responded to treatment at the third month, but four of them switched to canakinumab because of noncompliance, local side effects and active arthritis. Nine patients were treated with canakinumab, all responded. At follow-up, in two patients the dose had to be increased, and on the other hand, in three patients the interval was increased to every 12-16 weeks. In three patients, anti-IL1 treatment could be stopped and they are fine with colchicine. This case series describes the

  5. Anti-interleukin-1 treatment in 26 patients with refractory familial mediterranean fever.

    PubMed

    Kucuksahin, Orhan; Yildizgoren, Mustafa Turgut; Ilgen, Ufuk; Ates, Askin; Kinikli, Gülay; Turgay, Murat; Erten, Sukran

    2017-03-01

    To investigate the effect of anti-interleukin-1 (anti-IL-1) treatment on the frequency and severity of attacks and other disease-related clinical parameters and to evaluate the adverse effects associated with anti-IL-1 treatment in 26 patients with refractory familial mediterranean fever (FMF). The study included 26 FMF patients followed up in our centre using colchicine for 4 months to 30 years. The treatment was switched to anti-IL-1 treatment for various reasons; 20 cases were resistant to colchicine, 8 were intolerant to colchicine, and 3 had prolonged arthritis under colchicine. Clinical response was monitored through the number of attacks, and laboratory inflammation was monitored through erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A concentrations. Colchicine resistance was defined as at least two attacks/month together with C-reactive protein and serum amyloid A levels above the normal range between attacks. The colchicine dose was increased to 2 mg/day before they were considered colchicine-resistant. 24 patients used anakinra (100 mg/day), and 2 used canakinumab (150 mg/month), for -36 months. Sixteen patients with colchicine resistance had no attacks under anti-IL-1 treatment, and 4 had decreased frequency and duration of attacks. Seven of 8 patients intolerant to colchicine used anakinra, and 6 were attack-free under treatment, while 1 using canakinumab had attacks under treatment. One patient with prolonged arthritis used canakinumab but arthritis showed progression and the treatment was changed to IL-6 inhibitor. Three patients had injection site erythema and one had fatigue with anti-IL-1 treatment. Topical steroids with systemic antihistaminics were sufficient for symptom control in two cases, but canakinumab treatment was given due to severe injection site erythema in one case. Anti-IL-1 agents are rational treatment modalities in patients resistant or intolerant to colchicine. Anti-IL-1 agents can control FMF

  6. Usefulness of Small Intestinal Endoscopy in a Case of Adult-onset Familial Mediterranean Fever Associated with Jejunoileitis.

    PubMed

    Kitade, Takashi; Horiki, Noriyuki; Katsurahara, Masaki; Totoki, Toshiaki; Harada, Tetsuro; Tano, Shunsuke; Yamada, Reiko; Hamada, Yasuhiko; Inoue, Hiroyuki; Tanaka, Kyosuke; Gabazza, Esteban C; Hayashi, Hiroyuki; Tanaka, Masanori; Takei, Yoshiyuki

    2015-01-01

    A 66-year-old Japanese man consulted our institution due to paroxysmal and repetitive bouts of fever and abdominal pain that had persisted for more than one week. Capsule and double-balloon endoscopy (DBE) showed petal-shaped mucosal redness with white hemming in the jejunum and ileum, and histopathology of the biopsy specimens revealed villous atrophy and cryptitis with extensive severe neutrophil infiltration. A genetic examination disclosed compound heterozygous MEFV mutations (E84K, P369S), and familial Mediterranean fever was diagnosed. Treatment with colchicine and infliximab was very effective in inducing the complete disappearance of symptoms and normalization of the endoscopic findings. To the best of our knowledge, this is the first report to describe the findings of small intestinal endoscopic images obtained using capsule and DBE.

  7. The effect of plasminogen activator inhibitor-1 -675 4G/5G polymorphism on familial Mediterranean fever (FMF) disease.

    PubMed

    Ozel Demiralp, Duygu; Ekim, Mesiha; Akar, Nejat

    2009-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease that is the most common of a rare group of disorders collectively termed familial hereditary periodic fever syndromes, also known as autoinflammatory syndromes. FMF is predominantly affecting people of Mediterranean descent and clinically characterized by intermittent attacks of fever with peritonitis and abdominal pain, pleuritis, arthritis, or erysipelas-like rashes. Amyloidosis due to chronic inflammation progressing to renal failure is one of the most serious potential complications of this disease.Patients with inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis, and conditions with chronic subclinical inflammation, like obesity and diabetes mellitus, are now considered to have an increased risk of atherosclerotic cardiovascular complications. FMF is also an inflammatory disease, and it is accepted that even during attack-free periods significant inflammatory reaction continues. However, whether this inflammatory process causes premature atherosclerosis is not known due to a lack of data.Different studies have investigated the association between the fibrinolytic and inflammatory process parameters. PAI-1 is paracrine secretion of pro- and antiinflammatory cytokines, thereby playing a possible role in the adiposity-related inflammation and atherosclerosis. The patients with IRS have higher values of fibrinogen, factor VII, VIII, Von Willebrand factor and Plasminogen Activator Inhibitor (PAI) compared to control subjects. So that we aimed in this study to investigate whether FMF patients with/without amyloidosis and with M694V homozygote mutation, have increased risk for atherosclerotic cardiovascular complications and to determine the strength of association between MEFV gene-mutation types. To our knowledge, this is the first case control and cross-sectional study in the pediatric age groups.

  8. Association of familial Mediterranean fever in Turkish children with inflammatory bowel disease

    PubMed Central

    Beşer, Ömer Faruk; Çokuğraş, Fügen Çullu; Kutlu, Tufan; Erginöz, Ethem; Gülcü, Didem; Kasapçopur, Özgür; Erkan, Tülay

    2014-01-01

    Aim: Familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD) carry similar clinical and biological properties. Both are characterized with chronic inflammation attacks and neutrophil migration and impaired apoptosis mechanism are present in the areas of damage in both conditions. In our study, we aimed to determine the frequency of association of FMF in patients with IBD, to compare the demographic, clinical, laboratory and treatment response properties in these patients with the ones in other IBD patients and to determine association of FMF especially in treatment-resistant patients. Material and Methods: Fifty-three patients who were being followed up with a diagnosis of IBD aged between 0 and 18 years were included in the study. The patient group included the patients who were diagnosed with IBD according to clinical, serological, endoscopic and histopathological criteria, who were being followed up and whose therapies were continuing. Genetic analysis in terms of MEFV gene mutations was performed in all patients with a diagnosis of IBD. Acute phase reactants, complete blood count, immunoglobulin levels, stool analysis, “perinuclear anti-neutrophil cytoplasmic antibodies” (pANCA) and “anti-Saccharomyces cerevisiae antibodies” (ASCA) were studied at the time of diagnosis. The diagnosis of FMF was made according to detailed history, physical examination findings, laboratory tests and the results of genetic analyses in terms of MEFV gene mutations in accordance with the criteria defined in 2009. Results: We found that FMF accompanied in 14 (26.4%) of the patients who had a diagnosis of IBD. 3 of these 14 patients in whom FMF accompanied were being followed up with a diagnosis of Crohn disease and 11 were being followed up with a diagnosis of ulcerative colitis. All of these patients had MEFV gene mutation. These mutations included M694V (50%), K695R (21.4%), M680I (14.3%) and R202Q (14.3%) in order of frequency. When the laboratory data were

  9. [MEFV gene mutation spectrum in familial Mediterranean fever (FMF) : a single center study in the Aegean region of Turkey].

    PubMed

    Coker, I; Colak, A; Yolcu, I; Türkön, H; Nalbantoglu, S M

    2011-08-01

    Familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disorder, is characterized by recurrent, self-limiting fever and serositis which is frequently seen in Mediterranean populations. In this study, we retrospectively evaluated the MEFV gene mutation distribution of 883 citizens of the Aegean region with preliminary diagnosis of FMF who were referred to the Tepecik Research and Education Hospital's Tissue Typing and Molecular Diagnostic Laboratory (Izmir, Turkey) between 2006 and 2009. The FMF Strip Assay® (ViennaLab Diagnostics, Vienna, Austria) was used to determine the 12 most common MEFV gene mutations in patients prediagnosed with FMF. Allelic frequencies of the major mutations in the mutation positive groups, including M694V, E148Q, M680I(G>C), and V726A, accounted for 48.4, 16.5, 13.5, and 9.7%, respectively. The M694V mutation was found to be the most common mutation among FMF patients in the Aegean region, which is in accordance with mutation studies reported from other regions of the country and different ethnic populations. An English full-text version of this article is available at SpringerLink as supplemental.

  10. Colchicine, Biologic Agents and More for the Treatment of Familial Mediterranean Fever. The Old, the New, and the Rare.

    PubMed

    Portincasa, P

    2016-01-01

    Familial Mediterranean Fever (FMF) is a rare autosomal recessive autoinflammatory disorder involving the innate immunity and affecting almost exclusively populations with Mediterranean origin. Clinical features include recurrent episodes of fever, leukocitosis, serositis (peritonitis or pleuritis, arthritis), myalgia or erysipelas-like skin lesions, lasting 12-72 hrs. The MEFV gene mutations on chromosome 16p13.3 encodes the abnormal pyrin (marenostrin), a protein expressed in granulocytes, monocytes, serosal and synovial fibroblasts and involved in the activation of caspase-1 and the processing and release of active pro-inflammatory IL-1β. Since the first report in 1972, maintenance therapy with colchicine, a tricyclic neutral alkaloid, remains the mainstay of treatment in symptomatic FMF patients since it reduces the disease activity and prevents the development of secondary amyloidosis and renal damage. Adjunctive symptomatic therapy to colchicine includes nonsteroideal antinflammatory drugs and corticosteroids. In a small group of colchicine-intolerant or colchicine-resistant FMF patients, alternative treatments must be considered. Evolving experiences have focussed on the potential effectiveness of biologic agents working as TNF-α inhibitors (etanercept, infliximab), IL-1 trap (Rilonacept), IL-1 inhibitors (Anakinra, Canakinumab) and IL-6 receptor antibody (Tocilizumab). Interferon-α and thalidomide have also been employed in FMF patients. Still, clinical trials are mainly uncontrolled and restricted to few cases, thus requiring definitive conclusions. Old, and new treatments are discussed in the rare FMF disease, with the concept that any ideal treatment has to stand the test of time.

  11. Familial Mediterranean fever gene mutation frequencies and genotype-phenotype correlations in the Aegean region of Turkey.

    PubMed

    Ozalkaya, Elif; Mir, Sevgi; Sozeri, Betul; Berdeli, Afig; Mutlubas, Fatma; Cura, Alphan

    2011-06-01

    Familial Mediterranean fever (FMF) is a disease characterized by recurrent, self-limiting fever and serositis and caused by altered pyrin due to mutated MEFV gene. The aim of this study was to investigate clinical manifestations and MEFV mutations among patients with FMF and healthy controls in the Aegean region of Turkey. This study included 308 patients and 164 healthy controls. Patients were divided into three groups according to Tel-Hashomer criteria; definitive, probable, and suspicious. Among the patients, 146 were women (47.4%) and 162 were men (52.6%). The mean age (±SD) of the patients at the diagnosis was 9.6±3.95 (range 0.5-18). The mean age (±SD) at onset of the symptom was 6.2±3.95 (range 1-18). Symptoms were seen earlier onset in definitive group than the suspicious group in our cohort (4.7±3.9 years, 6.6±3.9 years, respectively; P=0.001). Clinical features were abdominal pain (83.1%), fever (55%), arthritis (17.1%), myalgia (4.5%), pleuritis (10%), and erysipelas-like erythema (7.7%). Fever, arthralgia, arthritis, chest pain, and amyloidosis were found statistically significant more in definitive group than suspicious group (P<0.001, P<0.001, P<0.001, P<0.05, and P<0.001, respectively). MEFV gene mutations were identified in 199 patients (64.6%). The most commonly encountered MEFV mutation among the patients was M694V homozygote (25%). M694V homozygous mutation was found most frequently in definitive FMF group than other groups (49, 9, 8.9%, respectively). To our knowledge that FMF should be suspected in the case of non-specific but recurrent attacks of serositis and high fever, and molecular analysis should be performed in order to make diagnosis of FMF.

  12. Phenotype-genotype updates from familial Mediterranean fever database registry of Mansoura University Children’ Hospital, Mansoura, Egypt

    PubMed Central

    Al-Haggar, Mohammad S.; Yahia, Sohier; Abdel-Hady, Dina; Al-Saied, Afaf; Al-Kenawy, Rasha; Abo-El-Kasem, Rabab

    2014-01-01

    BACKGROUND: Familial Mediterranean fever (FMF) is autosomal recessive disease that affects people from Mediterranean region, Europe and Japan. Its gene (Mediterranean fever [MEFV]) has more than 100 mostly non-sense mutations. OBJECTIVES: The objective of the following study is to provide some phenotype-genotype correlates in FMF by categorizing the Egyptian FMF cases from Delta governorates after analysis of the four most common mutations of MEFV gene (M680I, M694I, M694V, V726A). SUBJECTS AND METHODS: Clinically, suspected FMF cases using Tel-Hashomer criteria were enrolled in the study. Cases were referred to Mansoura University Children's Hospital that serves most of the most middle Delta governorates, in the period from 2006 to 2011. Subjects included 282 males and 144 females, mean age of onset 9.3 ± 2.2 years. All cases were analyzed for these mutations using amplification refractory mutation system based on the polymerase chain reaction technique. Five FMF patients agreed to undergo renal biopsy to check for development of amyloidosis. Analysis of data was carried out using SPSS (SPSS, Inc., Chicago, IL, USA). RESULTS: Mutation was found in 521 out of 852 studies alleles, the most frequent is M694V (35.4%) followed by M694I, V726A and M680I. 11 cases were homozygous; 7 M694V, 3 M680I and only one M694I case. Severe abdominal pain occurred in 31 (7.28%) but severe arthritis in 103 cases (24.2%). Strong association was found between arthritis and homozygous mutant compared with single and double heterozygous (72.7% vs. 33.3% and 20.24%, P < 0.001). Four amyloid cases were M694V positive. CONCLUSION: M694V allele is the most common among Egyptian FMF especially those with amyloidosis. We recommend routine check for amyloidosis in FMF cases to statistically validate this link. PMID:24959013

  13. Malignant Mediterranean spotted fever.

    PubMed

    Lunge, Snehal Balvant; Patil, Vaibhav; Ambar, Sameer; Naik, Vishwas

    2015-12-01

    Fever with rash is one of the most common causes of referral to a dermatologist. A plethora of conditions need to be considered in the differential diagnosis. They may be broadly classified into infectious causes, drug reactions, and autoimmune disorders. Here we present a rare case of rickettsial fever with cardiac involvement in an elderly male patient with no comorbidities.

  14. Malignant Mediterranean spotted fever

    PubMed Central

    Lunge, Snehal Balvant; Patil, Vaibhav; Ambar, Sameer; Naik, Vishwas

    2015-01-01

    Fever with rash is one of the most common causes of referral to a dermatologist. A plethora of conditions need to be considered in the differential diagnosis. They may be broadly classified into infectious causes, drug reactions, and autoimmune disorders. Here we present a rare case of rickettsial fever with cardiac involvement in an elderly male patient with no comorbidities. PMID:26904440

  15. Acute adrenal crisis mimicking familial Mediterranean fever attack in a renal transplant FMF patient with amyloid goiter.

    PubMed

    Emeksiz, Hamdi; Bakkaloglu, Sevcan; Camurdan, Orhun; Boyraz, Mehmet; Soylemezoglu, Oguz; Hasanoglu, Enver; Buyan, Necla

    2010-11-01

    The most devastating complication of familial Mediterranean fever (FMF) is amyloidosis which is capable of resulting in chronic renal failure. Although amyloid deposits are frequent in adrenal glands based on the autopsies of FMF patients however; to our knowledge, symptomatic adrenal insufficiency has not been reported yet. We describe a 21-year-old-FMF amyloidosis case with a well-functioning allograft who presented to the emergency clinic with the complaints of abdominal pain, vomiting and diarrhea mimicking FMF attack. adrenocorticotrophic hormone stimulation test was performed due to resistant hyponatremia and disclosed Addison disease. In countries with a high prevalence of FMF, adrenal crisis should be borne in mind in long standing FMF patients.

  16. Treatment of Crohn’s disease and familial Mediterranean fever by leukopheresis: Single shot for two targets

    PubMed Central

    Yuksel, Mahmut; Saygili, Fatih; Coskun, Orhan; Suna, Nuretdin; Kaplan, Mustafa; Kuzu, Ufuk Baris; Kilic, Zeki Mesut Yalin; Ozin, Yasemin Ozderin; Kayacetin, Ertugrul

    2015-01-01

    Coexistence of Crohn's disease (CD) and familial Mediterranean fever (FMF) is a rare condition and knowledge about this clinical situation is limited with a few case reports in the literature. The treatment of both diseases depends on their individual therapies. However, it is very hard to deal with this coexistence when CD is refractory to standard therapies. Ongoing activity of CD triggers the clinical attacks of FMF and the symptoms like abdominal pain interfere with both disease presentations which can cause problems about diagnostic and therapeutic approach. The main therapeutic agent for FMF is colchicine and diarrhea is the most common side effect of this drug. This side effect also causes problems about management of these diseases when both of them are clinically active. Here we report probably the first case in the literature with coexisting CD and FMF who was successfully treated by leukopheresis since he was refractory to conventional therapies for CD. PMID:25852296

  17. Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever: differences in genotype and clinical features between Japanese and Mediterranean populations.

    PubMed

    Kishida, Dai; Nakamura, Akinori; Yazaki, Masahide; Tsuchiya-Suzuki, Ayako; Matsuda, Masayuki; Ikeda, Shu-ichi

    2014-09-27

    Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis that mainly affects Mediterranean populations. Many patients with FMF have been reported in Japan due to increasing recognition of this condition and the availability of genetic analysis for the gene responsible, MEFV. The present study was performed to elucidate the clinical characteristics of Japanese FMF patients and to examine the precise genotype-phenotype correlation in a large cohort of Japanese FMF patients. We analyzed the MEFV genotypes and clinical manifestations in 116 patients clinically diagnosed as having FMF and with at least one mutation. The most frequent mutation in Japanese patients was E148Q (40.2%), followed by M694I (21.0%), L110P (18.8%), P369S (5.4%), and R408Q (5.4%). In contrast, common mutations seen in Mediterranean patients, such as M694V, V726A, and M680I, were not detected in this population. The clinical features with M694I were associated with more severe clinical course compared to those seen with E148Q. P369S/R408Q showed variable phenotypes with regard to both clinical manifestations and severity. Patients with M694I showed a very favorable response to colchicine therapy, while those with P369S and R408Q did not. Clinical features and efficacy of treatment in Japanese FMF patients vary widely according to the specific MEFV gene mutation, and therefore genetic analysis should be performed for diagnosis in cases of Japanese FMF.

  18. Familial Mediterranean fever with P369S/R408Q exon3 variant in pyrin presenting as symptoms of PFAPA.

    PubMed

    Yamagami, Keiko; Nakamura, Tomoyuki; Nakamura, Ryota; Hanioka, Yusuke; Seki, Kaori; Chiba, Hiroshi; Kobayashi, Keiko; Agematsu, Kazunaga

    2017-03-01

    Familial Mediterranean fever (FMF) can be classified into typical and incomplete/atypical types. Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome-like symptoms have been found in atypical type carrying P369S-R408Q mutations in the responsible gene MEFV. A 28-year-old female with recurrent fever and her young sisters and mother, all of whom had tonsillectomy for tonsillitis, carried heterozygous alterations involving E148Q/P369S/R408Q. A diagnosis of atypical FMF, MEFV exon3 variants with PFAPA syndrome-like symptoms, was made.

  19. Non-thrombocytopenic purpura in familial Mediterranean fever-comorbidity with Henoch-Schönlein purpura or an additional rare manifestation of familial Mediterranean fever?

    PubMed

    Ben-Chetrit, Eldad; Yazici, Hasan

    2016-07-01

    Henoch-Schönlein purpura is a relatively common vasculitis mainly affecting children. It is characterized by purpuric skin rash, abdominal cramping, and haematuria. Skin biopsies taken from Henoch-Schönlein purpura lesions disclose perivascular IgA deposits. FMF is an autoinflammatory disease characterized by recurrent attacks of fever lasting 2-3 days which resolve spontaneously. Typical manifestations of the disease are peritonitis, pleuritis, pericarditis, arthritis and erysipelas-like erythema usually affecting the lower limbs. Over the years many reviews emphasized the clinical impression that Henoch-Schönlein purpura is more common among FMF patients than in healthy control population. In this review we summarize these reports and show that sometimes Henoch-Schönlein purpura associated with FMF differs from typical isolated Henoch-Schönlein purpura, and this is also the case with polyarteritis nodosa and SpA associated with FMF. It is suggested that these clinical manifestations (polyarteritis nodosa, Henoch-Schönlein purpura and SpA) should be considered to be associated with FMF as part of what we call FMF rather than as co-existing additional separate clinical entities. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Familial Mediterranean fever (FMF) in Lebanon and Jordan: a population genetics study and report of three novel mutations.

    PubMed

    Medlej-Hashim, Myrna; Serre, Jean-Louis; Corbani, Sandra; Saab, Odile; Jalkh, Nadine; Delague, Valérie; Chouery, Eliane; Salem, Nabiha; Loiselet, Jacques; Lefranc, Gérard; Mégarbané, André

    2005-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease mostly frequent in Mediterranean populations. Over 50 mutations have been identified in the gene responsible for the disease, MEFV. The present study reports the frequencies of MEFV mutations in 558 Lebanese and 55 Jordanian FMF patients and points out the severity of the M694V frequently observed mutation among these patients. Three novel mutations, T177I, S108R and E474K were also identified in the Lebanese group. An excess of homozygotes and a deficit of heterozygotes were observed in both samples when compared to the expected number of observed genotypes under the Hardy-Weinberg hypothesis. Homozygotes for M694V and M694I were still in excess in the Lebanese group of patients, even after consanguinous homozygotes were removed, or population structure was considered. This excess is therefore neither due to consanguinity nor to subgroups in the Lebanese population, but rather to more remote consanguinity or to a selection bias favoring the census of these genotypes. The fact that FMF female patients were less censed than male patients may be due to the greater resistance of females to pain and to the possibility of confusing abdominal and gynecological pain. The phenotypic heterogeneity of the FMF could then originate both from genetic causes like allelic heterogeneity or modulating genes, and cultural background facing the physiological consequences of genotypes at risk.

  1. Genetic Profile of Patients with Familial Mediterranean Fever (FMF): Single Center Experience at King Hussein Medical Center (KHMC).

    PubMed

    Habahbeh, Lana Ayesh; Hiary, Mansour Al; Zaben, Samar F Al; Al-Momani, Asim; Khasawneh, Rame; Mallouh, Mervat Abu; Farahat, Hayab

    2015-12-01

    To describe the spectrum of genetic mutations in patients with clinical diagnosis of Familial Mediterranean Fever. This is a retrospective study of 3359 sera samples for patient with clinical diagnosis of FMF, over a period of 6 years. The samples were tested for 12 mutations of the MEFV gene by PCR& hybridization of the PCR product with Probes immobilized as an array of panel lines. A total of 1868 (55.6%) samples were found negative, and one or more mutations were detected in 1491 (44.4%) distributed along the mutations. Of the positive results, the Frequency of the mutations was as follows, the M694V was the most common mutation 30%, followed by E 148Q 21.5%, V 726 A 20%, M6801 G/C 9%, M6941 8.3%, P369s 3.7%, A744S 3.1% and 4.2% among the 4 remaining mutations. Frequency of common mutations in our study show similar results in comparisons with Mediterranean countries like Egypt, Turkey, and Syria with the most common mutation in our study being M694V followed by E148 Q.

  2. A population genetics study of the familial Mediterranean fever gene: evidence of balancing selection under an overdominance regime.

    PubMed

    Fumagalli, M; Cagliani, R; Pozzoli, U; Riva, S; Comi, G P; Menozzi, G; Bresolin, N; Sironi, M

    2009-12-01

    Familial Mediterranean Fever (FMF) is a recessively inherited systemic autoinflammatory disease caused by mutations in the MEFV gene. The frequency of different disease alleles is extremely high in multiple populations from the Mediterranean region, suggesting heterozygote advantage. Here, we characterize the sequence variation and haplotype structure of the MEFV 3' gene region (from exon 5 to the 3' UTR) in seven human populations. In non-African populations, we observed high levels of nucleotide variation, an excess of intermediate-frequency alleles, reduced population differentiation and a genealogy with two common haplotypes separated by deep branches. These features are suggestive of balancing selection having acted on this region to maintain one or more selected alleles. In line with this finding, an excess of heterozygotes was observed in Europeans and Asians, suggesting an overdominance regime. Our data, together with the earlier demonstration that the MEFV exon 10 has been subjected to episodic positive selection over primate evolution, provide evidence for an adaptive role of nucleotide variation in this gene region. Our data suggest that further studies aimed at clarifying the role of MEFV variants might benefit from the integration of molecular evolutionary and functional analyses.

  3. Localization of the familial Mediterranean fever gene (FMF) to a 250-kb interval in non-Ashkenazi Jewish founder haplotypes

    SciTech Connect

    1996-09-01

    Chromosome 16p13.3 harbors a gene (MEF) associated with familial Mediterranean fever (FMF), a recessive disease very common in populations of Mediterranean ancestry. In the course of positional cloning of MEF, we genotyped 26 non-Ashkenazi Jewish FMF pedigrees (310 meioses) with 15 microsatellite markers, most of which were recently developed by Genethon. Identification of recombination events in the haplotypes allowed narrowing of the MEF interval to a region between D16S3124 (telomeric) and D16S475 (centromeric). Two markers, D16S3070 and D16S3275, a microsatellite marker isolated from a YAC that also contains D16S3070, showed no recombination with the disease. Linkage disequilibrium and haplotype analysis high-lighted the existence of a founder haplotype in our population. The core ancestral alleles were present in 71% of MEF-bearing chromosomes at loci D16S3070 and D16S3275. Furthermore, identification of historical crossing-over events in these pedigrees indicated that MEF is located between these two loci, which are both contained in a 250-kb genomic fragment. 24 refs., 4 figs., 3 tabs.

  4. Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial mediterranean fever.

    PubMed

    Öksuz, Mustafa Ferhat; Karkucak, Mutlu; Görukmez, Orhan; Ocakoğlu, Gökhan; Yıldız, Abdulmecit; Ture, Mehmet; Yakut, Tahsin; Dilek, Kamil

    2016-02-21

    Various mutations have been identified in the Mediterranean Fever (MEFV) gene which is reported to be responsible from Familial Mediterranean Fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p<0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p>0.05). To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  5. Phenotype 2 familial mediterranean fever: evaluation of 22 case series and review of the literature on phenotype 2 FMF.

    PubMed

    Altunoğlu, Alpaslan; Erten, Şükran; Canoz, Mujdat Batur; Yuksel, Aydan; Ceylan, Gulay Gulec; Balci, Serdar; Dogan, Hayriye Tatli

    2013-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive autoimmune disorder characterized by recurrent bouts of fever and serosal inflammation. FMF may be complicated by AA-type amyloidosis, worsening the prognosis, with associated renal failure in some patients. Complication rate varies with race, being as high as 60% in Turks and as low as 2% in Armenians. In a few cases of patients with FMF (phenotype 2), amyloid nephropathy may be the presenting manifestation. This study included 420 patients who were admitted to the Nephrology and Rheumatology Departments of Atatürk Education and Research Hospital with unexplained proteinuria/nephrotic syndrome. The initial screening test for amyloidosis was the presence of significant proteinuria (300 mg/24 h). All MEFV gene exons were screened for causative mutations by direct DNA sequencing to check for any mutations. There were 22 phenotype 2 FMF patients with 27 allelic variants. The most prevalent allelic variants were M694V (10/27, 37%) and E148Q (7/27, 26%). Phenotype 2 FMF is not as rare as it was thought before; this should be kept in mind for all patients with unexplained proteinuria and/or acute phase response in high-risk ethnic groups for FMF.

  6. The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis.

    PubMed

    Kucuk, Adem; Erol, Mehmet Fatih; Senel, Soner; Eroler, Emir; Yumun, Havvanur Alparslan; Uslu, Ali Ugur; Erol, Asiye Mukaddes; Tihan, Deniz; Duman, Ugur; Kucukkartallar, Tevfik; Solak, Yalcin

    2016-03-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and diffuse abdominal pain. The primary concern with this presentation is to distinguish it from acute appendicitis promptly. Thus, we aimed to evaluate the role of neutrophil lymphocyte ratio (NLR) to leverage the differential diagnosis of acute FMF attack with histologically proven appendicitis. Twenty-three patients with histologically confirmed acute appendicitis and 88 patients with acute attack of FMF were included in the study. NLR, C-reactive protein and other hematologic parameters were compared between the groups. Neutrophil to lymphocyte ratio was significantly higher in patients with acute appendicitis compared to the FMF attack group (8.24 ± 6.31 vs. 4.16 ± 2.44, p = 0.007). The performance of NLR in diagnosing acute appendicitis with receiver operating characteristic analysis with a cut-off value of 4.03 were; 78% sensitivity, 62% specificity, and area under the curve 0.760 (95% confidence interval, 0.655 to 0.8655; p < 0.001). This study showed that NLR, the simple and readily available inflammatory marker may have a useful role in distinguishing acute FMF attack from acute appendicitis.

  7. The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis

    PubMed Central

    Kucuk, Adem; Erol, Mehmet Fatih; Senel, Soner; Eroler, Emir; Yumun, Havvanur Alparslan; Uslu, Ali Ugur; Erol, Asiye Mukaddes; Tihan, Deniz; Duman, Ugur; Kucukkartallar, Tevfik; Solak, Yalcin

    2016-01-01

    Background/Aims: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and diffuse abdominal pain. The primary concern with this presentation is to distinguish it from acute appendicitis promptly. Thus, we aimed to evaluate the role of neutrophil lymphocyte ratio (NLR) to leverage the differential diagnosis of acute FMF attack with histologically proven appendicitis. Methods: Twenty-three patients with histologically confirmed acute appendicitis and 88 patients with acute attack of FMF were included in the study. NLR, C-reactive protein and other hematologic parameters were compared between the groups. Results: Neutrophil to lymphocyte ratio was significantly higher in patients with acute appendicitis compared to the FMF attack group (8.24 ± 6.31 vs. 4.16 ± 2.44, p = 0.007). The performance of NLR in diagnosing acute appendicitis with receiver operating characteristic analysis with a cut-off value of 4.03 were; 78% sensitivity, 62% specificity, and area under the curve 0.760 (95% confidence interval, 0.655 to 0.8655; p < 0.001). Conclusions: This study showed that NLR, the simple and readily available inflammatory marker may have a useful role in distinguishing acute FMF attack from acute appendicitis. PMID:26864298

  8. Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children.

    PubMed

    Ozen, Seza; Demirkaya, Erkan; Amaryan, Gayane; Koné-Paut, Isabelle; Polat, Adem; Woo, Pat; Uziel, Yosef; Modesto, Consuelo; Finetti, Martina; Quartier, Pierre; Papadopoulou-Alataki, Efimia; Al-Mayouf, Sulaiman M; Fabio, Giovanna; Gallizzi, Romina; Cantarini, Luca; Frenkel, Joost; Nielsen, Susan; Hofer, Michael; Insalaco, Antonella; Acikel, C; Ozdogan, Huri; Martini, Alberto; Ruperto, Nicolino; Gattorno, Marco

    2014-04-01

    Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.

  9. Familial Mediterranean fever gene mutations in the inner northern region of Turkey and genotype-phenotype correlation in children.

    PubMed

    Yilmaz, Resul; Ozer, Samet; Ozyurt, Huseyin; Erkorkmaz, Unal; Sahin, Semsettin

    2009-11-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterised by recurrent episodes of fever, polyserositis and rash. The aim of this study was to determine the most common mutations and clinical features, and their relationships. The medical records of 78 patients were evaluated retrospectively. All of the patients had been diagnosed with FMF according to Tel Hashomer criteria between January 2005 and May 2008 in general paediatric clinics of the School of Medicine at Gaziosmanpasa University. Twelve mutations were detected in the 78 patients by polymerase chain reaction-enzyme-linked immunosorbent assay. The patients were classified into three groups according to allele status. The most prominent clinical symptoms were abdominal pain (95%), fever (90%), arthritis (33%) and pleuritis (31%). Seventeen different genotypes were identified. The mutations were homozygous in 25 (32%) patients, compound heterozygous in 28 (36%) patients and heterozygous in 22 (28%) patients. No mutation was detected in three (4%) patients. The most frequent mutations were M694V (55%), M680I (16%), E148Q (10%) and P369S (4%). The mean symptom severity score was highest in the homozygous group, and high levels of C-reactive protein were also detected in this group. In addition to clinical criteria, molecular studies for detecting disease-causing mutations are needed to establish the diagnosis of FMF. FMF patients who were homozygous for MEFV gene mutations had a higher symptom severity score and higher incidence of appendectomy. The broad spectrum of mutations may reflect intercultural interactions of ethnic groups in Anatolia. Nation-wide studies may help to determine the relationships among demographic, clinical and genetic features of FMF.

  10. The detection of a novel insertion mutation in exon 2 of the MEFV gene associated with familial mediterranean fever in a moroccan family.

    PubMed

    Mejtoute, Touhami; Sayel, Hanane; El-Akhal, Jamila; Moufid, Fatima Z; Bouguenouch, Laila; El Bouchikhi, Ihssane; Hida, Mustapha; Couissi, Driss; Ouldim, Karim

    2017-01-01

    Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease that is inherited in an autosomal recessive manner and is caused by mutations in the MEFV gene. As the name indicates, FMF occurs within families and is more common in individuals of Mediterranean descent than in persons of any other ethnicity. To date, 314 mutations have been reported. We studied a Moroccan family with a total of five members, including a mother who was presenting with symptoms of FMF, while her four children remained asymptomatic. The five patients were screened by DNA sequencing of exon 2 and exon 10 of the MEFV gene. Then, complete exome sequencing analysis of the MEFV gene was done for the patients in whom a novel mutation was detected. This analysis identified a novel single base Cytosine (C) insertion mutation in the coding region of the MEFV gene, named c.441dupC (p. Glu148Argfs*5 or E148RfsX5), which resulted in a mutated Pyrin/Marenostrin protein. This is the first report of a new mutation in exon 2 of the MEFV gene in a Moroccan family. This novel insertion mutation may provide important information for further studies of FMF pathogenesis.

  11. Interleukin-1 targeting drugs in familial Mediterranean fever: a case series and a review of the literature.

    PubMed

    Meinzer, Ulrich; Quartier, Pierre; Alexandra, Jean-François; Hentgen, Véronique; Retornaz, Frédérique; Koné-Paut, Isabelle

    2011-10-01

    Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disorder common in Mediterranean populations. FMF is associated with mutations of the MEFV gene, which encodes pyrin. Functional studies suggest that pyrin is implicated in the maturation and secretion of IL-1. The IL-1 receptor antagonist or anti-IL1 monoclonal antibody may therefore represent a new approach to treat FMF. The aim of this report was to evaluate and discuss treatment of FMF with interleukin-1 targeting drugs. Electronic mailing lists of French pediatric and adult rheumatologist associations were used to call for FMF patients treated with interleukin-1 antagonists. A search for published FMF patients treated with interleukin-1 targeting drugs was performed by screening PubMed. Here, we report 7 cases of FMF patients treated with anakinra and/or canakinumab and discuss the clinical situations that may indicate the use of IL-1 blocking agents in FMF. The use of interleukin-1 targeting drugs was beneficial to all patients. The reasons for using interleukin-1 targeting drugs in FMF patients were as follows: (1) incomplete control of disease activity despite colchicine treatment; (2) high serum amyloid A levels despite colchicine treatment; (3) impossibility to use colchicine treatment because of severe side effects; (4) FMF in association with vasculitis. Interleukin-1 targeting drugs may be good candidates when looking for an alternative or supplementary treatment to colchicine. These observations highlight the need for controlled trials to further evaluate the safety and efficacy of interleukin-1 antagonists in FMF patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update.

    PubMed

    Cerquaglia, C; Diaco, M; Nucera, G; La Regina, M; Montalto, M; Manna, R

    2005-02-01

    Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is characterised by recurrent attacks of fever and serositis, lasting 24-72 hours. Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is absorbed in the jejunum and ileum. It metabolised by liver and only small amounts are recovered unchanged in the urine. Really plasma half-life is prolonged in patients with liver or renal failure. Colchicine is able to prevent activation of neutrophils, binding beta-tubulin and making beta-tubulin-colchicine complexes; this way inhibits assembly of microtubules and mitotic spindle formation; moreover its mode of action includes modulation of chemokines, prostanoids production, inhibition of neutrophil and endothelial cell adhesion molecules. The minimal daily dose in adults is 1.0 mg/die, but in children there is not a definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug might interfere with male and female fertility and with children growth, but, according to current guidelines and because of rare side effects of the drug, FMF patients are recommended to take colchicine. Since colchicine treatment is often complicated by frequent gastrointestinal side effects, by our experience, in order to improve colchicine tolerance we recommend: lactose-free diet and treatment of intestinal bacterial overgrowth and/or Hp-infection, assessed by breath tests. Since our data showed that 10-15% of FMF patients seem are non-responders or intolerant to colchicine, today we are working in the design of colchicine analogues which may have lesser toxicities and a larger therapeutic window.

  13. Differential Expression of miR-4520a Associated With Pyrin Mutations in Familial Mediterranean Fever (FMF).

    PubMed

    Latsoudis, Helen; Mashreghi, Mir-Farzin; Grün, Joachim R; Chang, Hyun-Dong; Stuhlmüller, Bruno; Repa, Argyro; Gergiannaki, Irini; Kabouraki, Eleni; Vlachos, George S; Häupl, Thomas; Radbruch, Andreas; Sidiropoulos, Prodromos; Doukoumetzidis, Kimon; Kardassis, Dimitris; Niewold, Timothy B; Boumpas, Dimitrios T; Goulielmos, George N

    2017-06-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent, acute, and self-limiting attacks of fever. Mutations in MEFV gene encoding pyrin account for FMF, but the high number of heterozygote patients with typical symptoms of the disease has driven a number of alternative aetiopathogenic hypotheses. The MEFV gene was knocked down in human myelomonocytic cells that express endogenous pyrin to identify deregulated microRNAs (miRNAs). Microarray analyses revealed 29 significantly differentially expressed miRNAs implicated in pathways associated with cellular integrity and survival. Implementation of in silico gene network prediction algorithms and bioinformatics analyses showed that miR-4520a is predicted to target genes implicated in autophagy through regulation of RHEB/mTOR signaling. Differential expression levels of RHEB were confirmed by luciferase reporter gene assays providing further evidence that is directly targeted by miR-4520a. Although the relative expression levels of miR-4520a were variable among FMF patients, the statistical expression of miR-4520a was different between FMF mutation carriers and controls (P = 0.0061), indicating an association between miR-4520a expression and MEFV mutations. Comparison between FMF patients bearing the M694V mutation, associated with severe disease, and healthy controls showed a significant increase in miR-4520a expression levels (P = 0.00545). These data suggest that RHEB, the main activator of mTOR signaling, is a valid target of miR-4520a with the relative expression levels of the latter being significantly deregulated in FMF patients and highly dependent on the presence of pyrin mutations, especially of the M694V type. These results suggest a role of deregulated autophagy in the pathogenesis of FMF. J. Cell. Physiol. 232: 1326-1336, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Polyarteritis nodosa in patients with Familial Mediterranean Fever (FMF): a concomitant disease or a feature of FMF?

    PubMed

    Ozen, S; Ben-Chetrit, E; Bakkaloglu, A; Gur, H; Tinaztepe, K; Calguneri, M; Turgan, C; Turkmen, A; Akpolat, I; Danaci, M; Besbas, N; Akpolat, T

    2001-02-01

    Familial Mediterranean Fever (FMF) is caused by mutations in the gene encoding pyrin and is characterized by self-limited, recurrent attacks of fever and serositis. Vasculitis has been increasingly reported in FMF. A study evaluating the prognosis in FMF and polyarteritis nodosa (PAN) patients has not been reported previously. To determine the special characteristics and the prognosis of PAN in FMF patients. A questionnaire was used for the present survey. The setting was 7 referral centers from Turkey and Israel. Seventeen patients who were diagnosed with FMF and who developed PAN were included. PAN was diagnosed in those who met the Chapel Hill consensus criteria for microscopic polyarteritis or classic PAN. The clinical features of these 17 patients and the outcomes of their vasculitis were analyzed. The age at diagnosis of PAN in these FMF patients ranged from 3.5 to 37 years. All patients had constitutional symptoms, elevated acute phase reactants, and myalgia at the time PAN was diagnosed. The diagnosis of PAN was confirmed by renal angiography in 8 patients, by renal biopsy in 6 patients, and by muscle and/or nodule biopsies in 6 patients. A number of patients had definite features of both classic PAN and microscopic polyarteritis. When compared with other PAN patients, those with FMF tended to have a younger age at PAN onset, more frequent perirenal hematomas, and an overall better prognosis. The cases with overlapping features of microscopic and classic PAN pose a problem for the current classification of vasculitis. We suggest that the clinical representation of PAN in FMF patients has certain characteristics and may be a feature of FMF per se.

  15. Specific glycosylation of α1-acid glycoprotein characterises patients with familial Mediterranean fever and obligatory carriers of MEFV

    PubMed Central

    Poland, D; Drenth, J; Rabinovitz, E; Livneh, A; Bijzet, J; van het, Hof B; van Dijk, W

    2001-01-01

    BACKGROUND—Familial Mediterranean fever (FMF) is a periodic febrile disorder, characterised by fever and serositis. The acute phase response during attacks of FMF results from the release of cytokines, which in turn induce increased expression and changed glycosylation of acute phase proteins. A recent study indicated that attacks in FMF are accompanied by a rise of plasma concentrations of serum amyloid A (SAA) and C reactive protein (CRP), which remain significantly raised during remission relative to healthy controls. Another study suggested that obligatory heterozygotes also display an inflammatory acute phase response.
OBJECTIVE—To determine the state of inflammation in homozygotic and heterozygotic MEFV genotypes.
METHODS—CRP and SAA were studied by enzyme linked immunosorbent assay (ELISA). The glycosylation of the acute phase protein, α1-acid glycoprotein (AGP), was visualised with crossed affinoimmunoelectrophoresis with concanavalin A as diantennary glycan-specific component and Aleuria aurantia lectin as fucose-specific affinity component.
RESULTS—FMF attacks were associated with an increase (p<0.05) in the serum inflammation parameters CRP, SAA, and AGP. The glycosylation of AGP showed an increase (p<0.05) in fucosylated AGP glycoforms, whereas the branching of the glycans remained unaffected. The glycosylation of AGP in the MEFV carrier group, compared with that in a healthy control group, was characterised by a significant increase (p<0.05) in branching of the glycans, whereas the fucosylation remained unaffected.
CONCLUSION—The findings suggest an FMF-specific release of cytokines, resulting in a different glycosylation of AGP between a homozygotic and heterozygotic MEFV genotype.

 PMID:11454642

  16. A study of familial Mediterranean Fever (MEFV) gene mutations in Egyptian children with type 1 diabetes mellitus.

    PubMed

    Anwar, Ghada Mohammad; Fouad, Hanan M; Abd El-Hamid, Amal; Mahmoud, Faten; Musa, Noha; Lotfi, Hala; Salah, Nermine

    2015-01-01

    An association of type 1 DM and familial Mediterranean fever (FMF) has been newly reported in the medical literature. The aim of the present work was to investigate frequency of MEFV gene mutations in Egyptian children with type 1 diabetes mellitus. Forty five children with type 1 DM were screened for Mediterranean Fever (MEFV) gene mutation. Forty one healthy control subjects were included. Identification of FMF gene mutation was done based on polymerase chain reaction (PCR) and reverse hybridization. The assay covers 12 mutations in the FMF gene: E148Q - P369S - F479L - M680I (G/C) - M680I (G/A) - I692del - M694V - M694I - K695R-V726A - A744S and R761H. Among the screened diabetics, the overall frequency of MEFV gene mutations was 42.2% and among the control group it was 34.1% with no significant difference. Fourteen out of 45 diabetic children (31.1%) were heterozygous (E148Q in 7 children, A744S in 3 children, V726A in 2 children, M680I (G/C) in 1 child and P369S in1 child), while 5 children (11.1%) were compound heterozygous (M694V/M694I in 2 children, E148Q/K695R mutations in 1 child, E148Q/M694I in 1 child and E148Q/V726A in 1 child). The control group showed heterozygous mutation in 34.1% of cases (E148Q mutation in 14.6%, V726A in 12.2%, M680I (G/C) in 4.9% and M694V in 2.4%). No significant difference in mutation frequency between diabetic and non-diabetic children. We have high carrier rate of MEFV gene mutations among Egyptian population probably due to high consanguinity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Dramatic beneficial effect of interleukin-1 inhibitor treatment in patients with familial Mediterranean fever complicated with amyloidosis and renal failure.

    PubMed

    Stankovic Stojanovic, Katia; Delmas, Yahsou; Torres, Pablo Ureña; Peltier, Julie; Pelle, Gaëlle; Jéru, Isabelle; Colombat, Magali; Grateau, Gilles

    2012-05-01

    Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder, for which systemic AA amyloidosis is the major complication revealed most of the time by renal abnormalities. Current treatment is daily colchicine that prevents both recurrent inflammatory attacks and amyloidosis deposition in most patients. However, some patients still develop amyloidosis and renal failure. Functional studies suggest that interleukin (IL)-1 is implicated in the inflammatory reaction in FMF and therefore, IL-1 inhibitors could be a new approach to treat FMF. The aim of this series study was to evaluate anakinra in patients with FMF complicated with amyloidosis and renal failure. We studied a series of adult patients with FMF complicated with amyloidosis and treated with anakinra in one reference centre were reviewed. A search for published patients with FMF associated amyloidosis treated with anakinra was performed by screening PubMed. We report four cases of patients with FMF-associated amyloidosis treated with anakinra and discuss the clinical pertinence of its use in these particular clinical settings. Anakinra has a strong effect on both inflammatory attacks and general status in patients with FMF-associated amyloidosis. It may contribute to changing the prognosis of these patients. Long-term studies are needed to appreciate the effect of anakinra or other IL-1 inhibitors on the natural history of amyloidosis in these patients.

  18. Evaluation of the Effectiveness of Acupuncture Therapy by Verbal Pain Scale in Patients with Abdominal Pain of Familial Mediterranean Fever.

    PubMed

    Becel, Sinan; Sezgin, Yılmaz; Akçay, Fatih

    2016-10-01

    In this study, we evaluated the effectiveness of acupuncture therapy based on Verbal Pain Scale (VPS) scores in familial Mediterranean fever (FMF) patients admitted to the emergency department with attacks of abdominal pain. This observational study was conducted in Erzurum Regional Training and Research Hospital between August 2014 and December 2014. Twenty patients admitted to the emergency department with FMF attacks were included in the study. Acupuncture therapy was applied to three points including LI4 (Hegu), ST25 (Tianshu), and Ren12 (Zhongwan). The VPS test was applied to the patients before and after the treatment. Average VPS scores were found to be 8.45±0.75 before the treatment and 2.10±0.85 after the treatment. The difference of the VPS scores before and after treatment was statistically significant (p=0.001). To our knowledge, this is the first study evaluating the effectiveness of acupuncture therapy in the treatment of FMF attacks. Our results suggest that acupuncture therapy can be used as an effective treatment method in patients with FMF attacks. Copyright © 2016. Published by Elsevier B.V.

  19. Familial Mediterranean Fever Is Associated With Increased Mortality After Kidney Transplantation-A 19 Years' Single Center Experience.

    PubMed

    Green, Hefziba; Lichtenberg, Shelly; Rahamimov, Ruth; Livneh, Avi; Chagnac, Avry; Mor, Eytan; Rozen-Zvi, Benaya

    2017-10-01

    Current data regarding the outcome of kidney transplantation in patients with familial Mediterranean fever (FMF) who reach end-stage renal disease (ESRD) due to reactive amyloidosis A (AA) are scarce and inconclusive. The outcomes of 20 patients with FMF and biopsy-proven AA amyloidosis that were transplanted between 1995 and 2014 were compared with 82 control patients (32 with diabetes mellitus and 50 with nondiabetic kidney disease). Major outcome data included overall patient and graft survivals. During a mean overall follow-up of 116.6 ± 67.5 months 11 patients (55%) with FMF died versus 26 patients (31%) in the control group. Median time of death for patients with FMF was 61 months (range, 16-81) after transplantation. Estimated 5-year, 10-year, and actuarial 15-year overall patients survival rates were 73%, 45%, and 39%, respectively, for patients with FMF, versus 84%, 68% and 63%, respectively, for the control group (P = 0.028). FMF was associated with more than twofold increased risk for death after transplantation, and with a threefold increased risk for hospitalization because of infections during the first year. Infections and cardiovascular disease were the cause of death in the majority of patients with FMF. Overall graft survival was similar between the groups. Recurrence of AA amyloidosis was diagnosed in 2 patients during the first year after transplantation. FMF is associated with increased risk of mortality after kidney transplantation.

  20. Efficacy of anti-IL-1 treatment in familial Mediterranean fever: a systematic review of the literature

    PubMed Central

    van der Hilst, Jeroen CH; Moutschen, Michel; Messiaen, Peter E; Lauwerys, Bernard R; Vanderschueren, Steven

    2016-01-01

    Introduction In 5%–10% of patients with familial Mediterranean fever (FMF), colchicine is not effective in preventing inflammatory attacks. Another 5%–10% of patients are intolerant to effective doses of colchicine and experience serious side effects. Treatment with anti-interleukin-1 (IL-1) drugs may be an alternative for these patients, although it is not reimbursed for this indication in many countries. Methods We systematically searched PubMed, Web of Science, and Scopus for reports of anti-IL-1 treatment in FMF patients. Results Out of 284 potentially relevant articles, 27 eligible reports were identified and included in the data analysis. Conclusion A complete response to therapy without a single attack during treatment was reported in 76.5% of patients on anakinra treatment and in 67.5% of patients during canakinumab treatment. In patients with established type AA amyloidosis, anti-IL-1 treatment can reverse proteinuria. Anti-IL-1 therapy seems to be a safe and effective alternative for patients with FMF who do not respond to or cannot tolerate colchicine. PMID:27110096

  1. Efficacy of anti-IL-1 treatment in familial Mediterranean fever: a systematic review of the literature.

    PubMed

    van der Hilst, Jeroen Ch; Moutschen, Michel; Messiaen, Peter E; Lauwerys, Bernard R; Vanderschueren, Steven

    2016-01-01

    In 5%-10% of patients with familial Mediterranean fever (FMF), colchicine is not effective in preventing inflammatory attacks. Another 5%-10% of patients are intolerant to effective doses of colchicine and experience serious side effects. Treatment with anti-interleukin-1 (IL-1) drugs may be an alternative for these patients, although it is not reimbursed for this indication in many countries. We systematically searched PubMed, Web of Science, and Scopus for reports of anti-IL-1 treatment in FMF patients. Out of 284 potentially relevant articles, 27 eligible reports were identified and included in the data analysis. A complete response to therapy without a single attack during treatment was reported in 76.5% of patients on anakinra treatment and in 67.5% of patients during canakinumab treatment. In patients with established type AA amyloidosis, anti-IL-1 treatment can reverse proteinuria. Anti-IL-1 therapy seems to be a safe and effective alternative for patients with FMF who do not respond to or cannot tolerate colchicine.

  2. Genotypic diagnosis of familial Mediterranean fever (FMF) using new microsatellite markers: example of two extensive non-Ashkenazi Jewish pedigrees.

    PubMed Central

    Dupont, M; Dross, C; Smaoui, N; Nedelec, B; Grateau, G; Clépet, C; Gourdier, I; Koné-Paut, I; Delpech, M; Demaille, J; Touitou, I

    1997-01-01

    Familial Mediterranean fever is an autosomal recessive disease characterised by multiple attacks of serosal inflammation in the absence of treatment. In the absence of timely diagnosis, renal amyloidosis is a life threatening complication. The diagnosis is often missed because no specific test is available. Early colchicine treatment prevents attacks and renal complications. The FMF gene (MEF) has been mapped to chromosome 16p 13.3 but has not yet been identified. We compared the suitability of a series of microsatellite markers (four of them were new) and propose the routine use of seven of these markers, exhibiting alleles in strong linkage disequilibrium with the disease and informative in 100% of diagnosed patients. Moreover, the discovery of a homozygous status for the 3-3-9 (or 3-3-18) haplotype at the core loci (D16S3070, D16S3082, and D16S3275), which was found in 73% non-Ashkenazi Jewish patients, points to a diagnosis of FMF, even in sporadic cases, with a risk of error of only 2.10(-5). Two extensive pedigrees covering most indications for genetic counselling are presented, showing that it is now possible both prospectively and retrospectively to identify members likely to have MEF mutations. With the help of this accurate test, colchicine treatment can be better targeted, especially where the symptomatology is mild or atypical. PMID:9152834

  3. The report of sequence analysis on familial Mediterranean fever gene (MEFV) in South-eastern Mediterranean region (Kahramanmaraş) of Turkey.

    PubMed

    Kilinc, Metin; Ganiyusufoglu, Eda; Sager, Hatice; Celik, Ahmet; Olgar, Seref; Cetin, Gozde Yildirim; Davutoglu, Mehmet; Altunoren, Orcun

    2016-01-01

    Familial Mediterranean fever (FMF) is defined as an inherited and autosomal recessive disease. Many researches have been done about this subject, and we believe that it should be necessary to focus on phenotype-genotype correlation, especially novel mutation types. We aim to announce the results of FMF sequence analysis in Kahramanmaras/Turkey. The number of participants is 380 males and 451 females who clinically diagnosed as FMF subjects of different age groups. Genomic sequences of exons 2 and 10 and in some cases exon 3 of the MEFV gene were scanned for mutations by sequence analyzer. The most common mutation identified in 230 (57.07 %) patients is heterozygous. The frequencies of mutation types in heterozygous subjects are R202Q (39.13 %), E148Q (18.70 %), M680I (16.52 %), M694V (13.91 %), and V726A (4.78 %), respectively. The most striking point among the compound heterozygous subjects is R202Q/M694V mutation type found at the highest rate (32 subjects). Fever and peritonitis are the most frequent signs of homozygous M694V and combine heterozygous mutations. Interestingly, the rate of homozygous mutation types (M694V/M694V+ R202Q/R202Q) is 96.70 % among all compound homozygous mutation types. The most frequent rate of homozygous patients is M680I mutation types (68.42 % in all homozygous mutation types). Two novel mutations were found in this study: N206K (p.Asn206Lys) and S208T (p.Ser208Tyr). Our findings in this study on the FMF sequence analysis are different from the results obtained from the other regions of Turkey.

  4. Tocilizumab in the treatment of twelve cases with aa amyloidosis secondary to familial mediterranean fever.

    PubMed

    Ugurlu, Serdal; Hacioglu, Aysa; Adibnia, Yasaman; Hamuryudan, Vedat; Ozdogan, Huri

    2017-05-30

    There is no established treatment of AA amyloidosis, a long-term complication of various chronic inflammatory diseases associated with increased mortality, such as familial Mediterranian fever (FMF). Recently there are few reports pointing out that tocilizumab(TCZ), an anti IL-6 agent may be effective in AA amyloidosis resistant to conventional treatments. We report our data on the effect of TCZ in patients with FMF complicated with AA amyloidosis. FMF patients with histologically proven AA amyloidosis, treated with TCZ (8 mg/kg per month) were followed monthly and the changes in creatinine, creatinine clearance, the amount of 24-hour urinary protein, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were noted throughout the treatment period. Adverse effects of the treatment were closely monitored. TCZ was given to 12 patients (6 F, 6 M) who also continued to receive colchicine (1.9 ± 0.4 mg/day). Coexisting diseases were ankylosing spondylitis(4) and Crohn's disease(1). The mean age was 35.2 ± 10.0 years and the mean follow-up on TCZ was 17.5 ± 14.7 months. The renal functions remained stable (mean creatinine from 1.1 ± 0.9 mg/dl to 1.0 ± 0.6 mg/dl), while a significant decrease in acute phase response (the mean CRP from 18.1 ± 19.5 mg/L to 5.8 ± 7.1 mg/L and ESR from 48.7 ± 31.0 mm/h to 28.7 ± 28.3 mm/h) was observed and the mean 24-hour urinary protein excretion reduced from 6537.6 ± 6526.0 mg/dl to 4745.5 ± 5462.7 mg/dl. Two patients whose renal functions were impaired prior to TCZ therapy improved significantly on this regimen. No infusion reaction was observed. None of the patients experienced any FMF attack under TCZ treatment with the exception of 2, one of whom had less frequent attacks while the other had episodes of erysipelas-like erythema. CONCLUSıON: Tocilizumab improved the acute phase response and the renal function in this group of patients and was generally well

  5. The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population

    PubMed Central

    Battal, F; Silan, F; Topaloğlu, N; Aylanç, H; Köksal Binnetoğlu, F; Tekin, M; Kaymaz, N; Ozdemir, O

    2016-01-01

    Abstract The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 60 children diagnosed with familial Mediterranean fever (FMF) and to compare the phenotype-genotype correlation. Genomic DNA was isolated by the spin-column method from peripheral blood samples (collected in vacutainers containing EDTA) and buccal smears. The MEFV gene profiles for the current FMF cohort were genotyped by pyrosequencing and direct Sanger sequencing techniques for the target pathogenic variants. The most prominent clinical symptoms were abdominal pain (53.4%), fever (23.4%) and arthritis (23.3%). Eighteen different pathogenic variants were identified and the most frequent were p.Met694Val (20.0%), p.Glu148Gln (13.3%), p.Met680 Ile (11.7%) and p.Arg202Gln (11.7%). Abdominal pain, fever and arthritis were the most common presenting clinical characteristics. Results showed that not only clinical characteristics, but also genotyping of the MEFV gene is needed to establish the correct diagnosis of FMF in children and other family members. PMID:28289585

  6. The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population.

    PubMed

    Battal, F; Silan, F; Topaloğlu, N; Aylanç, H; Yıldırım, Ş; Köksal Binnetoğlu, F; Tekin, M; Kaymaz, N; Ozdemir, O

    2016-12-01

    The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 60 children diagnosed with familial Mediterranean fever (FMF) and to compare the phenotype-genotype correlation. Genomic DNA was isolated by the spin-column method from peripheral blood samples (collected in vacutainers containing EDTA) and buccal smears. The MEFV gene profiles for the current FMF cohort were genotyped by pyrosequencing and direct Sanger sequencing techniques for the target pathogenic variants. The most prominent clinical symptoms were abdominal pain (53.4%), fever (23.4%) and arthritis (23.3%). Eighteen different pathogenic variants were identified and the most frequent were p.Met694Val (20.0%), p.Glu148Gln (13.3%), p.Met680 Ile (11.7%) and p.Arg202Gln (11.7%). Abdominal pain, fever and arthritis were the most common presenting clinical characteristics. Results showed that not only clinical characteristics, but also genotyping of the MEFV gene is needed to establish the correct diagnosis of FMF in children and other family members.

  7. [Recurrent pericardial effusion due to familiar Mediterranean fever].

    PubMed

    Halabe-Cherem, José; Hamui-Sutton, Alicia; Cohen-Cohen, Salomón; Sacal-Dumani, Elisa; Shuchleib-Cung, Ariel; Nellen-Hummel, Haiko; Rábago-Arredondo, Julia

    2009-01-01

    Pericarditis is usually a complication of viral or bacterial infection. In addition, it can be associated to systemic diseases such as autoimmune disorders, rheumatic fever, cancer, tuberculosis and AIDS. It can also be related to familial Mediterranean fever, an autosomic recessive inflammatory disease, characterized by fever, abdominal pain, and pleuritis mainly seen in persons from the Mediterranean area. In this study, we described the evolution and treatment response to colchicine in three patients with pericarditis associated to familial Mediterranean fever. Two of the patients had a pericardiectomy showing in their biopsy nonspecified inflammatory changes. Later their diagnosis were confirmed by genetic markers, echocardiogram and EKG. They were treated with antiviral and antibiotics without any improvement; subsequently they had good results with colchicine.

  8. Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis.

    PubMed

    Shinar, Yael; Tohami, Tali; Livneh, Avi; Schiby, Ginette; Hirshberg, Abraham; Nagar, Meital; Goldstein, Itamar; Cohen, Rinat; Kukuy, Olga; Shubman, Ora; Sharabi, Yehonatan; Gonzalez-Roca, Eva; Arostegui, Juan I; Rechavi, Gideon; Amariglio, Ninnette; Salomon, Ophira

    2015-06-30

    A study was designed to identify the source of fever in a patient with post-polycythemia myelofibrosis, associated with clonal Janus Kinase 2 (JAK2) mutation involving duplication of exon 12. The patient presented with 1-2 day long self-limited periodic episodes of high fever that became more frequent as the hematologic disease progressed. After ruling out other causes for recurrent fever, analysis of the pyrin encoding Mediterranean fever gene (MEFV) was carried out by Sanger sequencing in peripheral blood DNA samples obtained 4 years apart, in buccal cells, laser dissected kidney tubular cells, and FACS-sorted CD3-positive or depleted mononucleated blood cells. Hematopoeitc cells results were validated by targeted deep sequencing. A Sanger sequence based screen for pathogenic variants of the autoinflammatory genes NLRP3, TNFRSF1A and MVK was also performed. A rare, c.1955G>A, p.Arg652His MEFV gene variant was identified at negligible levels in an early peripheral blood DNA sample, but affected 46 % of the MEFV alleles and was restricted to JAK2-positive, polymorphonuclear and CD3-depleted mononunuclear DNA samples obtained 4 years later, when the patient experienced fever bouts. The patient was also heterozygous for the germ line, non-pathogenic NLRP3 gene variant, p.Q705K. Upon the administration of colchicine, the gold standard treatment for familial Mediterranean fever (FMF), the fever attacks subsided. This is the first report of non-transmitted, acquired FMF, associated with a JAK2 driven clonal expansion of a somatic MEFV exon 10 mutation. The non-pathogenic germ line NLRP3 p.Q705K mutation possibly played a modifier role on the disease phenotype.

  9. Successful treatment with anti-tumor necrosis factor (anti-TNF)-alpha of proteinuria in a patient with familial mediterranean fever (FMF) resistant to colchicine: anti-TNF drugs and FMF.

    PubMed

    Erten, S; Erten, S F; Altunoglu, A

    2012-04-01

    Familial mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever, peritonitis, pleuritis, and genetically by autosomal recessive inheritance. The major renal involvement in FMF is the occurrence of amyloidosis that can be prevented by a daily regimen of colchicine. About 5-10% of cases with familial mediterranean fever may be resistant to colchicine. In literature, there is a controversy about the treatment of FMF patients resistant to colchicine. We describe a case with FMF, proteinuria, and bilateral sacroiliitis, which responded to anti-TNF (tumor necrosis factor)-alpha therapy with infliximab and etanercept.

  10. Familial Mediterranean fever (FMF) and multiple sclerosis: an association study in one of the world's largest FMF cohorts.

    PubMed

    Yahalom, G; Kivity, S; Lidar, M; Vaknin-Dembinsky, A; Karussis, D; Flechter, S; Ben-Chetrit, E; Livneh, A

    2011-09-01

      To describe and characterize the association between familial Mediterranean fever (FMF) and multiple sclerosis (MS).   The patient registry of The National Center for FMF was screened for the coexistence of FMF and MS. Tel-Hashomer criteria were used for the diagnosis of FMF, and FMF severity was evaluated, using the simplified FMF severity scale. McDonald criteria were used for the diagnosis of MS, and neurologic disability was measured using the expanded disability status scale (EDSS).   We identified nine patients, affected with both FMF and MS. The onset of the FMF averaged 15.6 (3-37) years. Most patients suffered from abdominal and joint attacks, and 50% of the patients sustained a moderate to severe FMF. The onset of the MS was at an average age of 31.6 (17-50) years. Neurologic manifestations varied individually, without a dominant deficit, and the course was in a relapsing-remitting pattern in most. The median EDSS was in general of low score (3.0), apart from the patients who were homozygous for the M694V mutation, in whom the MS was more severe. Based on our case series, the frequency of MS in our FMF population is 0.075%, twice higher the expected rate in the general population (P=0.0057).   Multiple sclerosis is more common in FMF than in the general Israeli population. Homozygosity for the M694V MEFV mutation may aggravate the phenotype of MS and predispose FMF patients to develop MS. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

  11. Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever

    PubMed Central

    Yasunami, Michio; Nakamura, Hitomi; Agematsu, Kazunaga; Nakamura, Akinori; Yazaki, Masahide; Kishida, Dai; Yachie, Akihiro; Toma, Tomoko; Masumoto, Junya; Ida, Hiroaki; Koga, Tomohiro; Kawakami, Atsushi; Eguchi, Katsumi; Furukawa, Hiroshi; Nakamura, Tadashi; Nakamura, Minoru; Migita, Kiyoshi

    2015-01-01

    Objectives The genotype-phenotype correlation of MEFV remains unclear for the familial Mediterranean fever (FMF) patients, especially without canonical MEFV mutations in exon 10. The risk of FMF appeared to be under the influence of other factors in this case. The contribution of HLA polymorphisms to the risk of FMF was examined as strong candidates of modifier genes. Methods Genotypes of HLA-B and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients, who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The effects of carrier status were evaluated for the risk of FMF by odds ratio (OR). The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with certain MEFV genotypes and responsiveness to colchicine treatment. Results The carriers of B*39:01 were increased in the patients (OR = 3.25, p = 0.0012), whereas those of DRB1*15:02 were decreased (OR = 0.45, p = 0.00050), satisfying Bonferroni’s correction for multiple statistical tests (n = 28, p<0.00179). The protective effect of DRB1*15:02 was completely disappeared in the co-existence of B*40:01. The HLA effects were generally augmented in the patients without a canonical MEFV variant allele M694I, in accordance with the notion that the lower penetrance of the mutations is owing to the larger contribution of modifier genes in the pathogenesis, with a few exceptions. Further, 42.9% of 14 colchicine-resistant patients and 13.5% of 156 colchicine-responders possessed B*35:01 allele, giving OR of 4.82 (p = 0.0041). Conclusions The differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations. PMID:25974247

  12. Familial Mediterranean fever (FMF) with proteinuria: clinical features, histology, predictors, and prognosis in a cohort of 25 patients.

    PubMed

    Kukuy, Olga; Livneh, Avi; Ben-David, Aharon; Kopolovic, Juri; Volkov, Alexander; Shinar, Yael; Holtzman, Eliezer; Dinour, Dganit; Ben-Zvi, Ilan

    2013-12-01

    Reactive (AA) amyloidosis may complicate familial Mediterranean fever (FMF), the prototype of autoinflammatory diseases. Thus, proteinuria in FMF is commonly viewed as resulting from amyloidosis, and kidney biopsy is deemed superfluous. However, nephropathy other than amyloidosis has been described in FMF, but its rate and distinctive characteristics are unknown. Our aim was to determine the rate and underlying pathology of FMF-related nonamyloidotic proteinuria and compare its clinical course, demographic, and genetic features to those of FMF-amyloid nephropathy. This study is a retrospective analysis of data from patients with FMF undergoing kidney biopsy for proteinuria above 0.5 g/24 h, over 10 years (2001-2011). Clinical, laboratory, genetic, and pathology data were abstracted from patient files. Biopsies were viewed by an experienced pathologist, as necessary. Of the 25 patients referred for kidney biopsy, only 15 (60%) were diagnosed with amyloid kidney disease (AKD), and 10 were diagnosed with another nephropathy. The AKD and nonamyloid kidney disease (NAKD) groups were comparable on most variables, but showed distinct characteristics with regard to the degree of proteinuria (6.45 ± 4.3 g vs 2.14 ± 1.6 g, p = 0.006), rate of severe FMF (14 vs 5 patients, p = 0.022), and rate of development of end stage renal disease (73.3% vs 20%, p = 0.015), respectively. NAKD is common in FMF and, compared to amyloidosis, it is featured with milder course and better prognosis. Contrary to common practice, it is highly recommended to obtain a kidney biopsy from patients with FMF and proteinuria more than 0.5 g/24 h.

  13. Comparison of serum oxidant and antioxidant parameters in familial Mediterranean fever patients (FMF) with attack free period.

    PubMed

    Şahin, Ali; Erten, Şükran; Altunoğlu, Alpaslan; Işıkoğlu, Semra; Neşelioğlu, Salim; Ergin, Merve; Atalay, Hacı Veli; Erel, Özcan

    2014-01-01

    Familial Mediterranean fever (FMF) is an autoinflammatory, autosomal recessive, inherited disease characterized by recurrent self-limiting attacks of serosal surfaces. The imbalance of oxidants/antioxidants may play a role in such attacks. In this study, we aimed to evaluate the relationship between serum paraoxonase (PON1) activity, PON1 phenotype, and other parameters in patients with FMF and healthy controls. A total of 120 FMF patients with an attack-free period (AFP) and 65 healthy subjects were included in this study. The serum PON1 activity, stimulated paraoxonase (SPON) activity, PON1 phenotype (representing Q192R polymorphism; QQ, QR, RR), arylesterase activity, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), advanced oxidative protein products (AOPP), total thiols (TTL), and ischemia-modified albumin (IMA) and cystatin-c (CYS-C) levels were measured. For the QQ phenotype, the median TTL and AOPP levels of the control group were 264.50 (57.75) mol/L and 21.26 (21.17) mmol/L, respectively, whereas the median TTL, AOPP levels of the patients were 309.00 (47.00) mol/L and 12.98 (6.96) mmol/L, respectively. There was a statistically significant difference between the patients and controls with the QQ phenotype in terms of TTL and AOPP (p< 0.001 and p= 0.004, respectively). However, there were no statistically significant differences between the QQ and QR+RR phenotypes with respect to TAC, TOS, OSI, or the other parameters. The FMF patients with AFP had higher TTL and lower AOPP levels than the controls. However, other oxidant and antioxidant parameters were similar among the patients during AFP and the controls.

  14. Vitamin D status, serum lipid concentrations, and vitamin D receptor (VDR) gene polymorphisms in Familial Mediterranean fever.

    PubMed

    Turhan, Turan; Doğan, Halef Okan; Boğdaycioğlu, Nihal; Eyerci, Nilnur; Omma, Ahmet; Sari, İsmail; Yeşilyurt, Ahmet; Karaaslan, Yaşar

    2017-09-18

    Vitamin D (VitD) is critical for the regulation of inflammatory processes, and VitD deficiency has been linked to several chronic inflammatory disorders. We aimed to investigate the concentrations of serum 25(OH)D3, lipid parameters, and three known VDR polymorphisms (BsmI, FokI, and TaqI) in patients with Familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disease. The study included 123 FMF patients and 105 controls. A total of 38 patients were in acute attacks at the time of investigation. Serum 25(OH)D3 concentrations were determined using liquid chromatography-tandem mass spectrometry. BsmI, FokI, and TaqI polymorphisms were analyzed by a competitive allele specific polymerase chain reaction assay (KASPar). Serum lipid parameters were measured with enzymatic colorimetric methods. 25(OH)D3 concentrations were lower in FMF patients compared to controls (p < 0.001). No difference was observed in 25(OH)D3 concentration between patients with acute attack and those in attack-free period (p = 0.193). The distributions of FokI and TaqI genotypes were not significantly different between FMF patients and controls. There was a significant difference in the distribution of AA BsmI genotype between male FMF patients and male controls. Increased concentrations of triglycerides (p = 0.012) and decreased concentrations of high-density lipoprotein cholesterol [HDL-C] (p = 0.006) were found in FMF patients compared to controls. Although lower 25(OH)D3 concentrations were observed in FMF patients versus controls, no association was determined between FMF attack frequency and 25(OH)D3 concentrations. We showed that the AA genotype of BsmI polymorphism is associated with FMF in males but not in females. The effects of decreased HDL-C and increased triglyceride concentrations on cardiovascular events in FMF patients should be further investigated.

  15. Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients.

    PubMed

    Bavbek, Nuket; Ceri, Mevlut; Akdeniz, Derya; Kargili, Ayse; Duranay, Murat; Erdemli, Kemal; Akcay, Ali; Guz, Galip

    2014-06-01

    Coagulation abnormalities have been reported in familial Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but there is not enough data about the continuity of the thrombogenic activity in FMF patients in clinical remission. The purpose of this study was to assess thrombin activatable fibrinolysis inhibitor (TAFI) levels and its relationship with fibrinolytic activity and also evaluate relationships between mutations and clinical signs in attack-free patients without amyloidosis. Seventy-nine FMF patients and 40 healthy adults were included. The study group was divided into five groups as follows: first group, homozygote M694V; second group, homozygote M680I; third group, M694V in one allele, the other allele have other mutations or not; fourth group, other mutations; and fifth group, no mutation. Serum TAFI levels were significantly increased in patients compared with healthy individuals (116.64 ± 21.8 vs. 78.48 ± 19.7 μg/mL, p < 0.001) and a positive correlation was detected between TAFI antigen level and erythrocyte sedimentation rate and C-reactive protein levels (r = 0.247, p = 0.029 and r = 0.252, p = 0.032, respectively). Mean fibrinogen and TAFI levels were significantly higher in Group 1 than the other groups (p = 0.04 and p = 0.001, respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p = 0.04 and p = 0.001, respectively). High level of TAFI antigen in attack-free period of FMF disease shows ongoing subclinical inflammation and hypercoagulability. Clinicians should be careful about thrombosis even in patients at clinical remission. Also, genetic tests must be considered to predict clinical outcome and to reduce complications of FMF disease.

  16. Long-term outcome of renal transplantation in patients with familial Mediterranean fever amyloidosis: a single-center experience.

    PubMed

    Abedi, A S; Nakhjavani, J M; Etemadi, J

    2013-01-01

    Familial Mediterranean fever (FMF) is an autosomal-recessive disorder, affecting multiple organs. The AA type of amyloidosis is most common and serious complication cause nephropathy and end-stage renal disease (ESRD). Renal transplantation (RTX) remains treatment of choice for ESRD. We aimed to investigate long-term results of RTX in patients with FMF amyloidosis. We compared the outcomes of 18 patients (12 men and 6 women) with FMF amyloidosis among 601 (2.9%) transplants with 200 control patients. Demographic data and gene analysis were evaluated. In our study the 1-year graft and patient survivals were 94.44% and 100%, respectively. At 5 years after RTX, they were 94.73% and 88.88%, respectively, in the FMF group without difference from controls. Mean creatinine level at 1 and 5 years were 1.43 ± 0.54 and 1.73 ± 0.89, respectively. The results of MEFV mutation analyses were: M694V/M694V homozygote in 1 patient, M694V/EQ148 in 3, M694V/V726A in 2, 680M-I/E148Q in 3, M694V/M680I in 5, R202Q/M680I in 2, and M694V/R202Q in 2. Recurrence was noticed in 1 patient with M694V/M680I. One patient died because of graft loss and cardiac complications with M694V/M680I gene analysis. Colchicine was reduced in 4 patients owing to side effects. Long-term outcomes of transplantation in patients with amyloidosis secondary to FMF is similar to that in the general transplant population and maintenance colchicine, even after decreasing its dose, effectively prevents recurrence of amyloidosis in the allograft. Copyright © 2013. Published by Elsevier Inc.

  17. Systemic Concentrations of Short Chain Fatty Acids Are Elevated in Salmonellosis and Exacerbation of Familial Mediterranean Fever

    PubMed Central

    Ktsoyan, Zhanna A.; Mkrtchyan, Mkhitar S.; Zakharyan, Magdalina K.; Mnatsakanyan, Armine A.; Arakelova, Karine A.; Gevorgyan, Zaruhi U.; Sedrakyan, Anahit M.; Hovhannisyan, Alvard I.; Arakelyan, Arsen A.; Aminov, Rustam I.

    2016-01-01

    Gut microbiota-produced short chain fatty acids (SCFAs) play an important role in the normal human metabolism and physiology. Although the gradients of SCFAs from the large intestine, where they are largely produced, to the peripheral blood as well as the main routes of SCFA metabolism by different organs are known well for the healthy state, there is a paucity of information regarding how these are affected in disease. In particular, how the inflammation caused by infection or autoinflammatory disease affect the concentration of SCFAs in the peripheral venous blood. In this work, we revealed that diseases caused either by infectious agents (two Salmonella enterica serovars, S. Enteritidis, and S. Typhimurium) or by the exacerbation of an autoinflammatory disease, familial Mediterranean fever (FMF), both result in a significantly elevated systemic concentration of SCFAs. In the case of salmonellosis the concentration of SCFAs in peripheral blood was significantly and consistently higher, from 5- to 20-fold, compared to control. In the case of FMF, however, a significant increase of SCFAs in the peripheral venous blood was detected only in the acute phase of the disease, with a lesser impact in remission. It seems counterintuitive that the dysbiotic conditions, with a reduced number of gut microorganisms, produce such an effect. This phenomenon, however, must be appraised within the context of how the inflammatory diseases affect the normal physiology. We discuss a number of factors that may contribute to the “leak” and persistence of gut-produced SCFAs into the systemic circulation in infectious and autoinflammatory diseases. PMID:27252692

  18. Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents

    PubMed Central

    Twig, Gilad; Livneh, Avi; Vivante, Asaf; Afek, Arnon; Shamiss, Ari; Derazne, Estela; Tzur, Dorit; Ben-Zvi, Ilan; Tirosh, Amir; Barchana, Micha; Shohat, Tamy; Golan, Eliezer; Amital, Howard

    2016-01-01

    Objective There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF. Methods We studied a nationwide, population-based, retrospective cohort of 1225 individuals with FMF (59% men) in a database of 1 244 350 adolescents (16–20 years of age) medically evaluated for military service between 1973 and 1997. This cohort was linked with the national mortality, cancer and end-stage renal disease (ESRD) registries in Israel. Study outcomes were all-cause mortality, occurrence of ESRD and malignancy by the age of 50 years. Results During 30 years of follow-up, death rates were 8.73/104 versus 4.32/104 person-years in the FMF and control groups, respectively (p=0.002). In a multivariable analysis adjusted for age, birth year, socio-economic status, education, ethnicity and body mass index, FMF was associated with increased mortality in men (HR=1.705 (95% CI 1.059 to 2.745), p=0.028) and women (HR=2.48 (1.032 to 5.992), p=0.042). Renal amyloidosis accounted for 35% and 60% of deaths in men and women, respectively. FMF was not associated with an increased incidence of cancer. Conclusions FMF is associated with increased all-cause mortality that is likely attributed to reduced colchicine compliance or responsiveness. Individuals with FMF do not have an increased incidence of cancer. These results support the awareness among medical community to decrease the higher than average mortality rate among participants with FMF. PMID:23505237

  19. Evaluation of subclinical inflammation in familial Mediterranean fever patients: relations with mutation types and attack status: a retrospective study.

    PubMed

    Kelesoglu, Fatih Mehmet; Aygun, Erhan; Okumus, Nazli Kubra; Ersoy, Ayşenur; Karapınar, Edanur; Saglam, Nesibe; Aydın, Nur Gokce; Senay, Beyza Betul; Gonultas, Sumeyye; Sarisik, Elif; Can, Melike Zeynep; Atay, Sirin; Basbug, Dilruba; Tiryaki, Feyza Kubra; Ozer, Sena; Durmus, Rana Berru; Orem, Fatih; Atay, Tugrul; Acar, Ahmet; Yilmaz, Yasin; Kaya, Seyma; Ciftkaya, Aylin; Sarac, Zeynep; Makar, Cagri Can; Saracoglu, Basak; Dogdu, Gafur; Omeroglu, Rukiye Eker

    2016-11-01

    Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease of childhood and adulthood. Development of systemic amyloidosis and frequent attack influence quality of life and survival. There is sporadic evidence indicating subclinical inflammation in patients with FMF. We aimed to assess subclinical inflammation using neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) in pediatric patients with FMF in the attack-free period. In this retrospective study, we reviewed the files of all FMF patients in our pediatric rheumatology outpatient clinic in a tertiary center and enrolled those with sufficient clinical and laboratory data. We also enrolled 73 controls. We grouped the patients according to being in attack period or attack-free period. We compared CRP, NLR, PLR, and WBC (white blood cell) levels between different mutations and polymorphisms. We also compared patients in the attack period with those in attack-free period. We enrolled 61 patients in attack period, 509 patients in attack-free period, and 73 controls. There was no difference between patients with different mutations with respect to NLR or PLR levels in the attack-free period. However, CRP levels were higher in patients with homozygous exon 10 mutations, especially those with homozygous M694V mutations compared with other mutations. However, CRP levels were mostly normal in these patients. Our data are against the reported fact that patients with FMF have higher NLR or PLR levels in attack-free periods. However, CRP levels were higher in the presence of homozygous exon 10 mutations (in particular homozygous M694V mutations).

  20. Colchicine-free remission in familial Mediterranean fever: featuring a unique subset of the disease-a case control study

    PubMed Central

    2014-01-01

    Background To demonstrate and clinically, genetically and demographically characterize familial Mediterranean fever (FMF) patients, maintaining remission despite colchicine abstinence. Methods FMF patients were screened for an endurance of prolonged remission (≥ 3 years), despite refraining from colchicine. Clinical, demographic and genetic parameters were collected. Data were compared with those of consecutive control FMF subjects, coming to the clinic for their periodic follow up examination. Results Of 1000 patients screened over 5 years, 33 manifested colchicine-free remission. The mean duration of the remission period was 12.6 ± 8.1 years. Patients in the remission group had milder severity of FMF, compared to the control group (22 vs. 11 patients with mild disease, respectively, p = 0.003) and a longer diagnosis delay (21 ± 15.7 vs. 13.4 ± 13.5 years, respectively, p = 0.04). Patients experiencing remission suffered mostly of abdominal attacks, low rate of attacks in other sites and low rate of chronic and non-attack manifestations. When the disease resumed activity, it responded well to colchicine, despite using a lower dose, as compared to the control subjects (p < 0.001). None of the patients in this group was homozygous for the M694V mutation (p = 0.0008). Conclusions Prolonged colchicine-free remission defines a rare and milder form of FMF with unique clinical, demographic, and molecular characteristics. PMID:24401676

  1. Is the IL-6 -174G/C Gene Polymorphism Related to the Disease Severity Score in Turkish Children with Familial Mediterranean Fever?

    PubMed

    Özer, Samet; Yilmaz, Resul; Sonmezgoz, Ergün; Ünuvar, Şeyma; Ates, Ömer

    2016-12-01

    Familial Mediterranean fever (FMF) is an autosomal recessively inherited disease characterized by recurrent self-limited attacks of fever accompanied by aseptic inflammation of serosal spaces, joints and skin, peritonitis, pleuritis, and arthritis. Clinical features differ according to genetics variants. The aim of this study was to identify relationship between IL-6 -174G/C gene polymorphisms and clinical features, disease severity score (DSS) and proteinuria in children diagnosed with FMF. In this study, 99 children who were followed-up in Gaziosmanpasa University Medical Faculty Department of Pediatrics and diagnosed with Familial Mediterranean fever according to Tel-Hashomer criteria were included. One hundred and fifty seven children who admitted to the hospital with any complain and found healthy included in control group. Genotyping was done for polymorphism in a promoter region of IL-6 gene (G/C at -174). The IL-6 -174G/C gene polymorphism and the clinical features of FMF, proteinuria, the DSS, and the healthy control group were investigated. Data for the clinical features were obtained retrospectively from the electronic records of patients. All of the genotyping of blood samples were done in Medical Genetic laboratory of Gaziosmanpasa University School of Medicine. The results revealed that the distribution of the genotypes and allele frequencies of the IL-6 -174G/C polymorphism were not significantly different between the FMF patients and the healthy controls. The IL-6 -174G/C polymorphisms did not affect proteinuria, the DSS, and the clinical features of FMF patients.

  2. LONG CHAIN FATTY ACID (LCFA) ABNORMALITIES IN HYPER IgD SYNDROME (HIDS) AND FAMILIAL MEDITERRANEAN FEVER (FMF): NEW INSIGHT INTO HERITABLE PERIODIC FEVERSa

    PubMed Central

    Simon, Anna; Drenth, Joost PH; Matern, Dietrich; Goetzman, Eric S.; Hager, Elizabeth J.; Gibson, K Michael

    2013-01-01

    Objective To examine essential fatty acids (EFAs) in hyper-IgD syndrome (HIDS) and Familial Mediterranean Fever (FMF). Methods EFAs were determined in sera derived from an archival, cross-sectional group of HIDS/FMF patients, stratified for presence and absence of fever. Control populations included healthy afebrile adults, and individuals with non-periodic fever (septic shock). EFAs were quantified using isotope dilution gas chromatography-mass spectrometry and data analyzed employing a Kruskal-Wallis non-parametric ANOVA with Dunn's post-hoc test. Results Sera samples derived from HIDS patients showed significantly decreased C20, C26, phytanic and pristanic acids during febrile crises that normalized in the afebrile state, and a significantly increased afebrile C22_ω46 level that normalized with fever. Samples derived from FMF patients revealed increased ω-oxidized LCFAs as compared to controls, and the trend was for these same species to be increased in comparison to febrile, but not afebrile, HIDS patients. Individuals with non-periodic fever demonstrated global decreases in C10–C24 fatty acids, both saturated and unsaturated, accompanied by an elevated triene/tetraene ratio. Conclusions Our results suggest that different mechanisms are active in hereditary periodic fever syndromes that appear unrelated to fever, including depletion of very long chain fatty acids (VLCFAs) in febrile HIDS patients and increased ω-oxidized LCFAs in patients with FMF. These findings underscore new roles for EFAs in the potential production of inflammatory species in patients with hereditary periodic fever. PMID:23375471

  3. Different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis.

    PubMed

    Akar, Servet; Solmaz, Dilek; Kasifoglu, Timucin; Bilge, Sule Yasar; Sari, Ismail; Gumus, Zeynep Zehra; Tunca, Mehmet

    2016-02-01

    The aim of this study was to evaluate whether there are clinical subgroups that may have different prognoses among FMF patients. The cumulative clinical features of a large group of FMF patients [1168 patients, 593 (50.8%) male, mean age 35.3 years (s.d. 12.4)] were studied. To analyse our data and identify groups of FMF patients with similar clinical characteristics, a two-step cluster analysis using log-likelihood distance measures was performed. For clustering the FMF patients, we evaluated the following variables: gender, current age, age at symptom onset, age at diagnosis, presence of major clinical features, variables related with therapy and family history for FMF, renal failure and carriage of M694V. Three distinct groups of FMF patients were identified. Cluster 1 was characterized by a high prevalence of arthritis, pleuritis, erysipelas-like erythema (ELE) and febrile myalgia. The dosage of colchicine and the frequency of amyloidosis were lower in cluster 1. Patients in cluster 2 had an earlier age of disease onset and diagnosis. M694V carriage and amyloidosis prevalence were the highest in cluster 2. This group of patients was using the highest dose of colchicine. Patients in cluster 3 had the lowest prevalence of arthritis, ELE and febrile myalgia. The frequencies of M694V carriage and amyloidosis were lower in cluster 3 than the overall FMF patients. Non-response to colchicine was also slightly lower in cluster 3. Patients with FMF can be clustered into distinct patterns of clinical and genetic manifestations and these patterns may have different prognostic significance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Effect of Helicobacter pylori infection and eradication therapy on interleukin-6 levels in patients with Familial Mediterranean Fever.

    PubMed

    Ozel, A M; Demirturk, L; Aydogdu, A; Gultepe, M; Yazgan, Y; Imirzalioglu, N; Gurbuz, A K; Narin, Y

    2008-05-01

    It is being questioned if Helicobacter pylori infection, which causes a chronic inflammatory response, can increase the frequency and severity of attacks in patients with Familial Mediterranean Fever (FMF) and if the impact of inflammatory response can be diminished by eradication of the infection. To evaluate if there is difference in interleukin (IL)-6 levels of H. pylori-positive and -negative patients both before and during FMF attacks; if there is a change in IL-6 levels following successful eradication treatment; and if MEFV gene mutations have an effect on IL-6 levels. IL-6 levels were evaluated in 47 FMF patients before and during FMF attacks. Genetic testing to determine M694V, M694I, E148Q, V726V, M680I mutations was also performed in all patients. IL-6 levels were also determined after successful eradication of the infection in H. pylori-positive patients. IL-6 levels were compared in H. pylori-positive and -negative patients, and before and after eradication treatment in patients who cleared the infection. Number of patients in tested mutation groups was not enough to compare IL-6 levels in these groups. Thirty-four patients (73.9%) were H. pylori-positive. Before FMF attack there was no statistically significant difference in IL-6 levels of H. pylori-positive and -negative groups. IL-6 levels were significantly higher in both groups during the attacks than before the attacks (p < 0.05). There was a statistically significant decline in IL-6 levels both before and during FMF attacks, following eradication therapy in patients who cleared the infection (p < 0.05). In patients with homozygous M694V mutation, IL-6 levels before and during the FMF attacks were not significantly different in H. pylori-positive and -negative groups, despite a much lower level found in H. pylori-negative group (p > 0.05). Comparisons were not performed in other mutation groups because of small number of patients in each group. C-reactive protein (CRP) and fibrinogen levels were

  5. Anakinra for Colchicine-Resistant Familial Mediterranean Fever: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Ben-Zvi, Ilan; Kukuy, Olga; Giat, Eitan; Pras, Elon; Feld, Olga; Kivity, Shaye; Perski, Oleg; Bornstein, Gil; Grossman, Chagai; Harari, Gil; Lidar, Merav; Livneh, Avi

    2017-04-01

    Familial Mediterranean fever (FMF) is refractory to colchicine prophylaxis in 10-20% of patients. In a number of patient series, treatment with anakinra, an interleukin-1-blocking agent, prevented FMF attacks in those with colchicine-resistant FMF. This study was undertaken to evaluate the efficacy and safety of anakinra in the treatment of colchicine-resistant FMF, using a randomized controlled trial. Patients with colchicine-resistant FMF receiving colchicine (dosage ≥1.5 to ≤3 mg/day) were recruited and randomly assigned to receive anakinra or placebo (vehicle). The treatment duration was 4 months. Primary efficacy outcomes were the number of attacks per month, and the number of patients with a mean of <1 attack per month. Quality of life was assessed using a 0-10-grade visual analog scale (VAS), and safety was assessed according to the number and severity of adverse events. Twenty-five patients with colchicine-resistant FMF (14 women) were enrolled, of whom 12 were randomized to receive anakinra and 13 to receive placebo. The mean ± SD number of attacks per patient per month was 1.7 ± 1.7 in those receiving anakinra and 3.5 ± 1.9 in those receiving placebo (P = 0.037). Six patients in the anakinra group, compared to none in the placebo group, had <1 attack per month (P = 0.005). A beneficial effect of anakinra was noted in the number of attacks in the joints per month in patients receiving anakinra (mean ± SD 0.8 ± 1.6 versus 2.1 ± 1.1 in the placebo group; P = 0.019) and in quality of life (mean ± SD VAS score 7.7 ± 2.3 in the anakinra group versus 4.2 ± 2.9 in the placebo group; P = 0.045). The number of adverse events per patient per month was comparable between the anakinra group and the placebo group (mean ± SD 2.03 ± 1.75 versus 3.34 ± 2.5; P = 0.22). There were no severe adverse events. In this randomized controlled trial, anakinra appears to be an effective and safe

  6. The detailed assessment of left and right ventricular functions by tissue Doppler imaging in patients with familial Mediterranean fever.

    PubMed

    Tavil, Yusuf; Ureten, Kemal; Oztürk, Mehmet Akif; Sen, Nihat; Kaya, Mehmet Güngör; Cemri, Mustafa; Cengel, Atiye

    2008-02-01

    In the contrary to other rheumatologic disorders, there have been limited numbers of studies investigating the cardiac involvement in patients with familial Mediterranean fever (FMF), although the disease may carry a potential for cardiovascular disorders because of sustained inflammation during its course. In the present study, we used high usefulness tissue Doppler echocardiography for detailed analysis of cardiac changes in FMF patients. The study population included 30 patients with FMF (11 men, 19 women; mean age, 35 +/- 7 years, mean disease duration, 15.4 +/- 7.6 years) and 30 healthy subjects as controls (12 men, 18 women; mean age, 33 +/- 7 years). The diagnosis of FMF was established according to the Tell-Hashomer criteria. Left and right ventricular functions were measured using echocardiography comprising standard two-dimensional, M-mode, and conventional Doppler as well as tissue Doppler imaging. The conventional echocardiographic paratemeters were similar apart from left ventricular relaxation time was longer (107 +/- 25 vs 85 +/- 10 ms, p < 0.001, respectively) in patients with FMF. According to the tissue Doppler measurements, while systolic velocities of both ventricles were not different, diastolic filling velocities of left ventricle including E'(m) (12.6 +/- 3.4 vs 14.7 +/- 3.3 cm/s, p = 0.04), A'(m) (10.1 +/- 2.6 vs 8.6 +/- 2.0 cm/s, p = 0.015), and E'(m)/ A'(m) (1.24 +/- 0.4 vs 1.71 +/- 0.5 cm/s, p = 0.012) values were statistically different between the groups. Left ventricular myocardial performance indices and right ventricular diastolic functions were found similar between two groups. In addition, there were no significant correlations between the disease duration, clinical features, and echocardiographic parameters. In conclusion, we have demonstrated that although systolic functions were comparable in the patients and controls, left ventricular diastolic function indices were impaired in FMF patients by using tissue Doppler analysis.

  7. P Wave Dispersion and QT Dispersion in Adult Turkish Migrants with Familial Mediterranean Fever Living in Germany

    PubMed Central

    Giese, Arnd; Örnek, Ahmet; Kurucay, Mustafa; Kara, Kaffer; Wittkowski, Helmut; Gohar, Faekah; Menge, Bjoern A.; Schmidt, Wolfgang E.; Zeidler, Christoph

    2014-01-01

    Background: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease associated with subclinical inflammation, which includes atherosclerosis arising from endothelial inflammation, which in turn increases the risk of atrial or ventricular arrhythmias. Conduction abnormalities can be detected using the electrocardiographic (ECG) indices P and QT dispersion (Pdisp and QTdisp). Currently, it is unknown whether patients with FMF are more likely to have abnormalities of these ECG indices. Moreover, existing studies were conducted in countries with higher FMF prevalence. We therefore perform the first prospective study assessing Pdisp and QTdisp in adult FMF patients in Germany, where prevalence of FMF is low. Method: Asymptomatic FMF patients (n=30) of Turkish ancestry living in Germany and age-matched healthy controls (n=37) were prospectively assessed using 12-lead ECG. Results: Patients and controls were comparable in gender and body mass index, and patients had higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum amyloid A (SAA) compared to controls (ESR: 23.7±14.3 vs. 16.1±13,3 mm/1sth, p=0.03, CRP: 0.73±0.9 vs. 0.26±0.4 g/dl, p=0.01, SAA: 3.14±4,8 vs. 0.37±0.3 mg/dl, p<0.01). No statistically significant difference between patients and controls respectively, for Pdisp (43.7±11.9 vs. 47.1±11.2ms, p=0.23), QTdisp (65.9±12.3 vs. 67.6±12.7 ms, p=0.58) or corrected QTdisp (cQTdisp: 73.9±15.0 vs. 76.0±13.3 ms, p=0.55) was found. No correlation could be found between Pdisp or QTdisp or cQTdisp and any of the biochemical markers of inflammation. Conclusion: FMF patients living in Germany show a Pdisp and QTdisp comparable to healthy controls, with no increased risk of atrial or ventricular arrhythmias indicated. PMID:25170297

  8. P wave dispersion and QT dispersion in adult Turkish migrants with familial mediterranean fever living in Germany.

    PubMed

    Giese, Arnd; Ornek, Ahmet; Kurucay, Mustafa; Kara, Kaffer; Wittkowski, Helmut; Gohar, Faekah; Menge, Bjoern A; Schmidt, Wolfgang E; Zeidler, Christoph

    2014-01-01

    Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease associated with subclinical inflammation, which includes atherosclerosis arising from endothelial inflammation, which in turn increases the risk of atrial or ventricular arrhythmias. Conduction abnormalities can be detected using the electrocardiographic (ECG) indices P and QT dispersion (Pdisp and QTdisp). Currently, it is unknown whether patients with FMF are more likely to have abnormalities of these ECG indices. Moreover, existing studies were conducted in countries with higher FMF prevalence. We therefore perform the first prospective study assessing Pdisp and QTdisp in adult FMF patients in Germany, where prevalence of FMF is low. Asymptomatic FMF patients (n=30) of Turkish ancestry living in Germany and age-matched healthy controls (n=37) were prospectively assessed using 12-lead ECG. Patients and controls were comparable in gender and body mass index, and patients had higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum amyloid A (SAA) compared to controls (ESR: 23.7±14.3 vs. 16.1±13,3 mm/1(st)h, p=0.03, CRP: 0.73±0.9 vs. 0.26±0.4 g/dl, p=0.01, SAA: 3.14±4,8 vs. 0.37±0.3 mg/dl, p<0.01). No statistically significant difference between patients and controls respectively, for Pdisp (43.7±11.9 vs. 47.1±11.2ms, p=0.23), QTdisp (65.9±12.3 vs. 67.6±12.7 ms, p=0.58) or corrected QTdisp (cQTdisp: 73.9±15.0 vs. 76.0±13.3 ms, p=0.55) was found. No correlation could be found between Pdisp or QTdisp or cQTdisp and any of the biochemical markers of inflammation. FMF patients living in Germany show a Pdisp and QTdisp comparable to healthy controls, with no increased risk of atrial or ventricular arrhythmias indicated.

  9. Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey.

    PubMed

    Canpolat, Mehmet; Gumus, Hakan; Gunduz, Zubeyde; Dusunsel, Ruhan; Kumandas, Sefer; Bayram, Ayşe Kaçar; Yel, Sibel; Poyrazoglu, Hatice Gamze; Yilmaz, Kenan; Doganay, Selim; Yikilmaz, Ali; Dundar, Munis; Per, Huseyin

    2017-04-01

    Background Familial Mediterranean fever (FMF) is an inherited inflammatory disorder characterized by attacks of fever with polyserositis. Objective The purpose of this study was to evaluate pediatric patients with FMF who had central nervous system (CNS) findings. Materials and Methods Our medical records database for 2003 to 2014 was screened retrospectively. In total, 104 patients with FMF were identified, 22 of whom had undergone neurological examination for CNS symptoms. Results Neurological findings included headache in 16 patients (72.7%), epilepsy in 6 patients (27.3%), pseudotumor cerebri in 2 patients (9.1%), multiple sclerosis in 1 patient (4.5%), and tremor in 1 patient (4.5%). The most common MEFV gene mutation was homozygous M694V (40.9%). Conclusions Patients with FMF can present with various CNS manifestations. Further studies that include large populations are needed to elucidate the neurological manifestations of FMF. Georg Thieme Verlag KG Stuttgart · New York.

  10. Familial Mediterranean fever

    MedlinePlus

    ... GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR, eds. Kelly's Textbook of Rheumatology . 9th ed. ... this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial ...

  11. The spectrum of Familial Mediterranean Fever gene (MEFV) mutations and genotypes in Iran, and report of a novel missense variant (R204H).

    PubMed

    Ebadi, Nader; Shakoori, Abbas; Razipour, Masoumeh; Salmaninejad, Arash; Yeganeh, Razieh Zarifian; Mehrabi, Saman; RezaRaees Karami, Seyed; Khaleghian, Malihea; Azhideh, Hamidreza

    2017-09-21

    Familial Mediterranean Fever (FMF) is an autosomal recessive disorder, characterized by recurrent and self-limited episodes of fever, abdominal pain, synovitis and pleuritis. FMF as the most common inherited monogenic autoinflammatory disease mainly affects ethnic groups of the Mediterranean basin, Arab, Jewish, Turkish, Armenian North Africans and Arabic descent. In the present study, we selected 390 unrelated FMF patients according to the Tel-Hashomer criteria, and analyzed all patients for 12 most common mutations of MEFV gene by reverse hybridization assay (FMF strip assay). We also investigated exon 2 and 10 of MEFV gene in 78 patients by Sanger sequencing. According to strip assay results, at least one mutation was found in 234 patients (60%), and no mutation was found in other 156 patients (40%). The five most common mutations and allelic frequencies were M694V (13.6%), E148Q (10.4%), M694I (6.5%), V726A (4.1%), and M680I (3.8%). Moreover, we detected a novel missense variant (R204H, c.611 G > A) (SCV000297822) and following rare mutations among sequenced samples; R202Q, P115T, G304R, and E230K. This study describes the MEFV mutations spectrum and distribution in Iranian population, and shows different mutation patterns among Iranian ethnicities. Moreover, M694V is the most common MEFV mutation in Iran. Copyright © 2017. Published by Elsevier Masson SAS.

  12. A very frequent mutation and remarkable association of R761H with M694V mutations in Turkish familial Mediterranean fever patients.

    PubMed

    Demirkaya, Erkan; Tunca, Yusuf; Gok, Faysal; Ozen, Seza; Gul, Davut

    2008-06-01

    Familial Mediterranean fever (FMF) is an autosomal-recessive disease. It is characterized by recurring fever, abdominal pain, and serositis. The Mediterranean fever (MEFV) gene is localized on 16p13.3 and more than 35 mutations have been described to date. There are some differences in the gene mutations of FMF in the various ethnic groups. The aim of this study is to determine the frequency of the mutations which has been reported comparatively rare, to define the most effective mutation set, and to select the most suitable DNA analysis system for Turkish FMF patients. Mutations in 330 Turkish FMF patients with typical phenotypes from various regions of Turkey were evaluated for the research purposes. These patients were analyzed for six MEFV gene mutations by the NanoChip Molecular Genetics Workstation. The most frequent mutation was M694V, identified in 50.00% of the alleles examined; M680I followed with 14.10% and V726A--9.70%. Consequently, we determined that R761H (n = 23; 3.48%) was the most frequent rare mutations in Turkish FMF patients. Frequency of the rare mutations were R761H (3.48%), E148Q (1.36%), and M694I (1.21%). All of these mutations were in the compound heterozygote state. Our study showed that R761H mutations were higher than it has been reported in literature until now and were mainly associated with M694V. We suggest that mutation R761H should be included in the mutation scanning analysis researches or considered if the patient has M694V/? mutation especially in Turkish FMF patients. Larger serial studies need to be done to investigate the rate and coexistence of these mutations.

  13. Successful treatment with humanized anti-interleukin-6 receptor antibody (tocilizumab) in a case of AA amyloidosis complicated by familial Mediterranean fever.

    PubMed

    Hamanoue, Satoshi; Suwabe, Tatsuya; Hoshino, Junichi; Sumida, Keiichi; Mise, Koki; Hayami, Noriko; Sawa, Naoki; Takaichi, Kenmei; Fujii, Takeshi; Ohashi, Kenichi; Yazaki, Masahide; Ikeda, Shuichi; Ubara, Yoshifumi

    2016-07-01

    Familial Mediterranean fever (FMF) is a well-known cause of secondary AA amyloidosis. Colchicine is generally considered to be the most effective treatment for FMF and FMF-associated amyloidosis, but the management of patients who are refractory to colchicine remains controversial. We encountered a 51-year-old Japanese man with suspected FMF, who had periodic fever with abdominal pain, polyarthritis, and nephropathy (serum creatinine of 1.9 mg/dL and 24-h protein excretion of 3.8 g). FMF was diagnosed by mutation analysis of the Mediterranean fever (MEFV) gene, which revealed that the patient was compound heterozygous for the marenostrin/pyrin variant E148Q/M694I. AA amyloidosis was diagnosed by renal and gastric biopsy. Colchicine was administered, but his arthritis persisted, and serum creatinine increased to 2.4 mg/dL. Therefore, a humanized anti-interleukin-6 receptor antibody (tocilizumab) was administered at a dose of 8 mg/kg on a monthly basis. Both arthritis and abdominal pain subsided rapidly, and C-reactive protein (CRP) decreased from 2.5 to 0.0 mg/dL. After 2 years, his serum creatinine was decreased to 1.5 mg/dL and proteinuria was improved to 0.3 g daily. In addition, repeat gastric biopsy showed a marked decrease of AA amyloidosis. This case suggests that tocilizumab could be a new therapeutic option for patients with FMF-associated AA amyloidosis if colchicine is not effective.

  14. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome.

    PubMed

    Ktsoyan, Zhanna A; Beloborodova, Natalia V; Sedrakyan, Anahit M; Osipov, George A; Khachatryan, Zaruhi A; Manukyan, Gayane P; Arakelova, Karine A; Hovhannisyan, Alvard I; Arakelyan, Arsen A; Ghazaryan, Karine A; Zakaryan, Magdalina K; Aminov, Rustam I

    2013-01-01

    In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

  15. Lactobacillus acidophilus INMIA 9602 Er-2 strain 317/402 probiotic regulates growth of commensal Escherichia coli in gut microbiota of familial Mediterranean fever disease subjects.

    PubMed

    Pepoyan, A Z; Balayan, M H; Manvelyan, A M; Mamikonyan, V; Isajanyan, M; Tsaturyan, V V; Kamiya, S; Netrebov, V; Chikindas, M L

    2017-04-01

    Previously, we reported a positive effect the probiotic formulation, Lactobacillus acidophilus INMIA 9602 Er-2 strain 317/402 (Narine strain), had on the blood characteristics of patients with familial Mediterranean fever disease (FMF). The aim of this investigation was to evaluate the effect of the Narine probiotic on growth characteristics in the predominant commensal Escherichia coli isolates from the gut microbiota in FMF-positive study participants. Bacterial growth of 192 prevalent commensal E. coli isolates found in the volunteer participants' guts was evaluated using Verhulst's logistic function. This study showed that the duration of the preparatory growth phase for the E. coli isolates collected from FMF-positive volunteers was significantly shorter, whereas the duration of the logarithmic growth phase was significantly longer (P < 0·03) than that of the isolates collected from healthy participants. The Narine probiotic formulation caused a significant extension (P < 0·001) of the preparatory growth phase in the commensal E. coli isolated from FMF subjects a month after the Narine probiotic administration was terminated. The data suggest that the mathematical model characterizes the growth of commensal E. coli isolates from FMF-positive participants and it can be useful in a decision-making process on the practical use of probiotics during FMF. This is the first study to demonstrate the effects of Narine, containing the probiotic Lactobacillus acidophilus, on the growth of gut commensal Escherichia coli from study participants with familial Mediterranean fever disease (FMF). Verhulst's logistic function was demonstrated to act as a possible tool for the evaluation and quantification of effects produced by the probiotic formulation in FMF participants. © 2017 The Society for Applied Microbiology.

  16. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease

    PubMed Central

    Kirino, Yohei; Zhou, Qing; Ishigatsubo, Yoshiaki; Mizuki, Nobuhisa; Tugal-Tutkun, Ilknur; Seyahi, Emire; Özyazgan, Yilmaz; Ugurlu, Serdal; Erer, Burak; Abaci, Neslihan; Ustek, Duran; Meguro, Akira; Ueda, Atsuhisa; Takeno, Mitsuhiro; Inoko, Hidetoshi; Ombrello, Michael J.; Satorius, Colleen L.; Maskeri, Baishali; Mullikin, James C.; Sun, Hong-Wei; Gutierrez-Cruz, Gustavo; Kim, Yoonhee; Wilson, Alexander F.; Kastner, Daniel L.; Gül, Ahmet; Remmers, Elaine F.

    2013-01-01

    Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 × 10−5), and one gene involved in innate immunity, TLR4 (P = 8.0 × 10−4), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063–0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 × 10−12). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis. PMID:23633568

  17. International Retrospective Chart Review of Treatment Patterns in Severe Familial Mediterranean Fever, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome, and Mevalonate Kinase Deficiency/Hyperimmunoglobulinemia D Syndrome.

    PubMed

    Ozen, Seza; Kuemmerle-Deschner, Jasmin B; Cimaz, Rolando; Livneh, Avi; Quartier, Pierre; Kone-Paut, Isabelle; Zeft, Andrew; Spalding, Steve; Gul, Ahmet; Hentgen, Veronique; Savic, Sinisa; Foeldvari, Ivan; Frenkel, Joost; Cantarini, Luca; Patel, Dony; Weiss, Jeffrey; Marinsek, Nina; Degun, Ravi; Lomax, Kathleen G; Lachmann, Helen J

    2017-04-01

    Periodic fever syndrome (PFS) conditions are characterized by recurrent attacks of fever and localized inflammation. This study examined the diagnostic pathway and treatments at tertiary centers for familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD)/hyperimmunoglobulinemia D syndrome (HIDS). PFS specialists at medical centers in the US, the European Union, and the eastern Mediterranean participated in a retrospective chart review, providing de-identified data in an electronic case report form. Patients were treated between 2008 and 2012, with at least 1 year of followup; all had clinical and/or genetically proven disease and were on/eligible for biologic treatment. A total of 134 patients were analyzed: FMF (n = 49), TRAPS (n = 47), and MKD/HIDS (n = 38). Fever was commonly reported as severe across all indications. Other frequently reported severe symptoms were serositis for FMF patients and elevated acute-phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 and 7.1 years, respectively) compared to a 1.8-year delay in FMF patients. An equal proportion of TRAPS patients first received anti-interleukin-1 (anti-IL-1) and anti-tumor necrosis factor (anti-TNF) biologic agents, whereas IL-1 blockade was the main choice for FMF patients resistant to colchicine and MKD/HIDS patients. For TRAPS patients, treatment with anakinra versus anti-TNF treatments as first biologic agent resulted in significantly higher clinical and biochemical responses (P = 0.03 and P < 0.01, respectively). No significant differences in responses were observed between biologic agents among other cohorts. Referral patterns and diagnostic delays highlight the need for greater awareness and improved diagnostics for PFS. This real-world treatment assessment supports the need for further

  18. A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups.

    PubMed

    Balow, J E; Shelton, D A; Orsborn, A; Mangelsdorf, M; Aksentijevich, I; Blake, T; Sood, R; Gardner, D; Liu, R; Pras, E; Levy, E N; Centola, M; Deng, Z; Zaks, N; Wood, G; Chen, X; Richards, N; Shohat, M; Livneh, A; Pras, M; Doggett, N A; Collins, F S; Liu, P P; Rotter, J I; Kastner, D L

    1997-09-15

    Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3. We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the approximately 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (approximately 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that some of these mutations arose before the affected Middle Eastern populations diverged from one another.

  19. The expanded clinical profile and the efficacy of colchicine therapy in Egyptian children suffering from familial Mediterranean fever: a descriptive study.

    PubMed

    Talaat, Hala Salah El-Din; Mohamed, Mohamed Farouk; El Rifai, Nihal Mohamed; Gomaa, Mohamed Ali

    2012-12-04

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limiting recurrent attacks of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. To detect variable clinical presentations and genotypic distribution of different groups of FMF patients and the efficacy of colchicine therapy in treatment of these groups of FMF after one year. A cross-sectional study was conducted on 70 patients already diagnosed with FMF and following-up at the Rheumatology Clinic, Children's Hospital - Cairo University. Diagnosis of FMF was determined according to Tel Hashomer criteria for FMF. All patients were subjected to a questionnaire including detailed history with emphasis on clinical manifestations and colchicine dose to control attacks. Mutational analysis was performed for all study subjects covering 12 mutations in the MEFV gene: E148Q, P369S, F479L, M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, A744S and R761H. Response to colchicine treatment was evaluated as complete, incomplete and unresponsive. Out of the 70 patients- 40 males and 30 females- fever was the most common presenting feature, followed by abdominal pain, and arthritis; documented in 95.7%, 94.3%, and 77.1% of cases respectively. Mutational analysis detected gene mutation on both alleles in 20 patients (homozygotes), on only 1 allele in 40 patients (heterozygotes), and on none of the alleles (uncharacterized cases). Mild to moderate disease severity score (according to Tel Hashomer key to severity score) was detected in a significant proportion of heterozygotes and the uncharacterized group than the homozygotes. All patients received colchicine therapy; 22.9% of them showed complete response, 74.3% showed incomplete response and 2.9% showed no response to therapy. The colchicine dose needed to control attacks was significantly lower in heterozygotes than the homozygotes(P=0.04). Also patients' response to colchicine therapy was

  20. High prevalence of spondyloarthritis and ankylosing spondylitis among familial Mediterranean fever patients and their first-degree relatives: further evidence for the connection

    PubMed Central

    2013-01-01

    Introduction Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by recurrent attacks of fever and serositis. Limited data suggest that the prevalence of sacroiliitis is increased in patients with FMF. In our present study, we assessed the prevalence of spondyloarthritis (SpA), including ankylosing spondylitis (AS), among a cohort of FMF patients and their unaffected first-degree relatives (FDRs). Methods The current study cohort comprised a consecutive group of 201 unrelated patients with FMF and 319 FDRs (≥ 16 years old). These subjects were examined according to a standard protocol. Results A total of 157 FMF patients (78.1%) and 233 (73%) unaffected FDRs reported back pain. Fifteen FMF patients (7.5%) and nine unaffected FDRs fulfilled the modified New York (mNY) criteria for AS. One additional FDR with AS was identified after review of the medical records. None of the FMF patients with AS was HLA-B27 positive. The allele frequency of M694V among the FMF patients with radiographic sacroiliitis was significantly higher in comparison with those without sacroiliitis (OR 4.3). When compared with the general population, the risk ratios for SpA and AS among the FDRs of our FMF patients were 3.3 (95% CI; 2.0 to 5.5) and for AS 2.9 (95% CI; 1.3 to 6.4), respectively. Conclusions Our study suggests that a) factors other than HLA-B27 play a role in the association of FMF and SpA/AS; b) MEFV gene variations may be one of the geographic/region-specific potential pathogenetic links between these two disorders in the Turkish population. PMID:23356447

  1. Evaluation of pathergy test positivity in familial Mediterranean fever patients and comparison of clinical manifestations of FMF with Behçet's disease.

    PubMed

    Aydin, Fatma; Akpolat, Tekin; Senturk, Nilgun; Bagci, Hasan; Yasar Turanli, Ahmet

    2009-11-01

    Familial Mediterranean fever (FMF) shares a number of features with Behçet's disease (BD), such as their common ethnic origin, etiopathogenetic mechanisms, symptoms, and treatment. Pathergy reaction is accepted as a major criterion in BD. We aimed to determine the frequency of pathergy positivity in FMF patients and compared clinical features between FMF and BD. Pathergy test was performed in patients with FMF, BD, and healthy controls. Diagnostic criteria for FMF and BD were screened in both groups. None of the FMF patients or healthy controls yielded positive pathergy test. Pathergy test was positive in 13 out of 31 (41.9%) of the patients with BD. None of the FMF patients fulfilled the International Study Group criteria for BD. None of the BD patients fulfilled the Livneh diagnostic criteria for FMF. BD and FMF are associated with neutrophilic dermatoses and neutrophil hyper-reactivity. Although pathergy test and erysipelas-like erythema share some histological findings, pathergy test was negative among FMF patients.

  2. Levels of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) in familial Mediterranean fever (FMF) patients and their first degree relatives.

    PubMed

    Oktem, S; Yavuzsen, T U; Sengül, B; Akhunlar, H; Akar, S; Tunca, M

    2004-01-01

    Familial Mediterranean Fever (FMF) is a hereditary disease characterized by recurrent inflammatory attacks. A subclinical inflammation may persist in periods between the attacks and heterozygotes may have higher than normal levels of acute phase proteins. We investigated the levels of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) in FMF patients and their obligatory carrier relatives. Serum levels of IL-6 and sIL-6R were measured during acute attacks (n = 18) and in attack-free FMF patients (n = 26), obligatory carriers of FMF (n = 17) and normal controls (n = 11). The median levels of IL-6 were significantly higher (45.71 pg/ mL, p = 0.001) during acute attacks of FMF only, and were normal (0.01 pg/ mL) in the other groups studied. There was no statistically significant difference in the median sIL-6R values between any of the groups (p = 0.22). IL-6 was extremely elevated during FMF attacks but could not detect hypothetical "subclinical" inflammation during attack-free intervals or in the heterozygote relatives of patients. Serum levels of sIL-6R were comparable in all four groups.

  3. Secondary amyloidosis in a patient carrying mutations in the familial Mediterranean fever (FMF) and tumour necrosis factor receptor-1 syndrome (TRAPS) genes.

    PubMed

    Clementi, Anna; Cruz, Dinna N; Granata, Antonio; Virzì, Grazia Maria; Battaglia, Giorgio

    2013-12-01

    Secondary amyloidosis (AA) is characterized by the extracellular tissue deposition of fibrils composed of fragments of an acute-phase reactant protein, serum amyloid A (SAA), due to chronic inflammatory diseases, infections and several neoplasms. AA amyloidosis may also complicate several hereditary diseases, where genetic factors play a pivotal role in the expression of amyloidosis. Familial Mediterranean fever (FMF) and tumour necrosis factor receptor-1 syndrome (TRAPS) are the most frequently involved. We describe a case of a 21-year-old Romanian woman who presented at the 35th week of gestation with acute abdominal pain, nausea and vomiting. The laboratory workup performed after delivery showed proteinuria in the nephrotic range and increased SAA protein. Kidney amyloid deposits were detected and genetic testing for secondary amyloidosis was performed identifying two mutations, one involving the gene of FMF (MEFV), and the other involving the tumour necrosis factor receptor-1 gene (TNFRSF1A). To our knowledge, this is the first case in the literature where secondary amyloidosis develops in a patient carrying mutations involving the genes of both FMF and TRAPS.

  4. Increased asymmetric dimethylarginine levels in young men with familial Mediterranean fever (FMF): is it early evidence of interaction between inflammation and endothelial dysfunction in FMF?

    PubMed

    Terekeci, Hakan M; Oktenli, Cagatay; Ozgurtas, Taner; Nalbant, Selim; Top, Cihan; Celik, Serkan; Tapan, Serkan; Kucukardali, Yasar; Sanisoglu, Yavuz S; Solmazgul, Emrullah; Sahan, Burak; Sayan, Ozkan

    2008-10-01

    Unlike in many other chronic inflammatory rheumatic diseases, studies investigating endothelial dysfunction and atherosclerosis in familial Mediterranean fever (FMF) are limited, and the results are controversial. Asymmetric dimethylarginine (ADMA) is considered an indicator for endothelial dysfunction and a sensitive marker for cardiovascular risk. There have been no reports on serum ADMA levels in patients with FMF. We aimed (1) to determine serum ADMA concentrations in 38 young male patients with FMF and 23 age- and body mass index-matched healthy volunteers; (2) to evaluate its correlations with MEFV mutations, C-reactive protein (CRP) levels, and lipid profile; and (3) to compare effects of colchicine on circulating ADMA concentrations. In patients with FMF, ADMA and CRP levels were higher than in healthy controls. The mean levels of ADMA and CRP were higher during acute attacks than in attack-free periods. Patients taking colchicine had lower serum ADMA levels than non-colchicine users. There was a positive strong correlation between ADMA and CRP in patients with FMF. Stepwise linear regression analysis in patients with FMF revealed that age and CRP levels were independently associated with serum ADMA levels. Our data imply that higher serum ADMA levels in FMF may indicate inflammation-related "endothelial dysfunction." It seems likely that regular use of colchicine is effective in preventing the development of and reversing not only amyloidosis but also endothelial dysfunction in patients with FMF.

  5. Construction of an ∼700-kb Transcript Map Around the Familial Mediterranean Fever Locus on Human Chromosome 16p13.3

    PubMed Central

    Centola, Michael; Chen, Xiaoguang; Sood, Raman; Deng, Zuoming; Aksentijevich, Ivona; Blake, Trevor; Ricke, Darrell O.; Chen, Xiang; Wood, Geryl; Zaks, Nurit; Richards, Neil; Krizman, David; Mansfield, Elizabeth; Apostolou, Sinoula; Liu, Jingmei; Shafran, Neta; Vedula, Anil; Hamon, Melanie; Cercek, Andrea; Kahan, Tanaz; Gumucio, Deborah; Callen, David F.; Richards, Robert I.; Moyzis, Robert K.; Doggett, Norman A.; Collins, Francis S.; Liu, P. Paul; Fischel-Ghodsian, Nathan; Kastner, Daniel L.

    1998-01-01

    We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequilibrium with FMF, was sequenced to completion, and the sequence annotated. A transcript map reflecting the minimal number of genes encoded within the ∼700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detectable on Northerns, in addition to three olfactory-receptor genes, a cluster of 18 tRNA genes, and two putative transcriptional units that have typical intron–exon splice junctions yet do not detect messages on Northerns. Four of the transcripts are identical to genes described previously, seven have been independently identified by the French FMF Consortium, and the others are novel. Six related zinc-finger genes, a cluster of tRNAs, and three olfactory receptors account for the majority of transcribed sequences isolated from a 315-kb FMF central region (between D16S468/D16S3070 and cosmid 377A12). Interspersed among them are several genes that may be important in inflammation. This transcript map not only has permitted the identification of the FMF gene (MEFV), but also has provided us an opportunity to probe the structural and functional features of this region of chromosome 16. PMID:9847080

  6. Relationship between genetic mutation variations and acute-phase reactants in the attack-free period of children diagnosed with familial Mediterranean fever

    PubMed Central

    Kosan, C.; Cayir, A.; Turan, M.I.

    2013-01-01

    Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease characterized by chronic inflammation. This study investigated the relationship between acute-phase reactants and gene mutations in attack-free periods of childhood FMF. Patients diagnosed with FMF were divided into four groups based on genetic features: no mutation, homozygous, heterozygous, and compound heterozygous. These groups were monitored for 2 years, and blood samples were collected every 6 months during attack-free periods. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and white blood cell count were measured. A disease severity score was determined for each patient. Mean values for erythrocyte sedimentation rate and fibrinogen were significantly different in the homozygous group. White blood cell count and C-reactive protein were similar between the groups. Disease severity score was higher in patients with the M694V mutation than in individuals without the mutation, as well as in those with other mutation groups. Periodic follow-up of patients with FMF MEFV mutations in subjects with acute-phase reactants may be useful in the prevention of morbidity. PMID:24141617

  7. The Effect of Rilonacept versus Placebo on Health-Related Quality of Life in Patients with Poorly Controlled Familial Mediterranean Fever

    PubMed Central

    Hashkes, Philip J.; Spalding, Steven J.; Hajj-Ali, Rula; Giannini, Edward H.; Johnson, Anne; Barron, Karyl S.; Weisman, Michael H.; Pashinian, Noune; Reiff, Andreas O.; Samuels, Jonathan; Wright, Dowain; Lovell, Daniel J.; Huang, Bin

    2014-01-01

    Objective. To examine the effect of rilonacept on the health-related quality of life (HRQoL) in patients with poorly controlled familial Mediterranean fever (FMF). Methods. As part of a randomized, double-blinded trial comparing rilonacept and placebo for the treatment of FMF, patients/parents completed the modified Child Health Questionnaire (CHQ) at baseline, and at the start and end of each of 4 treatment courses, 2 each with rilonacept and placebo. Results. Fourteen subjects were randomized; mean age was 24.4 ± 11.8 years. At baseline the physical HRQoL score was significantly less (24.2 ± 49.5) but the psychosocial score was similar to the population norm (49.5 ± 10.0). There were significant improvements in most HRQoL concepts after rilonacept but not placebo. Significant differences between rilonacept and placebo were found in the physical (33.7 ± 16.4 versus 23.7 ± 14.5, P = 0.021) but not psychosocial scores (51.4 ± 10.3 versus 49.8 ± 12.4, P = 0.42). The physical HRQoL was significantly impacted by the treatment effect and patient global assessment. Conclusion. Treatment with rilonacept had a beneficial effect on the physical HRQoL in patients with poorly controlled FMF and was also significantly related to the patient global assessment. This trial is registered with ClinicalTrials.gov Identifier NCT00582907. PMID:25147819

  8. Clinical features and functional significance of the P369S/R408Q variant in pyrin, the familial Mediterranean fever protein

    PubMed Central

    Ryan, JG; Masters, SL; Booty, MG; Habal, N; Alexander, JD; Barham, BK; Remmers, EF; Barron, KS; Kastner, DL; Aksentijevich, I

    2013-01-01

    Objectives Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin’s B-box domain is necessary for interactions with PSTPIP1. We aimed to characterize the phenotype of patients with these substitutions and to determine their functional significance. Methods A database of genetic tests undertaken in our institution was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Co-immunoprecipation techniques were employed to determine the variants’ effects on pyrin/PSTPIP1 interactions. Results We identified 40 symptomatic and 4 asymptomatic family members with these substitutions. P369S and R408Q were found in cis, and co-segregated in all patients sequenced. Clinical details were available on 22 patients. Five patients had symptoms and signs fulfilling a clinical diagnosis of FMF. Fourteen received colchicine. In patients not reaching the criteria, trials of anti-TNF agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Co-immunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1. Conclusions P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modeling studies suggest that these substitutions do not significantly affect pyrin’s interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms. PMID:19934105

  9. The gene for familial Mediterranean fever in both Armenians and non-Ashkenzai Jews is linked to the [alpha]-globin complex on 16p: Evidence for locus homogeneity

    SciTech Connect

    Shohat, M.; Shohat, T.; Magal, N.; Danon, Y. ); Xiangdong Bu; Fischel-Ghodsian, N.; Schwabe, A.D.; Rotter, J.I. ); Nakamura, Yusuke ); Schlezinger, M. )

    1992-12-01

    Familial Mediterranean fever (FMF) is a recurrent inflammatory disorder characterized by short episodes of fever, peritonitis, pleuritis, and arthritis. While FMF has been shown to be inherited in an autosomal recessive fashion in both non-Ashkenazi Jews and Armenian families, clinical differences have raised the possibility of genetic heterogeneity. As its pathogenesis is unknown, mapping of the gene for FMF may provide the first objective method for early and accurate diagnosis of this disease. After excluding 45% of the entire human genome, the authors studied 14 Armenian and 9 non-Ashkenazi Jewish families with FMF and tested linkage with the [alpha]-globin locus on chromosome 16. Analysis of the PvuII length polymorphism of the 3[prime] HVR (hypervariable region) probe showed significant linkage with the FMF gene (maximum lod score [lod[sub max

  10. The expanded clinical profile and the efficacy of colchicine therapy in Egyptian children suffering from familial mediterranean fever: a descriptive study

    PubMed Central

    2012-01-01

    Background Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limiting recurrent attacks of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Objective To detect variable clinical presentations and genotypic distribution of different groups of FMF patients and the efficacy of colchicine therapy in treatment of these groups of FMF after one year. Methods A cross-sectional study was conducted on 70 patients already diagnosed with FMF and following-up at the Rheumatology Clinic, Children's Hospital - Cairo University. Diagnosis of FMF was determined according to Tel Hashomer criteria for FMF. All patients were subjected to a questionnaire including detailed history with emphasis on clinical manifestations and colchicine dose to control attacks. Mutational analysis was performed for all study subjects covering 12 mutations in the MEFV gene: E148Q, P369S, F479L, M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, A744S and R761H. Response to colchicine treatment was evaluated as complete, incomplete and unresponsive. Results Out of the 70 patients- 40 males and 30 females- fever was the most common presenting feature, followed by abdominal pain, and arthritis; documented in 95.7%, 94.3%, and 77.1% of cases respectively. Mutational analysis detected gene mutation on both alleles in 20 patients (homozygotes), on only 1 allele in 40 patients (heterozygotes), and on none of the alleles (uncharacterized cases). Mild to moderate disease severity score (according to Tel Hashomer key to severity score) was detected in a significant proportion of heterozygotes and the uncharacterized group than the homozygotes. All patients received colchicine therapy; 22.9% of them showed complete response, 74.3% showed incomplete response and 2.9% showed no response to therapy. The colchicine dose needed to control attacks was significantly lower in heterozygotes than the homozygotes(P=0.04). Also patients

  11. Apoptosis-associated speck-like protein containing a CARD (ASC) expression profiles in familial Mediterranean fever (FMF) patients with different MEFV mutation patterns.

    PubMed

    Nalbantoglu, S; Tanyolac, B; Berdeli, A

    2013-01-01

    The inflammasome complex and the inflammatory pathway have been implicated in the pathogenesis of the most common autoinflammatory disorder, familial Mediterranean fever (FMF). Pyrin, the protein product of the FMF gene MEFV, interacts with the inflammasome complex adaptor protein ASC/PYCARD (apoptosis-associated speck-like protein with a CARD). Pyrin and ASC can both function as either inducers or suppressors of the cellular inflammatory response. We aimed to characterize ASC-induced gene expression profiles in FMF patients with different MEFV mutation patterns. A total of 165 Caucasian patients with clinical and molecular FMF diagnoses were enrolled in the study. ASC gene expression was quantified by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). ASC mRNA expression was increased in the MEFV mutation-positive group compared to the mutation-negative group (p = 0.001). The fold changes of ASC expression in the M694V homozygous (p = 0.02), M694V heterozygous (p = 0.012), compound heterozygous (p = 0.002), and R202Q/P369S/R408Q (p = 0.00) groups relative to the MEFV mutation-negative group were +2.4, +2.7, +3, and +3.4, respectively. qRT-PCR did not reveal a significant difference in ASC mRNA expression levels among the MEFV mutation-positive groups (p > 0.05). ASC mRNA expression was up-regulated in patients carrying MEFV mutations independent of mutation type. There was no significant relationship between specific MEFV genotypes and the level of ASC expression in the patient group analysed. Thus, the findings of this work may suggest a crucial relationship between mutant MEFV/pyrin and remarkable ASC up-regulation in FMF inflammation.

  12. Study of the association of IL-1β and IL-1RA gene polymorphisms with occurrence and severity of Familial Mediterranean fever.

    PubMed

    Ibrahim, José-Noel; Chouery, Eliane; Lecron, Jean-Claude; Mégarbané, André; Medlej-Hashim, Myrna

    2015-12-01

    Familial Mediterranean fever (FMF) is a recessive autoinflammatory disorder. The balance between the pro-inflammatory cytokine IL-1β and its receptor antagonist IL-1RA plays an important role in the development of FMF. In order to determine a possible association of polymorphisms in IL-1β and IL-1RA genes with occurrence and/or severity of the disease, 42 genetically confirmed FMF patients and 42 controls were genotyped for IL-1β(-511C/T), IL-1β(-31T/C), IL1-1β(+3954T/C) and IL-1RA VNTR polymorphisms. IL-1β and IL-1RA levels were evaluated by multiplex ELISA in supernatants of PBMC cultures of 30 FMF patients with and without 24h stimulation of monocytes by LPS. The CC genotype and C allele at positions -31 and + 3954 of IL-1β gene were more frequent in FMF patients than in controls. FMF patients carriers of IL-1β(-31) CC genotype were associated with a 2-fold increase in LPS-induced IL-1β secretion as well as a higher disease severity score (11.2 ± 2.9) when compared to patients carrying the TC and TT genotypes (6.1 ± 2.1 and 4.5 ± 2.4, respectively). These results indicate that IL-1β gene polymorphisms at positions -31 and + 3954 may be associated with an increased risk for FMF. IL-1β(-31) contributes also to the severity of the disease, probably by modulating IL-1β synthesis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Effects of anti-tumor necrosis factor agents for familial mediterranean fever patients with chronic arthritis and/or sacroiliitis who were resistant to colchicine treatment.

    PubMed

    Bilgen, Sule Apras; Kilic, Levent; Akdogan, Ali; Kiraz, Sedat; Kalyoncu, Umut; Karadag, Omer; Ertenli, Ihsan; Dogan, Ismail; Calguneri, Meral

    2011-10-01

    Effectiveness of anti-tumor necrosis factor (anti-TNF) agents in colchicine-resistant familial Mediterranean fever (FMF) patients has attracted attention in recent years. We analyzed the effect of anti-TNF agents on clinical findings of colchicine-resistant FMF patients with chronic arthritis and/or sacroiliitis. Data from 10 FMF patients (5 male and 5 female patients: mean age, 30.1 [SD, 8.5] years) with chronic arthritis and/or sacroiliitis who were on anti-TNF agents are reviewed. Frequency of FMF attacks before and after treatment with anti-TNF agents was recorded from hospital files. The effects of the anti-TNF treatment were determined by using the number of tender and/or swollen joints, serum acute phase reactant levels, and Bath Ankylosing Spondylitis Disease Activity Index scores. Change in urine protein loss was also evaluated in patients with amyloidosis. In 6 patients, FMF attacks had been considered to be unresponsive to colchicine, and 4 patients were partial responders before treatment with anti-TNF agents. Mean attack frequency of the patients in the 3 months' period before anti-TNF agent treatment was 3.8 (SD, 3.1). After anti-TNF treatment, in 3 patients, FMF attack frequency decreased, and in the remaining 7 patients, no attack occurred. Serum acute phase reactant levels were decreased significantly at 3 and 6 months after anti-TNF treatment (P < 0.05 for all). After anti-TNF treatment Bath Ankylosing Spondylitis Disease Activity Index scores were also decreased significantly (6.2 [SD], 1.7 vs. 2.1 [SD], 1.7; P = 0.012). In all 3 patients with amyloidosis, urine protein loss decreased without any increase in serum creatinine levels. Anti-TNF treatment can have beneficial effects for controlling FMF attacks in FMF patients with chronic arthritis and/or sacroiliitis.

  14. Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever--a randomized controlled noninferiority trial.

    PubMed

    Polat, Adem; Acikel, Cengizhan; Sozeri, Betul; Dursun, Ismail; Kasapcopur, Ozgur; Gulez, Nesrin; Simsek, Dogan; Saldir, Mehmet; Dokurel, Ipek; Poyrazoglu, Hakan; Bakkaloglu, Sevcan; Delibas, Ali; Ekinci, Zelal; Ayaz, Nuray A; Kandur, Yasar; Peru, Harun; Kurt, Yasemin G; Polat, Safiye R; Unsal, Erbil; Makay, Balahan; Gok, Faysal; Ozen, Seza; Demirkaya, Erkan

    2016-04-07

    In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF). In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement. A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group. Using colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage. ClinicalTrials.gov identifier NCT02602028 . Registered 5 November 2015.

  15. The Relationship Among the Level of Serum Amyloid A, High-Density Lipoprotein and Microalbuminuria in Patients With Familial Mediterranean Fever.

    PubMed

    Uslu, Ali Ugur; Aydin, Bahattin; Icagasıoğlu, Ibrahim Serhat; Balta, Sevket; Deveci, Köksal; Alkan, Filiz; Yıldız, Gürsel; Sahin, Ali

    2016-11-01

    Serum amyloid A (SAA), which is produced in the liver, acts as an apoprotein of high-density lipoprotein (HDL) accumulation in extracellular matrix of tissues and organs. SAA elevations play a significant role in the development of amyloidosis. Microalbuminuria (MAU) is the early period of amyloidosis in patients with familial Mediterranean fever (FMF). We assessed the association between SAA as an important factor for the development of amyloidosis in patients with FMF and cytokines, HDL, and MAU. A total of 40 FMF patients diagnosed with Tel-Hashomer criteria and making regular follow-up visits at the tertiary referral center from 2012 to 2013 were included in this study, besides 40 age- and sex-matched individuals as controls. Compared with controls, FMF patients had higher SAA (25.20 ± 45.78 vs. 1.68 ± 0.63 ng/ml; P = 0.002). Also, FMF patients had higher MAU than controls (23.20 ± 39.86 vs. 9.40 ± 5.32 mg/day; P = 0.036). HDL was significantly lower in the patient group than in controls (39.35 ± 10.45 vs. 47.82 ± 15.31 mg/dl; P = 0.023). Interleukin-1 beta (IL-1), IL-6, and tumor necrosis factor alpha (TNF-α) levels were higher in the FMF group than in controls (P < 0.0001, P = 0.009, P = 0.003, respectively). Our results suggest that IL-1, IL-6, TNF-α, SAA, and HDL may serve as markers of subclinical inflammation in FMF patients. Due to increased plasma HDL levels, antiinflammatory and antioxidant effects may elevate in FMF patients. © 2016 Wiley Periodicals, Inc.

  16. What is the best acute phase reactant for familial Mediterranean fever follow-up and its role in the prediction of complications? A systematic review.

    PubMed

    Erer, Burak; Demirkaya, Erkan; Ozen, Seza; Kallinich, Tilmann

    2016-04-01

    The most dreaded complication of familial Mediterranean fever (FMF) is amyloidosis; controversy exists as to what acute phase reactant (APR) should be monitored in these patients. To analyze the best acute phase reactant for FMF follow-up to help guide physicians to decide on what APR parameter to use, we also attempted to define the best APR in predicting the complications of FMF, specifically the development of amyloidosis. Systematic review based on a sensitive search to capture studies that: (1) included FMF patients; (2) measured serum amyloid A (SAA), CRP (C-reactive protein), proteinuria, or ESR (erythrocyte sedimentation rate); (3) amyloidosis were the outcome measure; (4) sensitivity, specificity, predictive value, and other performance parameters could be calculated; and (5) had a longitudinal design. Of 1905 captured items, 26 were selected for detailed review, of which only two finally met the criteria, and the quality was only moderate; the articles did not analyzed the performance by means of sensitivity and specificity to predict, or even detect, amyloidosis, and thus had to be calculated based on text. The 26 screened studies were very heterogeneous in designs, parameters measured, and results, despite being set from research questions similar to ours. They were mainly descriptive, and it was very difficult to interpret the true performance of the tests. The correlation between the various APR is low. The evidence supporting the monitoring of FMF with any APR over the others is limited. Well designed longitudinal studies with a mixture of outcomes should be undertaken. Until them, recommending an APR over other would be based on expert opinion and indirect evidence.

  17. The M694I/M694I genotype: A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever.

    PubMed

    Ait-Idir, Djouher; Djerdjouri, Bahia; Bouldjennet, Faiza; Taha, Rowaida Z; El-Shanti, Hatem; Sari-Hamidou, Rawda; Khellaf, Ghalia; Benmansour, Mustapha; Benabadji, Mohamed; Haddoum, Farid

    2017-03-01

    Familial Mediterranean fever (FMF, OMIM 249100) is the most common hereditary fever, resulting from mutations in MEFV. FMF is characterized by episodic febrile attacks and polyserositis. Renal AA-amyloidosis is a major complication, which often leads to end-stage renal disease in untreated patients. The data about the renal AA-amyloidosis secondary to FMF are scarce in North African countries and non-existent in Algeria. We aimed to investigate the MEFV mutations associated with this complication in an Algerian patient cohort. Molecular analysis included 28 unrelated Algerian FMF patients with ascertained amyloidosis, 23 of them were symptomatic and 5 were asymptomatic. For this study, a group of 20 FMF patients without renal amyloidosis were selected as controls according to their age, disease onset and disease duration. The mutations were detected by sequencing exon 10 of MEFV. A total of 87.5% (49/56) mutant alleles were identified in 27/28 analyzed patients; p.M694I was predominant and appeared with an allele frequency of 62.5%, followed by p.M694V (17.85%), p.M680I (5.35%) and p.I692Del (1.78%). Remarkably, only p.M694I mutation was observed among the asymptomatic patients. The M694I/M694I genotype, identified in 14/27 (52%) patients, was significantly associated with the development of amyloidosis compared to group of controls (p = 0.022). This study did not link the M694V/M694V genotype to the renal complication despite the fact that it has been observed only in the patients with amyloidosis (3/27; 11%) (p = 0.349). The association of other identified genotypes to this complication was statistically insignificant. The progression of amyloidosis led to end-stage renal disease in 14 patients with 6 deaths. This study shows that p.M694I homozygosity is a potential genetic risk factor for the development of renal AA-amyloidosis in Algerian FMF patients.

  18. The prevalence of Behçet's syndrome, familial Mediterranean fever, HLA-B51 and MEFV gene mutations among ethnic Armenians living in Istanbul, Turkey.

    PubMed

    Seyahi, Emire; Tahir Turanli, Eda; Mangan, Mehmet Serhat; Celikyapi, Gokce; Oktay, Veysel; Cevirgen, Dilsen; Kuzuoglu, Duygu; Ozoglu, Susan; Yazici, Hasan

    2010-01-01

    We investigated the prevalence of Behçet's syndrome (BS) among the ethnic Armenians in Istanbul using Familial Mediterranean Fever (FMF) as a comparator disease. We also studied HLA-B51 and MEFV mutations among a group of healthy Armenians and a non-Armenian population. The prevalence study was conducted in 2 parts in the Armenian primary schools in Istanbul, using the enrolled students as index cases to study the core family. In Part I, a questionnaire seeking only whether either parent had previously been diagnosed as having BS or FMF by a physician was distributed to a total of 1873 index students registered at 10 schools. A total of 1380 parents filled in the questionnaire, yielding a response rate of 37% (1380 / 3746). In Part II, eight schools participated with a response rate of 83 % (1183/1428). Also, genomic DNA samples of 108 healthy (14 M/94 F) Armenians and 97 (45 M/ 52 F) non-Armenians, were studied for HLAB51 and MEFV gene mutations. In Part I, none of the parents turned out to have been diagnosed as BS, whereas a total of 12 / 1380 (870/105) had been diagnosed as FMF. In the second part the estimated prevalence of BS was 90 /105 and that of FMF was 760/ 105. HLA-B51 carrier rate was found to be similar between the Armenian (27%, 29/108) and the non-Armenian participants (19%, 18/97), (p=0.158). Overall carrier rate of MEFV gene mutations was significantly higher in the Armenian group (36% vs. 20%, p=0.015). The genetic load for FMF is considerably higher among the Armenians when compared to the load for BS among the same ethnic group. On the other hand, the rather low frequency of BS among the Armenians when compared to the frequency among the general population living in the same environment is further evidence for a genetic predisposition to BS. HLA- B51 does not seem to play a dominant role in the said predisposition. Finally, as we have used an unorthodox epidemiological methodology in data collection our results might need to be further

  19. Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort.

    PubMed

    Soylemezoglu, Oguz; Kandur, Yasar; Duzova, Ali; Ozkaya, Ozan; Kasapcopur, Ozgür; Baskin, Esra; Fidan, Kibriya; Yalcinkaya, Fatos

    2015-01-01

    Presence of common MEFV gene mutations strengthened the diagnosis of FMF in addition to the typical clinical characteristics of FMF. However, there are also rare mutations. P369S, A744S, R761H, K695R, F479L are the main rare mutations in Turkish population. We aimed to evaluate FMF patients with a single allele MEFV mutation and to compare patients with common and rare mutations. We retrospectively reviewed the medical records of FMF patients with a single allele mutation who were followed up between 2008 and 2013 in six centres. We compared the patients with rare and common mutations for disease severity score, frequent exacerbations ( >1 attack per month), long attack period (>3 day), symptoms, age at the onset of symptoms, gender, consanguinity, and family history. Two hundred and seventeen patients (M/F=101/116) with the diagnosis of FMF and single mutation were included. Heterozygote mutations were defined as common (M694V, V726A, M68OI) and rare mutations (A744S, P369S, K695R, R761H, F479L). Sixty-seven patients (27 males, 40 females) had one single rare mutation and 150 (74 males, 76 females) had one single common mutation. No difference was found between the rare and common mutations with respect to the disease severity score. There was no significant difference between common and rare heterozygote form of mutations in terms of disease severity. Patients with typical characteristics of FMF, with some rare mutations (A744S, P369S) should be treated in the same manner as patients with a common mutation.

  20. Evaluation of IL-1β, IL-1ra, and IL-10 levels and outcome of periodontal therapy in chronic periodontitis with familial Mediterranean fever.

    PubMed

    Bostanci, Vildan; Toker, Hulya; Senel, Soner; Poyraz, Omer; Akpinar, Aysun; Görgün, Emine Pirim; Bakar, Olcay

    2017-01-01

    This study aimed to examine the IL-1β, IL-1ra, and IL-10 cytokine levels in gingival crevicular fluid (GCF) and serum of familial Mediterranean fever (FMF) and chronic periodontitis (CP) patients, and their response to nonsurgical periodontal therapy. A total of 50 patients, 15 FMF patients with generalized chronic periodontitis (FMF-CP), 15 systemically healthy patients with generalized chronic periodontitis (CP), ten systemically and periodontal healthy controls (HC), and ten periodontally healthy FMF patients (FMF-HC) were enrolled in the study. The cytokine levels in GCF and serum were determined by ELISA. Probing depth, clinical attachment level, and gingival and plaque indices in each participant were also measured. The GCF and clinical parameters at baseline and 6 weeks were recorded. The study indicated statistically significant healing of the clinical parameters in both FMF-CP and CP groups after periodontal treatment. GCF IL-1β levels at 6 weeks in FMF-CP group were significantly lower than the CP group (p < 0.05), and GCF IL-1ra levels were significantly decreased at 6 week in the FMF-CP group (p < 0.05). GCF IL-10 levels were significantly higher in the FMF-CP group than in the other groups at baseline and 6 weeks (p < 0.05). There were no significant differences in serum-IL-1β, IL-1ra, and IL-10 levels either FMF-CP or CP groups at baseline or 6 weeks (p > 0.05). The results of our study suggested that there was a positive correlation between gingival inflammation and serum cytokine levels in FMF patients and also colchicine treatment showed protective effects on GCF cytokine levels in FMF-CP group. Following treatment, GCF IL-1β and GCF IL-1ra levels were decreased in FMF-CP group. GCF IL-10 levels were increased in FMF-CP group compared to other groups. Also, the serum cytokine levels associated with periodontal inflammation in FMF patients.

  1. Effect of chronic periodontitis on serum and gingival crevicular fluid oxidant and antioxidant status in patients with familial Mediterranean fever before and after periodontal treatment.

    PubMed

    Bostanci, Vildan; Toker, Hulya; Senel, Soner; Ozdemir, Hakan; Aydin, Huseyin

    2014-05-01

    The aim of this study is to investigate the impact of periodontal status on oxidant/antioxidant status in patients with chronic periodontitis (CP) who experienced familial Mediterranean fever (FMF) and their response to non-surgical periodontal therapy. Data were obtained from 13 patients with FMF with generalized CP (FMF-CP), 15 systemically healthy patients with generalized CP, 15 systemically and periodontal healthy controls (HCs), and 14 periodontally healthy patients with FMF (FMF-HC). Each participant's total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) in their gingival crevicular fluid (GCF) and serum were recorded. Probing depth, clinical attachment level, and gingival and plaque indices in each participant were also measured. The GCF and clinical parameters at baseline and 6 weeks after periodontal treatment were recorded. The study showed statistically significant improvement of clinical parameters in both FMF-CP and CP groups after periodontal treatment. The baseline GCF-TOS and OSI levels were significantly higher in the CP group compared with the FMF-CP group (P <0.05). After periodontal treatment, the GCF-TOS levels were significantly reduced in members of the FMF-CP group (P <0.05). The GCF-TAS levels in members of the FMF-CP group were significantly higher than those of members of the HC group at baseline (P <0.05). Serum-TAS levels in the FMF-CP group were significantly higher than those in the CP and HC groups at baseline (P <0.05). The GCF-TOS level in the FMF-CP group was significantly higher than that in the FMF-HC group at baseline and 6 weeks. However, there were no significant differences in the serum-TOS and serum-OSI levels of those in the FMF-CP and CP groups at baseline and 6 weeks (P >0.05). The results of the present study show that patients with FMF-CP displayed reduced oxidative stress and increased antioxidant status compared with those in the CP and HC groups.

  2. Immune and inflammatory gene expressions are different in Behçet’s disease compared to those in Familial Mediterranean Fever

    PubMed Central

    Özdemir, Filiz Türe; Demiralp, Emel Ekşioğlu; Aydın, Sibel Z.; Atagündüz, Pamir; Ergun, Tülin; Direskeneli, Haner

    2016-01-01

    Objective The immune classification of Behçet’s disease (BD) is still controversial. In this study, we aimed to compare the immune/inflammatory gene expressions in BD with those in familial Mediterranean fever (FMF), an autoinflammatory disorder with innate immune activation. Material and Methods CD4+ T cells and CD14+ monocytes were isolated from the peripheral blood mononuclear cells of Behçet’s disease patients (n=10), FMF (n=6) patients, and healthy controls (n=4) with microbeads, and then, the mRNA was isolated. The expressions of 440 genes associated with immune and inflammatory responses were studied with a focused DNA microarray using a chemiluminescent tagging system. Changes above 1.5-fold and below 0.8-fold were accepted to be significant. Results In BD patients, in the CD4+ T-lymphocyte subset, interleukin 18 receptor accessory protein (1.7-fold), IL-7 receptor (1.9-fold), and prokineticin 2 (2.5-fold) were all increased compared to those in FMF patients, whereas chemokine (C-X3-C motif ) receptor-1 (CX3CR1) (0.7-fold) and endothelial cell growth factor-1 (0.6-fold) were decreased. In the CD14+ monocyte population, the V-fos FBJ murine osteosarcoma viral oncogene homolog (1.5-fold), Interleukin-8 (IL-8) (2.1-fold), and Tumor Necrosis Factor alpha (TNF-α) (1.8-fold) were all increased, whereas the chemokine (C-C motif ) ligand 5 (CCL5) (0.6-fold), C-C chemokine receptor type 7 (0.6-fold), and CX3CR1 (0.7-fold) were decreased, again when compared to those in FMF. Compared to healthy controls in the CD4+ T-lymphocyte population, in both BD and FMF patients, pro-platelet basic protein and CD27 had elevated expression. In BD and FMF patients, 24 and 19 genes, respectively, were downregulated, with 15 overlapping genes between both disorders. In the CD14+ monocytes population, chemokine (C-C motif ) receptor-1 (CCR1) was upregulated both in BD and FMF patients compared to that in the controls, whereas CCL5 was downregulated. Conclusion Immune and

  3. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway.

    PubMed

    Shoham, Nitza G; Centola, Michael; Mansfield, Elizabeth; Hull, Keith M; Wood, Geryl; Wise, Carol A; Kastner, Daniel L

    2003-11-11

    Pyrin, the familial Mediterranean fever protein, is found in association with the cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF-kappaB activation, and apoptosis. These effects are mediated in part through cognate interactions with the adaptor protein ASC, which shares an N-terminal motif with pyrin. We sought additional upstream regulators of inflammation by using pyrin as the bait in yeast two-hybrid assays. We now show that proline serine threonine phosphatase-interacting protein [PSTPIP1, or CD2-binding protein 1 (CD2BP1)], a tyrosine-phosphorylated protein involved in cytoskeletal organization, also interacts with pyrin. Recently, PSTPIP1/CD2BP1 mutations were shown to cause the syndrome of pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA), a dominantly inherited autoinflammatory disorder mediated predominantly by granulocytes. Endogenous PSTPIP1/CD2BP1 and pyrin are coexpressed in monocytes and granulocytes and can be coimmunoprecipitated from THP-1 cells. The B box segment of pyrin was necessary and the B box/coiled-coil segment sufficient for this interaction, whereas the SH3 and coiled-coil domains of PSTPIP1/CD2BP1 were both necessary, but neither was sufficient, for pyrin binding. The Y344F PSTPIP1/CD2BP1 mutation, which blocks tyrosine phosphorylation, was associated with a marked reduction in pyrin binding in pervanadate-treated cells. PAPA-associated A230T and E250Q PSTPIP1/CD2BP1 mutations markedly increased pyrin binding as assayed by immunoprecipitation and, relative to WT, these mutants were hyperphosphorylated when coexpressed with c-Abl kinase. Consistent with the hypothesis that these mutations exert a dominant-negative effect on the previously reported activity of pyrin, we found increased IL-1beta production by peripheral blood leukocytes from a clinically active PAPA patient with the A230T PSTPIP1/CD2BP1 mutation and in cell lines transfected with both PAPA-associated mutants.

  4. Climatic factors in resurgence of Mediterranean spotted fever

    SciTech Connect

    Arenas, E.E.; Creus, B.F.; Cueto, F.B.; Porta, F.S.

    1986-06-07

    There has been a recent resurgence of Mediterranean spotted fever in areas bordering the Mediterranean Sea. This disease is caused by Rickettsia conorii, the dog tick being the vector and main reservoir. Ticks prefer warm weather and their activity increases with rising temperature. In the Valles Occidental, Spain, the incidence of the disease is correlated with hotter and drier summers in the past ten years.

  5. A Rare Case of Mediterranean Spotted Fever and Encephalitis

    PubMed Central

    Pinto, Maria João; Matos Costa, João

    2016-01-01

    Mediterranean spotted fever is a tick-borne zoonotic disease caused by Rickettsia conorii. It is transmitted by the dog tick Rhipicephalus sanguineus. It usually presents as a benign self-limited disease characterized by a skin rash, high fever, and, sometimes, a characteristic ulcer at the tick bite site called tache noir. The course of this disease is usually benign, although severe manifestations have been previously described, mainly in adults. Neurological manifestations are very unusual. We present a case of Mediterranean spotted fever with encephalitis to highlight the importance of clinical suspicion, mainly in endemic areas, the potential severity of this disease, and the need of early initiation of therapy in order to prevent severe complications. PMID:28053795

  6. MEFV-Gene analysis in armenian patients with Familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications.

    PubMed Central

    Cazeneuve, C; Sarkisian, T; Pêcheux, C; Dervichian, M; Nédelec, B; Reinert, P; Ayvazyan, A; Kouyoumdjian, J C; Ajrapetyan, H; Delpech, M; Goossens, M; Dodé, C; Grateau, G; Amselem, S

    1999-01-01

    Familial Mediterranean fever (FMF) is a recessively inherited disorder that is common in patients of Armenian ancestry. To date, its diagnosis, which can be made only retrospectively, is one of exclusion, based entirely on nonspecific clinical signs that result from serosal inflammation and that may lead to unnecessary surgery. Renal amyloidosis, prevented by colchicine, is the most severe complication of FMF, a disorder associated with mutations in the MEFV gene. To evaluate the diagnostic and prognostic value of MEFV-gene analysis, we investigated 90 Armenian FMF patients from 77 unrelated families that were not selected through genetic-linkage analysis. Eight mutations, one of which (R408Q) is new, were found to account for 93% of the 163 independent FMF alleles, with both FMF alleles identified in 89% of the patients. In several instances, family studies provided molecular evidence for pseudodominant transmission and incomplete penetrance of the disease phenotype. The M694V homozygous genotype was found to be associated with a higher prevalence of renal amyloidosis and arthritis, compared with other genotypes (P=.0002 and P=.006, respectively). The demonstration of both the diagnostic and prognostic value of MEFV analysis and particular modes of inheritance should lead to new ways for management of FMF-including genetic counseling and therapeutic decisions in affected families. PMID:10364520

  7. [Molecular diagnostics of hereditary fever syndromes. Familial Mediterranean fever (FMF), hyperimmunoglobulin D syndrome (HIDS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS: FCAS, MWS, NOMID/CINCA)].

    PubMed

    Timmann, C; Horstmann, R

    2009-11-01

    Periodic episodes of fever and inflammation can have a genetic origin. Nowadays, the identification of the causative genetic variants in the majority of cases allows molecular genetic confirmation of the clinical diagnosis, which enables approaches with specific drug treatment and improves patient compliance as well as genetic counseling. Besides a detailed clinical examination a medical history including family history and an assessment of the ethnic origin are required. In order to make genetic testing straightforward and cost effective an iterative procedure should be followed which should include, in addition to clinical data, the frequencies of causative mutations in the various gene segments involved.

  8. Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

    PubMed

    Amaryan, G; Astvatsatryan, V; Gabrielyan, E; Panossian, A; Panosyan, V; Wikman, G

    2003-05-01

    Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special extracts standardized for the content of Andrographolide (4 mg/tablet), Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel groups of patients. The study was conducted in 24 (3-15 years of both genders) patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets of series A (verum) and 10 patients received series B product (placebo). The study medication was taken three times of four tablets daily for 1 month. Daily dose of the andrographolide--48 mg. The primary outcome measures in physician's evaluation were related to duration, frequency and severity of attacks in FMF patients (attacks characteristics score). The patient's self-evaluation was based mainly on symptoms--abdominal, chest pains, temperature, arthritis, myalgia, erysipelas-like erythema. All of 3 features (duration, frequency, severity of attacks) showed significant improvement in the verum group as compared with the placebo. In both clinical and self evaluation the severity of attacks was found to show the most significant improvement in the verum group. Both the clinical and laboratory results of the present phase II (pilot) clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug for the management of patients with FMF.

  9. [Cardiac tamponade as first manifestation in Mediterranean fever with autosomal dominant form].

    PubMed

    Sánchez Ferrer, F; Martinez Villar, M; Fernández Bernal, A; Martín de Lara, I; Paya Elorza, I

    2015-01-01

    Familial Mediterranean fever (FMF) is a hereditary disease characterized by brief, recurring and self-limited episodes of fever and pain with inflammation, of one or several serous (peritoneum, pleura, pericardium, synovial or vaginal tunic of the testicle). Amyloidosis is its more important complication and the principal reason of death in the cases in which it appears. Diagnosis is based on the clinic and is confirmed by genetic tests. The treatment with Colchicine (0,02-0,03 mg/kg/day) prevents the recurrence of FMF attacks and the development of secondary (AA) amyloidosis. We report a case of a 13-year-old child in which FMF was diagnosed after several coincidental episodes with fever, pericarditis and cardiac tamponade. The genetic confirmation showed an autosomal dominant inheritance that is less frecuent than the recesive form, in this disease.

  10. Questions on Mediterranean Spotted Fever a Century after Its Discovery

    PubMed Central

    Rovery, Clarisse; Brouqui, Philippe

    2008-01-01

    Mediterranean spotted fever (MSF) was first described in 1910. Twenty years later, it was recognized as a rickettsial disease transmitted by the brown dog tick. In contrast to Rocky Mountain spotted fever (RMSF), MSF was thought to be a benign disease; however, the first severe case that resulted in death was reported in France in the 1980s. We have noted important changes in the epidemiology of MSF in the last 10 years, with emergence and reemergence of MSF in several countries. Advanced molecular tools have allowed Rickettsia conorii conorii to be classified as a subspecies of R. conorii. New clinical features, such as multiple eschars, have been recently reported. Moreover, MSF has become more severe than RMSF; the mortality rate was as high as 32% in Portugal in 1997. Whether Rhipicephalus sanguineus is the only vector and reservoir for R. conorii conorii is a question not yet answered. PMID:18760001

  11. The familial Mediterranean fever (FMF) 50 score: does it work in a controlled clinical trial? Re-analysis of the trial of rilonacept for patients with colchicine-resistant or intolerant FMF.

    PubMed

    Hashkes, Philip J; Huang, Bin

    2015-03-01

    The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF. To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine. We re-analyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants) without worsening of the sixth criterion. In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered respondersto rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept. The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study.

  12. Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines.

    PubMed

    Ibrahim, José-Noel; Jounblat, Rania; Delwail, Adriana; Abou-Ghoch, Joelle; Salem, Nabiha; Chouery, Eliane; Megarbane, André; Medlej-Hashim, Myrna; Lecron, Jean-Claude

    2014-10-01

    In order to clarify the inflammatory mechanism underlying familial Mediterranean fever (FMF), we aimed to evaluate the ex vivo cytokine profile of FMF patients during acute attacks and attack-free periods, and compare it with that of healthy controls. The study included 34 FMF patients, of whom 9 were studied during attack and remission and 24 healthy controls. Cytokine levels were evaluated by Luminex technology in serum and supernatants of PBMC (Peripheral Blood Mononuclear Cells) cultures with and without 24h stimulation of monocytes by LPS and T lymphocytes by anti-CD3/CD28 beads. Levels of IL-6 and TNF-α were higher in unstimulated and LPS-stimulated PBMC supernatants of FMF patients in crises compared to controls. In response to LPS stimulation, higher levels of IL-1β and IL-1α were found in PBMC supernatants of patients during crises compared to those in remission and to controls. IFN-γ and IL-4 levels were the lowest in unstimulated and anti-CD3/CD28 stimulated PBMCs supernatants of patients during crises compared to remission and controls. The Th17 cytokines IL-17 and IL-22 were respectively higher in anti-CD3/CD28 stimulated PBMC supernatants of FMF patients during and between crises compared to controls. Amongst cytokines tested in serum, only IL-6 and TNFα were enhanced in FMF patients. The ex vivo study represents an interesting approach to evaluate cytokines' involvement in FMF. Our results suggest an ongoing subclinical inflammation and define an elevated inflammatory cytokine signature, distinctly for M694V homozygous patients. The absence of spontaneous IL-1β release by PBMCs reflects no constitutive activation of the inflammasome in FMF physiopathology.

  13. [Macrolides in the treatment of children with Mediterranean spotted fever].

    PubMed

    Cascio, Antonio; Colomba, Claudia

    2002-09-01

    Till now there is not a gold standard therapy for Mediterranean spotted fever (MSF) in children. Standard treatment for MSF is the administration of tetracycline or chloramphenicol, however both these drugs can cause significant adverse effects in children (tetracyclines can cause staining of teeth, chloramphenicol severe hematological adverse events such as aplastic anemia, gray baby syndrome and hemolytic anemia in patients with the Mediterranean form of G6PD deficiency). We conducted two randomized clinical trials; the first compared clarithromycin versus chloramphenicol: mean time to defervescence was 36.7 +/- 18.1 h in the clarithromycin group and 47.1+/- 21.9 h in the chloramphenicol group (P= 0.047). The second trial compared clarithromycin versus azithromycin and did not show any statistically significant difference: mean time to defervescence was 46.2 +/- 36.4 h in the clarithromycin group and 39.3 +/- 31.3 h in the azithromycin group (P= 0.34). On the basis of these studies we think that clarithromycin and azithromycin could constitute an acceptable alternative to chloramphenicol and to tetracyclines for the treatment of MSF in children

  14. Randomized Trial of Clarithromycin for Mediterranean Spotted Fever

    PubMed Central

    Muñoz, Tomas; Travería, Francisco Javier; Navarro, Gemma; Font, Bernat; Sanfeliu, Isabel; Segura, Ferran

    2015-01-01

    The classic antibiotic treatment for Mediterranean spotted fever (MSF) is based on tetracyclines or chloramphenicol, but chloramphenicol's bone marrow toxicity makes tetracyclines the treatment of choice. However, it is convenient to have alternatives available for patients who are allergic to tetracyclines, pregnant women, and children <8 years old. We conducted a randomized clinical trial to compare clarithromycin with doxycycline or josamycin in the treatment of MSF. Forty patients were evaluated (23 male; mean age, 39.87 years); 13 patients were aged <14 years. Seventeen patients received clarithromycin, and 23 received doxycycline or josamycin. The interval between the onset of symptoms and the start of treatment was 4.04 ± 1.70 days in the clarithromycin group versus 4.11 ± 1.60 days in the doxycycline/josamycin group (P = not significant [NS]). Time to the disappearance of fever after treatment was 2.67 ± 1.55 days in the clarithromycin group versus 2.22 ± 1.35 days in the doxycycline/josamycin (P = NS). The symptoms had disappeared at 4.70 ± 2.25 days in the clarithromycin group versus at 4.75 ± 3.08 days in the doxycycline/josamycin (P = NS). There were no adverse reactions to treatment or relapses in either group. In conclusion, clarithromycin is a good alternative to doxycycline or josamycin in the treatment of MSF. PMID:26711765

  15. [Mediterranean spotted fever in north Dalmatia: is there a problem?].

    PubMed

    Dzelalija, Boris; Medić, Alan; Lozancić, Toni

    2007-09-01

    We analyzed clinical and therapeutic characteristics of Mediterranean spotted fever (MSF) in north Dalmatia. Analysis was conducted in 93 patients hospitalized with MSF at Zadar General Hospital during the 1988-2000 period. The most frequently found signs of the disease were high fever (91; 97.8%), maculopapular rash (89; 95.7%), headaches (84; 90.3%), arthralgia (75; 80.6%), exhaustion (75; 80.6%) and nausea (65; 69.9%). Tache noire, as a pathognomonic sign of MSF, was found in 22 (23.7%) patients. The most frequently indicated diagnoses were febris cum exanthemate (43; 46.2), rickettsiosis suspecta (21; 22.6%) and exanthema maculopapulosum (15; 16.1%). Early therapeutic efficiency was achieved by doxycycline in 34/43 (79.1%), and by ciprofloxacin in 10/14 (71.4%) treated adult patients, and by azithromycin in 7/9 (77.8%) children. The identification of MSF endemic rickettsiosis in north Dalmatia, serious clinical forms of the disease and the success of early and adequate anti-rickettsial antibiotic therapy are a clear warning that our physicians must be very familiar with this disease and include this rickettsial disease in differential diagnosis of acute febrile diseases accompanied by rash.

  16. Mediterranean spotted fever and hearing impairment: a rare complication.

    PubMed

    Rossio, Raffaella; Conalbi, Valeria; Castagna, Valentina; Recalcati, Sebastiano; Torri, Adriana; Coen, Massimo; Cassulini, Lucia Restano; Peyvandi, Flora

    2015-06-01

    Mediterranean spotted fever (MSF) is caused by Rickettsia conorii and transmitted by the brown dog tick Rhipicephalus sanguineus. It is prevalent in southern Europe, Africa and central Asia. The disease usually has a benign course and is characterized by fever, myalgia and a characteristic papular rash with an inoculation eschar ('tache noir') at the site of the tick bite. Severe forms of disease can have cardiac, neurologic or renal involvement. Nervous system complications are unusual and may develop in the early phase of disease or as a delayed complication. Neurological symptoms include headache and alterations of the level of consciousness, and some cases of meningoenchefalitis and Guillain-Barrè syndrome have been also reported. Peripheral nerve involvement is reported only in a limited number of case reports. We describe a case of Rickettsia conorii that was complicated with hearing loss and did not respond to specific treatment. Hearing loss is a rare event, but clinicians should be aware of this complication. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Quality of life in adult patients with Familial Mediterranean fever living in Germany or Turkey compared to healthy subjects: a study evaluating the effect of disease severity and country of residence.

    PubMed

    Giese, Arnd; Kurucay, Mustafa; Kilic, Levent; Örnek, Ahmet; Şendur, Süleyman Nahit; Lainka, Elke; Henning, Bernhard Ferdinand

    2013-07-01

    We assessed quality of life (QOL) and disease activity in patients with Familial Mediterranean fever (FMF) of Turkish ancestry living in Germany or Turkey and conducted a correlation with FMF disease activity. 40 FMF patients in Turkey (TR), 40 FMF patients in Germany (G) and 40 healthy controls in Germany (C) were included. QOL was evaluated with the short form of the World Health Organisation Quality of Life scale (WHOQOL-BREF). FMF disease activity was examined with the Pras score. Mean age was TR 30.5 ± 10.6, G 35.2 ± 10.2, C 34.6 ± 10.7. Of the 120 participants, 77 were female. FMF patients in TR and G had a significantly decreased QOL physical health domain compared to controls (TR 59.7 ± 18.8, G 60.4 ± 19.4, C 76.5 ± 14.6). Turkish FMF patients had a lower QOL environment domain compared to controls (TR 62.3 ± 17.5, G 69.7 ± 16.5, C 72.3 ± 13.5). In the other QOL domains, no significant differences were found. The differences in QOL were robust to a regression analysis. No significant correlation between QOL and FMF disease activity was found. German FMF patients had longer duration of disease, younger age at onset and longer delay from disease onset to colchicine treatment. A total of 5 of 40 German FMF patients were not taking colchicine (TR:0). Erythrocyte sedimentation rate was lowest in TR with significant difference between TR and G as well as G and C (TR 13.2 ± 10.3, G 27.8 ± 19.4, C 16.3 ± 12.8 mm/h). C-reactive protein did not differ between TR and G. FMF has an important impact on QOL physical health domain. No correlation between FMF disease activity and the WHOQOL-BREF could be found.

  18. Multigene families in African swine fever virus: family 505.

    PubMed Central

    Rodriguez, J M; Yañez, R J; Pan, R; Rodriguez, J F; Salas, M L; Viñuela, E

    1994-01-01

    Sequencing of restriction fragment EcoRI A-SalI C of African swine fever virus has revealed the existence of a multigene family, designated family 505 because of the average number of amino acids in the proteins, composed of seven homologous and tandemly arranged genes. All the genes of family 505 are expressed during infection. Primer extension analysis showed that transcription is initiated a short distance (3 to 62 nucleotides) from the start codon of the corresponding open reading frame. The proteins of family 505 showed similarity to those of family 360 from African swine fever virus. In particular, a striking conservation of three regions at the amino terminus of the polypeptides was observed. Images PMID:8139051

  19. A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

    PubMed

    Aldea, Anna; Campistol, Josep M; Arostegui, Juan I; Rius, Josefa; Maso, Montserrat; Vives, Jordi; Yagüe, Jordi

    2004-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non-ancestral populations.

  20. [Is there a relationship between gouty arthritis and Mediterranean fever gene mutations?].

    PubMed

    Sari, Ismail; Simsek, Ismail; Tunca, Yusuf; Kisacik, Bunyamin; Erdem, Hakan; Pay, Salih; Cay, Hasan Fatih; Gul, Davut; Dinc, Ayhan

    2015-01-01

    Gouty arthritis and familial Mediterranean fever (FMF) share some clinical and pathological features such as being classified as auto inflammatory disease, association with inflammasome, short-lived intermittent arthritis, and good response to colchicine and anti-interleukin-1 treatments. As Mediterranean fever (MEFV) gene is the causative factor of FMF, we aimed to investigate the prevalence of MEFV gene mutations and their effect on disease manifestations in Turkish gouty arthritis patients. Ninety-seven patients diagnosed with primary gouty arthritis (93M and 4 F, 54 [37-84] years) and 100 healthy controls (94M and 6 F, 57 [37-86] years) included in the study. All subjects were genotyped for the MEFV variations. Number of gout attacks, diuretic use, and history of nephrolithiasis and presence of tophus were also recorded. The carriage rate of MEFV mutations for patients and controls were 22.7% (n=22) and 24% (n=24) respectively. The comparison of the patient and control groups yielded no significant difference in terms of the MEFV mutations carriage rate (p=0.87). The allelic frequencies of the MEFV mutations in patients were 11.9% (n=23) and 14% (n=28) in controls (p=0.55). The presence of MEFV variants did not show any association with clinical features of gouty arthritis. The subgroup analysis of patients revealed that gouty arthritis patients with mutations had similar frequencies of tophus, history of nephrolithiasis and podogra compared to the ones without mutations (p>0.05). This study does not provide support for a major role of MEFV mutations in Turkish gouty arthritis patients. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  1. Multigene families in African swine fever virus: family 360.

    PubMed Central

    González, A; Calvo, V; Almazán, F; Almendral, J M; Ramírez, J C; de la Vega, I; Blasco, R; Viñuela, E

    1990-01-01

    A group of cross-hybridizing DNA segments contained within the restriction fragments RK', RL, RJ, and RD' of African swine fever virus DNA were mapped and sequenced. Analysis of these sequences revealed the presence of a family of homologous open reading frames in regions close to the DNA ends. The whole family is composed of six open reading frames with an average length of 360 coding triplets (multigene family 360), four of which are located in the left part of the genome and two of which are in the right terminal EcoRI fragment. In close proximity to the right terminal inverted repeat, we found an additional small open reading frame which was homologous to the 5'-terminal portion of the other open reading frames, suggesting that most of that open reading frame has been deleted. These repeated sequences account for the previously described inverted internal repetitions (J.M. Sogo, J.M. Almendral, A. Talavera, and E. Viñuela, Virology 133:271-275, 1984). Most of the genes of multigene family 360 are transcribed in African swine fever virus-infected cells. A comparison of the predicted protein sequences of family 360 indicated that several residues are conserved, suggesting that an overall structure is maintained for every member of the family. The transcription direction of each open reading frame, as well as the evolutionary relationships among the genes, suggests that the family originated by gene duplication and translocation of sequences between the DNA ends. Images PMID:2325203

  2. Differential diagnosis of fever of unknown origin in children.

    PubMed

    Majeed, H A

    2000-09-01

    Fever of unknown origin in children follows two main clinical patterns, namely fever of unknown origin and chronic episodic fever of unknown origin. Fever of unknown origin is characterized by daily fever persisting for more than 3 weeks. The main causes are infectious, rheumatologic disorders, and malignancy. Chronic episodic fever of unknown origin is characterized by fever lasting for a few days to a few weeks, followed by a fever-free interval and a sense of well-being. The main causes are familial Mediterranean fever, the hyper-immunoglobulin D syndrome, familial Hibernian fever, Behcet disease, the syndrome of periodic fever, aphthous stomatitis, pharyngitis and adenitis, and cyclic neutropenia.

  3. [Characteristics of the rash in Mediterranean boutonneuse fever].

    PubMed

    Scaffidi, L; Scaffidi, A

    1981-09-01

    The typical papulomacular picture of boutonneuse fever is described. A series of atypical exanthemas is presented: simply erythemato-macular and typhus-like, nodular, vesicular. Skin biopsies showing the endothelial, thrombotic and parietal aspects of periadventitial infiltration (this being sometimes moderately and extensively pericapillary) are also presented. The reason for the absence of extensive thrombisation in extensive, marked rickettsiotic endothelitis are discussed, and stress is laid to the hitherto little-discussed, but significant involvement of dermal collagen.

  4. Mediterranean Spotted Fever: A Rare Non-Endemic Disease in the USA

    PubMed Central

    Oaks, Joshua Brad; LaCapra, Gina

    2017-01-01

    We report a case of a 43-year-old Israeli male who presented with an intermittent fever associated with a gradual appearance of diffusely scattered erythematous non-pruritic maculopapular lesions, generalized body malaise, muscle aches, and distal extremity weakness. He works in the Israeli military and has been exposed to dogs that are used to search for people in tunnels and claimed that he had removed ticks from the dogs. In the hospital, he presented with fever, a diffuse maculopapular rash, and an isolated round black eschar. He was started on doxycycline based on suspected Mediterranean spotted fever (MSF) in which he improved significantly with resolution of his clinical complaints. His immunoglobulin G (IgG) MSF antibody came back positive. PMID:28191378

  5. Fever, hepatosplenomegaly and pancytopenia in a patient living in the Mediterranean region.

    PubMed Central

    Büyükaşik, Y.; Ileri, N. S.; Haznedaroğlu, I. C.; Demiroğlu, H.; Dündar, S.

    1998-01-01

    A 24 year old woman living in the Mediterranean region of Turkey present with a three-month history of weight loss and irregular fever that was peaking at 40 degrees C with shivering. No definite aetiology could be identified in a local hospital. A bacterial infection had been suspected, but antibiotic therapy, at first with sulbactam-ampicillin and later with azithromycin, had no influence on the fever. Physical examination revealed an emaciated patient with fever (39 degrees C), pallor, and hepatosplenomegaly (spleen 9 cm and liver 5 cm palpable below the costal margin). No peripheral lymphadenopathy was present. The laboratory examinations are summarised in the table. Notably, a prominent increase of macrophages containing intracellular micro-organisms (figures 1 and 2) was seen in the bone marrow smears. The same micro-organisms were also identified within the Kupffer cells in liver biopsy. Images Figures 1 and 2 PMID:9683980

  6. Clarithromycin versus azithromycin in the treatment of Mediterranean spotted fever in children: a randomized controlled trial.

    PubMed

    Cascio, Antonio; Colomba, Claudia; Antinori, Spinello; Paterson, David L; Titone, Lucina

    2002-01-15

    We conducted an open-label randomized controlled trial to compare the efficacy and safety of clarithromycin (15/mg/kg/day in 2 divided doses for 7 days) with those of azithromycin (10 mg/kg/day in 1 dose for 3 days) in the treatment of children with Mediterranean spotted fever. Until now, there has not been a gold-standard therapy for this rickettsial disease in children. Eighty-seven children were randomized to receive 1 of the 2 drugs. The mean time to defervescence (+/- standard deviation) was 46.2+/-36.4 h in the clarithromycin group and 39.3+/-31.3 h in the azithromycin group. These differences were not statistically significant and both drugs were equally well-tolerated. Clarithromycin and azithromycin could be acceptable therapeutic alternatives to chloramphenicol and tetracyclines for children aged < or =8 years with Mediterranean spotted fever. Azithromycin, because it has a long half-life, offers the advantages of administration in a single daily dose and a shorter duration of therapy, which could increase compliance in children.

  7. Family cluster of Mayaro fever, Venezuela.

    PubMed

    Torres, Jaime R; Russell, Kevin L; Vasquez, Clovis; Barrera, Roberto; Tesh, Robert B; Salas, Rosalba; Watts, Douglas M

    2004-07-01

    A cluster of protracted migratory polyarthritis involving four adult family members occurred in January 2000 after a brief overnight outing in a rural area of Venezuela. Laboratory testing demonstrated Mayaro virus as the cause of the cluster. These results documented the first human cases of Mayaro virus in Venezuela.

  8. Family Cluster of Mayaro Fever, Venezuela

    PubMed Central

    Russell, Kevin L.; Vasquez, Clovis; Tesh, Robert B.; Salas, Rosalba; Watts, Douglas M.

    2004-01-01

    A cluster of protracted migratory polyarthritis involving four adult family members occurred in January 2000 after a brief overnight outing in a rural area of Venezuela. Laboratory testing demonstrated Mayaro virus as the cause of the cluster. These results documented the first human cases of Mayaro virus in Venezuela. PMID:15324555

  9. Myocarditis in Mediterranean spotted fever: a case report and a review of the literature

    PubMed Central

    Siracusa, Lucia; Trizzino, Marcello; Gioè, Claudia; Giammanco, Anna; Cascio, Antonio

    2016-01-01

    Introduction: Mediterranean spotted fever (MSF) is a tick-borne acute febrile disease caused by Rickettsia conorii. Most cases follow a benign course, with a case fatality rate of 3–7 % among hospitalized patients. Complications are described mainly in adult patients and include hepatic, renal, neurological and cardiac impairment. Among cardiac complications, pericarditis, myocarditis and heart rhythm disorders are uncommon complications in MSF and only a few cases have been reported in the literature. Case Presentation: We describe a new case of acute myocarditis complicating MSF in an immunocompetent adult patient without risk factors for severe MSF. Conclusion: Myocarditis is an uncommon but severe complication of MSF. Clinicians should be aware of a possible cardiac involvement in patients with MSF. Close monitoring and an aggressive approach are essential to reduce mortality rates of MSF. PMID:28348768

  10. Mediterranean spotted fever: clinical and laboratory characteristics of 415 Sicilian children

    PubMed Central

    Colomba, Claudia; Saporito, Laura; Polara, Valentina Frasca; Rubino, Raffaella; Titone, Lucina

    2006-01-01

    Background Mediterranean spotted fever (MSF) is an acute febrile, zoonotic disease caused by Rickettsia conorii and transmitted to humans by the brown dogtick Rhipicephalus sanguineus. Nearly four hundred cases are reported every year (mainly from June to September) on the Italian island of Sicily. The aim of the study was to analyze the clinical and laboratory characteristics of patients with MSF and the efficacy of the drugs administered. Methods Our study was carried out on 415 children with MSF, during the period January 1997 – December 2004, at the "G. Di Cristina" Children's hospital in Palermo, Sicily, Italy. On admission patients' clinical history, physical and laboratory examination and indirect immunofluorescence antibody test (IFAT) for Rickettsia conorii were performed. Diagnosis was considered confirmed if the patients had an MSF diagnostic score greater than or equal to 25 according to the Raoult's scoring system. All patients were treated with chloramphenicol or with macrolides (clarithromycin or azithromycin). Results Fever, rash and tache noire were present in 386 (93%), 392 (94.5%) and 263 (63.4%) cases respectively. Eighteen (4.6%) children showed atypical exanthema. Chloramphenicol and newer macrolides all appeared to be effective and safe therapies. Conclusion Clinical features of 415 children with MSF were similar to those reported by other authors except for a lower incidence of headache, arthralgia and myalgia and a higher frequency of epato-splenomegaly. Concerning therapy, clarithromycin can be considered a valid alternative therapy to tetracyclines or chloramphenicol especially for children aged < eight years. PMID:16553943

  11. Mediterranean spotted fever: case series of 24 years (1989-2012).

    PubMed

    Crespo, Pedro; Seixas, Diana; Marques, Nuno; Oliveira, Joaquim; da Cunha, Saraiva; Meliço-Silvestre, A

    2015-01-01

    Mediterranean spotted fever (MSF) is the most prevalent zoonosis in Portugal. To characterize it's evolution between 1989 and 2012, the authors reviewed the cases diagnosed at their unit during this period. Review of clinical records of patients with MSF diagnosis, between 1989 and 2012. Data from 250 patients was included, 54% male. Mean age at diagnosis was 58 years (11-92). Mean annual incidence was 10 cases, with clear summer predominance. Most patients, 78% lived in rural areas, 34% had contact with dogs and 10% noticed the tick bite. Most common symptoms were: fever (98%), myo-arthralgia (64%) and headache (48%). Maculopapular rash was noticed in 87%, affecting palms in 77% and soles in 69%. Inoculation eschar was found in 60%, mostly located on the trunk. Treatment included doxycycline in 86% and chloramphenicol in 12%, with a mean duration of 8 days. Most frequent blood test abnormalities were C-reactive protein, lactate dehydrogenase, aspartate aminotransferase and alanine transaminase elevations and thrombocytopenia. First serologic evaluation was positive in 37% (78/212), having seroconversion been documented in 85% (72/85). Most frequent complication was acute renal injury. ICU admission occurred in 5%. Average length of hospital stay was 11.2 days (1-106), with a mortality of 3.6%. In our series, there was clear summer predominance of MSF, which had rural origin in 78%. Most common symptoms were fever, myo-arthralgia and headache. Maculopapular rash was noticed in 87% of cases and inoculation eschar in 60%. Most cases had favourable outcome, having 5% been admitted to ICU. Mortality was 3.6%.

  12. Thoracic and lung involvement in familial Mediterranean fever (FMF).

    PubMed

    Lidar, Merav; Pras, Mordechai; Langevitz, Pnina; Livneh, Avi

    2002-06-01

    Lung involvement in FMF is limited mainly to transient pleuritis during acute attacks. Amyloidosis of the lung is rare and is associated with symptomatic involvement of other organs while remaining subclinical in itself. Vasculitis of the lung in FMF is possible because of the strong association between FMF and a variety of vasculitides. With the exception of one case of isolated pulmonary vasculitis, vasculitis of the lung in FMF has not been described. The claim that FMF protects against asthma has not been established, but this inverse association, if present, may be traced to linkage disequilibrium in which MEFV modifies the effect of asthma and atopic-related genes, or to eosinophil function. Mesothelioma has been reported in at least four patients with FMF and is related to chronic or recurrent stimulation of the serous membrane. Three patients had peritoneal mesothelioma, while one developed mesothelioma of the lung. Finally, thromboembolism should be considered, particularly in patients with FMF amyloidosis who present with respiratory distress.

  13. Dysregulated mature IL-1β production in familial Mediterranean fever.

    PubMed

    Migita, Kiyoshi; Izumi, Yasumori; Fujikawa, Keita; Agematsu, Kazunaga; Masumoto, Junya; Jiuchi, Yuka; Kozuru, Hideko; Nonaka, Fumiaki; Shimizu, Toshimasa; Nakamura, Tadashi; Iwanaga, Nozomi; Furukawa, Hiroshi; Yasunami, Michio; Kawakami, Atsushi; Eguchi, Katsumi

    2015-04-01

    The aim of this study was to analyse the role of circulating cleaved IL-1β in patients with FMF. We enrolled 20 patients with FMF (5 males and 15 females), 22 patients with RA (4 males and 18 females) and 22 healthy controls (6 males and 16 females). Serum levels of serum amyloid A (SAA) were measured by ELISA. We also determined whether IL-1β was present as the cleaved form (p17) in the sera of FMF patients by immunoblotting using anti-cleaved IL-1β antibody. Although SAA concentrations were elevated in the sera, there was no significant difference in these concentrations between FMF patients and RA patients. Immunoblot analysis demonstrated that the cleaved form of IL-1β (p17) was present in sera from FMF patients during febrile attack periods, but not in healthy controls. Bands representing the cleaved form of IL-1β were not detected in serum from FMF patients at non-febrile attack periods or remission periods under colchicine treatment. The amounts of cleaved IL-1β (p17) were significantly higher in patients with FMF compared with those in patients with RA in the inflammatory phase. The cleaved form of IL-1β is a valuable biomarker for monitoring disease activity and response to colchicine treatment in patients with FMF. It might be useful to discriminate FMF from other non-IL-1β-mediated inflammatory disorders. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Serum soluble fas ligand levels in familial Mediterranean fever.

    PubMed

    Ceri, Mevlut; Unverdi, Selman; Senes, Mehmet; Altay, Mustafa; Yilmaz, Rahmi; Yucel, Dogan; Duranay, Murat

    2013-07-01

    Fas/FasL system plays an important role in the regulation of cell life and death, and circulating levels of sFasL have been shown to increase in some inflammatory conditions. However, there is no sufficient information about the levels of sFasL in patients with FMF. This study was designed to evaluate the serum sFasL levels in patients with FMF during attack and attack-free periods. Twenty-five FMF patients in attack and forty-four in free-attack period, and 20 age-, sex-, and BMI-matched healthy controls were included in this study. Participants with any chronic diseases were excluded. Blood samples were obtained within the first 24 h of the attack period and between febrile attacks, and levels of WBC, ESR, Fibrinogen, hsCRP and sFasL were determined. The levels of traditional acute phase reactants during the attack were significantly higher than the attack-free and controls (p < 0.05). The serum sFasL levels in the FMF study groups did not differ from the control group (0.70 ± 0.08 vs. 0.73 ± 0.12; 0.70 ± 0.08 vs. 0.83 ± 0.14; 0.73 ± 0.12 vs. 0.83 ± 0.14, respectively, p > 0.05). Moreover, the sFasL levels during the attack were not significantly different from those in attack-free patients (0.70 ± 0.08 vs. 0.83 ± 0.14, p > 0.05). In this study, we demonstrated that serum sFasL levels were not markedly affected in FMF and cannot be used as a supportive marker to differentiate attacks from attack-free periods. However, further studies are needed to determine its usefulness as a marker in clinical practice.

  15. The rate and significance of Mediterranean fever gene mutations in patients with ankylosing spondylitis: a three-month, longitudinal clinical study.

    PubMed

    Cinar, Muhammet; Dinc, Ayhan; Simsek, Ismail; Erdem, Hakan; Koc, Bayram; Pay, Salih; Tunca, Yusuf; Kilic, Selim; Gul, Davud

    2008-11-01

    In this study, our aim was to investigate the prevalence of Mediterranean fever (MEFV) gene mutations in patients with ankylosing spondylitis (AS) and assessing their clinical significance. Ninety-five consecutive patients (12 women, 83 men) with active AS were included to the study. All patient's relevant clinical data were recorded at the beginning and patient assessment measures were performed. The frequency of the eight most common MEFV mutations: M694V, V726A, E148Q, M680I, M694I, P369S, F479L, and the R761H were determined. Genetic analysis was carried out by the NanoChip Molecular Genetics Workstation. NSAIDs were given to patients for treatment. The rate of MEFV mutations and their clinical significance were assessed. With regard to the MEFV mutation analysis, 30.5% of AS patients were found to have at least one mutation. The response rate to the NSAIDs (P=0.825) or frequency of patients having active disease (P=0.066) after the treatment, were not found different between the patients those have MEFV mutations and the patients those were non-carriers. Furthermore, no clinical and laboratory difference between MEFV mutation carriers and non-carriers were found. We think that although prevalence of MEFV mutations is significantly high in AS patients without clinical features of familial Mediterranean fever, its influence to the prognosis is less likely. Further investigations are needed to define the impact of MEFV mutations on the disease course of ankylosing spondylitis.

  16. Line blot and western blot immunoassays for diagnosis of Mediterranean spotted fever.

    PubMed Central

    Raoult, D; Dasch, G A

    1989-01-01

    The line blot, a new immunoassay in which antigens are placed on nitrocellulose as narrow lines, was evaluated for its sensitivity and specificity relative to the microimmunofluorescence assay for the diagnosis of Mediterranean spotted fever (MSF). The line blot assay was only slightly less sensitive and less specific than the microimmunofluorescence assay for detection of immunoglobulin M (IgM) or IgG in 100 serum specimens from 42 patients with MSF. No line blot reactions were observed among 50 control serum specimens from febrile patients with other illnesses. The line blot assay was largely group reactive for spotted fever rickettsiae, but 26% of the positive serum specimens also cross-reacted by IgM with Rickettsia typhi. Western immunoblotting was used to characterize the antigenic components recognized by 19 MSF serum specimens. For both IgM and IgG, lipopolysaccharide was the cross-reactive group antigen, whereas the high-molecular-weight species-specific protein antigens (SPAs) were the only reactive proteins. Relative to the other nine rickettsiae, Rickettsia bellii was unique both in exhibiting no SPA reactions and in having a lipopolysaccharide with a predominantly high-molecular-weight distribution. Although most of the 19 MSF serum specimens examined by Western blotting exhibited preferential reactivity to SPAs of two strains of R. conorii and weaker reactions to the other rickettsiae, 2 serum specimens exhibited SPA reactions consistent with typhus infections. In comparison with other assays, the line blot and Western blot immunoassays have advantages which may permit an improvement in the general availability and commercialization of assays for the serodiagnosis of rickettsial infections. Images PMID:2506223

  17. Analysis of surveillance systems in place in European Mediterranean countries for West Nile virus (WNV) and Rift Valley fever (RVF).

    PubMed

    Cito, F; Narcisi, V; Danzetta, M L; Iannetti, S; Sabatino, D D; Bruno, R; Carvelli, A; Atzeni, M; Sauro, F; Calistri, P

    2013-11-01

    West Nile virus (WNV) and Rift Valley fever virus (RVFV) represent an important group of viral agents responsible for vector-borne zoonotic diseases constituting an emerging sanitary threat for the Mediterranean Basin and the neighbouring countries. WNV infection is present in several Mediterranean countries, whereas RVF has never been introduced into Europe, but it is considered a major threat for North African countries. Being vector-borne diseases, they cannot be prevented only through an animal trade control policy. Several approaches are used for the surveillance of WNV and RVFV. With the aim of assessing the surveillance systems in place in Mediterranean countries, two disease-specific questionnaires (WNV, RVFV) have been prepared and submitted to Public Health and Veterinary Authorities of six EU countries. This study presents the information gathered through the questionnaires and describes some critical points in the prevention and surveillance of these diseases as emerged by the answers received.

  18. [Fever of unknown cause and autoinflammatory disease].

    PubMed

    Hara, Toshiro

    2011-09-01

    Autoinflammatory diseases are often associated with various kinds of febrile episodes such as fever of unknown origin, periodic fever and recurrent fever. Therefore, in the differential diagnosis of fever of unknown cause, autoinflammatory diseases should be considered after exclusion of infections, malignancy and autoimmune diseases. As autoinflammatory diseases now include TRAPS (TNF receptor-associated periodic syndrome), CAPS (cryopyrin -associated periodic syndromes), FMF(familial Mediterranean fever), MAPS (mevalonate kinase-associated periodic fever syndrome, hyper-IgD syndrome) and many others, and show symptoms and signs of wide variations, we need to make an accurate diagnosis of them to prevent possible complications such as amyloidosis.

  19. Mediterranean spotted fever in Spain, 1997-2014: Epidemiological situation based on hospitalization records

    PubMed Central

    Fernandez-Martinez, Amalia; Gomez-Barroso, Diana; León, Inmaculada; Vieira, Carmen; Muro, Antonio; Benito, Agustín

    2017-01-01

    Introduction Mediterranean spotted fever (MSF) is a zoonotic disease caused by Rickettsia conorii. In Spain, deficiencies in the official reporting result in misreporting of this disease. This study aims to describe the clinical and temporal-spatial characteristics of MSF hospitalizations between 1997 and 2014. Materials and methods We performed a retrospective descriptive study using the Hospitalization Minimum Data Set (CMBD). All CMBD’s hospital discharges with ICD-9 CM code 082.1 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed. Results A total of 4,735 hospitalizations with MSF diagnosis were recorded during the study period, out of which 62.2% were male, mean age of 48. Diabetes mellitus, alcohol dependence syndrome, and chronic liver disease occurred in 10.8%, 2.4% and 2.8% hospitalizations, respectively. The median annual hospitalization rate showed a decreasing trend from a maximum of 12.9 in 1997 to a minimum rate of 3.1 in 2014. Most admissions occurred during the summer, showing a significant annual seasonal behavior. Important regional differences were found. Discussion Although MSF hospitalization rates have decreased considerably, it remains a public health problem due to its severity and economic impact. Therefore, it would be desirable to improve its oversight and surveillance. PMID:28355307

  20. The importance of serial measurements of cytokine levels for the evaluation of their role in pathogenesis in familial Mediterraean fever.

    PubMed

    Akcan, Y; Bayraktar, Y; Arslan, S; Van Thiel, D H; Zerrin, B C K; Yildiz, O

    2003-07-31

    Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent fever of unknown origin, renal amyloidosis, peritonitis, pleuritis and/or synovitis. There have been many studies to elucidate the etiopathogenesis of FMF. IL-6 is a cytokine that can induce the formation of serum amyloid A and C-reactive protein, both of which are important in development of amyloidosis. IL-6 was determined to be strongly associated in the etiopathogenesis of periodic fever in Chinese-pei dogs. The dogs with this syndrome experience periodic fever, arthritis, renal amyloidosis, a clinical picture very alike of human FMF. Here, we aimed to study mainly whether IL-6 had a similar etiopathogenetic role in human FMF as in Chinese-pei dogs syndrome. The median IL-6 blood levels were found to be higher in patients with acute (n=8) FMF attack (1.85 U/ml) compared to those (n=33) with asymptomatic ones (1.0 U/ml) (p=0.16). There are mainly two results: first; the study should be designed with a larger sample size of patients with acute attack in order to alleviate underestimation of significance, second; sampling time may give various results because of dynamic changes of cytokine levels during acute attack period.

  1. Comparison of Western immunoblotting and microimmunofluorescence for diagnosis of Mediterranean spotted fever.

    PubMed Central

    Teysseire, N; Raoult, D

    1992-01-01

    One-hundred serum samples from 41 patients suffering from Mediterranean spotted fever (MSF) were tested by microimmunofluorescence (MIF) and Western blot (WB; immunoblot). Immunoglobulin G (IgG), IgM, and IgA antibody-specific responses to the high-molecular-mass species-specific protein antigens (115 kDa and 135 kDa) of Rickettsia conorii, as well as to cross-reactive lipopolysaccharide (LPS) antigens, were observed. The WB assay detected IgM-type antibodies earlier than did the MIF assay. These antibodies were often directed against nonspecific LPS and may have a questionable positive predictive value. In addition, an IgG reaction to a 60-kDa protein was observed in four cases of malignant forms of MSF but was never observed in cases of mild forms. This reaction could be correlated with a marker of the severity of the development of MSF. From a previous MIF survey of blood donors, 9 negative, 11 IgG-positive, and 6 IgM-positive serum samples were selected for comparison by WB. Sera negative by MIF were also negative by WB. MIF IgG-positive sera showed a specific response to R. conorii in the WB assay, but the six serum samples from this seroepidemiological study positive for IgM by MIF were almost all negative by the WB assay. One was positive for IgM against the LPS but was considered a false positive. The WB is shown to provide a new tool for serodiagnosis. Images PMID:1537916

  2. Mediterranean spotted fever in Portugal: risk factors for fatal outcome in 105 hospitalized patients.

    PubMed

    de Sousa, Rita; Nóbrega, Sónia Dória; Bacellar, Fátima; Torgal, Jorge

    2003-06-01

    Mediterranean spotted fever (MSF) is the most important tick-borne disease in Portugal. It is a notifiable disease and during 1989-2000 the annual incidence rate in Portugal was 9.8/10(5) inhabitants. Although recognized as a benign acute disease and treated mainly with ambulatory procedures, some cases are severe and fatalities have increased in the last few years. In 1997, MSF mortality became more evident in Beja, a Portuguese southern district, with a case fatality rate of 32.3% in hospitalized patients. Analysis of 55 variables regarding epidemiologic, clinical, laboratory, and therapeutic data of fatal and nonfatal MSF cases were compared to identify risk factors in 105 patients hospitalized in Beja District Hospital, between 1994 and 1998. It was statistically significant that the patients dying in 1997 were younger than those in other years. The risk of dying is statistically significant in those who presented with diabetes, vomiting, dehydration, and uremia. The interval between the onset of symptoms to administration of anti-rickettsial therapy was the same for all patients. Therapy delay, reported by some authors to be associated with mortality of MSF, was not a risk factor in our study. The patients who died in 1997 died faster than those in other years. The variables studied could not explain the higher mortality rates observed in our study. Although one may speculate that the pathogenic strain of Israeli tick typhus, isolated in 1997, could be responsible for this increase of fatality rate, inherited patient factors might also be strongly associated with mortality.

  3. Fever

    MedlinePlus

    ... MoreBMI Calculator FeverA fever is defined as a temperature 1° or more above the normal 98.6°. Minor infections may cause mild or short-term temperature elevations. Temperatures of 103° and above are considered ...

  4. Fever

    MedlinePlus

    A fever is a body temperature that is higher than normal. It is not an illness. It is part of your body's defense against infection. Most bacteria ... cause infections do well at the body's normal temperature (98.6 F). A slight fever can make ...

  5. Not just a spring fever... Information and advice to help families with hay fever sufferers.

    PubMed

    Emberlin, Jean; Bartle, Janette; Bryant, Celia

    2011-01-01

    Hay fever is an allergy to pollen or spores presenting as an allergic inflammatory response in all mucous membranes of the upper airway. The UK has one of the highest rates (it's estimated one in four of us have hay fever) and symptoms are often trivialised, even though the socio-economic and health costs are huge. If left treated, for example, a hay fever sufferer risks developing asthma. Also paediatric allergists now consider the combination of eczema and hay fever to be a significant marker, indicating an atopic child's propensity to develop more serious allergic disease. Unfortunately childhood hay fever is often poorly treated, but a combination of sensible allergen avoidance measures and appropriate medication or treatments is usually sufficient to control symptoms.

  6. Prevalence of antibodies to spotted fever group rickettsiae in human beings and dogs from and endemic area of mediterranean spotted fever in Catalonia, Spain.

    PubMed

    Segura-Porta, F; Diestre-Ortin, G; Ortuño-Romero, A; Sanfeliu-Sala, I; Font-Creus, B; Muñoz-Espin, T; de Antonio, E M; Casal-Fábrega, J

    1998-06-01

    We assessed the prevalence of antibodies to spotted fever group rickettsiae in human beings and dogs by indirect immunofluorescence in the region of 'Vallés Occidental', Barcelona (Spain). In the group of 150 serum samples from patients without former history of Mediterranean spotted fever, 12 had antibodies to Rickettsia conori. The overall seroprevalence was 8% (95% confidence interval, 4.6% to 13.5%). There were no statistically significant differences between the mean ages of patients with positive and negative antibodies to R. conorii. However, seropositivity was significantly more common among patients living in semi-rural areas. In the group of 138 dog serum samples, 36 (26.1%) sera had antibodies to R. conorii. When the present results were compared with those obtained in a previous seroepidemiological survey carried out in the same geographical region in 1987, no significant differences were found. Therefore, although the epidemiological markers have dropped, this does not absolutely confirm the decrease of the presence of R. conorii in this area.

  7. Economic impact of dengue fever/dengue hemorrhagic fever in Thailand at the family and population levels.

    PubMed

    Clark, Danielle V; Mammen, Mammen P; Nisalak, Ananda; Puthimethee, Virat; Endy, Timothy P

    2005-06-01

    Dengue fever and dengue hemorrhagic fever constitute a substantial health burden on the population in Thailand. In this study, the impact of symptomatic dengue virus infection on the families of patients hospitalized at the Kamphaeng Phet Provincial Hospital with laboratory-confirmed dengue in 2001 was assessed, and the disability-adjusted life years (DALYs) lost for fatal and non-fatal cases of dengue were calculated using population level data for Thailand. When we accounted for the direct cost of hospitalization, indirect costs due to loss of productivity, and the average number of persons infected per family, we observed a financial loss of approximately US$61 per family, which is more than the average monthly income in Thailand. The DALYs were calculated using select results from a family level survey, and resulted in an estimated 427 DALYs/million population in 2001. This figure is of the same order of magnitude as the impact of several diseases currently given priority in southeast Asia, such as the tropical cluster (trypanosomiasis, Chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, and onchocerciasis), malaria, meningitis, and hepatitis. These results indicate that dengue prevention, control, and research should be considered equally important as that of diseases currently given priority.

  8. Perinatal risk factors for hay fever--a study among 2550 Finnish twin families.

    PubMed

    Räsänen, M; Kaprio, J; Laitinen, T; Winter, T; Koskenvuo, M; Laitinen, L A

    2001-10-01

    Previous studies have suggested that perinatal factors influence the risk for asthma but population studies on perinatal factors and risk for hay fever are few. We studied the effect of perinatal factors on the risk for hay fever among adolescent twins by a questionnaire study involving five consecutive nation-wide birth cohorts of 16-year-old twins and their parents. The risk for parent-reported, doctor-diagnosed hay fever in the adolescents associated with several perinatal characteristics was assessed with logistic regression analysis among individuals and by a discordant pair analysis. In the univariate analysis of the birth factors, the risk for hay fever increased with increasing birth weight (p for trend = 0.048, OR for those > or = 3000 g 1.35, 95% CI 0.91-2.02 compared to those < 2000 g) and gestational age (p for trend = 0.04, OR for those born after 40 weeks of gestation 2.24, 95% CI 1.03-4.86, compared to those born before 33 weeks of gestation) and was lower in those subjects hospitalised in the neonatal period (OR 0.74, 95% CI 0.58-0.93). Because of significant interactions between parental hay fever status and birth factors (ponderal index, p = 0.03 and maternal age p = 0.04), stratified analysis were performed. The positive association between birth weight and hay fever was most obvious among adolescents with no parental history of hay fever (p for trend = 0.03). Similar, though not significant, trends were found with other birth factors among these families, whereas no such trend was found among adolescents with parental hay fever, suggesting that gestational maturity increases the risk for hay fever in the absence of genetic predisposition. However, of the perinatal factors only neonatal hospitalisation (OR 0.75, 95% CI 0.59-0.96) remained a significant risk factor for the development of hay fever, when adjusted for non-perinatal factors.

  9. Current status of Crimean-Congo haemorrhagic fever in the World Health Organization Eastern Mediterranean Region: issues, challenges, and future directions.

    PubMed

    Al-Abri, Seif S; Abaidani, Idris Al; Fazlalipour, Mehdi; Mostafavi, Ehsan; Leblebicioglu, Hakan; Pshenichnaya, Natalia; Memish, Ziad A; Hewson, Roger; Eskild Petersen, Jorgen; Mala, Peter; Nhu Nguyen, Tran Minh; Rahman Malik, Mamunur; Formenty, Pierre; Jeffries, Rosanna Lucy

    2017-03-01

    Crimean-Congo haemorrhagic fever (CCHF) is the most widespread, tick-borne viral disease affecting humans. The disease is endemic in many regions, such as Africa, Asia, Eastern and Southern Europe, and Central Asia. Recently, the incidence of CCHF has increased rapidly in the countries of the World Health Organization Eastern Mediterranean Region (WHO EMR), with sporadic human cases and outbreaks of CCHF being reported from a number of countries in the region. Despite the rapidly growing incidence of the disease, there are currently no accurate data on the burden of the disease in the region due to the different surveillance systems used for CCHF in these countries. In an effort to increase our understanding of the epidemiology and risk factors for the transmission of the CCHF virus (CCHFV; a Nairovirus of the family Bunyaviridae) in the WHO EMR, and to identify the current knowledge gaps that are hindering effective control interventions, a sub-regional meeting was organized in Muscat, Oman, from December 7 to 9, 2015. This article summarizes the current knowledge of the disease in the region, identifies the knowledge gaps that present challenges for the prevention and control of CCHFV, and details a strategic framework for research and development activities that would be necessary to curb the ongoing and new threats posed by CCHFV.

  10. An outbreak of cerebrospinal fever in a 19th century British Mediterranean naval base.

    PubMed

    Savona-Ventura, C

    1994-10-01

    Epidemic Meningococcal meningitis first made its definite appearance in Europe in the beginning of the nineteenth century. The first recorded epidemic in the Maltese Islands, which straddled the sea-routes of the Mediterranean, occurred in the late nineteenth century. This paper describes a manuscript report prepared at the request of the Lieutenant Governor regarding this epidemic in the light of the contemporary knowledge about the infection.

  11. First External Quality Assessment of Molecular and Serological Detection of Rift Valley Fever in the Western Mediterranean Region.

    PubMed

    Monaco, Federica; Cosseddu, Gian Mario; Doumbia, Baba; Madani, Hafsa; El Mellouli, Fatiha; Jiménez-Clavero, Miguel Angel; Sghaier, Soufien; Marianneau, Philippe; Cetre-Sossah, Catherine; Polci, Andrea; Lacote, Sandra; Lakhdar, Magtouf; Fernandez-Pinero, Jovita; Sari Nassim, Chabane; Pinoni, Chiara; Capobianco Dondona, Andrea; Gallardo, Carmina; Bouzid, Taoufiq; Conte, Annamaria; Bortone, Grazia; Savini, Giovanni; Petrini, Antonio; Puech, Lilian

    2015-01-01

    Rift Valley fever (RVF) is a mosquito-borne viral zoonosis which affects humans and a wide range of domestic and wild ruminants. The large spread of RVF in Africa and its potential to emerge beyond its geographic range requires the development of surveillance strategies to promptly detect the disease outbreaks in order to implement efficient control measures, which could prevent the widespread of the virus to humans. The Animal Health Mediterranean Network (REMESA) linking some Northern African countries as Algeria, Egypt, Libya, Mauritania, Morocco, Tunisia with Southern European ones as France, Italy, Portugal and Spain aims at improving the animal health in the Western Mediterranean Region since 2009. In this context, a first assessment of the diagnostic capacities of the laboratories involved in the RVF surveillance was performed. The first proficiency testing (external quality assessment--EQA) for the detection of the viral genome and antibodies of RVF virus (RVFV) was carried out from October 2013 to February 2014. Ten laboratories participated from 6 different countries (4 from North Africa and 2 from Europe). Six laboratories participated in the ring trial for both viral RNA and antibodies detection methods, while four laboratories participated exclusively in the antibodies detection ring trial. For the EQA targeting the viral RNA detection methods 5 out of 6 laboratories reported 100% of correct results. One laboratory misidentified 2 positive samples as negative and 3 positive samples as doubtful indicating a need for corrective actions. For the EQA targeting IgG and IgM antibodies methods 9 out of the 10 laboratories reported 100% of correct results, whilst one laboratory reported all correct results except one false-positive. These two ring trials provide evidence that most of the participating laboratories are capable to detect RVF antibodies and viral RNA thus recognizing RVF infection in affected ruminants with the diagnostic methods currently

  12. First External Quality Assessment of Molecular and Serological Detection of Rift Valley Fever in the Western Mediterranean Region

    PubMed Central

    Monaco, Federica; Cosseddu, Gian Mario; Doumbia, Baba; Madani, Hafsa; El Mellouli, Fatiha; Jiménez-Clavero, Miguel Angel; Sghaier, Soufien; Marianneau, Philippe; Cetre-Sossah, Catherine; Polci, Andrea; Lacote, Sandra; Lakhdar, Magtouf; Fernandez-Pinero, Jovita; Sari Nassim, Chabane; Pinoni, Chiara; Capobianco Dondona, Andrea; Gallardo, Carmina; Bouzid, Taoufiq; Conte, Annamaria; Bortone, Grazia; Savini, Giovanni; Petrini, Antonio; Puech, Lilian

    2015-01-01

    Rift Valley fever (RVF) is a mosquito-borne viral zoonosis which affects humans and a wide range of domestic and wild ruminants. The large spread of RVF in Africa and its potential to emerge beyond its geographic range requires the development of surveillance strategies to promptly detect the disease outbreaks in order to implement efficient control measures, which could prevent the widespread of the virus to humans. The Animal Health Mediterranean Network (REMESA) linking some Northern African countries as Algeria, Egypt, Libya, Mauritania, Morocco, Tunisia with Southern European ones as France, Italy, Portugal and Spain aims at improving the animal health in the Western Mediterranean Region since 2009. In this context, a first assessment of the diagnostic capacities of the laboratories involved in the RVF surveillance was performed. The first proficiency testing (external quality assessment—EQA) for the detection of the viral genome and antibodies of RVF virus (RVFV) was carried out from October 2013 to February 2014. Ten laboratories participated from 6 different countries (4 from North Africa and 2 from Europe). Six laboratories participated in the ring trial for both viral RNA and antibodies detection methods, while four laboratories participated exclusively in the antibodies detection ring trial. For the EQA targeting the viral RNA detection methods 5 out of 6 laboratories reported 100% of correct results. One laboratory misidentified 2 positive samples as negative and 3 positive samples as doubtful indicating a need for corrective actions. For the EQA targeting IgG and IgM antibodies methods 9 out of the 10 laboratories reported 100% of correct results, whilst one laboratory reported all correct results except one false-positive. These two ring trials provide evidence that most of the participating laboratories are capable to detect RVF antibodies and viral RNA thus recognizing RVF infection in affected ruminants with the diagnostic methods currently

  13. Hemorrhagic Fevers

    MedlinePlus

    ... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

  14. 38-year-old woman with recurrent abdominal pain, but no fever

    PubMed Central

    Iwata, Kentaro; Toma, Tomoko; Yachie, Akihiro

    2012-01-01

    A 38-year-old woman presented with 2 days history of left-flank pain. She had similar episodes of abdominal pain as well as chest pain several times, but symptoms disappeared spontaneously. Each time she developed pain, there was no fever. After ruling out common causes of recurrent abdominal pain, familial Mediterranean fever (FMF) was considered as a potential diagnosis. Genetic tests revealed multiple heterozygote mutations, which may be associated with FMF. Patients with Mediterranean fever mutations may present with atypical presentations without fever, like in this case. Astute clinical suspicion is required to make an accurate diagnosis. PMID:22505824

  15. Mediterranean diet and familial dysmetabolism as factors influencing the development of acne.

    PubMed

    Skroza, Nevena; Tolino, Ersilia; Semyonov, Leda; Proietti, Ilaria; Bernardini, Nicoletta; Nicolucci, Francesca; La Viola, Giorgio; Del Prete, Giuseppe; Saulle, Rosella; Potenza, Concetta; La Torre, Giuseppe

    2012-07-01

    To investigate the effects of adherence to the Mediterranean diet and familial dysmetabolisms on acne development. A community-based case-control study was carried out in Italy enrolling cases as acneic outpatients of a dermatological ambulatory service and controls as clinically healthy acne-free subjects. Food consumption were evaluated with a validated food-frequency questionnaire, exploring the consumption of pasta, meat, cheese, fish, fruit, vegetables, and olive oil. Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean diet scale that incorporated the main characteristics of this diet. A logistic regression analysis estimated the variables who predicted the odds of being case, using those variables that at the univariate analysis yielded a p-value <0.25. Results are presented as odds ratio (OR) or adjusted OR (AOR). The study included 93 cases (36.6% males, median age 17 years) and 200 controls (32% males, median age 16 years). The Mediterranean diet score ≥6 revealed a protective effect towards acne (crude OR 0.22, 95% CI 0.08-0.64). Logistic regression analysis showed that familial hypercholesterolaemia, diabetes, and hypertension are strong risk factors for acne (AOR 8.79, 95% CI 1.67-46.22; 3.32, 95% CI 1.27-8.63; and 2.73, 95% CI 1.07-6.96, respectively), while the Mediterranean diet represents a protective factor (score ≥6, AOR 0.31, 95% CI 0.11-0.89). The odds for familial dysmetabolisms was higher in cases than in controls, confirming their role in determining or maintaining acne. Moreover, this is the first study demonstrating a protective role of the Mediterranean diet in the pathogenesis of acne.

  16. Spotted fever Rickettsia species in Hyalomma and Ixodes ticks infesting migratory birds in the European Mediterranean area

    PubMed Central

    2014-01-01

    Background A few billion birds migrate annually between their breeding grounds in Europe and their wintering grounds in Africa. Many bird species are tick-infested, and as a result of their innate migratory behavior, they contribute significantly to the geographic distribution of pathogens, including spotted fever rickettsiae. The aim of the present study was to characterize, in samples from two consecutive years, the potential role of migrant birds captured in Europe as disseminators of Rickettsia-infected ticks. Methods Ticks were collected from a total of 14,789 birds during their seasonal migration northwards in spring 2009 and 2010 at bird observatories on two Mediterranean islands: Capri and Antikythira. All ticks were subjected to RNA extraction followed by cDNA synthesis and individually assayed with a real-time PCR targeting the citrate synthase (gltA) gene. For species identification of Rickettsia, multiple genes were sequenced. Results Three hundred and ninety-eight (2.7%) of all captured birds were tick-infested; some birds carried more than one tick. A total number of 734 ticks were analysed of which 353 ± 1 (48%) were Rickettsia-positive; 96% were infected with Rickettsia aeschlimannii and 4% with Rickettsia africae or unidentified Rickettsia species. The predominant tick taxon, Hyalomma marginatum sensu lato constituted 90% (n = 658) of the ticks collected. The remaining ticks were Ixodes frontalis, Amblyomma sp., Haemaphysalis sp., Rhipicephalus sp. and unidentified ixodids. Most ticks were nymphs (66%) followed by larvae (27%) and adult female ticks (0.5%). The majority (65%) of ticks was engorged and nearly all ticks contained visible blood. Conclusions Migratory birds appear to have a great impact on the dissemination of Rickettsia-infected ticks, some of which may originate from distant locations. The potential ecological, medical and veterinary implications of such Rickettsia infections need further examination. PMID:25011617

  17. Phylogenomic analyses of a Mediterranean earthworm family (Annelida: Hormogastridae).

    PubMed

    Novo, Marta; Fernández, Rosa; Andrade, Sónia C S; Marchán, Daniel F; Cunha, Luis; Díaz Cosín, Darío J

    2016-01-01

    Earthworm taxonomy and evolutionary biology remain a challenge because of their scarce distinct morphological characters of taxonomic value, the morphological convergence by adaptation to the uniformity of the soil where they inhabit, and their high plasticity when challenged with stressful or new environmental conditions. Here we present a phylogenomic study of the family Hormogastridae, representing also the first piece of work of this type within earthworms. We included seven transcriptomes of the group representing the main lineages as previously-described, analysed in a final matrix that includes twelve earthworms and eleven outgroups. While there is a high degree of gene conflict in the generated trees that obscure some of the internal relationships, the origin of the family is well resolved: the hormogastrid Hemigastrodrilus appears as the most ancestral group, followed by the ailoscolecid Ailoscolex, therefore rejecting the validity of the family Ailoscolecidae. Our results place the origin of hormogastrids in Southern France, as previously hypothesised.

  18. Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case–control study

    PubMed Central

    Coşkun, Salih; Varol, Sefer; Özdemir, Hasan H; Çelik, Sercan Bulut; Balduz, Metin; Camkurt, Mehmet Akif; Çim, Abdullah; Arslan, Demet; Çevik, Mehmet Uğur

    2016-01-01

    Migraine pathogenesis involves a complex interaction between hormones, neurotransmitters, and inflammatory pathways, which also influence the migraine phenotype. The Mediterranean fever gene (MEFV) encodes the pyrin protein. The major role of pyrin appears to be in the regulation of inflammation activity and the processing of the cytokine pro-interleukin-1β, and this cytokine plays a part in migraine pathogenesis. This study included 220 migraine patients and 228 healthy controls. Eight common missense mutations of the MEFV gene, known as M694V, M694I, M680I, V726A, R761H, K695R, P369S, and E148Q, were genotyped using real-time polymerase chain reaction with 5′ nuclease assays, which include sequence specific primers, and probes with a reporter dye. When mutations were evaluated separately among the patient and control groups, only the heterozygote E148Q carrier was found to be significantly higher in the control group than in the patient group (P=0.029, odds ratio [95% confidence interval] =0.45 [0.21–0.94]). In addition, the frequency of the homozygote and the compound heterozygote genotype carrier was found to be significantly higher in patients (n=8, 3.6%) than in the control group (n=1, 0.4%) (P=0.016, odds ratio [95% confidence interval] =8.57 [1.06–69.07]). However, there was no statistically significant difference in the allele frequencies of MEFV mutations between the patients and the healthy control group (P=0.964). In conclusion, the results of the present study suggest that biallelic mutations in the MEFV gene could be associated with a risk of migraine in the Turkish population. Moreover, MEFV mutations could be related to increased frequency and short durations of migraine attacks (P=0.043 and P=0.021, respectively). Future studies in larger groups and expression analysis of MEFV are required to clarify the role of the MEFV gene in migraine susceptibility. PMID:27621632

  19. Hyperimmunoglobulinaemia D and periodic fever: a new syndrome.

    PubMed

    van der Meer, J W; Vossen, J M; Radl, J; van Nieuwkoop, J A; Meyer, C J; Lobatto, S; van Furth, R

    1984-05-19

    Six patients of Dutch ancestry with a long history of recurrent attacks of fever of unknown cause were found to have a high serum IgD level and a large number of plasma cells with cytoplasmic IgD in the bone marrow. Because the clinical picture in some ways resembled that of familial Mediterranean fever (FMF), sera of patients with FMF were also investigated; only one of eight such patients had a raised serum IgD.

  20. Family Cluster Analysis of Severe Fever with Thrombocytopenia Syndrome Virus Infection in Korea

    PubMed Central

    Yoo, Jeong Rae; Heo, Sang Taek; Park, Dahee; Kim, Hyemin; Fukuma, Aiko; Fukushi, Shuetsu; Shimojima, Masayuki; Lee, Keun Hwa

    2016-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is tick-borne viral disease that was first suspected in China in 2009. The causative virus (SFTSV) was isolated in 2009 and reported in 2011, and SFTSV expanded its geographic distribution in 2012–2013, from China to South Korea and Japan. Most SFTSV infections occur through Haemaphysalis longicornis. However, SFTSV infection can also occur between family members, and nosocomial transmission of SFTSV is also possible through close contact with a patient. In this study, we first analyzed clinical, epidemiological, and laboratory data for SFTS patients and family members of an index patient in Korea. The S segment of SFTSV was amplified from the sera of three patients, and the S segment of SFTSV and IgG specific to SFTSV were detected in the serum from one family member; although this individual had no history of exposure to H. longicornis, she frequently had close contact with the index patient. In Korea, SFTSV infection among family members does not have to be reported, and we suggest that person-to-person transmission of SFTSV among family members is possible in Korea. PMID:27928083

  1. [Periodic fever in children: keep in mind the PFAPA syndrome].

    PubMed

    Hofer, M; Rossetti, G

    2008-02-27

    The autoinflammatory diseases should be considered in the differential diagnosis of recurrent fever in childhood. These diseases are characterized by inflammatory episodes without an evident cause. Some of these diseases, like the Familial Mediterranean Fever, have a genetic origin and need a chronic treatment to avoid severe complications on the long term. PFAPA syndrome is the most frequent cause of recurrent fever and is diagnosed based on unspecific criteria. The treatment is still controversial. One dose of Prednisone is able to interrupt the flare and tonsillectomy may induce a remission in the majority of the cases.

  2. The prevalence of Familial Mediterranean Fever common gene mutations in patients with simple febrile seizures.

    PubMed

    Ozen, F; Kocak, N; Kelekci, S; Yildirim, I H; Hacimuto, G; Ozdemir, O

    2014-01-01

    Febrile seizures (FS) represent the most common form of childhood seizures that occurs in 2-5 % of the children younger than 6 years. There have been many recent reports on the molecular genetic and pathogenesis of FC. It has been recognized that there is significant genetic component for susceptibility of FC with different reported mutation. FEB1, FEB2, FEB4, SCNA1, SCNA2, GABRG2 and IL-1β are related to with febrile convulsions (FCs). Interleukin 1β (IL-1β) is a cytokine that contributes to febrile inflammatory responses. There are conflicting results on increasing this cytokine in serum during FC. The determine the association between mutations of MEFV gene product pyrine and febrile seizures. The study was carried out on 104 children that were diagnosed as FS and 96 healthy children. MEFV gene mutations were detected and analyzed with PyroMark Q24. PCR was performed using the PyroMark PCR Kit and pyrosequencing reaction was conducted on instrument instructions. M694V is the most common mutation in our patient group and we found a significant association between MEFV gene mutations and FSs. Of 104 patients, 68 were heterozygotes for any mutation and 10 patients were compound. 17.7% of control group were heterozygotes for any studied mutation.Statistical analyses showed that there was strongly significant statistical difference between results obtained from FS and control group (X = 46.20, p < 0.0001). MEFV gene mutations, especially M694V mutation, are positively associated with FSs.

  3. The frequency of familial mediterranean Fever related amyloidosis in renal waiting list for transplantation.

    PubMed

    Keles, Mustafa; Eyerci, Nilnur; Uyanik, Abdullah; Aydinli, Bulent; Sahin, Gonul Zisan; Cetinkaya, Ramazan; Pirim, Ibrahim; Polat, Kamil Yalcin

    2010-04-01

    Our goal is to investigate the distribution of MEFV mutations in patients with renal amyloidosis who are in renal transplant waiting list which is prepared for transplantation. FMF was diagnosed in 25 of the 297 patients between the years 2004 and 2008, who were involved in the study (15 male, 10 female; age 34±7.8). 5 out of 25 patients were transplanted, remaining were waiting for Tx. Biopsy results were amyloidosis and taken from renal (n:16), rectal (n:8) and duodenal (1).All of them were carrier of mutations in both pyrin alleles.The primer cause of chronic renal failure in our group was secondary AA amyloidosis. DNA was isolated from 25 whole blood samples. The NanoChip Molecular Biology Workstation (Nanogen) uses electronic microarrays for mutation detection. Exon 2,3,5 and 10 of pyrin gene genotypes were identified in the NanoChip. Genetic analysis of the patients demonstrated that each subject carries either homozygote or compound heterozygote mutations of the gene. The most common mutations were M694V, V726A, E148Q and M680I. The clinic manifestation and complain of our patients were febrile and painful attacks such as in the abdomen, chest and joints due to inflammation of the peritoneum, pleura and synovial membrane. The major problem in FMF is the occurrence of amyloidosis that primarily affects the kidneys causing proteinuria and renal failure. Dialysis and renal transplantation can be treatment, but it is important to diagnose FMF at earliest stages. The percentage of FMF patients in our waiting list was 8.4%. Moreover, in our region FMF incidence is highly frequent, so FMF should be chased by genetically so as to prevent chronic renal failure due to amyloidosis.

  4. The Frequency of Familial Mediterranean Fever Related Amyloidosis in Renal Waiting List for Transplantation

    PubMed Central

    Keles, Mustafa; Eyerci, Nilnur; Uyanik, Abdullah; Aydinli, Bulent; Sahin, Gonul Zisan; Cetinkaya, Ramazan; Pirim, Ibrahim; Polat, Kamil Yalcin

    2010-01-01

    Objective: Our goal is to investigate the distribution of MEFV mutations in patients with renal amyloidosis who are in renal transplant waiting list which is prepared for transplantation. Materials and Methods: FMF was diagnosed in 25 of the 297 patients between the years 2004 and 2008, who were involved in the study (15 male, 10 female; age 34±7.8). 5 out of 25 patients were transplanted, remaining were waiting for Tx. Biopsy results were amyloidosis and taken from renal (n:16), rectal (n:8) and duodenal (1).All of them were carrier of mutations in both pyrin alleles.The primer cause of chronic renal failure in our group was secondary AA amyloidosis. DNA was isolated from 25 whole blood samples. The NanoChip Molecular Biology Workstation (Nanogen) uses electronic microarrays for mutation detection. Exon 2,3,5 and 10 of pyrin gene genotypes were identified in the NanoChip. Results: Genetic analysis of the patients demonstrated that each subject carries either homozygote or compound heterozygote mutations of the gene. The most common mutations were M694V, V726A, E148Q and M680I. Conclusions: The clinic manifestation and complain of our patients were febrile and painful attacks such as in the abdomen, chest and joints due to inflammation of the peritoneum, pleura and synovial membrane. The major problem in FMF is the occurrence of amyloidosis that primarily affects the kidneys causing proteinuria and renal failure. Dialysis and renal transplantation can be treatment, but it is important to diagnose FMF at earliest stages. The percentage of FMF patients in our waiting list was 8.4%. Moreover, in our region FMF incidence is highly frequent, so FMF should be chased by genetically so as to prevent chronic renal failure due to amyloidosis. PMID:25610112

  5. Serum Bone Markers Levels and Bone Mineral Density in Familial Mediterranean Fever

    PubMed Central

    Aydın, Teoman; Taspınar, Ozgur; Akbal, Yildiz; Peru, Celaleddin; Guler, Mustafa; Uysal, Omer; Yakıcıer, M. Cengiz

    2014-01-01

    [Purpose] The aim of this study was to measure bone mineral density, serum and urinary bone turnover parameters, and to evaluate the influence of demographic and genetic factors on these parameters in FMF patients. [Subjects and Methods] Twenty-seven attack-free patients who were diagnosed with FMF (in accordance with Tel Hashomer criteria) were recruited at outpatient rheumatology clinics. We investigated whether there were any differences between the FMF patients and a control group in terms of lumbar and femur bone mineral density (BMD), standard deviation scores (Z scores and T scores) and bone markers. [Results] In terms of the median values of lumbar BMD (p = 0.21), lumbar T (p = 0.098) and Z (p = 0.109) scores, femoral neck BMD, femoral T and Z scores and total femur BMD, T (p = 0.788) and Z scores, there were no significant differences. [Conclusion] In our study, no statistically significant differences were found between FMF patients and a control group in terms of osteoporosis. The 25-OH vitamin D was found to be significantly lower in FMF patients than in the control group. PMID:25276036

  6. Family History in Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.

    PubMed

    Manthiram, Kalpana; Nesbitt, Emily; Morgan, Thomas; Edwards, Kathryn M

    2016-09-01

    The goal of this study was to describe family history and inheritance patterns in patients with periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. We performed a case-control study to compare the family histories of patients with PFAPA recruited from Vanderbilt University Medical Center and matched healthy control subjects from a pediatric primary care practice in Nashville, Tennessee, by using a structured questionnaire. Characteristics of paired case subjects, control subjects, and their family members were compared by using McNemar's test and Wilcoxon signed-rank tests. Eighty PFAPA index case subjects and 80 control subjects were recruited. Eighteen PFAPA case subjects (23%) had ≥1 family member with PFAPA. Parents of PFAPA index case subjects were more likely to have recurrent pharyngitis (36% vs 16%; P < .001) and recurrent aphthous stomatitis (46% vs 28%; P = .002) compared with parents of control subjects. Siblings of case subjects had a higher prevalence of PFAPA (10% vs 2%; P = .04), recurrent pharyngitis (24% vs 10%; P = .03), and recurrent aphthous stomatitis (27% vs 7%; P = .003) compared with siblings of control subjects. A portion of PFAPA case subjects seems to be familial, implying an inherited genetic predisposition to the disorder and/or shared environmental exposures. First-degree relatives (parents and siblings) of patients with PFAPA have a higher prevalence of recurrent pharyngitis and aphthous stomatitis than relatives of control subjects, which suggests that these disorders represent reduced penetrance phenotypes of PFAPA. Further characterization of the genetics and inflammatory profiles of these patients and their relatives is warranted. Copyright © 2016 by the American Academy of Pediatrics.

  7. [Autoinflammatory syndromes/fever syndromes].

    PubMed

    Schedel, J; Bach, B; Kümmerle-Deschner, J B; Kötter, I

    2011-05-01

    Hereditary periodic (fever) syndromes, also called autoinflammatory syndromes, are characterized by relapsing fever and additional manifestations such as skin rashes, mucosal manifestations, or joint symptoms. Some of these disorders present with organ involvement and serological signs of inflammation without fever. There is a strong serological inflammatory response with an elevation of serum amyloid A (SAA), resulting in an increased risk of secondary amyloidosis. There are monogenic disorders (familial mediterranean fever (FMF), hyper-IgD-syndrome (HIDS), cryopyrin-associated periodic syndromes (CAPS), "pyogenic arthritis, acne, pyoderma gangrenosum" (PAPA), and "pediatric granulomatous arthritis (PGA) where mutations in genes have been described, which in part by influencing the function of the inflammasome, in part by other means, lead to the induction of the production of IL-1β. In "early-onset of enterocolitis (IBD)", a functional IL-10 receptor is lacking. Therapeutically, above all, the IL-1 receptor antagonist anakinra is used. In case of TRAPS and PGA, TNF-antagonists (etanercept) may also be used; in FMF colchicine is first choice. As additional possible autoinflammatory syndromes, PFAPA syndrome (periodic fever with aphthous stomatitis, pharyngitis and adenitis), Schnitzler syndrome, Still's disease of adult and pediatric onset, Behçet disease, gout, chronic recurrent multifocal osteomyelitis (CRMO) and Crohn's disease also are mentioned.

  8. Balibalosides, an Original Family of Glucosylated Sesterterpenes Produced by the Mediterranean Sponge Oscarella balibaloi

    PubMed Central

    Audoin, Coralie; Bonhomme, Dominique; Ivanisevic, Julijana; de la Cruz, Mercedes; Cautain, Bastien; Monteiro, Maria Cândida; Reyes, Fernando; Rios, Laurent; Perez, Thierry; Thomas, Olivier P.

    2013-01-01

    The chemical investigation of the recently described Mediterranean Homoscleromorpha sponge Oscarella balibaloi revealed an original family of five closely related glucosylated sesterterpenes 1–4, named balibalosides. Their structure elucidation was mainly inferred from NMR and HRMS data analyses. Balibalosides differ by the pattern of acetyl substitutions on the three sugar residues linked to the same aglycone sesterterpenoid core. From a biosynthetic perspective, these compounds may represent intermediates in the pathways leading to more complex sesterterpenes frequently found in Dictyoceratida, a sponge Order belonging to Demospongiae, a clade which is phylogenetically distinct from the Homoscleromorpha. While steroid and triterpenoid saponins were already well known from marine sponges, balibalosides are the first examples of glycosilated sesterterpenes. PMID:23648552

  9. Overt and occult rheumatic diseases: the child with chronic fever.

    PubMed

    Frenkel, Joost; Kuis, Wietse

    2002-07-01

    Identification of the genes involved in hereditary periodic fever syndromes has led to the recognition of a new pathophysiological category, the autoinflammatory disorders. The main non-hereditary autoinflammatory disease in childhood is systemic juvenile idiopathic arthritis (sJIA), others being the chronic infantile neurological cutaneous arthropathy (CINCA) syndrome and the periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. Familial Mediterranean fever (FMF) has been traced to mutations in the MEFV gene. Mutations in the MVK gene, encoding the enzyme mevalonate kinase, cause the hyper-IgD periodic fever syndrome (HIDS). The tumour necrosis factor(TNF)-receptor-associated periodic syndromes (TRAPS) have been linked to mutations in theTNFRSF1A gene, encoding a TNF-alpha receptor, and the CIAS1 gene is mutated in familial cold autoinflammatory syndrome. We discuss how this knowledge has influenced diagnosis and treatment of these rare genetic disorders and how it might change our approach to the more common rheumatic diseases.

  10. Life history of the deep-sea cephalopod family Histioteuthidae in the western Mediterranean

    NASA Astrophysics Data System (ADS)

    Quetglas, Antoni; de Mesa, Aina; Ordines, Francesc; Grau, Amàlia

    2010-08-01

    The life cycle of the two species of the deep-sea family Histioteuthidae inhabiting the Mediterranean Sea ( Histioteuthis reversa and Histioteuthis bonnellii) was studied from monthly samples taken throughout the year during daytime hours by bottom trawl gears. A small sample of individuals found floating dead on the sea surface was also analyzed. Both species were caught exclusively on the upper slope at depths greater than 300 m. Their frequency of occurrence increased with depth and showed two different peaks, at 500-600 m and 600-700 m depth in H. bonnellii and H. reversa, respectively, which might indicate spatial segregation. Maturity stages were assigned using macroscopic determination and confirmed with histological analyses. Although mature males were caught all year round, no mature females were found, which suggests that their sexual maturation in the western Mediterranean takes place deeper than the maximum depth sampled (800 m). In fact, the increase in mean squid size with increasing depth in H. reversa indicates an ontogenetic migration to deeper waters. The individuals of both species found floating dead on the sea surface were spent females which had a relatively large cluster of small atresic eggs and a small number of remaining mature eggs scattered in the ovary and mantle cavity. The sizes of these females were clearly larger than the largest individuals caught with bottom trawls. A total of 12 and 7 different types of prey, belonging to three major taxonomic groups (crustaceans, osteichthyes and cephalopods), were identified in the stomach contents of H. reversa and H. bonnellii, respectively. In both species fishes were by far the main prey followed by crustaceans, whereas cephalopods were found only occasionally. The preys identified, mainly myctophids and natantian crustaceans, indicate that both histioteuthids base their diet on pelagic nictemeral migrators.

  11. Viral Hemorrhagic Fevers

    MedlinePlus

    ... The CDC Cancel Submit Search The CDC Viral Hemorrhagic Fevers (VHFs) Note: Javascript is disabled or is not ... please visit this page: About CDC.gov . Viral Hemorrhagic Fevers (VHFs) Virus Families Arenaviruses Old World/New World ...

  12. Periodic Fever: a review on clinical, management and guideline for Iranian patients - part I.

    PubMed

    Ahmadinejad, Zahra; Mansori, Sedigeh; Ziaee, Vahid; Alijani, Neda; Aghighi, Yahya; Parvaneh, Nima; Mordinejad, Mohammad-Hassan

    2014-02-01

    Periodic fever syndromes are a group of diseases characterized by episodes of fever with healthy intervals between febrile episodes. The first manifestation of these disorders are present in childhood and adolescence, but infrequently it may be presented in young and middle ages. Genetic base has been known for all types of periodic fever syndromes except periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). Common periodic fever disorders are Familial Mediterranean fever (FMF) and PFAPA. In each patient with periodic fever, acquired infection with chronic and periodic nature should be ruled out. It depends on epidemiology of infectious diseases. Some of them such as Familial Mediterranean fever and PFAPA are common in Iran. In Iran and other Middle East countries, brucellosis, malaria and infectious mononucleosis should be considered in differential diagnosis of periodic fever disorders especially with fever and arthritis manifestation. In children, urinary tract infection may be presented as periodic disorder, urine analysis and culture is necessary in each child with periodic symptoms. Some malignancies such as leukemia and tumoral lesions should be excluded in patients with periodic syndrome and weight loss in any age. After excluding infection, malignancy and cyclic neutropenia, FMF and PFAPA are the most common periodic fever disorders. Similar to other countries, Hyper IgD, Chronic Infantile Neurologic Cutaneous and Articular, TRAPS and other auto-inflammatory syndromes are rare causes of periodic fever in Iranian system registry. In part 1 of this paper we reviewed the prevalence of FMF and PFAPA in Iran. In part 2, some uncommon auto-inflammatory disorders such as TRAPS, Hyper IgD sydrome and cryopyrin associated periodic syndromes will be reviewed.

  13. Periodic Fever: A Review on Clinical, Management and Guideline for Iranian Patients - Part I

    PubMed Central

    Ahmadinejad, Zahra; Mansori, Sedigeh; Ziaee, Vahid; Alijani, Neda; Aghighi, Yahya; Parvaneh, Nima; Mordinejad, Mohammad-Hassan

    2014-01-01

    Periodic fever syndromes are a group of diseases characterized by episodes of fever with healthy intervals between febrile episodes. The first manifestation of these disorders are present in childhood and adolescence, but infrequently it may be presented in young and middle ages. Genetic base has been known for all types of periodic fever syndromes except periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). Common periodic fever disorders are Familial Mediterranean fever (FMF) and PFAPA. In each patient with periodic fever, acquired infection with chronic and periodic nature should be ruled out. It depends on epidemiology of infectious diseases. Some of them such as Familial Mediterranean fever and PFAPA are common in Iran. In Iran and other Middle East countries, brucellosis, malaria and infectious mononucleosis should be considered in differential diagnosis of periodic fever disorders especially with fever and arthritis manifestation. In children, urinary tract infection may be presented as periodic disorder, urine analysis and culture is necessary in each child with periodic symptoms. Some malignancies such as leukemia and tumoral lesions should be excluded in patients with periodic syndrome and weight loss in any age. After excluding infection, malignancy and cyclic neutropenia, FMF and PFAPA are the most common periodic fever disorders. Similar to other countries, Hyper IgD, Chronic Infantile Neurologic Cutaneous and Articular, TRAPS and other auto-inflammatory syndromes are rare causes of periodic fever in Iranian system registry. In part 1 of this paper we reviewed the prevalence of FMF and PFAPA in Iran. In part 2, some uncommon auto-inflammatory disorders such as TRAPS, Hyper IgD sydrome and cryopyrin associated periodic syndromes will be reviewed. PMID:25793039

  14. Autoinflammatory Diseases with Periodic Fevers.

    PubMed

    Sag, Erdal; Bilginer, Yelda; Ozen, Seza

    2017-07-01

    One purpose of this review was to raise awareness for the new autoinflammatory syndromes. These diseases are increasingly recognized and are in the differential diagnosis of many disease states. We also aimed to review the latest recommendations for the diagnosis, management, and treatment of these patients. Familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), and hyperimmunoglobulinemia D and periodic fever syndrome/mevalonate kinase deficiency (HIDS/MVKD) are the more common autoinflammatory diseases that are characterized by periodic fevers and attacks of inflammation. Recently much collaborative work has been done to understand the characteristics of these patients and to develop recommendations to guide the physicians in the care of these patients. These recent recommendations will be summarized for all four diseases. FMF is the most common periodic fever disease. We need to further understand the pathogenesis and the role of single mutations in the disease. Recently, the management and treatment of the disease have been nicely reviewed. CAPS is another interesting disease associated with severe complications. Anti-interleukin-1 (anti-IL-1) treatment provides cure for these patients. TRAPS is characterized by the longest delay in diagnosis; thus, both pediatricians and internists should be aware of the characteristic features and the follow-up of these patients. HIDS/MVKD is another autoinflammatory diseases characterized with fever attacks. The spectrum of disease manifestation is rather large in this disease, and we need further research on biomarkers for the optimal management of these patients.

  15. African swine fever virus multigene family 360 and 530 genes affect host interferon response.

    PubMed

    Afonso, C L; Piccone, M E; Zaffuto, K M; Neilan, J; Kutish, G F; Lu, Z; Balinsky, C A; Gibb, T R; Bean, T J; Zsak, L; Rock, D L

    2004-02-01

    African swine fever virus (ASFV) multigene family 360 and 530 (MGF360/530) genes affect viral growth in macrophage cell cultures and virulence in pigs (L. Zsak, Z. Lu, T. G. Burrage, J. G. Neilan, G. F. Kutish, D. M. Moore, and D. L. Rock, J. Virol. 75:3066-3076, 2001). The mechanism by which these novel genes affect virus-host interactions is unknown. To define MGF360/530 gene function, we compared macrophage transcriptional responses following infection with parental ASFV (Pr4) and an MGF360/530 deletion mutant (Pr4 Delta 35). A swine cDNA microarray containing 7,712 macrophage cDNA clones was used to compare the transcriptional profiles of swine macrophages infected with Pr4 and Pr4 Delta 35 at 3 and 6 h postinfection (hpi). While at 3 hpi most (7,564) of the genes had similar expression levels in cells infected with either virus, 38 genes had significantly increased (>2.0-fold, P < 0.05) mRNA levels in Pr4 Delta 35-infected macrophages. Similar up-regulation of these genes was observed at 6 hpi. Viral infection was required for this induced transcriptional response. Most Pr Delta 35 up-regulated genes were part of a type I interferon (IFN) response or were genes that are normally induced by double-stranded RNA and/or viral infection. These included monocyte chemoattractant protein, transmembrane protein 3, tetratricopeptide repeat protein 1, a ubiquitin-like 17-kDa protein, ubiquitin-specific protease ISG43, an RNA helicase DEAD box protein, GTP-binding MX protein, the cytokine IP-10, and the PKR activator PACT. Differential expression of IFN early-response genes in Pr4 Delta 35 relative to Pr4 was confirmed by Northern blot analysis and real-time PCR. Analysis of IFN-alpha mRNA and secreted IFN-alpha levels at 3, 8, and 24 hpi revealed undetectable IFN-alpha in mock- and Pr4-infected macrophages but significant IFN-alpha levels at 24 hpi in Pr4 Delta 35-infected macrophages. The absence of IFN-alpha in Pr4-infected macrophages suggests that MGF360/530 genes

  16. A common pathway in periodic fever syndromes.

    PubMed

    McDermott, Michael F

    2004-09-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease due to mutations in pyrin, which normally inhibits pro-interleukin-1beta (IL-1beta) cytokine processing to the active form. A novel role for pyrin has been proposed by Shoham et al., who studied patients with an autosomal dominant disease called pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. They demonstrated an interaction between pyrin and proline serine threonine phosphatase-interacting protein 1 (PSTPIP1), the protein involved in PAPA, and thus revealed a biochemical pathway common to both FMF and PAPA.

  17. Differentiating PFAPA syndrome from monogenic periodic fevers.

    PubMed

    Gattorno, Marco; Caorsi, Roberta; Meini, Antonella; Cattalini, Marco; Federici, Silvia; Zulian, Francesco; Cortis, Elisabetta; Calcagno, Giuseppina; Tommasini, Alberto; Consolini, Rita; Simonini, Gabriele; Pelagatti, Maria Antonietta; Baldi, Maurizia; Ceccherini, Isabella; Plebani, Alessandro; Frenkel, Joost; Sormani, Maria Pia; Martini, Alberto

    2009-10-01

    To analyze whether there were clinical differences between genetically positive and negative patients fulfilling periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome criteria and to test the accuracy of the Gaslini diagnostic score for identifying patients with PFAPA syndrome with higher probabilities of carrying relevant mutations in genes associated with periodic fevers. Complete clinical and genetic information was available for 393 children with periodic fever; 82 had positive genetic test results, 75 had incomplete genetic test results, and 236 had negative results for MVK, TNFRSF1A, and MEFV mutations. Current diagnostic criteria for PFAPA syndrome were applied. Of 393 children, 210 satisfied PFAPA syndrome criteria; 43 carried diagnostic mutations (mevalonate kinase deficiency: n = 33; tumor necrosis factor receptor-associated periodic syndrome: n = 3; familial Mediterranean fever: n = 7), 37 displayed low-penetrance mutations or incomplete genotypes, and 130 demonstrated negative genetic testing results. Genetically positive patients had higher frequencies of abdominal pain and diarrhea (P < .001), vomiting (P = .006), and cutaneous rash and arthralgia (P = .01). Genetically negative patients had a higher frequency of exudative pharyngitis (P = .010). Genetically undetermined patients showed the same pattern of symptom frequency as genetically negative patients. The Gaslini diagnostic score was able to identify 91% of genetically positive patients correctly, with a global accuracy of 66%. The Gaslini diagnostic score represents a useful tool to identify patients meeting PFAPA syndrome criteria and at low risk of carrying relevant mutations in genes associated with periodic fevers.

  18. Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) Syndrome in Iranian Children First Report of Iranian Periodic Fever and Autoinflammatory Registry (IPFAIR)

    PubMed Central

    Mehregan, Fatemeh Fereshteh; Ziaee, Vahid; Ahmadinejad, Zahra; Tahghighi, Fatemeh; Sabouni, Farah; Moradinejad, Mohamad-Hassan

    2014-01-01

    Objective: The periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a nonhereditary idiopathic febrile syndrome belonging to the group of autoinflammatory diseases. No longtime sequel was reported in this disease. Early diagnosis can lead physicians to treatment of this disorder with a short course steroid application and provide satisfaction of the patient’s family. Methods: This study is a prospective review of patients diagnosed with PFAPA syndrome who were registered in Iranian Periodic Fever and Autoinflammatory Registry (IPFAIR) through periodic fever clinic in the Children's Medical Center, Pediatric Center of Excellence in Tehran, Iran from January 2013 to March 2014. Findings: One hundred thirty patients were registered in our databases. Twenty-one (16.1%) patients including 15 males and 6 females had PFAPA. Normal growth was seen in all patients. The median age at onset was 18 months. The mean duration of fever was 4 days and the mean duration of intervals between fever episodes 21 days. Along with fever, all patients had characteristic symptoms. All patients were asymptomatic between fever episodes. Steroid was used in all patients and causing immediate reduction by 84.61%. Two patients received both steroid and colchicine because of their clinical feature and positive laboratory tests for PFAPA and familial Mediterranean fever. No patient received biological therapy or a tonsillectomy. Conclusion: The long diagnostic delay of PFAPA gives cause to concern indicating a need for greater awareness of the disease so that the diagnosis may be made timely. PMID:25793068

  19. Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) Syndrome in Iranian Children First Report of Iranian Periodic Fever and Autoinflammatory Registry (IPFAIR).

    PubMed

    Mehregan, Fatemeh Fereshteh; Ziaee, Vahid; Ahmadinejad, Zahra; Tahghighi, Fatemeh; Sabouni, Farah; Moradinejad, Mohamad-Hassan

    2014-10-01

    The periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a nonhereditary idiopathic febrile syndrome belonging to the group of autoinflammatory diseases. No longtime sequel was reported in this disease. Early diagnosis can lead physicians to treatment of this disorder with a short course steroid application and provide satisfaction of the patient's family. This study is a prospective review of patients diagnosed with PFAPA syndrome who were registered in Iranian Periodic Fever and Autoinflammatory Registry (IPFAIR) through periodic fever clinic in the Children's Medical Center, Pediatric Center of Excellence in Tehran, Iran from January 2013 to March 2014. One hundred thirty patients were registered in our databases. Twenty-one (16.1%) patients including 15 males and 6 females had PFAPA. Normal growth was seen in all patients. The median age at onset was 18 months. The mean duration of fever was 4 days and the mean duration of intervals between fever episodes 21 days. Along with fever, all patients had characteristic symptoms. All patients were asymptomatic between fever episodes. Steroid was used in all patients and causing immediate reduction by 84.61%. Two patients received both steroid and colchicine because of their clinical feature and positive laboratory tests for PFAPA and familial Mediterranean fever. No patient received biological therapy or a tonsillectomy. The long diagnostic delay of PFAPA gives cause to concern indicating a need for greater awareness of the disease so that the diagnosis may be made timely.

  20. [Hyperimmunoglobulinemia D and periodic fever syndrome].

    PubMed

    Agbo-kpati, K-P; Condor, R; Hollenberg, H; Chalvon Demersay, A; Cuisset, L; Quartier, P

    2014-07-01

    We report the cases of two sisters born of parents who were first-degree cousins, who started recurrent fever with lymph node and digestive tract involvement at the age of 2 years. There was no mutation of the familial Mediterranean fever gene and a diagnosis of partial mevalonate kinase (MVK) deficiency was made. However, immunoglobulin (Ig) D and A levels were normal. Elevated mevalonic acid in the patients' urine during an episode and MVK gene analysis provided the diagnosis. Clinical remission was obtained under anti-TNF-alpha treatment with etanercept. These observations and those of several previously reported patients, particularly in French and Dutch series, illustrate the importance of considering the diagnosis in a child with early-onset auto-inflammatory syndrome even in the absence of hyper-IgD or -IgA.

  1. Mediterranean diet and breast density in the Minnesota Breast Cancer Family Study

    PubMed Central

    Tseng, Marilyn; Sellers, Thomas A.; Vierkant, Robert A.; Kushi, Lawrence H.; Vachon, Celine M.

    2008-01-01

    Mediterranean populations’ lower breast cancer incidence has been attributed to a traditional Mediterranean diet, but few studies have quantified Mediterranean dietary pattern intake in relation to breast cancer. We examined the association of a Mediterranean diet scale (MDS) with mammographic breast density as a surrogate marker for breast cancer risk. Participants completed a dietary questionnaire and provided screening mammograms for breast density assessment using a computer-assisted method. Among 1,286 women, MDS was not clearly associated with percent density in multivariate linear regression analyses. Because of previous work suggesting dietary effects limited to smokers, we conducted stratified analyses and found MDS and percent density to be significantly, inversely associated among current smokers (β=−1.68, p=0.002), but not among non-smokers (β=−0.08, p=0.72) (p for interaction = 0.008). Our results confirm a previous suggestion that selected dietary patterns may be protective primarily in the presence of pro-carcinogenic compounds such as those found in tobacco smoke. PMID:19005969

  2. Periodic Fever: A Review on Clinical, Management and Guideline for Iranian Patients - Part II

    PubMed Central

    Ahmadinejad, Zahra; Mansouri, Sedigeh; Ziaee, Vahid; Aghighi, Yahya; Moradinejad, Mohammad-Hassan; Fereshteh-Mehregan, Fatemeh

    2014-01-01

    Periodic fever syndromes are a group of diseases characterized by episodes of fever with healthy intervals between febrile episodes. In the first part of this paper, we presented a guideline for approaching patients with periodic fever and reviewed two common disorders with periodic fever in Iranian patients including familial Mediterranean fever (FMF) and periodic fever syndromes except for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). In this part, we review other autoinflammatory disorders including hyper IgD, tumor necrosis factor receptor–associated periodic syndrome (TRAPS), cryopyrin associated periodic syndromes, autoinflammatory bone disorders and some other rare autoinflammatory disorders such as Sweet’s and Blau syndromes. In cryopyrin associated periodic syndromes group, we discussed chronic infantile neurologic cutaneous and articular (CINCA) syndrome, Muckle-Wells syndrome and familial cold autoinflammatory syndrome. Autoinflammatory bone disorders are categorized to monogenic disorders such as pyogenic arthritis, pyoderma ;gangraenosum and acne (PAPA) syndrome, the deficiency of interleukine-1 receptor antagonist (DIRA) and Majeed syndrome and polygenic background or sporadic group such as chronic recurrent multifocal osteomyelitis (CRMO) or synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome are classified in sporadic group. Other autoinflammatory syndromes are rare causes of periodic fever in Iranian system registry. PMID:25562014

  3. Periodic Fever: A Review on Clinical, Management and Guideline for Iranian Patients - Part II.

    PubMed

    Ahmadinejad, Zahra; Mansouri, Sedigeh; Ziaee, Vahid; Aghighi, Yahya; Moradinejad, Mohammad-Hassan; Fereshteh-Mehregan, Fatemeh

    2014-06-01

    Periodic fever syndromes are a group of diseases characterized by episodes of fever with healthy intervals between febrile episodes. In the first part of this paper, we presented a guideline for approaching patients with periodic fever and reviewed two common disorders with periodic fever in Iranian patients including familial Mediterranean fever (FMF) and periodic fever syndromes except for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). In this part, we review other autoinflammatory disorders including hyper IgD, tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin associated periodic syndromes, autoinflammatory bone disorders and some other rare autoinflammatory disorders such as Sweet's and Blau syndromes. In cryopyrin associated periodic syndromes group, we discussed chronic infantile neurologic cutaneous and articular (CINCA) syndrome, Muckle-Wells syndrome and familial cold autoinflammatory syndrome. Autoinflammatory bone disorders are categorized to monogenic disorders such as pyogenic arthritis, pyoderma ;gangraenosum and acne (PAPA) syndrome, the deficiency of interleukine-1 receptor antagonist (DIRA) and Majeed syndrome and polygenic background or sporadic group such as chronic recurrent multifocal osteomyelitis (CRMO) or synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome are classified in sporadic group. Other autoinflammatory syndromes are rare causes of periodic fever in Iranian system registry.

  4. Periodic fevers and autoinflammatory syndromes in childhood.

    PubMed

    Ostring, Genevieve T; Singh-Grewal, Davinder

    2016-09-01

    Recurrent fever is a common presentation in paediatric practice and can be caused by a wide variety of diseases including autoinflammatory conditions. The innate immune system plays an essential role in the 'first line' response to infection through mediation of inflammatory responses. Inflammasomes are part of the regulatory process for this system and result in the production of the powerful pro-inflammatory cytokine interleukin-1B. Dysregulation of inflammasomes, and Interleukin 1 production, contributes to the pathogenesis of autoinflammatory diseases. This review focuses on described periodic fever syndromes (PFS) which are now collectively referred to as autoinflammatory syndromes. Conditions discussed include periodic fever aphthous stomatitis pharyngitis and cervical adenopathy, familial Mediterranean fever, tumour necrosis factor receptor-associated periodic syndromes, hyperimmunoglobulinaemia D and the cryopyrin-associated periodic syndromes. Presenting features, complications, diagnostic and treatment approaches for these conditions are discussed. Nonetheless, as most of these conditions are rare and may have significant long-term complications, it is recommended that they be managed in consultations with a physician experienced in managing PFS.

  5. Q fever.

    PubMed Central

    Reimer, L G

    1993-01-01

    Q fever is an acute febrile illness first described in 1935 and now seen in many parts of the world. Human infection follows exposure to animals, especially domestic livestock. Recent outbreaks in metropolitan areas have implicated cats as the carrier of disease to humans. The etiologic agent, Coxiella burnetti, belongs to the family Rickettsiaceae, although it has distinct genetic characteristics and modes of transmission. Most recent attention has been focused on a number of large outbreaks of Q fever associated with medical research involving pregnant sheep. Although most infections are self-limited, some patients require prolonged treatment. Recent vaccines have had encouraging success in the prevention of disease in individuals at high risk of exposure. PMID:8358703

  6. Development of a medication adherence scale for familial Mediterranean fever (MASIF) in a cohort of Turkish children.

    PubMed

    Yesilkaya, Sirzat; Acikel, Cengizhan; Fidanci, Berna Eren; Polat, Adem; Sozeri, Betül; Ayaz, Nuray Aktay; Makay, Balahan Bora; Simsek, Dogan; Akinci, Nurver; Özçelik, Gul; Kavukçu, Salih; Emre, Sevinc; Donmez, Osman; Delibas, Ali; Yüksel, Selcuk; Berdeli, Afig; Poyrazoglu, Hakan; Saldir, Mehmet; Fidanci, Kursat; Çakar, Nilgun; Peru, Harun; Bakkaloglu, Sevcan; Tabel, Yilmaz; Sari, Oktay; Aydogan, Umit; Ozenc, Salim; Basbozkurt, Gokalp; Unsal, Erbil; Kasapcopur, Özgür; Gok, Faysal; Ozen, Seza; Demirkaya, Erkan

    2015-01-01

    To develop and assess the validity and reliability of an adherence scale concerning medical treatment in paediatric FMF patients. The Medication Adherence Scale in FMF Patients (MASIF) is a 18-item questionnaire that evaluates adherence to medication in four domains. Validation of the instrument was accomplished in paediatric FMF patients (aged 2-18 years) under medication at least for 6 months. The first step was to build up the scale through qualitative approach (with interviews using semi-structured questions). Validation analyses included assessment of feasibility, face and content validity; construct validity, internal consistency and test-retest reliability. One hundred and fifty patients with FMF were enrolled in the study. The mean age of the patients was 11.11±4.02 years and 48.7% of them were male. The MASIF was found to be feasible and valid for both face and content. It correlated with the Morisky Medication Adherence Scale as a gold standard thereby demonstrating good construct validity (r=0.515, p<0.001). Assessment of content validity identified four subscales. The internal consistency, Cronbach's alpha was 0.728. There was a positive and significant correlation between test and retest scores (r=0.843; p<0.001). Also, a significant correlation between parents' and children's reports (r=0.781, p<0.001). Based on these results, the use of this scale to assess and follow up the adherence to treatment in paediatric FMF patients under medical treatment is recommended.

  7. The significance of urinary beta-2 microglobulin level for differential diagnosis of familial Mediterranean fever and acute appendicitis.

    PubMed

    Ugan, Yunus; Korkmaz, Hakan; Dogru, Atalay; Koca, Yavuz Savas; Balkarlı, Ayse; Aylak, Firdevs; Tunc, Sevket Ercan

    2016-07-01

    The clinical and laboratory parameters widely used are not specific to discriminate the abdominal pain due to FMF attack from that of acute appendicitis. The present study aims to investigate the urinary beta-2 microglobulin (U-β2M) level as a potential parameter to identify these two diseases mimicking each other. A total of 51 patients with established FMF diagnosis due to Tel Hashomer criteria on colchicine treatment (1-1.5 mg/day), 15 patients with acute appendicitis who had appropriate clinical picture and were also supported pathologically after the surgery, and 20 healthy controls were enrolled in the study. Of the 51 patients with FMF, 25 were at an attack period, while remaining 26 were not. For the diagnosis of acute attack, as well as physical examination, laboratory tests including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were performed. From urine specimens U-β2M, microalbumin, and N-acetyl glucosaminidase (U-NAG) were measured. U-β2M levels were significantly higher in acute appendicitis group compared to FMF attack, FMF non-attack, and control groups (p < 0.001, p < 0.001, and p < 0.001, respectively). U-NAG and microalbuminuria were significantly higher in acute appendicitis, FMF attack, and FMF non-attack groups compared to controls (U-NAG p < 0.001, p = 0.016, p = 0.004, microalbuminuria p < 0.001, p < 0.001, p < 0.001, respectively). Microalbuminuria was significantly higher in acute appendicitis group compared to the FMF attack group (p = 0.004). Determination of U-β2M levels may be helpful for differential diagnosis of peritonitis attacks of FMF patients on colchicine treatment and acute appendicitis. However, this finding should be substantiated with other studies.

  8. Concordance between CRP and SAA in familial Mediterranean fever during attack-free period: A study of 218 patients.

    PubMed

    Stankovic Stojanovic, Katia; Hentgen, Véronique; Fellahi, Soraya; Georgin-Lavialle, Sophie; Amselem, Serge; Grateau, Gilles; Bastard, Jean-Philippe; Steichen, Olivier

    2017-03-01

    Monitoring SAA level in attack-free FMF patients is recommended in order to adjust colchicine dose, and minimize the risk of AA amyloidosis. In countries where this test is not available, C-reactive protein (CRP), another acute phase reactant, is used instead. However, CRP is low and SAA is increased in some patients and vice versa. To determine the threshold of CRP corresponding to SAA<10mg/L in patients with FMF and to assess their concordance at the patient level. Consecutive FMF patients in attack-free period and no other cause of intermittent inflammation including infections were recruited during their regular visits in the French reference center for FMF. Demographic and genetic data were recorded; CRP and SAA were tested simultaneously. The threshold value of CRP corresponding to 10mg/L for SAA was determined and the concordance between the two markers was assessed with Cohen's kappa index. 399 samples were obtained from 218 patients, mean age of 27years (33% under 18years old), 55% of female, from Sephardic Jewish origin in 71%. MEFV mutation was M694V homozygous or compound heterozygous in 52%, and simple heterozygous in 18%. Six patients had AA amyloidosis. The appropriate CRP threshold was found to be 5mg/L in children and 8.75mg/L in adults. Global agreement with SAA<10mg/L was 84% [95% confidence interval: 82 to 86%], leading to a kappa index at 0.62 [95% confidence interval: 0.57 to 0.68]. CRP<5mg/L in FMF children or 8.75mg/L in FMF adults during attack-free periods might be a convenient substitute to guide therapeutic decisions when SAA is unavailable. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  9. Sensitivity of African swine fever virus to type I interferon is linked to genes within multigene families 360 and 505.

    PubMed

    Golding, Josephine P; Goatley, Lynnette; Goodbourn, Steve; Dixon, Linda K; Taylor, Geraldine; Netherton, Christopher L

    2016-06-01

    African swine fever virus (ASFV) causes a lethal haemorrhagic disease of pigs. There are conflicting reports on the role of interferon in ASFV infection. We therefore analysed the interaction of ASFV with porcine interferon, in vivo and in vitro. Virulent ASFV induced biologically active IFN in the circulation of pigs from day 3-post infection, whereas low virulent OUR T88/3, which lacks genes from multigene family (MGF) 360 and MGF505, did not. Infection of porcine leucocytes enriched for dendritic cells, with ASFV, in vitro, induced high levels of interferon, suggesting a potential source of interferon in animals undergoing acute ASF. Replication of OUR T88/3, but not virulent viruses, was reduced in interferon pretreated macrophages and a recombinant virus lacking similar genes to those absent in OUR T88/3 was also inhibited. These findings suggest that as well as inhibiting the induction of interferon, MGF360 and MGF505 genes also enable ASFV to overcome the antiviral state. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Typhoid Fever

    DTIC Science & Technology

    2005-01-01

    In addition to the usual causes of fever, the EP must consider less common diseases in the differential diagnosis. We present a case of typhoid fever , one of the most common causes of fever in the international traveler.

  11. Characterization of the oxysterol-binding protein gene family in the yellow fever mosquito, Aedes aegypti

    PubMed Central

    Fu, Qiang; Lynn-Miller, Ace; Lan, Que

    2011-01-01

    The oxysterol-binding protein (OSBP) and related proteins (ORPs) are sterol-binding proteins that may be involved in cellular sterol transportation, sterol metabolism and signal transduction pathways. Four ORP genes were cloned from Aedes aegypti. Based on amino acid sequence homology to human proteins, they are AeOSBP, AeORP1, AeORP8 and AeORP9. Splicing variants of AeOSBP and AeORP8 were identified. The temporal and spatial transcription patterns of members of the AeOSBP gene family through developmental stages and the gonotrophic cycle were profiled. AeORP1 transcription seemed to be head tissue-specific, whereas AeOSBP and AeORP9 expressions were induced by a blood meal. Furthermore, over-expression of AeORPs facilitated [3H]-cholesterol uptake in Aedes aegypti cultured Aag-2 cells. PMID:21699592

  12. Big defensins and mytimacins, new AMP families of the Mediterranean mussel Mytilus galloprovincialis.

    PubMed

    Gerdol, Marco; De Moro, Gianluca; Manfrin, Chiara; Venier, Paola; Pallavicini, Alberto

    2012-02-01

    Antimicrobial peptides (AMPs) play a fundamental role in the innate immunity of invertebrates, preventing the invasion of potential pathogens. Mussels can express a surprising abundance of cysteine-rich AMPs pertaining to the defensin, myticin, mytilin and mytimycin families, particularly in the circulating hemocytes. Based on deep RNA sequencing of Mytilus galloprovincialis, we describe the identification, molecular diversity and constitutive expression in different tissues of five novel transcripts pertaining to the macin family (named mytimacins) and eight novel transcripts pertaining to the big defensins family (named MgBDs). The predicted antimicrobial peptides exhibit a N-terminal signal peptide, a positive net charge and a high content in cysteines, allegedly organized in intra-molecular disulfide bridges. Mytimacins and big defensins therefore represent two novel AMP families of M. galloprovincialis which extend the repertoire of cysteine-rich AMPs in this bivalve mollusk.

  13. Mycobacterium tuberculosis Latin American-Mediterranean Family and Its Sublineages in the Light of Robust Evolutionary Markers

    PubMed Central

    Vyazovaya, Anna; Narvskaya, Olga

    2014-01-01

    Mycobacterium tuberculosis has a clonal population structure, and the Latin American-Mediterranean (LAM) family is one of the largest and most widespread within this species, showing evidence for remarkable pathobiology and a confusing phylogeny. Here, we applied robust phylogenetic markers to study the evolution of the LAM family and its major sublineages circulating in Russia and neighboring countries. A total of 250 M. tuberculosis isolates were confirmed to belong to the LAM family based on the analysis of the LAM-specific single-nucleotide polymorphisms (SNPs) in the Rv3062 and Rv0129c genes. At this stage, the family status was rectified for 121 isolates misleadingly assigned by CRISPR spoligotyping to non-LAM families (T1- or T5-RUS1). Consequently, the reestimated LAM prevalence rate increased 2-fold in Russia and Kazakhstan and 4-fold in Belarus. The majority (91.8 to 98.7%) of the LAM isolates from all three countries belonged to the LAM-RUS sublineage. In contrast, the Ibero-American LAM RD-Rio sublineage was identified in only 7 Russian isolates. Taken together, our findings and further analyses suggest a monophyletic origin of LAM-RUS: at a historically distant time, in Russia, in a small founding bacterial/human population. Its dissemination pattern and high prevalence rate in Northern Eurasia may indicate a long-term coexistence of the LAM-RUS sublineage and local human populations hypothetically leading to coadaptation and reduced pathogenicity of the relatively more ancient clones, such as spoligotype international type 254 (SIT254), compared to the more recent SIT252 and SIT266 clones. In contrast, rare LAM RD-Rio isolates were likely brought to Russia through occasional human contact. The spread of RD-Rio strains is not as global as commonly claimed and is determined largely by human migration flows (rather than by pathobiological properties of these strains). Consequently, a host population factor appears to play a major role in shaping the in

  14. Chikungunya fever. Rheumatic manifestations of an emerging disease in Europe.

    PubMed

    Horcada, M Loreto; Díaz-Calderón, Carlos; Garrido, Laura

    2015-01-01

    Chikungunya fever is a viral disease caused by an alphavirus belonging to the Togaviridae family, transmitted by several species of Aedes mosquitoes: Aedes aegypti and Aedes albopictus (A. albopictus). It is endemic in Africa and Asia with recurrent outbreaks. It is an emerging disease and cases in Europe transmitted by A. albopictus have been established in Mediterranean areas. The first autochthonous cases detected on the Caribbean islands suppose a serious threat of spreading disease to America, which so far has been disease free. Clinical symptoms begin abruptly with fever, skin rash and polyarthritis. Although mortality is low, a high percentage of patients develop a chronic phase defined by persistent arthritis for months or even years. A severe immune response is responsible for joint inflammation. The absence of specific treatment and lack of vaccine requires detailed studies about its immunopathogenesis in order to determine the most appropriate target.

  15. Shell-vial culture, coupled with real-time PCR, applied to Rickettsia conorii and Rickettsia massiliae-Bar29 detection, improving the diagnosis of the Mediterranean spotted fever.

    PubMed

    Segura, Ferran; Pons, Immaculada; Sanfeliu, Isabel; Nogueras, María-Mercedes

    2016-04-01

    Rickettsia conorii and Rickettsia massiliae-Bar29 are related to Mediterranean spotted fever (MSF). They are intracellular microorganisms. The Shell-vial culture assay (SV) improved Rickettsia culture but it still has some limitations: blood usually contains low amount of microorganisms and the samples that contain the highest amount of them are non-sterile. The objectives of this study were to optimize SV culture conditions and monitoring methods and to establish antibiotic concentrations useful for non-sterile samples. 12 SVs were inoculated with each microorganism, incubated at different temperatures and monitored by classical methods and real-time PCR. R. conorii was detected by all methods at all temperatures since 7th day of incubation. R. massiliae-Bar29 was firstly observed at 28°C. Real-time PCR allowed to detected it 2-7 days earlier (depend on temperature) than classical methods. Antibiotics concentration needed for the isolation of these Rickettsia species from non-sterile samples was determined inoculating SV with R. conorii, R. massiliae-Bar29, biopsy or tick, incubating them with different dilutions of antibiotics and monitoring them weekly. To sum up, if a MSF diagnosis is suspected, SV should be incubated at both 28°C and 32°C for 1-3 weeks and monitored by a sensitive real-time PCR. If the sample is non-sterile the panel of antibiotics tested can be added.

  16. Recurrent Fever of Unknown Origin (FUO) Due to Periodic Fever, Aphthous Stomatititis, Pharyngitis and Adenitis (FAPA) Syndrome in an Adult.

    PubMed

    Muñoz-Gómez, Sigridh; Cunha, Burke A

    2013-08-19

    FAPA syndrome (periodic fever, aphthous stomatititis, pharyngitis and adenitis) is a relatively new entity described in pediatric patients. In adults, reports of FAPA are limited to rare case reports. The differential diagnosis of FAPA in adults includes Behcet's syndrome, familial Mediterranean fever (FMF), Hyper IgD syndrome and juvenile rheumatoid arthritis (JRA), i.e., adult Still's disease. With FAPA syndrome, between episodes patients are completely asymptomatic and serologic inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and white blood cell (WBC) count are normal. The etiology of FAFA is unknown, but lack of secondary cases or clustering in close contacts, lack of seasonality, and the lack of progression for years argue against an infectious etiology. We describe an extremely rare case of an adult with a recurrent FUO with profuse night sweats and prominent chills due to FAPA syndrome.

  17. Childhood Fever: parental beliefs and management.

    PubMed

    Stephenson, M J; Rosencrantz, A; Kneller, P

    1988-01-01

    Childhood fever is often seen in family-practice. Clinical experience has shown the authors that parental anxiety often initiates early, aggressive treatment of fever with antipyretics. The authors studied parents' beliefs and practices relating to fever control in their children, and who or what their information sources were. The findings indicate that parents are commonly misinformed about the nature of childhood fever and its management, and that physicians need to learn more about conveying information on fever to patients.

  18. Rift Valley fever vaccines

    PubMed Central

    Ikegami, Tetsuro; Makino, Shinji

    2009-01-01

    Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a tripartite RNA genome. RVFV is transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis or ocular diseases, whereas ruminants experience abortions during outbreak. Effective vaccination of both humans and ruminants is the best approach to control Rift Valley fever. This article summarizes the development of inactivated RVFV vaccine, live attenuated vaccine, and other new generation vaccines. PMID:19837291

  19. Dynamics of the marine planktonic diatom family Chaetocerotaceae in a Mediterranean coastal zone

    NASA Astrophysics Data System (ADS)

    Bosak, Sunčica; Godrijan, Jelena; Šilović, Tina

    2016-10-01

    The planktonic diatoms belonging to two genera Chaetoceros and Bacteriastrum, included within the family Chaetocerotaceae, are ecologically important as they represent an important component of the phytoplankton in the coastal regions and are often among bloom-forming taxa. We analysed the chaetocerotacean species composition and abundances in the coastal area of northeastern Adriatic in a biweekly study conducted from September 2008 to October 2009 with the aim of investigating seasonal dynamics and species succession on a fine temporal scale and determining the most important ecological factors influencing their distribution. The study identified seven Chaetoceros and three Bacteriastrum species as major phytoplankton components showing the clear annual succession and two types of blooms (one species/multi species) governed by differing ecological conditions. Autumn bloom was composed of 20 chaetocerotacean species with Chaetoceros contortus and Chaetoceros vixvisibilis alternating in dominance. The summer period was characterized by spreading of freshwater from the Po River up to the eastern coast increasing availability of phosphate which triggered the monospecific Chaetoceros vixvisibilis bloom. We explained the chaetocerotacean dominant species succession pattern by the environmental parameters, with the temperature, salinity and phosphate availability as most important factors driving the species seasonality.

  20. Yellow Fever

    MedlinePlus

    ... Search Form Controls Cancel Submit Search The CDC Yellow Fever Note: Javascript is disabled or is not supported ... CDC.gov . Recommend on Facebook Tweet Share Compartir Yellow fever virus is found in tropical and subtropical areas ...

  1. Dengue Fever

    MedlinePlus

    ... away from areas that have a dengue fever epidemic, the risk of contracting dengue fever is small for international travelers./p> Reviewed by: Elana ... Transfusions Cholera West Nile Virus First Aid: Vomiting Are Insect ...

  2. [Q fever].

    PubMed

    Frangoulidis, Dimitrios; Fischer, Silke F

    2015-08-01

    The article summarizes some important recently identified findings about the Coxiella burnetii disease, Q fever. Beside new diagnostic parameters for follow-up issues, the importance of a timely identification of chronic Q fever and the peculiarities of the post Q fever fatigue syndrome are depicted. © Georg Thieme Verlag KG Stuttgart · New York.

  3. [Family planning and reproductive behavior in Islamic countries in the Mediterranean area].

    PubMed

    Angeli, A; Salvini, S

    1990-01-01

    Recently, in countries like Egypt, Tunisia, and Turkey, reproductive behavior has modified. Yet, according the World Fertility Survey (WFS), the number of children wanted is still rather high, ranging between 5.5 and 6.4, especially in countries of the near ear like Syria and Jordan. In Egypt, Morocco, and Tunisia, where government-sponsored family planning (FP) programs have been instituted, the number is 4. FP affects socioeconomic transformation. There has been a global reduction of fertility and improvement in the status of women as a result of the modification of the model of nuptiality and the increase of education. Intermediate variables include contraceptive behavior and postpartum infertility, as proposed by the Bongaarts model examining the effects of marriage, postpartum infertility, and contraception. Jordan, Syria, and Morocco showed high values on these indices because low age at marriage and meager access to contraceptives elevated fertility. Tunisia, Lebanon, and Algeria evinced very low indices and reduced potential fertility. Syria and Jordan had a very high postpartum infertility index. These values depend in part on less prolonged breast feeding. According to the Bongaarts model, Egypt (1980) had total fertility rate (TFR) of 5.21, Morocco (1979-80) had 5.82, Tunisia (1978) had 5.83, Syria (1978) had 7.46, Lebanon (1976) had 4,72, Jordan (1976) had 7,63, and Algeria (1986) had 5,41. During the decade of 1965-75, as a result of modification of the marriage model and contraceptive behavior in Morocco and Tunisia, there was a decrease in births. In Egypt, no significant difference occurred in the rate of decline. In Lebanon, Syria, and Jordan, the intervention policy appeared feeble, and the access to services was unsatisfactory. In Turkey, Egypt, Algeria, and Morocco, the individual approach to intervention and the organization of services and assistance was clearer. FP showed a decreasing trend during the 1970s. During 1980-85, TFR was: Algeria 6

  4. Autoinflammatory syndromes behind the scenes of recurrent fevers in children.

    PubMed

    Rigante, Donato

    2009-08-01

    Many children experience recurrent fevers with no easily identifiable source and only a careful follow-up helps in the early identification of other presenting symptoms of other defined conditions which require medical intervention. Autoinflammatory syndromes are rare childhood-onset disorders of the innate immunity in which recurrent flares of fever and inflammation affecting skin, joints, the gastrointestinal tube, or serous membranes are the most striking signs, without any evidence of autoantibody production or underlying infections. Among the pediatric conditions belonging to this group we can consider hereditary recurrent fevers (familial Mediterranean fever, mevalonate kinase deficiency syndrome, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndromes), pyogenic disorders (PAPA syndrome, CRMO syndrome, Majeed syndrome), immune-mediated granulomatous diseases (Blau syndrome, Crohn's disease), and idiopathic febrile syndromes (systemic-onset juvenile idiopathic arthritis, PFAPA syndrome, Behçet syndrome). Their genetic background has only been partially elucidated and advances in their molecular pathogenesis are shedding new light on the innate immune system, whilst more and more diseases are being reconsidered at a pathogenetic level and included in this new chapter of postgenomic medicine. The diagnosis of most autoinflammatory syndromes relies on clinical history, demonstration of an increased acute-phase response during inflammatory attacks, and, possibly, genetic confirmation, which is still elusive especially for idiopathic febrile syndromes. This astonishing progress in the awareness and knowledge of autoinflammatory syndromes has anticipated the actual possibilities of medical intervention and rationalized treatment with targeted biologic agents.

  5. [New beta0-thalassaemic insertion mutation (CD 7/8, +G) in a Slovak family, associated with the Mediterranean haplotype IX].

    PubMed

    Kynclová, E; Divoký, V; Kovaríková, L; Melichárková, R; Indráková, J; Divoká, M; Hammerová, T; Sakalová, A; Hudecek, J; Indrák, K

    1999-03-01

    The authors describe a newly identified beta0-thalassaemic mutation found in two subjects from two generations of a Slovak family. The beta0-thalassaemic allele developed by insertion of one nucleotide (+G, CD 7/8) into the first exon of the beta-globin gene. The mutation causes a shift of the open globin reading frame which leads to the development of a terminal codon in codon 22. The thalassaemic allele is associated with the mediterranean haplotype IX. The mutation has in both heterozygotes the phenotype of beta0-thalassaemia minor with a slightly elevated level of HbF.

  6. [The Alkhurma virus (family Flaviviridae, genus Flavivirus): an emerging pathogen responsible for hemorrhage fever in the Middle East].

    PubMed

    Charrel, R N; de Lamballerie, X

    2003-01-01

    To date tick-borne flaviviruses causing hemorrhagic fevers in humans have been isolated in Siberia (Omsk hemorrhagic fever virus), India (Kyasanur Forest disease virus), and Saudi Arabia (Akhurma virus). Because of their potential use as biological weapons for bioterrorism, these 3 viruses require level 4 biosafety handling facilities and have been listed as hypervirulent pathogens by the Center for Disease Control and Prevention. Alkhurma virus was isolated in 1995 from patients with hemorrhagic fever in Saudi Arabia. Current evidence suggests that transmission to humans can occur either transcutaneously either by contamination of a skin wound with the blood of an infected vertebrate or bites of an infected tick or orally by drinking unpasteurized contaminated milk. To date a total of 24 symptomatic human cases have been recorded with a mortality rate at 25% (6/24). Pauci-symptomatic or asymptomatic cases are likely but epidemiologic data are currently unavailable. The complete coding sequence of the prototype strain of Alkhurma virus was determined and published in 2001 based on international research project involving investigators from France, Great Britain, and Saudi Arabia. Phylogenetic studies demonstrate that closest known relative of Alkhurma virus is Kyasanur Forest disease virus and that both viruses share a common ancestor. Genetic analysis of several human strains sequentially isolated over a 5-year period showed a very low diversity. This finding has important potential implications for diagnosis and vaccination.

  7. Rift Valley Fever Review

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is a disease of animals and humans that occurs in Africa and the Arabian Peninsula. A Phlebovirus in the family Bunyaviridae causes the disease that is transmitted by mosquitoes. Epidemics occur during years of unusually heavy rainfall that assessment models are being develo...

  8. Dengue fever.

    PubMed

    Skinner, Anita

    Dengue fever is a notifiable infectious disease in England because of its geographic expansion and the increase in the number of epidemics. The article highlighted the importance of informing overseas travellers of the risk of acquiring dengue fever and advising them on personal protective measures.

  9. [A group fever: safari's fever].

    PubMed

    Cantiniaux, S; Serratrice, J; De Roux-Serratrice, C; Disdier, P; Perez, L; Bricaire, F; Caumes, E; Mary, C; Weiller, P J

    2004-12-01

    Acute schistosomiasis, called safari's fever in Africa and Katayama fever in Japan, is an immunoallergic reaction due to transcutaneous penetration of infective cercaria. We report the collective case of seven young adults spending holidays in Mali. An eighteen years-old girl presents fever, headache, diarrhoea and abdominal pains at return from Dogon country (south of Mali). After turned down malaria and with the notion of bathing in fresh water followed by pruritus, we think to safari's fever. So we alarm all other members of the group. All can be treated to avoid chronic schistosomiasis. These observations recall that acute schistosomiasis is a real danger for tourists when bathing in fresh water in endemic areas of Africa. Education of travellers is necessary. Occurrence of safari's fever should alert physicians to prevent chronic schistosomiasis.

  10. Pathogenesis of Lassa fever.

    PubMed

    Yun, Nadezhda E; Walker, David H

    2012-10-09

    Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host's immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.

  11. Pathogenesis of Lassa Fever

    PubMed Central

    Yun, Nadezhda E.; Walker, David H.

    2012-01-01

    Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents. PMID:23202452

  12. Recurrent Fever in Children

    PubMed Central

    Torreggiani, Sofia; Filocamo, Giovanni; Esposito, Susanna

    2016-01-01

    Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time. PMID:27023528

  13. Recurrent Fever in Children.

    PubMed

    Torreggiani, Sofia; Filocamo, Giovanni; Esposito, Susanna

    2016-03-25

    Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time.

  14. Yellow fever.

    PubMed

    Monath, Thomas P; Vasconcelos, Pedro F C

    2015-03-01

    Yellow fever, a mosquito-borne flavivirus disease occurs in tropical areas of South America and Africa. It is a disease of major historical importance, but remains a threat to travelers to and residents of endemic areas despite the availability of an effective vaccine for nearly 70 years. An important aspect is the receptivity of many non-endemic areas to introduction and spread of yellow fever. This paper reviews the clinical aspects, pathogenesis, and epidemiology of yellow fever, with an emphasis on recent changes in the distribution and incidence of the disease. Recent knowledge about yellow fever 17D vaccine mechanism of action and safety are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Typhoid fever

    MedlinePlus

    ... most commonly caused due to a bacteria called Salmonella typhi ( S typhi ). Causes S typhi is spread through contaminated ... as food handlers. Alternative Names Enteric fever Images Salmonella typhi organism Fly Digestive system organs References Harris ...

  16. Valley fever

    MedlinePlus

    ... southwestern United States, and in Central and South America. You get it by breathing in the fungus ... that causes Valley fever) Chest x-ray Sputum culture Sputum smear (KOH test) Tests done for more ...

  17. Q Fever

    MedlinePlus

    ... infects some animals, such as goats, sheep and cattle. C. burnetii bacteria are found in the birth ... your physician... Diagnosis and Testing Recommended tests… Treatment Antibiotics to treat Q fever... Prevention Avoid getting infected... ...

  18. Yellow fever

    MedlinePlus

    ... liver, and kidney. Bleeding disorders, seizures, coma, and delirium may also occur. Symptoms may include: Fever, headache, ... tongue Yellow skin and eyes (jaundice) Decreased urination Delirium Irregular heartbeats (arrhythmias) Bleeding (may progress to hemorrhage) ...

  19. Enteric Fever.

    PubMed

    Kumar, Praveen; Kumar, Ruchika

    2017-03-01

    Enteric fever is an important public-health problem in India. The clinical presentation of typhoid fever is very variable, ranging from fever with little other morbidities to marked toxemia and associated multisystem complications. Fever is present in majority of patients (>90 %) irrespective of their age group. Mortality is higher in younger children. Blood culture remains gold standard for diagnosis. Widal test has low sensitivity and specificity but may be used in second week to support the diagnosis. Emerging resistance to several antibiotics should be kept in mind when selecting antibiotics or revising the treatment. The key preventive strategies are safe water, safe food, personal hygiene, and appropriate sanitation. Vaccination is an additional effective tool for prevention.

  20. Hay Fever

    MedlinePlus

    ... and throat. This can trigger a type of allergy called hay fever. Symptoms can include Sneezing, often ... to use distilled or sterilized water with saline. Allergy shots can help make you less sensitive to ...

  1. Lassa Fever

    MedlinePlus

    ... an acute viral illness that occurs in west Africa. The illness was discovered in 1969 when two ... Lassa fever is endemic in parts of west Africa including Sierra Leone, Liberia, Guinea and Nigeria; however, ...

  2. Q Fever

    PubMed Central

    Maurin, M.; Raoult, D.

    1999-01-01

    Q fever is a zoonosis with a worldwide distribution with the exception of New Zealand. The disease is caused by Coxiella burnetii, a strictly intracellular, gram-negative bacterium. Many species of mammals, birds, and ticks are reservoirs of C. burnetii in nature. C. burnetii infection is most often latent in animals, with persistent shedding of bacteria into the environment. However, in females intermittent high-level shedding occurs at the time of parturition, with millions of bacteria being released per gram of placenta. Humans are usually infected by contaminated aerosols from domestic animals, particularly after contact with parturient females and their birth products. Although often asymptomatic, Q fever may manifest in humans as an acute disease (mainly as a self-limited febrile illness, pneumonia, or hepatitis) or as a chronic disease (mainly endocarditis), especially in patients with previous valvulopathy and to a lesser extent in immunocompromised hosts and in pregnant women. Specific diagnosis of Q fever remains based upon serology. Immunoglobulin M (IgM) and IgG antiphase II antibodies are detected 2 to 3 weeks after infection with C. burnetii, whereas the presence of IgG antiphase I C. burnetii antibodies at titers of ≥1:800 by microimmunofluorescence is indicative of chronic Q fever. The tetracyclines are still considered the mainstay of antibiotic therapy of acute Q fever, whereas antibiotic combinations administered over prolonged periods are necessary to prevent relapses in Q fever endocarditis patients. Although the protective role of Q fever vaccination with whole-cell extracts has been established, the population which should be primarily vaccinated remains to be clearly identified. Vaccination should probably be considered in the population at high risk for Q fever endocarditis. PMID:10515901

  3. Assessment of Attention Deficit/Hyperactivity Disorder among children in families and schools in Mediterranean and continental Croatian towns.

    PubMed

    Karlović, Dalibor; Martinac, Marko; Gale, Ruza; Markić, Josko; Marcinko, Darko

    2005-06-01

    Among one of the biggest difficulties in diagnosis and treatment of Attention Deficit/Hyperactivity Disorder (AD/HD) is firstly the involvement of different persons, especially parents and teachers, who, together with experts, make the unavoidable subjects in the process of detecting and treating children with AD/HD. Adding to that the standards of living environment, the process becomes even more complex. The aim of this research is to detect if there is a difference in the assessment of AD/HD, given by the parents and teachers in two urban areas, which have culturally and geographically different characteristics (Middle European and Mediterranean). The assessments of children's behavior were conducted in two randomly selected schools; one in Zadar (Mediterranean town on the Adriatic coast) and the other in Zagreb (Middle European city). The children were evaluated by the experts using DSM IV as a gold standard, and by the parents and teachers using Conners rating scales. Analysis of results showed that there were differences in assessment of AD/HD among experts and parents/teachers, and among parents from two towns. Different results given by parents in Zadar and Zagreb, we reasoned, were obtained because of different sensitivity to the problems of hyperactive/impulsive/attention deficiency children's behavior.

  4. [Endemic zoonosis in Mediterranean area].

    PubMed

    Fenga, Concettina; Pugliese, Michela

    2013-01-01

    The Mediterranean is historically considered an area of high concentration of zoonoses. Mediterranean countries socio-economic features have favoured, over time, the onset of different types of zoonosis. Many of these may affect many occupational categories, first of all farmers, people working in abattoirs and processing products of animal origin. New farming activities and technologies have generated new occupational and zoonotic risks. These changes have influenced zoonosis epidemiology and have led to a gradual decrease in the number of diseases and to a reduction of some biological risks. However, brucellosis, Q fever, bovine tuberculosis cystic echinococcosis remain a strong example of zoonosis and a real risk, in the Mediterranean area especially. Therefore, an interdisciplinary collaboration between Veterinary Service, Public Health and Occupational medicine is necessary in order to plan territorial prevention.

  5. Childhood fever.

    PubMed

    Chong, C Y; Allen, D M

    1996-02-01

    Childhood fever is a common symptom, reflective of multiple causes. As the child is often unable to express himself, the physician must rely on parents' observations and the physical examination. The majority of febrile children have non-bacterial upper respiratory tract infection and indiscriminate use of antibiotics is inappropriate, ineffective and leads to drug-resistance such as the emergence of Penicillin-resistant Streptococcus pneumoniae. In this article, we attempt to identify the possible causes of fever by a simple approach using the presence or absence of associated or localising symptoms. Infants less than 3 months constitute a unique group as the fever may be related to perinatal events and as serious bacterial infections can still occur despite unremarkable physical findings. Management of fever needs to take into account the toxicity, immune status and age of the patients as well as the source of the infection. Zealous overprescription of antipyretics needs to be avoided with attention directed to the cause of the fever, the child's capacity to cope with the illness and parental education.

  6. Ebola hemorrhagic Fever.

    PubMed

    Burnett, Mark W

    2014-01-01

    Ebola hemorrhagic fever is an often-fatal disease caused by a virus of the Filoviridae family, genus Ebolavirus. Initial signs and symptoms of the disease are nonspecific, often progressing on to a severe hemorrhagic illness. Special Operations Forces Medical Providers should be aware of this disease, which occurs in sporadic outbreaks throughout Africa. Treatment at the present time is mainly supportive. Special care should be taken to prevent contact with bodily fluids of those infected, which can transmit the virus to caregivers.

  7. [Zika fever].

    PubMed

    Eftekhari-Hassanlouie, S; Le Guern, A; Oehler, E

    2017-02-08

    Zika virus infection is an emerging arboviral disease which presented as a mild flu-like or algo-eruptive syndrome with fever, arthralgia, myalgia and a maculopapulous eruption. Severe neurological and fetal complications have recently been highlighted. Diagnosis is established by detection of viral RNA by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Many publications report on the progress of knowledge on zika and its complications. Treatment is symptomatic, mainly with analgesics. Prevention is essential through individual and collective vector control. Faced with this emerging arbovirus, health authorities of many countries have implemented significant resources to accelerate research efforts including on diagnostic tests and on the development of vaccines. In Europe, the presence of Aedes albopictus, a mosquito vector of the virus zika, runs the risk of autochthonous cases as well as autochthonous dengue or chikungunya fever. Hence, autochthonous zika fever is not excluded to appear during the warmest months in metropolitan French departments colonized by A. albopictus.

  8. Yellow Fever Vaccine

    MedlinePlus

    What is yellow fever?Yellow fever is a serious disease caused by the yellow fever virus. It is found in certain parts of Africa and South America. Yellow fever is spread through the bite of an infected ...

  9. Dengue Fever Treatment

    MedlinePlus

    ... linkedin Dengue Fever Treatment Dengue Fever Dengue Fever Biology and Transmission Prevention Diagnosis Treatment Featured Research NIAID- ... last reviewed on February 8, 2011 Dengue Fever Biology and Transmission Prevention Diagnosis Treatment Featured Research ^ Return ...

  10. Dengue fever (image)

    MedlinePlus

    Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

  11. [Viral haemorrhagic fevers--evolution of the epidemic potential].

    PubMed

    Markin, V A; Markov, V I

    2002-01-01

    In this review modern data on dangerous and particularly dangerous viral haemorrhagic fevers caused by a group of viruses belonging to the families of phylo-, arena-, flavi-, bunya- and togaviruses are presented. Morbidity rates and epidemics caused by Marburg virus, Ebola fever virus, Lassa fever virus, Argentinian and Bolivian haemorrhagic fever viruses, dengue haemorrhagic fever virus, Crimean haemorrhagic fever virus, Hantaviruses are analyzed. Mechanisms of the evolution of the epidemic manifestation of these infections are considered. The importance of the development of tools and methods of diagnosis, rapid prevention and treatment of exotic haemorrhagic fevers is emphasized.

  12. E180splice mutation in the growth hormone receptor gene in a Chilean family with growth hormone insensitivity: a probable common Mediterranean ancestor.

    PubMed

    Espinosa, Claudia; Sjoberg, Marcela; Salazar, Teresa; Rodriguez, Adrian; Cassorla, Fernando G; Mericq, M Veronica; Carvallo, Pilar

    2008-12-01

    Mutations in the GH receptor gene have been identified as the cause of growth hormone insensitivity syndrome (GHIS), a rare autosomal recessive disorder. We studied the clinical and biochemical characteristics and the coding sequence and intron-exon boundaries of the GH receptor gene in a consanguineous family with severe short stature which consisted of two patients, their parents and five siblings. The two adolescents had heights of -4.7 and -5.5 SDS, respectively, with elevated growth hormone associated with low IGF-I, IGFBP-3 and GHBP concentrations. Molecular analysis of the GH receptor gene revealed a mutation in exon 6, present in both patients This mutation, E180 splice, has been previously described in an Ecuadorian cohort, and in one Israeli and six Brazilian patients. We determined the GH receptor haplotypes based on six polymorphic sites in intron 9. Co-segregation of the E180splice mutation with haplotype I was found in this family, compatible with a common Mediterranean ancestor, as shown for previous cases with the E180splice mutation described to date.

  13. Three-day fever.

    PubMed

    Akakpo, A J

    2015-08-01

    Three-day fever is a viral disease caused by an Ephemerovirus of the family Rhabdoviridae, transmitted by arthropod vectors. It is common in tropical and sub-tropical regions, where it affects mainly domestic cattle and buffaloes, especially in intensive dairy or fattening production systems. It is of economic importance because it reduces milk production and fertility and causes abortion. The disease is generally benign. It manifests in several susceptible subjects simultaneously, with a sudden episode of fever accompanied by muscle involvement with arthritis, stiffness of the limbs, and lameness, followed by rapid recovery. The presence of a serofibrinous exudate in the joints is indicative of the disease. Clinical diagnosis is often difficult in the absence of pathognomonic signs. Epidemiological factors (proliferation of arthropod vectors), associated with a short-lived fever and the presence of many immature neutrophils, point strongly to three-day fever. In the absence of any specific treatment, the symptoms are treated with antibiotics and anti-inflammatories. Medical prophylaxis currently uses