Ichthyosiform sarcoidosis: report of three cases from Japan and literature review.

PubMed

Miura, Takako; Kato, Yasunobu; Yamamoto, Toshiyuki

2016-12-23

Cutaneous lesions of sarcoidosis present with various manifestations including specific and non-specific cutaneous lesions. Ichthyosiform sarcoidosis is a rare form of cutaneous sarcoidosis, presenting with asymptomatic, adherent, polygonal scales, mainly appearing on the lower limbs.  Ichthyosiform sarcoidosis has a predilection for dark-skinned races, and cases affecting Japanese patients have rarely been reported in English literature.  We herein describe three Japanese cases of ichthyosiform sarcoidosis on the lower limbs. All of the patients were female, with an age range of 57-69 years old.  Histologically, sarcoidal granulomas were located in the mid- to lower dermis.  All cases had scar sarcoidosis on the knees.  Furthermore, Case 1 presented with papular sarcoidosis on the back, and Case 3 presented with subcutaneous nodules on the buttock as well as erythema nodosum-like lesions on the lower legs.  All patients had lung sarcoidosis, but ocular sarcoidosis was seen in only Case 2. Case 3 showed Heerfordt syndrome with facial nerve paralysis. Histological features showed that the granular layers were scarcely detected in the overlying epidermis; however, filaggrin expression was not decreased.  Sarcoidal granulomas accumulated around the sweat glands in one case, whereas those features were not detected in the other two cases. In conclusion, ichthyosiform cutaneous sarcoidosis may be overlooked or misdiagnosed as xerotic dry skin which is frequently found in elderly people, and ichthyosiform cutaneous lesions may be more prevalent than previously estimated.

Acute vision loss: a fuzzy presentation of sarcoidosis.

PubMed

Austin, Andrea L; Day, Luke T; Bishop, Frank M

2013-04-01

Acute vision loss is a devastating problem for patients and a challenging diagnostic dilemma for Emergency Physicians. This chief complaint is one in which we must be adept at quickly evaluating and initiating either care or referral. This case reviews the approach to acute vision loss and shows the importance of expanding the differential in atypical and complex presentations. A 31-year-old, previously healthy, white woman presented to the Emergency Department (ED) with 1 day of painless right eye vision loss. Ocular ultrasound and slit-lamp examination were unremarkable. Fundoscopic examination revealed retinal hemorrhages and papillitis. Her chest X-ray study was significant for bilateral hilar adenopathy, and subsequent lymph node biopsy confirmed the diagnosis of sarcoidosis. Although sarcoidosis is more common in African Americans, it must be considered in all patients in the appropriate clinical context. Sarcoidosis is an important diagnosis to include on the differential of many chief complaints that present to the ED, including acute vision loss and dyspnea. Published by Elsevier Inc.

Clinical Course of Sarcoidosis in World Trade Center-Exposed Firefighters.

PubMed

Hena, Kerry M; Yip, Jennifer; Jaber, Nadia; Goldfarb, David; Fullam, Kelly; Cleven, Krystal; Moir, William; Zeig-Owens, Rachel; Webber, Mayris P; Spevack, Daniel M; Judson, Marc A; Maier, Lisa; Krumerman, Andrew; Aizer, Anthony; Spivack, Simon D; Berman, Jessica; Aldrich, Thomas K; Prezant, David J

2018-01-01

Sarcoidosis is believed to represent a genetically primed, abnormal immune response to an antigen exposure or inflammatory trigger, with both genetic and environmental factors playing a role in disease onset and phenotypic expression. In a population of firefighters with post-World Trade Center (WTC) 9/11/2001 (9/11) sarcoidosis, we have a unique opportunity to describe the clinical course of incident sarcoidosis during the 15 years postexposure and, on average, 8 years following diagnosis. Among the WTC-exposed cohort, 74 firefighters with post-9/11 sarcoidosis were identified through medical records review. A total of 59 were enrolled in follow-up studies. For each participant, the World Association of Sarcoidosis and Other Granulomatous Diseases organ assessment tool was used to categorize the sarcoidosis involvement of each organ system at time of diagnosis and at follow-up. The incidence of sarcoidosis post-9/11 was 25 per 100,000. Radiographic resolution of intrathoracic involvement occurred in 24 (45%) subjects. Lung function for nearly all subjects was within normal limits. Extrathoracic involvement increased, most prominently joints (15%) and cardiac (16%) involvement. There was no evidence of calcium dysmetabolism. Few subjects had ocular (5%) or skin (2%) involvement, and none had beryllium sensitization. Most (76%) subjects did not receive any treatment. Extrathoracic disease was more prevalent in WTC-related sarcoidosis than reported for patients with sarcoidosis without WTC exposure or for other exposure-related granulomatous diseases (beryllium disease and hypersensitivity pneumonitis). Cardiac involvement would have been missed if evaluation stopped after ECG, 48-h recordings, and echocardiogram. Our results also support the need for advanced cardiac screening in asymptomatic patients with strenuous, stressful, public safety occupations, given the potential fatality of a missed diagnosis. Copyright © 2017 American College of Chest Physicians

Virulence, Speciation and Antibiotic Susceptibility of Ocular Coagualase Negative Staphylococci (CoNS)

PubMed Central

Priya, Ravindran; Mythili, Arumugam; Singh, Yendremban Randhir Babu; Sreekumar, Haridas; Manikandan, Palanisamy; Panneerselvam, Kanesan

2014-01-01

Background: Coagulase negative Staphylococci (CoNS) are common inhabitants of human skin and mucous membranes. With the emergence of these organisms as prominent pathogens in patients with ocular infections, investigation has intensified in an effort to identify important virulence factors and to inform new approaches to treatment and prevention. Aim: To isolate CoNS from ocular specimens; to study the possible virulence factors; speciation of coagulase negative staphylococci (CoNS) which were isolated from ocular complications; antibiotic susceptibility testing of ocular CoNS. Materials and Methods: The specimens were collected from the target patients who attended the Microbiology Laboratory of a tertiary care eye hospital in Coimbatore, Tamilnadu state, India. The isolates were subjected to tube and slide coagulase tests for the identification of CoNS. All the isolates were subjected to screening for lipase and protease activities. Screening for other virulence factors viz., slime production on Congo red agar medium and haemagglutination assay with use of 96-well microtitre plates. These isolates were identified upto species level by performing biochemical tests such as phosphatase test, arginine test, maltose and trehalose fermentation tests and novobiocin sensitivity test. The isolates were subjected to antibiotic susceptibility studies, based on the revised standards of Clinical and Laboratory Standards Institutes (CLSI). Results: During the one year of study, among the total 260 individuals who were screened, 100 isolates of CoNS were obtained. Lipolytic activity was seen in all the isolates, whereas 38 isolates showed a positive result for protease. A total of 63 isolates showed slime production. Of 100 isolates, 30 isolates were analyzed for haemagglutination, where 4 isolates showed the capacity to agglutinate the erythrocytes. The results of the biochemical analysis revealed that of the 100 isolates of CoNS, 43% were Staphylococcus epidermidis. The other

Sarcoidosis

MedlinePlus

... the elbow Sarcoidosis on the nose and forehead Respiratory system Erythema nodosum associated with sarcoidosis References Judson MA, Morgenthau AS, Baughman RP. Sarcoidosis. In: Broaddus VC, Mason RJ, Ernst ... of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

Animal models of sarcoidosis.

PubMed

Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

2017-03-01

Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

Characteristics of sarcoidosis in Maori and Pacific Islanders.

PubMed

Wilsher, Margaret L; Young, Lisa M; Hopkins, Raewyn; Cornere, Megan

2017-02-01

Ethnicity is strongly associated with variable clinical presentation in sarcoidosis but the association between ethnicity and clinical characteristics has not previously been described in patients of Polynesian ancestry, Maori and Pacific Islander (PI). The objective of this study was to describe the clinical characteristics of sarcoidosis in Maori and PI patients and determine if those were different to European patients. A retrospective review of the medical records of 406 patients (69 Maori/PI) attending a specialist interstitial lung disease (ILD) clinic. The population (207 females, mean age at presentation: 36) reflected the current New Zealand census data (2013) with only people of Indian ethnicity over-represented. Parenchymal lung involvement was uncommon in Maori and PI patients (21% Scadding stage 2, 2% stage 3), and no patient had extensive pulmonary fibrosis (stage 4). Computed tomography (CT) patterns of sarcoid parenchymal lung involvement were less commonly reported for Maori/PI. There were no differences in respect of baseline lung function or requirement for treatment. Ocular and skin involvement occurred more frequently in Maori and PI (P = 0.0045, P = 0.03), and erythema nodosum was more common in Caucasians (P = 0.0008). People of Polynesian ancestry appear to have less pulmonary and more extra-pulmonary manifestations of sarcoidosis. This adds to our knowledge that sarcoidosis heterogeneity is influenced by ethnicity. © 2016 Asian Pacific Society of Respirology.

Cutaneous sarcoidosis.

PubMed

Noe, Megan H; Rosenbach, Misha

2017-09-01

Cutaneous sarcoidosis occurs in up to 30% of patients with sarcoidosis and skin findings are often the initial presenting symptom. Cutaneous sarcoidosis is a rare skin disease and many aspects of the disease presentation and treatment are not well understood. This review will highlight developments in the epidemiology, clinical presentation, diagnosis and treatment of cutaneous sarcoidosis over the past several years. Epidemiological studies from several different populations reaffirm that cutaneous sarcoidosis is more common in women and is often the presenting symptom of systemic sarcoidosis. Recently, more cases are being reported in association with oncologic immune modulators, which will be of great interest as use of those agents increases. Also, ultrasound has shown promise for the imaging of cutaneous granulomas for disease assessment and measuring response to treatment. Finally, the treatment of cutaneous sarcoidosis remains difficult and is based largely on retrospective data with a paucity of large, prospective trials. There have been recently introduced and validated cutaneous scoring tools which show promise and may lead to more high-quality studies going forward. The recent developments in cutaneous sarcoidosis have identified many new pharmacologic and physical triggers of disease, but the evidence for effective treatment is still lacking. Further research is necessary to improve the care of patients with cutaneous sarcoidosis.

Sarcoidosis

MedlinePlus

Sarcoidosis is a disease that leads to inflammation, usually in your lungs, skin, or lymph nodes. It starts as tiny, grain-like lumps, called granulomas. Sarcoidosis can affect any organ in your body. No ...

Biomarkers in sarcoidosis.

PubMed

Chopra, Amit; Kalkanis, Alexandros; Judson, Marc A

2016-11-01

Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis. Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science. Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.

Subcutaneous sarcoidosis.

PubMed

Marcoval, Joaquim; Moreno, Abelardo; Mañá, Juan; Peyri, Jordi

2008-10-01

Subcutaneous sarcoidosis has been reported to occur in 1.4% to 6% of patients with systemic sarcoidosis. Most reported cases are in women, most often in their fifth and sixth decades, and appear as multiple, asymptomatic, hardly indurated subcutaneous nodules without changes in the overlying epidermis. The lesions are characteristically located in the upper extremities, mainly in the forearms, and usually are bilateral and asymmetric. In most cases the lesions appear at the beginning of systemic sarcoidosis and are not associated with chronic fibrotic disease. Histopathologically, sarcoidosis is characterized by noncaseating naked granulomas involving fat lobules, with minimal to no septal involvement.

Sarcoidosis Occurring After Lymphoma

PubMed Central

London, Jonathan; Grados, Aurélie; Fermé, Christophe; Charmillon, Alexandre; Maurier, François; Deau, Bénédicte; Crickx, Etienne; Brice, Pauline; Chapelon-Abric, Catherine; Haioun, Corinne; Burroni, Barbara; Alifano, Marco; Le Jeunne, Claire; Guillevin, Loïc; Costedoat-Chalumeau, Nathalie; Schleinitz, Nicolas; Mouthon, Luc; Terrier, Benjamin

2014-01-01

Abstract Sarcoidosis is a granulomatous disease that most frequently affects the lungs with pulmonary infiltrates and/or bilateral hilar and mediastinal lymphadenopathy. An association of sarcoidosis and lymphoproliferative disease has previously been reported as the sarcoidosis-lymphoma syndrome. Although this syndrome is characterized by sarcoidosis preceding lymphoma, very few cases of sarcoidosis following lymphoma have been reported. We describe the clinical, biological, and radiological characteristics and outcome of 39 patients presenting with sarcoidosis following lymphoproliferative disease, including 14 previously unreported cases and 25 additional patients, after performing a literature review. Hodgkin lymphoma and non-Hodgkin lymphoma were equally represented. The median delay between lymphoma and sarcoidosis was 18 months. Only 16 patients (41%) required treatment. Sarcoidosis was of mild intensity or self-healing in most cases, and overall clinical response to sarcoidosis was excellent with complete clinical response in 91% of patients. Sarcoidosis was identified after a follow-up computerized tomography scan (CT-scan) or 18fluorodeoxyglucose-positron emission tomography/computerized tomography (18FDG-PET/CT) evaluation in 18/34 patients (53%). Sarcoidosis is therefore a differential diagnosis to consider when lymphoma relapse is suspected on a CT-scan or 18FDG-PET/CT, emphasizing the necessity to rely on histological confirmation of lymphoma relapse. PMID:25380084

Papular sarcoidosis of the knees. A frequent form of presentation of systemic sarcoidosis.

PubMed

Marcoval, Joaquim; Mañá, Juan

2016-03-29

In recent years we have observed with increasing frequency granulomatous papular lesions involving the knees, for which we proposed the term papular sarcoidosis of knees. To evaluate the clinicopathological features of papular sarcoidosis of the knees. Patients with papular lesions of the knees and histopathologically sarcoid granulomas were included in the study. Systemic sarcoidosis was investigated in all cases. Clinical charts were retrospectively retrieved. Biopsy specimens were evaluated under polarized light to detect foreign bodies. Fifty-three patients fulfilled inclusion criteria. In 36 cases systemic sarcoidosis was diagnosed and these cases were considered as papular sarcoidosis of the knees. Foreign particles were observed in 21 of these 36 patients. In only 9/36 patients did the activity of systemic disease persist over two years. In 17 cases sarcoidosis could not be demonstrated during follow-up. Papular sarcoidosis of the knees can be considered a relatively frequent form of cutaneous sarcoidosis usually present at the beginning of the disease that can be useful for the diagnosis of sarcoidosis. It is mainly observed in acute forms of sarcoidosis and can be considered a sign of good prognosis.

Subacute sarcoid myositis with ocular muscle involvement; a case report and review of the literature.

PubMed

Hayashi, Y; Ishii, Yoshiki; Nagasawa, J; Arai, S; Okada, H; Ohmi, F; Umetsu, T; Machida, Y; Kurasawa, K; Takemasa, A; Suzuki, S; Senoh, T; Sada, T; Hirata, K

2016-10-07

Sarcoidosis is a chronic granulomatous disease that can affect multiple organs. The lungs, eyes, and skin are known to be highly affected organs in sarcoidosis. There have been reports based on random muscle biopsy that 32-80% of systemic sarcoidosis comprises noncaseating granulomas; however, muscle involvement in sarcoidosis is generally asymptomatic and has an unknown frequency. We describe a case of acute to subacute sarcoid myositis of the skeletal and extraocular muscles. Typical ophthalmic involvement (manifested by infiltration of the ocular adnexa, intraocular inflammation, or infiltration of the retrobulbar visual pathways) and extraocular sarcoid myositis (as with the present case) is infrequently reported. It is important to keep in mind the rare yet perhaps underestimated entity of sarcoid myositis, and to utilize muscle biopsy and imaging tests for appropriate diagnosis and management of patients with sarcoidosis.

Sarcoidosis diagnostic score (SDS): a systematic evaluation to enhance the diagnosis of sarcoidosis.

PubMed

Bickett, Alexandra N; Lower, Elyse E; Baughman, Robert P

2018-05-17

The diagnosis of sarcoidosis is made by the combination of clinical features and biopsy results. The clinical features of sarcoidosis can be quite variable. We developed a Sarcoidosis Diagnostic Score (SDS) to summarize the clinical features of possible sarcoidosis patients. Biopsy confirmed sarcoidosis patients seen during a seven-month time period at the University of Cincinnati Sarcoidosis clinic were prospectively identified. Non-sarcoidosis patients seen at the same clinic were used as controls. Using a modified WASOG organ assessment instrument, we scored all patients for presence of biopsy, one or more highly probable symptom, and one or more at least probable symptom for each area. Two sarcoidosis scores were generated: SDS biopsy (with biopsy) and SDS clinical (without biopsy). The 980 evaluable patients were divided into two cohorts: an initial 600 patients (450 biopsy confirmed sarcoidosis, 150 controls) to establish cut-off values for SDS biopsy and SDS clinical and a validation cohort of 380 patients (103 biopsy confirmed sarcoidosis patients and 277 controls). The best cutoff value for SDS biopsy was > 6 (sensitivity =99.3%; specificity=100%). For the total the 980 patients, an SDS clinical > 3 had a sensitivity of 94.2%, specificity of 88.8%, and a likelihood ratio of 7.9. An SDS clinical score > 4 had a lower sensitivity of (76.9%) but higher specificity (98.6%). For sarcoidosis, the presence of specific clinical features, especially multi-organ involvement, can enhance the diagnostic certainty. The SDS scoring system quantitated the clinical features consistent with sarcoidosis. Copyright © 2018. Published by Elsevier Inc.

Chest Radiographic Screening for Sarcoidosis in the Diagnosis of Patients with Active Uveitis.

PubMed

Groen, Fahriye; van Laar, Jan A M; Rothova, Aniki

2017-06-01

Although chest radiography is currently recommended for the initial evaluation of patients with new-onset uveitis, the efficacy of this diagnostic screening modality is not known. To evaluate the diagnostic value of chest radiographs in patients with active uveitis of recent onset in a tertiary center in Western Europe. A retrospective cross-sectional study was conducted by reviewing all chest imaging for adults with new-onset (<1 yr) uveitis of unknown origin undergoing initial evaluation in the Department of Ophthalmology at Erasmus University Medical Center (Rotterdam, the Netherlands). Radiographic findings were related to clinical and other imaging characteristics and to final diagnoses. Screening chest radiographs were abnormal for 30 of 200 patients (15%) included in this study. Twenty-two of the 200 patients (11%) had biopsy-confirmed sarcoidosis, and an additional 12 patients were presumed to have sarcoidosis. The finding of chest radiographic abnormalities interpreted as typical of sarcoidosis was specific (91%; 95% confidence interval, 85.9-94.4%) but not sensitive (64%; 95% confidence interval, 43.0-80.3%) for biopsy-confirmed sarcoidosis. The combination of elevated serum angiotensin-converting enzyme level and chest radiographic findings typical of sarcoidosis increased the sensitivity to 79%. Biopsy-confirmed sarcoidosis was more common in patients with panuveitis (17 of 84; 20%) compared to patients with other anatomical locations of uveitis (5 of 116, 4%; P < 0.001). One patient was diagnosed with active pulmonary and ocular tuberculosis. Abnormal chest radiographs were found in 15% of patients with active uveitis of unknown origin and onset within 1 year of referral to a tertiary center in the Netherlands. A majority of the abnormal chest radiographs showed findings compatible with a diagnosis of sarcoidosis.

Foundation for Sarcoidosis Research

MedlinePlus

... a Clinical Trial Our mission is to stop sarcoidosis — join us. The sarcoidosis community needs your help ... receive periodic emails from the Foundation. Foundation For Sarcoidosis Research 1820 W. Webster Ave., Ste 304 Chicago, ...

Job and industry classifications associated with sarcoidosis in A Case-Control Etiologic Study of Sarcoidosis (ACCESS).

PubMed

Barnard, Juliana; Rose, Cecile; Newman, Lee; Canner, Martha; Martyny, John; McCammon, Chuck; Bresnitz, Eddy; Rossman, Milt; Thompson, Bruce; Rybicki, Benjamin; Weinberger, Steven E; Moller, David R; McLennan, Geoffrey; Hunninghake, Gary; DePalo, Louis; Baughman, Robert P; Iannuzzi, Michael C; Judson, Marc A; Knatterud, Genell L; Teirstein, Alvin S; Yeager, Henry; Johns, Carol J; Rabin, David L; Cherniack, Reuben

2005-03-01

To determine whether specific occupations and industries may be associated with sarcoidosis. A Case Control Etiologic Study of Sarcoidosis (ACCESS) obtained occupational and environmental histories on 706 newly diagnosed sarcoidosis cases and matched controls. We used Standard Industrial Classification (SIC) and Standard Occupational Classification (SOC) to assess occupational contributions to sarcoidosis risk. Univariable analysis identified elevated risk of sarcoidosis for workers with industrial organic dust exposures, especially in Caucasian workers. Workers for suppliers of building materials, hardware, and gardening materials were at an increased risk of sarcoidosis as were educators. Work providing childcare was negatively associated with sarcoidosis risk. Jobs with metal dust or metal fume exposures were negatively associated with sarcoidosis risk, especially in Caucasian workers. In this study, we found that exposures in particular occupational settings may contribute to sarcoidosis risk.

[Many faces of sarcoidosis].

PubMed

Prosch, H; Vonbank, K; Loewe, C; Beitzke, D

2016-01-01

Sarcoidosis is a systemic, inflammatory, granulomatous disease of unknown origin that can involve any organ. More than 90% of patients have thoracic sarcoidosis, which most frequently presents with bilateral hilar lymphadenopathy. In approximately 20% of patients with thoracic sarcoidosis there is involvement of the lung parenchyma as well as mostly asymptomatic cardiac sarcoidosis in up to 55% of patients. Most patients are asymptomatic and the diagnosis is an incidental finding on chest X-ray or during clarification of unspecific symptoms, such as fatigue or cough. In approximately two thirds of patients the disease undergoes spontaneous remission and in one third the disease follows a chronic or even progressive course. Furthermore, sarcoidosis can also be manifested in the abdominal organs, the central nervous system (CNS) and the musculoskeletal system. These manifestations are frequently subclinical and require targeted diagnostics when sarcoidosis is clinically suspected.

Pulmonary sarcoidosis.

PubMed

Spagnolo, Paolo; Rossi, Giulio; Trisolini, Rocco; Sverzellati, Nicola; Baughman, Robert P; Wells, Athol U

2018-05-01

Sarcoidosis is a granulomatous disease of unknown cause, occurs worldwide and has a highly variable prevalence. The disease is typically dominant in the lungs, although it can affect virtually any organ and is unpredictable in its clinical course. The severity of pulmonary sarcoidosis ranges from incidentally discovered radiographic abnormalities in asymptomatic patients to a chronic progressive disease that is refractory to treatment. Mortality from sarcoidosis appears to have increased in the past three decades, with respiratory failure being the most common cause of sarcoidosis-related death. Pulmonary fibrosis, extensive disease on high-resolution chest CT, impaired lung function, and pulmonary hypertension are well established predictors of poor clinical outcomes. In patients who need systemic therapy to control their disease, corticosteroids are the most commonly used first-line treatment, with antimetabolites generally representing an alternative for patients who are unresponsive to corticosteroids or who cannot tolerate them. Indeed, corticosteroid therapy is associated with toxic effects that correlate with both the cumulative dose and duration of treatment. The scarcity of truly effective therapies and shortage of reliable predictors of the unpredictable development of disease in individual patients greatly contribute to making sarcoidosis such a difficult disease to manage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diagnosis of sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, O.P.

1983-07-01

During the last decade, many biochemical and immunologic advances have been made in the treatment and understanding of sarcoidosis. These studies have helped us to understand the basic mechanisms involved in granuloma formation, and many clinicians have used the information to diagnose and assess the activity of sarcoidosis. Further studies are needed to clearly establish the role of these advances in the everyday management of patients with sarcoidosis.

Administering the Sarcoidosis Health Questionnaire to sarcoidosis patients in Serbia.

PubMed

Mihailović-Vučinić, Violeta; Gvozdenović, Branislav; Stjepanović, Mihailo; Vuković, Mira; Marković-Denić, Ljiljana; Milovanović, Aleksandar; Videnović-Ivanov, Jelica; Žugić, Vladimir; Škodrić-Trifunović, Vesna; Filipović, Snežana; Omčikus, Maja

2016-04-01

The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients.

Administering the Sarcoidosis Health Questionnaire to sarcoidosis patients in Serbia

PubMed Central

Mihailović-Vučinić, Violeta; Gvozdenović, Branislav; Stjepanović, Mihailo; Vuković, Mira; Marković-Denić, Ljiljana; Milovanović, Aleksandar; Videnović-Ivanov, Jelica; Žugić, Vladimir; Škodrić-Trifunović, Vesna; Filipović, Snežana; Omčikus, Maja

2016-01-01

Objective: The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. Methods: This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. Results: The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. Conclusions: The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients. PMID:27167430

[Cardiac sarcoidosis - clinical manifestation and diagnosis].

PubMed

Błaut-Jurkowska, Justyna; Podolec, Piotr; Olszowska, Maria

2016-08-01

Sarcoidosis is a multisystem inflammatory disease defined histologically by the formation of noncaseating granulomas. The etiology of sarcoidosis remains unknown. Heart involvement in the course of sarcoidosis concerns about 5% of patients. The most common manifestation of cardiac sarcoidosis are conduction abnormalities, arrhythmias and heart failure. The diagnostic algorithm includes performing a clinical history, a 12-lead electrocardiogram (ECG) and an echocardiogram. If any of the initial screening investigations yields an abnormality, diagnostics should be continue using advanced imaging techniques: cardiovascular magnetic resonance (CMR) or fluorodeoxyglucose positron emission tomography (FDG-PET). Nowadays endomyocardial biopsy is not performed routinely.The clinical picture of cardiac sarcoidosis is highly variable. Screening for cardiac sarcoidosis should be performed in all patients diagnosed with extracardiac sarcoidosis. Cardiac sarcoidosis should also be suspected in young patients without a diagnosis of sarcoidosis who present with conduction abnormalities of unknown etiology, because cardiac sarcoidosis may be the first or the only manifestation of the disease. © 2016 MEDPRESS.

Musculoskeletal involvement in sarcoidosis*, **

PubMed Central

Nessrine, Akasbi; Zahra, Abourazzak Fatima; Taoufik, Harzy

2014-01-01

Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management. PMID:24831403

Psychological stress in sarcoidosis.

PubMed

Wilsher, Margaret L

2012-09-01

Sarcoidosis is a chronic illness associated with emotional and physical consequences which impact on quality of life. Although the impact of fatigue is well understood, emotional impacts of sarcoidosis are less commonly recognized and addressed in routine clinical practice. The purpose of this review is to highlight that sarcoidosis can result in considerable psychological distress. Not only is there a high prevalence of depressive symptoms in sarcoidosis, but clinical depressive and anxiety disorders are more common than seen in the general population. Patients with sarcoidosis have perceptions and beliefs about their disease that may impact on their willingness to engage in recommended therapies. They may also exhibit a disordered perception of their disease and a personality profile of neuroticism. Understanding the minimally important clinical difference in the Fatigue Assessment Scale (FAS) and validation of the Sarcoidosis Health Questionnaire (SHQ) across different populations supports the use of these tools in routine clinical practice and clinical trials. Understanding the global impact of sarcoidosis is important for patients and clinicians, and use of validated instruments, such as the SHQ and FAS, allows for more comprehensive assessment of the disease and the impact of any interventions.

Bronchoscopic modalities to diagnose sarcoidosis.

PubMed

Benzaquen, Sadia; Aragaki-Nakahodo, Alejandro Adolfo

2017-09-01

Several studies have investigated different bronchoscopic techniques to obtain tissue diagnosis in patients with suspected sarcoidosis when the diagnosis cannot be based on clinicoradiographic findings alone. In this review, we will describe the most recent and relevant evidence from different bronchoscopic modalities to diagnose sarcoidosis. Despite multiple available bronchoscopic modalities to procure tissue samples to diagnose sarcoidosis, the vast majority of evidence favors endobronchial ultrasound transbronchial needle aspiration to diagnose Scadding stages 1 and 2 sarcoidosis. Transbronchial lung cryobiopsy is a new technique that is mainly used to aid in the diagnosis of undifferentiated interstitial lung disease; however, we will discuss its potential use in sarcoidosis. This review illustrates the limited information about the different bronchoscopic techniques to aid in the diagnosis of pulmonary sarcoidosis. However, it demonstrates that the combination of available bronchoscopic techniques increases the diagnostic yield for suspected sarcoidosis.

Morbidity and Mortality in Sarcoidosis

PubMed Central

Gerke, Alicia K.

2015-01-01

Purpose of Review Chronic sarcoidosis is a complex disease with numerous comorbid conditions and can be fatal in some cases. Recognizing causes of morbidity and mortality is important to effectively select treatments, manage symptoms, and improve outcomes. The purpose of this review is to examine emerging knowledge on morbidity and mortality in sarcoidosis. Recent Findings Approximately one to five percent of patients with sarcoidosis die from complications of sarcoidosis. Recent population studies indicate that mortality may be increasing over the past decade. The reasons behind these trends are unclear, but could include increasing incidence, detection rates, severity of disease, or age of the population. Morbidity of sarcoidosis is reflected by a trend of increased hospitalizations over recent years and increased use of healthcare resources. Morbidity can be caused by organ damage from granulomatous inflammation, treatment complications, and psychosocial effects of the disease. Recent studies are focused on morbidity related to cardiopulmonary complications, bone health, and aging within the sarcoidosis population. Last, sarcoidosis is associated with autoimmune diseases, pulmonary embolism, and malignancy; however, the underlying mechanisms linking diseases continue to be debated. Summary Morbidity in sarcoidosis is significant and multifactorial. Mortality is infrequent, but may be increasing over the years. PMID:25029298

Respiratory muscle involvement in sarcoidosis.

PubMed

Schreiber, Tina; Windisch, Wolfram

2018-07-01

In sarcoidosis, muscle involvement is common, but mostly asymptomatic. Currently, little is known about respiratory muscle and diaphragm involvement and function in patients with sarcoidosis. Reduced inspiratory muscle strength and/or a reduced diaphragm function may contribute to exertional dyspnea, fatigue and reduced health-related quality of life. Previous studies using volitional and non-volitional tests demonstrated a reduced inspiratory muscle strength in sarcoidosis compared to control subjects, and also showed that respiratory muscle function may even be significantly impaired in a subset of patients. Areas covered: This review examines the evidence on respiratory muscle involvement and its implications in sarcoidosis with emphasis on pathogenesis, diagnosis and treatment of respiratory muscle dysfunction. The presented evidence was identified by a literature search performed in PubMed and Medline for articles about respiratory and skeletal muscle function in sarcoidosis through to January 2018. Expert commentary: Respiratory muscle involvement in sarcoidosis is an underdiagnosed condition, which may have an important impact on dyspnea and health-related quality of life. Further studies are needed to understand the etiology, pathogenesis and extent of respiratory muscle involvement in sarcoidosis.

Causes of death in patients with chronic sarcoidosis.

PubMed

Hu, Xiaowen; Carmona, Eva M; Yi, Eunhee S; Pellikka, Patricia A; Ryu, Jay

2016-10-07

Sarcoidosis is a multi-system, granulomatous disorder of unknown etiology that is associated with a variable prognosis and sometimes results in death. There are conflicting reports regarding the causes of death in patients with sarcoidosis. Forty-four consecutive patients with sarcoidosis who underwent an autopsy (35 patients) or died at Mayo Clinic (Rochester, MN, USA) over a 20-yr period, from January 1, 1994 to December 31, 2013 were analyzed. The median age at death was 63 years (range, 33-94 years) and there were 22 (50%) women. Sarcoidosis had not been clinically diagnosed in 16 (36%) patients before death. Fifteen deaths (34%) were related to sarcoidosis and included seven deaths (16%) from cardiac sarcoidosis and four deaths (9%) from progressive pulmonary sarcoidosis. Other sarcoidosis-related causes of death included advanced hepatic sarcoidosis (5%) and opportunistic infections (5%) related to immunosuppressive therapy for treating sarcoidosis. Among seven patients dying from cardiac sarcoidosis, three had been diagnosed with sarcoidosis during life and cardiac involvement was known in two of them. Six of seven deaths from cardiac sarcoidosis occurred in the autopsied cohort while all four deaths from pulmonary sarcoidosis occurred in those not autopsied. In the majority of patients dying with sarcoidosis the cause of death is unrelated to sarcoidosis. Cardiac involvement is the most common cause of sarcoidosis-related deaths in patients subjected to postmortem examination and was usually undiagnosed during life. The cause distribution of death in patients with sarcoidosis differed depending on whether autopsy was performed.

Radiology of sarcoidosis.

PubMed

James, D G; Timmis, B; Barter, S; Carstairs, S

1989-03-01

This review of the radiology of sarcoidosis encompasses intrathoracic involvement, upper respiratory tract sarcoidosis, pleural disease, and involvement of bone, joint, neurological system, heart, kidney and alimentary tract. Attention is drawn to the value of CT scans, magnetic resonance imaging, gallium, and neutron activation analysis.

Abdominal Sarcoidosis Mimicking Peritoneal Carcinomatosis.

PubMed

Roh, Won Seok; Lee, Seungho; Park, Ji Hyun; Kang, Jeonghyun

2018-04-01

We present a patient diagnosed with skin sarcoidosis, breast cancer, pulmonary tuberculosis, and peritoneal sarcoidosis with a past history of colorectal cancer. During stage work up for breast cancer, suspicious lesions on peritoneum were observed in imaging studies. Considering our patient's history and imaging findings, we initially suspected peritoneal carcinomatosis. However, the peritoneal lesion was diagnosed as sarcoidosis in laparoscopic biopsy. This case demonstrates that abdominal sarcoidosis might be considered as a differential diagnosis when there is a lesion suspected of being peritoneal carcinomatosis with nontypical clinical presentations.

Development and testing of item response theory-based item banks and short forms for eye, skin and lung problems in sarcoidosis.

PubMed

Victorson, David E; Choi, Seung; Judson, Marc A; Cella, David

2014-05-01

Sarcoidosis is a multisystem disease that can negatively impact health-related quality of life (HRQL) across generic (e.g., physical, social and emotional wellbeing) and disease-specific (e.g., pulmonary, ocular, dermatologic) domains. Measurement of HRQL in sarcoidosis has largely relied on generic patient-reported outcome tools, with little disease-specific measures available. The purpose of this paper is to present the development and testing of disease-specific item banks and short forms of lung, skin and eye problems, which are a part of a new patient-reported outcome (PRO) instrument called the sarcoidosis assessment tool. After prioritizing and selecting the most important disease-specific domains, we wrote new items to reflect disease-specific problems by drawing from patient focus group and clinician expert survey data that were used to create our conceptual model of HRQL in sarcoidosis. Item pools underwent cognitive interviews by sarcoidosis patients (n = 13), and minor modifications were made. These items were administered in a multi-site study (n = 300) to obtain item calibrations and create calibrated short forms using item response theory (IRT) approaches. From the available item pools, we created four new item banks and short forms: (1) skin problems, (2) skin stigma, (3) lung problems, and (4) eye Problems. We also created and tested supplemental forms of the most common constitutional symptoms and negative effects of corticosteroids. Several new sarcoidosis-specific PROs were developed and tested using IRT approaches. These new measures can advance more precise and targeted HRQL assessment in sarcoidosis clinical trials and clinical practice.

Validation of the King's Sarcoidosis Questionnaire (KSQ) in a Dutch sarcoidosis population.

PubMed

Van Manen, Mirjam J G; Wapenaar, Monique; Strookappe, Bert; Drent, Marjolein; Elfferich, Marjon; de Vries, Jolanda; Gosker, Harry R; Birring, Surinder S; Patel, Amit S; van den Toorn, Leon; van den Blink, Bernt; Boomars, Karin; Hoitsma, Elske; Wijsenbeek, Marlies S

2016-03-29

The King's Sarcoidosis Questionnaire (KSQ) is a brief questionnaire assessing health status using five modules (General Health Status, Lung, Eyes, Skin, Medication) in patients with sarcoidosis. The KSQ was only validated in one English sarcoidosis cohort. The aim of this study was to validate the KSQ in a Dutch sarcoidosis population. The KSQ was translated according to international guidelines and tested in interviews with patients. Consecutive outpatients completed multiple questionnaires twice, two weeks apart. Construct validity, internal consistency and repeatability were determined. Of the 98 patients included 85 had lung, 22 skin and 24 eye disease. There was good construct validity of the KSQ General Health Status module against the World Health Organization Quality of Life-BREF questionnaire. The Medication module correlated weak to moderate with most questionnaires. The correlations with organ-specific questionnaires varied from strong for Eyes (r=0.75), Skin (r=-0.62) to moderate for Lung (r=-0.45 with MRC breathlessness scale). Internal consistency was good for all KSQ modules (Cronbach's α 0.72-0.93). Intraclass correlation coefficients (0.70-0.90) and Bland-Altman plots showed good repeatability of the KSQ. The Dutch KSQ is the first translation of the English KSQ, validated in a Dutch sarcoidosis population.

Nonsteroidal therapy of sarcoidosis.

PubMed

Korsten, Peter; Mirsaeidi, Mehdi; Sweiss, Nadera J

2013-09-01

None of the medications used in clinical practice to treat sarcoidosis have been approved by the regulatory authorities. Understanding how to use disease-modifying antisarcoid drugs, however, is essential for physicians treating patients with sarcoidosis. This review summarizes the recent studies of medications used for sarcoidosis with a focus on nonsteroidal therapies. Studies from 2006 to 2013 were considered for review to update clinicians on the most relevant literature published over the last few years. Several recently published pieces of evidence have helped expand our ability to more appropriately sequence second-line and third-line therapies for sarcoidosis. For instance, methotrexate and azathioprine may be useful and well tolerated medications as second-line treatment. Mycophenolate mofetil might have a role in neurosarcoidosis. TNF-α blockers and other biologics seem to be well tolerated medications for the most severely affected patients. Corticosteroids remain the first-line therapy for sarcoidosis as many patients never require treatment or only necessitate a short treatment duration. Second-line and third-line therapies described in this article should be used in patients with progressive or refractory disease or when life-threatening complications are evident at the time of presentation.

Subcutaneous sarcoidosis: a clinical analysis of nine patients.

PubMed

Ando, Masaru; Miyazaki, Eishi; Hatano, Yutaka; Nishio, Suehiro; Torigoe, Chihiro; Yamasue, Mari; Mukai, Yutaka; Nureki, Shin-Ichi; Kadota, Jun-Ichi

2016-09-01

Subcutaneous sarcoidosis is the specific subset of cutaneous sarcoidosis frequently associated with systemic disease. However, the disease activity, severity, and prognosis have not yet been elucidated due to the limited number of reported cases. The purpose of this study was to identify the clinical, laboratory, and prognostic differences between subcutaneous sarcoidosis and other type of cutaneous sarcoidosis. All patients with sarcoidosis diagnosed histopathologically from 2000 to 2012 at our institution were enrolled. The clinical, laboratory, chest X-ray, and pulmonary function test results were retrospectively evaluated in the patients with cutaneous sarcoidosis. In the 130 patients with sarcoidosis, cutaneous sarcoidosis was diagnosed in 37 patients (28.4 %), and 9 (6.9 %) of these patients had subcutaneous sarcoidosis. The serum levels of soluble interleukin-2 receptor (sIL-2R) were significantly elevated in the group of patients with subcutaneous sarcoidosis in comparison to the patients with other types of cutaneous sarcoidosis, whereas there was no significant difference in the severity score between the two groups. Following a 2-year observation period, three patients were in remission, five patients demonstrated stable disease, and one patient had progressive disease. Subcutaneous sarcoidosis may be associated with the disease activity, although it was not found to be associated with the disease severity and it was not a predictive factor for the prognosis. Furthermore, the prevalence of subcutaneous sarcoidosis may be higher than that in previously reported series.

Evidence for Mycobacteria in Sarcoidosis

PubMed Central

Brownell, Isaac; Ramírez-Valle, Francisco; Sanchez, Miguel

2011-01-01

Despite its recognition as a distinct granulomatous disease for over a century, the etiology of sarcoidosis remains to be defined. Since the early 1900s, infectious agents have been suspected in causing sarcoidosis. For much of this time, mycobacteria were considered a likely culprit, yet until recently, the supporting evidence has been tenuous at best. In this review, we evaluate the reported association between mycobacteria and sarcoidosis. Historically, mycobacterial infection has been investigated using histologic stains, cultures of lesional tissue or blood, and identification of bacterial nucleic acids or bacterial antigens. More recently, advances in biochemical, molecular, and immunological methods have produced a more rigorous analysis of the antigenic drivers of sarcoidosis. The result of these efforts indicates that mycobacterial products likely play a role in at least a subset of sarcoidosis cases. This information, coupled with a better understanding of genetic susceptibility to this complex disease, has therapeutic implications. PMID:21659662

Successful treatment with adalimumab for severe multifocal choroiditis and panuveitis in presumed (early-onset) ocular sarcoidosis.

PubMed

Achille, Marino; Ilaria, Pagnini; Teresa, Giani; Roberto, Caputo; Ilir, Arapi; Piergiorgio, Neri; Rolando, Cimaz; Gabriele, Simonini

2016-02-01

Early-onset sarcoidosis (EOS) and Blau syndrome are rare auto-inflammatory diseases characterized by a triad of skin rash, granulomatous uveitis, and symmetrical polyarthritis occurring in early childhood. In this paper, we describe a case report very interesting for the multidisciplinary management (pediatric rheumatologist and ophthalmologist), the challenging diagnosis and the difficult choice of the best treatment. We describe a case report of an 8-year old with recurrent episodes of acute uveitis that developed bilateral granulomatous panuveitis initially treated with topical and systemic steroids. Genetic testing for NOD2/CARD15 revealed a heterozygous mutation on exon 4 in the NBD domain (P268S/SNP5). Therefore, an incomplete EOS was suspected. Because uveitis worsening with multifocal chorioretinitis aggravation, intravenous boluses of methylprednisolone were administered. During the steroids tapering, she flared again, and methotrexate was started along with corticosteroids pulse therapy. However, new ocular granuloma appeared, macular oedema with poor visual outcome occurred, and therefore, adalimumab was added to MTX and steroids. After 6 months since the new therapy started, she had a complete visual recovery, and she was able to stop steroid treatment. At 2 years of follow-up, she is still in remission on treatment, and her visual acuity is normal. No side effects were observed. In our patient, we found a heterozygous mutation on exon 4 in the NBD domain (P268S/SNP5) of NOD2/CARD15 gene and an incomplete EOS was hypothesized. The role of this variant is currently under study. Adalimumab use dramatically changed the course of eye disease, prompting to stop steroid treatment and preserving visual acuity.

[Epidemiology and Clinical Presentation of Sarcoidosis].

PubMed

Costabel, U; Wessendorf, T E; Bonella, F

2017-06-01

Sarcoidosis is a systemic disease of unknown aetiology. Typical histology shows epithelioid cell granulomas, and typical immunopathology enhanced Th1 type immune responses in the involved organs. The disease occurs worldwide, but more frequently in northern countries than in the south. In Germany, the incidence is estimated to be 10 per 100,000, and the prevalence 44-48 per 100,000. Sarcoidosis usually affects adults under 50 years of age, but can also be seen in children, adolescents and in the elderly. Women are more frequently affected than men. Familial clusters can occur. The clinical presentation of sarcoidosis varies widely and depends on the manifestations in the individual organ. Systemic symptoms include fatigue, night sweats, weight loss, fever, arthralgia and myalgia. Organ-specific symptoms include cough and dyspnoea, with pulmonary involvement, headache and palsy in neurosarcoidosis, arrhythmias and heart failure in cardiac sarcoidosis, and manifold skin lesions with skin involvement. Relapses are rarely seen in acute sarcoidosis, whereas the chronic form tends to relapse more frequently. Löfgren's syndrome, a specific phenotype of acute sarcoidosis, is characterised by bihilar lymphadenopathy, ankle arthritis and erythema nodosum. Chronic sarcoidosis can be asymptomatic, despite radiological changes, which may be extensive. By definition, sarcoidosis has become chronic after 2 years of disease with ongoing signs of activity. The long-term prognosis is generally good, but depends on the different organ manifestations and complications. Georg Thieme Verlag KG Stuttgart · New York.

FDG PET/CT in bone sarcoidosis.

PubMed

Grozdic Milojevic, Isidora; Sobic-Saranovic, Dragana; Videnovic-Ivanov, Jelica; Saranovic, Djordjije; Odalovic, Strahinja; Artiko, Vera

2016-03-29

Bone sarcoidosis is rare manifestation of disease usually accompanied with pulmonary involvement. Until today, exact prevalence of bone sarcoidosis is not known, since reported prevalence varies widely depending on the studied population and the used diagnostic techniques. To determine the prevalence of bone involvement and distribution pattern in active chronic sarcoidosis by using FDG PET/CT. Between January 2010 and December 2011, 98 patients with chronic sarcoidosis and presence of prolonged symptoms or other findings suggestive of active disease were referred to FDG PET/CT examination. Active disease was found in 82 patients, and they all were screened for presence of bone sarcoidosis on FDG PET/CT. All patients also underwent MDCT and assessment of serum ACE level. Bone sarcoidosis was present in 18/82 patients with active sarcoidosis. FDG uptake in bones was focal in 8 (44.4%), diffuse in 6 (33.3%) and both diffuse and focal in 4 (22.2%) patients. CT indicated bone abnormalities only in 5% patients. Osseous involvement was present in: pelvis (61.1%), vertebrae (44.4%), ribs (27.8%) and bone marrow (16.7%). Some patients had two or more locations of disease. Follow-up FDG PET/CT showed normal findings in two patients, same localization of active disease in four patients and progression of disease in one. In patients with active chronic sarcoidosis 22% of patients had osseous abnormalities on FDG PET/CT that mostly were not detected on CT.

Nonsteroidal therapy of sarcoidosis

PubMed Central

Korsten, Peter; Mirsaeidi, Mehdi; Sweiss, Nadera J.

2014-01-01

Purpose of review None of the medications used in clinical practice to treat sarcoidosis have been approved by the regulatory authorities. Understanding how to use disease-modifying antisarcoid drugs, however, is essential for physicians treating patients with sarcoidosis. This review summarizes the recent studies of medications used for sarcoidosis with a focus on nonsteroidal therapies. Studies from 2006 to 2013 were considered for review to update clinicians on the most relevant literature published over the last few years. Recent findings Several recently published pieces of evidence have helped expand our ability to more appropriately sequence second-line and third-line therapies for sarcoidosis. For instance, methotrexate and azathioprine may be useful and well tolerated medications as second-line treatment. Mycophenolate mofetil might have a role in neurosarcoidosis. TNF-α blockers and other biologics seem to be well tolerated medications for the most severely affected patients. Summary Corticosteroids remain the first-line therapy for sarcoidosis as many patients never require treatment or only necessitate a short treatment duration. Second-line and third-line therapies described in this article should be used in patients with progressive or refractory disease or when life-threatening complications are evident at the time of presentation. PMID:23884295

Thyroid stimulating antibodies in sarcoidosis.

PubMed

Attali, J R; Valensi, P; Valeyre, D; Sandre-Banon, D; Sebaoun, J; Battesti, J P

1994-06-01

Thyroid disorders, particularly euthyroid goiters and hyperthyroidism, can be observed in sarcoidosis. The aim of this study was to analyze the presence of thyroid stimulating antibodies (TSAb) in 21 patients with sarcoidosis. 12 patients out of 21 had simultaneous euthyroid goiter. The others were euthyroid and free of goiter. The TSAb testing was carried out using the rat thyroid fragment perifusion technique. Thyroid response to IgG was determined by the mean rate of T4 release (R) during a 30-min perifusion and the secretion peak (Imax). Antibodies inhibiting TSH binding to its receptors were also looked for. Ten patients were TSAb+ and eleven were TSAb-. There was no difference between the TSAb+ and TSAb- groups in the clinical parameters for sarcoidosis, nor in the number of goiters found (n = 6 for both groups). In 5 out of the 6 cases where goiter was present in the TSAb+ group it was homogeneous and diagnosed at the same time as or after the first signs of sarcoidosis, whereas in 5 out of the 6 cases of goiter in TSAb- patients, it was nodular, diagnosed before sarcoidosis in 3 of them, endemic in one of them, and familial in another. The search for antibodies inhibiting TSH binding to its receptors was negative in 10 out of 21 patients tested. Although the presence of thyroid-stimulating antibodies in the serum of patients with sarcoidosis, found here for the first time, remains to be explained, it pleads in favor of the immunologic nature of the association of sarcoidosis with thyroid disorders.

[Opportunistic infections and sarcoidosis].

PubMed

Jamilloux, Y; Bernard, C; Lortholary, O; Kerever, S; Lelièvre, L; Gerfaud-Valentin, M; Broussolle, C; Valeyre, D; Sève, P

2017-05-01

Opportunistic infections (OI) are uncommon in sarcoidosis (1 to 10%) and mostly occur in patients with previously diagnosed disease or can rarely be the presenting manifestation. The most common OIs are, in descending order: aspergillosis, cryptococcosis, and mycobacterial infections. Treatment with corticosteroids is the most frequent risk factor for OI occurrence during sarcoidosis but immunosuppressive drugs and therapy with anti-TNFα are also risk factors. Overall, clinical presentation, treatment, and outcome are identical to that occur in other conditions complicated with the occurrence of OIs. However, some atypical presentations of OIs can mimic sarcoidosis exacerbation and misdiagnosis may lead clinicians to increase immunosuppression, causing worsening of the OI. The meticulous collection of patient's history along with factors differentiating OI from sarcoidosis exacerbation is key factor to optimally manage these patients. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Endobronchial Mucosal Neuroma with Sarcoidosis.

PubMed

Erdem, Ipek; Duman, Dildar; Eroglu, Selma; Agca, Meltem; Erdagi, Aykut; Turker, Hatice; Hazar, Armagan

2018-02-01

A first case of endobronchial mucosal neuroma with sarcoidosis is hereby reported. A 67-year female patient, who was diagnosed as sarcoidosis previously, was admitted to our hospital with symptoms of dyspnea, chest pain and fatigue. Middle lobe atelectasis and endobronchial lesion were observed in thorax computed tomography (CT). Fiberoptic bronchoscopy revealed polypoid lesions and histopathological examination of biopsy material showed clustered nerve bundles consistent with mucosal neuroma and non-necrotising granulomas consistent with sarcoidosis. Mucosal neuromas are pathognomonic features of multiple endocrine neoplasia (MEN) type 2B. But other components of MEN type 2B such as medullary tyroid carcinoma or pheochromocytoma were not detected in our patient. Hence, a diagnosis of solitary mucosal neuroma and sarcoidosis in the bronchi was made.

Clinical characteristics of patients with bone sarcoidosis.

PubMed

Zhou, Ying; Lower, Elyse E; Li, Huiping; Farhey, Yolanda; Baughman, Robert P

2017-08-01

To assess the clinical features, diagnosis, and treatment of bone sarcoidosis in the United States. Patients with bone sarcoidosis were identified and matched to sarcoidosis patients based on race, gender, and age. Detailed characteristics were obtained by medical record review. A total of 64 patients with bone sarcoidosis were enrolled in this study. The female:male ratio was 1.46:1 and the white:black ratio was 3:1. Thirty-eight (59.4%) of 64 patients had bone symptoms. Compared to matched cases, bone sarcoidosis patients have more multi-organ involvement and higher incidence with liver, spleen, and extrathoracic lymph node involvement than controls (P < 0.05). Spine was the most commonly affected bone in 44 (68.8%) of patients, followed by pelvis (35.9%), and hands (15.6%). MRI and PET/CT scan was the common imaging technology, which performed in 36 patients and 32 patients, respectively, and with 97.2% and 93.8% positive bone uptake. Laboratory test indicated anemia was more common in bone sarcoidosis group than controls (P = 0.044). Infliximab was more commonly used in bone sarcoidosis patients than controls (P = 0.009). Bone sarcoidosis was associated with multi-organs affection, and high frequency of liver, spleen, or extrathoracic lymph node involvement. Infliximab should be considered in those patients with aggressive and refractory bone sarcoidosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Isolated thyroid gland sarcoidosis and hyperthyroidism].

PubMed

Langsteger, W; Lind, P; Beham, A; Költringer, P; Eber, O

1989-04-29

A case of isolated sarcoidosis of the thyroid gland, associated with hyperthyroidism, is reported in a 28-year-old male patient whose thyroid was removed for hyperthyroid multinodular goitre. Histology revealed a regressive adenoma and sarcoidosis in non-adenomatous thyroid residue. Further diagnosis, therapeutic management and a 3-year follow-up did not disclose any specific changes or involvement of other tissues. Isolated thyroidal sarcoidosis with hyperthyroid alterations are extremely rare and mostly chance findings; simultaneous occurrence of thyroid sarcoidosis and hyperthyroidism may be a symptom of gland infiltration for which an adequate explanation is still lacking.

Multisystemic Sarcoidosis Presenting as Pretibial Leg Ulcers.

PubMed

Wollina, Uwe; Baunacke, Anja; Hansel, Gesina

2016-09-01

Sarcoidosis is a multisystemic disease of unknown etiology. Up to 30% of patients develop cutaneous manifestations, either specific or nonspecific. Ulcerating sarcoidosis leading to leg ulcers is a rare observation that may lead to confusions with other, more common types of chronic leg ulcers. We report the case of a 45-year-old female patient with chronic multisystemic sarcoidosis presenting with pretibial leg ulcers. Other etiology could be excluded. Histology revealed nonspecific findings. Therefore, the diagnosis of nonspecific leg ulcers in sarcoidosis was confirmed. Treatment consisted of oral prednisolone and good ulcer care. Complete healing was achieved within 6 months. Sarcoidosis is a rare cause of leg ulcers and usually sarcoid granulomas can be found. Our patient illustrates that even in the absence of sarcoid granulomas, leg ulcers can be due to sarcoidosis. © The Author(s) 2016.

Extensive upper respiratory tract sarcoidosis

PubMed Central

Soares, Mafalda Trindade; Sousa, Carolina; Garanito, Luísa; Freire, Filipe

2016-01-01

Sarcoidosis is a chronic granulomatous disease of unknown aetiology. It can affect any part of the organism, although the lung is the most frequently affected organ. Upper airway involvement is rare, particularly if isolated. Sarcoidosis is a diagnosis of exclusion, established by histological evidence of non-caseating granulomas and the absence of other granulomatous diseases. The authors report a case of a man with sarcoidosis manifesting as a chronic inflammatory stenotic condition of the upper respiratory tract and trachea. PMID:27090537

Sarcoidosis extent relates to molecular variability.

PubMed

Monast, C S; Li, K; Judson, M A; Baughman, R P; Wadman, E; Watt, R; Silkoff, P E; Barnathan, E S; Brodmerkel, C

2017-06-01

The molecular basis of sarcoidosis phenotype heterogeneity and its relationship to effective treatment of sarcoidosis have not been elucidated. Peripheral samples from sarcoidosis subjects who participated in a Phase II study of golimumab [anti-tumour necrosis factor (TNF)-α] and ustekinumab [anti-interleukin (IL)-12p40] were used to measure the whole blood transcriptome and levels of serum proteins. Differential gene and protein expression analyses were used to explore the molecular differences between sarcoidosis phenotypes as defined by extent of organ involvement. The same data were also used in conjunction with an enrichment algorithm to identify gene expression changes associated with treatment with study drugs compared to placebo. Our analyses revealed marked heterogeneity among the three sarcoidosis phenotypes included in the study cohort, including striking differences in enrichment of the interferon pathway. Conversely, enrichments of multiple pathways, including T cell receptor signalling, were similar among phenotypes. We also identify differences between treatment with golimumab and ustekinumab that may explain the differences in trends for clinical efficacy observed in the trial. We find that molecular heterogeneity is associated with sarcoidosis in a manner that may be related to the extent of organ involvement. These findings may help to explain the difficulty in identifying clinically efficacious sarcoidosis treatments and suggest hypotheses for improved therapeutic strategies. © 2017 British Society for Immunology.

Hypothalamic digoxin, hemispheric chemical dominance, and sarcoidosis.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-11-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with systemic sarcoidosis. All l5 patients with sarcoidosis were right-handed/left hemispheric dominant by the dichotic listening test. The pathway was also studied in normal right hemispheric, left hemispheric, and bihemispheric dominant individuals for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis. In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these patients. The neurotransmitter/digoxin-mediated increased intra cellular calcium induced immune activation, ubiquinone deficiency-related mitochondrial dysfunction/free radical generation, and increased dolichol-related altered glycoconjugate metabolism/endogenous self-glycoprotein antigen generation are crucial to the pathogenesis of sarcoidosis. The biochemical patterns obtained in sarcoidosis are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with sarcoidosis were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Sarcoidosis occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

[Sarcoidosis and uveitis : An update].

PubMed

Garweg, J G

2017-06-01

Ocular involvement in sarcoidosis is present in up to one third of patients and is frequently manifested before the underlying systemic disease has been diagnosed. With a view to the therapeutic consequences an early diagnosis of the underlying disease is advantageous. In cases of visual loss early diagnostic measures include invasive procedures, such as ultrasound-guided bronchoalveolar lavage and transbronchial biopsy, if nodular conjunctival or cutaneous manifestations which would confirm the diagnosis are not present. Sufficiently sensitive biomarkers of disease activity have not yet been identified. As elevated activity of angiotensin-converting enzyme (ACE) and lysozyme are associated with disease activity they may be supportive of but not specific for the diagnosis. Other indicators include calcemia, calciuria, augmented activity of hepatic enzymes, cutaneous anergy and hilar changes in the lungs. In patients with newly diagnosed anterior uveitis presenting with granulomatous mutton-fat corneal precipitates, snow balls and vitreous body base condensates with mild retinal periphlebitis in intermediate uveitis as well as multifocal choroiditis (creamy choroidal lesions at different stages of activity and approximately 500 µm in diameter), a diagnosis of sarcoidosis has to be considered and tuberculosis should be excluded, even in the absence of a known systemic disease. Anterior uveitis is frequently a self-limiting condition, which can be well-controlled with topical steroids. On the other hand, intermediate, posterior and panuveitis are typically associated with a chronic course and require systemic therapy to prevent severe loss of vision. If the response to systemic corticosteroids is insufficient, treatment with immunomodulatory agents and biologics is initiated at progressively earlier stages, with a view to averting permanent organ damage and frequently with a positive impact on the short and long-term outcomes, even in therapy-refractive cases.

Sarcoidosis presenting as non-scarring non-scalp alopecia.

PubMed

Dan, Luke; Relic, John

2016-08-01

In this article we describe a 39-year-old man who presented with non-scarring non-scalp alopecia of his limbs as the initial presentation of sarcoidosis. Alopecia is a rare cutaneous manifestation of sarcoidosis. A literature review has found only one other example of sarcoidosis presenting as non-scarring non-scalp alopecia in an area other than the scalp in a patient who was otherwise asymptomatic. Several reported cases have described scarring alopecia of the scalp, which is the area of skin most commonly affected by sarcoidosis. There has been one documented case of sarcoidosis manifesting as total body non-scarring alopecia in a patient who had systemic symptoms of sarcoidosis. Other cases have presented rare cutaneous manifestations of sarcoidosis but in all these cases several other organ systems have been involved, and the patient has had systemic symptoms on presentation or the cutaneous presentation did not include non-scalp non-scarring alopecia. © 2015 The Australasian College of Dermatologists.

Cardiac sarcoidosis: challenges in clinical practice.

PubMed

Bakker, Anne L; Grutters, Jan C; Keijsers, Ruth G; Post, Martijn C

2017-09-01

To address the current recommendations for screening, diagnosis, and treatment of cardiac sarcoidosis and the difficulties to put these recommendations into clinical practice. The incidence of cardiac sarcoidosis appears to be higher than earlier reported, probably because of improved imaging techniques. Late gadolinium enhancement with cardiac MRI (LGE-CMR) and fluorodeoxyglucose positron emission tomography obtained a central role in the diagnostic algorithm and monitoring of disease activity. New techniques are being investigated: T1 and T2 mapping for early detection in CMR, a sarcoid-specific tracer in PET, integrated positron emission tomography/MRI scanners, and assessment of scar with LGE in cardiac computed tomography. Isolated cardiac sarcoidosis is an increasingly recognized phenotype, but still an enormous challenge in clinical practice. The prognostic value of (and extent of) LGE-CMR should be taken into account for risk assessment and internal cardiac defbrillator therapy, even in patients with preserved left ventricular function. Unfortunately, randomized controlled trials to guide immunosuppressive therapy are still lacking. A multidisciplinary approach to diagnose and treat cardiac sarcoidosis patients in specialized centers is strongly recommendable. Cardiac sarcoidosis is increasingly recognized because of improved imaging techniques; however, treatment of cardiac sarcoidosis is still mainly based on expert opinion.

Radioisotope scanning in osseous sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rohatgi, P.K.

1980-01-01

Technetium-99m (/sup 99m/Tc)-labeled pyrophosphate or diphosphonate compounds and gallium-67 citrate (/sup 67/Ga) are two radionuclide scanning agents that are in widespread use in clinical practice. Technetium-99m pyrophosphate is used extensively for bone scanning to detect metastatic bone disease, benign bone tumors, osteomyelitis, benign hypertrophic osteoarthropathy, and Paget's disease. Only two reports describe abnormal /sup 99m/Tc/ pyrophosphate bone scans in four patients with osseous sarcoidosis. Gallium-67 scans are used primarily to localize neoplastic or inflammatory lesions anywhere in the body. In recent years /sup 67/Ga scans have also been used to detect the presence of both pulmonary and extrapulmonary sarcoidosis, butmore » there are no reports describing abnormal uptake of gallium in patients with osseous sarcoidosis. This report describes experience with radioisotope scanning in two patients with osseous sarcoidosis.« less

Sarcoidosis with prominent necrosis on histopathology.

PubMed

Rosenstein, Rachel; Orme, Charisse; Kim, Randie H; Meehan, Shane A; Femia, Alisa

2016-12-15

Sarcoidosis is a multiorgan inflammatory diseasewith variable clinical presentations and the commonhistopathologic finding of noncaseating granulomas.The etiology of the disease is not known, butevidence suggests both environmental and geneticcontributions to the pathogenesis. Depending onthe severity of cutaneous disease and extent ofextracutaneous involvement, therapies range fromtopical and intralesional glucocorticoids to systemicimmunomodulatory and immunosuppressiveagents. We present the case of a patient withcutaneous sarcoidosis with prominent necrosis onhistopathologic examination in the setting of severepulmonary sarcoidosis.

Cardiac Involvement in Sarcoidosis: Evolving Concepts in Diagnosis and Treatment

PubMed Central

Lynch, Joseph P.; Hwang, Jennifer; Bradfield, Jason; Fishbein, Michael; Shivkumar, Kalyanam; Tung, Roderick

2014-01-01

Clinically evident sarcoidosis involving the heart has been noted in at least 2 to 7% of patients with sarcoidosis, but occult involvement is much higher (> 20%). Cardiac sarcoidosis is often not recognized antemortem, as sudden death may be the presenting feature. Cardiac involvement may occur at any point during the course of sarcoidosis and may occur in the absence of pulmonary or systemic involvement. Sarcoidosis can involve any part of the heart, with protean manifestations. Prognosis of cardiac sarcoidosis is related to extent and site(s) of involvement. Most deaths due to cardiac sarcoidosis are due to arrhythmias or conduction defects, but granulomatous infiltration of the myocardium may be lethal. The definitive diagnosis of isolated cardiac sarcoidosis is difficult. The yield of endomyocardial biopsies is low; treatment of cardiac sarcoidosis is often warranted even in the absence of histologic proof. Radionuclide scans are integral to the diagnosis. Currently, 18F-fluorodeoxyglucose positron emission tomography/computed tomography and gadolinium-enhanced magnetic resonance imaging scans are the key imaging modalities to diagnose cardiac sarcoidosis. The prognosis of cardiac sarcoidosis is variable, but mortality rates of untreated cardiac sarcoidosis are high. Although randomized therapeutic trials have not been done, corticosteroids (alone or combined with additional immunosuppressive medications) remain the mainstay of treatment. Because of the potential for sudden cardiac death, implantable cardioverter-defibrillators should be placed in any patient with cardiac sarcoidosis and serious ventricular arrhythmias or heart block, and should be considered for cardiomyopathy. Cardiac transplantation is a viable option for patients with end-stage cardiac sarcoidosis refractory to medical therapy. PMID:25007089

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

PubMed

Moller, David R; Koth, Laura L; Maier, Lisa A; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K; Collman, Ronald G; Hamzeh, Nabeel; Sweiss, Nadera J; Zhang, Yingze; O'Neal, Scott; Senior, Robert M; Becich, Michael; Hochheiser, Harry S; Kaminski, Naftali; Wisniewski, Stephen R; Gibson, Kevin F

2015-10-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol

PubMed Central

Koth, Laura L.; Maier, Lisa A.; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K.; Collman, Ronald G.; Hamzeh, Nabeel; Sweiss, Nadera J.; Zhang, Yingze; O’Neal, Scott; Senior, Robert M.; Becich, Michael; Hochheiser, Harry S.; Kaminski, Naftali; Wisniewski, Stephen R.; Gibson, Kevin F.

2015-01-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant’s clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis. PMID:26193069

The Pathogenesis of Pulmonary Sarcoidosis and Implications for Treatment.

PubMed

Patterson, Karen C; Chen, Edward S

2018-06-01

Thoracic sarcoidosis is the most common form of sarcoidosis, encompassing a heterogeneous group of patients with a wide range of clinical features and associated outcomes. The distinction between isolated thoracic lymphadenopathy and pulmonary involvement matters. Morbidity is often higher, and long-term outcomes are worse for the latter. Although inflammatory infiltrates in pulmonary sarcoidosis may resolve, persistent disease activity is common and can result in lung fibrosis. Given the distinct clinical features and natural history of pulmonary sarcoidosis, its pathogenesis may differ in important ways from other sarcoidosis manifestations. This review highlights recent advances in the pathogenesis of pulmonary sarcoidosis, including the nature of the sarcoidosis antigen, the role of serum amyloid A and other host factors that contribute to alterations in innate immunity, factors that shape adaptive T-cell profiles in the lung, and how these mechanisms influence the maintenance of granulomatous inflammation in sarcoidosis. We discuss questions raised by recent findings, including the role of innate immunity in the pathogenesis, the meaning of immune cell exhaustion, and mechanisms that may contribute to lung fibrosis in sarcoidosis. We conclude with a reflection on when and how immunosuppressive therapies may be helpful for pulmonary sarcoidosis, a consideration of nonpharmacologic management strategies, and a survey of potential novel therapeutic targets for this vexing disease. Copyright © 2017 American College of Chest Physicians. All rights reserved.

How are cancer and connective tissue diseases related to sarcoidosis?

PubMed

Chopra, Amit; Judson, Marc A

2015-09-01

Several studies have suggested an association between sarcoidosis and cancer, and between sarcoidosis and connective tissue diseases (CTDs). In this review, we discuss the evidence supporting and refuting these associations. In terms of a cancer risk in sarcoidosis patients, the data are somewhat conflicting but generally show a very small increased risk. The data supporting an association between sarcoidosis and CTD are not as robust as for cancer. However, it appears that scleroderma is the CTD most strongly associated with sarcoidosis. There are several important clinical and research-related implications of the association of sarcoidosis and CTDs. First, rigorous efforts should be made to exclude alternative causes for granulomatous inflammation before establishing a diagnosis of sarcoidosis. Second, the association between sarcoidosis and both cancer and CTDs may yield important insights into the immunopathogenesis of all three diseases. Finally, these data provide insight in answering a common question asked by sarcoidosis patients, 'Am I at an increased risk of developing cancer?' We believe that although there is an increased (relative) risk of cancer in sarcoidosis patients compared with the general population, that increased risk is quite small (low absolute risk).

Multimodality Imaging in Cardiac Sarcoidosis: Is There a Winner?

PubMed Central

Perez, Irving E.; Garcia, Mario J.; Taub, Cynthia C.

2016-01-01

Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect the heart. Cardiac sarcoidosis may be present in as many as 25% of patients with systemic sarcoidosis, and it is frequently underdiagnosed. The early and accurate diagnosis of myocardial involvement is challenging. Advanced imaging techniques play important roles in the diagnosis and management of patients with cardiac sarcoidosis. PMID:25784137

[Sarcoidosis of the female genital tract].

PubMed

Šefčíková, A; Turková, M; Žurková, M

To present the findings of sarcoidosis on female genital tract. Review. Department of Obstetric and Gynecology, Silesian Hospital Opava. Overview of published findings from case studies. Sarcoidosis is a multisystem granulomatous disorder of unclear cause. It typically involves the lymph nodes of mediastinum, predominantly billateral and/or pulmonary infiltrates. We find extrapulmonary involvement in 30-50% of cases. Sarcoidosis of the female reproductive system is a rare, it represent less than 1% cases of sarcoidosis. Lesions there may affect any organ, including the vulva, vagina, cervix, uterus, fallopian tube and ovary, but also for example placenta and breast. There is also recorded the incidence of multiple localization on female genitalia. Since sarcoidosis of this area is so rare, often proceeds asymptomatic and recognized only as an incidental finding, there are mention only the case histories in literature yet.Clinical symptoms may be non-specific, often imitating a tumor, or tend to be specific, depending on the localization of disability such as perineal pain, pain in the scar after the previous birth trauma, persistent pruritus, itching, irritation, dyspareunia, menstrual cycle disorders, menorrhagia, metrorrhagia, postmenopausal bleeding, amenorrhoe, abdominal pain, endometrial polypoid lesions, recurrent or persistent serometra or discharge. The diagnosis is made up of histologically - we are demonstrating noncaseating granulomas.The therapy is difficult, there are no available official guidelines. If the lesions are clinically silent, we can observed them because they may spontaneously disappear. If we are embarking on medical therapy, we start from a local application, and if this is unsuccessful then we approach the systemic administration. Corticosteroids are the drug of choice. If we diagnose the sarcoidosis of the female genital organs we must exclude systemic disease of sarcoidosis. The prognosis of disease is good.

The etiologic role of infectious antigens in sarcoidosis pathogenesis

PubMed Central

Celada, Lindsay J.; Hawkins, Charlene; Drake, Wonder P.

2015-01-01

Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th1 immunophenotype, most commonly involving the lung, skin, lymph node and eyes. Molecular and immunologic studies continue to strengthen the association of sarcoidosis with infectious antigens, particularly those derived from Propionibacterium and Mycobacterium species. Independent studies report the presence of microbial nucleic acids and proteins within sarcoidosis specimens. Complementary immunologic studies also support the role of infectious agents in sarcoidosis pathogenesis. Th-1 immune responses directed against mycobacterial virulence factors have been detected within sarcoidosis diagnostic bronchoalveolar lavage (BAL). Th1 and Th17 immune responses against propionibacteria have also been reported. More recently, case reports and clinical trials from Japanese, European and American investigators have emerged regarding the efficacy of antimicrobials against Propionibacterium and Mycobacterium species on pulmonary and cutaneous sarcoidosis. While these clinical investigations are not conclusive, they support increasing efforts to identify novel therapeutics, such as antimicrobials, that will impact the observed increase in sarcoidosis morbidity and mortality. PMID:26593133

Drug-induced sarcoidosis-like reactions (DISR).

PubMed

Chopra, Amit; Nautiyal, Amit; Kalkanis, Alexander; Judson, Marc A

2018-04-23

A drug-induced sarcoidosis-like reaction (DISR) is a systemic granulomatous reaction that is indistinguishable from sarcoidosis and occurs in temporal relationship with initiation of an offending drug. DISRs typically improve or resolve after the withdrawal of offending drug. Four common categories of drugs that have been associated with the development of a DISR are immune checkpoint inhibitors (ICIs), highly active anti-retroviral therapy (HAART), interferons (IFNs) and tumor necrosis factor alpha antagonists (TNF-alpha antagonists). Similar to sarcoidosis, DISRs do not necessarily require treatment, as they may cause no significant symptoms, quality of life impairment or organ dysfunction. When treatment of a DISR is required, standard anti-sarcoidosis regimens seem to be effective. As a DISR tends to improve or resolve when the offending drug is discontinued, this is another effective treatment for a DISR. However, the offending drug need not be discontinued if it is useful, and anti-granulomatous therapy can be added. In some situations, the development of a DISR may suggest a beneficial effect of the inducing drug. Understanding the mechanisms leading to DISRs may yield important insights into the immunopathogenesis of sarcoidosis. Copyright © 2018. Published by Elsevier Inc.

Sarcoidosis Presenting as Bilateral Vocal Fold Immobility.

PubMed

Hintze, Justin M; Gnagi, Sharon H; Lott, David G

2018-05-01

Bilateral true vocal fold paralysis is rarely attributable to inflammatory diseases. Sarcoidosis is a rare but important etiology of bilateral true vocal fold paralysis by compressive lymphadenopathy, granulomatous infiltration, and neural involvement. We describe the first reported case of sarcoidosis presenting as bilateral vocal fold immobility caused by direct fixation by granulomatous infiltration severe enough to necessitate tracheostomy insertion. In addition, we discuss the presentation, the pathophysiology, and the treatment of this disease with a review of the literature of previously reported cases of sarcoidosis-related vocal fold immobility. Sarcoidosis should therefore be an important consideration for the otolaryngologist's differential diagnosis of true vocal fold immobility. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Perceptions and beliefs in sarcoidosis.

PubMed

Ireland, J; Wilsher, M

2010-07-01

Sarcoidosis is a chronic multisystem disease with a high prevalence of depression although this is often not recognised. It is not known how patients perceive their disease or the medications required for treatment. We hypothesised that perceptions of illness and beliefs about medications may relate to psychological distress in this condition. 81(42 female) patients with sarcoidosis completed the following: Hospital Anxiety and Depression Scale, Illness Perception Questionnaire, Beliefs about Medications Questionnaire. Demographic and clinical data were collected and the physician's perception of symptom severity and relationship to sarcoidosis recorded. The prevalence of depression (23%) and anxiety (33%) was high and related to self reported symptoms of sarcoidosis. Those on current treatment reported different illness perceptions than those not, and illness perceptions related to anxiety and depression scores. The majority of the sample felt that sarcoid medications were unnecessary but few patients reported concerns about potential adverse consequences of taking them. Beliefs about medications were related to illness perceptions but not associated with anxiety or depression scores or with clinical perception of disease state. There were significant gender differences in perceptions of illness and beliefs about medications. These data confirm earlier reports that anxiety and depression are common in patients with sarcoidosis and in turn perceptions of illness impact on emotional wellness in this disorder. Use of the Illness Perceptions Questionnaire in clinical practice may help to identify those patients who would benefit from interventions to change their perceptions of illness.

[Sarcoidosis flare after autologous stem cell transplantation: An immune paradox?

PubMed

Marchal, A; Charlotte, F; Maksud, P; Haroche, J; Lifferman, F; Miyara, M; Choquet, S; Amoura, Z; Cohen Aubart, F

2017-09-01

Sarcoidosis is a systemic granulomatous disorder of unknown cause. Apparition or flare of previously diagnosed sarcoidosis following hematopoietic stem cell transplantation (HSCT) has rarely been reported. We report a 62-year-old woman who presented a radiological flare of sarcoidosis post-autologous stem cell transplantation for a POEMS syndrome. Imaging findings and lymph node histology, which revealed non-caseating granuloma, were consistent with the sarcoidosis diagnosis. The patient was asymptomatic and was kept free of treatment. Sarcoidosis must be considered ahead of compatible clinicoradiological presentation occurring after HSCT. Sarcoidosis can mimic metastatic cancer or lymphatic relapse. Tissue biopsies and exclusion of differential diagnosis of granuloma diseases are warranted to confirm sarcoidosis diagnosis. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Nephrolithiasis as a presenting feature of chronic sarcoidosis.

PubMed Central

Rizzato, G.; Fraioli, P.; Montemurro, L.

1995-01-01

BACKGROUND--Renal calculi have been reported to occur in about 10% of patients with chronic sarcoidosis, but nephrolithiasis as a presentation of this disease has not been studied. METHODS--The charts of 618 patients with histologically proven sarcoidosis, seen in the period October 1978-1992, were reviewed in order to identify nephrolithiasis at presentation. RESULTS--Seventeen patients had renal calculi which preceded other manifestations of sarcoidosis. In six the occurrence of calculi suggested the diagnosis. Another eight patients had a previous history of recurrent colic with calculi. The time intervals between the first calculus and the appearance of other manifestations of sarcoidosis ranged from one to 25 years, but it was over four years in only two cases and all had at least one calculus in the year before the diagnosis was made. In the other three patients appearance of the calculus was distant in time and was probably unrelated to their sarcoidosis. In most cases the sarcoidosis was chronic and needed long term treatment with corticosteroids. Four patients had further calculi during follow up (one month to 16 years) due to an improper withdrawal of treatment decided by the patient in two cases, and to the reduction in the corticosteroid dose in the other two. CONCLUSIONS--Calculi were the presenting feature of sarcoidosis in six (1%) patients, and were the first manifestation of the disease in a total of 14 (2.2%). This frequency is over 20 times the likely incidence of calculi in the general population. Renal calculi may therefore be a rare primary manifestation of sarcoidosis. In such cases the disease is likely to be chronic and to require long term corticosteroid therapy. Sarcoidosis should always be suspected in cases of nephrolithiasis of unknown origin. PMID:7597671

Noncoding RNAs: New Players in Pulmonary Medicine and Sarcoidosis.

PubMed

Salamo, Oriana; Mortaz, Esmaeil; Mirsaeidi, Mehdi

2018-02-01

Noncoding RNAs (ncRNAs) are coded by 98% of human genomic DNA. They are grouped into two major classes according to length: small ncRNAs and long ncRNAs. They regulate genome organization, stability, and physiological processes that maintain cellular homeostasis. Recently, great interest has emerged in ncRNAs because of their significant roles in the development of inflammatory diseases, including sarcoidosis. Some have been introduced as novel markers for disease activity, such as increased levels of microRNA-34a in peripheral blood mononuclear cells of patients with sarcoidosis, re-emphasizing the inflammatory component in sarcoidosis. They are also important factors in the outcome of sarcoidosis. Dysregulation of microRNA-let7f leads to overexpression of profibrotic factors and could be related to the pathogenesis of pulmonary fibrosis in patients with sarcoidosis, owing to their stimulatory effect on collagen expression and deposition. However, many unanswered questions remain about the association of ncRNAs and sarcoidosis. By understanding the functions of ncRNAs in T-helper cell type 1 and T-helper cell type 17, we may uncover the mechanism of action of those cells in sarcoidosis. Further translational research is needed to define the RNA gene fingerprint of different sarcoidosis stages.

Ninth International Conference on Sarcoidosis.

DTIC Science & Technology

1981-10-15

conference on sarcoidosis the author discusses the current status of sarcoidosis research and the latest developments in clinical treatment a they were...related at the conference. He also refers to the differing opinions that were presented about diagnosis and treatment of the dibease, as well as...clinical indices listed by Lebacq were uveitis , erythema nodosum, polyarthropathy, dactylitis, granulomatous infiltration of a scar, myopathy

Sarcoidosis Occurring After Solid Cancer: A Nonfortuitous Association

PubMed Central

Grados, Aurélie; Ebbo, Mikael; Bernit, Emmanuelle; Veit, Véronique; Mazodier, Karin; Jean, Rodolphe; Coso, Diane; Aurran-Schleinitz, Thérèse; Broussais, Florence; Bouabdallah, Reda; Gravis, Gwenaelle; Goncalves, Anthony; Giovaninni, Marc; Sève, Pascal; Chetaille, Bruno; Gavet-Bongo, Florence; Weitten, Thierry; Pavic, Michel; Harlé, Jean-Robert; Schleinitz, Nicolas

2015-01-01

Abstract The association between cancer and sarcoidosis is controversial. Some epidemiological studies show an increase of the incidence of cancer in patients with sarcoidosis but only few cases of sarcoidosis following cancer treatment have been reported. We conducted a retrospective case study from internal medicine and oncology departments for patients presenting sarcoidosis after solid cancer treatment. We also performed a literature review to search for patients who developed sarcoidosis after solid cancer. We describe the clinical, biological, and radiological characteristics and outcome of these patients. Twelve patients were included in our study. Various cancers were observed with a predominance of breast cancer. Development of sarcoidosis appeared in the 3 years following cancer and was asymptomatic in half of the patients. The disease was frequently identified after a follow-up positron emission tomography computerized tomography evaluation. Various manifestations were observed but all patients presented lymph node involvement. Half of the patients required systemic therapy. With a median follow-up of 73 months, no patient developed cancer relapse. Review of the literature identified 61 other patients for which the characteristics of both solid cancer and sarcoidosis were similar to those observed in our series. This report demonstrates that sarcoidosis must be considered in the differential diagnosis of patients with a history of malignancy who have developed lymphadenopathy or other lesions on positron emission tomography computerized tomography. Histological confirmation of cancer relapse is mandatory in order to avoid unjustified treatments. This association should be consider as a protective factor against cancer relapse. PMID:26181571

Cardiac sarcoidosis resembling panic disorder: a case report.

PubMed

Tokumitsu, Keita; Demachi, Jun; Yamanoi, Yukichi; Oyama, Shigeto; Takeuchi, Junko; Yachimori, Koji; Yasui-Furukori, Norio

2017-01-13

Sarcoidosis is a systemic disease of unknown etiology, in which granulomas develop in various organs, including the skin, lungs, eyes, or heart. It has been reported that patients with sarcoidosis are more likely to develop panic disorder than members of the general population. However, there are many unknown factors concerning the causal relationship between these conditions. We present the case of a 57-year-old woman who appeared to have panic disorder, as she experienced repeated panic attacks induced by transient complete atrioventricular block, associated with cardiac sarcoidosis. Psychotherapy and pharmacotherapy were not effective in the treatment of her panic attacks. However, when we implanted a permanent pacemaker and initiated steroid treatment for cardiac sarcoidosis, panic attacks were ameliorated. Based on these findings, we diagnosed the patient's symptoms as an anxiety disorder associated with cardiac sarcoidosis, rather than panic disorder. This report highlights the importance of considering cardiac sarcoidosis in the differential diagnosis of panic disorder. This cardiac disease should be considered especially in patients have a history of cardiac disease (e.g., arrhythmia) and atypical presentations of panic symptoms. Panic disorder is a psychiatric condition that is typically diagnosed after other medical conditions have been excluded. Because the diagnosis of sarcoidosis is difficult in some patients, caution is required. The palpitations and symptoms of heart failure associated with cardiac sarcoidosis can be misdiagnosed as psychiatric symptoms of panic disorder. The condition described in the current case study appears to constitute a physical disease, the diagnosis of which requires significant consideration and caution.

Sarcoidosis-lymphoma syndrome.

PubMed

Brandy-García, Anahy M; Caminal-Montero, Luis; Fernández-García, María Soledad; Saiz Ayala, Angel; Cabezas-Rodríguez, Ivan; Morante-Bolado, Isla

A 65 year-old female with a history of sarcoidosis with pulmonary and joint involvement, who after 5 years of diagnosis begins with central nervous system involvement manifesting as diplopia. She presents normal analysis results. In imaging results, a mass is identified in the right intraconal space; it depends of right optic nerve, and shows multiple lymph node involvement. Biopsy was performed diagnosed with large B-cell lymphoma, an atypical form of tumor associated with sarcoidosis. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Sarcoidosis in America. Analysis Based on Health Care Use.

PubMed

Baughman, Robert P; Field, Shelli; Costabel, Ulrich; Crystal, Ronald G; Culver, Daniel A; Drent, Marjolein; Judson, Marc A; Wolff, Gerhard

2016-08-01

There have been no recent comprehensive studies of the epidemiology of sarcoidosis in the United States. Changes in health care use have made available access to data on large numbers of patients with sarcoidosis. To use a U.S. national health care database to gather data on patients with sarcoidosis identified over a 3-year period who were 18 years of age and older, and to determine health care costs for these patients. The Optum health care database was queried for a 3-year period (2010-2013). This database includes approximately 15% of U.S. residents. The incidence rate of sarcoidosis was calculated for new cases identified in each year. Calculation of prevalence was based on any patient with sarcoidosis seen during the year. Incidence and prevalence rates are reported per 100,000 patients. A total of 29,372 adult patients with sarcoidosis were identified. Of these, 14,700 (55%) were over 55 years of age at the time of diagnosis. The incidence and prevalence rates were higher for African Americans (17.8 and 141.4 per 100,000, respectively) than for white individuals (8.1 and 49.8), Hispanics (4.3 and 21.7), or Asians (3.2 and 18.9). Women were two times more likely to have sarcoidosis, with the highest prevalence for sarcoidosis noted in African American women (178.5). Overall, the yearly health care cost reported for patients with sarcoidosis was low, with a median of $18,663 per year. However, the yearly cost for the top 5% was $93,201. For patients 18 years of age and older enrolled in a U.S. national administrative database, sarcoidosis was more common among African Americans, but it was reported for all four of the major ethnic groups studied. While health care costs were relatively small for most patients, the cost of care for some patients was considerable.

Cutaneous sarcoidosis: clinicopathologic study of 76 patients from Lebanon.

PubMed

Ishak, Rim; Kurban, Mazen; Kibbi, Abdul-Ghani; Abbas, Ossama

2015-01-01

Sarcoidosis is a multi-system granulomatous disease of unknown etiology. The skin is involved in 25% of cases. Studies on cutaneous sarcoidosis from our region are lacking. This study was conducted to describe clinical and histopathologic findings in all patients diagnosed with cutaneous sarcoidosis at the American University of Beirut Medical Center between 1992 and 2010 and to compare findings with those published in the literature. Clinical charts of patients with cutaneous sarcoidosis were retrospectively reviewed. Extracutaneous lesions were classified by organ involvement. Treatment was documented. Pathology specimens were reviewed. Cutaneous sarcoidosis was diagnosed in 76 Lebanese patients, 79% of whom were women. Mean age at diagnosis was 48 years. A total of 29% of patients had systemic disease that was commonly associated with lupus pernio lesions and subcutaneous sarcoidosis. The most common cutaneous lesions were sarcoidal plaques. The histopathologic features in our series did not differ from those described in the literature, except for the documented presence of a grenz zone. Interestingly, 23% of biopsy specimens contained perineural granulomas, raising the possibility of tuberculoid or borderline tuberculoid leprosy. Foreign bodies were detected in 10% of cases (all had systemic involvement), supporting the opinion that sarcoidosis and granulomatous foreign body reaction are not mutually exclusive. The clinical and histopathologic features of cutaneous sarcoidosis patients in the present series are generally comparable with those published in the literature, with minor differences. Clinically, the most commonly seen lesion was plaque. Microscopically, cutaneous sarcoidosis may exhibit a grenz zone and may show perineural inflammation and foreign bodies. © 2014 The International Society of Dermatology.

Sarcoidosis Presenting Addison's Disease.

PubMed

Takahashi, Kentaro; Kagami, Shin-Ichiro; Kawashima, Hirotoshi; Kashiwakuma, Daisuke; Suzuki, Yoshio; Iwamoto, Itsuo

2016-01-01

We herein describe a second Japanese case of sarcoidosis presenting Addison's disease. A 52-year-old man was diagnosed with sarcoidosis based on clinical and laboratory findings, including bilateral hilar lymphadenopathy and elevated levels of serum angiotensin-converting enzyme and lysozyme, as well as the presence of noncaseating epithelioid granulomas. The patient also exhibited general fatigue, pigmentation, weight loss, hypotension and hyponatremia, suggestive of chronic adrenocortical insufficiency. An endocrine examination confirmed primary adrenocortical insufficiency. This case suggests the direct involvement of sarcoid granuloma in the adrenal glands.

Hypothalamic digoxin, hemispheric chemical dominance and sarcoidosis.

PubMed

Ravi Kumar, A; Kurup, Parameswara Achutha

2004-06-01

The isoprenoid pathway produces three key metabolites: endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). The role of the isoprenoid pathway in the pathogenesis of sarcoidosis in relation to hemispheric dominance was studied. The isoprenoid pathway-related cascade was assessed in patients with systemic sarcoidosis with pulmonary involvement. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis. In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in the cholesterol:phospholipid ratio and a reduction in the glycoconjugate level of red blood cell (RBC) membrane in this group of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. In individuals with left hemispheric dominance the patterns were reversed. Endogenous digoxin, by activating the calcineurin signal transduction pathway of T cells, can contribute to immune activation in sarcoidosis. An altered glycoconjugate metabolism can lead to the generation of endogenous self-glycoprotein antigens in the lung as well as other tissues. Increased free radical generation can also lead to immune activation. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of sarcoidosis in relation to right hemispheric chemical dominance is discussed. All the patients with sarcoidosis were right-handed/left hemispheric dominant according to the dichotic listening test, but their biochemical patterns

Proangiogenic and Profibrotic Markers in Pulmonary Sarcoidosis.

PubMed

Tuleta, I; Biener, L; Pizarro, C; Nickenig, G; Skowasch, D

2018-04-21

The aim of our study was to determine the blood levels of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2, and platelet-derived growth factor (PDGF)-AB in different stages of pulmonary sarcoidosis. There were 92 patients in sarcoidosis stages I + II, III, and IV enrolled into the study. All the patients underwent lung diffusing capacity and blood sampling. We found that VEGF levels differed significantly between the stage groups with the peak VEGF concentrations in stage III. TGF-β1 levels were similar in stages I + II and III, and tended to be lower in stage IV. The analysis of the subgroups showed increased VEGF and FGF-2, and reduced TGF-β1 concentration in stages I + II patients with relevantly reduced lung diffusing capacity or increased sarcoidosis activity compared to patients with normal lung diffusing capacity or inactive sarcoidosis. A tendency towards increased VEGF, PDGF-AB and TGF-β1 levels was observed in the analogical subgroup analysis within the stage III. We conclude that proangiogenic VEGF, and profibrotic FGF-2 and PDGF-AB may contribute to the progression of sarcoidosis, whereas TGF-β1, with its dual anti-inflammatory and profibrotic actions, may play a dichotomous protective or deleterious role. Reduced diffusing capacity and active sarcoidosis are associated with an unfavorable constellation of the markers studied, which predicts a progressive disease course.

Annular lesions of cutaneous sarcoidosis with granulomatous vasculitis.

PubMed

Mizuno, Kana; Nguyen, Chuyen Thi Hong; Ueda-Hayakawa, Ikuko; Okamoto, Hiroyuki

2017-05-01

Sarcoidosis is known to be involved in diseases with vasculitis as sarcoid vasculitis. However, vasculitis in cutaneous sarcoidal lesions is extremely rare. Here we describe a case of sarcoidosis with multiple annular skin lesions with granulomatous vasculitis. A 62-year-old female was diagnosed with sarcoidosis by chest-abdominal computed tomographic examination and laboratory tests. The skin lesions had appeared on her lower limbs 2 years before. Physical examination showed multiple infiltrated annular eruptions on the lower extremities. A skin biopsy of an area of erythema showed multiple non-caseating epithelioid cell granulomas in the dermis and subcutaneous fat and granulomatous vasculitis with fibrinoid degeneration in the subcutaneous fat. There are two types of vasculitis in sarcoidosis: leukocytoclastic and granulomatous vasculitis. Ulcers and livedo were more common in granulomatous vasculitis than in leukocytoclastic vasculitis. The present case had unique annular skin lesions of sarcoidosis with granulomatous vasculitis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcriptome profiles in sarcoidosis and their potential role in disease prediction.

PubMed

Schupp, Jonas C; Vukmirovic, Milica; Kaminski, Naftali; Prasse, Antje

2017-09-01

Sarcoidosis is a systemic disease defined by the presence of nonnecrotizing granuloma in the absence of any known cause. Although the heterogeneity of sarcoidosis is well characterized clinically, the transcriptome of sarcoidosis and underlying molecular mechanisms are not. The signal of all transcripts, small and long noncoding RNAs, can be detected using microarrays or RNA-Sequencing. Analyzing the transcriptome of tissues that are directly affected by granulomas is of great importance to understand biology of the disease and may be predictive of disease and treatment outcome. Multiple genome wide expression studies performed on sarcoidosis affected tissues were published in the last 11 years. Published studies focused on differences in gene expression between sarcoidosis vs. control tissues, stable vs. progressive sarcoidosis, as well as sarcoidosis vs. other diseases. Strikingly, all these transcriptomics data confirm the key role of TH1 immune response in sarcoidosis and particularly of interferon-γ (IFN-γ) and type I IFN-driven signaling pathways. The steps toward transcriptomics of sarcoidosis in precision medicine highlight the potentials of this approach. Large prospective follow-up studies are required to identify signatures predictive of disease progression and outcome.

Current and emerging pharmacological treatments for sarcoidosis: a review

PubMed Central

Beegle, Scott H; Barba, Kerry; Gobunsuy, Romel; Judson, Marc A

2013-01-01

The treatment of sarcoidosis is not standardized. Because sarcoidosis may never cause significant symptoms or organ dysfunction, treatment is not mandatory. When treatment is indicated, oral corticosteroids are usually recommended because they are highly likely to be effective in a relative short period of time. However, because sarcoidosis is often a chronic condition, long-term treatment with corticosteroids may cause significant toxicity. Therefore, corticosteroid sparing agents are often indicated in patients requiring chronic therapy. This review outlines the indications for treatment, corticosteroid treatment, and corticosteroid sparing treatments for sarcoidosis. PMID:23596348

Efficacy and safety of TNF antagonists in sarcoidosis: data from the Spanish registry of biologics BIOBADASER and a systematic review.

PubMed

Maneiro, Jose Ramon; Salgado, Eva; Gomez-Reino, Juan J; Carmona, Loreto

2012-08-01

To evaluate the safety, efficacy, and effectiveness of TNF antagonists in patients with sarcoidosis. A descriptive study of a case series registered in BIOBADASER and a systematic review was performed. The search strategy of articles published between 1998 and July 2011 in Medline, Embase, and the Cochrane Library included synonyms of sarcoidosis and synonyms of TNF antagonists. Seven patients treated with infliximab (IFX) and 1 with etanercept (ETN) switched to IFX for inefficacy were registered in BIOBADASER 2.0. In 3, treatment is still ongoing. Reasons for discontinuation were serious adverse events in 2 cases, inefficacy in 2 cases, and complete clinical response in 2 cases. Eight serious adverse events were reported. In the selected 69 of 2262 reports and 1 abstract of the review, 232 patients (89.9%) were treated with IFX and 26 (10.0%) were treated with ETN. In 2 randomized clinical trials, favorable response of the lung disease was reported with IFX. In other randomized clinical trials, no improvement of ocular manifestations was reported with ETN. In the cases series, results were diverse. Mean weighted rates of adverse events, infections, serious infections, and malignancy were 39.9, 22.1, 5.9, and 1.0 per 100 patient-years, respectively. There is insufficient evidence to ensure the efficacy of TNF antagonists in sarcoidosis. Nevertheless, IFX may be effective in selected manifestations of the disease. Before starting treatment of sarcoidosis with IFX, a careful evaluation of the benefit/risk ratio must be considered on an individual basis. Copyright © 2012 Elsevier Inc. All rights reserved.

Cutaneous sarcoidosis successfully treated with alefacept.

PubMed

Garcia-Zuazaga, Jorge; Korman, Neil J

2006-01-01

Sarcoidosis is a systemic granulomatous disease of unknown etiology that affects multiple organ systems, including the pulmonary, lymphatic, skeletal, and integumentary systems. Improved understanding of the intrinsic immunology and molecular biology in sarcoidosis can be applied to the treatment of this disease. Alefacept is a human fusion protein consisting of the extracellular domain of leukocyte function-associated antigen 3 fused with the Fc portion of human immunoglobulin G1. It works by blocking the interaction between antigen-presenting cells and T cells to inhibit activation and by inducing apoptosis of CD4+ T cells. In this case report, we describe a 46-year-old patient with recalcitrant lupus pernio who was successfully treated with alefacept. To determine whether T-cell inhibition, specifically the use of alefacept, may be used to treat a patient with recalcitrant cutaneous sarcoidosis. Case report. There was a modest clinical improvement after 8 weeks of intramuscular injections of alefacept. This case report provides further evidence of successful treatment of sarcoidosis with biologic agents directed against T-lymphocyte activation.

[Cardiac sarcoidosis: Diagnosis and therapeutic challenges].

PubMed

Cohen Aubart, F; Nunes, H; Mathian, A; Haroche, J; Hié, M; Le-Thi Huong Boutin, D; Cluzel, P; Soussan, M; Waintraub, X; Fouret, P; Valeyre, D; Amoura, Z

2017-01-01

Sarcoidosis is a granulomatous disorder of unknown cause characterized by non-caseating granuloma in young adults. Cardiac involvement is rare and range from 2 to 75% depending on diagnostic criteria. Cardiac involvement in sarcoidosis may be asymptomatic or may manifest as rhythm/conduction troubles or congestive heart failure. The diagnosis and treatment of cardiac sarcoidosis may be challenging. However, advances have come in recent years from the use of cardiac MRI and 18 FDG-TEP scanner, as well as from the stratification of the risk of ventricular tachycardia/fibrillation. Due to the rarity of the disease, there is no reliable prospective large study to guide therapeutic strategy for cardiac sarcoidosis. Corticosteroids are probably efficacious, in particular in case of atrio-ventricular block or moderate heart failure. Immunosuppressive drugs have not been largely studied but methotrexate could be helpful. In refractory forms, TNF-α antagonists have been used with success. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Influence of stressful life events on the onset of sarcoidosis.

PubMed

Yamada, Yoshihito; Tatsumi, Koichiro; Yamaguchi, Tetsuo; Tanabe, Nobuhiro; Takiguchi, Yuichi; Kuriyama, Takayuki; Mikami, Riichiro

2003-06-01

The onset of sarcoidosis may be triggered by any hereditary and/or environmental factor. Among these factors, psychosocial stress may play a critical role in the onset of sarcoidosis. The aim of the present study was to evaluate the influence of stressful life events on the onset of sarcoidosis. The social and/or life events experienced prior to diagnosis in 55 patients with sarcoidosis, were evaluated quantitatively using the Social Readjustment Rating Scale (SRRS), the most authoritative method to quantify the magnitude of the events requiring changes in lifestyle. In addition, personality with respect to stress-reactivity was simultaneously evaluated using the Minnesota Multiphasic Personality Inventory (MMPI) alexithymia scale. Both the degree of stress, evaluated by SRRS, and stress-reactivity, evaluated by MMPI scale, of sarcoidosis patients were compared with those of 92 healthy controls. The magnitude of stressful life events was significantly higher in patients with sarcoidosis compared with healthy controls. In addition, capacity for coping with stress was found to be inferior in sarcoidosis patients compared with that in the control groups. These results indicated that psychosocial stress assessed on the basis of alexithymic characteristics of the self perception of stress may be partly implicated in the development of sarcoidosis.

Nuclear Imaging in Sarcoidosis.

PubMed

Piekarski, Eve; Benali, Khadija; Rouzet, François

2018-05-01

Sarcoidosis is a multisystem granulomatosis which may result in a wide variety of clinical and biological presentations. Symptoms are often nonspecific, and incidental abnormal findings on chest radiography is rather common. Although sarcoidosis resolves favorably in most cases, some localizations can provoke functional impairment or even impact on patients' prognosis. The diagnosis is based on a pathological hallmark which is the non-necrotizing epithelioid-cell rich granuloma. Owing to the ability to detect inflammation throughout the body with a high sensibility, FDG-PET/CT gained a central role in sarcoidosis because it can suggest the diagnosis in certain clinical context, guide biopsy, evaluate the extent of the disease, help assess the prognosis, and monitor immunosuppressive therapy. This review will briefly describe clinical and typical findings of conventional imaging according to organ involvement, in order to highlight the additional information provided by nuclear imaging. In the future, we can expect to further improve diagnostic performance of imaging in some indications through the availability of more specific radiopharmaceuticals and the wider use of combined PET/MRI. Copyright © 2018 Elsevier Inc. All rights reserved.

Characteristics of Sarcoidosis in Patients with Previous Malignancy: Causality or Coincidence?

PubMed

Arish, Nissim; Kuint, Rottem; Sapir, Eli; Levy, Liran; Abutbul, Avraham; Fridlender, Zvi; Laxer, Uri; Berkman, Neville

2017-01-01

The association between sarcoidosis and malignancy is poorly defined. Sarcoidosis can precede, be diagnosed concurrently with, or follow malignancy. We describe the clinical and radiological features of patients with sarcoidosis following malignancy to determine whether this association is causal or coincidental. We performed a search for all patients with confirmed sarcoidosis following malignancy in our institution during 2001-2015. Clinical and radiological features, bronchoscopic findings, bronchoalveolar lavage cell counts, and pulmonary function tests (PFTs) were reviewed to evaluate patterns of disease involvement. Details of the histological type of cancer, staging, treatment, and follow-up were reviewed. Twenty-nine patients were identified. The most prevalent malignancies were breast cancer and lymphoma (24% each). Based on the incidence of these malignancies, we estimated the incidence of sarcoidosis was 175 times higher after lymphoma and 38 times higher after breast cancer as compared to the general population. Most patients had early stage cancer (stage I, II) (75%), and only 2 patients (7%) had recurrence of their malignancy after diagnosis of sarcoidosis. Sarcoidosis was diagnosed within 5 years of malignancy in over half the patients, 76% were asymptomatic and 69% had normal PFTs. Mediastinal lymphadenopathy was present in 81% of cases, hilar lymphadenopathy in 67%, and pulmonary parenchymal involvement in 41%. Fifty percent of patients had received Adriamycin, 38% cyclophosphamide, and 33% vincristine. Sarcoidosis following malignancy is indistinguishable from "idiopathic" sarcoidosis, although it is frequently asymptomatic. The high frequency of sarcoidosis after specific cancers but not others, suggests a causative association between malignancy and development of sarcoidosis. © 2017 S. Karger AG, Basel.

Symptomatic muscular sarcoidosis: Lessons from a nationwide multicenter study.

PubMed

Cohen Aubart, Fleur; Abbara, Salam; Maisonobe, Thierry; Cottin, Vincent; Papo, Thomas; Haroche, Julien; Mathian, Alexis; Pha, Micheline; Gilardin, Laurent; Hervier, Baptiste; Soussan, Michael; Morlat, Philippe; Nunes, Hilario; Benveniste, Olivier; Amoura, Zahir; Valeyre, Dominique

2018-05-01

To describe clinicopathologic features of muscular sarcoidosis and the associated sarcoidosis phenotype through a nationwide multicenter study. Patients were included if they had histologically proven sarcoidosis and symptomatic muscular involvement confirmed by biological, imaging, or histologic examinations. Forty-eight patients (20 males) were studied, with a median age at muscular symptoms onset of 45 years (range 18-71). Four patterns were identified: a nodular pattern (27%); smoldering phenotype (29%); acute, subacute, or progressive myopathic type (35%); and combined myopathic and neurogenic pattern (10%). In all patterns, sarcoidosis was multivisceral with a median of 3 extramuscular organs involved (mostly lungs, lymph nodes, eyes, and skin) and a prolonged course with long-term use of corticosteroids and immunosuppressive drugs. Muscular patterns differed according to clinical presentation (myalgia, nodules, or weakness), electromyographic findings, muscular MRI, and response to sarcoidosis treatment. The myopathic and neuromuscular patterns were more severe. This nationwide study of muscular sarcoidosis allowed the identification of 4 patterns of granulomatous myositis, which differed by phenotypes and the clinical course.

Cardiac Sarcoidosis: Clinical Manifestations, Imaging Characteristics, and Therapeutic Approach

PubMed Central

Houston, Brian A; Mukherjee, Monica

2014-01-01

Sarcoidosis is a multi-system disease pathologically characterized by the accumulation of T-lymphocytes and mononuclear phagocytes into the sine qua non pathologic structure of the noncaseating granuloma. Cardiac involvement remains a key source of morbidity and mortality in sarcoidosis. Definitive diagnosis of cardiac sarcoidosis, particularly early enough in the disease course to provide maximal therapeutic impact, has proven a particularly difficult challenge. However, major advancements in imaging techniques have been made in the last decade. Advancements in imaging modalities including echocardiography, nuclear spectroscopy, positron emission tomography, and magnetic resonance imaging all have improved our ability to diagnose cardiac sarcoidosis, and in many cases to provide a more accurate prognosis and thus targeted therapy. Likewise, therapy for cardiac sarcoidosis is beginning to advance past a “steroids-only” approach, as novel immunosuppressant agents provide effective steroid-sparing options. The following focused review will provide a brief discussion of the epidemiology and clinical presentation of cardiac sarcoidosis followed by a discussion of up-to-date imaging modalities employed in its assessment and therapeutic approaches. PMID:25452702

Clinical and prognostic significance of muscle biopsy in sarcoidosis.

PubMed

Yanardag, Halil; Tetikkurt, Cuneyt; Bilir, Muammer

2018-04-30

The main objective of this study was to evaluate the influence of muscle involvement on the clinical features, prognostic outcome, extrapulmonary organ, and endobronchial involvement in sarcoidosis patients. The second aim was to assess the diagnostic yield of muscle biopsy for the histopathologic identification of sarcoidosis.  Fifty sarcoidosis patients participated in the study. The patients were classified into two groups according to the histopathologic presence of non-caseating granulomatous inflammatory pattern of the muscle biopsy samples and were evaluated retrospectively in regard to clinical features, prognosis, extrapulmonary, and endobronchial disease involvement. Pathologic examination of the muscle biopsy samples revealed non-caseating granulomas in eighteen and myositis in seven patients compatible with sarcoidosis. The diagnostic yield of muscle biopsy for demonstrating non-caseating granulomatous inflammation was fifty percent. Patients with muscle sarcoidosis showed a worse prognosis and a more severe extrapulmonary organ involvement than the patients without muscle disease. Muscle biopsy was not statistically significant to delineate diffuse endobronchial involvement while it was suggestive for endobronchial disease clinically. The results of our study reveal that muscle biopsy appears to be a useful diagnostic tool along with its safety and easy clinical applicability. It is a rewarding utility to predict the prognostic outcome and extrapulmonary involvement in sarcoidosis patients. Positive biopsy on the other hand confirms the identification of sarcoidosis in patients with single organ involvement carrying an equivocal diagnostic clinical pattern. Muscle biopsy may be considered as the initial step for the final diagnosis of sarcoidosis in such cases.

Racial Difference in Sarcoidosis Mortality in the United States

PubMed Central

Machado, Roberto F.; Schraufnagel, Dean; Sweiss, Nadera J.; Baughman, Robert P.

2015-01-01

BACKGROUND: The clinical presentation and outcome of sarcoidosis varies by race. However, the race difference in mortality outcome remains largely unknown. METHODS: We studied mortality related to sarcoidosis from 1999 through 2010 by examining data on multiple causes of death from the National Center for Health Statistics. We compared the comorbid conditions between sarcoidosis-related deaths with deaths caused by car accidents (previously healthy control subjects) and rheumatoid arthritis (chronic disease control subjects) in both African Americans and Caucasians. RESULTS: From 1999 through 2010, sarcoidosis was reported as an immediate cause of death in 10,348 people in the United States with a combined overall mean age-adjusted mortality rate of 2.8 per 1 million person-years. Of these, 6,285 were African American and 3,984 Caucasian. The age-adjusted mortality rate for African Americans was 12 times higher than for Caucasians. African Americans died at an earlier age than Caucasians. African Americans living in the District of Columbia and North Carolina and Caucasians living in Vermont had higher mortality rates. Although the total sarcoidosis age-adjusted mortality rate had not changed over the 12 year period studied, this rate increased for Caucasians (R = 0.747, P = .005) but not for African Americans. Compared with the control groups, pulmonary hypertension was significantly more common in individuals with sarcoidosis. CONCLUSIONS: This nationwide population-based study exposes a significant difference in ethnicity and sex among people dying of sarcoidosis in the United States. Pulmonary hypertension investigation should be considered in all patients with sarcoidosis, especially African Americans. PMID:25188873

Cutaneous sarcoidosis masquerading as chronic cutaneous lupus erythematosus - case report.

PubMed

Vatanchi, Marjon; Sobhani, Kaivon; Fisher, Valerie T; Meffert, Jeffrey J

2016-09-20

Sarcoidosis is a multisystemic granulomatous disease of unknown origin. Chronic cutaneous lupus erythematosus (CCLE) is an autoimmune disease that is associated with autoantibody production and T-cell dysfunction. Cutaneous manifestations of sarcoidosis may mimic CCLE and vice versa making it difficult to reach a diagnosis clinically. We present a case of a 57-year-old woman with long-standing sarcoidosis who presented to clinic with diffuse painful plaques that were very distinct and suggestive of CCLE. She had a family history of both sarcoidosis and CCLE. The patient was immediately started on topical corticosteroids and oral hydroxychloroquine. Skin biopsy and the absence of direct immunofluorescence confirmed a skin manifestation of her previously diagnosed sarcoidosis, despite the clinical morphology favoring classic CCLE. Sarcoidosis may have diverse manifestations and may mimic other disease processes. A detailed history along with a low threshold for biopsy is important for determining a diagnosis.

Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis

PubMed Central

Sweiss, Nadera J.; Chen, Edward S.; Moller, David R.; Knox, Kenneth S.; Ma, Shwu-Fan; Wade, Michael S.; Noth, Imre; Machado, Roberto F.; Garcia, Joe G. N.

2012-01-01

Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ∼20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n = 39) from healthy controls (n = 35, 86% classification accuracy) and which served as a molecular signature for complicated sarcoidosis (n = 17). As aberrancies in T cell receptor (TCR) signaling, JAK-STAT (JS) signaling, and cytokine-cytokine receptor (CCR) signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR) was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1). In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis. PMID:22984568

Role of serum angiotensin converting enzyme in sarcoidosis.

PubMed

Khan, A H; Ghani, F; Khan, A; Khan, M A; Khurshid, M

1998-05-01

This study was conducted to determine the role of Serum Angiotensin Converting Enzyme (SACE) as a marker in the differential diagnosis of pulmonary diseases and prognosis of sarcoidosis. A retrospective analysis of 113 medical records of patients at The Aga Khan University Hospital, with laboratory investigation for SACE was performed. Among 113 patients, 51 cases were found to have sarcoidosis, 44 of them had SACE levels greater than 52 IU/L (mean ACE 104.44). SACE levels were also found elevated in other clinical conditions like tuberculosis (mean 58.64 IU/L), but the enzyme level were less (p 0.04) than those found in sarcoidosis (mean (92.97 IU/L). SACE activity was found to be considerably lower in other chronic lung diseases such as, fibrosing alveolitis (mean 43.98 IU/L), interstitial lung disease (mean 42.11 IU/L) and chronic obstructive lung disease (mean 40.85 IU/L). Twenty patients of sarcoidosis, who received steroid treatment subsequently showed a decline in the SACE levels. SACE is a useful marker in differential diagnosis as 37.2% cases of sarcoidosis compared to only 9.09% of tuberculosis had SACE levels greater than 100 IU/L. In addition, our data also suggest that serum ACE is useful for the diagnosis as well as monitoring prognosis in sarcoidosis.

Nutrition and corticosteroids in the treatment of sarcoidosis.

PubMed

Bast, Aalt; Semen, Khrystyna O; Drent, Marjolein

2018-06-22

Sarcoidosis is a chronic disease, which is routinely treated with corticosteroids. Steroid resistance or steroid-induced adverse effects require alternatives. Other immune-modulating pharmacological treatments have been developed, and therefore expanded tremendously. Until now, the role of nutrition in the overall management of sarcoidosis has been neglected although anti-inflammatory properties of nutritional components have been known for many years now. New nutritional possibilities emerge from already existing data and offer new therapeutic avenues in the treatment of sarcoidosis. Various dietary components have been shown to reduce pulmonary inflammatory processes. It is increasingly recognized, however, that the specificity and magnitude of the effect of nutrition differs from pharmacological interventions. Conventional randomized clinical trials are less suitable to test the effect of nutrition in comparison with testing drugs. Mechanistic knowledge on the action of dietary components in conjunction with an increasing understanding of the molecular processes underlying steroid resistance (as investigated in asthma and COPD and unfortunately hardly in sarcoidosis) lead to exciting suggestions on combinations of nutrition/nutritional bioactive compounds and corticosteroids that may benefit sarcoidosis patients. In order to understand the effects of nutrition in chronic disease, it is important to elucidate mechanisms and pathways of effects. Several complementing lines of evidence should be integrated in order to be able to advise sarcoidosis patients on a healthy diet as such or in combination with prescribed anti-inflammatory therapy.

Sarcoidosis: an update on current pharmacotherapy options and future directions.

PubMed

Brito-Zerón, Pilar; Pérez-Alvarez, Roberto; Pallarés, Lucio; Retamozo, Soledad; Baughman, Robert P; Ramos-Casals, Manuel

2016-12-01

Sarcoidosis is a systemic disease of unknown etiology characterized by the development of non-caseating epitheloid granulomas. The lungs are the most commonly involved organ (>90% of cases), followed by the lymph nodes, the skin, and the eyes. Areas covered: This review summarizes current pharmacotherapy options and future directions for the development of new therapies. Glucocorticoids are the first-line therapy for sarcoidosis. For patients with the most severe forms of sarcoidosis (who will need glucocorticoids for long periods) and for those intolerant or refractory, immunosuppressive drugs are used as sparing agents. The management of extrathoracic sarcoidosis must be tailored to the specific organ or organs involved; however, there is limited data from controlled trials to guide the treatment of these patients. The emergence of biological therapies has increased the therapeutic armamentarium available to treat sarcoidosis, with monoclonal anti-TNF agents being the most promising, but their use is still limited by a lack of licensing and costs. Expert commentary: The treatment of sarcoidosis is still not totally standardized. New effective therapies are urgently needed to enable the reduction or replacement of long-term therapy with glucocorticoids in patients with sarcoidosis.

[Vertebral sarcoidosis. Spontaneous favorable outcome: A case report and literature review].

PubMed

Salmon, J-H; Perotin, J-M; Direz, G; Brochot, P; Laredo, J-D; Eschard, J-P

2013-01-01

The prevalence of vertebral sarcoidosis is highly variable (1 to 36% of reported case series). Because of limited clinical expression, its frequency is probably underestimated. Its proper management is not clearly defined. A 42-year-old woman who had a past medical history of cutaneous and pulmonary sarcoidosis presented with low back pain that was refractory to usual medical treatment. A diagnosis of vertebral localisation of sarcoidosis was considered on the history of proven sarcoidosis, radiological features, and the absence of evidence of an alternative diagnosis. In the absence of other clinical or biological evidence of active sarcoidosis, a simple follow-up was planned. MRI control at 1 year showed the resolution of vertebral sarcoidosis lesions. Spontaneous regression is a possible outcome of vertebral sarcoidosis. Initiation of a specific treatment should be discussed in the absence of other visceral involvement. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets

PubMed Central

Celada, Lindsay J.; Polosukhin, Vasiliy V.; Atkinson, James B.; Drake, Wonder P.

2016-01-01

Sarcoidosis is a granulomatous disease of unknown cause. Prior molecular and immunologic studies have confirmed the presence of mycobacterial virulence factors, such as catalase peroxidase and superoxide dismutase A, within sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of known antibiotics classes. Currently, major antibiotics are directed against DNA synthesis, protein synthesis, and cell wall formation. We conducted molecular analysis of 40 sarcoidosis diagnostic specimens and compared them with 33 disease control specimens for the presence of mycobacterial genes that encode antibiotic targets. We assessed for genes involved in DNA synthesis (DNA gyrase A [gyrA] and DNA gyrase B), protein synthesis (RNA polymerase subunit β), cell wall synthesis (embCAB operon and enoyl reductase), and catalase peroxidase. Immunohistochemical analysis was conducted to investigate the locale of mycobacterial genes such as gyrA within 12 sarcoidosis specimens and 12 disease controls. Mycobacterial DNA was detected in 33 of 39 sarcoidosis specimens by quantitative real-time polymerase chain reaction compared with 2 of 30 disease control specimens (P < 0.001, two-tailed Fisher’s test). Twenty of 39 were positive for three or more mycobacterial genes, compared with 1 of 30 control specimens (P < 0.001, two-tailed Fisher’s test). Immunohistochemistry analysis localized mycobacterial gyrA nucleic acids to sites of granuloma formation in 9 of 12 sarcoidosis specimens compared with 1 of 12 disease controls (P < 0.01). Microbial genes encoding enzymes that can be targeted by currently available antimycobacterial antibiotics are present in sarcoidosis specimens and localize to sites of granulomatous inflammation. Use of antimicrobials directed against target enzymes may be an innovative treatment alternative. PMID:26807608

Evidence for local dendritic cell activation in pulmonary sarcoidosis

PubMed Central

2012-01-01

Background Sarcoidosis is a granulomatous disease characterized by a seemingly exaggerated immune response against a difficult to discern antigen. Dendritic cells (DCs) are pivotal antigen presenting cells thought to play an important role in the pathogenesis. Paradoxically, decreased DC immune reactivity was reported in blood samples from pulmonary sarcoidosis patients. However, functional data on lung DCs in sarcoidosis are lacking. We hypothesized that at the site of disease DCs are mature, immunocompetent and involved in granuloma formation. Methods We analyzed myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in broncho-alveolar lavage (BAL) and blood from newly diagnosed, untreated pulmonary sarcoidosis patients and healthy controls using 9-color flowcytometry. DCs, isolated from BAL using flowcytometric sorting (mDCs) or cultured from monocytes (mo-DCs), were functionally assessed in a mixed leukocyte reaction with naïve allogeneic CD4+ T cells. Using Immunohistochemistry, location and activation status of CD11c+DCs was assessed in mucosal airway biopsies. Results mDCs in BAL, but not in blood, from sarcoidosis patients were increased in number when compared with mDCs from healthy controls. mDCs purified from BAL of sarcoidosis patients induced T cell proliferation and differentiation and did not show diminished immune reactivity. Mo-DCs from patients induced increased TNFα release in co-cultures with naïve allogeneic CD4+ T cells. Finally, immunohistochemical analyses revealed increased numbers of mature CD86+ DCs in granuloma-containing airway mucosal biopsies from sarcoidosis patients. Conclusion Taken together, these finding implicate increased local DC activation in granuloma formation or maintenance in pulmonary sarcoidosis. PMID:22513006

Histologic Review of Sarcoidosis in a Neck Lymph Node.

PubMed

Welter, Shannon M; DeLuca-Johnson, Javier; Thompson, Keith

2018-06-01

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. It may occur at any age, but is most commonly seen in young to middle age adults. Sarcoidosis remains more common in women regardless of geographic or racial boundaries. Although the etiology remains unclear, the most common explanation is that sarcoidosis is a disease of immunologic dysregulation triggered by an as yet unidentified environmental or microbial antigen in genetically susceptible persons. We review a case of sarcoidosis with was initially diagnosed in a neck lymph node that was removed for evaluation of metastatic squamous cell carcinoma with a discussion on the clinical and histologic characteristic of the disease.

Atypical Cutaneous Presentations of Sarcoidosis: Two Case Reports and Review of the Literature.

PubMed

Leverenz, David L; Henderson, Christopher; Shah, Ankoor

2018-06-14

The goal of this review is to provide the reader with an updated summary of the cutaneous manifestations of systemic sarcoidosis, with a particular emphasis on the predilection of sarcoidosis for scars, tattoos, and other areas of traumatized skin. While the mechanism underlying the propensity for traumatized skin to develop sarcoidosis lesions remains unclear, several theories have been proposed including the idea that cutaneous sarcoidosis represents an exuberant, antigen-driven foreign-body response, as well as the theory that traumatized skin represents an immunocompromised district with altered local immune trafficking and neural signaling. In this review, we present two cases in which the development of cutaneous lesions in scars and tattoos was integral to the diagnosis of systemic sarcoidosis. We then review the various cutaneous manifestations of systemic sarcoidosis, the clinical characteristics and differential diagnosis of scar and tattoo sarcoidosis, the proposed mechanism by which traumatized skin is prone to developing sarcoidosis lesions, and current treatments for cutaneous sarcoidosis.

EEG in Sarcoidosis Patients Without Neurological Findings.

PubMed

Bilgin Topçuoğlu, Özgür; Kavas, Murat; Öztaş, Selahattin; Arınç, Sibel; Afşar, Gülgün; Saraç, Sema; Midi, İpek

2017-01-01

Sarcoidosis is a multisystem granulomatous disease affecting nervous system in 5% to 10% of patients. Magnetic resonance imaging (MRI) is accepted as the most sensitive method for detecting neurosarcoidosis. However, the most common findings in MRI are the nonspecific white matter lesions, which may be unrelated to sarcoidosis and can occur because of hypertension, diabetes mellitus, smoking, and other inflammatory or infectious disorders, as well. Autopsy studies report more frequent neurological involvement than the ante mortem studies. The aim of this study is to assess electroencephalography (EEG) in sarcoidosis patients without neurological findings in order to display asymptomatic neurological dysfunction. We performed EEG on 30 sarcoidosis patients without diagnosis of neurosarcoidosis or prior neurological comorbidities. Fourteen patients (46.7%) showed intermittant focal and/or generalized slowings while awake and not mentally activated. Seven (50%) of these 14 patients with EEG slowings had nonspecific white matter changes while the other half showed EEG slowings in the absence of MRI changes. We conclude that EEG slowings, when normal variants (psychomotor variant, temporal theta of elderly, frontal theta waves) are eliminated, may be an indicator of dysfunction in brain activity even in the absence of MRI findings. Hence, EEG may contribute toward detecting asymptomatic neurological dysfunction or probable future neurological involvement in sarcoidosis patients. © EEG and Clinical Neuroscience Society (ECNS) 2016.

Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations.

PubMed

Sweiss, Nadera J; Salloum, Rafah; Gandhi, Seema; Ghandi, Seema; Alegre, Maria-Luisa; Sawaqed, Ray; Badaracco, Maria; Pursell, Kenneth; Pitrak, David; Baughman, Robert P; Moller, David R; Garcia, Joe G N; Niewold, Timothy B

2010-02-05

Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4x10(-10)). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment.

Significant CD4, CD8, and CD19 Lymphopenia in Peripheral Blood of Sarcoidosis Patients Correlates with Severe Disease Manifestations

PubMed Central

Sweiss, Nadera J.; Salloum, Rafah; Ghandi, Seema; Alegre, Maria-Luisa; Sawaqed, Ray; Badaracco, Maria; Pursell, Kenneth; Pitrak, David; Baughman, Robert P.; Moller, David R.; Garcia, Joe G. N.; Niewold, Timothy B.

2010-01-01

Background Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. Methodology/Principal Findings Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4×10−10). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. Conclusions/Significance Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment. PMID:20140091

Polymorphism of angiotensin-converting enzyme gene in sarcoidosis.

PubMed

Arbustini, E; Grasso, M; Leo, G; Tinelli, C; Fasani, R; Diegoli, M; Banchieri, N; Cipriani, A; Gorrini, M; Semenzato, G; Luisetti, M

1996-02-01

Sarcoidosis is the disease in which increased levels of serum Angiotensin-converting enzyme (sACE) are most often detected. It has recently been shown that the deletion (D) or the insertion (I) of a 250bp-DNA fragment in the ACE gene accounts for three main ACE genotypes (i.e., II, ID, and DD) and for 47% of total phenotypic variance in sACE level. The aim of our work was to investigate whether or not patients with sarcoidosis have an increased incidence of those ACE genotypes coding for highest sACE levels and to investigate whether or not sACE level in sarcoidosis is related to ACE genotypes. We studied 61 unrelated patients with sarcoidosis (test group) and 80 unrelated healthy control subjects (control group). The ACE I and D alleles were detected with polymerase chain reaction on genomic DNA. In the control group we found an ACE genotype distribution that agreed with the Hardy-Weinberg proportion. The ACE genotype distribution was not significantly different in the test group. There was no correlation between ACE genotype and roentgenologic stage of sarcoidosis. Plotting the sACE level in the control group against ACE genotype, we found a trend of increasing mean sACE value according to the order II < ID < DD. The same trend for ACE genotype was found in the test group, in which it also paralleled the trend of sACE values plotted against roentgenologic stage, according to the order Stage I < Stage II < Stage III. We conclude that in sarcoidosis the ACE genotype distribution is not altered. The trends for increasing sACE values in sarcoidosis according to both ACE genotype and roentgenologic stage would suggest that both mechanisms play a role in determining sACE level.

Evidence for a genetic component in familial sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rybicki, B.A.; Harrington, D.; Major, M.

1994-09-01

Sarcoidosis is a disease with reported familial clustering, but a putative hereditary component has not been established. We analyzed 33 sarcoid index cases with a positive family history and their 596 1st and 2nd degree relatives to determine if the distribution of disease was consistent with a genetic etiology. Prevalence of sarcoidosis was twice as high in 1st degree relatives of index cases compared to 2nd degree relatives (8.5% vs. 3.9%; p=0.016). Recurrence risk ratios (defined as the risk of disease in relatives divided by the population prevalence) were calculated in 2nd degree relatives after making an ascertainment correction. Amore » single gene model fit the observed results better than a polygenic model for a range of sarcoidosis prevalance. A greater shared environment among siblings compared to parents and offspring did not appear to increase risk of sarcoidosis based on a higher prevalance of disease in the latter (7.1% vs. 10.7%; p=0.313). However, the age of diagnosis in affected parent-offspring pairs was more consistent with a combined genetic and environmental etiology than either component alone. In summary, these results suggest a genetic component, possibly a single gene, increases disease risk in family members of sarcoidosis cases. A segregation analysis is planned to more thoroughly evaluate the evidence for both genetic and non-genetic transmission of sarcoidosis in these families.« less

Pulmonology meets rheumatology in sarcoidosis: a review on the therapeutic approach.

PubMed

Drent, Marjolein; Cremers, Johanna P; Jansen, Tim L

2014-05-01

Sarcoidosis is a systemic disease characterized by the formation of granulomas in various organs, mainly lungs and lymphatic system. Joint, muscle, and bone involvement is also rather common. Recent studies on its pathogenesis and therapeutic management are reviewed here. The pathogenesis of sarcoidosis is not fully elucidated. An exaggerated granulomatous reaction after exposure to unidentified antigens in genetically susceptible individuals evokes a clinical situation which we call sarcoidosis. No firm guidelines exist on whether, when, and how treatment should be started. Treatment is dependent on the presentation and the distribution, extensiveness and severity of sarcoidosis. Treatment of Löfgren's triad-related symptoms starts with NSAIDs; in other more extensive manifestations of sarcoidosis, the initiating dosage of glucocorticosteroids is approximately 20 mg daily. In terms of evidence-based treatment for sarcoidosis, only a few randomized controlled trials have been done. There is no cure for chronic sarcoidosis, and treatment only changes the granulomatous process and its clinical consequences. Identified associations of certain polymorphisms with severity of the disease and treatment response suggest future research questions as well as finding the cause(s) of sarcoidosis, and the elucidation of relevant biomarkers and new efficient treatments. Between 20 and 70% of patients need systemic therapy. The increased awareness of long-term side-effects of glucocorticosteroids and the emergence of new drugs have changed the treatment of sarcoidosis. Alternative or additional options to corticosteroids should be assessed.

Sarcoidosis presenting with pleurisy and bilateral pleural effusions.

PubMed Central

Johnson, N. M.; Martin, N. D.; McNicol, M. W.

1980-01-01

A patient with acute sarcoidosis is described who presented with pleurisy and bilateral pleural effusions, but no other abnormalities on examination or chest X-ray. This presentation of sarcoidosis is unusual and is discussed. Images Fig. 1 PMID:7433329

Tenth international conference on sarcoidosis and other granulomatous disorder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johns, C.J.

1986-01-01

This book contains papers divided among three sections: Basic Mechanisms of Sarcoidosis; Other Granulomatous Disorders; and Clinical Studies of Sarcoidosis. Some of the paper titles are: Radionuclides in Detecting Active Granuloma Formation: Gallium-67 Scintigraphy and Histopathology with Autoradiographic; a European Survey on the Usefulness of /sup 67/Ga Lung Scans in Assessing Sarcoidosis: Experience in 14 Research Centers in Seven Different Countries; and Reassessing the Standard Chest Radiograph for Intraparenchymal Activity.

Management of extrapulmonary sarcoidosis: challenges and solutions

PubMed Central

Al-Kofahi, Khalid; Korsten, Peter; Ascoli, Christian; Virupannavar, Shanti; Mirsaeidi, Mehdi; Chang, Ian; Qaqish, Naim; Saketkoo, Lesley A; Baughman, Robert P; Sweiss, Nadera J

2016-01-01

Background Sarcoidosis is a chronic multisystem disease of unknown etiology characterized by noncaseating granulomas that most often involves the lungs, but frequently has extrapulmonary manifestations, which might be difficult to treat in individual patients. Objective To review different disease manifestations, focusing on extrapulmonary organ systems, and to provide treatment options for refractory cases. Materials and methods We performed a literature search using Medline and Google Scholar for individual or combined keywords of “sarcoidosis, extrapulmonary, treatment, kidney, neurosarcoidosis, cardiovascular, gastrointestinal, transplantation, musculoskeletal, rheumatology, arthritis, and skin”. Peer-reviewed articles, including review articles, clinical trials, observational trials, and case reports that were published in English were included. References from retrieved articles were also manually searched for relevant articles. Results and conclusion Isolated involvement of a single organ or organ system is rare in sarcoidosis, and thus all patients must be thoroughly evaluated for additional disease manifestations. Cardiac sarcoidosis and neurosarcoidosis may be life-threatening. Clinicians need to assess patients comprehensively using clinical, laboratory, imaging, and histopathological data to recommend competently the best and least toxic treatment option for the individual patient. PMID:27853374

The role of pattern recognition receptors in lung sarcoidosis.

PubMed

Mortaz, Esmaeil; Adcock, Ian M; Abedini, Atefhe; Kiani, Arda; Kazempour-Dizaji, Mehdi; Movassaghi, Masoud; Garssen, Johan

2017-08-05

Sarcoidosis is a granulomatous disorder of unknown etiology. Infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. The etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. Inflammation results from recognition of evolutionarily conserved structures of pathogens (Pathogen-associated molecular patterns, PAMPs) and/or from reaction to tissue damage associated patterns (DAMPs) through recognition by a limited number of germ line-encoded pattern recognition receptors (PRRs). Due to the similar clinical and histopathological picture of sarcoidosis and tuberculosis, Mycobacterium tuberculosis antigens such early secreted antigen (ESAT-6), heat shock proteins (Mtb-HSP), catalase-peroxidase (katG) enzyme and superoxide dismutase A peptide (sodA) have been often considered as factors in the etiopathogenesis of sarcoidosis. Potential non-TB-associated PAMPs include lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria, peptidoglycan, lipoteichoic acid, bacterial DNA, viral DNA/RNA, chitin, flagellin, leucine-rich repeats (LRR), mannans in the yeast cell wall, and microbial HSPs. Furthermore, exogenous non-organic antigens such as metals, silica, pigments with/without aluminum in tattoos, pesticides, and pollen have been evoked as potential causes of sarcoidosis. Exposure of the airways to diverse infectious and non-infectious agents may be important in the pathogenesis of sarcoidosis. The current review provides and update on the role of PPRs and DAMPs in the pathogenesis of sarcoidsis. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatic sarcoidosis: pathogenesis, clinical context, and treatment options.

PubMed

Syed, Umer; Alkhawam, Hassan; Bakhit, Mena; Companioni, Rafael A Ching; Walfish, Aron

2016-09-01

Sarcoidosis is typically characterized as a non-caseating granulomatous disease that has the ability to affect multiple different organ systems. Although extra-thoracic sarcoidosis can occur in the presence and also without lung involvement, isolated extra-pulmonary disease is rare. The liver is the third most commonly affected organ system after the lungs and lymph nodes. When discussing hepatic sarcoidosis it is important to keep in mind that many patients in this population may not present as one would typically expect since most of the patients are asymptomatic or have mild presentations. Therefore, the diagnosis can be difficult at times since no single laboratory or imaging study can definitively diagnose this systemic disease. In the rare case of some patients where there is difficulty in discerning between different pathologies, the use of image-guided tissue biopsy may be necessary to establish a diagnosis. At the current time, there are no clear guidelines for the management of hepatic sarcoidosis and are mostly dependent on a patient's clinical status at time of presentation. The current body of research in regard to treatment suggests steroids to be the mainstay of therapy. However, there is a role for additional immunosuppressive therapy in cases where the initial treatment is refractory to steroids. In this manuscript, we discussed the pathogenesis of liver sarcoidosis and context of its presentation. In addition, the differential diagnosis and imaging evaluation in this population is discussed. Finally, treatment options are reviewed in setting of previous studies for liver sarcoidosis.

Physical activity and training in sarcoidosis: review and experience-based recommendations.

PubMed

Strookappe, Bert; Saketkoo, Lesley Ann; Elfferich, Marjon; Holland, Anne; De Vries, Jolanda; Knevel, Ton; Drent, Marjolein

2016-10-01

Sarcoidosis is a multisystemic inflammatory disorder with a great variety of symptoms, including fatigue, dyspnea, pain, reduced exercise tolerance and muscle strength. Physical training has the potential to improve exercise capacity and muscle strength, and reduce fatigue. The aim of this review and survey was to present information about the role of physical training in sarcoidosis and offer practical guidelines. A systematic literature review guided an international consensus effort among sarcoidosis experts to establish practice-basic recommendations for the implementation of exercise as treatment for patients with various manifestations of sarcoidosis. International sarcoidosis experts suggested considering physical training in symptomatic patients with sarcoidosis. Expert commentary: There is promising evidence of a positive effect of physical training. Recommendations were based on available data and expert consensus. However, the heterogeneity of these patients will require modification and program adjustment of the standard rehabilitation format for e.g. COPD or interstitial lung diseases. An optimal training program (types of exercise, intensities, frequency, duration) still needs to be defined to optimize training adjustments, especially reduction of fatigue. Further randomized controlled trials are needed to consolidate these findings and optimize the comprehensive care of sarcoidosis patients.

G908R NOD2 variant in a family with sarcoidosis.

PubMed

Besnard, Valérie; Calender, Alain; Bouvry, Diane; Pacheco, Yves; Chapelon-Abric, Catherine; Jeny, Florence; Nunes, Hilario; Planès, Carole; Valeyre, Dominique

2018-03-20

Sarcoidosis is a systemic disease characterized by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Exaggerated granulomatous reaction might be triggered in response to unidentified antigens in individuals with genetic susceptibility. The present study aimed to determine the genetic variants implicated in a familial case of sarcoidosis. Sarcoidosis presentation and history, NOD2 profile, NF-κB and cytokine production in blood monocytes/macrophages were evaluated in individuals from a family with late appearance of sarcoidosis. In the present study, we report a case of familial sarcoidosis with typical thoracic sarcoidosis and carrying the NOD2 2722G > C variant. This variant is associated with the presence of three additional SNPs for the IL17RA, KALRN and EPHA2 genes, which discriminate patients expressing the disease from others. Despite a decrease in NF-κB activity, IL-8 and TNF-A mRNA levels were increased at baseline and in stimulated conditions. Combination of polymorphisms in the NOD2, IL17RA, EPHA2 and KALRN genes could play a significant role in the development of sarcoidosis by maintaining a chronic pro-inflammatory status in macrophages.

Economic burden of sarcoidosis in a commercially-insured population in the United States.

PubMed

Rice, J Bradford; White, Alan; Lopez, Andrea; Conway, Alexandra; Wagh, Aneesha; Nelson, Winnie W; Philbin, Michael; Wan, George J

2017-10-01

Sarcoidosis is a multi-system inflammatory disorder characterized by the presence of non-caseating granulomas in involved organs. Patients with sarcoidosis have a reduced quality-of-life and are at an increased risk for several comorbidities. Little is known about the direct and indirect cost of sarcoidosis following the initial diagnosis. To provide an estimate of the healthcare resource utilization (HCRU) and costs borne by commercial payers for sarcoidosis patients in the US. Patients with a first diagnosis of sarcoidosis between January 1, 1998 and March 31, 2015 ("index date") were selected from a de-identified privately-insured administrative claims database. Sarcoidosis patients were required to have continuous health plan enrollment 12 months prior to and following their index dates. Propensity-score (1:1) matching of sarcoidosis patients with non-sarcoidosis controls was carried out based on a logistic regression of baseline characteristics. Burden of HCRU and work loss (disability days and medically-related absenteeism) were compared between the matched groups over the 12-month period following the index date ("outcome period"). A total of 7,119 sarcoidosis patients who met the selection criteria were matched with a control. Overall, commercial payers incurred $19,714 in mean total annual healthcare costs per sarcoidosis patient. The principle cost drivers were outpatient visits ($9,050 2015 USD, 46%) and inpatient admissions ($6,398, 32%). Relative to controls, sarcoidosis patients had $5,190 (36%) higher total healthcare costs ($19,714 vs $14,524; p < 0.001). Sarcoidosis patients also had significantly more work loss days (15.9 vs 11.3; p < 0.001) and work loss costs ($3,288 vs $2,527; p < 0.001) than matched controls. Sarcoidosis imposes an estimated total direct medical cost of $1.3-$8.7 billion to commercial payers, and an indirect cost of $0.2-$1.5 billion to commercial payers in work loss. Sarcoidosis imposes a significant economic

Hospitalization Among Patients with Sarcoidosis: A Population-Based Cohort Study 1987-2015.

PubMed

Ungprasert, Patompong; Crowson, Cynthia S; Achenbach, Sara J; Carmona, Eva M; Matteson, Eric L

2017-08-01

There is little information about healthcare utilization for sarcoidosis. This study examined need for hospitalization as a measure of healthcare burden in this disease. A cohort of Olmsted County, Minnesota residents diagnosed with sarcoidosis between January 1, 1976 and December 31, 2013 was identified using the resources of the Rochester Epidemiology Project. Diagnosis was made based on individual medical record review. For each sarcoidosis subject, one sex- and age-matched comparator without sarcoidosis was randomly selected from the same population. Data on hospitalizations were retrieved electronically from billing data of the Mayo Clinic, the Olmsted Medical Center, and their affiliated hospitals. These data were available from 1987 to 2015. Subjects who died or emigrated from Olmsted County prior to 1987 were excluded. 332 incident cases of sarcoidosis and 342 comparators were included. Hospitalization rates were significantly higher among patients with sarcoidosis than comparators [rate ratio (RR) 1.37; 95% confidence interval (CI) 1.24-1.52]. Analysis based on sex revealed a significantly increased rate among females (RR 1.60; 95% CI 1.40-1.82) but not among males (RR 1.06; 95% CI 0.91-1.25). The overall age- and sex-adjusted rates of hospitalization were stable from 1987 to 2015 for both cases and comparators. The average length of stay was similar (4.6 and 4.4 days for sarcoidosis and non-sarcoidosis hospitalizations, respectively, p = 0.87). In this population, patients with sarcoidosis had a significantly higher rate of hospitalization than patients without sarcoidosis, driven by higher rates in females.

An atypical sarcoidosis involvement in FDG PET/CT

PubMed Central

Robin, Philippe; Benigni, Paolo; Feger, Benoit; Salaun, Pierre-Yves; Abgral, Ronan

2016-01-01

Abstract Rationale: Sarcoidosis is an idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis which involve various organs. Laryngeal involvement is extremely rare, with a prevalence of about 0.5 to 1%. Diagnoses: Here we present a case of laryngeal involvement of sarcoidosis demonstrated on 18F-Fluorodesoxyglucose Positron-Emission Tomography/Computed Tomography (FDG PET/CT). Patient concerns: A 63 year-old man suffering from dysphonia was referred to our department for characterization of laryngeal lesion suspicious for cancer with non-informative biopsy, the sample was not sufficient for diagnosis. Interventions: FDG PET/CT showed a pathological uptake on the right vocal cord, but also highlighted a bilateral uptake in intrathoracic hilar lymphadenopathy areas, typically found in several inflammatory diseases. Outcomes: New laryngeal targeted biopsies revealed non-caseating epithelioid granulomas suggesting sarcoidosis involvement. After 6 months of systemic steroid treatment, FDG PET/CT showed a significant decrease of the laryngeal uptake. Lessons: This case shows the usefulness of FDG PET/CT to accurately assess inflammatory activity in rare extra-pulmonary sarcoidosis involvement. Moreover, this case emphasizes that FDG PET/CT is an interesting tool for assessing therapeutic efficacy of inflammatory diseases such as sarcoidosis. PMID:28033265

Smoking, obesity and risk of sarcoidosis: A population-based nested case-control study.

PubMed

Ungprasert, Patompong; Crowson, Cynthia S; Matteson, Eric L

2016-11-01

Smoking and obesity might alter the risk of sarcoidosis. However, the data remained inconclusive. A cohort of Olmsted County, Minnesota residents diagnosed with sarcoidosis between January 1, 1976 and December 31, 2013 was identified based on individual medical record review. For each sarcoidosis subject, one sex and aged-matched control without sarcoidosis was randomly selected from the same underlying population. Medical records of cases and controls were reviewed for smoking status at index date and body mass index (BMI) within 1 year before to 3 months after index date. 345 incident cases of sarcoidosis and 345 controls were identified. The odds ratio of sarcoidosis comparing current smokers with never smokers adjusted for age and sex was 0.34 (95% confidence interval (CI), 0.23-0.50). The odds ratio of sarcoidosis comparing current smokers with never smokers and former smokers adjusted for age and sex was 0.38 (95% CI, 0.26-0.56). The odds ratio of sarcoidosis comparing overweight subjects (BMI ≥ 25 kg/m 2 but < 30 kg/m 2 ) with subjects with normal/low BMI was 1.12 (95% CI, 0.72-1.75). The odds ratio of sarcoidosis comparing obese subjects (BMI ≥ 30 kg/m 2 ) with subjects with normal/low BMI was 2.54 (95% CI, 1.58-4.06). The odds ratio of sarcoidosis comparing obese subjects with non-obese subjects was 2.38 (95% CI, 1.60-3.56). In this population, current smokers have a lower risk of developing sarcoidosis while subjects with obesity have a higher risk of developing sarcoidosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cutaneous localization of Ga-67 in systemic sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rohatgi, P.K.

1981-03-01

/sup 67/Ga scans have been used in patients with sarcoidosis to assess noninvasively the intensity of alveolitis and to detect areas of extrathoracic involvement. To the author's knowledge, this is the first report of the localization of gallium in cutaneous lesions of a patient with sarcoidosis.

[Morpheiform sarcoidosis as atypical manifestation of sarcoidosis. Review of the literature and differential diagnosis].

PubMed

Castellanos-González, María; Picazo Talavera, María Remedios

2016-09-16

Sarcoidosis is an idiopathic multisystem granulomatous disease that commonly involves the skin in 25% of affected patients. Because lesions assume a vast array of morphologies, a classification dividing them into specific (with presence of typical granulomas in the biopsy) or nonspecific (not containing granulomas) has been proposed. In the first group the variant morpheaform is considered exceptional. We review the cases reported in the literature and describe the possible differential diagnosis. We highlight the importance of recognizing the very atypical presentation of sarcoidosis and its ability to mimic morpheaform or sclerosis diseases in our patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Neutrophil gelatinase-associated lipocalin in patients with sarcoidosis.

PubMed

Kato, Shinpei; Inui, Naoki; Hozumi, Hironao; Inoue, Yusuke; Yasui, Hideki; Karayama, Masato; Kono, Masato; Suzuki, Yuzo; Furuhashi, Kazuki; Enomoto, Noriyuki; Fujisawa, Tomoyuki; Nakamura, Yutaro; Watanabe, Hiroshi; Suda, Takafumi

2018-05-01

Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein that is involved in the innate immune system and increased expression has been detected in diverse diseases. Sarcoidosis is a systemic granulomatous disorder and its clinical course and prognosis are changeable and highly divergent. This study aimed to examine the expression of NGAL in patients with sarcoidosis. In addition, we examined whether NGAL could serve as a marker of disease activity and prognosis. Ninety-six sarcoidosis patients were studied. Serum samples collected at the time of diagnosis were examined for NGAL by cellular enzyme-linked immunosorbent assay. The level of NGAL was compared with clinical, radiological and laboratory data. Patients with sarcoidosis had significantly higher levels of NGAL (the median [interquartile range] was 35.1 ng/mL [23.5-60.8] in sarcoidosis patients versus 17.2 ng/mL [13.0-27.0] in the reference population, p < .0001). NGAL levels were not correlated with markers for disease activity. During the follow-up period, 26 patients (27.1%) deteriorated and received systemic corticosteroid therapy for organ dysfunction. In those patients, NGAL levels were significantly higher than in those who did not receive corticosteroid therapy (56.5 ng/mL [27.3-92.3] versus 34.3 ng/mL [23.0-53.0], p = .0201). Upon multivariate logistic regression analysis, elevated NGAL levels at diagnosis were associated with subsequent use of systemic corticosteroid therapy (hazard ratio, 1.20; 95% confidence interval, 1.09-1.31; p = .0004). NGAL may be a useful marker to predict the disease course of sarcoidosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sarcoidosis in Black Women in the United States

PubMed Central

Berman, Jeffrey S.; Palmer, Julie R.; Boggs, Deborah A.; Serlin, David M.; Rosenberg, Lynn

2011-01-01

Background: Sarcoidosis is a systemic granulomatous disorder of unknown cause that occurs among men and women of all races. In the United States, black women are most frequently and most severely affected. There have been few epidemiologic studies of sarcoidosis focusing on black women. Methods: In this article, we present data on incidence, prevalence, and clinical characteristics of sarcoidosis among participants in the Black Women’s Health Study, a cohort study of 59,000 black women from across the United States. Data on incident disease and potential risk factors are obtained through biennial questionnaires. Follow-up has been > 80% through six completed cycles. Results: There were 685 prevalent cases of sarcoidosis at baseline in 1995 and 435 incident cases reported during 611,585 person-years of follow-up through 2007, for an average annual incidence rate of 71/100,000 and a current prevalence of 2.0%. The sarcoid diagnosis was confirmed in 96% of self-reported cases for whom medical records or physician checklists were obtained. The most frequently affected site was the lung. Most patients also had extrapulmonary involvement, with the most common sites being lymph nodes, skin, and eyes. Prednisone had the highest prevalence of use, followed by inhaled corticosteroids. Conclusions: This study confirms previous reports of high incidence and prevalence of sarcoidosis among black women, as well as the extent of extrapulmonary disease, frequent need for steroid therapy, and comorbid conditions in this population. The prospective identification of sarcoidosis cases from a defined population will enable a valid assessment of risk factors for incident disease as follow-up continues. PMID:20595459

Cardiac resynchronization therapy for patients with cardiac sarcoidosis.

PubMed

Sairaku, Akinori; Yoshida, Yukihiko; Nakano, Yukiko; Hirayama, Haruo; Maeda, Mayuho; Hashimoto, Haruki; Kihara, Yasuki

2017-05-01

Sarcoidosis with cardiac involvement is a rare pathological condition, and therefore cardiac resynchronization therapy (CRT) for patients with cardiac sarcoidosis is even further rare. We aimed to clarify the clinical features of patients with cardiac sarcoidosis who received CRT. We retrospectively reviewed the clinical data on CRT at three cardiovascular centres to detect cardiac sarcoidosis patients. We identified 18 (8.9%) patients with cardiac sarcoidosis who met the inclusion criteria out of 202 with systolic heart failure who received CRT based on the guidelines. The majority of the patients were female [15 (83.3%)] and underwent an upgrade from a pacemaker or implantable cardioverter defibrillator [13 (72.2%)]. We found 1 (5.6%) cardiovascular death during the follow-up period (mean ± SD, 4.7 ± 3.0 years). Seven (38.9%) patients had a composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Twelve (66.7%) patients had a history of sustained ventricular arrhythmias or those occurring after the CRT. Among the overall patients, no significant improvement was found in either the end-systolic volume or left ventricular ejection fraction (LVEF) 6 months after the CRT. A worsening LVEF was, however, more likely to be seen in 5 (27.8%) patients with ventricular arrhythmias after the CRT than in those without (P = 0.04). An improved clinical composite score was seen in 10 (55.6%) patients. Cardiac sarcoidosis patients receiving CRT may have poor LV reverse remodelling and a high incidence of ventricular arrhythmias. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Current concepts regarding calcium metabolism and bone health in sarcoidosis.

PubMed

Baughman, Robert P; Papanikolaou, Ilias

2017-09-01

Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.

Recognition of distinctive patterns of gallium-67 distribution in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sulavik, S.B.; Spencer, R.P.; Weed, D.A.

1990-12-01

Assessment of gallium-67 ({sup 67}Ga) uptake in the salivary and lacrimal glands and intrathoracic lymph nodes was made in 605 consecutive patients including 65 with sarcoidosis. A distinctive intrathoracic lymph node {sup 67}Ga uptake pattern, resembling the Greek letter lambda, was observed only in sarcoidosis (72%). Symmetrical lacrimal gland and parotid gland {sup 67}Ga uptake (panda appearance) was noted in 79% of sarcoidosis patients. A simultaneous lambda and panda pattern (62%) or a panda appearance with radiographic bilateral, symmetrical, hilar lymphadenopathy (6%) was present only in sarcoidosis patients. The presence of either of these patterns was particularly prevalent in roentgenmore » Stages I (80%) or II (74%). We conclude that simultaneous (a) lambda and panda images, or (b) a panda image with bilateral symmetrical hilar lymphadenopathy on chest X-ray represent distinctive patterns which are highly specific for sarcoidosis, and may obviate the need for invasive diagnostic procedures.« less

Enhanced LPS-induced activation of IL-27 signalling in sarcoidosis.

PubMed

Ringkowski, Sabine; Loke, Joshua; Huang, Shuying; Ahmadzai, Hasib; Herth, Felix J F; Thomas, Paul S; Herbert, Cristan

2016-08-01

Granulomas in sarcoidosis have recently been described as containing Interleukin (IL)-27, one of the members of the IL-12 family of cytokines, which also includes IL-35. Levels of these cytokines and the IL-27 receptor subunits were hypothesised to differ between patients with sarcoidosis compared to healthy controls in peripheral blood. Using a cross-sectional study design, plasma and peripheral blood mononuclear cells (PBMC) were collected from patients and control subjects. Protein and mRNA (in PBMC) levels for IL-27 and IL-35 (IL27, EBI3, IL12A subunits) as well as IL-27 receptor (IL6ST and IL27RA subunits) were assessed spontaneously and following direct (LPS) and indirect (anti-CD3/28 activation beads) macrophage stimulation using RT- PCR, ELISA and flow cytometry. Following stimulation with LPS, PBMC of patients with sarcoidosis displayed significantly enhanced expression of IL27 and EBI3 mRNA (p = 0.020 and p = 0.037 respectively) compared to PBMCs from healthy controls. There was also significantly enhanced production of IL-27 by PBMC from patients with sarcoidosis compared to healthy controls in response to LPS stimulation (p = 0.027). IL6ST mRNA and IL6ST protein were significantly lower in patients with sarcoidosis (mRNA p = 0.0002; MFI p = 0.0015) whilst IL27RA protein levels were significantly higher in patients with sarcoidosis compared to healthy controls (MFI p < 0.0001). Plasma IL-35 protein levels did not differ between control and sarcoidosis subjects (p = 0.23). These results suggest there may be exaggerated activation of IL-27 signalling in response to LPS in sarcoidosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinicopathological study of glomerular diseases associated with sarcoidosis: a multicenter study

PubMed Central

2013-01-01

Background The association between sarcoidosis and glomerular diseases has not been extensively investigated in a large series and the potential features of this uncommon association remain to be determined. Methods We retrospectively identified 26 patients with biopsy-proven glomerular lesions that occurred in a sarcoidosis context. Potential remission of glomerular disease and sarcoidosis under specific treatment (steroid and/or immunosuppressive agents) was recorded for all patients. Demographic, clinical and biological characteristics were assessed at the time of kidney biopsy for each patient. Therapeutic data were analyzed for all patients. Results Glomerular disease occurred after the diagnosis of sarcoidosis in 11 of 26 cases (42%) (mean delay of 9.7 years). In six patients (23%), the glomerulopathy preceded the sarcoidosis diagnosis (mean delay 8 years). In the last nine patients (35%), both conditions occurred simultaneously. The most frequent glomerular disease occurring in sarcoidosis patients was membranous nephropathy in eleven cases. Other glomerular lesions included IgA nephropathy in six cases, focal segmental glomerulosclerosis in four patients, minimal change nephrotic syndrome for three patients and proliferative lupus nephritis in two patients. Granulomatous interstitial nephritis was associated with glomerular disease in six patients and was exclusively found in patients in whom the both disease occurred simultaneously. In nine patients with simultaneous glomerular and sarcoidosis diseases, we observed a strong dissociation between glomerular disease and sarcoidosis in terms of steroid responsiveness. At the end of the follow-up (mean of 8.4 years), six patients had reached end-stage renal disease and three patients had died. Conclusions A wide spectrum of glomerular lesions is associated with sarcoidosis. The close temporal relationship observed in some patients suggests common causative molecular mechanisms of glomerular injury but

[Features of prevalence of sarcoidosis among the inhabitants of Moscow].

PubMed

2012-01-01

The present study was designed to investigate the prevalence of sarcoidosis in Moscow under the impact of various social-hygienic factors. 302 residents in Moscow with a confirmed diagnosis of "sarcoidosis" were examined. Relationships between exposure to social-hygienic factors and epidemiological characteristics of the patients' population have been analyzed The requirement of separate analysis of male and female populations of patients with sarcoidosis has been established in connection with independent formation of these samples, as well as differences in their response to the social and hygienic factors. The results indicate that male and female populations of patients with sarcoidosis are formed independently, express different reaction to social-hygienic factors and should be analyzed separately.

Necrotizing crescentic glomerulonephritis related to sarcoidosis: a case report.

PubMed

Maroz, Natallia; Field, Halle

2015-12-14

Renal injury due to sarcoidosis develops in less than a quarter of patients with this systemic disease. In most cases, granulomatous tissue alters the production of vitamin D, which leads to hypercalciuria, nephrocalcinosis, and nephrolithiasis. Granulomatous interstitial nephritis is another well-recognized pathological process associated with sarcoidosis. However, a glomerular pathology is very rarely noted, and only a few cases are reported to have cellular crescentic glomerulonephritis. We describe the case of a 26-year-old African American woman with systemic sarcoidosis, with a unique constellation of renal lesions, including noncaseating epithelioid granulomatous necrotizing interstitial nephritis, cellular crescent formation, and necrotizing vasculitis. Immunosuppressive therapy was helpful for alleviating her nephrotic syndrome and maintaining the stability of her renal function over a 30-month period. Glomerular involvement of sarcoidosis needs to be considered in the differential diagnosis in cases of rapidly progressive glomerular nephritis.

Sarcoidosis-Like Lesions: Another Paradoxical Reaction to Anti-TNF Therapy?

PubMed

Decock, Amelie; Van Assche, Gert; Vermeire, Séverine; Wuyts, Wim; Ferrante, Marc

2017-03-01

Since the introduction of anti-tumour necrosis factor [TNF] therapy in inflammatory diseases, paradoxical reactions are increasingly being reported. One of these paradoxical reactions is the development of sarcoidosis-like lesions. This presentation is paradoxical since anti-TNF therapy can also be therapeutic in refractory cases of sarcoidosis. We report two cases of sarcoidosis-like lesions under anti-TNF therapy. Both were patients with inflammatory bowel disease [IBD], treated successfully with adalimumab. Next, we reviewed the literature for similar cases. Medical subject heading terms 'adalimumab', 'infliximab', 'etanercept', 'golimumab' or 'certolizumab', and 'sarcoidosis' were used to perform key word searches of the PubMed database. We identified 90 reported cases of sarcoidosis-like lesions, which developed during anti-TNF therapy. In most cases, the anti-TNF drug involved was etanercept. The median age was 43 years and there was a predominance of female patients. The underlying disease was rheumatoid arthritis in most cases, followed by ankylosing spondylitis and psoriasiform arthritis. In six cases, the underlying disease was IBD. In 71 cases there was at least a partial resolution by discontinuation of the anti-TNF treatment, initiation of steroids or both. Re-initiation of anti-TNF therapy gave relapse in seven out of 20 cases. Sarcoidosis-like lesions are increasingly reported during anti-TNF treatment. Vigilance is appropriate when patients present with symptoms compatible with sarcoidosis. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Treatment of neuro-ophthalmic sarcoidosis.

PubMed

Frohman, Larry P

2015-03-01

Because of the rarity of neuro-ophthalmic sarcoidosis, there are no therapeutic guidelines based on evidence-based medicine for this disorder. Review of literature combined with personal experience. Corticosteroids are the preferred initial therapy for neuro-ophthalmic sarcoidosis. If patients cannot tolerate the requisite dose of corticosteroid needed to control their disease, or if corticosteroids fail to adequately control the disease process, the choices of a second agent are based on the consideration of rapidity of clinical response and the safety profile. Although methotrexate and mycophenolate mofetil are the medications that are often selected after corticosteroid failure, more rapidly acting agents that have been used are infliximab and intravenous cyclophosphamide.

Comorbid autoimmune diseases in patients with sarcoidosis: A nationwide case-control study in Taiwan.

PubMed

Wu, Chi-Hung; Chung, Pei-I; Wu, Chen-Yi; Chen, Yen-Ta; Chiu, Yun-Wen; Chang, Yun-Ting; Liu, Han-Nan

2017-04-01

The association between sarcoidosis and autoimmune comorbidities has been reported, however, it has seldom been confirmed by a large nationwide study. Our study aimed to clarify the association between sarcoidosis and autoimmune comorbidities in the Taiwanese. A total of 1237 patients with sarcoidosis and 4948 age- and sex-matched control subjects were selected from the National Health Insurance Research Database of Taiwan from 1997 to 2010. Multiple logistic regressions were performed to calculate the odds of comorbidities between the two groups. The prevalence of sarcoidosis was 2.17/100 000 individuals in Taiwan. Sarcoidosis patients tended to run a higher risk of autoimmune comorbidities than the control group (17.6% vs 9.4%, P < 0.05). Autoimmune thyroid disease (adjusted odd ratio [aOR], 1.32; 95% confidence interval [CI], 1.05-1.64), Sjögren's syndrome (aOR, 11.6; 95% CI, 4.36-31.0) and ankylosing spondylitis (aOR, 3.80; 95% CI, 2.42-5.97) were significantly associated with sarcoidosis. The sex-stratified analyses were carried out to demonstrate a significant association of sarcoidosis with ankylosing spondylitis in both sexes, but with autoimmune thyroid disease in male patients and with Sjögren's syndrome female patients, respectively. Besides, the diagnosis of the autoimmune comorbidities strongly associated with sarcoidosis tended to be established after that of sarcoidosis. This study demonstrated that patients with sarcoidosis tended to have autoimmune thyroid disease, Sjögren's syndrome and ankylosing spondylitis, and the diagnosis of sarcoidosis usually preceded that of associated comorbidities. Clinicians should be alert to autoimmune comorbidities in patients with sarcoidosis. © 2016 Japanese Dermatological Association.

Gallium scanning in sarcoidosis. [/sup 67/Ga tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Israel, H.L.; Park, C.H.; Mansfield, C.M.

1976-01-01

The uptake of gallium-67 by pulmonary sarcoidosis was noted by Langhammer et al. in 1972 and by McKusick et al. in 1973. Heshiki et al. studied the application of this procedure in the diagnosis of sarcoidosis and concluded that although gallium-67 uptake in lungs and hilar regions correlated poorly with clinical activity, its measurement might prove useful in the diagnosis of sarcoidosis and in the measurement of response to therapy. We have undertaken to evaluate further the clinical usefulness of this technique. Thirty-six patients, 27 of whom had sarcoidosis, were given intravenous injections of 3 ml of commercially obtained (/supmore » 67/Ga) citrate. None were receiving corticosteroid therapy at the time of the initial study. Three days later simultaneous anterior and posterior scans of the thorax and the upper abdomen were performed in the supine position. 1 table.« less

Gallium-67 activity in bronchoalveolar lavage fluid in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trauth, H.A.; Heimes, K.; Schubotz, R.

1986-01-01

Roentgenograms and gallium-67 scans and gallium-67 counts of BAL fluid samples, together with differential cell counts, have proved to be useful in assessing activity and lung involvement in sarcoidosis. In active pulmonary sarcoidosis gallium-67 scans are usually positive. Quantitation of gallium-67 uptake in lung scans, however, may be difficult. Because gallium-67 uptake and cell counts in BAL fluid may be correlated, we set out to investigate gallium-67 activity in BAL fluid recovered from patient of different groups. Sixteen patients with recently diagnosed and untreated sarcoidosis, nine patients with healthy lungs, and five patients with CFA were studied. Gallium-67 uptake ofmore » the lung, gallium-67 activity in the lavage fluid, SACE and LACE levels, and alpha 1-AT activity were measured. Significantly more gallium-67 activity was found in BAL fluid from sarcoidosis patients than in that from CFA patients (alpha = .001) or patients with healthy lungs (alpha = .001). Gallium-67 activity in BAL fluid could be well correlated with the number of lymphocytes in BAL fluid, but poorly with the number of macrophages. Subjects with increased levels of SACE or serum alpha 1-AT showed higher lavage gallium-67 activity than did normals, but no correlation could be established. High gallium-67 activity in lavage fluid may be correlated with acute sarcoidosis or physiological deterioration; low activity denotes change for the better. The results show that gallium-67 counts in BAL fluid reflects the intensity of gallium-67 uptake and thus of activity of pulmonary sarcoidosis.« less

Sarcoidosis Related Novel Candidate Genes Identified by Multi-Omics Integrative Analyses.

PubMed

Hočevar, Keli; Maver, Aleš; Kunej, Tanja; Peterlin, Borut

2018-05-01

Sarcoidosis is a multifactorial systemic disease characterized by granulomatous inflammation and greatly impacting on global public health. The etiology and mechanisms of sarcoidosis are not fully understood. Recent high-throughput biological research has generated vast amounts of multi-omics big data on sarcoidosis, but their significance remains to be determined. We sought to identify novel candidate regions, and genes consistently altered in heterogeneous omics studies so as to reveal the underlying molecular mechanisms. We conducted a comprehensive integrative literature analysis on global data on sarcoidosis, including genomic, transcriptomic, proteomic, and phenomic studies. We performed positional integration analysis of 38 eligible datasets originating from 17 different biological layers. Using the integration interval length of 50 kb, we identified 54 regions reaching significance value p ≤ 0.0001 and 15 regions with significance value p ≤ 0.00001, when applying more stringent criteria. Secondary literature analysis of the top 20 regions, with the most significant accumulation of signals, revealed several novel candidate genes for which associations with sarcoidosis have not yet been established, but have considerable support for their involvement based on omic data. These new plausible candidate genes include NELFE, CFB, EGFL7, AGPAT2, FKBPL, NRC3, and NEU1. Furthermore, annotated data were prepared to enable custom visualization and browsing of these sarcoidosis related omics evidence in the University of California Santa Cruz (UCSC) Genome Browser. Further multi-omics approaches are called for sarcoidosis biomarkers and diagnostic and therapeutic innovation. Our approach for harnessing multi-omics data and the findings presented herein reflect important steps toward understanding the etiology and underlying pathological mechanisms of sarcoidosis.

Socio-demographic profile of patients with sarcoidosis vis-à-vis tuberculosis.

PubMed

Gupta, D; Vinay, N; Agarwal, R; Agarwal, A N

2013-11-25

Sarcoidosis and tuberculosis closely resemble each other and Mycobacterium tuberculosis has been implicated as a causative agent for sarcoidosis. Herein we explore the socio-demographic features of patients with sarcoidosis vis-a-vis tuberculosis. In a prospective case-control design, we studied hundred patients each of newly diagnosed sarcoidosis, bacteriologically confirmed pulmonary tuberculosis and healthy controls. Socio-demographic profile was recorded on a standardized questionnaire. Information about tobacco smoking, exposure to environmental tobacco smoke (ETS) and cooking fuels was also collected. Various parameters were compared among the three groups. Compared to tuberculosis, patients with sarcoidosis were elder, had better body mass index (BMI), higher urban residence (OR 2.19, 95% CI: 1.02-4.69), were better educated (ORs 8.50 to 74.25 for different categories), had higher per capita income (OR 13.33; 95% CI: 6.79-26.19) and belonged to better overall socio-economic status (SES) (ORs 8.57-195.0 for different categories). All these differences were also significant when sarcoidosis patients were compared to healthy controls albeit to a lesser degree. Tobacco smoking, ETS exposure and use of fossil/biomass fuels for cooking were more commonly seen in TB patients. In the multivariate analysis, as compared to TB or controls, sarcoidosis patients had higher odds for a better SES after adjusting for age, gender, BMI, religion, smoking, ETS exposure and cooking fuel. Patients with sarcoidosis are likely to be better educated and more affluent compared to those with tuberculosis and healthy controls and this can be useful in clinical differential diagnosis of the two conditions in populations with high prevalence of TB.

Serum angiotensin-converting enzyme (SACE) in sarcoidosis and other granulomatous disorders.

PubMed

Studdy, P; Bird, R; James, D G

Serum angiotensin-converting enzyme (SACE) activity was significantly higher in 90 patients with sarcoidosis (55 +/- [S.D.] 23 nmol min-1 ml-1) than in 80 healthy controls (34 +/- 9 nmol min-1 ml-1). Steroid therapy modified SACE activity; 60 sarcoidosis patients who were not being treated with steroids had significantly higher enzyme activities (58 +/- 24 nmol min-1 ml-1) than 30 steroid-treated sarcoidosis patients (40 +/- 19 nmol min-1 ml-1). In 50% of the non-steroid treated sarcoidosis patients SACE activity was more than 2 S.D. above the mean value for the controls. SACE activity was measured in 22 tuberculous patients (38 +/- 14 nmol min-1 ml-1), 20 leprosy patients (34 +/- 9 nmol min-1 ml-1), 31 with primary biliary cirrhosis (44 +/- 20 nmol min-1 ml-1), 26 with inflammatory bowel disease (31 +/- 9 nmol min-1 ml-1), 8 with hepatic granulomatous disease, 5 with Hodgkin's disease, and 2 with schistosomiasis. The combined false-positive rate for these non-sarcoidosis patients was 10%. Serial SACE assays provide useful information on the course of sarcoidosis and response to steroid treatment.

Serum angiotensin--converting enzyme (SACE) in sarcoidosis and other granulomatous disorders.

PubMed

Studdy, P; Bird; James, D G; Sherlock, S

Serum angiotensin-converting enzyme (SACE) activity was significantly higher in 90 patients with sarcoidosis (55 +/- [S.D.] 23 nmol min-1 ml-1) than in 80 healthy controls (34 +/- 9 nmol min-1 ml-1). Steroid therapy modified SACE activity; 60 sarcoidosis patients who were not being treated with steroids had significantly higher enzyme activities (58 +/- 24 nmol min-1 ml-1) than 30 steroid-treated sarcoidosis patients (40 +/- 19 nmol min-1 ml-1). In 50% of the non-steroid treated sarcoidosis patients SACE activity was more than than 2 S.D. above the mean value for the controls. SACE activity was measured in 22 tuberculous patients (38 +/- 14 nmol min-1 ml-1), 20 leprosy patients (34 +/- 9 nmol min-1 ml-1), 31 with primary biliary cirrhosis (44 +/- 20 nmol min-1 ml-1), 26 with inflammatory bowel disease (31 +/- 9 nmol min-1 ml-1), eight with hepatic granulomatous disease, five with Hodgkin's disease, and two with schistosomiasis. The combined false-positive rate for these non-sarcoidosis patients was 10%. Serial SACE assays provide useful information on the course of sarcoidosis and response to steroid treatment.

Differential Expression of MicroRNA and Predicted Targets in Pulmonary Sarcoidosis

PubMed Central

Crouser, Elliott D.; Julian, Mark W.; Crawford, Melissa; Shao, Guohong; Yu, Lianbo; Planck, Stephen R.; Rosenbaum, James T.; Nana-Sinkam, S. Patrick

2014-01-01

Background Recent studies show that various inflammatory diseases are regulated at the level of RNA translation by small non-coding RNAs, termed microRNAs (miRNAs). We sought to determine whether sarcoidosis tissues harbor a distinct pattern of miRNA expression and then considered their potential molecular targets. Methods and Results Genome-wide microarray analysis of miRNA expression in lung tissue and peripheral blood mononuclear cells (PBMCs) was performed and differentially expressed (DE)-miRNAs were then validated by real-time PCR. A distinct pattern of DE-miRNA expression was identified in both lung tissue and PBMCs of sarcoidosis patients. A subgroup of DE-miRNAs common to lung and lymph node tissues were predicted to target transforming growth factor (TGFβ)-regulated pathways. Likewise, the DE-miRNAs identified in PBMCs of sarcoidosis patients were predicted to target the TGFβ-regulated “wingless and integrase-1” (WNT) pathway. Conclusions This study is the first to profile miRNAs in sarcoidosis tissues and to consider their possible roles in disease pathogenesis. Our results suggest that miRNA regulate TGFβ and related WNT pathways in sarcoidosis tissues, pathways previously incriminated in the pathogenesis of sarcoidosis. PMID:22209793

Fatigue in sarcoidosis and idiopathic pulmonary fibrosis: differences in character and severity between diseases.

PubMed

Atkins, Christopher Peter; Gilbert, Daniel; Brockwell, Claire; Robinson, Sue; Wilson, Andrew Malcolm

2016-08-01

Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two common forms of interstitial lung disease. Fatigue is a recognised feature of sarcoidosis but an association between IPF and fatigue has not been investigated. To investigate the frequency and severity of fatigue in these groups, and variables affecting fatigue scores. A cross-sectional questionnaire study of patients with sarcoidosis and IPF followed-up at a single hospital was undertaken. Questionnaire data included validated measures of fatigue, anxiety, depression, sleepiness and dyspnoea, plus measures of disease severity including spirometry data. Questionnaires were administered to 232 patients (82 healthy volunteers, 73 sarcoidosis patients and 77 IPF patients). Sarcoidosis patients had statistically higher sleepiness scores but no significant difference was seen between overall measures of fatigue, anxiety or depression. Stratification by severity revealed a non-statistically significant tendency towards more severe fatigue scores in sarcoidosis. Regression analysis failed to identify any significant predictor variables measured in the sarcoidosis cohort, though in the IPF group both dyspnoea and sleepiness scores were significant predictors of fatigue (R2=0.74). Both sarcoidosis and IPF patients suffer with fatigue, although sarcoidosis patients tended towards reporting more severe fatigue scores, suggesting a subgroup with severe fatigue. The fatigue experienced by the two groups appears to be different; sarcoidosis patients report greater frequency of mental fatigue whereas IPF patients appear to suffer exhaustion, potentially related to dyspnoea. Dyspnoea and sleepiness scores modeled the majority of fatigue in the IPF group, whereas no single factor was able to predict fatigue in sarcoidosis.

Childhood Sarcoidosis Presenting as Recurrent Facial Palsy.

PubMed

Passi, Gouri Rao; Arora, Kriti; Gokhale, Narendra

2018-04-15

Recurrent facial palsy in a patient merits investigation for underlying etiology. 8-year-old boy with erythematous itchy skin lesion and recurrent facial palsy. He had a past history of aseptic meningitis and nephrocalcinosis. Raised angiotensin converting enzyme levels, interstitial lung disease on CT chest, and non caseating granulomas on skin biopsy clinched the diagnosis of sarcoidosis. Multisystem involvement and recurrent lower motor facial nerve palsy is a clinical clue for sarcoidosis.

Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma.

PubMed

Reddy, Swathi B; Possick, Jennifer D; Kluger, Harriet M; Galan, Anjela; Han, Dale

2017-10-01

Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis. Of note, both patients developed sarcoidosis only after undergoing immune checkpoint inhibitor therapy. In 1 patient, sarcoidosis developed after initiation of anti-PD-1 therapy, 3 months after the last dose of anti-CTLA-4 monotherapy, suggesting a synergistic immune dysmodulating effect of both checkpoint inhibitors. Ultimately, both patients' symptoms and radiologic findings resolved with corticosteroid treatment, and both patients have tolerated retreatment with PD-1 inhibitors. Sarcoidosis is a rare complication of immune checkpoint inhibitors and can manifest with severe pulmonary manifestations. However, sarcoidosis in this setting is responsive to corticosteroids and does not necessarily recur with retreatment. It is yet unclear whether the development of sarcoidosis in these patients represents unmasking of preexisting autoimmune tendencies or is a marker of oncologic response.

Treatment of sarcoidosis: grading the evidence.

PubMed

James, W Ennis; Baughman, Robert

2018-06-18

Treatment of sarcoidosis recommendations are often based on clinical experience and expert opinion. However, there are an increasing number of studies which are providing evidence to support decisions regarding treatment. Areas covered: Several studies have identified factors associated with increased risk for organ failure or death ('danger'). There have been several studies focused on the role of treatment to improve quality of life for the patient. Sarcoidosis treatment often follows a progression, based on response. Corticosteroids remain the initial treatment of choice for most patients. Second-line therapy includes cytotoxic agents. Immunosuppressives such as methotrexate, azathioprine, leflunomide, and mycophenolate have all been reported as effective in sarcoidosis. Biologics and other agents are third-line therapy. The monoclonal antibodies directed against tumor necrosis factor have been shown to be particularly effective for advanced disease. Infliximab has been the most studied drug in this class. Newer treatments, including repository corticotropin injection and rituximab have been reported as effective in some cases. Expert commentary: In this review, we use the GRADE system to evaluate the currently available evidence and make recommendations regarding treatment.

Cardiac Sarcoidosis: The Impact of Age and Implanted Devices on Survival.

PubMed

Zhou, Ying; Lower, Elyse E; Li, Hui-Ping; Costea, Alexandru; Attari, Mehran; Baughman, Robert P

2017-01-01

To assess the clinical characteristics, diagnosis, and outcome of cardiac sarcoidosis in a single institution sarcoidosis clinic. Patients with cardiac sarcoidosis were identified using refined World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) criteria of highly probable and probable. Patient demographics, local and systemic treatments, and clinical outcome were collected. Of the 1,815 patients evaluated over a 6-year period, 73 patients met the WASOG criteria for cardiac sarcoidosis. The median age at diagnosis was 46 years, with a median follow-up of 8.8 years. Reduced left ventricular ejection fraction (LVEF) was the most common manifestation (54.8%). Patients with arrhythmias experienced ventricular tachycardia or severe heart block, (35.6% and 19.2%, respectively) with or without reduced LVEF. A total of 45 (61.6%) patients underwent cardiac PET scan and/or MRI, with 41 (91.1%) having a positive study. During follow-up, 10 patients (13.7%) either underwent transplant (n = 3) or died (n = 7) from sarcoidosis. Kaplan-Meier survival curves revealed 5- and 10-year survival rates of 95.5% and 93.4%, respectively. Univariate factors of age at diagnosis < 46 years, implantation of pacemaker or defibrillator, mycophenolate treatment, or LVEF > 40% were associated with improved survival. Cox regression analysis demonstrated that age ≥ 46 years and lack of an implanted pacemaker or defibrillator were the only independent predictors of mortality. The new WASOG criteria were able to characterize cardiac involvement in our sarcoidosis clinic. Age and lack of pacemaker or defibrillator were the significant predictors of mortality for cardiac sarcoidosis, and reduced LVEF < 40% was associated with worse prognosis. ClinicalTrials.gov; No.: NCT02356445; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Sarcoidosis in a case of MuSK-positive myasthenia gravis.

PubMed

Spengos, Konstantinos; Vassilopoulou, Sofia; Christou, Yiolanda; Manta, Panagiota

2008-11-01

Whereas the coexistence of different autoimmune or rheumatologic diseases with myasthenia gravis is well documented, the combination of myasthenia with sarcoidosis is extremely rare. There very few case reports of patients suffering from these two immune-mediated diseases. Nearly all had acetylcholine receptor antibodies. As far as we know myasthenia gravis with antibodies to muscle-specific tyrosine kinase-MuSK--has not been associated with any form of sarcoidosis. We present probably the first case of MuSK-positive myasthenia gravis with concurrent, asymptomatic pulmonary sarcoidosis.

Sarcoidosis with fever and a splenic infarct due to CMV or lymphoma?

PubMed

Cunha, Burke A; Sivarajah, Thulashie; Jimada, Ismail

We present a case of an adult female with a past history of pulmonary sarcoidosis who presented with fever, night sweats, profound fatigue, and LUQ abdominal pain. Sarcoidosis is an afebrile disorder (excluding Lofgren's syndrome, Heerfordt's syndrome or neurosarcoidosis). Therefore, the presence of fever with sarcoidosis should suggest infection, usually viral, or lymphoma. Sarcoidosis-lymphoma syndrome describes the evolution of a lymphoma in long standing sarcoidosis. Fever aside, possible lymphoma is suggested by otherwise unexplained fever, pleural unilateral effusion, highly elevated ESR or ferritin levels. In this case, a viral etiology was suggested because of atypical lymphocytosis and mildly elevated transaminases. In this patient, CMV IgM titers and elevated CMV PCR viral load confirmed the diagnosis of CMV infectious mononucleosis with lung and liver involvement. In this case CMV infectious mononucleosis was accompanied by procoagulant activity which resulted a DVT, pulmonary emboli and splenic infarct. We believe this to be the first reported case of CMV infectious mononucleosis splenic infarct in a patient with a history of sarcoidosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

2013-01-01

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Using 19-G Needle for Sarcoidosis.

PubMed

Balwan, Akshu

2018-05-16

Flexible bronchoscopy with endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is increasingly being used to obtain pathology specimens for diagnosis of sarcoidosis. There is wide variation in reported diagnostic yield in literature. New TBNA needles are available in the market but data are lacking about their diagnostic yield especially for sarcoidosis. This study reports the diagnostic yield of bronchoscopy with EBUS-TBNA using ViziShot FLEX 19-G needle in a series of patients with suspected sarcoidosis. This is a retrospective chart review for diagnostic yield of the 19-G EBUS-TBNA needle for suspected sarcoidosis. Eighty-six EBUS bronchoscopies were performed, 15 were done with clinical suspicion of sarcoidosis. The 19-G needle was used for all cases of suspected sarcoidosis. The procedure was diagnostic of sarcoidosis in 14 (93.3%) patients by TBNA with 1 nondiagnostic bronchoscopy. Procedural diagnostic yield was 93.3%. Eighty-five percent (28/33) of sampled lymph nodes were positive for noncaseating granulomas. The yield of transbronchial lung biopsy (TBLB) and endobronchial lung biopsy was 38% (5/13) and 43% (6/14), respectively. TBLB and endobronchial lung biopsy did not add to the diagnostic yield of the procedure. No significant adverse events were noted. This series reports a higher diagnostic yield than most other published studies and opens platform for direct comparison of each available needle. It also adds to the safety data for this larger needle. In addition, it raises doubt into utility of TBLB for diagnosis of sarcoidosis, which can increase the procedural complications.

[Sarcoidosis related pleural effusion: 6 case reports and literatures review].

PubMed

Wang, Feng; Tong, Zhaohui; Wang, Zhen; Wang, Xiaojuan; Xu, Lili

2015-02-01

To summarize the clinical features and the diagnosis-treatment points of sarcoidosis related pleural effusion. Six typical sarcoidosis related pleural effusion cases with pathological evidence were reviewed, and the clinical data of these cases were retrospectively analyzed and the related literatures were reviewed. The literature review was carried out respectively with "sarcoidosis", "pleural disease" and "pleural effusion" as the keywords in CNKI and PubMed database by January 2014. Six cases, including 1 male and 5 females, with sarcoidosis related pleural effusions were reported. 3 cases had bilateral effusions, 2 cases had left effusion and 1 case had right effusion. The pleural effusion routine test had a low specificity, which demonstrated that the fluid was exudate and consisted with large number of lymphocytes. 3 of these cases were diagnosed by medical thoracoscopy. Medical thoracoscopy revealed that pleural involvement was variable with multiple nodulespresent in some cases and subtle change in others. A total of 28 literatures and 92 cases with pleural involvement in sarcoidosis were retrieved from CNKI and PubMed database (time range: 2004.1-2014.1), including 59 cases of pleural effusion, 29 cases of pleural thickening, 3 cases of pneumothorax and 1 case of nodules in pleura. Pleural involvement in sarcoidosis was often misdiagnosed or mistreated as tuberculous pleurisy because the routine tests regarding pleural effusion usually had a low specificity. Medical thoracoscopy could provide clinicians with important clues to assist differentiation of the cause for non-conclusive pleural effusion in this situation.

A sarcoidosis clinician's perspective of MHC functional elements outside the antigen binding site.

PubMed

Judson, Marc A

2018-05-30

Sarcoidosis is a multisystem granulomatous disease of unknown cause. Evidence supports an integral role for interactions at the MHC binding site in the development of sarcoidosis. However, despite this evidence, there are clinical data that suggest that additional mechanisms are involved in the immunopathogenesis of this disease. This manuscript provides a brief clinical description of sarcoidosis, and a clinician's perspective of the immunopathogenesis of sarcoidosis in terms of the MHC binding site, MHC functional elements beyond the binding site, and other possible alternative mechanisms. Input from clinicians will be essential in establishing the immunologic cause of sarcoidosis as a detailed phenotypic characterization of disease will be required. Copyright © 2018. Published by Elsevier Inc.

Cardiac manifestations of sarcoidosis: diagnosis and management.

PubMed

Birnie, David H; Kandolin, Riina; Nery, Pablo B; Kupari, Markku

2017-09-14

Approximately 5% of patients with sarcoidosis will have clinically manifest cardiac involvement presenting with one or more of ventricular arrhythmias, conduction abnormalities, and heart failure. Cardiac presentations can be the first (and/or an unrecognized) manifestation of sarcoidosis in a variety of circumstances. Cardiac symptoms are usually dominant over extra-cardiac as most patients with clinically manifest disease have minimal extra-cardiac disease and up to two-thirds have isolated cardiac sarcoidosis (CS). It is estimated that another 20-25% of pulmonary/systemic sarcoidosis patients have asymptomatic cardiac involvement (clinically silent disease). The extent of left ventricular dysfunction seems to be the most important predictor of prognosis among patients with clinically manifest CS. In addition, the extent of myocardial late gadolinium enhancement is emerging as an important prognostic factor. The literature shows some controversy regarding outcomes for patients with clinically silent CS and larger studies are needed. Immunosuppression therapy (usually with corticosteroids) has been suggested for the treatment of clinically manifest CS despite minimal data supporting it. Fluorodeoxyglucose Positron Emission Tomography imaging is often used to detect active disease and guide immunosuppression. Patients with clinically manifest disease often need device therapy, typically with implantable cardioverter defibrillators. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Tattoo-associated uveitis with or without systemic sarcoidosis: a comparative review of the literature.

PubMed

Kluger, N

2018-05-15

Sarcoidosis is a systemic disease of unknown aetiology characterized by the presence of non-caseating epithelioid cell granulomas in multiple organs, mainly the lungs and the lymphatic system. It is also one of the leading cause of inflammatory eye diseases. For the past 70 years, sarcoidal granulomas on tattoos and permanent make-up have been documented. They can be the first and sometimes unique cutaneous manifestation of systemic sarcoidosis. A few cases of sarcoidosis with uveitis and granulomatous reactions within tattoos have been described. However, since the end 60s, a singular entity has been reported associating isolated uveitis with granulomatous cutaneous reaction restricted to tattoos in the notable absence of systemic sarcoidosis. It remains unclear whether this entity must be distinguished from sarcoidosis. This review summarizes the currently available data on this topic and compares cases of sarcoidosis with granulomatous tattoo reaction and uveitis to the cases without notable sarcoidosis. We propose the acronym TAGU (TAttoo Granulomas with Uveitis) as an exclusion diagnosis that emcompasses the patients for whom we fail to find any sarcoidosis or other causes after extensive investigation. © 2018 European Academy of Dermatology and Venereology.

Coexistence of Sarcoidosis and Gouty Arthritis.

PubMed

Semiz, Hüseyin; Kobak, Senol

2017-08-21

Sarcoidosis is an inflammatory disease with unknown cause characterized by non-caseating granuloma formations. It may present with bilateral hilar lymphadenopathy, skin lesions, the involvement of eye and symptoms on the locomotor system. Gouty arthritis is an autoinflammatory disease characterized by hyperuricemia, recurrent arthritis attacks and the deposition of monosodium urate crystals in the joints and the surrounding tissues. We reported the coexistence of sarcoidosis and gouty arthritis in this paper. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China.

PubMed

Li, Cheng-Wei; Tao, Ru-Jia; Zou, Dan-Feng; Li, Man-Hui; Xu, Xin; Cao, Wei-Jun

2018-02-16

Sarcoidosis is a multisystem disease characterised by the formation of granulomas within various organs, mainly the lungs. Several studies from different countries have been undertaken to investigate sarcoidosis with extrapulmonary involvement except from China. The objective of this study is to investigate a comparative clinical analysis in patients with pulmonary sarcoidosis with and without extrapulmonary involvement from China. Data from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital (Shanghai, China) between January 2009 and December 2014 were retrospectively collected and analysed. Six hundred and thirty-six patients with biopsy-proven sarcoidosis were included in the study, including 378 isolated pulmonary sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement. Two hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis had extrapulmonary involvement. Extrapulmonary localisations were detected mostly in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant differences were demonstrated between patients with pulmonary sarcoidosis plus extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0±46.9 IU/L vs 69.7±38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%, P<0.05). Extrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sarcoidosis Th17 Cells are ESAT-6 Antigen Specific but Demonstrate Reduced IFN-γ Expression

PubMed Central

Richmond, Bradley W.; Ploetze, Kristen; Isom, Joan; Chambers-Harris, Isfahan; Braun, Nicole A.; Taylor, Thyneice; Abraham, Susamma; Mageto, Yolanda; Culver, Dan A.; Oswald-Richter, Kyra A.; Drake, Wonder P.

2013-01-01

Rationale Sarcoidosis is a granulomatous disease of unknown etiology. Many patients with sarcoidosis demonstrate antigen-specific immunity to mycobacterial virulence factors. Th-17 cells are crucial to the immune response in granulomatous inflammation, and have recently been shown to be present in greater numbers in the peripheral blood and bronchoalveolar lavage (BAL) fluid (BALF) of sarcoidosis patients than healthy controls. It is unclear whether Th-17 cells in sarcoidosis are specific for mycobacterial antigens, or whether they have similar functionality to control Th-17 cells. Methods Flow cytometry was used to determine the numbers of Th-17 cells present in the peripheral blood and BALF of patients with sarcoidosis, the percentage of Th-17 cells that were specific to the mycobacterial virulence factor ESAT-6, and as well as to assess IFN-γ expression in Th-17 cells following polyclonal stimulation. Results Patients with sarcoidosis had greater numbers of Th-17 cells in the peripheral blood and BALF than controls and produced significantly more extracellular IL-17A (p=0.03 and p=0.02, respectively). ESAT-6 specific Th-17 cells were present in both peripheral blood and BALF of sarcoidosis patients (p<0.001 and p=0.03, respectively). After polyclonal stimulation, Th-17 cells from sarcoidosis patients produced less IFN-γ than healthy controls. Conclusions Patients with sarcoidosis have mycobacterial antigen-specific Th-17 cells peripherally and in sites of active sarcoidosis involvement. Despite the Th1 immunophenotype of sarcoidosis immunology, the Th-17 cells have reduced IFN-γ expression, compared to healthy controls. This reduction in immunity may contribute to sarcoidosis pathogenesis. PMID:23073617

Proteomic Analysis of Kveim Reagent Identifies Targets of Cellular Immunity in Sarcoidosis

PubMed Central

Parker, Robert; Siddiqui, Nazneen; Potiphar, Lee; Goldin, Rob; Timms, John F.; Wells, Athol U.; Kon, Onn M.; Wickremasinghe, Melissa; Mitchell, Donald; Weeks, Mark E.; Lalvani, Ajit

2017-01-01

Background Kveim-reagent (Kv) skin testing was a historical method of diagnosing sarcoidosis. Intradermal injection of treated sarcoidosis spleen tissue resulted in a granuloma response at injection site by 4–6 weeks. Previous work indicates proteins as the possible trigger of this reaction. We aimed to identify Kv-specific proteins and characterise the ex vivo response of Peripheral Blood Mononuclear Cells (PBMCs) from sarcoidosis, tuberculosis and healthy control patients when stimulated with both Kv and selected Kv-specific proteins. Methods Kv extracts were separated by 1D-SDS-PAGE and 2D-DIGE and then underwent mass spectrometric analysis for protein identification. Sarcoidosis and control PBMCs were first stimulated with Kv and then with three selected recombinant protein candidates which were identified from the proteomic analysis. PBMC secreted cytokines were subsequently measured by Multiplex Cytokine Assay. Results We observed significantly increased IFN-γ and TNF-α secretion from Kv-stimulated PBMCs of sarcoidosis patients vs. PBMCs from healthy volunteers (IFN-γ: 207.2 pg/mL vs. 3.86 pg/mL, p = 0.0018; TNF-α: 2375 pg/mL vs. 42.82 pg/mL, p = 0.0003). Through proteomic approaches we then identified 74 sarcoidosis tissue-specific proteins. Of these, 3 proteins (vimentin, tubulin and alpha-actinin-4) were identified using both 1D-SDS-PAGE and 2D-DIGE. Data are available via ProteomeXchange with identifier PXD005150. Increased cytokine secretion was subsequently observed with vimentin stimulation of sarcoidosis PBMCs vs. tuberculosis PBMCs (IFN-γ: 396.6 pg/mL vs 0.1 pg/mL, p = 0.0009; TNF-α: 1139 pg/mL vs 0.1 pg/mL, p<0.0001). This finding was also observed in vimentin stimulation of sarcoidosis PBMCs compared to PBMCs from healthy controls (IFN-γ: 396.6 pg/mL vs. 0.1 pg/mL, p = 0.014; TNF-α: 1139 pg/mL vs 42.29 pg/mL, p = 0.027). No difference was found in cytokine secretion between sarcoidosis and control PBMCs when stimulated with either tubulin

Musculoskeletal manifestations of sarcoidosis: A review article.

PubMed

Shariatmaghani, Somayeh; Salari, Roshanak; Sahebari, Maryam; Shalchiantabrizi, Payman; Salari, Masoumeh

2018-04-24

Sarcoidosis is a multisystem inflammatory disease with an etiology that is not clearly understood. Amongst the different organs that may be affected, the lungs are the most common. Musculoskeletal manifestations of the disease are uncommon. They include arthropathy, bone lesions, or myopathy, all of which may occur as initial symptoms or develop during the course of the disease. Articular involvement my present as arthralgia or arthritis. Skeletal complications usually develop in the chronic state of the disease. Muscular disease is rare and usually asymptomatic. Appropriate imaging modalities including X-ray, MRI, FDG-PET/CT assist in the diagnosis of rheumatic sarcoidosis. However, biopsy is necessary for definite diagnosis. In most cases of musculoskeletal involvement, NSAIDs and corticosteroids are sufficient for symptomatic management. For more resistant cases immunosuppressive drugs (i.e., methotrexate) and TNF-? inhibitors are used. Our aim is to review various types of musculoskeletal involvement in sarcoidosis and their existing treatment options. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Angiotensin converting enzyme genotype affects development and course of sarcoidosis in Asian Indians.

PubMed

Tahir, Mohammad; Sharma, S K; Ashraf, Shazia; Mishra, Hemant K

2007-09-01

Studies of serum angiotensin converting enzyme (SACE) activity and its association with ACE gene insertion/deletion (I/D) polymorphism in relation to sarcoidosis have yielded variable results. This has been attributed to possible ethnic differences. Present study was designed to evaluate the relationship between I/D polymorphism and susceptibility to develop sarcoidosis and its effect on SACE activity and disease course in Asian Indian patients with sarcoidosis. ACE genotyping was performed in 72 consecutive patients with sarcoidosis and 199 controls (96 normal healthy individuals and 103 tuberculosis patients taken as disease controls). SACE activity was determined in all patients with sarcoidosis. Various parameters were compared amongst patients with different genotypes as well as between sarcoidosis and control groups. Gene frequency of I and D in control group was 0.6 and 0.4, whereas in patients with sarcoidosis it was 0.35 and 0.65 respectively (p < 0.001). For individuals with D allele (DD&ID genotypes), odds ratios for developing sarcoidosis were 9.0 (95% CI: 3.4; 23.7) and 5.5 (95% CI: 2.2; 13.6) respectively considering individuals with II genotype as reference. Mean SACE activity was highest in patients with DD genotype and followed an order of DD > ID > II. Good response to initial corticosteroids was seen in 6 of 6 (100%) patients with II genotype whereas in only 32 of 37 (84%) with ID and 16 of 25 (64%) with DD (p = 0.013). In Asian Indian population 'D' allele is associated with an increased risk for development of sarcoidosis and patients with 'D' allele show poor response to corticosteroids.

Cutaneous sarcoidosis in Asians: a report of 25 patients from Singapore.

PubMed

Chong, W-S; Tan, H-H; Tan, S-H

2005-03-01

Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin involving multiple organ systems. There has been no report so far to describe the epidemiological pattern of cutaneous involvement in sarcoidosis in South-East Asia with diverse ethnic groups. A retrospective study examining the clinicopathological features of all patients diagnosed with sarcoidosis at a tertiary dermatology centre in Singapore from 1980 to 2003 was conducted. Cutaneous sarcoidosis was diagnosed in 25 patients: 13 were Indian, 11 were Chinese and one was Eurasian. Cutaneous manifestations included papules, nodules, plaques and scarring alopecia. Extracutaneous involvement of lymph nodes (four patients), lungs (eight patients) and eyes (two patients) was seen. Eight patients had abnormal chest radiographic findings. Histopathological examination of skin lesions revealed noncaseating, epithelioid granulomatous infiltration in the dermis without evidence of mycobacterial infection, deep fungal infection or polarizable birefringent material. Treatment modalities included corticosteroids, hydroxychloroquine, isotretinoin, methotrexate and surgical excision. Five patients had complete resolution of the cutaneous lesions. Cutaneous sarcoidosis is rare in Asia and indeed in Singapore. Extracutaneous involvement is not uncommon and a thorough clinical evaluation should be undertaken.

Cutaneous sarcoidosis: a new subset in the spectrum of paraneoplastic dermatoses.

PubMed

El-Khalawany, M; Mosbeh, A; Aboeldahab, S; Ali, S

2018-05-20

Sarcoidosis is a well-described disease that can be associated with various malignancies; however, this correlation is still not fully clarified. To determine the clinical and histological features, demographic characteristics, and prognosis of patients diagnosed with paraneoplastic sarcoidosis (PS). This observational cohort prospective study included all patients diagnosed as cutaneous sarcoidosis. All patients were monitored for therapeutic response, prognosis, and any associated diseases or malignancies. Out of 94 patients with cutaneous sarcoidosis, we identified 12 patients (12.8%) with PS. There was a male (n = 8) preponderance (ratio 2 : 1),and the mean ± SD age of patients was 64.6 ± 13.21 years. The spectrum of paraneoplastic malignancies included six cases of Hodgkin lymphoma, five of multiple myeloma and one of non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma). The underlying malignancy was usually diagnosed within 4-25 months (mean ± SD 12.7 ± 6.85) from diagnosis of cutaneous sarcoidosis. The response to systemic steroid was relatively poor and patients on combination therapy showed frequent relapses. However, after treatment of the associated malignancy, seven patients (58.3%) showed complete resolution of the lesions and five (41.7%) showed moderate improvement. During follow-up, there was no relapse reported for either PS or malignancy. Our results suggest that sarcoidosis is a new subset in the spectrum of paraneoplastic syndrome. We propose that lymphoproliferative disorders should be considered in patients with cutaneous sarcoidosis who have a poor response to conventional therapy or whose skin biopsy shows a significant number of mitoses. © 2018 British Association of Dermatologists.

Mortality among African American women with sarcoidosis: Data from the Black Women’s Health Study

PubMed Central

Tukey, Melissa H.; Berman, Jeffrey S.; Boggs, Deborah A; White, Laura F.; Rosenberg, Lynn; Cozier, Yvette C.

2013-01-01

Rationale Sarcoidosis is a chronic systemic granulomatous disease of unknown etiology that disproportionately affects black females. Few studies have specifically addressed causes of death in this population. Objectives To assess rates and causes of death among women with sarcoidosis in a prospective cohort study of U.S. black women. Methods The Black Women’s Health Study is a follow-up study of 59,000 U.S. black women aged 21–69 (median age 38) at entry in 1995. Data on demographic and lifestyle factors and medical conditions, including sarcoidosis, were obtained through biennial questionnaires. Deaths and causes of death from 1995 through 2009 among study subjects were identified from National Death Index data. Measurements We assessed mortality rates among women with and without a history of sarcoidosis. Poisson regression models were used to estimate age-adjusted mortality rates. Cox proportional-hazards models were used to estimate hazard ratios for mortality and 95% confidence intervals (95% CI). Main Results A total of 121 deaths occurred among 1,192 women with a history of sarcoidosis and 2813 deaths among women without the diagnosis. Mortality was greater at every age among women with sarcoidosis and the overall multivariable-adjusted hazard ratio was 2.44 (95% CI 2.03–2.93, p<0.0001). Of the deaths among women with sarcoidosis, 24.7% were directly attributable to sarcoidosis. Conclusions In the Black Women’s Health Study, women with sarcoidosis were more than twice as likely to die as women without the disease, with many of the deaths directly attributable to sarcoidosis. Sarcoidosis is an important cause of premature death among black women with the disease. PMID:24071884

Managing fatigue in sarcoidosis - A systematic review of the evidence.

PubMed

Atkins, Chris; Wilson, Andrew M

2017-05-01

Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on fatigue. This review aimed to assess the treatment options targeting sarcoidosis-associated fatigue. Medline and Web of Science were searched in November 2015; the bibliographies of these papers, and relevant review papers, were also searched. Studies were included if they reported on the efficacy of interventions (both pharmacological and non-pharmacological) on fatigue scores in sarcoidosis patients. Eight studies were identified that fulfilled the inclusion criteria. These studies evaluated six different interventions (infliximab, adalimumab, ARA 290, methylphenidate, armodafinil and exercise programmes). There is evidence to support a treatment effect of anti-tumour necrosis factor (TNF)-αtherapies (adalimumab and infliximab) and neurostimulants (methylphenidate and armodafinil), but within five of the studies, the risk of bias was high within most domains and the remaining three studies included only small numbers of participants and were short in duration. Trial evidence for treating fatigue as a manifestation of sarcoidosis is limited and requires further investigation. Anti-TNF-α therapies may be beneficial in patients with organ-threatening disease. Neurostimulants have some trial evidence supporting improvements in fatigue but further investigation is needed before they can be recommended.

Increased risk of ventricular tachycardia in patients with sarcoidosis during the very long term follow-up.

PubMed

Te, Abigail Louise D; Lin, Yenn-Jiang; Chen, Yun-Yu; Chung, Fa-Po; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Chao, Tze-Fan; Liao, Jo-Nan; Lin, Chin-Yu; Chang, Yao-Ting; Chien, Kuo-Liong; Chen, Shih-Ann

2017-02-01

Sarcoidosis is an important diagnostic consideration in patients with ventricular tachycardia (VT) of unknown origin. The clinical course of VT as the primary presentation in patients with sarcoidosis is mostly unknown. This study aimed to investigate the incidence of life-threatening VT and mortality during long term follow-up in patients with sarcoidosis. We analyzed the epidemiological features of sarcoidosis in Taiwan using the National Health Insurance Research Database from 2000 to 2004. Patients with sarcoidosis were identified, and healthy controls without prior histories of structural heart disease were matched with a 1:1 propensity-score to the sarcoidosis group. The risk of life-threatening VT and mortality with sarcoidosis was analyzed. A total of 2237 sarcoidosis cases were enrolled with a matching number of healthy controls, and the baseline characteristics between the two groups were similar. After a mean follow-up of 11.4±2.15years (IQR: 12, 11.3-12), the VT incidence in the sarcoidosis group was higher than in healthy controls (0.94% [85 per 100,000 person-year] in the sarcoidosis group, and 0.09% [8 per 100,000 person-year] in healthy controls). After a multivariate adjustment including the sex, age, and other comorbidities, the VT risk was still higher in the sarcoidosis group (hazard ratio: 12.7, 95% confidence interval: 2.82-56.9; P<0.001). The risk of defibrillator implantations for secondary prevention, cardiovascular death, and total mortality between the groups was equivalent. Sarcoidosis may increase the predisposition to ventricular arrhythmias with a cumulative incidence of 0.94% during a very long term follow-up of nearly 10years from initially diagnosing sarcoidosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sudden cardiac death and sarcoidosis of the heart in a young patient.

PubMed

Jotterand, Morgane; Grabherr, Silke; Lobrinus, Johannes Alexandre; Michaud, Katarzyna

Sarcoidosis is a granulomatous disease of unknown etiology affecting any organ, microscopically characterized by noncaseating granulomata. Cardiac involvement in sarcoidosis has been reported. It might be symptomatic or not and even revealed by sudden death. Heart conduction system is rarely investigated at autopsy, even in cases of sudden cardiac death. We present a case of a 32-year-old woman who died suddenly. The examination of the heart conduction system revealed a cardiac sarcoidosis that could explain the sudden death. The review of clinical data of the patient revealed some symptoms consistent/in agreement with this hypothesis. Cardiac sarcoidosis remains a diagnostic challenge and can be easily missed, clinically and pathologically. The retrospective analysis of clinical data and autopsy results of fatal and unusual cases might help to better understand sarcoidosis and its clinical presentations. Examination of the cardiac conduction system is crucial in selected cases of sudden cardiac death. Copyright © 2017 Elsevier Inc. All rights reserved.

Current management of sarcoidosis I: pulmonary, cardiac, and neurologic manifestations.

PubMed

West, Sterling G

2018-05-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation of multiple organ systems. Pulmonary, cardiac, and neurologic involvements have the worst prognosis. Current recommendations for the therapeutic management and follow-up of sarcoidosis involving these critical organs will be reviewed. In those sarcoidosis patients requiring immunosuppressive therapy, corticosteroids are used first at varying doses depending on the presenting manifestation. Patients with symptomatic pulmonary, cardiac, or neurologic involvement will be maintained on corticosteroids for at least a year. Many require a second immunosuppressive agent with methotrexate used most commonly. Anti-tumor necrosis factor agents, especially infliximab, are effective and recommendations for their use have been proposed. Evidence-based treatment guidelines do not exist for most sarcoidosis clinical manifestations. Therefore, clinical care of these patients must rely on expert opinion. Patients are best served by a multidisciplinary approach to their care. Future research to identify environmental triggers, genetic associations, biomarkers for treatment response, and where to position new steroid-sparing immunosuppressive agents is warranted.

[A specific etiology of radiologic cannon balls: sarcoidosis. Apropos of a case].

PubMed

Blanc-Jouvan, F; Andre-Poyaud, P; Perrin, C; Brambilla, E; Brambilla, C

1988-01-01

A distinctive form of sarcoidosis is reported. A young woman, without any past medical history, presented with a cannon-ball radiographic appearance and a fever, suggesting an infection or underlying neoplasm. A lung biopsy gave the diagnosis of sarcoidosis after negative fibreoptic bronchoscopy, bronchial lavage and needle biopsy. This macronodular form of sarcoidosis is known but rarely described. There was a favourable clinical and radiological outcome, which occurred spontaneously.

Sarcoidosis with involvement of the paranasal sinuses - a retrospective analysis of 12 biopsy-proven cases

PubMed Central

2013-01-01

Background Extrapulmonary involvement by sarcoidosis is observed in about 30–40% of patients with sarcoidosis. Little is known about the frequency and clinical characteristics of sinonasal sarcoidosis. Methods We retrospectively analyzed 12 cases of biopsy-proven sinonasal sarcoidosis. Patients were identified from a patient population of 1360 patients with sarcoidosis at the Outpatient Clinic for Sarcoidosis and Rare Lung Diseases at LungClinic Grosshansdorf, a tertiary care hospital for respiratory medicine. Results The most frequent signs and symptoms were nasal polyps (4 cases), epistaxis (3 cases), nasal crusts (8 cases) and anosmia (5 cases). Pulmonary sarcoidosis of the patients was staged as stage I (n = 1) and stage II (n = 11) on chest radiographs. Spirometry was normal in 11 patients. 7 patients had a diffusion capacity of the lung for carbon monoxide of less than 90% of predicted. Other organs were affected in 8 patients. All patients received systemic corticosteroid treatment and most patients received topical steroids. 5 patients received steroid sparing agents. Repeated sinus surgery had to be performed in 4 patients. Conclusions Sinonasal involvement is a rare disease manifestation of sarcoidosis with a frequency slightly lower than 1% in our patient population. The clinical course of sinonasal sarcoidosis can be complicated by relapse despite systemic immunosuppressive treatment and repeated sinus surgery. PMID:24070015

The Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis of Cardiac Sarcoidosis.

PubMed

Stanton, Kelly M; Ganigara, Madhusudan; Corte, Peter; Celermajer, David S; McGuire, Mark A; Torzillo, Paul J; Corte, Tamera J; Puranik, Rajesh

2017-11-01

Autopsy reports suggest that cardiac sarcoidosis occurs in 20 to 25% of patients with pulmonary sarcoidosis, yet the clinical ante-mortem diagnosis is made in only 5% of cases. Current diagnostic algorithms are complex and lack sensitivity. Cardiac Magnetic Resonance imaging (CMR) provides an opportunity to detect myocardial involvement in sarcoidosis. The aim of this study is to determine the prevalence and clinical significance of late gadolinium enhancement (LGE) on CMR in patients with sarcoidosis. Consecutive patients with biopsy-proven sarcoidosis undergoing CMR were retrospectively evaluated for cardiac sarcoidosis. Medical records were correlated with CMR. Forty-six patients were evaluated. Late gadolinium enhancement was present in 22%, indicating myocardial involvement, and 70% had corresponding hyper-intense T2 signal indicating active inflammation. Late gadolinium enhancement was 18%+/-9.7% of overall left ventricular (LV) mass and most commonly located in the basal to mid septum. There was no association between LGE and cardiovascular symptoms or pulmonary stage. Eighty per cent of patients with LGE did not fulfill conventional diagnostic criteria for cardiac sarcoidosis. However, LGE was associated with clinically significant arrhythmia (p<0.01) and a lower LVEF (p=0.04). Using CMR, we identified a higher prevalence of cardiac sarcoidosis than previously reported clinical studies, a prevalence which is more consistent with autopsy data. The presence of LGE was highly correlated with clinically significant arrhythmias and lower LVEF. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

Anxiety, its relation to symptoms severity and anxiety sensitivity in sarcoidosis.

PubMed

Holas, Pawel; Krejtz, Izabela; Urbankowski, Tomasz; Skowyra, Artur; Ludwiniak, Anna; Domagala-Kulawik, Joanna

2013-12-17

Sarcoidosis is a chronic systemic granulomatous disease of unknown etiology. Previous studies demonstrated that patients with sarcoidosis had high rates of depression and anxiety, and high magnitude of stressful life events. To date, however, studies have not examined the anxiety sensitivity in sarcoid patients and the relationship between psychopathology and symptom severity of sarcoidosis.The aims of this study were to evaluate prevalence of depression and anxiety in sarcoid patients, to assess their relationship with the disease symptom severity, and to investigate the relationship between sarcoidosis and anxiety sensitivity. Thirty three sarcoid patients and thirty three control subjects completed the following:Hospital Anxiety and Depression Scale, Anxiety Sensitivity Index-3. The prevalence of depression (29%) and anxiety (31%) was high among patients and comparable to results from other research groups. Anxiety was significantly correlated with symptom severity and was the main covariate of physical symptoms reported by sarcoid patients. Patients exhibited an increase of their total anxiety sensitivity index and had an increased number of physical concerns. These data confirmed earlier reports that anxiety and depression are common in patients with sarcoidosis and expanded on the previous results by showing that patients exhibited increased anxiety sensitivity and a fear of physical sensations. These results, together with the findings that anxiety was associated with sarcoidosis symptom severity, suggest that targeting anxiety and the physical health concerns may be important in the diagnosis and management of this disease.

Musculoskeletal involvements in sarcoidosis: A narrative review.

PubMed

Salari, Roshanak; Shariatmaghani, Somayeh; Sahebari, Maryam; Shalchiantabrizi, Payman; Salari, Masoumeh

2018-05-14

Sarcoidosis is a multisystem inflammatory disease with an etiology that is not clearly understood. Amongst the different organs that may be affected, the lungs are the most common. Musculoskeletal manifestations of the disease are uncommon. They include arthropathy, bone lesions, or myopathy, all of which may occur as initial symptoms or develop during the course of the disease. Articular involvement my present as arthralgia or arthritis. Skeletal complications usually develop in the chronic state of the disease. Muscular disease is rare and usually asymptomatic. Appropriate imaging modalities including X-ray, MRI, FDG-PET/CT assist in the diagnosis of rheumatic sarcoidosis. However, biopsy is necessary for definite diagnosis. In most cases of musculoskeletal involvement, NSAIDs and corticosteroids are sufficient for symptomatic management. For more resistant cases immunosuppressive drugs (i.e., methotrexate) and TNF-α inhibitors are used. Our aim is to review various types of musculoskeletal involvement in sarcoidosis and their existing treatment options. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

High prevalence of Mycobacterium tuberculosis DNA in biopsies from sarcoidosis patients from Catalonia, Spain.

PubMed

Fité, E; Fernández-Figueras, M T; Prats, R; Vaquero, M; Morera, J

2006-01-01

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The presence of mycobacterial nucleic acid components in patients with sarcoidosis has been demonstrated with varying degrees of success. The aim of this study was to estimate the presence of Mycobacterium tuberculosis DNA in tissues from sarcoidosis patients, in Catalonia, Spain, as well as to assess the long-term clinical course in these patients. Fifty-eight paraffin-embedded tissue biopsies corresponding to cases of sarcoidosis (n = 23), lung neoplasm (n = 23), and lung tuberculosis (n = 12) available in 1996 were analyzed in a retrospective study by means of a nested polymerase chain reaction using primers corresponding to the insertion element IS6110 of M. tuberculosis complex. For greater sensitivity, Southern blot hybridization was performed. Clinical data were recorded prior to and after PCR analysis (follow-up reported until 2002). M. tuberculosis DNA was present in 9 out of 23 sarcoidosis biopsies (39%), in 1 out of 23 control patients (4%) (p < 0.01), and in all tissue samples from the 12 control patients with tuberculosis. To date, none of these sarcoidosis patients has developed tuberculosis over a mean (+/-SD) follow-up period of 11 (+/-3.4) years. In our setting, M. tuberculosis DNA is present in tissue biopsies of significantly more sarcoidosis patients than controls. However, these results do not demonstrate causality, although they may suggest a link between M. tuberculosis infection and sarcoidosis in some cases. Follow-up of these patients suggests that M. tuberculosis-DNA-positive sarcoidosis patients are not at greater risk of developing tuberculosis than M. tuberculosis-DNA-negative patients. Copyright 2006 S. Karger AG, Basel.

GSTT1 and GSTM1 gene polymorphisims in sarcoidosis.

PubMed

Coskun, Funda; Karkucak, Mutlu; Yilmaz, Dilber; Yakut, Tahsin; Uzaslan, Esra

2016-10-07

Sarcoidosis is a granulomatous disease of unknown cause, which affects all systems, especially the lungs and the lymphatic system. Genetic and environmental factors are held accountable for the etiology. Based on the general opinion, sarcoidosis develops after exposure to a specific environmental agent by genetically susceptible individuals.  The present study aimed to evaluate the disease susceptibility of the GSTT1 and GSTM1 gene polymorphisms in the patients with sarcoidosis. The present study included 78 patients; 38 patients with histopathologically verified sarcoidosis and 40 control subjects. Multiplex PCR method was used to determine the GSTT1 and GSTM1 gene polymorphisms. The genotype was determined based on the bands formed in the agarose gel electrophoresis. The statistical analysis was done using the chi-square test. The positive/negative genotype rates were 79%/21% and 53%/47%, respectively in the case group for the GSTT1 and GSTM1 gene polymorphisms, whereas the positive/negative genotype rates were 77%/23% and 55%/45% in the control group. There was no statistically significant difference in the positive and negative genotypes compared with the case group and the control group for the GSTT1 and GSTM1 gene polymorphisms (p > 0.05). The results from the present study suggest that there is not any association with the control group for the disease susceptibility of the GSTT1 and GSTM1 gene polymorphisms in patients with sarcoidosis, and this result should be supported by large-scale studies because of the limited number of cases in the present study.

Improvement with Infliximab of a Disseminated Sarcoidosis in a Patient with Crohn's Disease

PubMed Central

Piégay, Fabrice; Traclet, Julie; Mion, François; Mornex, Jean-François

2014-01-01

Sarcoidosis and Crohn's disease are systemic granulomatous disorders affecting the lung and the intestine, respectively, with variable involvement of other organs and are seldom associated. While anti-TNFα is a recognized treatment of Crohn's disease, its usage is discussed in sarcoidosis. A 42-year-old man presented with an 11-year-long history of Crohn's disease; upon discovery of an abnormal chest CT scan the diagnosis of multivisceral sarcoidosis was made and, later, a treatment with an anti-TNFα agent, infliximab, was started, because of worsening Crohn's disease recurrences. CT scan demonstrated net regression of pulmonary opacities and hepatosplenic lesions. Pathologies obtained from the intestinal tract and the bronchi of the patient were, respectively, characteristic of Crohn's disease and sarcoidosis leading to the diagnosis of both diseases. We report a rare case of steroid resistant Crohn's disease associated with multivisceral sarcoidosis, treated successfully by an anti-TNFα agent, infliximab. PMID:24653848

Th17-lineage cells in pulmonary sarcoidosis and Löfgren's syndrome: Friend or foe?

PubMed

Miedema, Jelle R; Kaiser, Ylva; Broos, Caroline E; Wijsenbeek, Marlies S; Grunewald, Johan; Kool, Mirjam

2018-02-01

Sarcoidosis, a multisystem granulomatous disorder, has historically been classified as Th1-driven disease. However, increasing data demonstrate a key role of Th17-cell plasticity in granuloma formation and maintenance. In Löfgren's syndrome (LS), an acute and distinct phenotype of sarcoidosis with a favorable outcome, differences in Th17-lineage cell subsets, cytokine expression and T-cell suppressive mechanisms may account for differences in clinical presentation as well as prognosis compared to non-LS sarcoidosis. In contrast with LS, up to 20% of non-LS sarcoidosis patients may progress to irreversible pulmonary fibrosis. In non-LS sarcoidosis patients, IFN-γ-producing Th17.1-cells appear to be more pathogenic and possibly linked to disease progression, while a broader range of cytokines is found in bronchoalveolar lavage fluid (BALF) in LS patients. Differences in Cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression on Th17-cells and regulatory T-cells (Treg) could contribute to Th17-cell pathogenicity and consequently to either disease resolution or ongoing inflammation in sarcoidosis. Furthermore, several genes and SNPs are associated with disease susceptibility and outcome in sarcoidosis, the majority of which are involved in antigen presentation, T-cell activation or regulation of T-cell survival. Novel insights into the role of Th17-cells in the pathogenesis of both LS and non-LS sarcoidosis will unravel pathogenic and benign Th17-lineage cell function and drivers of Th17-cell plasticity. This will also help identify new treatment strategies for LS and non-LS sarcoidosis patients by altering Th17-cell activation, suppress conversion into more pathogenic subtypes, or influence cytokine signaling towards a beneficial signature of Th17-lineage cells. In this review, we summarize new insights into Th17-cell plasticity in the complex pathogenesis of sarcoidosis and connect these cells to the different disease phenotypes, discuss the role of genetic

Characterization of chronic fatigue in patients with sarcoidosis in clinical remission.

PubMed

Korenromp, Ingrid H E; Heijnen, Cobi J; Vogels, Oscar J M; van den Bosch, Jules M M; Grutters, Jan C

2011-08-01

Patients with sarcoidosis frequently complain of fatigue, even when sarcoidosis has come into clinical remission. The primary aim of this study was to assess the severity of fatigue in patients with sarcoidosis in clinical remission and to characterize it according to the international criteria for chronic fatigue syndrome (CFS). Furthermore, we evaluated whether fatigue is associated with depression and anxiety, health status, and patient-reported sleep quality, and we recorded physical activity levels and muscle strength as objective assessments of fatigue. Data on 75 patients with sarcoidosis in clinical remission were obtained by questionnaires (Checklist Individual Strength [CIS], Symptom Checklist-90, Beck Depression Inventory for primary care, Medical Outcomes Study 36-Item Short-Form Health Survey), standardized interview (CFS criteria), sleep diary, accelerometer, and muscle strength tests. Fatigue severity mean score in patients with sarcoidosis in clinical remission was high (CIS fatigue severity 30.5 ± 15.5), and criteria for CFS were met in 47% of fatigued participants. Median time since diagnosis was 9 years. Fatigue was associated with depression (P = .01), anxiety (P = .013), and reduced health status (P < .001). Scores on sleep quality were normal. Physical activity levels were reduced in fatigued participants. Muscle strength, particularly handgrip (P = .006) and quadriceps strength (P < .001), was significantly associated with fatigue. Fatigue in patients with sarcoidosis in clinical remission is a frequent symptom and can be characterized as a severe and long-lasting problem, symptomatically similar to CFS. Psychologic distress and reduced health status are associated with fatigue. Interestingly, we observed significantly reduced physical activity and muscle weakness in fatigued patients.

Sarcoidosis Increases Risk of Hospitalized Infection. A Population-based Study, 1976-2013.

PubMed

Ungprasert, Patompong; Crowson, Cynthia S; Matteson, Eric L

2017-05-01

Patients with sarcoidosis may have an increased risk of infection similar to other immune-mediated disorders. However, the data are still limited. To investigate the risk of hospitalized infection among patients with sarcoidosis, using a population-based cohort. Using the Rochester Epidemiology Project record-linkage system, a cohort of incident cases of sarcoidosis in Olmsted County, Minnesota from 1976 to 2013 was identified. Diagnosis was confirmed by individual medical record review. For each patient with sarcoidosis, a sex- and age-matched comparator without sarcoidosis was randomly selected from the same population. Medical records of cases and comparators were individually reviewed for hospitalized infection that occurred after the index date. The cumulative incidence of hospitalized infection overall and by type of infection, adjusted for the competing risk of death, was estimated. Cox models were used to compare the rate of first hospitalized infection between cases and comparators and to evaluate the association between use of immunosuppressive agents and hospitalized infection among cases. Three hundred and forty-five cases and 345 comparators were identified. Patients with sarcoidosis had a higher risk of a hospitalized infection with a hazard ratio (HR) of 2.00 (95% confidence interval [CI], 1.41-2.84), adjusted for age, sex, and calendar year of index date. Use of oral glucocorticoids was a significant predictor of hospitalized infection with an HR of 3.03 (95% CI, 1.33-6.90) for oral glucocorticoids not exceeding 10 mg/day and an HR of 4.48 (95% CI, 1.54-13.03) for oral glucocorticoids greater than 10 mg/day. Patients with sarcoidosis are at increased risk of hospitalized infection. Glucocorticoid therapy is strongly associated with this increased risk.

Pulmonary granulomatous reaction: talc pneumoconiosis or chronic sarcoidosis?

PubMed Central

Tukiainen, P; Nickels, J; Taskinen, E; Nyberg, M

1984-01-01

A chronic pulmonary granulomatous reaction was associated with an almost identical clinical picture in two patients exposed to talc. In both patients lung biopsy showed the deposition of talc particles and a heavy granulomatous reaction. At the time of diagnosis the Kveim test result was negative in both patients, urinary calcium excretion was normal, and there were no extrapulmonary manifestations and no response to steroid treatment. These findings point against sarcoidosis. The serum angiotensin-converting enzyme level, however, was raised in both patients. It was concluded that the patient who was exposed to talc in the rubber industry had a true talc pneumoconiosis. The other patient, who was exposed to cosmetic talcum powder, suffered from chronic sarcoidosis with talc deposition in the lungs, since an enlarged axillar lymph node containing granulomatous inflammation was discovered after two years' follow up. These cases show that it may be extremely difficult to differentiate between chronic sarcoidosis and talc pneumoconiosis even after careful clinical and histological analysis. Images PMID:6691939

Specific Skin Lesions of Sarcoidosis Located at Venipuncture Points for Blood Sample Collection.

PubMed

Marcoval, Joaquim; Penín, Rosa M; Mañá, Juan

2018-05-01

It has been suggested that the predilection of sarcoidosis to affect scars is due to the presence of antigens or foreign bodies that can serve as a stimulus for granuloma formation. Several patients with sarcoidosis-specific skin lesions in venous puncture sites have been reported. However, in these patients the pathogenesis of the cutaneous lesions is not clear because the presence of foreign bodies is not to be expected. Our objective was to describe 3 patients who developed specific lesions of sarcoidosis in areas of venipuncture and to discuss their possible pathogenesis. The database of the Sarcoid Clinic of Bellvitge Hospital (an 800-bed university referral center providing tertiary care to approximately 1 million people in Barcelona, Spain) was reviewed to detect those patients with specific cutaneous lesions of systemic sarcoidosis in areas of venipuncture. Three patients with biopsy-proven specific cutaneous lesions of systemic sarcoidosis in areas of venipuncture for blood collection were detected (3 women, mean age 56 years). In one case, the histopathological image shows the hypothetical path of a needle through the skin. In 2 cases, an amorphous birefringent material was detected under polarized light. This material was consistent with silicone. In patients who are developing sarcoidosis, the smallest amount of oil used as lubricant in the needle for sample blood collection may induce the formation of granulomas. In addition to exploring scars, it is advisable to explore the cubital folds to detect specific cutaneous lesions of sarcoidosis.

Sarcoidosis during etanercept treatment for rheumatoid arthritis in women with a history of bilateral oophorectomy.

PubMed

Sawahata, Michiru; Sigiyama, Yukihiko; Yamasawa, Hideaki; Miki, Atsushi; Yamamoto, Hisashi; Muto, Shigeaki; Yamamoto, Hironori; Bando, Masashi

2016-08-01

nd in immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Paradoxically, this treatment induces sarcoidosis in a small population of RA patients as a class effect. A safer anti-TNF therapeutic strategy requires understanding of the risk factors for sarcoidosis. In Japan, TNF inhibitor was introduced in 2003. We reviewed 226 consecutive patients (65 men and 161 women) who were newly diagnosed with sarcoidosis between 2003 and 2012 at Jichi Medical University Hospital, Japan. We detected 3 cases in which sarcoidosis developed during etanercept treatment for RA. All 3 cases were women who had undergone bilateral oophorectomy more than 20 years earlier. Taken together with our previous epidemiologic findings of a consistently maintained second peak after menopause in the age-specific distribution of sarcoidosis in women over four decades, long-term insidious ovarian dysfunction was a possible risk factor for sarcoidosis under certain conditions, especially during etanercept treatment.

Appendectomy, tonsillectomy, and risk for sarcoidosis - A hospital-based case-control study in Japan.

PubMed

Sawahata, Michiru; Nakamura, Yosikazu; Sugiyama, Yukihiko

2017-05-01

The role of surgery in the onset of sarcoidosis is unclear. We investigated whether surgery is an internal environmental factor for sarcoidosis onset within the Japanese population. We enrolled 222 patients diagnosed with sarcoidosis (78 men, 144 women) who were admitted to our department between 1984 and 2012. We also enrolled 529 control subjects (251 men, 278 women), who were matched for sex, age at admission, and year of admission. Surgical history, family history, and smoking status were evaluated. Multivariate analysis correlated history of appendectomy (OR, 1.55; 95% CI, 1.05-2.29) and tonsillectomy (OR, 2.79; 95% CI, 0.91-8.56) with the occurrence of sarcoidosis; other surgical procedures had no correlation. In women, appendectomy had a stronger association with sarcoidosis (OR, 1.69; 95% CI, 1.05-2.73), as opposed to that in men (OR, 1.39; 95% CI, 0.68-2.85). This association was greater in women aged ≥45 years than in those aged <45 years. There was a stronger correlation between tonsillectomy and sarcoidosis in women (OR, 3.30; 95% CI, 0.88-12.39), than in men (OR, 1.26; 95% CI, 0.10-16.52). ORs for sarcoidosis were 5.55 (95% CI, 2.02-15.27) and 0.97 (95% CI, 0.52-1.84) in women aged ≥45 years with a history of appendectomy at <20 years and ≥20 years, respectively, with the former being statistically significant. Appendix and tonsil removal was associated with sarcoidosis onset, suggesting their potential protective role against sarcoidosis development. Further studies are needed to minimize possible confounding factors. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013.

PubMed

Ungprasert, P; Crowson, C S; Matteson, E L

2017-06-01

Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with hazard ratio (HR) of 2.18. Several chronic inflammatory disorders increase the risk of fragility fracture. However, little is known about the risk of fragility fracture in patients with sarcoidosis. This study was conducted using a previously identified population-based cohort of 345 patients with incident sarcoidosis from Olmsted County, Minnesota. Diagnosis of sarcoidosis required physician diagnosis supported by biopsy showing non-caseating granuloma, radiographic evidence of intrathoracic sarcoidosis, and compatible clinical presentations without evidence of other granulomatous diseases. Sex and age-matched subjects randomly selected from the same underlying population were used as comparators. Medical records of cases and comparators were reviewed for baseline characteristics and incident fragility fracture. Fragility fractures were observed in 34 patients with sarcoidosis, corresponding to a cumulative incidence of 5.6% at 10 years, while 18 fragility fractures were observed among comparators for a cumulative incidence of 2.4% at 10 years. The HR of fragility fractures among cases compared with comparators was 2.18 (95% confidence interval [CI], 1.23-3.88). The risk of fragility fracture by site was significantly higher among patients with sarcoidosis, and was due to a higher rate of distal forearm fracture (HR 3.58; 95% CI 1.53-8.40). Statistically non-significant increased risk was also observed in proximal femur (HR 1.66; 95% CI 0.45-6.06) and proximal humerus (HR 3.27; 95% CI 0.66-16.21). Risk of vertebral fracture was not increased (HR 1.00; 95% CI 0.32-3.11). Patients with sarcoidosis have an increased risk of fragility fracture which is primarily driven by the higher incidence of distal forearm fracture.

HTLV-1 seroprevalance in sarcoidosis. A clinical and laboratory study in northeast of Iran.

PubMed

Saghafi, Massoud; Rezaieyazdi, Zahra; Nabavi, Shima; Mirfeizi, Zahra; Sahebari, Maryam; Salari, Masoumeh

2018-06-01

Sarcoidosis is an autoimmune multiorgan granulomatosis disease with unknown origin. Some environmental factors such as viruses may induce the disease in genetically susceptible individuals. Human T cell lymphotropic virus type 1 (HTLV-1) can dysregulate the human immune system and the role of this virus in the pathogenesis of autoimmune diseases has been investigated and documented, such as in uveitis. In this study, we have focused on the seroprevalence of HTLV-1 in sarcoidosis in comparison to the normal population in the northeast of Iran, an endemic area for HTLV-1. This cross-sectional study enrolled 125 patients with established sarcoidosis to evaluate the frequency of HTLV-1 and compare it with the normal population of Mashhad, Iran. Participants' blood samples were analyzed for HTLV-1 antibody by an enzyme-linked immunosorbent assay kit. Positive results were confirmed by polymerase chain reaction method. Finally, data were analyzed using SPSS 11. Among sarcoidosis patients 106 (84.8%) patients had a history of acute course and 19 (15.2%) had chronic sarcoidosis. Four percent of the patients versus 2.12% of the Mashhad population were HTLV-1 positive with no statistical difference (P = 0.201). In age- and sex-matched selected controls, 3.6% were HTLV-1 positive again with no statistical difference by sarcoidosis group (P = 0.52). There was no statistical difference between arthritis, erythema nodusom, uveitis, constitutional symptoms, abnormal chest radiography (parahilar lymphadenopathy) and computed tomography scan findings, respiratory symptoms, sex, the course of the sarcoidosis in HTLV-1 positive and negative sarcoidosis patients. The frequency of HTLV-1 in 125 sarcoidosis patients was 4%. In comparison with prevalence of HTLV-1 in Mashhad, HTLV-1 seroprevalence did not show any significant difference. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity

PubMed Central

Braun, Nicole A.; Celada, Lindsay J.; Herazo-Maya, Jose D.; Abraham, Susamma; Shaginurova, Guzel; Sevin, Carla M.; Grutters, Jan; Culver, Daniel A.; Dworski, Ryszard; Sheller, James; Massion, Pierre P.; Polosukhin, Vasiliy V.; Johnson, Joyce E.; Kaminski, Naftali; Wilkes, David S.; Oswald-Richter, Kyra A.

2014-01-01

Rationale: Effective therapeutic interventions for chronic, idiopathic lung diseases remain elusive. Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important inhibitors of T-cell function. Objectives: To determine the effects of PD-1 pathway blockade on sarcoidosis CD4+ T-cell proliferative capacity. Methods: Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage–derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. Immunohistochemistry analysis for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy control lung specimens. Measurements and Main Results: Microarray analysis demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis peripheral blood mononuclear cells. Immunohistochemistry analysis revealed increased PD-L1 expression within sarcoidosis granulomas and lung malignancy, but this was absent in healthy lungs. Increased numbers of sarcoidosis PD-1+ CD4+ T cells are present systemically, compared with healthy control subjects (P < 0.0001). Lymphocytes with reduced proliferative capacity exhibited increased proliferation with PD-1 pathway blockade. Longitudinal analysis of subjects with sarcoidosis revealed reduced PD-1+ CD4+ T cells with spontaneous clinical resolution but not with disease progression. Conclusions: Analogous to the effects in other chronic lung diseases, these findings demonstrate that the PD-1 pathway is an important contributor to sarcoidosis CD4+ T-cell proliferative capacity and clinical outcome. Blockade of the PD-1 pathway may be a

The role of serum amyloid A staining of granulomatous tissues for the diagnosis of sarcoidosis.

PubMed

Huho, Albert; Foulke, Llewellyn; Jennings, Timothy; Koutroumpakis, Efstratios; Dalvi, Siddhartha; Chaudhry, Haroon; Chopra, Amit; Modi, Aakash; Rane, Neha; Prezant, David J; Sheehan, Christine; Yucel, Recai; Patel, Mehul; Judson, Marc A

2017-05-01

Previous studies demonstrated that SAA staining of sarcoidosis granulomas was qualitatively and quantitatively different from other granulomatous diseases. These data suggest that positive SAA staining of granulomatous tissue may have adequate specificity to establish a diagnosis of sarcoidosis. Our objective was to determine the diagnostic specificity of SAA staining for sarcoidosis relative to other granulomatous disorders. Pathological specimens demonstrating granulomatous inflammation were retrospectively identified at one institution, plus 4 specimens were obtained from New York City firefighters with biopsy-confirmed World Trade Center "sarcoidosis-like" pulmonary disease. Specimens were analyzed if specific diagnoses related to the granulomatous inflammation were confirmed through medical record review. SAA staining was performed using previously developed methods. Two pathologists, blinded to each other and the diagnoses, determined if the stained material was SAA positive or negative. Discordant results were adjudicated by the two pathologists. 106 specimens were analyzed from 100 patients, with 36 biopsies (34%) from sarcoidosis tissues and 70 (66%) from other granulomatous disorders. The Cohen Kappa correlation between the two pathologists for SAA staining positivity was excellent (0.85, 0.73-0.98). The overall specificity of SAA staining for the diagnosis of sarcoidosis was 84% (59/70). The sensitivity was 44% (16/36). Although SAA staining of various granulomatous tissues was fairly specific for the diagnosis of sarcoidosis, the specificity was inadequate for SAA staining to be used as a diagnostic test for sarcoidosis in isolation. These data suggest that SAA production may not be a universal mechanism in the development of sarcoidosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical Characteristics and Outcome of Hepatic Sarcoidosis: A Population-Based Study 1976-2013.

PubMed

Ungprasert, Patompong; Crowson, Cynthia S; Simonetto, Douglas A; Matteson, Eric L

2017-10-01

Data on clinical manifestations and outcome of hepatic sarcoidosis are scarce. This study aimed to use a population-based cohort of patients with incident sarcoidosis to better describe the characteristics of hepatic sarcoidosis. A cohort of incident cases of sarcoidosis in Olmsted County, MN, USA, from 1976 to 2013 was identified from the database. Diagnosis was verified by individual medical record review. Confirmed cases of sarcoidosis were then reviewed for liver involvement. Data on clinical manifestations, imaging study, liver biochemical tests, treatment, and outcome were collected. Cumulative incidence of cirrhosis adjusted for the competing risk of death was estimated. A total of 345 cases of incident sarcoidosis were identified. Of these, 19 cases (6%) had liver involvement (mean age 46.1 years, 53% female and 79% Caucasian). Most patients had asymptomatic liver disease and were discovered in pursuit of abnormal biochemical tests and imaging studies. Alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were elevated in the majority of patients (88 and 90%, respectively). Elevated transaminases were less common and less severe. About half of patients had abnormal imaging study with hypodense nodular lesions being the most common abnormality (six patients) followed by hepatomegaly (three patients). Liver biopsy revealed non-caseating granuloma in 88% (14 of 16 patients). A total of four patients developed cirrhosis. Involvement of the liver by sarcoidosis was seen in 6% of patients with sarcoidosis. The majority of patients were asymptomatic. Elevated ALP and GGT were the most common abnormal biochemical tests. Liver biopsy revealed non-caseating granuloma in almost all cases. Cirrhosis was seen in a significant number of patients. Generalizability of the observations to other populations may be limited, as the studied population was predominantly Caucasian. The prevalence of liver disease may be higher in more diverse populations.

Two cases of sarcoidosis presenting as longitudinally extensive transverse myelitis.

PubMed

Scott, Amanda Mary; Yinh, Janeth; McAlindon, Timothy; Kalish, Robert

2018-05-17

Neurosarcoidosis is uncommon with an incidence of approximately 5 to 15%. Central nervous system involvement can be divided into brain and spinal cord neurosarcoidosis. Spinal cord sarcoidosis is extremely rare, occurring in less than 1% of all sarcoidosis cases. Its manifestations may include cauda equina syndrome, radiculopathy, syringomyelia, cord atrophy, arachnoiditis, and myelopathy or transverse myelitis. We highlight two cases of spinal cord sarcoidosis, each presenting with longitudinally extensive transverse myelitis, that demonstrate the dilemmas that physicians face with regard to diagnosis and treatment. Given its rarity and the diversity of possible manifestations, establishing the diagnosis of spinal cord sarcoidosis is often very difficult. Extensive evaluation must be conducted to rule out primary neurologic, primary rheumatologic, infectious, and neoplastic diseases. MRI often demonstrates hyperintensity on T2-weighted images and enhancement following gadolinium administration. CSF analysis most consistently shows a lymphocytic pleocytosis and elevated proteins. While these less invasive investigations may be helpful, the gold standard for diagnosis is biopsy of neurologic or non-neurologic tissue confirming the presence of non-caseating granulomas. Evidence-based guidelines for the treatment of transverse myelitis secondary to sarcoidosis are lacking due to its rarity; therefore, therapy is based on expert and anecdotal experience and usually consists of high doses of steroids in combination with various immunosuppressive agents. The use of infliximab in particular appears promising, but there is a need for further investigation into the ideal treatment regimen.

Extrapulmonary involvement in patients with sarcoidosis and comparison of routine laboratory and clinical data to pulmonary involvement.

PubMed

Zurkova, Monika; Kolek, Vitezslav; Tomankova, Tereza; Kriegova, Eva

2014-12-01

Patients with pulmonary and pulmonary plus extrapulmonary sarcoidosis differ in symptom severity and health status impairment. To date there is no information on differences in clinical and laboratory parameters between these phenotypes and limited information on extrapulmonary involvement in Czech sarcoidosis patients exists. We therefore compared clinical data (age, gender, organ involvement, lung function tests) and laboratory data (blood counts, bronchoalveolar fluid (BAL) cellular profile, serum levels of CRP, SACE, sIL-2R, neopterin) between patients with newly diagnosed pulmonary sarcoidosis (n=107) and those with pulmonary plus extrapulmonary sarcoidosis (n=54). Extrapulmonary sarcoidosis was diagnosed in 33% of patients, mostly affecting lymph nodes and skin and having hypercalciuria. There was no difference in the prevalence of extrapulmonary sarcoidosis between genders. Patients with extrapulmonary sarcoidosis were older and mostly non-smokers when compared to those with limited pulmonary form. X-ray Stage I and erythema nodosum were less frequent in extrapulmonary disease. Serum levels of CRP, SACE, sIL-2R and neopterin and BAL cellular profile did not differ between both phenotypes. We observed lower platelets, FEV1, VC, and BAL CD19+ in females with extrapulmonary involvement than in those with pulmonary disease. Affected lymph nodes, skin and hypercalciuria were the most common in sarcoidosis patients with extrapulmonary involvement. Pulmonary sarcoidosis did not differ in clinical and routine laboratory parameters from pulmonary plus extrapulmonary sarcoidosis. Observation of low platelets, VC, FEV1 and BAL CD19+ in females with extrapulmonary sarcoidosis needs further verification in larger cohort.

Extensive intramuscular manifestation of sarcoidosis with initially missed diagnosis and delayed therapy: a case report.

PubMed

Meyer, Niklaus; Sutter, Reto; Schirp, Udo; Gutzeit, Andreas

2017-08-24

Sarcoidosis is a multisystemic granulomatous disorder, which in nearly all cases involves the lungs and other organs. Isolated forms of sarcoidosis within the muscles, but without lung involvement, are extremely rare and can lead to delayed or even false diagnosis. A 52-year-old white, Swiss man presented with painful arm cramps and a history of symptoms over the previous 3 years. In the initial clinical investigation, our patient also showed edema in both legs without any other complaints. After performing an magnetic resonance imaging scan of his extremities and a positron emission tomography/computed tomography scan, diffuse myositis was described. The subsequent muscle biopsy provided the surprising diagnosis of muscle sarcoidosis, without involvement of the lungs or any other organ. After starting therapy with glucocorticoids, his symptoms improved immediately. Sarcoidosis is a common disorder, which in most cases affects the lungs. In this case report an isolated sarcoidosis is described without lung involvement, but with involvement of the muscles of the extremities and the trunk. Reported cases of sarcoidosis only involving skeletal muscle and without lung involvement are extremely rare. Radiologists should consider this presentation of sarcoidosis to avoid delayed diagnosis and therapy.

Sudden multiple fractures in a patient with sarcoidosis in multiple organs.

PubMed

Sada, Mitsuru; Saraya, Takeshi; Ishii, Haruyuki; Goto, Hajime

2014-04-07

A 30-year-old man who incidentally fractured his right olecranon and other multiple phalanges was admitted to our hospital. He had a 2-year history of uveitis and bilateral hilar lymphadenopathy (BHL), and pulmonary sarcoidosis was diagnosed from transbronchial lung biopsy. Right elbow arthrodesis was performed, and biopsied specimens showed non-caseating epithelioid cell granuloma, suggesting osseous sarcoidosis. He was discharged uneventfully without further treatment, but BHL had progressed with the appearance of lung parenchymal lesions 3 months later. At that time, involvement of other organs was also noted on Gallium-67 scintigraphy, showing accumulations in BHL, axillary and inguinal lymph nodes, enlarged liver and spleen and subcutaneous areas. After initiation of steroid therapy, multiple organ involvement improved, and no further bone involvement has been recognised to date. Osseous sarcoidosis complicated by bone fracture is an extremely rare presentation, but should be considered in patients with sarcoidosis, especially when multiple organs are involved.

[Sarcoidosis of the skeleton. Review of the literature and case report. (author's transl)].

PubMed

Uehlinger, E; Wurm, K

1976-08-01

The frequency of sarcoidosis in the skeleton varies between 3 and 36%. Skeletal sarcoidosis is rare in early stages (Löfgren-syndrom), relatively frequent in late stages. The initial phase is characterized by the formation of miliary non-caseating epitheloid-cell granulomas in the bone marrow. The invasion of the bone marrow may either be tolerated by the bone tissue or it initiates a perifocal osteosclerosis or a osteolysis. Correspondingly the X-ray of the skeleton shows normal structure or focal osteosclerosis or osteolysis. Therefore in the first case the sarcoidosis cannot be identified by X-ray. Most frequent locations are the phalanges of the fingers and toes, less common the stem skelton (skull, vertebrae, pelvis) and very rare the long tubular bones. In most cases the skeletal sarcoidosis is well tolerated. Report of a case of osteosclerotic sarcoidosis of the pelvis of a 39-years old woman with generalized sarcoidosis which was diagnozed four years earlier. The X-rays of the phalanges were normal. The biopsy of the iliac crest shows miliary sarcoid granuloma of the bone marrow and accretion of lamellar bone on the surface of the bone trabeculi with a distinct mosaic pattern. Treatment with steroids during the following five years was ineffective.

Sarcoidosis diagnosed after September 11, 2001, among adults exposed to the World Trade Center disaster.

PubMed

Jordan, Hannah T; Stellman, Steven D; Prezant, David; Teirstein, Alvin; Osahan, Sukhminder S; Cone, James E

2011-09-01

Explore relationships between World Trade Center (WTC) exposures and sarcoidosis. Sarcoidosis has been reported after exposure to the WTC disaster. We ascertained biopsy-proven post-9/11 sarcoidosis among WTC Health Registry enrollees. Cases diagnosed after Registry enrollment were included in a nested case-control study. Controls were matched to cases on age, sex, race or ethnicity, and eligibility group (eg, rescue or recovery worker). We identified 43 cases of post-9/11 sarcoidosis. Twenty-eight incident cases and 109 controls were included in the case-control analysis. Working on the WTC debris pile was associated with sarcoidosis (odds ratio 9.1, 95% confidence interval 1.1 to 74.0), but WTC dust cloud exposure was not (odds ratio 1.0, 95% confidence interval 0.4 to 2.8). Working on the WTC debris pile was associated with an elevated risk of post-9/11 sarcoidosis. Occupationally exposed workers may be at increased risk. (C)2011The American College of Occupational and Environmental Medicine

Exercise capacity, muscle strength and fatigue in sarcoidosis.

PubMed

Marcellis, R G J; Lenssen, A F; Elfferich, M D P; De Vries, J; Kassim, S; Foerster, K; Drent, M

2011-09-01

The aim of this case-control study was to investigate the prevalence of exercise intolerance, muscle weakness and fatigue in sarcoidosis patients. Additionally, we evaluated whether fatigue can be explained by exercise capacity, muscle strength or other clinical characteristics (lung function tests, radiographic stages, prednisone usage and inflammatory markers). 124 sarcoidosis patients (80 males) referred to the Maastricht University Medical Centre (Maastricht, the Netherlands) were included (mean age 46.6±10.2 yrs). Patients performed a 6-min walk test (6MWT) and handgrip force (HGF), elbow flexor muscle strength (EFMS), quadriceps peak torque (QPT) and hamstring peak torque (HPT) tests. Maximal inspiratory pressure (P(I,max)) was recorded. All patients completed the Fatigue Assessment Scale (FAS) questionnaire. The 6MWT was reduced in 45% of the population, while HGF, EFMS, QPT and HPT muscle strength were reduced in 15, 12, 27 and 18%, respectively. P(I,max) was reduced in 43% of the population. The majority of the patients (81%) reported fatigue (FAS ≥22). Patients with reduced peripheral muscle strength of the upper and/or lower extremities were more fatigued and demonstrated impaired lung functions, fat-free mass, P(I,max), 6MWT and quality of life. Fatigue was neither predicted by exercise capacity, nor by muscle strength. Besides fatigue, exercise intolerance and muscle weakness are frequent problems in sarcoidosis. We therefore recommend physical tests in the multidisciplinary management of sarcoidosis patients, even in nonfatigued patients.

Extrapulmonary sites of radiogallium accumulation in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sulavik, S.B.; Palestro, C.J.; Spencer, R.P.

1990-12-01

In an effort to detect extrapulmonary sites of radiogallium accumulation in cases of sarcoidosis, 145 separate Ga-67 citrate studies of 114 patients with biopsy-proven sarcoidosis were examined. The most characteristic extrapulmonary radiogallium uptake pattern was the panda sign in 47 patients (41%). The most common site of prominent extrapulmonary radiogallium uptake was the lacrimal glands in 101 patients (88%). Second most common was activity in one or more superficial lymph node regions such as the cervical, axillary, femoral, or inguinal in 19 patients (17%). Other extrapulmonary sites included breast uptake in 6 out of 80 women (8%), prominent splenic andmore » nasal uptake in 9 (8%) patients, periportal accumulation in 7 (6%), and cutaneous/subcutaneous activity in 4 (4%). Because many of these individuals were receiving corticosteroids, the natural (untreated) prevalence of extrapulmonary findings may be even higher. Although the sensitivity and specificity of extrapulmonary radiogallium accumulation has still to be determined, many of the sites may be accessible to biopsy both for diagnostic purposes and to follow the effects of medications. It is therefore suggested that whole-body imaging be performed when radiogallium is administered to patients with suspected or known sarcoidosis.« less

Immune response CC chemokines CCL2 and CCL5 are associated with pulmonary sarcoidosis

PubMed Central

2011-01-01

Background Pulmonary sarcoidosis involves an intense leukocyte infiltration of the lung with the formation of non-necrotizing granulomas. CC chemokines (chemokine (C-C motif) ligand 2 (CCL2)-CCL5) are chemoattractants of mononuclear cells and act through seven transmembrane G-coupled receptors. Previous studies have demonstrated conflicting results with regard to the associations of these chemokines with sarcoidosis. In an effort to clarify previous discrepancies, we performed the largest observational study to date of CC chemokines in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis. Results BALF chemokine levels from 72 patients affected by pulmonary sarcoidosis were analyzed by enzyme-linked immunosorbent assay (ELISA) and compared to 8 healthy volunteers. BALF CCL3 and CCL4 levels from pulmonary sarcoidosis patients were not increased compared to controls. However, CCL2 and CCL5 levels were elevated, and subgroup analysis showed higher levels of both chemokines in all stages of pulmonary sarcoidosis. CCL2, CCL5, CC chemokine receptor type 1 (CCR1), CCR2 and CCR3 were expressed from mononuclear cells forming the lung granulomas, while CCR5 was only found on mast cells. Conclusions These data suggest that CCL2 and CCL5 are important mediators in recruiting CCR1, CCR2, and CCR3 expressing mononuclear cells as well as CCR5-expressing mast cells during all stages of pulmonary sarcoidosis. PMID:21463523

Immune response CC chemokines CCL2 and CCL5 are associated with pulmonary sarcoidosis.

PubMed

Palchevskiy, Vyacheslav; Hashemi, Nastran; Weigt, Stephen S; Xue, Ying Ying; Derhovanessian, Ariss; Keane, Michael P; Strieter, Robert M; Fishbein, Michael C; Deng, Jane C; Lynch, Joseph P; Elashoff, Robert; Belperio, John A

2011-04-04

Pulmonary sarcoidosis involves an intense leukocyte infiltration of the lung with the formation of non-necrotizing granulomas. CC chemokines (chemokine (C-C motif) ligand 2 (CCL2)-CCL5) are chemoattractants of mononuclear cells and act through seven transmembrane G-coupled receptors. Previous studies have demonstrated conflicting results with regard to the associations of these chemokines with sarcoidosis. In an effort to clarify previous discrepancies, we performed the largest observational study to date of CC chemokines in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis. BALF chemokine levels from 72 patients affected by pulmonary sarcoidosis were analyzed by enzyme-linked immunosorbent assay (ELISA) and compared to 8 healthy volunteers. BALF CCL3 and CCL4 levels from pulmonary sarcoidosis patients were not increased compared to controls. However, CCL2 and CCL5 levels were elevated, and subgroup analysis showed higher levels of both chemokines in all stages of pulmonary sarcoidosis. CCL2, CCL5, CC chemokine receptor type 1 (CCR1), CCR2 and CCR3 were expressed from mononuclear cells forming the lung granulomas, while CCR5 was only found on mast cells. These data suggest that CCL2 and CCL5 are important mediators in recruiting CCR1, CCR2, and CCR3 expressing mononuclear cells as well as CCR5-expressing mast cells during all stages of pulmonary sarcoidosis.

Factors signifying gender differences in clinical presentation of sarcoidosis among Estonian population.

PubMed

Lill, Hille; Kliiman, Kai; Altraja, Alan

2016-05-01

Sarcoidosis is endemically prevalent in Northern Europe, but gender differences among the sarcoidosis population have not yet been compositely addressed. To reveal independent factors that formulate gender differences in the presentation of sarcoidosis. All Caucasian patients with confirmed sarcoidosis were recruited from the outpatient department of the Lung Clinic of the Tartu University Hospital, Estonia, between February 2009 and April 2011. Data on demographics, complaints, symptoms, clinical presentation, extrapulmonary manifestations, radiographic stage, lung function parameters and sarcoidosis-related laboratory indices were all drawn from patients' clinical records at presentation. Factors characteristic of female gender were estimated using multivariate logistic regression analysis. Of 230 cases included, there were significantly more females (56.5%, P = 0.005). After adjustment for age, females appeared distinguishable from males by older age [adjusted odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.07], less frequent smoking (OR 0.25, 95% CI 0.13-0.49), higher probability of extrapulmonary complaints (OR 2.06, 95% CI 1.16-3.65) and musculoskeletal sarcoidosis (OR 3.22, 95% CI 1.65-6.29), and after adjustment for both age and smoking status lower forced expiratory volume in 1 s and lung carbon monoxide diffusing coefficient % predicted (OR 0.89, 95% CI 0.82-0.97 and OR 0.98, 95% CI 0.96-0.995, respectively), but by higher forced vital capacity % predicted (OR 1.12, 95% CI 1.03-1.22). Women with sarcoidosis are independently characterized by greater airflow obstruction, lower lung diffusing coefficient, older age, less smoking, and more frequent extrapulmonary complaints and musculoskeletal involvement. This may urge special attention when addressing female patients in both differential diagnostic and management settings. © 2014 John Wiley & Sons Ltd.

The Fatigue Assessment Scale: quality and availability in sarcoidosis and other diseases.

PubMed

Hendriks, Celine; Drent, Marjolein; Elfferich, Marjon; De Vries, Jolanda

2018-06-07

Fatigue is a problem experienced by many patients suffering from chronic diseases, including sarcoidosis patients. It has a substantial influence on patients' quality of life (QoL). It is, therefore, important to properly assess fatigue with a valid and reliable measure. The Fatigue Assessment Scale (FAS) is the only validated self-reporting instrument classifying fatigue in sarcoidosis. The aim of this review was to examine the psychometric properties of the FAS and the diseases and languages in which it has been used. Studies among sarcoidosis patients were also reviewed in terms of outcomes. Studies were identified by searching the electronic bibliographic database Pubmed. Search terms used were: FAS and fatigue. Articles were included in the review if the FAS had been used to assess fatigue. Since its introduction, the FAS was used in 26 different diseases or conditions, including stroke, neurologic disorders, rheumatoid arthritis, idiopathic pulmonary fibrosis and sarcoidosis. Its reliability and validity have proved to be good. Unidimensionality has been established. So far, the FAS is available in 20 languages and widely used in sarcoidosis. Digital versions as well as PDFs of various languages are available online (www.wasog.org). The FAS has good psychometric qualities for the diseases in which it has been examined, including sarcoidosis, and can be used in clinical practice. Healthcare workers can use the FAS to assess fatigue in the management, follow-up and clinical care programmes for their patients consistently across countries, as well as in clinical research.

Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, P.J.; Salama, A.

1994-10-01

Whole-body PET scanning was performed using {sup 18}F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma. Both patients were later proven to have sarcoidosis. Uptake of {sup 18}FDG was seen in both intra- and extrathoracic lesions as well as in associated erythema nodosum. One patient underwent a repeat scan after steroid therapy where a marked decrease in hilar uptake was seen. Fluorine-18-fluorodeoxyglucose uptake is observed in lymph nodes with sarcoid involvement. Further investigation is necessary to assess if quantitative differences exist between sarcoid and malignant lymphadenopathy. 30 refs., 3 figs.

Angiotensin-converting Enzyme as a Predictor of Extrathoracic Involvement of Sarcoidosis.

PubMed

Yasar, Zehra; Özgül, Mehmet Akif; Cetinkaya, Erdoğan; Kargi, Aysel; Gül, Şule; Talay, Fahrettin; Tanriverdi, Elif; Dincer, H Erhan

2016-01-18

Sarcoidosis is a multisystem disease, with extrathoracic involvement occurring in 25-50% of patients. Multi-organ involvement is often associated with a more chronic and severe course. The value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in diagnosing extrathoracic involvement in sarcoidosis has been demonstrated; however, because of the radiation dose and high cost, indications for its use must be well defined. Angiotensin-converting enzyme (ACE) is produced by active granuloma cells; thus, serum ACE (sACE) levels may reflect the total granuloma load. In this retrospective study, we evaluated the diagnostic value of sACE in the detection of extrathoracic involvement in sarcoidosis. 43 patients with biopsy-proven sarcoidosis underwent FDG-PET/CT during the initial workup. Positive findings were classified as thoracic and/or extrathoracic. The diagnostic value of sACE was estimated using sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs). Of the 43 patients studied, 17 (39.7%) had extrathoracic involvement. In this group, sACE values were higher than in patients without extrathoracic involvement (331 vs. 150, p=0.002) and correlated positively with extrathoracic involvement (R:0.532 p=0.02). Receiver operator characteristic curve analysis revealed an AUC of 0.816 [95% confidence interval: 0.669-0.963, p=0.002], 70.6% sensitivity and 80% specificity at the sACE cut-off value. In sarcoidosis, extrathoracic involvement may be life threatening or indicative of poor outcome. sACE levels are easily determined and may predict extrathoracic involvement. In patients with sarcoidosis, sACE levels can be used to better define those who would benefit from FDG-PET/CT examination to detect extrathoracic involvement.

[Roentgenological semiotics of sarcoidosis].

PubMed

Terpigorev, S A; Stashuk, G A; Dubrova, S E

2008-01-01

The aim of this review was to summarize semiotics of X-ray and CT-observable manifestations of intrathoracic sarcoidosis and clarify the role of conventional X-ray examination and CT (including high resolution CT) in the diagnosis of this disease and its complications. Also analysed are changes in pulmonary parenchyma compared with those detected in morphological studies.

Acute kidney injury as the presenting manifestation of sarcoidosis: A case series and review of literature.

PubMed

Rajkumar, Theepika; Lea-Henry, Tom; Chacko, Bobby

2018-06-01

Acute kidney injury is rarely the presenting feature of sarcoidosis. We present a case series of patients whose diagnosis of sarcoidosis was only brought to light by the development of renal impairment. Concurrent hypercalcaemia was noted, prompting further investigation. The patients discussed experienced a significant and rapid improvement in both renal function and hypercalcaemia in response to therapy with prednisolone. This is out of keeping with previous reports of sarcoidosis-induced renal impairment. Our case series highlights the importance of testing for hypercalcaemia in the context of acute kidney injury. Sarcoidosis is primarily a disease of the lungs and reticuloendothelial system; however, the prevalence of renal involvement with sarcoidosis may be under-recognized. The renal manifestations of sarcoidosis are discussed in the context of the current literature. Furthermore, from our experience, we postulate that in the context of sarcoidosis-induced renal injury, concurrent hypercalcaemia may present prior to the development of chronic renal injury and therefore these patients may be more likely to recover renal function. © 2017 Asian Pacific Society of Nephrology.

Insertion/Deletion Polymorphisms and Serum Angiotensin-converting Enzyme Levels in Iranian Patients with Sarcoidosis

PubMed Central

JAVADI, Alireza; SHAMAEI, Masoud; ZAREI, Masoud; REZAEIAN, Lida; KIANI, Arda; ABEDINI, Atefeh

2016-01-01

Background: Sarcoidosis is a multisystem inflammatory disease of unknown origin with characterization of small granulomas. Angiotensin-converting enzyme (ACE) is a pathophysiologic marker of sarcoidosis. We present the ACE insertion/deletion (I/D) polymorphism in correlation with serum ACE level in Iranian patients with sarcoidosis. Methods: From Jan 2014 to Jan 2015, 102 Iranian patients who histopathologically diagnosed for sarcoidosis and 192 healthy age and sex-matched controls were recruited. PCR was used for detection of I/D polymorphism in ACE gene. Results: Frequency of II/ID/DD genotype in sarcoidosis disease was 17%, 35.5%, and 47.1%, respectively. The frequency of D allele was 0.65. A significant association between I/D genotypes and mean of sACE level was seen (DD=85.2±22.9, P<0.001). More frequent genotype in sarcoidosis patients was DD (47%), ID genotype (45.9%) was found more in controls. Logistic regression analysis adjusting age and sex showed that ID to II (OR=0.35, 95%CI=0.17–0.73, P=0.005) and DD to II (OR=2.11, 95%CI=0.98–4.54, P=0.05) could be considered as a predictor factor for the disease activity. No significant model for men in sarcoidosis group was seen, while women with II/ID were associated with a reduced risk for the disease. Conclusion: Although more regional studies with appropriate statistical scale must be done to provide a better diagnosis and prognostic tool for this disease, this study demonstrates that ID and DD genotype could be predictive factors for sarcoidosis. PMID:28032065

An epidemiological perspective of the pathology and etiology of sarcoidosis.

PubMed

Sawahata, Michiru; Sugiyama, Yukihiko

2016-08-01

To update current knowledge on the pathology and etiology of sarcoidosis, here we review previous epidemiological research and discuss age-related differences and historical changes in the clinical characteristics of sarcoidosis we identified over the last four decades in Japan. Extrathoracic lymph node involvement was more common in young patients, while extrathoracic involvement of non-lymphatic organs and hypercalcemia were more common in older patients. Most patients in their 20s presented with bilateral hilar lymphadenopathy, but this was consistently less common among older patients. Over time, the distribution of age at diagnosis has shifted toward the older age group in the United States, Denmark, and Japan. In Japan, the incidence rate has been decreasing among young people, but there has consistently been a second peak among postmenopausal women. Age-related differences in the clinical presentation of sarcoidosis may reflect the pathways of causative antigens and the strengthening of immunoregulatory mechanisms with age. Internal and external environmental factors, such as exposure to diverse microorganisms, ovarian insufficiency, and active vitamin D deficiency, that may contribute to the onset of sarcoidosis must be identified in order to develop strategies for prevention and treatment.

Rare coexistence of sarcoidosis and lung adenocarcinoma.

PubMed

Kachalia, Amit Girish; Ochieng, Pius; Kachalia, Kinjal; Rahman, Habibur

2014-01-01

An eighty year old African-American female was evaluated for cough, chest pain, asymptomatic anemia and 21 pound weight loss over a six month period. Computerized tomography (CT) revealed a spiculated 2.8 cm right upper lobe lung nodule, other smaller nodules and lymphadenopathy. Gallium scan revealed abnormal uptake of radiotracer in lacrimal, hilar and mediastinal glands. Broncho-alveolar lavage showed CD4/CD8 ratio of 2:1 with 15% lymphocytes. Biopsy of right upper lobe lesion and mediastinoscopic lymph node biopsy showed numerous matured uniform non-caseating granulomatous inflammation, however stains and culture for Acid fast bacilli (AFB)/fungal organisms were negative. Patient improved on oral steroids. Six months later she returned with worsening dyspnea and chest X-ray showed bilateral pleural effusions. Thoracocentesis revealed Thyroid transcription factor 1 (TTF1) positive adenocarcinoma cells and Video assisted thoracic surgery (VATS) procedure revealed numerous pleural, pericardial, diaphragmatic metastasis. Biopsy also was positive for TTF1 adenocarcinoma and positive for Epidermal Growth Factor receptor (EGFR) mutation, however negative for Anaplastic Lymphoma Kinase (ALK). Talc pleurodesis was performed. She was treated with erlotinib while steroid was kept on hold. Initial tumor burden decreased but follow-up PET scan six months later showed progression of tumor with lymphadenopathy. After discussion with patient and family, patient opted for hospice care. Oncocentric theory postulates sarcoidosis as an immunological reaction to dispersal of tumor antigen. Sarcocentric theory postulates that cell-mediated immune abnormalities induced by sarcoidosis in CD4 and CD8 cells is involved in the onset of lung cancer. Thus considerable controversy exists regarding sarcoidosis and malignancy. In our case, TTF1 adenocarcinoma cells from thoracocentesis suggest peripheral nodules in right upper lobe and lingula were likely metastatic, presenting as malignant

Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease.

PubMed

Gupta, Arjun; Ayyar, Balaji; Zia, Hamid; Chen, Weina; Harris, Samar; Naina, Harris V

2016-06-01

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease.

Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk

PubMed Central

Fischer, Annegret; Ellinghaus, David; Nutsua, Marcel; Hofmann, Sylvia; Montgomery, Courtney G.; Iannuzzi, Michael C.; Rybicki, Benjamin A.; Petrek, Martin; Mrazek, Frantisek; Pabst, Stefan; Grohé, Christian; Grunewald, Johan; Ronninger, Marcus; Eklund, Anders; Padyukov, Leonid; Mihailovic-Vucinic, Violeta; Jovanovic, Dragana; Sterclova, Martina; Homolka, Jiri; Nöthen, Markus M.; Herms, Stefan; Gieger, Christian; Strauch, Konstantin; Winkelmann, Juliane; Boehm, Bernhard O.; Brand, Stephan; Büning, Carsten; Schürmann, Manfred; Ellinghaus, Eva; Baurecht, Hansjörg; Lieb, Wolfgang; Nebel, Almut; Müller-Quernheim, Joachim; Franke, Andre

2015-01-01

Rationale: Genetic variation plays a significant role in the etiology of sarcoidosis. However, only a small fraction of its heritability has been explained so far. Objectives: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. Methods: Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1,726 German sarcoidosis cases and 5,482 control subjects were genotyped for 128,705 single-nucleotide polymorphisms using the Illumina Immunochip for the screening step. The remaining 3,955 cases, 7,514 control subjects, and 684 parents of affected offspring were used for validation and replication of 44 candidate and two established risk single-nucleotide polymorphisms. Measurements and Main Results: Four novel susceptibility loci were identified with genome-wide significance in the European case-control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1), and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA-DPB1 (rs9277542), and found another novel independent signal near IL23R (rs12069782) on chromosome 1p31.3. Conclusions: Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17 signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics PMID:26051272

Pancreatic sarcoidosis discovered during Whipple procedure.

PubMed

Cook, Jonathan; Spees, Tanner; Telefus, Phillip; Ranaudo, Jeffrey M; Carryl, Stephen; Xiao, Philip

2013-04-04

Pancreatic sarcoidosis is a rare variant of systemic sarcoidosis, with cases described in literature as recently as January 2010. We present here a case of pancreatic involvement with non-caseating granulomas discovered on laparotomy in a patient with a preoperative diagnosis of pancreatic carcinoma. Computer tomography scan without contrast revealed a well-marginated smooth-shaped tumor in the head of the pancreas morphologically consistent with malignancy. During Whipple procedure, the mass was found to be a large lymph node that contained numerous non-caseating granulomas. Radiologically and clinically, non-caseating granulomas of the pancreas are often misdiagnosed as malignant tumor. Special attention given to this differential diagnosis by surgeons, pathologists and clinicians can avoid misdiagnosis and unnecessary treatment. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2013.

The Association between ANXA11 Gene Polymorphisms and Sarcoidosis: a Meta-Analysis and systematic review.

PubMed

Zhou, Hongfei; Diao, Mengyuan; Zhang, Mingyue

2016-08-01

The associations of ANXA11 gene polymorphisms and susceptibility to sarcoidosis have been evaluated in recent years. However, the results remain controversial, especially in different ethnicity. To assess the associations between ANXA11 and sarcoidosis, we conducted this meta-analysis. Articles were searched in MEDLINE, EMBASE and PubMed from their establishment date to August of 2014, and 4,567 sarcoidosis patients and 4,278 controls from 6 studies were included. The strength of associations was determined by ORs with 95% CIs. The associations between ANXA11 SNP rs1049550, rs2573346, rs2789679 polymorphisms and sarcoidosis risk were assessed using additive, recessive and dominant models. ANXA11 SNP rs2573346 and rs2789679 T allele conferred protection against sarcoidosis (OR: 0.664, 95% CI: 0.607-0.726 for rs2573346, and OR: 0.698, 95% CI: 0.640-0.762 for rs2789679). For SNP rs1049550, individuals carrying the ''T'' allele (TT+CT) had a nearly 46% increased risk for the development of sarcoidosis, when compared with CC homozygotes (OR: 1.461, 95% CI: 1.183-1.803) in overall population. A significant association was also found in additive model (OR: 1.477, 95% CI: 1.328-1.642 for CC vs. CT; OR: 0.610, 95% CI: 0.412-0.905 for TT vs. CC). In addition, ethnicity factors may contribute to the disease risk. The meta-analysis revealed that ''T'' allele of ANXA11 SNP rs2573346 and rs2789679 conferred protection against sarcoidosis. ''C'' allele of SNP rs1049550 may be a risk factor for sarcoidosis in overall population. Our study shows that ANXA11 closely associated with the development of sarcoidosis but further studies in different ethnicity were needed.

High throughput 16SrRNA gene sequencing reveals the correlation between Propionibacterium acnes and sarcoidosis.

PubMed

Zhao, Meng-Meng; Du, Shan-Shan; Li, Qiu-Hong; Chen, Tao; Qiu, Hui; Wu, Qin; Chen, Shan-Shan; Zhou, Ying; Zhang, Yuan; Hu, Yang; Su, Yi-Liang; Shen, Li; Zhang, Fen; Weng, Dong; Li, Hui-Ping

2017-02-01

This study aims to use high throughput 16SrRNA gene sequencing to examine the bacterial profile of lymph node biopsy samples of patients with sarcoidosis and to further verify the association between Propionibacterium acnes (P. acnes) and sarcoidosis. A total of 36 mediastinal lymph node biopsy specimens were collected from 17 cases of sarcoidosis, 8 tuberculosis (TB group), and 11 non-infectious lung diseases (control group). The V4 region of the bacterial 16SrRNA gene in the specimens was amplified and sequenced using the high throughput sequencing platform MiSeq, and bacterial profile was established. The data analysis software QIIME and Metastats were used to compare bacterial relative abundance in the three patient groups. Overall, 545 genera were identified; 38 showed significantly lower and 29 had significantly higher relative abundance in the sarcoidosis group than in the TB and control groups (P < 0.01). P. acnes 16SrRNA was exclusively found in all the 17 samples of the sarcoidosis group, whereas was not detected in the TB and control groups. The relative abundance of P. acnes in the sarcoidosis group (0.16% ± 0. 11%) was significantly higher than that in the TB (Metastats analysis: P = 0.0010, q = 0.0044) and control groups (Metastats analysis: P = 0.0010, q = 0.0038). The relative abundance of P. granulosum was only 0.0022% ± 0. 0044% in the sarcoidosis group. P. granulosum 16SrRNA was not detected in the other two groups. High throughput 16SrRNA gene sequencing appears to be a useful tool to investigate the bacterial profile of sarcoidosis specimens. The results suggest that P. acnes may be involved in sarcoidosis development.

Diagnostic value of quantitative assessment of cardiac 18F-fluoro-2-deoxyglucose uptake in suspected cardiac sarcoidosis.

PubMed

Lebasnier, Adrien; Legallois, Damien; Bienvenu, Boris; Bergot, Emmanuel; Desmonts, Cédric; Zalcman, Gérard; Agostini, Denis; Manrique, Alain

2018-06-01

The identification of cardiac sarcoidosis is challenging as there is no gold standard consensually admitted for its diagnosis. The aim of this study was to evaluate the diagnostic value of the assessment of cardiac dynamic 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG PET/CT) and net influx constant (Ki) in patients suspected of cardiac sarcoidosis. Data obtained from 30 biopsy-proven sarcoidosis patients suspected of cardiac sarcoidosis who underwent a 50-min list-mode cardiac dynamic 18 F-FDG PET/CT after a 24 h high-fat and low-carbohydrate diet were analyzed. A normalized coefficient of variation of quantitative glucose influx constant, calculated as the ratio: standard deviation of the segmental Ki (min -1 )/global Ki (min -1 ) was determined using a validated software (Carimas ® 2.4, Turku PET Centre). Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare criteria. Receiving operating curve analysis was performed to determine sensitivity and specificity of cardiac dynamic 18 F-FDG PET/CT analysis to diagnose cardiac sarcoidosis. Six out of 30 patients (20%) were diagnosed as having cardiac sarcoidosis. Myocardial glucose metabolism was significantly heterogeneous in patients with cardiac sarcoidosis who showed significantly higher normalized coefficient of variation values compared to patients without cardiac sarcoidosis (0.513 ± 0.175 vs. 0.205 ± 0.081; p = 0.0007). Using ROC curve analysis, we found a cut-off value of 0.38 for the diagnosis of cardiac sarcoidosis with a sensitivity of 100% and a specificity of 91%. Our results suggest that quantitative analysis of cardiac dynamic 18 F-FDG PET/CT could be a useful tool for the diagnosis of cardiac sarcoidosis.

Conjunctival Biopsy as a First Choice to Confirm a Diagnosis of Sarcoidosis.

PubMed

Korkmaz Ekren, Pervin; Mogulkoc, Nesrin; Toreyin, Zehra Nur; Egrilmez, Sait; Veral, Ali; Akalın, Taner; Bacakoglu, Feza

2016-10-07

Sarcoidosis is a granulomatous systemic disease of unknown aetiology. The diagnosis needs histological confirmation of the presence of non-caseating granulomata. One option is a conjunctival biopsy. The aims of this study were to evaluate conjunctival biopsy for the diagnosis of sarcoidosis with respect to its sensitivity and to assess its cost effectiveness by comparison with other histopathological diagnostic procedures. Patients were identified from the database of the Interstitial Lung Disease Clinic (ILDC) of the Chest Department of Ege University Hospital from May 2008 to June 2014.  The patients who had biopsy procedures performed for the definitive diagnosis of sarcoidosis were assessed. Their diagnostic procedures and the cost of procedures were recorded. The cost per positive result for each procedure was calculated.  Results: In total, 280 patients were followed up with a diagnosis of sarcoidosis, of whom 174 had histological confirmation; these constitute the study population. There were 127 females and 47 males with a median age of 46 years (range 14-78 years). Forty three patients had conjunctival biopsy and we could establish a diagnosis in 54% of these by means of conjunctival biopsy. Moreover, we showed that this biopsy can provide positive result for sarcoidosis patients who lack abnormal eye findings. Additionally, it is cost effective approach and without complications. This study re-asserts the value of  conjunctival biopsy, which was described in the past but is not commonly used nowadays. In the presence of suggestive clinic and radiologic findings, we recommend conjunctival biopsy as the first choice for the histopathological confirmation of sarcoidosis.

Cutaneous sarcoidosis: A retrospective case series and a hospital-based case-control study in Taiwan.

PubMed

Liu, Kwei-Lan; Tsai, Wen-Chien; Lee, Chih-Hung

2017-10-01

Sarcoidosis is a systemic granulomatous disorder of unknown etiology often involving skin. Studies on cutaneous sarcoidosis and comorbidities are limited. This study is aimed to describe the clinical features of cutaneous sarcoidosis diagnosed in our hospital and to determine the relationships between cutaneous sarcoidosis and comorbidities.This retrospective study evaluates patients with cutaneous sarcoidosis in a tertiary center in Taiwan from 1996 to 2015. The records of 38 patients with cutaneous sarcoidosis were reviewed for clinical characteristics and evaluated by analysis of variance. A 1:4 case-control analysis was conducted with 152 age- and sex-matched controls who underwent biopsy for other benign skin tumors.The male to female ratio was 1:4.4. The average age at diagnosis was 51.7 years. Female patients were on average 13.9 years older than male patients. The correlation of age with gender was statistically significant (P = .037). The most common cutaneous lesions were plaques (47.4%) and confined to the face (71.1%). Of the 38 patients, 26.3% had diabetes mellitus. Age over 40 (P = .014) and female (P = .014) were associated with facial involvement. In the case-control study, a higher percentage of patients with cutaneous sarcoidosis than of control subjects had diabetes mellitus (P = .001), hearing loss (P = .031) and eye diseases (P = .047).The present study demonstrates a striking female predominance and high proportions of facial involvement. Diabetes mellitus, hearing loss, and eye diseases may be associated with Taiwanese patients with cutaneous sarcoidosis.

Direct quantitation of thoracic gallium-67 uptake in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourguet, P.; Delaval, P.; Herry, J.Y.

1986-10-01

A method of direct quantitation of /sup 67/Ga uptake in the lung is described. The attenuation coefficient requires calculation and is obtained simply for each patient by transmission using a planar radionuclide source. The validity of the method was tested with a phantom (error less than 10%). Forty-three patients with pulmonary and/or mediastinal sarcoidosis were classified. The different groups of patients as defined clinically and radiographically (controls, nonactive, and active sarcoidosis) were well-differentiated (p less than 0.001).

In-Hospital Disease Burden of Sarcoidosis in Switzerland from 2002 to 2012.

PubMed

Pohle, Susanne; Baty, Florent; Brutsche, Martin

2016-01-01

Sarcoidosis is a multisystem disease with an unpredictable and sometimes fatal course while the underlying pathomechanism is still unclear. Reasons of the increasing hospitalization rate and mortality in the United States remain in dispute but incriminated are a number of distinct comorbidities and risk factors as well as the application of more aggressive therapeutic agents. Studies reflecting the recent development in central Europe are lacking. Our aim was to investigate the recent mortality and hospitalization rates as well as the underlying comorbidities of hospitalized sarcoidosis patients in Switzerland. In this longitudinal, nested case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2012 (n = 15,627,573) was analyzed. There were 8,385 cases with a diagnosis of sarcoidosis representing 0.054% (8,385 / 15,627,573) of all hospitalizations in Switzerland. These cases were compared with age- and sex-matched controls without the diagnosis of sarcoidosis. Hospitalization and mortality rates in Switzerland remained stable over the observed time period. Comorbidity analysis revealed that sarcoidosis patients had significantly higher medication-related comorbidities compared to matched controls, probably due to systemic corticosteroids and immunosuppressive therapy. Sarcoidosis patients were also more frequently re-hospitalized (median annual hospitalization rate 0.28 [IQR 0.15-0.65] vs. 0.19 [IQR 0.13-0.36] per year; p < 0.001), had a longer hospital stay (6 [IQR 2-13] vs. 4 [IQR 1-8] days; p < 0.001), had more comorbidities (4 [IQR 2-7] vs. 2 [IQR 1-5]; p < 0.001), and had a significantly higher in-hospital mortality (2.6% [95% CI 2.3%-2.9%] vs. 1.8% [95% CI 1.5%-2.1%] (p < 0.001). A worse outcome was observed among sarcoidosis patients having co-occurrence of associated respiratory diseases. Moreover, age was an important risk factor for re-hospitalization.

Sarcoidosis Increases Risk of Hospitalized Infection. A Population-based Study, 1976–2013

PubMed Central

Crowson, Cynthia S.; Matteson, Eric L.

2017-01-01

Rationale: Patients with sarcoidosis may have an increased risk of infection similar to other immune-mediated disorders. However, the data are still limited. Objectives: To investigate the risk of hospitalized infection among patients with sarcoidosis, using a population-based cohort. Methods: Using the Rochester Epidemiology Project record-linkage system, a cohort of incident cases of sarcoidosis in Olmsted County, Minnesota from 1976 to 2013 was identified. Diagnosis was confirmed by individual medical record review. For each patient with sarcoidosis, a sex- and age-matched comparator without sarcoidosis was randomly selected from the same population. Medical records of cases and comparators were individually reviewed for hospitalized infection that occurred after the index date. The cumulative incidence of hospitalized infection overall and by type of infection, adjusted for the competing risk of death, was estimated. Cox models were used to compare the rate of first hospitalized infection between cases and comparators and to evaluate the association between use of immunosuppressive agents and hospitalized infection among cases. Results: Three hundred and forty-five cases and 345 comparators were identified. Patients with sarcoidosis had a higher risk of a hospitalized infection with a hazard ratio (HR) of 2.00 (95% confidence interval [CI], 1.41–2.84), adjusted for age, sex, and calendar year of index date. Use of oral glucocorticoids was a significant predictor of hospitalized infection with an HR of 3.03 (95% CI, 1.33–6.90) for oral glucocorticoids not exceeding 10 mg/day and an HR of 4.48 (95% CI, 1.54–13.03) for oral glucocorticoids greater than 10 mg/day. Conclusions: Patients with sarcoidosis are at increased risk of hospitalized infection. Glucocorticoid therapy is strongly associated with this increased risk. PMID:28177656

Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association

PubMed Central

Nair, Vidya; Prajapat, Deepak; Talwar, Deepak

2016-01-01

Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%), but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently. PMID:26933313

The influence of comorbidities on mortality in sarcoidosis: a observational prospective cohort study.

PubMed

Nowiński, Adam; Puścińska, Elzbieta; Goljan, Anna; Peradzynska, Joanna; Bednarek, Michal; Korzybski, Damian; Kamiński, Dariusz; Stokłosa, Anna; Czystowska, Monika; Śliwiński, Pawel; Górecka, Dorota

2017-09-01

The aim of this study was to identify the frequency and prevalence of comorbidities in sarcoid patients and to assess their influence on overall mortality in the cohort of patients with sarcoidosis. A cohort of 557 patients with histologically confirmed sarcoidosis diagnosed between 2007 and 2011 and a group of non-sarcoid controls were observed. All patients were carefully observed for comorbidities and mortality. 291 males (52.2%) and 266 females (47.8%) with mean age 48.4 ± 12.0 years in sarcoidosis group and a group of 100 controls with mean age (49.25 ± 10.3) were observed. The mean number of comorbidities in both groups was similar (0.9 ± 0.99 vs 0.81 ± 0.84 NS). The frequency of thyroid disease was significantly higher in sarcoidosis group comparing to controls at the time of diagnosis (OR = 3.62 P = 0.0144). During the observation period (median 58.0 months), 16 patients died (2.9%). The mean number of comorbidities was significantly higher in the groups of non-survivors as compared to survivors (2.8 ± 1.0, vs 0.8 ± 0.9), P < 0.0001. The comorbidity burden has strong impact on mortality in sarcoidosis. Thyroid diseases are more frequent in sarcoidosis than in non-sarcoid controls. © 2015 John Wiley & Sons Ltd.

Nanocrystal for ocular drug delivery: hope or hype.

PubMed

Sharma, Om Prakash; Patel, Viral; Mehta, Tejal

2016-08-01

The complexity of the structure and nature of the eye emanates a challenge for drug delivery to formulation scientists. Lower bioavailability concern of conventional ocular formulation provokes the interest of researchers in the development of novel drug delivery system. Nanotechnology-based formulations have been extensively investigated and found propitious in improving bioavailability of drugs by overcoming ocular barriers prevailing in the eye. The advent of nanocrystals helped in combating the problem of poorly soluble drugs specifically for oral and parenteral drug delivery and led to development of various marketed products. Nanocrystal-based formulations explored for ocular drug delivery have been found successful in achieving increase in retention time, bioavailability, and permeability of drugs across the corneal and conjunctival epithelium. In this review, we have highlighted the ocular physiology and barriers in drug delivery. A comparative analysis of various nanotechnology-based ocular formulations is done with their pros and cons. Consideration is also given to various methods of preparation of nanocrystals with their patented technology. This article highlights the success achieved in conquering various challenges of ocular delivery by the use of nanocrystals while emphasizing on its advantages and application for ocular formulation. The perspectives of nanocrystals as an emerging flipside to explore the frontiers of ocular drug delivery are discussed.

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis.

PubMed

Takemoto, Y; Sakatani, M; Takami, S; Tachibana, T; Higaki, J; Ogihara, T; Miki, T; Katsuya, T; Tsuchiyama, T; Yoshida, A; Yu, H; Tanio, Y; Ueda, E

1998-06-01

Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

Gallium scan in intracerebral sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makhija, M.C.; Anayiotos, C.P.

1981-07-01

Sarcoidosis involving the nervous system probably occurs in about 4% of patients. The usefulness of brain scintigraphy in these cases has been suggested. In this case of cerebral sarcoid granuloma, gallium imaging demonstrated the lesion before treatment and showed disappearance of the lesion after corticosteroid treatment, which correlated with the patient's clinical improvement.

T wave amplitude in lead aVR as a novel diagnostic marker for cardiac sarcoidosis.

PubMed

Tanaka, Yoshihiro; Konno, Tetsuo; Yoshida, Shohei; Tsuda, Toyonobu; Sakata, Kenji; Furusho, Hiroshi; Takamura, Masayuki; Yoshimura, Kenichi; Yamagishi, Masakazu; Hayashi, Kenshi

2017-03-01

It is vital to identify cardiac involvement (CI) in patients with sarcoidosis as the condition could initially lead to sudden cardiac death. Although the T wave amplitude in lead aVR (TWAaVR) is reportedly associated with adverse cardiac events in various cardiovascular diseases, only scarce data are available concerning the utility of lead aVR in identifying CI in patients with sarcoidosis. We retrospectively investigated the diagnostic values of TWAaVR in patients with sarcoidosis in comparison with conventional electrocardiography parameters such as bundle branch block (BBB). From January 2006 to December 2014, 93 consecutive patients with sarcoidosis were enrolled (mean age, 55.7 ± 15.7 years; male, 31 %; cardiac involvement, n = 26). TWAaVR showed the greatest sensitivity (39 %) and specificity (92 %) in distinguishing between sarcoidosis patients with and without CI, at a cutoff value of -0.08 mV. The diagnostic value of BBB for cardiac involvement was significantly improved when combined with TWAaVR (sensitivity: 61-94 %, specificity: 97-89 %, area under the curve: 0.79-0.92, p = 0.018). Multivariate logistic regression analysis indicated that TWAaVR and BBB were independent electrocardiography parameters associated with CI. In summary, we observed that sarcoidosis patients exhibiting a high TWAaVR were likely to have CI. Thus, the application of a combination of BBB with TWAaVR may be useful when screening for CI in sarcoidosis patients.

A diagnostic predicament: activated sarcoidosis or pulmonary histoplasmosis. A case report.

PubMed

Lingscheid, Tilman; von Heinz, Marie; Klages, Birgit; Rickerts, Volker; Tintelnot, Kathrin; Gerhold, Manuela; Oestmann, Jörg-Wilhelm; Becker, Markus; Temmesfeld-Wollbrück, Bettina; Suttorp, Norbert; Hübner, Ralf-Harto

2017-05-01

We report a case of a 41-year-old man presenting with persisting fevers over 2 weeks. The patient had spent 4 weeks in Central America. He was in control of a stable stage II sarcoidosis. Laboratory and various microbiological tests as well as chest radiography led to no diagnosis. Activated sarcoidosis was hypothesized as the most likely diagnosis. However, we considered an infectious process as a differential diagnosis, in detail, the travel history imposed histoplasmosis. Chest-CT documented localized interstitial consolidations. Bronchoscopy with bronchoalveolar lavage (BAL) and biopsy was performed. Results of BAL fluid, biopsy, distinct sarcoidosis serum markers and a borderline positive histoplasmosis-serology yielded in a diagnostic dilemma as no distinct diagnosis was drawable. After the patient was already started on a prednisolone trial, the final diagnosis - pulmonary histoplasmosis - could be achieved via positive culture and PCR out of the BAL fluid. This case shows the difficult differentiation between an acute exacerbation of a chronic pulmonary disease and a concomitant infection, which was especially aggravated in this case as the histoplasmosis masqueraded an acute picture of sarcoidosis. © 2015 John Wiley & Sons Ltd.

Radioisotope bone scanning in a case of sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cinti, D.C.; Hawkins, H.B.; Slavin, J.D. Jr.

1985-03-01

The application of radioisotope scanning to osseous involvement from systemic sarcoidosis has been infrequently described in the scientific literature. Most commonly, the small bones of the hands and feet are affected if sarcoidosis involves the skeleton. Nonetheless, there are also occasional manifestations of sarcoid in the skull, long bones, and vertebral bodies. This paper describes a case of sarcoid involving the lung parenchyma with multiple lesions in the skull and ribs demonstrated by bone scanning with Tc-99m MDP. Following treatment with steroids, the bone scan showed complete resolution of the rib lesions and almost complete resolution of the lesions inmore » the calvarium.« less

A rare presentation of histologically proven sarcoidosis of the knee: A case report and brief review of the literature.

PubMed

Deschuyteneer, Evan; Rongé, R; Riffi, A; De Pierre, K; Vandenbroucke, F; Boulet, C; Goossens, A; Vincken, W

2017-06-01

We here report a patient with histologically proven sarcoidosis of the knee, a rare localization of sarcoidosis, which usually presents itself as a pulmonary disease. Case reports of radiological images that suggest osseous sarcoidosis of the appendicular skeleton are not so rare, however few are histologically proven. Since in our patient MRI could not distinguish between sarcoidosis and another (possibly malignant) disease, histological proof was obtained through a CT-guided biopsy. Imaging and treatment guidelines for extrapulmonary sarcoidosis are inexistent, due to lack of randomized trials.

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis

PubMed Central

Takemoto, Y.; Sakatani, M.; Takami, S.; Tachibana, T.; Higaki, J.; Ogihara, T.; Miki, T.; Katsuya, T.; Tsuchiyama, T.; Yoshida, A.; Yu, H.; Tanio, Y.; Ueda, E.

1998-01-01

BACKGROUND—Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken.
METHODS—ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2 ) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls.
RESULTS—There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis.
CONCLUSIONS—The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

 PMID:9713444

The impact of ACE gene polymorphism on the incidence and phenotype of sarcoidosis in rural and urban settings.

PubMed

Kieszko, Robert; Krawczyk, Paweł; Powrózek, Tomasz; Szudy-Szczyrek, Aneta; Szczyrek, Michał; Homa, Iwona; Daniluk, Jadwiga; Milanowski, Janusz

2016-12-01

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Current theory on the etiology of this disease involves participation of genetic factors and unknown antigens present in the patients' environment. The aim of the study was to evaluate the prevalence of different polymorphic forms of the ACE gene in healthy individuals and sarcoidosis patients, and to estimate the risk of sarcoidosis in carriers of different ACE genotypes living in rural and urban settings. The study group included 180 patients with pulmonary sarcoidosis. Assessment of the disease was based on clinical features, laboratory and imaging examinations, as well as bronchoscopy with bronchoalveolar lavage (BAL). ACE gene polymorphism was examined in DNA isolated from peripheral blood or BAL fluid (BALF) leukocytes. Incidence of sarcoidosis was not influenced by gender, age or place of residence of the patients. There were no differences in the frequency of particular genotypes in patients with sarcoidosis and in healthy individuals. The risk of disease did not depend on the ACE gene polymorphism. There were no differences in the frequencies of the different genotypes and alleles of the ACE gene in patients with sarcoidosis divided by gender, age and place of residence or by clinical manifestation of sarcoidosis. Our results do not support the previous concept which suggested a higher incidence of sarcoidosis in individuals living in rural areas and in carriers of selected ACE genotypes. It is possible that this is related to the changing environment of rural areas, increasing urbanization and pollution.

Humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and Löfgren's syndrome using high-content peptide microarrays.

PubMed

Ferrara, Giovanni; Valentini, Davide; Rao, Martin; Wahlström, Jan; Grunewald, Johan; Larsson, Lars-Olof; Brighenti, Susanna; Dodoo, Ernest; Zumla, Alimuddin; Maeurer, Markus

2017-03-01

Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches. Inclusion/exclusion and significance analyses were performed according to published methods. Each study group recognized 68-78% M. tuberculosis peptides at least once. M. tuberculosis epitope recognition by sarcoidosis patient sera was 42.7%, and by TB patient sera was 39.1%. Seven and 16 peptides were recognized in 9/12 (75%) and 8/12 (67%) sarcoidosis patient sera but not in TB patient sera, respectively. Nine (75%) and eight (67%) out of twelve TB patient sera, respectively recognized M. tuberculosis peptides that were not recognized in sarcoidosis patient sera. Specific IgG recognition patterns for M. tuberculosis antigens in sarcoidosis patients re-affirm mycobacterial involvement in sarcoidosis, providing biologically relevant targets for future studies pertaining to diagnostics and immunotherapy. Copyright © 2017. Published by Elsevier Ltd.

Acute renal failure as a form of presentation of sarcoidosis in a young adult: a case report

PubMed Central

2014-01-01

Introduction Sarcoidosis is a systemic granulomatous disease. Renal involvement is a rare initial presentation of this disease. Few articles on renal involvement as an initial presentation of sarcoidosis have been published in the literature. Case presentation A 26-year-old Caucasian woman presented with acute renal failure as an initial manifestation of sarcoidosis. Conclusions Renal involvement is an uncommon feature of sarcoidosis and it is essential to establish a fast and correct diagnosis because early therapy avoids progression to terminal renal failure. PMID:25124289

Association Between Occupational Exposures and Sarcoidosis: An Analysis From Death Certificates in the United States, 1988-1999.

PubMed

Liu, Hongbo; Patel, Divya; Welch, Alison M; Wilson, Carla; Mroz, Margaret M; Li, Li; Rose, Cecile S; Van Dyke, Michael; Swigris, Jeffrey J; Hamzeh, Nabeel; Maier, Lisa A

2016-08-01

Sarcoidosis is a disease that is associated with occupational and environmental antigens, in the setting of a susceptible host. The aim of this study was to examine the association between sarcoidosis mortality and previously reported occupational exposures based on sex and race. The decedents enrolled in this study were derived from United States death certificates from 1988-1999. Cause of death was coded according to ICD-9 and ICD-10. The usual occupation was coded with Bureau of the Census Occupation Codes. Mortality odds ratio (MOR) were determined and multiple Poisson regression were performed to evaluate the independent exposure effects after adjustment for age, sex, race and other occupational exposures. Of the 7,118,535 decedents in our study, 3,393 were identified as sarcoidosis-related, including 1,579 identified as sarcoidosis being the underlying cause of death. The sarcoidosis-related MOR of any occupational exposure was 1.52 (95% CI, 1.35-1.71). Women with any exposure demonstrated an increased MOR compared to women without (MOR 1.65, 95% CI, 1.45-1.89). The mortality risk was significantly elevated in those with employment involving metal working, health care, teaching, sales, banking, and administration. Higher sarcoidosis-related mortality risks associated with specific exposures were noted in women vs men and blacks vs whites. Findings of prior occupations and risk of sarcoidosis were verified using sarcoidosis mortality rates. There were significant differences in risk for sarcoidosis mortality by occupational exposures based on sex and race. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Infliximab for chronic cutaneous sarcoidosis: a subset analysis from a double-blind randomized clinical trial.

PubMed

Baughman, Robert P; Judson, Marc A; Lower, Elyse E; Drent, Marjolein; Costabel, Ulrich; Flavin, Susan; Lo, Kim Hung; Barnathan, Elliot S

2016-01-15

Limited evidence exists demonstrating an effective treatment for chronic cutaneous sarcoidosis. To determine infliximab's effectiveness in sarcoidosis. We conducted a subset analysis from a randomized, double-blind, placebo-controlled trial for chronic pulmonary sarcoidosis to determine infliximab's effectiveness. Patients with chronic cutaneous sarcoidosis received infliximab (3 or 5 mg/kg) or placebo over 24 weeks. Of 138 patients, the subset analysis evaluated 17 patients with chronic facial and another 9 patients with nonfacial skin involvement. The SASI evaluated lesions for degree of erythema, desquamation, induration, and percentage of area involved. Facial and nonfacial lesions were scored in a blinded manner. Among 5 placebo-treated and 12 infliximab-treated patients, an improvement was observed with infliximab versus placebo in change from baseline to weeks 12 and 24 in desquamation (P<0.005) and induration (P<0.01) at week 24. Erythema, percentage of area involved and the evaluation of paired photographs did not reveal significant differences. Sample size; more extensive disease in placebo patients; chronic therapy upon enrollment; lung as primary organ of sarcoidosis involvement; limited investigator experience with SASI. Infliximab appears to be a beneficial treatment for chronic cutaneous sarcoidosis. The SASI scoring system demonstrated significant improvement versus placebo in lesion desquamation and induration.

Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobs, M.P.; Baughman, R.P.; Hughes, J.

1985-05-01

Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (includingmore » 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).« less

Systemic sclerosis and sarcoidosis: a rare case of chronic intestinal pseudo-obstruction.

PubMed

Bernardo, Sónia; Gonçalves, Ana Rita; Araújo-Correia, Luís

2018-06-01

The coexistence of systemic sclerosis (SSc) and sarcoidosis is an extremely rare phenomenon; some studies question its existence. We report the case of a male with a diagnosis of sarcoidosis that was admitted due to abdominal distension and pain. After a thorough investigation, he was diagnosed with severe chronic intestinal pseudo-obstruction as a manifestation of SSc.

A Genome-wide Admixture Scan for Ancestry-linked Genes Predisposing to Sarcoidosis in African Americans

PubMed Central

Rybicki, Benjamin A.; Levin, Albert M.; McKeigue, Paul; Datta, Indrani; Gray-McGuire, Courtney; Colombo, Marco; Reich, David; Burke, Robert R.; Iannuzzi, Michael C.

2010-01-01

Genome-wide linkage and association studies have uncovered variants associated with sarcoidosis, a multi-organ granulomatous inflammatory disease. African ancestry may influence disease pathogenesis since African Americans are more commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis genome-wide ancestry scan using a map of 1,384 highly ancestry informative single nucleotide polymorphisms genotyped on 1,357 sarcoidosis cases and 703 unaffected controls self-identified as African American. The most significant ancestry association was at marker rs11966463 on chromosome 6p22.3 (ancestry association risk ratio (aRR)= 1.90; p=0.0002). When we restricted the analysis to biopsy-confirmed cases, the aRR for this marker increased to 2.01; p=0.00007. Among the eight other markers that demonstrated suggestive ancestry associations with sarcoidosis were rs1462906 on chromosome 8p12 which had the most significant association with European ancestry (aRR=0.65; p=0.002), and markers on chromosomes 5p13 (aRR=1.46; p=0.005) and 5q31 (aRR=0.67; p=0.005), which correspond to regions we previously identified through sib pair linkage analyses. Overall, the most significant ancestry association for Scadding stage IV cases was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; p=2×10−5), a region not associated with disease susceptibility. In summary, through admixture mapping of sarcoidosis we have confirmed previous genetic linkages and identified several novel putative candidate loci for sarcoidosis. PMID:21179114

Sarcoidosis onset simulating a unique hepatic metastasis.

PubMed

Diéguez Castillo, Carmelo; Martín-Lagos Maldonado, Alicia; Ríos Pelegrina, Rosa María; Díaz Alcázar, María Del Mar; Roa Colomo, Amparo; Ruiz Escolano, Elena

2018-06-22

Sarcoidosis is a systemic granulomatous disease with an uncertain etiology, characterized by the production of non-necrotizing granulomas. The most frequent presentation is pulmonary and mediastinal, although it might affect any other organ. Hepatic alterations occur in 50 to 65% of the cases. Nevertheless, it is commonly subclinical or detected during a study of the alteration of liver enzymes. It is very unusual that disease onset occurs as an isolated hepatic tumor. A hepatic biopsy is usually required to confirm the diagnosis. A differential diagnosis must be established via any hepatic granulomatous disease, infectious or autoimmune disease as well as the exclusion of malignancy. We present a clinical case of a female diagnosed with an isolated hepatic sarcoidosis that simulated a unique hepatic metastatic lesion. The hepatic biopsy was diagnostic.

Cardiac sarcoidosis demonstrated by Tl-201 and Ga-67 SPECT imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taki, J.; Nakajima, K.; Bunko, H.

1990-09-01

Ga-67 and Tl-201 SPECT was performed to evaluate cardiac sarcoidosis in a 15-year-old boy. Tl-201 SPECT imaging showed decreased uptake in the inferior to lateral wall and Ga-67 accumulation in the area of decreased Tl-201 uptake. These findings suggested cardiac sarcoidosis, and cardiac biopsy confirmed this diagnosis. After corticosteroid therapy, myocardial uptake of Ga-67 disappeared and myocardial TI-201 uptake became more homogeneous.

Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis.

PubMed

Crouser, Elliott D; Ruden, Emily; Julian, Mark W; Raman, Subha V

2016-08-01

Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0±5.5 vs 59.2±6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy. Copyright © 2016 American Federation for Medical Research.

Extrapulmonary localization of gallium in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rohatgi, P.K.; Singh, R.; Vieras, F.

1987-01-01

This paper describes the spectrum of extrapulmonary localization of gallium in patients with sarcoidosis. The usefulness of Ga-67 scintiscans in detecting clinically occult lesions, in directing clinicians to accessible sites for biopsy, and in following the course of extrapulmonary sites of involvement with therapy is emphasized.

Early detection of cardiac involvement in sarcoidosis with 2-dimensional speckle-tracking echocardiography.

PubMed

Schouver, Elie-Dan; Moceri, Pamela; Doyen, Denis; Tieulie, Nathalie; Queyrel, Viviane; Baudouy, Delphine; Cerboni, Pierre; Gibelin, Pierre; Leroy, Sylvie; Fuzibet, Jean-Gabriel; Ferrari, Emile

2017-01-15

Cardiac sarcoidosis (CS) is associated with high morbidity and sudden death. The absence of specific symptoms and lack of diagnostic gold standard technique is challenging. New imaging methods could improve the diagnosis of CS. The aim of our study was to assess the role of left ventricular (LV) longitudinal and circumferential strain as estimated by 2D speckle-tracking imaging in patients with diagnosed sarcoidosis without cardiac involvement according to the current guidelines. We investigated the prevalence of LV strain impairment in this population and assessed its relationship with clinical outcomes, composite of mortality, heart failure, arrhythmia and/or secondarily development of CS and cardiac device implantation. We performed a prospective case-control longitudinal study including 35 patients with diagnosed sarcoidosis and normal cardiac function as assessed by standard transthoracic echocardiography and 35 healthy age- and gender-matched controls. All patients underwent a comprehensive echocardiographic study. Mean age of patients was 47.9±14.8years old (22 women). Compared with controls, global LV longitudinal strain (LV GLS) was reduced in sarcoidosis patients: (-17.2±3.1 vs -21.3±1.5%, p<0.0001). Circumferential LV strain was preserved in patients compared to controls (-19.9±-4.3% vs -21.3±1.5%, p=0.12). Impaired LV GLS was significantly associated with clinical outcomes (HR 1.56; [1.16-2.11], p<0.01) on univariate analysis. Speckle-tracking echocardiography revealed decreased longitudinal LV strain in sarcoidosis patients that was associated with outcomes. LV GLS may represent an early marker of myocardial involvement in sarcoidosis patients that needs to be studied further. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sarcoidosis in Israel: Clinical Outcome Status, Organ Involvement, and Long-Term Follow-Up.

PubMed

Markevitz, Natalia; Epstein Shochet, Gali; Levi, Yair; Israeli-Shani, Lilach; Shitrit, David

2017-08-01

Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology with heterogeneous outcomes. This study reviewed the clinical outcome status (COS) and organ involvement of Israeli sarcoidosis patients during a five-year period. Further, we compared our results to the 'World Association of Sarcoidosis and Other Granulomatous Disease' (WASOG) COS and the 'A Case Control Etiologic Study of Sarcoidosis' (ACCESS) instruments in order to evaluate their relevance to the Israeli population. The retrospective study group consisted of 166 sarcoidosis patients for the period of 2010-2015. Data on demographic characteristics, presenting symptoms, co-morbidities, disease duration, lung function tests, treatment program, chest X-ray, and chest high-resolution computed tomography were collected. The median patient age was 62 ± 14, which was significantly higher than the WASOG and ACCESS cohorts (p < 0.0001), and the average disease duration was 9.8 ± 7.5 years. Resembling the ACCESS cohort, most patients were women (67.5%). The majority of patients suffered from constitutional symptoms (86%), as well as from respiratory symptoms (38.5%). Similarly to the ACCESS cohort, 91% of patients presented with lung involvement. However, significant differences in the involvement of other organs were noted, including lymph nodes (3 vs. 15.2%), liver (3.6 vs. 11.5%), CNS (7.2 vs. 4.6%), and joints (3.6 vs. 0.5%). In addition, significant differences were observed in the COS of the Israeli population in comparison to the WASOG data (p < 0.01). Sarcoidosis in Israel is a unique and challenging disease with its clinical presentations that differ from previously reported studies.

Efficacy and safety of infliximab biosimilar Inflectra® in severe sarcoidosis.

PubMed

Schimmelpennink, Milou C; Vorselaars, Adriane D M; van Beek, Frouke T; Crommelin, Heleen A; Deneer, Vera H M; Keijsers, Ruth G M; Veltkamp, Marcel

2018-05-01

Infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α) is effective third-line therapy in severe sarcoidosis. The originator product of Infliximab, Remicade ® , is expensive, limiting universal access. Recently, a less expensive biosimilar of infliximab, Inflectra ® , has become available, but the efficacy and tolerability has not been studied in sarcoidosis. In this retrospective cohort study, 29 patients treated with the infliximab biosimilar Inflectra ® , were analysed. Patients received Inflectra ® intravenously monthly at a dose of 5 mg/kg. We measured trough levels before every infusion. Before and after 6 months of induction therapy pulmonary function and disease activity were evaluated using Standardised Uptake Value (SUV) of the 18 F-fluorodeoxyglucose by positron emission tomography ( 18 F-FDG PET), soluble interleukin-2 receptor (sIL-2R), angiotensin converting enzyme (ACE) and health-related quality of life (HRQOL). In patients with pulmonary sarcoidosis as main treatment indication (n = 15) the predicted FVC improved with 8.1%, p < 0.05. Furthermore, in the whole group HRQoL improved significantly (p < 0.001), whereas SUVmax and sIL-2R significantly reduced (p < 0.001 and p = 0.001 respectively). Hospitalisation due to infections occurred in four patients. None of the patients discontinued Inflectra ® due to side-effects. Furthermore, all patients had detectable trough levels indicating development of neutralizing antibodies. Infliximab biosimilar Inflectra ® seems effective in the treatment of refractory sarcoidosis with a comparable safety profile to the reference product Remicade ® . Inflectra ® can be considered as an alternative and less expensive option for patients with refractory sarcoidosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Solitary nodular sarcoidosis demonstrating reversed tuberculin skin reaction].

PubMed

Osoreda, Hisayuki; Kobayashi, Hideo; Kanoh, Soichiro; Motoyoshi, Kazuo

2008-08-01

A 29-year-old woman was admitted because of chest radiograph abnormality. She had no respiratory complaints. Chest CT demonstrated an ill-defined nodule of 20mm with the "sarcoid galaxy sign" in the right upper lobe. Transbronchial biopsy (TBB) specimens from right S2 revealed non-caseating epithelioid cell granuloma. Initial clinical findings suggested mycobacterial infection. However, while waiting for the results of mycobacterial cultures in bronchial washing fluid, the tuberculin skin reaction was found to be negative, and enlargement of nodule, mediastinal lymphadenopathy and elevated soluble IL-2R were observed. Cultures for mycobacterium were negative and repeat TBB specimens revealed granulomatous inflammation. We diagnosed with sarcoidosis based on these findings. Solitary nodular sarcoidosis is rare with only 17 cases having been reported. These cases were diagnosed with difficulty because of non-specific clinical findings and of the 17, 16 cases (94%) were diagnosed by surgical procedures. We observed the clinico-radiological course of solitary nodules and the change in tuberculin reaction. Although a negative tuberculin skin reaction was commonly recognized in sarcoidosis patients, we confirmed that initial positive tuberculin reaction changed to negative according to disease progress. To the best of our knowledge, this is the first case report in adults.

Sarcoidosis with Pancreatic Mass, Endobronchial Nodules, and Miliary Opacities in the Lung.

PubMed

Matsuura, Shun; Mochizuka, Yasutaka; Oishi, Kyohei; Miyashita, Koichi; Naoi, Hyogo; Mochizuki, Eisuke; Mikura, Shinichiro; Tsukui, Masaru; Koshimizu, Naoki; Ohata, Akihiko; Suda, Takahumi

2017-11-15

Sarcoidosis affects multiple organs and rarely has unusual manifestations. A 78-year-old woman was referred to our hospital for coughing symptoms. A chest computed tomography (CT) scan revealed bilateral diffuse miliary patterns and right pleural effusion. Bronchoscopy showed multiple nodules in the carina and the bronchus intermedius. A CT scan of her abdomen revealed hypovascular lesions involving the pancreatic head and body. A transbronchial lung biopsy, bronchial mucosal biopsy, and endoscopic ultrasound-guided fine-needle aspiration of the pancreatic mass demonstrated non-caseating granulomas. We diagnosed the patient with sarcoidosis. She received no treatment for sarcoidosis and has been followed up for one year, during which no pulmonary disease progression had been observed and the pancreatic masses partially regressed.

Parotid gland biopsy and /sup 67/Ga imaging correlation in systemic sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brantley, S.D.; Orzel, J.A.; Weiland, F.L.

1987-03-01

We correlated the results of parotid gland biopsy, chest roentgenograms, and gallium citrate scintigraphy in 24 patients evaluated for possible systemic sarcoidosis. Of 19 patients ultimately proven to have sarcoidosis, 11 (57.9 percent) had positive parotid gland biopsy. The yield of parotid gland biopsy in patients with abnormal gallium parotid activity was only marginally higher (64.7 percent). Abnormal parotid gland uptake of gallium citrate was seen in 17 of these 19 patients (89.5 percent) and was always associated with abnormal lung or perihilar activity. The parotid gland biopsy is a useful technique for obtaining the tissue diagnosis of sarcoidosis; however,more » gallium scintigraphy should not be performed to select patients as this will only marginally increase the biopsy yield.« less

Clinical significance of the "galaxy sign" in patients with pulmonary sarcoidosis in a Japanese single-center cohort.

PubMed

Koide, Takashi; Saraya, Takeshi; Tsukahara, Yayoi; Bonella, Francesco; Börner, Eda; Ishida, Manabu; Ogawa, Yukari; Hirukawa, Ichiro; Oda, Miku; Shimoda, Masafumi; Ohkuma, Kosuke; Fujiwara, Masachika; Takata, Saori; Yokoyama, Takuma; Kurai, Daisuke; Ishii, Haruyuki; Goto, Hajime; Takizawa, Hajime

2016-10-07

The galaxy sign is an irregularly marginated pulmonary nodule formed by a confluence of multiple small nodules, and it is a diagnostic radiological finding for pulmonary sarcoidosis. However, the clinical significance of the galaxy sign for sarcoidosis has been poorly investigated. This study aimed to investigate the clinical significance and detailed radiological features of the galaxy sign in patients with pulmonary sarcoidosis. We retrospectively reviewed 87 patients with biopsy-proven sarcoidosis and 108 patients with pulmonary tuberculosis. Galaxy sign incidence was assessed on thoracic high-resolution computed tomography (HRCT) images from each group. Correlations of galaxy sign with clinical characteristics and disease outcomes were evaluated for patients with sarcoidosis. HRCT findings were available for 65 of 87 patients with pulmonary sarcoidosis and all 108 patients with pulmonary tuberculosis. Galaxy sign incidence was significantly higher in patients with pulmonary sarcoidosis (n=15, 23.1%) than in those with pulmonary tuberculosis (n=2, 1.9%, p<0.001). Among the 65 patients with pulmonary sarcoidosis, those with galaxy signs (n=15) were significantly younger (median: 32 years, interquartile range [IQR] 28-38 years) than those without (n=50) (median: 62 years, IQR 37.7-73 years). The CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) was also significantly lower in the former group (median: 2.6, IQR 2.0-3.9 vs. median 5.8, IQR 3.7-8.6, p<0.001). Galaxy signs are associated with younger age and low BALF CD4/CD8 ratio but not disease severity.

Tumoral calcinosis associated with sarcoidosis and positive bone and gallium imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolpe, F.M.; Khedkar, N.Y.; Gordon, D.

1987-07-01

A 63-year-old female with biopsy proven tumoral calcinosis presented with progressive and recurrent swelling and tenderness of the right hip, thigh, elbow, and wrist. Both gallium and bone imaging demonstrated intense, congruent uptake in these areas. This is the third case of tumoral calcinosis with sarcoidosis documented in the literature. However, these are the first published bone and gallium scans in a patient with a history of sarcoidosis and tumoral calcinosis.

Is there any association between Sarcoidosis and infectious agents?: a systematic review and meta-analysis.

PubMed

Esteves, Tiago; Aparicio, Gloria; Garcia-Patos, Vicente

2016-11-28

During the last few years, investigators have debated the role that infectious agents may have in sarcoidosis pathogenesis. With the emergence of new molecular biology techniques, several studies have been conducted; therefore, we performed a meta-analysis in order to better explain this possible association. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the Cochrane collaboration guidelines. Four different databases (Medline, Scopus, Web of Science, and Cochrane Collaboration) were searched for all original articles published from 1980 to 2015. The present meta-analysis included case-control studies that reported the presence of microorganisms in samples of patients with sarcoidosis using culture methods or molecular biology techniques. We used a random effects or a fixed-effect model to calculate the odds ratio (OR) and 95% confidence intervals (CI). Sensitivity and subgroup analyses were performed in order to explore the heterogeneity among studies. Fifty-eight studies qualified for the purpose of this analysis. The present meta-analysis, the first, to our knowledge, in evaluation of all infectious agents proposed to be associated with sarcoidosis and involving more than 6000 patients in several countries, suggests an etiological link between Propionibacterium acnes and sarcoidosis, with an OR of 18.80 (95% CI 12.62, 28.01). We also found a significant association between sarcoidosis and mycobacteria, with an OR of 6.8 (95% CI 3.73, 12.39). Borrelia (OR 4.82; 95% CI 0.98, 23.81), HHV-8 (OR 1.47; 95% CI 0.02, 110.06) as well as Rickettsia helvetica, Chlamydia pneumoniae, Epstein-barr virus and Retrovirus, although suggested by previous investigations, were not associated with sarcoidosis. This meta-analysis suggests that some infectious agents can be associated with sarcoidosis. What seems clear is that more than one infectious agent might be implicated in the

Association between ACE gene I/D polymorphism and clinical presentation and prognosis of sarcoidosis.

PubMed

Alía, P; Mañá, J; Capdevila, O; Alvarez, A; Navarro, M A

2005-01-01

Serum angiotensin converting enzyme (SACE) concentration is considered a marker of sarcoidosis activity. This concentration is influenced by an insertion/deletion (I/D) polymorphism of the ACE gene, such that SACE levels follow the pattern DD>ID>II. The aim of our work was to study the relationship between I/D polymorphism and susceptibility to sarcoidosis, as well as the relation between this polymorphism and the clinical presentation and evolution of the disease in 177 sarcoidosis patients. A group of 104 individuals without sarcoidosis was included as control. Genotyping was done by a polymerase chain reaction (PCR) method, and SACE concentration at diagnosis was determined by a kinetic method. No differences were observed in genotype or allele distributions between patients and controls, nor between patients considering the type of presentation (Löfgren versus non-Löfgren) and evolution of the disease (acute versus chronic). As reported for healthy populations, SACE concentrations followed the pattern DD>ID>II in sarcoidosis patients, but significant differences between genotypes existed only in the Löfgren group (p = 0.003) and in acute patients (p = 0.02). SACE concentrations at diagnosis were lower in acute patients (p = 0.05) and in Löfgren's syndrome (p = 0.04), but this seemed to occur only in ID individuals (p = 0.02 and p = 0.01, respectively). No relation was thus found between I/D polymorphism and susceptibility to sarcoidosis, but ACE I/D genotyping may improve the assessment of disease activity, both at diagnosis and during the follow-up of treated and untreated patients.

White donor, younger donor and double lung transplant are associated with better survival in sarcoidosis patients.

PubMed

Salamo, Oriana; Roghaee, Shiva; Schweitzer, Michael D; Mantero, Alejandro; Shafazand, Shirin; Campos, Michael; Mirsaeidi, Mehdi

2018-05-03

Sarcoidosis commonly affects the lung. Lung transplantation (LT) is required when there is a severe and refractory involvement. We compared post-transplant survival rates of sarcoidosis patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). We also explored whether the race and age of the donor, and double lung transplant have any effect on the survival in the post transplant setting. We analyzed 9,727 adult patients with sarcoidosis, COPD, and IPF who underwent LT worldwide between 2005-2015 based on United Network for Organ Sharing (UNOS) database. Survival rates were compared with Kaplan-Meier, and risk factors were investigated by Cox-regression analysis. 469 (5%) were transplanted because of sarcoidosis, 3,688 (38%) for COPD and 5,570 (57%) for IPF. Unadjusted survival analysis showed a better post-transplant survival rate for patients with sarcoidosis (p < 0.001, Log-rank test). In Cox-regression analysis, double lung transplant and white race of the lung donor showed to have a significant survival advantage. Since double lung transplant, those who are younger and have lower Lung Allocation Score (LAS) at the time of transplant have a survival advantage, we suggest double lung transplant as the procedure of choice, especially in younger sarcoidosis subjects and with lower LAS scores.

Somatostatin receptor scintigraphy in sarcoidosis: relation to selected clinical and laboratory markers.

PubMed

Piotrowski, Wojciech J; Bieńkiewicz, Małgorzata; Frieske, Izabella; Marczak, Jerzy; Antczak, Adam; Górski, Paweł; Kuśmierek, Jacek; Płachcińska, Anna

2012-01-01

Discriminating between active and inactive sarcoidosis may be problematic in everyday clinical practice. There are numerous biochemical markers used in the diagnosis and monitoring of sarcoidosis. Somatostatin receptor (SR) scintigraphy with the use of 99mTc-octreotide may be used to estimate disease activity. The aim of the paper was to assess the value of traditional biomarkers (serum angiotensin-converting enzyme [SACE], C-reactive protein, markers of calcium metabolism, bronchoalveolar lavage fluid [BALF] lymphocytes) and a novel biomarker, 8-isoprostane (8-IP) in exhaled breath condensate (EBC), in the assessment of sarcoidosis activity in relation to somatostatin receptor scintigraphy. The study included 32 patients with sarcoidosis. Scintigraphy was performed using somatostatin analogue, 99mTc-HYNIC-TOC; planar and SPECT/CT images were recorded. The study group was divided into a subgroup with positive radiotracer uptake (n = 20) and without a visible uptake (n = 12). 8-IP levels were measured in EBC by an immunoenzymatic assay. RESULTS We observed a significantly higher EBC 8-IP levels in the subgroup with positive uptake compared with those with negative uptake (19.1 ± 19.8 vs. 5.4 ± 3.5 pg/ml, P = 0.02). The levels of SACE and the percentage of BALF lymphocytes were also nonsignificantly elevated. In the group of patients with positive scintigraphy results, a positive correlation was observed between the uptake ratio and SACE (r = 0.44, P = 0.041). The results indicate low value of biochemical markers in the assessment of disease activity. SR scintigraphy may have practical usefulness in the monitoring of sarcoidosis.

SPECT imaging with Tl-201 and Ga-67 in myocardial sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurata, C.; Sakata, K.; Taguchi, T.

1990-06-01

Two patients with myocardial sarcoidosis are presented, both of whom underwent SPECT imaging with Tl-201 and Ga-67. The first had Ga-67 myocardial uptake with a Tl-201 defect, which disappeared with corticosteroid therapy. The second had multiple Tl-201 defects without Ga-67 uptake, which persisted despite corticosteroid therapy. Therefore, the combination of Tl-201 and Ga-67 imaging may be useful for recognizing myocardial sarcoidosis and for predicting the response to corticosteroid therapy.

Sarcoidosis of the lacrimal gland as a first manifestation.

PubMed

Peralta-Gómez, M Y; Ávila-Ocampo, K A; Huerta-Velázquez, S; Rivera-Salgado, M I

2018-04-01

The first manifestation of sarcoidosis is usually at the pulmonary level. The case is described of a 40-year-old female patient, who presented with an increased volume of the lacrimal gland and mechanical ptosis of upper left eyelid as the first expression of this disease. The diagnosis of systemic sarcoidosis with primary presentation of the lacrimal gland was made after performing several immunological studies with negative results, imaging studies, and taking of glandular and lymph node biopsies. A favourable response was achieved with oral methotrexate treatment. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

F-18 sodium fluoride PET/CT does not effectively image myocardial inflammation due to suspected cardiac sarcoidosis.

PubMed

Weinberg, Richard L; Morgenstern, Rachelle; DeLuca, Albert; Chen, Jennifer; Bokhari, Sabahat

2017-12-01

Sarcoidosis is an inflammatory disorder of unknown etiology that can involve the heart. While effective in imaging cardiac sarcoidosis, F-18 fluorodeoxyglucose (FDG) PET/CT often shows non-specific myocardial uptake. F-18 sodium fluoride (NaF) has been used to image inflammation in coronary artery plaques and has low background myocardial uptake. Here, we evaluated whether F-18 NaF can image myocardial inflammation due to clinically suspected cardiac sarcoidosis. We performed a single institution pilot study testing if F-18 NaF PET/CT can detect myocardial inflammation in patients with suspected cardiac sarcoidosis. Patients underwent cardiac PET/CT with F-18 FDG as part of their routine care and subsequently received an F-18 NaF PET/CT scan. Three patients underwent F-18 FDG and F-18 NaF imaging. In all patients, there was F-18 FDG uptake consistent with cardiac sarcoidosis. The F-18 NaF PET/CT scans showed no myocardial uptake. In this small preliminary study, PET/CT scan using F-18 NaF does not appear to detect myocardial inflammation caused by suspected cardiac sarcoidosis.

Microbial and human heat shock proteins as 'danger signals' in sarcoidosis.

PubMed

Dubaniewicz, Anna

2013-12-01

In the light of the Matzinger's model of immune response, human heat shock proteins (HSPs) as main 'danger signals' (tissue damage-associated molecular patterns-DAMPs) or/and microbial HSPs as pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid granuloma by both infectious and non-infectious factors in genetically different predisposed host. Regarding infectious causes of sarcoid models, low-virulence strains of, e.g. mycobacteria and propionibacteria recognized through changed PRR and persisting in altered host phagocytes, generate increased release of both human and microbial HSPs with their molecular and functional homology. High chronic spread of human and microbial HSPs altering cytokines, co-stimulatory molecules, and Tregs expression, apoptosis, oxidative stress, induces the autoimmunity, considered in sarcoidosis. Regarding non-infectious causes of sarcoidosis, human HSPs may be released at high levels during chronic low-grade exposure to misfolding amyloid precursor protein in stressed cells, phagocyted metal fumes, pigments with/without aluminum in tattoos, and due to heat shock in firefighters. Therefore, human HSPs as DAMPs and/or microbial HSPs as PAMPs produced as a result of non-infectious and infectious factors may induce different models of sarcoidosis, depending on the genetic background of the host. The number/expression of PRRs/ligands may influence the occurrence of sarcoidosis in particular organs. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

The Roles of T Helper 1, T Helper 17 and Regulatory T Cells in the Pathogenesis of Sarcoidosis.

PubMed

Mortaz, Esmaeil; Rezayat, Fatemeh; Amani, Davar; Kiani, Arda; Garssen, Johan; Adcock, Ian M; Velayati, Aliakbar

2016-08-01

Sarcoidosis is a systemic granulomatous disorder of unidentified etiology, with a heterogeneous clinical presentation. It is characterized by a reduced delayed-type hypersensitivity to tuberculin and common antigens. The balance between Th1, Th17 and Regulatory T(Treg) cells controls T-cell proliferation and activation.The Th17/Treg ratio in the peripheral blood and bronchoalveolar lavage fluidis increased in patients with active sarcoidosis. Amplified IL-17A expression in granulomas and the presence of IL-17A+, IL-17A+IL-4+ and IL-17A+IFN-γ+ memory T helper cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction and/or maintenance in sarcoidosis. Sarcoidosis should therefore be considered as a Th1/Th17 multisystem disorder and anti-IL-17/Th17 approaches that control and reduce IL-17Amay be an option, therefore, for the treatment of sarcoidosis.Here we provide a short overview as to the role of Th17 cells as critical cells in the pathogenesis of sarcoidosis.

Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis.

PubMed

Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta

2016-09-01

In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded.

Histopathologic aid to diagnosis of sarcoidosis: report of 8 cases.

PubMed

Manonukul, Jane; Wanitphakdeedecha, Rungsima; Wisuthsarewong, Wanee; Thirapote, Panitta

2006-06-01

Sarcoidosis is a multisystemic disease of unknown etiology. The disease is common in blacks and is very rare in Thailand. It presents as one of the most variable manifestations usually affecting the lungs and intrathoracic lymph nodes. Other organs such as liver, spleen, joints and eyes including skin are also involved The common cutaneous lesions are maculopapular, erythematous plaque, subcutaneous nodule, scar and lupus pernio. No reliable indicator is useful for diagnosis except the histopathologic change which is the only way for approaching this disease. Sarcoidosis is the disease of exclusion. Various infections producing granulomas should be excluded histologically. The ultimate diagnosis requires clinical correlation, laboratory investigations, chest X-ray as well as available tissue culture. Herein, the authors reported eight cases of sarcoidosis by retrospective study primarily diagnosed by histopathological findings at Siriraj Hospital from January, 1997 to December, 2004 with many different clinical presentations. Despite the diverse clinical pictures, interestingly, the presented patients almost had the same histopathologic findings as small, uniform, discrete naked granulomas usually without necrosis. These findings act as a hallmark for diagnosis of this disease.

Right ventricular sarcoidosis: is it time for updated diagnostic criteria?

PubMed

Vakil, Kairav; Minami, Elina; Fishbein, Daniel P

2014-04-01

A 55-year-old woman with a history of complete heart block, atrial flutter, and progressive right ventricular failure was referred to our tertiary care center to be evaluated for cardiac transplantation. The patient's clinical course included worsening right ventricular dysfunction for 3 years before the current evaluation. Our clinical findings raised concerns about arrhythmogenic right ventricular cardiomyopathy. Noninvasive imaging, including a positron emission tomographic scan, did not reveal obvious myocardial pathologic conditions. Given the end-stage nature of the patient's right ventricular failure and her dependence on inotropic agents, she underwent urgent listing and subsequent heart transplantation. Pathologic examination of the explanted heart revealed isolated right ventricular sarcoidosis with replacement fibrosis. Biopsy samples of the cardiac allograft 6 months after transplantation showed no recurrence of sarcoidosis. This atypical presentation of isolated cardiac sarcoidosis posed a considerable diagnostic challenge. In addition to discussing the patient's case, we review the relevant medical literature and discuss the need for updated differential diagnostic criteria for end-stage right ventricular failure that mimics arrhythmogenic right ventricular cardiomyopathy.

Activated alveolar macrophage and lymphocyte alveolitis in extrathoracic sarcoidosis without radiological mediastinopulmonary involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallaert, B.; Ramon, P.; Fournier, E.C.

1986-01-01

Cellular characteristics of BAL were investigated in 18 patients with proved extrathoracic sarcoidosis (that is, sarcoidosis that affected the skin, eyes, parotid glands, stomach, nose, kidneys, or meninges) without clinical or radiological mediastinopulmonary involvement. Computed tomography of the thorax was performed on five patients: four patients were normal, and one had enlarged lymph nodes (these enlargements were not detectable on the patient's chest roentgenogram). The results of pulmonary function tests were normal in all patients. The total BAL cell count did not differ significantly between controls and patients. Abnormal percentages of alveolar lymphocytes (from 18 to 87%) were noted inmore » 15 out of 18 patients. SACE levels were normal in 15 patients. No pulmonary gallium uptake was detected. The chemiluminescence of AM's, whether spontaneous or PMA induced, was increased in five out of seven patients. The percentages of T3+ lymphocytes in sarcoidosis patients did not significantly differ from those in controls. The T4+:T8+ ratio was normal in four patients and slightly increased in one. Follow-up of patients showed that alveolar lymphocytosis is as lasting as extrathoracic involvement. Our data demonstrate increased percentages of lymphocytes and activated AM's in the BAL of patients with extrathoracic sarcoidosis. This may be due to the initial involvement of the respiratory tract in extrathoracic sarcoidosis or to the diffusion of activated macrophages and lymphocytes from an extrathoracic site into the lung.« less

Sarcoidosis in an Italian province. Prevalence and environmental risk factors

PubMed Central

Beghè, Deborah; Dall’Asta, Luca; Garavelli, Claudia; Pastorelli, Augusto Alberto; Muscarella, Marilena; Saccani, Gloria; Aiello, Marina; Corradi, Massimo; Stacchini, Paolo; Chetta, Alfredo; Bertorelli, Giuseppina

2017-01-01

Background and aim Sarcoidosis is a systemic granulomatous inflammatory disease whose causes are still unknown and for which epidemiological data are often discordant. The aim of our study is to investigate prevalence and spatial distribution of cases, and identify environmental exposures associated with sarcoidosis in an Italian province. Methods After georeferentiation of cases, the area under study was subdivided with respect to Municipality and Health Districts and to the altitude in order to identify zonal differences in prevalence. The bioaccumulation levels of 12 metals in lichen tissues were analyzed, in order to determine sources of air pollution. Finally, the analysis of the correlation between metals and between pickup stations was performed. Results 223 patients were identified (58.3% female and 41.7% male of total) and the mean age was 50.6±15.4 years (53.5±15.5 years for the females and 46.5±14.4 for the males). The mean prevalence was 49 per 100.000 individuals. However, we observed very heterogeneous prevalence in the area under study. The correlations among metals revealed different deposition patterns in lowland area respect to hilly and mountain areas. Conclusions The study highlights a high prevalence of sarcoidosis cases, characterized by a very inhomogeneous and patchy distribution with phenomena of local aggregation. Moreover, the bioaccumulation analysis was an effective method to identify the mineral particles that mostly contribute to air pollution in the different areas, but it was not sufficient to establish a clear correlation between the onset of sarcoidosis and environmental risk factors. PMID:28475583

A case of acute kidney injury caused by granulomatous interstitial nephritis associated with sarcoidosis.

PubMed

Horino, Taro; Matsumoto, Tatsuki; Inoue, Kosuke; Ichii, Osamu; Terada, Yoshio

2018-05-01

Sarcoidosis affects multiple organs including lung, heart and kidney. Sarcoidosis causes hypercalcemia, hypergammaglobulinemia, and rarely, granulomatous interstitial nephritis, resulting in renal stromal damage. Granulomatous interstitial nephritis is characterized as interstitial nephritis with noncaseating epithelioid granulomas. Diagnosing granulomatous interstitial nephritis before patient's death is challenging; hence, only few cases proven by renal biopsy have been reported till date. We present a case of acute kidney injury caused by granulomatous interstitial nephritis as a renal manifestation of sarcoidosis proven by renal biopsy, which can be confirmed by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Glucocorticoid therapy was helpful for improving and maintaining her renal function over a 6-year period.

Certolizumab Pegol-Induced Folliculitis-Like Lichenoid Sarcoidosis in a Patient with Rheumatoid Arthritis

PubMed Central

Sakai, Hiroyuki; Nomura, Wakana; Sugawara, Motoshi

2017-01-01

Anti-tumor necrosis factor α (TNF-α) biologic agents are used for treating refractory sarcoidosis. However, sarcoidosis-like epithelioid cell granulomas may develop during anti-TNF-α treatment. A 63-year-old man suffering from rheumatoid arthritis was treated with oral methotrexate and methylprednisolone for 4 years. He subsequently started biweekly subcutaneous injections of certolizumab pegol. Three months later, light red follicular papules developed on his chest and they spread over the trunk and bilateral upper arms. Histopathology of a lesion showed a sharply demarcated noncaseating epithelioid cell granuloma with multi-nucleated giant cells in the upper perifollicular area. The follicular papules subsided following discontinuation of certolizumab pegol. Folliculitis-like lichenoid sarcoidosis should be included among the adverse cutaneous reactions of anti-TNF-α treatment. PMID:29033821

Multi-organ sarcoidosis treatment with fumaric acid esters: a case report and review of the literature.

PubMed

Zouboulis, Christos C; Lippert, Undine; Karagiannidis, Ioannis

2014-01-01

Sarcoidosis is a rare, systemic disease that is characterized by the formation of granulomas in various organs, including the skin. As the etiology remains unknown, the treatment of sarcoidosis is challenging. We present a 47-year-old female patient with progressive, multi-organ sarcoidosis who had a complete clinical improvement of the skin lesions, a moderate reduction in pulmonary opacities on chest X-ray, a marked subjective improvement in general status and pulmonary efficiency and a marked reduction in serum angiotensin-converting enzyme and soluble interleukin-2 receptor after 6 months of therapy with fumaric acid esters. The present case and similar reports in the literature highlight the probable efficacy of fumaric acid esters in the treatment of sarcoidosis and other non-infectious, granulomatous diseases. © 2014 S. Karger AG, Basel.

Acute pleurisy in sarcoidosis.

PubMed Central

Gardiner, I T; Uff, J S

1978-01-01

A 47-year-old white man with sarcoidosis presented with a six-week history of acute painful pleurisy. On auscultation a loud pleural rub was heard at the left base together with bilateral basal crepitations. The chest radiograph showed hilar enlargement as well as diffuse lung shadowing. A lung biopsy showed the presence of numerous epithelioid and giant-cell granulomata, particularly subpleurally. A patchy interstitial pneumonia was also present. He was given a six-month course of prednisolone, and lung function returned to normal. Images PMID:644534

Bronchoalveolar Lavage Fluid Characteristics of Patients With Sarcoidosis and Nonsarcoidosis Interstitial Lung Diseases: Ten-Year Experience of a Single Center in Turkey

PubMed Central

Tanriverdi, Hakan; Erboy, Fatma; Altinsoy, Bulent; Uygur, Firat; Arasli, Mehmet; Ozel Tekin, Ishak; Tor, Muge Meltem; Atalay, Figen

2015-01-01

Background: Bronchoalveolar lavage (BAL) is a noninvasive and useful technique for evaluating interstitial lung diseases (ILDs). Flow cytometric analysis of BAL fluid reveals specific diagnostic information in some unusual ILDs, and helps to narrow down the possible causes of interstitial diseases in most patients with more common disorders. A high BAL CD4/CD8 ratio is highly specific for sarcoidosis but can also be seen in other ILDs. Objectives: In this retrospective, descriptive, cross-sectional study, we compared BAL fluid characteristics and clinical variables in patients with sarcoidosis and non-sarcoidosis ILDs in a large cohort. Patients and Methods: The study was conducted in a tertiary university hospital in Zonguldak, the biggest city of the western Black Sea region of Turkey. Between 2004 and 2014, all patients who underwent both fiberoptic bronchoscopy and BAL with a suspicion of ILD were included in the study, retrospectively. Patients were divided into two main groups: sarcoidosis and non-sarcoidosis ILDs. Non-sarcoidosis ILDs were further divided into subgroups: pneumoconiosis, tuberculosis (TB), collagen vascular diseases, idiopathic interstitial pneumonias, malignancies, and unclassified ILDs. The clinical data of patients, including age, gender, smoking status, pulmonary function tests, and BAL flow cytometric analysis results, were compared among groups. Results: In total, 261 patients (119 sarcoidosis and 142 non-sarcoidosis ILDs) were enrolled. The median (interquartile range) BAL CD4/CD8 ratio and lymphocyte fraction were significantly higher in sarcoidosis than in non-sarcoidosis ILDs: 3.88 (3.76) versus 0.88 (1.01), respectively, and 20.6 (28.3) versus 6.0 (13.7), respectively. T cell receptor γ delta, CD16+56+, CD103+, CD8+103+, and CD3+16+56+ cells were significantly lower in sarcoidosis than in non-sarcoidosis ILDs. The median BAL CD4/CD8 ratios were significantly higher in patients with TB (1.87, P = 0.01) and malignancies (1.69, P = 0

Severe infections in sarcoidosis: Incidence, predictors and long-term outcome in a cohort of 585 patients.

PubMed

Duréault, Amélie; Chapelon, Catherine; Biard, Lucie; Domont, Fanny; Savey, Léa; Bodaghi, Bahram; Pourcher, Valérie; Rigon, Matthieu Resche; Cacoub, Patrice; Saadoun, David

2017-12-01

Sarcoidosis is associated with cell-mediated immunodeficiency and treatment of symptomatic sarcoidosis usually includes systemic immunosuppressants. Data relative to incidence, prognosis factors, and outcome of infections are scarce.Retrospective cohort study of 585 patients with biopsy proven sarcoidosis in a tertiary referral specialist clinic, with a nested case-control analysis. Twenty nine patients (4.9%) with severe infections were compared to 116 controls subjects with sarcoidosis, matched according to their gender, ethnicity, age at diagnosis, and treatment with corticosteroids.After a median follow-up of 8 years [range; 1-46], 38 severe infections [mycobacterial infections (n = 14), fungal infections (n = 10), bacterial (n = 8), viral (n = 3) and parasitic (n = 1)] were observed in 30 patients. The incidence of severe infections was 0.71% persons-year (CI 95% 0.5-0.98) and 0.43% persons-year (CI 95% 0.27-0.66). Patients with severe infection were more frequently of male gender (60% vs 46%) and were more likely treated by ≥ 3 immunosuppressive agents (OR = 3.8, IC 95% [1.5-9.64], P = .005) and by cyclophosphamide (OR = 5.55, IC 95% [1.9-16.1], P = .002), and with neurological (OR = 3.36 CI 95% [1.37-8.25], P = .008), or cardiac (OR = 2.65 CI 95% [1.09-6.43], P = .031) involvement of the sarcoidosis, compared to the controls. Two patients died within the 6 months following infection, due to progressive multifocal leucoencephalopathy (n = 1), and of peritonitis (n = 1).Severe infections are observed in 5.1% of our patients with sarcoidosis after a median follow-up of 8 years. Risk factors for severe infections included neurological or cardiac involvement of sarcoidosis, the use of immunosuppressive agents and mainly cyclophosphamide.

Value of different bronchoscopic sampling techniques in diagnosis of sarcoidosis: a prospective study of 151 patients.

PubMed

Goyal, Abhishek; Gupta, Dheeraj; Agarwal, Ritesh; Bal, Amanjit; Nijhawan, Raje; Aggarwal, Ashutosh N

2014-07-01

The exact position of routine bronchoscopic sampling techniques in diagnostic workup of sarcoidosis is often debated. Herein, we ascertain the role of transbronchial needle aspiration (TBNA), endobronchial ultrasound-guided TBNA (EBUS-TBNA), transbronchial lung biopsy (TBLB), and endobronchial biopsy (EBB) in diagnosis of sarcoidosis. Consecutive patients with suspected sarcoidosis who underwent fiberoptic bronchoscopy were studied. TBLB, EBB, TBNA, or EBUS-TBNA was performed as indicated in a standardized manner. A diagnosis of sarcoidosis was established based on the finding of non-necrotizing granulomas or on clinical grounds at 6-month follow-up. Individual and cumulative yield of various procedures and their correlation with clinicoradiologic parameters was analyzed. Of the 164 patients studied, 151 were finally diagnosed as sarcoidosis. Granulomas were demonstrated in 127 (84.2%) patients. Diagnostic yield of TBLB, EBB, TBNA, and EBUS-TBNA was 68.7%, 49.6%, 22.43%, and 57.1%, respectively. Cumulative yields of various procedures were: EBB+TBLB 81.4%; TBLB+TBNA 73.7%; TBNA+EBB 62.9%; TBLB+EBB+TBNA 86.9%; and TBLB+EBB+EBUS-TBNA 86.4%. In those with visible mucosal abnormalities, TBLB+EBB conferred the highest diagnostic yield (92.8%). Clinical findings or radiologic stage had no impact on diagnostic yield. TBLB is an important tool in bronchoscopic diagnosis of sarcoidosis. If endobronchial abnormalities are seen during bronchoscopy, TBLB with EBB gives the best results otherwise TBLB combined with conventional TBNA and EBB or EBUS-TBNA are required to maximize the diagnostic yield.

Prognostic Value of Myocardial Scarring on CMR in Patients With Cardiac Sarcoidosis.

PubMed

Coleman, G Cameron; Shaw, Peter W; Balfour, Pelbreton C; Gonzalez, Jorge A; Kramer, Christopher M; Patel, Amit R; Salerno, Michael

2017-04-01

This study sought to perform a systematic review and meta-analysis to understand the prognostic value of myocardial scarring as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging in patients with known or suspected cardiac sarcoidosis. Although CMR is increasingly used for the diagnosis of cardiac sarcoidosis, the prognostic value of CMR has been less well described in this population. PubMed, Cochrane CENTRAL, and metaRegister of Controlled Trials were searched for CMR studies with ≥1 year of prognostic data. Primary endpoints were all-cause mortality and a composite outcome of arrhythmogenic events (ventricular arrhythmia, implantable cardioverter-defibrillator shock, sudden cardiac death) plus all-cause mortality during follow-up. Summary effect estimates were generated with random-effects modeling. Ten studies were included, involving a total of 760 patients with a mean follow-up of 3.0 ± 1.1 years. Patients had a mean age of 53 years, 41% were male, 95.3% had known extracardiac sarcoidosis, and 21.6% had known cardiac sarcoidosis. The average ejection fraction was 57.8 ± 9.1%. Patients with LGE had higher odds for all-cause mortality (odds ratio [OR]: 3.06; p < 0.03) and higher odds of the composite outcome (OR: 10.74; p < 0.00001) than those without LGE. Patients with LGE had an increased annualized event rate of the composite outcome (11.9% vs. 1.1%; p < 0.0001). In patients with known or suspected cardiac sarcoidosis, the presence of LGE on CMR imaging is associated with increased odds of both all-cause mortality and arrhythmogenic events. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A rare presentation of pulmonary sarcoidosis as a solitary lung mass: a case report.

PubMed

Kelleher, Dylan W; Yaggi, Madeleine; Homer, Robert; Herzog, Erica L; Ryu, Changwan

2018-04-13

Sarcoidosis is a multisystem, chronic granulomatous disease of unknown etiology that predominantly affects the lungs. Pulmonary sarcoidosis classically presents with constitutional symptoms and computed tomographic scan findings of bilateral, symmetric micronodules in a peribronchovascular distribution with upper and middle lung zone predominance accompanied by bilateral, symmetric hilar lymphadenopathy. A solitary lung mass is a rare finding for pulmonary sarcoidosis, and with its associated constitutional symptoms, it strongly mimics a malignancy. We aimed to provide further insight into the broad differential diagnosis of a lung mass by describing our experiences in the care of a patient who presented with clinical and radiographic features of lung cancer who was ultimately found to have an atypical manifestation of stage II pulmonary sarcoidosis. A 44-year-old African American woman with a history of childhood asthma and type 2 diabetes mellitus presented with shortness of breath. After being treated for a presumed asthma exacerbation with prednisone, she experienced worsening dyspnea, night sweats, and unintentional weight loss. Further evaluation revealed a large left lower lobe mass and hilar lymphadenopathy. A computed tomography-guided biopsy of the lung mass revealed a multifocal non-necrotizing granuloma with multinucleated giant cells. Although consistent with sarcoidosis, this finding could represent a sarcoid-like reaction secondary to an occult malignancy. A more extensive repeat biopsy via bronchoscopy and mediastinoscopy revealed granulomatous inflammation without evidence of malignancy or infection. These procedures confirmed the diagnosis of pulmonary sarcoidosis, and she was started on treatment with high-dose prednisone. Her treatment course was complicated by hyperglycemia necessitating insulin therapy, but after 3 months of therapy, she reported improvement in her dyspnea, and repeat imaging revealed a significant decrease in the size of the

Assessment of gallium-67 scanning in pulmonary and extrapulmonary sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Israel, H.L.; Gushue, G.F.; Park, C.H.

1986-01-01

Gallium-67 scans have been widely employed in patients with sarcoidosis as a means of indicating alveolitis and the need for corticosteroid therapy. Observation of 32 patients followed 3 or more years after gallium scans showed no correlation between findings and later course: of 10 patients with pulmonary uptake, 7 recovered with minor residuals; of 18 patients with mediastinal of extrathoracic uptake, 10 had persistent or progressive disease; of 4 patients with negative initial scans, 2 had later progression. The value of gallium-67 scans as an aid to diagnosis was studied in 40 patients with extrapulmonary sarcoidosis. In 12 patients, abnormalmore » lacrimal, nodal, or pulmonary uptake aided in selection of biopsy sites. Gallium-67 scans and serum ACE levels were compared in 97 patients as indices of clinical activity. Abnormal gallium-67 uptake was observed in 96.3% of the tests in active disease, and ACE level elevation occurred in 56.3%. In 24 patients with inactive or recovered disease, abnormal gallium-67 uptake occurred in 62.5% and ACE level elevation in 37.5%. Gallium-67 scans have a limited but valuable role in the diagnosis and management of sarcoidosis.« less

[Sudden cardiac death due to sarcoidosis. Case report].

PubMed

Sejben, István; Som, Zoltán; Cserni, Gábor

2017-07-01

Sarcoidosis is a systemic granulomatous disease of unknown aetiology, which is characterized by bilateral hilar lymphadenopathy and pulmonary disease. Clinically detected cardiac involvement occurs in 5% of sarcoid patients, although cardiac manifestations are discovered in 25% of the cases at autopsy. Sarcoid heart disease frequently causes atrioventricular block. The authors present the case of a 44-year-old man with bradycardia. On admission, second degree Mobitz II, then third degree atrioventricular block was diagnosed. Coronarography showed normal coronary arteries. 2.5 years following artificial Biotronik Entovis DR type pacemaker implantation, sudden cardiac death occurred. Autopsy revealed sarcoidosis with cardiac, pulmonary, splenic, renal and lymph node involvement. In case of young or middle-aged patients with atrioventricular block, it is best to search for other causes if the most common coronary origin can be excluded. Orv Hetil. 2017; 158(27): 1067-1070.

Ga-67 uptake in the lung in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, D.G.; Johnson, S.M.; Harris, C.C.

1984-02-01

Images were obtained with Ga-67 and bronchopulmonary lavage performed in 21 patients with sarcoidosis (31 studies). The Ga-67 index, a semiquantitative criterion, was compared to a quantitative computer index based on lung:liver activity ratios; accuracy in predicting active alveolitis (defined by lavage lymphocyte counts) was assessed and differences between 24- and 48-hour studies examined. Computer activity ratios correlated well with the Ga-67 index, which had a sensitivity of 64%, specificity of 71%, 82%, and 77%, respectively, for the computer scores. Scores at 24 and 48 hours were similar. These results suggest that (a) Ga-67 scanning is useful in staging activitymore » in pulmonary sarcoidosis, (b) quantitative computer scores are accurate in predicting disease activity, and (c) scanning can be performed 24 or 48 hours after injection.« less

Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013-supplementary presentation.

PubMed

Ungprasert, P; Crowson, C S; Matteson, E L

2018-05-01

Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age- and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with a hazard ratio (HR) of 2.18.

The importance of histopathology in the diagnosis of isolated renal sarcoidosis: a case report.

PubMed

Trindade Filho, João Onofre; Amaro, Kaline Daniele de Souza; Oliveira, Allana Desirée Teixeira de; Gomes, Cecília Neta Alves Pegado; Costa, Hermann Ferreira; Trajano, Vinicius Nogueira

2018-06-18

Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the presence of non-caseating granulomas in several organs; renal impairment alone is a rare condition. When it affects the kidneys, the most prevalent manifestations are hypercalcemia and hypercalciuria. This paper aims to address the topic of renal sarcoidosis, by means of a case report, and reinstate the importance of histopathology in its diagnosis. The data came from an observational clinical study with a qualitative approach, through an interview with the renal sarcoidosis patient and data from her medical records. Patient D.M.S., 50 years old, Caucasian, presented with reddish eyes and body pains lasting for fifteen days as first manifestations of the disease. Upon kidney ultrasound scan, we found renal parenchymal nephropathy. Serial renal function and metabolic tests reported anemia and progressive urea and creatinine changes, as well as hypercalcemia and hypercalciuria, confirming acute kidney failure (AKF). A histopathological examination suggested the diagnosis, which was confirmed by clinical, laboratory and histopathological data. There was therapeutic resolution after steroid therapy. The symptomatology of sarcoidosis is diverse and often non-specific. Renal manifestation, which usually occurs after organ involvement, is present in less than 5% of patients, and about 1% to 2% of these patients may develop AKF. The use of histopathology together with clinical and laboratory data to diagnose isolated renal sarcoidosis, rule out other etiologies and introduce early treatment is of paramount importance.

Sarcoidosis of the cauda equina mimicking Guillain-Barré syndrome.

PubMed

Shah, Jagdish R; Lewis, Richard A

2003-04-15

Neurosarcoidosis is a great mimicker. It is often difficult to diagnose particularly when there is no prior history of systemic sarcoidosis. Although certain sites of the neuraxis are more commonly involved than others, any site of the central or peripheral nervous system can be affected. We report a case of sarcoidosis involving the cauda equina in a 38-year-old African American male without prior history of systemic disease. Initial clinical presentation was suggestive of Guillian-Barré syndrome, but the evaluation proved this case to be neurosarcoidosis involving the cauda equina. We have followed this patient for 8 years, and he remains clinically stable on prednisone 5 mg/day.

/sup 67/Ga-citrate uptake by the parotid glands in sarcoidosis. [Effectiveness for differential diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiener, S.N.; Patel, B.P.

1979-03-01

Bilateral accumulation of /sup 66/Ga-citrate by the parotid glands was observed in 9 of 27 patients (33%) with sarcoidosis and in a subgroup of 12 with systemic symptoms such as fever or clinically acute, progressive disease (75%). Asymptomatic patients or those with probable sarcoidosis associated with hilar and/or paratracheal adenopathy will not have parotid uptake. Similarly, uptake seldom occurs in normal patients or in those with untreated lymphoma or Hodgkin disease. If other inflammatory or granulomatous processes such as tuberculosis can be excluded, and if there is no history of head and neck irradiation, then this finding in acutely illmore » patients suggests sarcoidosis.« less

Cardiac Sarcoidosis Concomitant with Large-vessel Aortitis Detected by 18F-fluorodeoxyglucose Positron Emission Tomography.

PubMed

Higuchi, Yoshihiro; Kimoto, Yasutaka; Tanoue, Rika; Tokunou, Tomotake; Tomonari, Kenichiro; Maeda, Toyoki; Horiuchi, Takahiko

2018-06-01

We herein report a case of concurrent cardiac sarcoidosis and large-vessel aortitis detected by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and followed up during immunosuppressive therapy. After high-dose prednisolone administration (1 mg/kg), serial FDG-PET showed that almost all of the abnormal FDG uptake in the heart and extracardiac region, including the abdominal to bilateral iliac arteries, had been disappeared. During the tapering of prednisolone, additive methotrexate therapy was needed to treat the recurrence of cardiac sarcoidosis. FDG-PET is a useful tool for detecting cardiac sarcoidosis concomitant with large-vessel aortitis and monitoring the effectiveness of immunosuppressive therapy.

Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis

PubMed Central

Hawkins, Charlene; Shaginurova, Guzel; Shelton, D. Auriel; Herazo-Maya, Jose D.; Oswald-Richter, Kyra A.; Young, Anjuli; Celada, Lindsay J.; Kaminski, Naftali; Sevin, Carla

2017-01-01

Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis. We characterized sarcoidosis CD4+ T cell immune function in systemic and local environments among subjects undergoing disease progression compared to those experiencing disease resolution. Spontaneous and TCR-stimulated Th1 cytokine expression and proliferation assays were performed in 53 sarcoidosis subjects and 30 healthy controls. PD-1 expression and apoptosis were assessed by flow cytometry. Compared to healthy controls, sarcoidosis CD4+ T cells demonstrated reductions in Th1 cytokine expression, proliferative capacity (p < 0.05), enhanced apoptosis (p < 0.01), and increased PD-1 expression (p < 0.001). BAL-derived CD4+ T cells also demonstrated multiple facets of T cell exhaustion (p < 0.05). Reversal of CD4+ T cell exhaustion was observed in subjects undergoing spontaneous resolution (p < 0.05). Sarcoidosis CD4+ T cells exhibit loss of cellular function during progressive disease that follows the archetype of T cell exhaustion. PMID:29234685

Sarcoidosis: a state of the art review from the Thoracic Society of Australia and New Zealand.

PubMed

Ahmadzai, Hasib; Huang, Shuying; Steinfort, Chris; Markos, James; Allen, Roger Ka; Wakefield, Denis; Wilsher, Margaret; Thomas, Paul S

2018-06-18

Sarcoidosis is a systemic disease of unknown aetiology, characterised by non-caseating granulomatous inflammation. It most commonly manifests in the lungs and intrathoracic lymph nodes but can affect any organ. This summary of an educational resource provided by the Thoracic Society of Australia and New Zealand outlines the current understanding of sarcoidosis and highlights the need for further research. Our knowledge of the aetiology and immunopathogenesis of sarcoidosis remains incomplete. The enigma of sarcoidosis lies in its immunological paradox of type 1 T helper cell-dominated local inflammation co-existing with T regulatory-induced peripheral anergy. Although specific aetiological agents have not been identified, mounting evidence suggests that environmental and microbial antigens may trigger sarcoidosis. Genome-wide association studies have identified candidate genes conferring susceptibility and gene expression analyses have provided insights into cytokine dysregulation leading to inflammation. Sarcoidosis remains a diagnosis of exclusion based on histological evidence of non-caseating granulomas with compatible clinical and radiological findings. In recent years, endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated the diagnosis, and whole body positron emission tomography scanning has improved localisation of disease. No single biomarker is adequately sensitive and specific for detecting and monitoring disease activity. Most patients do not require treatment; when indicated, corticosteroids remain the initial standard of care, despite their adverse side effect profile. Other drugs with fewer side effects may be a better long term choice (eg, methotrexate, hydroxychloroquine, azathioprine, mycophenolate), while tumour necrosis factor-α inhibitors are a treatment option for patients with refractory disease.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance

PubMed Central

van Geuns, Robert‐Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J.G.M.

2017-01-01

Abstract Aims Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast‐enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. Methods and results We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast‐enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non‐invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Conclusions Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. PMID:29154434

Spontaneous Reduction in Abnormal Myocardial Uptake of Fluorine-18 Fluorodeoxygluose in a Patient with Cardiac Sarcoidosis.

PubMed

Terasaki, Fumio; Fujita, Shu-Ichi; Kanzaki, Yumiko; Hirose, Yoshinobu; Ishizaka, Nobukazu

2018-05-30

Fluorine-18 fluorodeoxygluose ( 18 F-FDG) positron emission tomography (PET) is a useful tool for evaluating disease activity in sarcoidosis including cardiac involvement. A 67-year-old patient who developed atrioventricular block requiring permanent pacemaker implantation was diagnosed with cardiac sarcoidosis. The patient did not undergo steroid or immunosuppressive therapy but underwent serial 18 F-FDG PET examination, which showed spontaneous reduction in the myocardial FDG uptake, indicating the remission of immune-inflammatory activity. Although the global systolic function remained preserved, thinning of the septal wall emerged during the clinical course of follow-up, which is characteristic for cardiac sarcoidosis.

Thallium-201 scintigraphy in the diagnosis and management of myocardial sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fields, C.L.; Ossorio, M.A.; Roy, T.M.

1990-03-01

We have described three patients with clinical evidence of myocardial sarcoidosis to illustrate the utility of thallium-201 scintigraphy in demonstrating the myocardial lesions. Both the symptomatic and asymptomatic individuals studied showed the characteristic reverse redistribution phenomenon. No abnormalities were seen during the exercise phase of the thallium study, but myocardial defects were detected in each patient when repeat studies were obtained at rest six hours later. Steroid therapy resolved the defects in each case. We propose thallium-201 scintigraphy of the heart as a safe and useful tool for documenting myocardial involvement in sarcoidosis and following the effects of therapy.

TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis.

PubMed

Facco, M; Cabrelle, A; Calabrese, F; Teramo, A; Cinetto, F; Carraro, S; Martini, V; Calzetti, F; Tamassia, N; Cassatella, M A; Semenzato, G; Agostini, C

2015-01-01

TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place. In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects. Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1. These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.

Computed tomography in pulmonary sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lynch, D.A.; Webb, W.R.; Gamsu, G.

1989-05-01

We studied the high resolution CT (HRCT) scans of 15 patients with biopsy-proven sarcoidosis and correlated the findings with pulmonary function tests (12 patients), 67Ga scans (10 patients), bronchoalveolar lavage (five patients), recent transbronchial biopsy (six patients), and recent open lung biopsy (three patients). The HRCT features included small nodules, thickened interlobular septa, patchy focal increase in lung density, honeycombing, and central conglomeration of vessels and bronchi. Active alveolitis was present by gallium scanning criteria in 5 of 10 cases. By bronchoalveolar lavage criteria, activity was present in three of five cases. Patchy increase in density may correlate with activemore » alveolitis as seen on /sup 67/Ga scanning. High resolution CT was better than chest X-radiography for demonstration of patchy increase in density and for distinguishing nodules from septal thickening. Both nodules and patchy density were partly reversible following therapy. Nodular densities seen on CT correlated with the presence of granulomata on histology. Resting pulmonary function tests correlated poorly with presence and extent of lung disease on HRCT. The presence on HRCT of focal fine nodules, patchy focal increase in lung density, and central crowding of bronchi and vessels should suggest the diagnosis of sarcoidosis. In some patients, HRCT can identify unsuspected parenchymal lung disease and document the reversible components of sarcoid lung disease.« less

[Retrospective evaluation of sarcoidosis patients 1970-1979 at the Bad Berka Central Clinic for Heart and Lung Diseases for the detection of possible heart involvement].

PubMed

Kirsten, D; Schaedel, H; Kessler, G

1984-01-01

Cardiac involvement in pulmonary sarcoidosis was found in a higher percentage than formerly reported, by careful observation. In a retrospective analysis of 1 236 patients with pulmonary sarcoidosis we found a possible cardiac involvement in 15.1%. In cases of pulmonary sarcoidosis or lymph node sarcoidosis combined with sarcoid lesions in other organs (liver, eyes, skin etc.) cardiac involvement is possible. Heart sarcoidosis was found in all roentgenographic stages and without sex difference. Patients with possible heart sarcoidosis suffer from dyspnoe , thoracical pain, heart discomfort, or angina pectoris in a higher part than without it. Enlargement of the heart and/or cardiac failure are signs of sarcoid involvement in patient with sarcoidosis, also in elderly patients. There are some difficulties in differential diagnosis of sarcoid cardiac involvement and ischaemic heart disease.

Unmasking sarcoidosis following surgery for Cushing disease.

PubMed

Diernaes, Jon E F; Bygum, Anette; Poulsen, Per L

2016-01-01

We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed clinically and a suspicion of underlying sarcoidosis was substantiated by lung imaging and elevated plasma interleukin (IL)-2 receptor. One month later, the lesions spontaneously resolved without therapy other than maintenance glucocorticoid replacement. Physicians should be aware that patients undergoing successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease.

Clinical features of Sarcoidosis in Oman: A report from the Middle East region.

PubMed

Jayakrishnan, B; Al-Busaidi, Nasser; Al-Lawati, Ahsan; George, Jojy; Al-Rawas, Omar A; Al-Mahrouqi, Yaqoub; Al-Lawati, Nabil

2016-10-07

Though clinical features of sarcoidosis follow a similar pattern, some heterogeneity is seen in different ethnic and racial groups. To describe for the first time the clinical characteristics of sarcoidosis patients in the Sultanate of Oman. The data on all cases of sarcoidosis followed up in the two tertiary hospitals in Oman were retrieved retrospectively. Of the 92 patients, for representing the ethnic data only Omani patients (n=83) were included. The mean age was 52.90±12.35 years. Majority were females (72.3%, n=60). Cough (n=44, 53.0%), dyspnea (n=39, 47%), arthralgia (n=26, 31.3%) and fatigue (30.1%) were the major symptoms. Arthralgia was reported by 41.7% of the females and 4.3% of the males (p= 0.001). Uveitis was present in 16 (19.3%), erythema nodosum in 8 (9.6%) and hypercalcemia in 13 (15.7%). The radiological stage at presentation was stage 0, 18.7%; I, 28%; II, 17.3%; III, 24% and IV, 12%. Majority (61.4%) of the patients had tissue diagnosis; intra-thoracic site 70.6%. Pulmonary function showed abnormal diffusion in 75%. Sixty eight received treatment, 81.9% took prednisolone. Based on radiograph good outcome (Resolving) was noted in 20.9%, intermediate (Stable) in 73.1% and poor (Progressive) in 6%. Lung function wise, resolving, stable and progressive disease was seen in 31.4%, 40.0% and 28.6% respectively. The clinical picture of the patients with sarcoidosis from Oman was similar to that reported from the rest of the world. Region wise, our patients were older and arthralgia and hypercalcemia were more common. The management of sarcoidosis needs a more organized approach in the country with clear guidelines on monitoring and treatment.

18-FDG-PET in a patient cohort suspected for cardiac sarcoidosis: Right ventricular uptake is associated with pathological uptake in mediastinal lymph nodes.

PubMed

Tuominen, Heikki; Haarala, Atte; Tikkakoski, Antti; Kähönen, Mika; Nikus, Kjell; Sipilä, Kalle

2018-05-02

In up to 65% of cardiac sarcoidosis patients, the disease is confined to the heart. Diagnosing isolated cardiac sarcoidosis is challenging due to the low sensitivity of endomyocardial biopsy. If cardiac sarcoidosis is part of biopsy-confirmed systemic sarcoidosis, the diagnosis can be based on cardiac imaging studies. We compared the imaging features of patients with isolated cardiac FDG uptake on positron emission tomography with those who had findings indicative of systemic sarcoidosis. 137 consecutive cardiac FDG-PET/CT studies performed on subjects suspected of having cardiac sarcoidosis were retrospectively analyzed. 33 patients had pathological left ventricular FDG uptake, and 12 of these also had pathological right ventricular uptake. 16/33 patients with pathological cardiac uptake had pathological extracardiac uptake. 10/12 patients with both LV- and RV-uptake patterns had extracardiac uptake compared to 6/21 of those with pathological LV uptake without RV uptake. SUVmax values in the myocardium were higher among patients with abnormal extracardiac uptake. The presence of extracardiac uptake was the only imaging-related factor that could predict a biopsy indicative of sarcoidosis. Right ventricular involvement seems to be more common in patients who also have findings suggestive of suspected systemic sarcoidosis, compared with patients with PET findings indicative of isolated cardiac disease.

Gallium-67 uptake in meningeal sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ayres, J.G.; Hicks, B.H.; Maisey, M.N.

1986-07-01

A case of sarcoidosis limited to the central nervous system is described in which the diagnosis was suggested by high Ga-67 uptake in the cranial and spinal meninges. The diagnosis was confirmed by meningeal biopsy. Treatment with oral corticosteroids resulted in clinical improvement and marked reduction in Ga-67 uptake in the meninges. This is the first reported case of the central nervous system sarcoid diagnosed by Ga-67 imaging.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance.

PubMed

Smedema, Jan-Peter; van Geuns, Robert-Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J G M

2017-11-01

Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast-enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast-enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non-invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of

Sarcoidosis in children: HRCT findings and correlation with pulmonary function tests.

PubMed

Sileo, C; Epaud, R; Mahloul, M; Beydon, N; Elia, D; Clement, A; Le Pointe, H Ducou

2014-12-01

High-resolution computed tomography (HRCT) plays an important role in the diagnosis and staging of pulmonary sarcoidosis, but implies radiation exposure. In this light, we aimed to describe HRCT findings as well as their relationship with pulmonary function tests (PFT) in children with pulmonary sarcoidosis. In a retrospective study, 18 pediatric patients with sarcoidosis, including 12 with pulmonary abnormalities (PA group) and 6 without pulmonary abnormalities (APA group) were followed over a 16-year period. Relationships between HRCT scores and PFT were studied by non-parametric Spearman's test at diagnosis and by restricted maximum likelihood (REML) analysis during follow-up. Forty-three HRCT were scored. Twelve patients showed abnormal HRCT findings at diagnosis with multiple nodules or micronodules, while ground-glass opacities were seen in 11 patients. Ten patients exhibited pleural thickening or thickening of the fissure and 6 had interlobular septal thickening at diagnosis. No correlation between HRCT and forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow during the mid-half of the FVC (FEF(25-75)) and specific dynamical compliance (SpecC(Ldyn)) was found at diagnosis. However, linear mixed models showed that changes in total HRCT scores over time were significantly associated with SpecC(Ldyn), FVC, and FEV1 modifications. Radiologic findings in children with pulmonary sarcoidosis were similar to those in adults. HRCT and PFT are both essential investigations at diagnosis; however, the correlation between HRCT pulmonary parenchymal findings and PFT over time suggests the possibility of reducing the number of HRCT during follow-up to decrease unnecessary radiation exposure. © 2013 Wiley Periodicals, Inc.

Prognostic significance of ventricular late potentials in patients with pulmonary sarcoidosis.

PubMed

Yodogawa, Kenji; Seino, Yoshihiko; Ohara, Toshihiko; Iwasaki, Yu-Ki; Hayashi, Meiso; Miyauchi, Yasushi; Azuma, Arata; Shimizu, Wataru

2018-06-01

Early detection of cardiac involvement in sarcoidosis is difficult but essential to achieve optimal treatment. Signal-averaged electrocardiography (SAECG) can detect subtle cardiac electrical abnormalities termed late potentials (LPs) and would be useful for the early diagnosis of cardiac involvement. This study aims to investigate the prognostic significance of LP in patients with pulmonary sarcoidosis. We prospectively studied 74 patients with pulmonary sarcoidosis without overt electrocardiographic abnormalities. All participants underwent SAECG, cardiac echocardiography, and 24-hour ambulatory Holter monitoring. Serum angiotensin-converting enzyme and B-type natriuretic peptide levels were also evaluated. We followed these patients for the evaluation of incidence of cardiac events including cardiac death, arrhythmias, and heart failure requiring hospital admission. Of the studied population, 29 patients (39.2%) had detectable LP. During a mean follow-up period of 9.8 years, 8 patients with LPs had cardiovascular events, including development of complete atrioventricular block (n = 4), ventricular tachycardia (n = 2), and heart failure (n = 2). Meanwhile, only 1 of 45 patients without LP developed cardiac event (heart failure). Multivariate analyses revealed that LPs were associated with an increased risk of developing cardiac events (hazard ratio 9.66; 95% confidence interval 1.20-78.01; P = .033) whereas age, sex, serum angiotensin-converting enzyme and B-type natriuretic peptide levels, number of premature ventricular contractions on 24-hour Holter monitoring, and echocardiographic parameters were not associated with subsequent cardiac events. SAECG might possibly be useful for the early detection of cardiac sarcoidosis and, if independently validated, could eventually be considered as a screening test for further risk stratification. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences

PubMed Central

Ronninger, Marcus; Shchetynsky, Klementy; Franke, Andre; Nöthen, Markus M.; Müller-Quernheim, Joachim; Schreiber, Stefan; Adrianto, Indra; Karakaya, Bekir; van Moorsel, Coline H. M.; Navratilova, Zdenka; Kolek, Vitezslav; Rybicki, Benjamin A.; Iannuzzi, Michael C.; Petrek, Martin; Grutters, Jan C.; Montgomery, Courtney; Fischer, Annegret; Eklund, Anders; Padyukov, Leonid; Grunewald, Johan

2016-01-01

Rationale: Sarcoidosis is a multisystem disease of unknown cause. Löfgren’s syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype, non-LS sarcoidosis. Objectives: To address the genetic architecture of sarcoidosis phenotypes, LS and non-LS. Methods: An association study in a white Swedish cohort of 384 LS, 664 non-LS, and 2,086 control subjects, totaling 3,134 subjects using a fine-mapping genotyping platform was conducted. Replication was performed in four independent cohorts, three of white European descent (Germany, n = 4,975; the Netherlands, n = 613; and Czech Republic, n = 521), and one of black African descent (United States, n = 1,657), totaling 7,766 subjects. Measurements and Main Results: A total of 727 LS-associated variants expanding throughout the extended major histocompatibility complex (MHC) region and 68 non-LS–associated variants located in the MHC class II region were identified and confirmed. A shared overlap between LS and non-LS defined by 17 variants located in the MHC class II region was found. Outside the MHC region, two LS-associated loci, in ADCY3 and between CSMD1 and MCPH1, were observed and replicated. Conclusions: Comprehensive and integrative analyses of genetics, transcription, and pathway modeling on LS and non-LS indicates that these sarcoidosis phenotypes have different genetic susceptibility, genomic distributions, and cellular activities, suggesting distinct molecular mechanisms in pathways related to immune response with a common region. PMID:26651848

Systemic sarcoidosis with bone marrow involvement responding to therapy with adalimumab: a case report.

PubMed

Patel, Supen R

2009-07-29

Sarcoidosis is an inflammatory disorder characterized by the presence of non-caseating granulomas in affected organs. The presence of CD4-positive T lymphocytes and macrophages in affected organs suggests an ongoing immune response. Systemic corticosteroids remain the mainstay of treatment, but therapy is often limited by adverse effects. This is the first report of the use of adalimumab (HUMIRA((R)), Abbott Laboratories, North Chicago, IL, USA), an anti-tumor necrosis factor monoclonal antibody, in a patient with systemic sarcoidosis with bone marrow involvement. A 42-year-old African-American man with a medical history significant for hypertension and diabetes mellitus presented with anemia and thrombocytopenia of two months duration. The patient underwent physical examination, bone marrow aspiration and biopsy, chest X-ray, acid-fast bacilli stain, computed tomography with contrast, and additional laboratory tests. He was diagnosed with systemic sarcoidosis with splenomegaly and bone marrow involvement. Drug therapy included prednisone, which had to be discontinued owing to adverse effects, and adalimumab. This is the first report describing the use of adalimumab in a patient with systemic sarcoidosis with bone marrow involvement. Tumor necrosis factor antagonism with adalimumab was efficacious and well-tolerated in this patient and may be considered as a treatment option for similar cases.

Light and Laser Modalities in the Treatment of Cutaneous Sarcoidosis: A Systematic Review.

PubMed

Lima, Ana Luiza; Goetze, Steven; Illing, Tanja; Elsner, Peter

2018-04-27

Sarcoidosis is a systemic non-caseating granulomatous disease of unknown aetiology. Cutaneous manifestations are present in approximately 10-30% of the patients with the systemic form. Therapy is indicated in case of disabling symptoms, organ dysfunction or cosmetically distressing manifestation. Despite different therapeutic possibilities, cutaneous sarcoidosis remains exceptionally difficult to treat. Light and laser therapy may be a promising alternative. In this systematic review, we summarised the available treatments according to the literature concerning light and laser therapy for cutaneous sarcoidosis. Publications written in English and German, published between January 1990 and July 2016 in the database PubMed, MEDLINE, Embase, and Scopus were analysed. Light therapy with intense pulsed light, photodynamic therapy, and ultraviolet A light therapy, as well as laser therapy with pulsed dye laser, YAG laser, and Q-switched ruby laser were described. The results are based on individual case reports and small case series. Randomised controlled studies are lacking.

Serum fibroblastic growth factor 23 in acute Sarcoidosis and normal kidney function.

PubMed

Sexton, Donal J; O'Reilly, M W; Geoghegan, P; Kinsella, S M; Moran, P J; O'Regan, A W

2016-08-01

Serum fibroblastic growth factor (FGF) 23 has recently been established as a major physiological regulator of phosphate homeostasis and may have a causal role in adverse cardiovascular and bone outcomes. However its role in states of disordered phosphate homeostasis and normal kidney function is as yet under characterised. To investigate whether this biomarker of vascular calcification and adverse bone outcomes is detectable in patients with sarcoidosis. We conducted a cross sectional study on a convenience sample of patients presenting with acute sarcoidosis to a respiratory tertiary referral unit. We set out to systematically examine the characteristics and determinants of serum FGF-23 in patients presenting with acute sarcoidosis. We studied 39 patients, 26 were male. Mean (SD) age was 33 (9.6) years. 15.4% of patients had a serum level of FGF-23 ≥ 9.9 pg/mL. The remaining 84.6% of patients had a serum FGF-23 < 9.9 pg/mL. Those with a detectable serum FGF-23 had a significantly higher serum calcium (P = 0.007), and lower serum iPTH (P<0.001). Serum phosphate and 25-hydroxyvitamin D were not statistically significantly different between groups (P=0.25 and P=0.83). The proportion of patients with stage II disease on CXR was higher in those with a detectable FGF-23 (P<0.001). Serum FGF-23 was below the level of detection in the majority of this cohort of patients presenting with acute sarcoidosis. A detectable serum FGF-23 was associated with a higher serum calcium and lower serum iPTH.

Identifying novel biomarkers in sarcoidosis using genome-based approaches

PubMed Central

Knox, Kenneth S.; Garcia, Joe G.N.

2015-01-01

Synopsis We briefly review conventional biomarkers used clinically to 1) support a diagnosis and 2) monitor disease progression in patients with sarcoidosis. We describe potential new biomarkers identified by genome-wide screening and the approaches to discover these biomarkers. PMID:26593137

[Perioperative onset of sarcoidosis : Rare differential diagnosis of a difficult airway].

PubMed

Jansen, G; Nowak, A

2018-05-01

Sarcoidosis is a rare multisystemic chronic inflammatory condition. Typically, there is a big discrepancy between the patient's subjectively perceived symptoms and the presence of clinical signs. Due to the high number of potential sites of onset (e. g. larynx, lungs, heart, liver, kidneys) the affected organs may show functional restrictions that are relevant for decisions related to anesthesia. Therefore, an anesthetists working in a clinical setting should be familiar with the special needs of this patient collective. This article describes the onset of sarcoidosis in a case of an unexpected difficult airway.

Pleural sarcoidosis diagnosed on the basis of an increased CD4/CD8 lymphocyte ratio in pleural effusion fluid: a case report.

PubMed

Kumagai, Toru; Tomita, Yasuhiko; Inoue, Takako; Uchida, Junji; Nishino, Kazumi; Imamura, Fumio

2015-08-14

Pleural effusion induced by sarcoidosis is rare, and pleural sarcoidosis is often diagnosed by thoracoscopic surgery. The diagnosis of pleural sarcoidosis using thoracentesis may be less invasive when sarcoidosis is already diagnosed histologically in more than one organ specimen. Here we report the case of a 64-year-old woman with pleural sarcoidosis diagnosed on the basis of an increased CD4/CD8 lymphocyte ratio in pleural effusion fluid obtained by thoracentesis. This case report is important because it highlights the usefulness of the CD4/CD8 lymphocyte ratio in pleural effusion as an indicator of pleural involvement of sarcoidosis. A 64-year-old Japanese woman visited our hospital with an initial symptom of dyspnea on exertion for a period of 4 months. Chest computed tomography showed bilateral hilar and multiple mediastinal lymphadenopathy, multiple small nodular shadows in her bilateral lungs, small nodular shadows along the interlobar pleura, and bilateral pleural effusion. Her serum angiotensin-converting enzyme and soluble interleukin-2 receptor levels were elevated. Histological analysis of a resected subcutaneous nodule, and biopsy specimens from a right mediastinal lymph node and from her right lung revealed non-caseous epithelioid granulomas. Her bronchoalveolar lavage fluid exhibited a predominance of lymphocytes together with an increase in the CD4/CD8 lymphocyte ratio. The lymphocytic predominance and the increased CD4/CD8 lymphocyte ratio were also detected in the right-sided pleural effusion fluid obtained by thoracentesis. We diagnosed sarcoidosis with pleural involvement. Because pleural effusion did not resolve spontaneously and her symptom of dyspnea on exertion worsened, corticosteroid therapy was initiated, which ameliorated the sarcoidosis and the pleuritis. Analysis of the CD4/CD8 lymphocyte ratio in pleural effusion fluid obtained by thoracentesis may be helpful for the diagnosis of pleural sarcoidosis when the diagnosis is already made

Dual Inhibition of Rip2 and IRAK1/4 Regulates IL-1β and IL-6 in Sarcoidosis Alveolar Macrophages and Peripheral Blood Mononuclear Cells

PubMed Central

Talreja, Jaya; Talwar, Harvinder; Ahmad, Nisar; Rastogi, Ruchi; Samavati, Lobelia

2016-01-01

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that primarily affects the lungs. Our previous work indicates that activation of p38 plays a pivotal role in sarcoidosis inflammatory response. Therefore, we investigated the upstream kinase responsible for activation of p38 in sarcoidosis alveolar macrophages (AMs) and peripheral mononuclear cells (PBMCs). We identified that sustained p38 phosphorylation in sarcoidosis AMs and PBMCs is associated with active MKK4 but not with MKK3/6. Additionally, we found that sarcoidosis AMs exhibit a higher expression of IRAK1, IRAK-M and Rip2. Surprisingly, ex vivo treatment of sarcoidosis AMs or PBMCs with IRAK1/4 inhibitor led to a significant increase in IL-1β mRNA expression both spontaneously and in response to TLR2 ligand. However, a combination of Rip2 and IRAK-1/4 inhibitors significantly decreased both IL-1β and IL-6 production in sarcoidosis PBMCs and moderately in AMs. Importantly, a combination of Rip2 and IRAK-1/4 inhibitors led to decreased IFN-γ and IL-6, and decreased percentage of activated CD4+CD25+ cells in PBMCs. These data suggest that in sarcoidosis both pathways, namely IRAK and Rip2 are deregulated. Targeted modulation of Rip2 and IRAK pathways may prove to be a novel treatment for sarcoidosis. PMID:27402699

Laboratory diagnosis of ophthalmic sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weinreb, R.N.; Tessler, H.

Because the eye is involved in about 25% of patients with active sarcoid, the ophthalmologist is often the first physician to see these patients. Although clinical findings may suggest sarcoid, laboratory tests (e.g., x-ray, skin tests, blood chemistries, etc.) may be normal or inconclusive. Thus, it is important that the ophthalmologist be aware of the availability and limitations of the various biochemical, immunological, radiological, and histopathological tests that contribute to the early diagnosis of sarcoidosis. The authors review diagnostic procedures and present a flowchart detailing indications for each.

The impact of gas exchange measurement during exercise in pulmonary sarcoidosis.

PubMed

Kollert, Florian; Geck, Barbara; Suchy, Rolf; Jörres, Rudolf A; Arzt, Michael; Heidinger, Dominic; Hamer, Okka W; Prasse, Antje; Müller-Quernheim, Joachim; Pfeifer, Michael; Budweiser, Stephan

2011-01-01

Pulmonary sarcoidosis shows a remarkable heterogeneity of phenotypes ranging from bihilar lymphadenopathy to progressive fibrosis. Individual disease assessment is demanding and requires sensible, practical measures. We tested whether gas exchange measurements during exercise reflects disease activity and clinical course in sarcoidosis. In 149 patients with proven pulmonary sarcoidosis the alveolar-arterial oxygen pressure gradient (P(A-a)O(2)) during exercise was assessed and compared with chest X-ray typing, pulmonary function, single breath-diffusing capacity for carbon monoxide (DL(CO)), serological markers, cell composition of bronchoalveolar lavage fluid (BALF) and clinical course. Patients were categorized according to thresholds of P(A-a)O(2) during exercise. Chest X-ray typing, pulmonary function, DL(CO) and the need for immunosuppressive treatment differed between the disease categories based on P(A-a)O(2) during exercise (p < 0.0001 each). Patients with an impairment of gas exchange during exercise also showed elevated levels of neopterin (p = 0.002) and higher percentages of neutrophils (p = 0.013) and eosinophils (p < 0.0001) in BALF. Multivariate regression analysis showed that forced vital capacity (FVC) (p = 0.009) and P(A-a)O(2) during exercise (p < 0.0001) were independently associated with a prolonged need for immunosuppressive treatment (>1 year), but not DL(CO). About 50% (n = 75) of the study population showed a normal spirometry. Even in this subgroup 23% had an impaired gas exchange during exercise, which correlated with chest X-ray types (p < 0.0001) and the need for immunosuppressive treatment (p < 0.005). Impaired gas exchange during exercise reflects disease activity and its extent and is associated with a prolonged need for immunosuppressive treatment during follow-up in patients with pulmonary sarcoidosis. Copyright © 2010 Elsevier Ltd. All rights reserved.

Combined pulmonary involvement in hereditary lysozyme amyloidosis with associated pulmonary sarcoidosis: a case report.

PubMed

McCarthy, Cormac; Deegan, Alexander P; Garvey, John F; McDonnell, Timothy J

2013-12-17

Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis.

A complete heart block in a young male: a case report and review of literature of cardiac sarcoidosis.

PubMed

Patel, Brijesh; Shah, Mahek; Gelaye, Alehegn; Dusaj, Raman

2017-01-01

Cardiac sarcoidosis is one of the uncommon causes of heart failure. Generally, it presents in the form of varying clinical manifestations ranging from asymptomatic to fatal arrhythmias such as ventricular tachycardia and complete heart block. It is difficult to make a diagnosis strictly based on clinical grounds. However, in the setting of extracardiac sarcoidosis and patients presenting with advanced heart block or ventricular arrhythmia, direct cardiac involvement should be suspected. The definitive diagnosis of cardiac sarcoidosis can be made from endomyocardial biopsy, but it is falling out of favor due to patchy myocardial involvement, considerable procedure-related risks, and advancement in additional imaging modalities. Once cardiac sarcoidosis has been diagnosed, management of the disease remains challenging. Steroids are considered the mainstay of therapy, and implantable cardioverter defibrillator therapy can be considered in a selected group of patients at greater risk for malignant ventricular arrhythmias.

Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D.

PubMed

Levy, Y; Hayek, T; Finkelstein, R

1996-09-01

We report a case of a female patient with sarcoidosis who presented with a generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis. Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with a normal plasma 1,25-dihydroxy vitamin D concentration occurred later. Corticosteroid therapy resulted in prompt clinical and biochemical responses with normalization of plasma calcium and a significant reduction in 1,25-dihydroxy vitamin D concentration. This is an exceptional presentation of sarcoidosis with severe hypercalcaemia and normal vitamin D metabolites.

The high frequency of healthcare use in patients one year prior to a sarcoidosis diagnosis

PubMed Central

Gerke, Alicia K.; Tang, Fan; Pendergast, Jane; Cavanaugh, Joseph E.; Polgreen, Philip M.

2015-01-01

Background The clinical presentation of sarcoidosis can be varied. Prior investigations have shown that diagnosis is often delayed over six months, particularly in patients with pulmonary symptoms. Delays may lead to high healthcare use prior to diagnosis. Objective To investigate healthcare use prior to diagnosis of sarcoidosis for a cohort of insured patients. Methods We conducted a case-control study using a de-identified limited dataset of private health insurance claims. Cases were identified as persons with sarcoidosis from 2003-2009. Controls with other respiratory-related diagnoses (asthma, chronic obstructive pulmonary disease, pneumonia) were matched by age, gender, and diagnosis date. We compared frequencies of doctor visits, prescriptions, and imaging in the year prior to established diagnosis. Results We identified 206 cases and 2060 controls and compared healthcare use patterns in the year prior to diagnosis. Among those receiving prescriptions, a larger proportion of cases received two or more antibiotic courses (69% vs. 55%, p=0.0020) or two or more corticosteroid prescriptions (63% vs. 50%, p=0.0137). On average, cases had more doctor visits (14.7 vs. 7.8, p<0.0001), saw more specialties (3.9 vs. 2.1, p<0.0001), and underwent more chest x-rays (2.0 vs. 1.5, p<0.0001). A larger proportion of cases underwent two or more chest x-rays (54% vs. 24%, p<0.0001). Conclusions Patients with sarcoidosis undergo a large amount of healthcare prior to diagnosis, some of which may not be necessary, compared to controls with respiratory-related disease. These results highlight the need for improved diagnostic algorithms to identify patients with sarcoidosis and avoid potentially excessive delays in diagnosis. PMID:25363229

Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

Gallium 67 citrate scans and serum angiotension converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestation. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r = .436; p < .005). The frequency ofmore » abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical identification of inactive sarcoidosis.« less

Magnetic resonance imaging in central nervous system sarcoidosis.

PubMed

Miller, D H; Kendall, B E; Barter, S; Johnson, G; MacManus, D G; Logsdail, S J; Ormerod, I E; McDonald, W I

1988-03-01

We performed brain MRIs on 21 patients with CNS sarcoidosis. Brain CTs were performed in 18 of these. Parenchymal lesions were seen in 17 of 21 with MRI, compared with 9 of 18 with CT. MRI detected a greater number of parenchymal lesions in cases where both CT and MRI were positive, and some lesions appeared more extensive with MRI than with CT. The most common MRI pattern was one of periventricular and multifocal white matter lesions (14 cases). Such a pattern is not specific, and other recognized causes for it were identified in four cases. It is likely, however, that sarcoid tissue causes this pattern in some cases, and confirmation was obtained from cerebral biopsy in one. In six patients, the white matter changes were indistinguishable from those seen in multiple sclerosis. Contrast-enhanced CT in two patients showed diffuse meningeal involvement not seen with MRI. MRI is the investigation of choice in detecting parenchymal changes in the brain of patients with CNS sarcoidosis and may prove useful in monitoring treatment in such cases.

Cutaneous annular sarcoidosis developing on a background of exogenous ochronosis: a report of two cases and review of the literature.

PubMed

Moche, M J; Glassman, S J; Modi, D; Grayson, W

2010-06-01

Exogenous (cosmetic) ochronosis is caused by the long term use of skin-lightening creams containing hydroquinone. Three cases of systemic sarcoidosis with cutaneous sarcoidal granulomas, which developed on ochronotic skin were last described by Jacyk in 1995. Dogliotti and Leibowitz previously reported cases of granulomatous ochronosis with sarcoid-like histological changes but with no associated systemic sarcoidosis. We report two additional cases of cutaneous sarcoidal granulomas, which developed on a background of cosmetic ochronosis in patients recently diagnosed with systemic sarcoidosis.

Sarcoidosis as an adverse effect of tumor necrosis factor inhibitors.

PubMed

Cathcart, Shelley; Sami, Naveed; Elewski, Boni

2012-05-01

Tumor necrosis factor inhibitors are valuable tools for dermatologists. As their use increases, rare adverse events are more likely to be encountered. We describe one patient who developed sarcoidosis while being treated for psoriasis with etanercept. We sought to review to previously reported cases and further characterize the nature of this reaction. A literature search was performed with the key words "sarcoidosis, sarcoid, etanercept, infliximab, adalimumab, granulomatous, and drug reaction." All relevant cases in the English language were included and evaluated for demographic data, duration of therapy prior to developing sarcoid, duration of sarcoid signs/symptoms, treatments used and time to resolution after discontinuation of the drug. Including the present case, there are 34 cases of sarcoidosis developing during anti-tumor necrosis factor therapy. All previously reported cases were patients with a primarily rheumatologic diagnosis. In all but one case, discontinuation of the drug resulted in complete resolution of symptoms. The lung and surrounding lymph nodes were the areas most commonly affected. The average amount of time between initiation of therapy and onset of symptoms was 22 months. The average time to resolution of symptoms after discontinuation of the drug was 5.2 months. This is a retrospective case review. These data indicated that sarcoid is a possible adverse effect of tumor necrosis factor inhibitor therapy that should be noted by dermatologists using these drugs. While it has been reported in the rheumatology literature, it may be under-recognized by dermatologists.

Diabetes insipidus secondary to sarcoidosis presenting with caseating granuloma

PubMed Central

Alam, Taimour; Thomas, Steven

2011-01-01

Diabetes insipidus is a rare complication of sarcoid infiltration of the hypothalamic-pituitary region. Non-caseating granuloma formation is typical of sarcoidosis. Anterior and posterior pituitary function may be affected. MRI coupled with endocrinology assessment is the usual method of investigation. A 25-year-old Caucasian male with no significant medical history presented with polyuria and polydipsia. Water deprivation test confirmed diabetes insipidus. CT scanning of the chest confirmed lymphadenopathy. Lymph node biopsy revealed caseating granuloma. Extensive investigation for tuberculosis was negative. The patient was started on intranasal desmopressin and steroids with marked improvement in symptoms. This is the first reported case of neurosarcoidosis with diabetes insipidus and caseation on histology that we are aware of. Differentiating between caseation due to sarcoidosis and tuberculosis on histology is possible by the use of special stains. Return of normal endocrine function is unusual and the patient is likely to require desmopressin therapy for life. PMID:22707619

Bilateral parotitis as the initial presentation of childhood sarcoidosis.

PubMed

Banks, Gretchen C; Kirse, Daniel J; Anthony, Evelyn; Bergman, Simon; Shetty, Avinash K

2013-01-01

The differential diagnosis of bilateral parotid gland enlargement in children includes infectious, inflammatory, and neoplastic disorders. We present the case of a 13-year-old male who presented with a 5-week history of bilateral parotid swelling. On exam, both parotid glands were nontender, smooth, and diffusely enlarged. He had slightly elevated inflammatory markers, but other lab results were normal. A neck CT revealed symmetric enlargement of the parotid, submandibular, and sublingual glands. A chest CT revealed scattered peripheral pulmonary nodules and bilateral hilar adenopathy. A parotid gland biopsy showed multiple noncaseating granulomas with multinucleated giant cells surrounded by lymphocytes, consistent with the diagnosis of sarcoidosis. Special stains for acid-fast and fungal organisms were negative. Using this illustrative case, we discuss the differential diagnosis of bilateral salivary gland enlargement in children and review the etiology, diagnosis, clinical manifestations, and treatment of pediatric sarcoidosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Bronchoalveolar lavage, serum angiotensin-converting enzyme, and /sup 67/Ga scanning in extrathoracic sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallaert, B.; Ramon, P.; Fournier, E.

1982-11-01

Results of bronchoalveolar lavage (BAL), 67Ga scanning, and serum angiotensin-converting enzyme (SACE) assay are compared in the assessment of pulmonary involvement in ten cases of extrathoracic sarcoidosis. Standard clinical, radiologic, and pulmonary function tests detected no pulmonary changes in these patients, but BAL demonstrated an increased alveolar lymphocytosis in eight of ten cases. SACE levels were increased in two cases, and the thoracic gallium uptake was normal in all cases. BAL appears to be the best technique for diagnosing latent pulmonary involvement in extrathoracic sarcoidosis.

Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis

PubMed Central

Mañá, Juan; Rubio-Rivas, Manuel; Villalba, Nadia; Marcoval, Joaquim; Iriarte, Adriana; Molina-Molina, María; Llatjos, Roger; García, Olga; Martínez-Yélamos, Sergio; Vicens-Zygmunt, Vanessa; Gámez, Cristina; Pujol, Ramón; Corbella, Xavier

2017-01-01

Abstract Cohort studies of large series of patients with sarcoidosis over a long period of time are scarce. The aim of this study is to report a 40-year clinical experience of a large series of patients at Bellvitge University Hospital, a tertiary university hospital in Barcelona, Spain. Diagnosis of sarcoidosis required histological confirmation except in certain specific situations. All patients underwent a prospective study protocol. Clinical assessment and follow-up of patients were performed by a multidisciplinary team. From 1976 to 2015, 640 patients were diagnosed with sarcoidosis, 438 of them (68.4%) were female (sex ratio F/M 2:1). The mean age at diagnosis was 43.3 ± 13.8 years (range, 14–86 years), and 613 patients (95.8%) were Caucasian. At diagnosis, 584 patients (91.2%) showed intrathoracic involvement at chest radiograph, and most of the patients had normal pulmonary function. Erythema nodosum (39.8%) and specific cutaneous lesions (20.8%) were the most frequent extrapulmonary manifestations, but there was a wide range of organ involvement. A total of 492 patients (76.8%) had positive histology. Follow-up was carried out in 587 patients (91.7%), over a mean of 112.4 ± 98.3 months (range, 6.4–475 months). Corticosteroid treatment was administered in 255 patients (43.4%), and steroid-sparing agents in 49 patients (7.7%). Outcomes were as follows: 111 patients (18.9%) showed active disease at the time of closing this study, 250 (42.6%) presented spontaneous remission, 61 (10.4%) had remission under treatment, and 165 (28.1%) evolved to chronic sarcoidosis; among them, 115 (19.6%) with mild disease and 50 (8.5%) with moderate to severe organ damage. A multivariate analysis showed that at diagnosis, age more than 40 years, the presence of pulmonary involvement on chest radiograph, splenic involvement, and the need of treatment, was associated with chronic sarcoidosis, whereas Löfgren syndrome and mediastinal lymphadenopathy on chest

Sarcoidosis: nail dystrophy without underlying bone changes.

PubMed

Wakelin, S H; James, M P

1995-06-01

Sarcoidosis is a chronic granulomatous disease of unknown origin that affects multiple organs and may present with a variety of skin lesions. Involvement of the nails is rare and almost invariably associated with underlying bone disease. We describe a patient with sarcoid nail dystrophy in whom this diagnosis was confirmed by a proximal nail fold biopsy. Radiologic investigation did not show evidence of an associated bone dystrophy in this case.

Hepatic sarcoidosis in patients presenting with liver dysfunction: imaging appearance, pathological correlation and disease evolution.

PubMed

Fetzer, David T; Rees, Mitchell A; Dasyam, Anil K; Tublin, Mitchell E

2016-09-01

We hypothesize that hepatic sarcoidosis is a dynamic process that can lead to cirrhosis and portal hypertension, independent of the course of thoracic disease. Therefore, we assess the imaging appearance and progression of hepatic sarcoidosis in subjects presenting with hepatic dysfunction. An IRB-approved, HIPAA-compliant, single-institution retrospective review identified 39 subjects with sarcoidosis-related liver dysfunction. Clinical information was collected. Two abdominal radiologists analyzed baseline and follow-up imaging studies, scoring features of cirrhosis. Chest CT was also analyzed. At presentation, 23 subjects (59.0 %) exhibited >3 cirrhotic features and 15 (38.5 %) >2 findings of portal hypertension. Of subjects with available follow-up, 57.9 % (19 subjects; mean interval 4.7 years) showed worsening of >3 cirrhotic features (Pearson rho = 0.58; p = 0.009). Parenchymal nodules were uncommon (25.6 %), and most regressed. Although 87.2 % of subjects were diagnosed with thoracic sarcoidosis, there was poor correlation between severity of hepatic and chest disease (Pearson rho = 0.30; p = 0.119). A mean of 7.2 years elapsed between diagnosis of pulmonary and liver involvement. Sarcoidosis may present as liver dysfunction, cirrhosis or portal hypertension. Sarcoid-related liver disease may progress and can manifest without, alongside or significantly after a diagnosis of pulmonary disease. • Patients often present with elevated liver function tests indicating cholestasis. • Patients may present with portal hypertension, and some progress to cirrhosis. • Though biopsy can be considered for focal liver lesions, most will regress. • Extent of intra-abdominal involvement may not correlate with severity of thoracic disease. • Liver disease may manifest alongside, prior to or significantly after initial diagnosis.

Enhanced CD8+ cytolytic T cell responses in the peripheral circulation of patients with sarcoidosis and non-Löfgren's disease.

PubMed

Parasa, Venkata Ramanarao; Forsslund, Helena; Enger, Tobias; Lorenz, Daniel; Kullberg, Susanna; Eklund, Anders; Sköld, Magnus; Wahlström, Jan; Grunewald, Johan; Brighenti, Susanna

2018-05-01

The role of CD4 + T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8 + cytolytic T cells (CTLs). CD8 + CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8 + T cells, using flow cytometry. Cytolytic function in blood lymphocytes was assessed using a standard 51 Cr-release assay. Patients with Löfgren´s syndrome (LS) and an acute disease onset, were compared to non-LS patients with an insidious onset. Higher proportions of peripheral CD8 + CTLs expressing perforin and granzyme B were observed in sarcoidosis compared to healthy controls. Blood CTLs from non-LS patients had significantly higher expression of perforin, granzyme B and granulysin compared to matched BAL, while LS patients maintained lower levels of effector molecules in both compartments. Mitogen-stimulated peripheral lymphocytes from sarcoidosis patients, particularly from the non-LS group, showed a higher target cell lysis compared to controls. These results demonstrated enhanced peripheral CD8 + CTL responses in sarcoidosis, especially in non-LS patients who have an increased risk of chronic disease. Further comprehensive clinical studies are warranted to increase our understanding of CD8 + CTL responses in sarcoidosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Vesico-cutaneous fistula revealing abdominal wall malakoplakia accompanied by Boeck's sarcoidosis].

PubMed

Knausz, József; Lipták, József; Andrásovszky, Zsolt; Baranyay, Ferenc

2010-02-07

Malakoplakia is an acquired granulomatous disorder first described by Michaelis and Gutmann in 1902. The pathogenesis of malakoplakia is hardly known, but it thought to be secondary to an acquired bactericidal defect in macrophages occurring mostly in immunosuppressed patients. 63-year-old female patient had been treated with methylprednisolone for ten years, because of pulmonary sarcoidosis. For six month, recurrent abdominal abscess and vesico-cutaneous fistula developed. Histological examination proved malakoplakia, and Escherichia coli was detected in the abscess cavity. Hematoxyline eosin staining, periodic acid-Schiff, Berlin-blue and Kossa reactions were performed. Microscopically malakoplakia consists of mainly macrophages, known as von Hansemann cells with scattered targetoid intracytoplasmic inclusions known as Michaelis-Gutmann bodies. In our presented case, after urological-surgical intervention and antibiotic therapy, the patient became free from complaints and symptoms. Malakoplakia has been described in numerous anatomic locations, mainly in the urogenital tract. Malakoplakia may be complicated with fistulas in different locations: vesico-coccygeal, rectoprostatic, anorectal fistulas have been were reported in the literature, while 6 cases of malakoplakia with Boeck's sarcoidosis are published. In the presented case sarcoidosis and the 10-year immunosuppressive treatment with methylprednisolone might have been in the background of abdominal wall malakoplakia, complicated by vesico-cutaneous fistula. The patient was successfully treated with surgery and the followed antibiotic therapy.

High-Cost Sarcoidosis Patients in the United States: Patient Characteristics and Patterns of Health Care Resource Utilization.

PubMed

Rice, J Bradford; White, Alan; Lopez, Andrea; Nelson, Winnie W

2017-12-01

Sarcoidosis is a multisystem inflammatory disorder characterized by the presence of noncaseating granulomas in involved organs. Prior research has found that sarcoidosis imposes a significant economic burden to U.S. payers. However, the drivers of high health care costs among sarcoidosis patients are unknown. To characterize sarcoidosis patients who were among the top 20% of total health care costs. Patients with a first diagnosis of sarcoidosis between January 1, 1998, and March 31, 2015 (index date) were selected from a deidentified privately insured administrative claims database. Study patients must have at least 12 months of continuous health plan enrollment prior to the index date. High-cost patients were those in the top 20% of total health care costs during the 12 months following the index date (follow-up period), and the remaining patients were classified as lower-cost patients. Patient characteristics, comorbidities, health care resource use, and health care costs in the study period were compared between the high-cost and lower-cost patients. Multiple logistic regression was used to assess the relationship between patient characteristics and being a high-cost sarcoidosis patient. A total of 7,173 sarcoidosis patients met the selection criteria. The 20% of patients classified as high-cost patients accounted for approximately 72% of the total health care costs in the 12-month follow-up period. Compared with lower-cost patients, high-cost patients were slightly older (50.6 vs. 49.1 years) and had a higher comorbidity burden at baseline (Charlson Comorbidity Index = 1.8 vs. 0.7). Mean annual total health care cost for high-cost sarcoidosis patients was 10 times that of their lower-cost counterparts ($73,345 vs. $7,073). Mean annual health care cost was $119,878 for patients in the 95th-99th percentile and $375,436 for patients in the top 1% of spend. High-cost patients had greater medical resource use and costs across all places of service (i.e., inpatient

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of /sup 99m/Tc pyrophosphate and gallium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forman, M.B.; Sandler, M.P.; Sacks, G.A.

1983-03-01

A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, /sup 201/Tl, /sup 67/Ga, and /sup 99m/Tc pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.

Search for sarcoidosis candidate genes by integration of data from genomic, transcriptomic and proteomic studies.

PubMed

Maver, Ales; Medica, Igor; Peterlin, Borut

2009-12-01

The search for gene candidates in multifactorial diseases such as sarcoidosis can be based on the integration of linkage association data, gene expression data, and protein profile data from genomic, transcriptomic and proteomic studies, respectively. In this study we performed a literature-based search for studies reporting such data, followed by integration of collected information. Different databases were examined--Medline, HugGE Navigator, ArrayExpress and Gene Expression Omnibus (GEO). Candidate genes were defined as genes which were reported in at least 2 different types of omics studies. Genes previously investigated in sarcoidosis were excluded from further analyses. We identified 177 genes associated with sarcoidosis as potential new candidate genes. Subsequently, 9 gene candidates identified to overlap in 2 different types of studies (genomic, transcriptomic and/or proteomic) were consistently reported in at least 3 studies: SERPINB1, FABP4, S100A8, HBEGF, IL7R, LRIG1, PTPN23, DPM2 and NUP214. These genes are involved in regulation of immune response, cellular proliferation, apoptosis, inhibition of protease activity, lipid metabolism. Exact biological functions of HBEGF, LRIG1, PTPN23, DPM2 and NUP214 remain to be completely elucidated. We propose 9 candidate genes: SERPINB1, FABP4, S100A8, HBEGF, IL7R, LRIG1, PTPN23, DPM2 and NUP214, as genes with high potential for association with sarcoidosis.

Comparative evaluation of 18F-FLT and 18F-FDG for detecting cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis.

PubMed

Norikane, Takashi; Yamamoto, Yuka; Maeda, Yukito; Noma, Takahisa; Dobashi, Hiroaki; Nishiyama, Yoshihiro

2017-08-29

18 F-FDG PET has been used in sarcoidosis for diagnosis and determination of the extent of the disease. However, assessing inflammatory lesions in cardiac sarcoidosis using 18 F-FDG can be challenging because it accumulates physiologically in normal myocardium. Another radiotracer, 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT), has been investigated as a promising PET tracer for evaluating tumor proliferative activity. In contrast to 18 F-FDG, 18 F-FLT uptake in the normal myocardium is low. The purpose of this retrospective study was to compare the uptake of 18 F-FLT and 18 F-FDG in the evaluation of cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis. Data for 20 patients with newly diagnosed sarcoidosis were examined. 18 F-FLT and 18 F-FDG PET/CT studies had been performed at 1 h after each radiotracer injection. The patients had fasted for at least 18 h before 18 F-FDG PET/CT but were given no special dietary instructions regarding the period before 18 F-FLT PET/CT. Uptake of 18 F-FLT and 18 F-FDG was examined visually and semiquantitatively using maximal standardized uptake value (SUVmax). Two patients had cardiac sarcoidosis, 7 had extra-cardiac thoracic sarcoidosis, and 11 had both cardiac and extra-cardiac thoracic sarcoidosis. On visual analysis for diagnosis of cardiac sarcoidosis, 4/20 18 F-FDG scans were rated as inconclusive because the 18 F-FDG pattern was diffuse, whereas no FLT scans were rated as inconclusive. The sensitivity of 18 F-FDG PET/CT for detection of cardiac sarcoidosis was 85%; specificity, 100%; and accuracy, 90%. The corresponding values for 18 F-FLT PET/CT were 92, 100, and 95%, respectively. Using semiquantitative analysis of cardiac sarcoidosis, the mean 18 F-FDG SUVmax was significantly higher than the mean 18 F-FLT SUVmax (P < 0.005). Both 18 F-FDG and 18 F-FLT PET/CT studies detected all 24 extra-cardiac lesions. Using semiquantitative analysis of extra-cardiac sarcoidosis, the mean 18

Everyday cognitive failure and depressive symptoms predict fatigue in sarcoidosis: A prospective follow-up study.

PubMed

Hendriks, Celine; Drent, Marjolein; De Kleijn, Willemien; Elfferich, Marjon; Wijnen, Petal; De Vries, Jolanda

2018-05-01

Fatigue is a major and disabling problem in sarcoidosis. Knowledge concerning correlates of the development of fatigue and possible interrelationships is lacking. A conceptual model of fatigue was developed and tested. Sarcoidosis outpatients (n = 292) of Maastricht University Medical Center completed questionnaires regarding trait anxiety, depressive symptoms, cognitive failure, dyspnea, social support, and small fiber neuropathy (SFN) at baseline. Fatigue was assessed at 6 and 12 months. Sex, age, and time since diagnosis were taken from medical records. Pathways were estimated by means of path analyses in AMOS. Everyday cognitive failure, depressive symptoms, symptoms suggestive of SFN, and dyspnea were positive predictors of fatigue. Fit indices of the model were good. The model validly explains variation in fatigue. Everyday cognitive failure and depressive symptoms were the most important predictors of fatigue. In addition to physical functioning, cognitive and psychological aspects should be included in the management of sarcoidosis patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Muscle cramps in the calf as presenting symptom of sarcoidosis.

PubMed Central

Janssen, M; Dijkmans, B A; Eulderink, F

1991-01-01

A patient is described, who presented with pain in the calf due to a palpable nodule as the presenting symptom of sarcoidosis. The patient was treated with rest and diclofenac, followed by intralesional injections with triamcinolone hexacetonide and became free from pain. Images PMID:1994868

Programmed Death-1 Inhibition of Phosphatidylinositol 3-Kinase/AKT/Mechanistic Target of Rapamycin Signaling Impairs Sarcoidosis CD4+ T Cell Proliferation.

PubMed

Celada, Lindsay J; Rotsinger, Joseph E; Young, Anjuli; Shaginurova, Guzel; Shelton, Debresha; Hawkins, Charlene; Drake, Wonder P

2017-01-01

Patients with progressive sarcoidosis exhibit increased expression of programmed death-1 (PD-1) receptor on their CD4 + T cells. Up-regulation of this marker of T cell exhaustion is associated with a reduction in the proliferative response to T cell receptor (TCR) stimulation, a defect that is reversed by PD-1 pathway blockade. Genome-wide association studies and microarray analyses have correlated signaling downstream from the TCR with sarcoidosis disease severity, but the mechanism is not yet known. Reduced phosphatidylinositol 3-kinase (PI3K)/AKT expression inhibits proliferation by inhibiting cell cycle progression. To test the hypothesis that PD-1 expression attenuates TCR-dependent activation of PI3K/AKT activity in progressive systemic sarcoidosis, we analyzed PI3K/AKT/mechanistic target of rapamycin (mTOR) expression at baseline and after PD-1 pathway blockade in CD4 + T cells isolated from patients with sarcoidosis and healthy control subjects. We confirmed an increased percentage of PD-1 + CD4 + T cells and reduced proliferative capacity in patients with sarcoidosis compared with healthy control subjects (P < 0.001). There was a negative correlation with PD-1 expression and proliferative capacity (r = -0.70, P < 0.001). Expression of key mediators of cell cycle progression, including PI3K and AKT, were significantly decreased. Gene and protein expression levels reverted to healthy control levels after PD-1 pathway blockade. Reduction in sarcoidosis CD4 + T cell proliferative capacity is secondary to altered expression of key mediators of cell cycle progression, including the PI3K/AKT/mTOR pathway, via PD-1 up-regulation. This supports the concept that PD-1 up-regulation drives the immunologic deficits associated with sarcoidosis severity by inducing signaling aberrancies in key mediators of cell cycle progression.

Programmed Death-1 Inhibition of Phosphatidylinositol 3-Kinase/AKT/Mechanistic Target of Rapamycin Signaling Impairs Sarcoidosis CD4+ T Cell Proliferation

PubMed Central

Celada, Lindsay J.; Rotsinger, Joseph E.; Young, Anjuli; Shaginurova, Guzel; Shelton, Debresha; Hawkins, Charlene

2017-01-01

Patients with progressive sarcoidosis exhibit increased expression of programmed death-1 (PD-1) receptor on their CD4+ T cells. Up-regulation of this marker of T cell exhaustion is associated with a reduction in the proliferative response to T cell receptor (TCR) stimulation, a defect that is reversed by PD-1 pathway blockade. Genome-wide association studies and microarray analyses have correlated signaling downstream from the TCR with sarcoidosis disease severity, but the mechanism is not yet known. Reduced phosphatidylinositol 3-kinase (PI3K)/AKT expression inhibits proliferation by inhibiting cell cycle progression. To test the hypothesis that PD-1 expression attenuates TCR-dependent activation of PI3K/AKT activity in progressive systemic sarcoidosis, we analyzed PI3K/AKT/mechanistic target of rapamycin (mTOR) expression at baseline and after PD-1 pathway blockade in CD4+ T cells isolated from patients with sarcoidosis and healthy control subjects. We confirmed an increased percentage of PD-1+ CD4+ T cells and reduced proliferative capacity in patients with sarcoidosis compared with healthy control subjects (P < 0.001). There was a negative correlation with PD-1 expression and proliferative capacity (r = −0.70, P < 0.001). Expression of key mediators of cell cycle progression, including PI3K and AKT, were significantly decreased. Gene and protein expression levels reverted to healthy control levels after PD-1 pathway blockade. Reduction in sarcoidosis CD4+ T cell proliferative capacity is secondary to altered expression of key mediators of cell cycle progression, including the PI3K/AKT/mTOR pathway, via PD-1 up-regulation. This supports the concept that PD-1 up-regulation drives the immunologic deficits associated with sarcoidosis severity by inducing signaling aberrancies in key mediators of cell cycle progression. PMID:27564547

Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Line, B.R.; Hunninghake, G.W.; Keogh, B.A.

1981-04-01

Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, we studied 41 patients with this disorder and correlated estimates of pulmonary 67Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of 67Ga accumulation in the lung compared with control subjects, only weak correlations (r lessmore » than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of 67Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because 67Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.« less

Isolated muscular sarcoidosis causing fever of unknown origin: The value of gallium-67 imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, N.; Krasnow, A.; Sebastian, J.L.

1991-02-01

An unusual case of a patient with a long-standing fever of unknown origin (FUO) is presented whose gallium-67 ({sup 67}Ga) images revealed increased activity only in the calf muscles bilaterally. Other imaging modalities also failed to show chest or other abnormal findings. Subsequent biopsy of the right gastrocnemius muscle revealed noncaseating granulomas consistent with the diagnosis of sarcoidosis. When using {sup 67}Ga to evaluate a patient with a FUO, imaging of the extremities should always be included. Also, when abnormal Ga-67 uptake is present in the extremities, sarcoidosis should be included in the differential diagnosis.

The alveolitis of pulmonary sarcoidosis. Evaluation of natural history and alveolitis-dependent changes in lung function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keogh, B.A.; Hunninghake, G.W.; Line, B.R.

1983-08-01

Current concepts of the pathogenesis of pulmonary sarcoidosis suggest that a mononuclear cell alveolitis, comprised of activated T-lymphocytes and activated alveolar macrophages, precedes and modulates the formation of granuloma and fibrosis. To evaluate the natural history of this alveolitis and determine the relationship it has to subsequent changes in lung function, 19 untreated patients with pulmonary sarcoidosis without extrapulmonary manifestations were studied with bronchoalveolar lavage, /sup 67/Ga scanning, and pulmonary function tests to evaluate lung T-cells, lung alveolar macrophages, and lung function, respectively. In patients with sarcoidosis, low intensity alveolitis (lung T-cells less than or equal to 28% of allmore » lung effector cells and/or /sup 67/Ga scan negative) was much more common (80% of all observations) than high intensity alveolitis (lung T-cells greater than 28% and /sup 67/Ga scan positive, 20% of all observations). Conventional clinical, roentgenographic, or physiologic studies could not predict the alveolitis status. Interestingly, of the 51 alveolitis evaluations in the 19 patients, there were 24 occurrences (47%) where the alveolitis was ''split,'' i.e., /sup 67/Ga scans positive and T-cells low (39%) or /sup 67/Ga negative and T-cells high (8%). Most untreated patients with sarcoidosis without extrapulmonary symptoms may have some inflammatory processes ongoing in their alveolar structures. Overall, whenever a high intensity alveolitis episode occurred, it was followed by deterioration over the next 6 months in at least one lung function parameter. A low intensity alveolitis episode was followed by functional deterioration only 8% of the time. The alveolitis parameters (lavage and /sup 67/Ga scanning) clearly predicted prognosis. These observations should prove useful in understanding the natural history of pulmonary sarcoidosis, in staging patients with this disease, and in making rational therapy decisions.« less

Cardiac Sarcoidosis: A Review of Contemporary Challenges in Diagnosis and Treatment.

PubMed

Yatsynovich, Yan; Dittoe, Nathaniel; Petrov, Mikhail; Maroz, Natallia

2018-02-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomas and is often a diagnosis of exclusion. The actual prevalence of cardiac sarcoidosis (CS) is unknown, as studies have demonstrated mixed data. CS may be asymptomatic and is likely more frequently encountered than previously thought. Sudden death may often be the presenting feature of CS. Most deaths attributed to CS are caused by arrhythmias or conduction system disease, and congestive heart failure may occur. Current expert consensus on diagnosis of CS continues to rely on endomyocardial biopsy, in the absence of which, histologic proof of extracardiac sarcoid involvement is necessitated. Emergence of newer noninvasive imaging modalities such as cardiac magnetic resonance imaging and positron emission tomography, have become increasingly popular tools utilized in patients with both clinical and asymptomatic CS, and have demonstrated good diagnostic capability. The main therapeutic approaches in patients with CS can be broadly divided into the following 2 categories: pharmacological management and invasive or device oriented. However, much remains unknown about the optimal screening protocols of asymptomatic patients with extracardiac sarcoidosis and treatment of biopsy-proven CS. Our knowledge about CS has amplified significantly over the last 30 years and the growing realization that this process is often asymptomatic is paving the way for better screening protocols and earlier detection of this serious condition. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Role of Xpert MTB/RIF in differentiating tuberculosis from sarcoidosis in patients with mediastinal lymphadenopathy undergoing EBUS-TBNA: a study of 147 patients.

PubMed

Dhooria, Sahajal; Gupta, Nalini; Bal, Amanjit; Sehgal, Inderpaul Singh; Aggarwal, Ashutosh Nath; Sethi, Sunil; Behera, Digambar; Agarwal, Ritesh

2016-10-07

In patients with intrathoracic lymphadenopathy, differentiating tuberculosis from sarcoidosis is often difficult. We hypothesized that Xpert MTB/RIF assay, a semi-automated hemi-nested PCR would help in this regard. To evaluate the performance of Xpert MTB/RIF in the differential diagnosis of tuberculosis and sarcoidosis. This was a retrospective analysis of patients with intrathoracic lymphadenopathy who underwent endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA), and were diagnosed as either tuberculosis or sarcoidosis. The results of Xpert MTB/RIF assay, tuberculin skin test and endosonographic characteristics (heterogeneous echotexture and coagulation necrosis sign) of the lymph nodes were compared between the two groups. During the study period, 465 EBUS procedures were performed and a diagnosis of sarcoidosis (n=94) or tuberculosis (n=53) was made in 147 patients. Xpert MTB/RIF was positive in 26 (49.1%) and two (2.1%) patients with tuberculosis and sarcoidosis, respectively. The sensitivity, specificity, positive and negative predictive values of Xpert MTB/RIF in the diagnosis of tuberculosis were 49.1 %, 97.9%, 92.9% and 77.3%, respectively. The presence of any of the four features namely positive Xpert MTB/RIF, positive tuberculin skin test, heterogeneous echotexture of the lymph nodes, or the presence of endosonographic coagulation necrosis sign yielded a sensitivity and negative predictive value of 83.0% and 88.0%, respectively in the diagnosis of tuberculosis versus sarcoidosis. Xpert MTB/RIF has good specificity and positive predictive value in the diagnosis of tuberculosis, and is a useful investigation in separating tuberculosis from sarcoidosis.

Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis.

PubMed

Crawshaw, Anjali; Kendrick, Yvonne R; McMichael, Andrew J; Ho, Ling-Pei

2014-07-01

Sarcoidosis is a multisystem granulomatous disorder characterized by marked T-cell expansion of T helper 1 (Th1) cells. The cause of T-cell overactivity is unknown. We hypothesized that interleukin-10 (IL-10) production by a yet undefined cell type might be defective, resulting in loss of regulation of T-cell activity. Focusing on IL-10-producing monocytes, we first showed that monocytes isolated from the peripheral blood of corticosteroid-naïve sarcoidosis patients (n = 51) produced less IL-10 compared to controls, and were less able to suppress T-cell proliferation. In addition, monocytic IL-10 production correlated negatively with disease activity score. As invariant natural killer T (iNKT) cells are known to both interact with monocytes and be reduced in sarcoidosis patients, we then asked whether iNKT-specific defects might be responsible for this reduced IL-10 production. We found that greater numbers of circulating iNKT cells was associated with higher IL-10 production. Moreover, iNKT cells enhanced monocytic IL-10 production in vitro. Defective IL-10 production and T-cell suppression by sarcoidosis monocytes could be restored following their coculture with iNKT cells, in a CD1d- and cell contact-dependent process. We suggest that reduced iNKT-cell numbers in sarcoidosis may lead to impaired monocytic IL-10 production and unchecked T-cell expansion in sarcoidosis. These findings provide fresh insight into the mechanism of sarcoidosis disease, and interaction between iNKT cells and monocytes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tellier, P.; Paycha, F.; Antony, I.

1988-08-01

In order to clarify the significance of anginal pain and myocardial thallium-201 scan defects in cardiac sarcoidosis, the pharmacologic effect of dipyridamole on myocardial perfusion was assessed by planar thallium-201 myocardial scintigraphy in patients with sarcoidosis. Thallium-201 myocardial scintigraphy was performed at rest and after 0.56 mg/kg intravenous dipyridamole during four minutes in 16 patients with sarcoidosis. The myocardial scan (45-degree and 70-degree left anterior oblique, and anterior views) was divided into 15 segments. Results were evaluated by the number of segmental defects and with a global perfusion score (from 0 to 60) by a semi-quantitative index depending on themore » size and severity of myocardial thallium-201 defects. Thirteen of the 16 patients showed partial or total reversion of their thallium-201 defects on redistribution scanning either at rest or after dipyridamole. The mean (+/- SD) number of myocardial perfusion defects that were present in all the patients decreased from 5.31 +/- 1.78 at rest to 3.25 +/- 2.52 after redistribution (p less than 0.001) and to 2.19 +/- 2.10 after dipyridamole (p less than 0.001). The mean global perfusion score increased from 53.2 +/- 3.0 at rest to 56.2 +/- 2.9 after redistribution (p less than 0.001) and to 57.2 +/- 2.7 after dipyridamole (p less than 0.001). A significant correlation (r = 0.82, p less than 0.001) was found between the increase of global perfusion score on redistribution and after dipyridamole. The reversibility of myocardial scan defects is a common finding in sarcoidosis. It makes unlikely the role of scar fibrosis or extensive confluent granulomas as a mechanism for such defects. The effect of dipyridamole suggests the presence of reversible disorders lying at the coronary microvascular level.« less

The usefulness of left atrial volume index and left ventricular mass index in determining subclinical cardiac involvement in patients with early-stage sarcoidosis.

PubMed

Kasapkara, H A; Şentürk, A; Bilen, E; Duran Karaduman, B; Ayhan, H; Özen, M B; Durmaz, T; Keleş, T; Bozkurt, E

2016-08-01

Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology. The present study has been designed to evaluate the importance of diastolic dysfunction with left atrial volume index (LAVi) and left ventricular mass index (LVMi) in determining subclinical cardiac involvement in subjects with stage I-II pulmonary sarcoidosis. A total of 54 patients under follow-up for sarcoidosis without cardiac involvement and 56 healthy subjects were included in the study. The echocardiographic assessment of the patients revealed no significant difference between the two groups regarding left ventricular end-systolic and end-diastolic diameters, ejection fraction (LVEF) and annular velocity determined by tissue Doppler evaluation. The LVEF calculated was 61.8 ± 7.8 % in the sarcoidosis group versus 64.1 ± 2.7 % in the control group (p = 0.04). Left ventricular interventricular septum thickness, posterior wall thickness, and relative wall thickness were significantly higher in the sarcoidosis group compared to the control group (p < 0.001). The sarcoidosis group had higher LVM and LVMi values compared to the control group (145 ± 18.1 and 79 ± 14 g/m(2), 135 ± 27.7 and 74 ± 14.2 g/m(2); p = 0.020 and p = 0.021, respectively). Left atrial end-systolic volume and LAVi were higher in the sarcoidosis group (28.7 ± 18.5; 15.6 ± 10.2) compared to the control group (16.6 ± 10.9; 8.9 ± 5.5) with a statistically significant difference (p < 0.001). The present study indicates diastolic dysfunction and increased LVMi despite normal systolic function in patients with early-stage sarcoidosis without cardiac involvement. Also, the diastolic parameters were normal without showing any significant difference compared to the control group while there was a statistically significant increase in LAVi. This finding suggests that LAVi may be the earliest marker of diastolic dysfunction in patients with early-stage sarcoidosis without cardiac

Propionibacterium acnes-derived insoluble immune complexes in sinus macrophages of lymph nodes affected by sarcoidosis.

PubMed

Suzuki, Yoshimi; Uchida, Keisuke; Takemura, Tamiko; Sekine, Masaki; Tamura, Tomoki; Furukawa, Asuka; Hebisawa, Akira; Sakakibara, Yumi; Awano, Nobuyasu; Amano, Tomonari; Kobayashi, Daisuke; Negi, Mariko; Kakegawa, Tomoya; Wada, Yuriko; Ito, Takashi; Suzuki, Takashige; Akashi, Takumi; Eishi, Yoshinobu

2018-01-01

Propionibacterium acnes is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect P. acnes-derived immune complexes in sarcoid lesions. We evaluated formalin-fixed and paraffin-embedded lymph node samples from 38 sarcoidosis patients and 90 non-sarcoidosis patients (27 patients with necrotizing lymphadenitis, 28 patients with reactive lymphadenitis, 16 patients with colon cancer, 19 patients with gastric cancer) by immunohistochemistry using anti-human immunoglobulins (IgG, IgA, and IgM) and complement (C1q and C3c) antibodies, and a P. acnes-specific monoclonal antibody (PAB antibody) that reacts with the membrane-bound lipoteichoic acid of P. acnes. Small round bodies (SRBs) bound to IgA, IgM, or IgG were detected in sinus macrophages, in 32 (84%), 32 (84%), or 11 (29%) sarcoid samples, respectively, and in 19 (21%), 26 (29%), or no (0%) control samples, respectively. Some of these insoluble immune complexes (IICs) also bound to C1q and C3c. We developed a microwave treatment followed by brief trypsin digestion (MT treatment) to detect PAB-reactive SRBs bound to immunoglobulins (IIC-forming P. acnes). MT treatment revealed abundant IIC-forming P. acnes in most (89%) of the sarcoid samples and sparse distribution in some (20%) of the control samples with lymphadenitis, but no IIC-forming P. acnes was detected in control samples without inflammation. IIC-forming P. acnes were mostly bound to both IgA and IgM. The PAB-reactive antigen and immunoglobulins were both located at the peripheral rim of the IIC-forming P. acnes. Conventional electron microscopy identified many SRBs (0.5-2.0 μm diameter) in sinus macrophages of sarcoid lymph nodes with many IIC-forming P. acnes, some of which were in phagolysosomes with a degraded and lamellar appearance. P. acnes-derived IICs in sinus macrophages were frequent and abundant in sarcoid lymph nodes, suggesting a potential etiologic link between

Redistribution on the thallium scan in myocardial sarcoidosis: concise communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makler, P.T.; Lavine, S.J.; Denenberg, B.S.

1981-05-01

Resting and redistribution thallium studies were performed in four young patients with sarcoidosis to evaluate the possibility of myocardial involvement. In each case the resting scan showed marked defects that resolved on the redistribution studies. In a different patient population, these results would have implied significant coronary artery disease.

Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Line, B.R.; Hunninghake, G.W.; Keogh, B.A.

1981-04-01

Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, researchers studied 41 patients with this disorder and correlated estimates of pulmonary /sup 67/Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of /sup 67/Ga accumulation in the lung compared with control subjects, only weak correlationsmore » (r less than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of /sup 67/Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because /sup 67/Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.« less

Significant elevation of the levels of B-cell activating factor (BAFF) in patients with sarcoidosis.

PubMed

Ando, Masaru; Goto, Akihiko; Takeno, Yukiko; Yamasue, Mari; Komiya, Kosaku; Umeki, Kenji; Nureki, Shin-Ichi; Miyazaki, Eishi; Kadota, Jun-Ichi

2018-06-23

B-cell activating factor (BAFF) plays an important role in the survival and differentiation of B-cells and production of antibodies. Recent studies show that the serum BAFF levels are elevated in patients with sarcoidosis; however, they have not studied the relationship of the finding with the clinical features of the disease. The purpose of the present study is to analyze the BAFF and to elucidate the relationship between BAFF levels and the disease activity or severity of sarcoidosis. Eighty-eight patients with sarcoidosis and 21 healthy volunteers were enrolled in the present study. The BAFF levels were measured by an enzyme-linked immunosorbent assay. To assess the disease severity, we examined the number of affected organs, Schadding stages, respiratory function impairment (RFI), and the scoring system developed by Wasfi et al. The serum BAFF levels in sarcoidosis patients were significantly higher than those in healthy volunteers (median 1553.0 vs 984.6 pg/ml, p < 0.001). There were positive correlations between the serum BAFF level and disease activity markers. In addition, there were positive correlations between the BAFF levels and the disease severity score in both the serum (R = 0.367, p < 0.001) and bronchoalveolar lavage fluid (BALF) (R = 0.376, p < 0.001). This study demonstrated that the BAFF levels in both the serum and BALF were positively correlated with the disease activity markers and disease severity. BAFF may be useful as an indicator of both the disease activity and severity.

Impact of early initiation of corticosteroid therapy on cardiac function and rhythm in patients with cardiac sarcoidosis.

PubMed

Padala, Santosh K; Peaslee, Samuel; Sidhu, Mandeep S; Steckman, David A; Judson, Marc A

2017-01-15

There is limited data on the effect of corticosteroid therapy in patients with cardiac sarcoidosis (CS). We sought to examine the impact of early initiation of corticosteroid therapy, within a month of CS diagnosis, on left ventricular ejection fraction (LVEF), ventricular arrhythmias (VAs), and atrioventricular (AV) block. We retrospectively identified 30 CS patients from a large university sarcoidosis clinic. The effect of early initiation of corticosteroid therapy on LVEF was assessed by serial echocardiography, and on VAs and AV block was assessed by Holter monitoring and/or device interrogations. The median time from diagnosis of extra-cardiac sarcoidosis to CS was 40months. 90% (27/30) of the CS patients received corticosteroid therapy and 85% percent (23/27) had early initiation of corticosteroid therapy. Fourteen patients (47%) had reduced EF<50%. 9/14 patients who had early initiation of corticosteroid therapy had improvement in mean EF (25% to 46%, P<0.001); 5/14 patients who had a delay in initiation or who did not receive corticosteroids had no improvement in mean EF (41% to 37%, P=0.47). Fourteen patients (47%) had VAs and 5 patients (17%) had advanced AV block. Early initiation of corticosteroid therapy resulted in no VA recurrences in 8/11 patients (72%), and complete recovery of AV conduction in 2/3 patients (67%). Patients with VAs (n=3) or advanced AV block (n=2) who failed to receive early corticosteroid therapy did not show improvement. There is often a delay in manifestation of cardiac sarcoidosis for several years from the diagnosis of extra-cardiac sarcoidosis. Prompt initiation of corticosteroid therapy in CS patients may improve outcomes whereas delayed initiation of corticosteroids or failure to use corticosteroids may be associated with worse outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Development of sarcoidosis during adalimumab therapy for chronic plaque psoriasis.

PubMed

Marcella, Stefanie; Welsh, Belinda; Foley, Peter

2011-08-01

A 38-year-old woman developed clinical, biochemical, radiological and histopathological evidence of cutaneous and pulmonary sarcoidosis 5 months after commencing adalimumab for chronic plaque psoriasis. Signs and symptoms resolved within 3 months of cessation of adalimumab. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

Cutaneous Manifestation of Sarcoidosis in Lower-Back Tattoo With Increased Uptake of 18F-FDG.

PubMed

Grosse, Jirka; Menhart, Karin; Schmidbauer, Benedikt; Hellwig, Dirk

2018-06-01

Sarcoidosis, a granulomatous T-cell-mediated multisystem disease with a yearly incidence of 10.9 to 35.5 cases per 100,000 in the United States, affects a variety of organ systems. Although the characteristic radiological finding of a bihilar lymphadenopathy still plays a diagnostic key role, FDG PET/CT is more sensitive in detecting and monitoring various manifestations. We present a rare case of a 37-year-old woman with bihilar, mediastinal, and abdominal lymphadenopathy in conjunction with a histologically proven cutaneous manifestation of sarcoidosis in a tattoo of the lower back exhibiting an increased uptake of FDG.

ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.

PubMed

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-11-08

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD.

ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density

PubMed Central

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-01-01

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD. PMID:24136731

Epidemiology and clinical characteristics of sarcoidosis: an update from a population-based cohort study from Olmsted County, Minnesota.

PubMed

Ungprasert, P; Crowson, C S; Matteson, E L

2017-05-22

Information about the epidemiology, clinical manifestations and comorbidities of sarcoidosis among Caucasians is relatively scarce. This review focuses primarily on the data from a recently published Caucasianpredominant population-based cohort from Olmsted County, Minnesota. Overall, the incidence rate was 10.0 per 100,000 population, which suggested that sarcoidosis is less common in Caucasians than in Blacks, but is more common in Caucasians than in Asians. Intrathoracic involvement was seen in the vast majority of patients, but less than half have respiratory symptoms. The most common extra-thoracic manifestations were skin rash followed by arthralgia, ophthalmologic involvement, hepatic involvement, splenomegaly, renal involvement, neurological involvement, extra-thoracic lymphadenopathy, exocrine gland involvement, upper respiratory tract involvement and cardiac involvement. Compared to sex and age-matched subjects, patients with sarcoidosis suffer from increased rates of cardiovascular disease, venous thromboembolism and hospitalized infection.

Patient confidence and quality of life in idiopathic pulmonary fibrosis and sarcoidosis.

PubMed

Kotecha, Jalpa; Atkins, Christopher; Wilson, Andrew

2016-12-23

Idiopathic pulmonary fibrosis (IPF) and sarcoidosis impact significantly on health-related quality of life (HRQOL). There are few studies on the impact of patient confidence on HRQOL in these conditions. 1. To investigate whether patient confidence is associated with HRQOL, anxiety, depression, dyspnoea or fatigue. 2. To assess if patient confidence is associated with inpatient admissions, access to community healthcare and, for IPF patients, mortality and disease severity. Study participants self-completed seven questionnaires: Hospital Anxiety and Depression Scale, EuroQol 5D (EQ5D), King's Brief Interstitial Lung Disease questionnaire, St George's Respiratory Questionnaire, MRC dyspnoea scale, Fatigue Assessment Scale and a non-validated questionnaire assessing patient confidence, symptom duration and access to community healthcare. Lung function and follow-up data were collected from hospital electronic databases. Spearman's rank correlation coefficients were calculated to assess for correlation between patient confidence, questionnaire variables and inpatient admissions. Chi-square tests were performed to assess for association between patient confidence, mortality and disease severity. 75 IPF patients and 69 sarcoidosis patients were recruited to the study. Patient confidence in IPF was significantly negatively correlated with depression and fatigue, and significantly positively correlated with EQ5D scores, but not healthcare outcomes. No associations were found between confidence and any of the variables assessed in sarcoidosis. Lower levels of confidence in IPF patients are associated with higher levels of depression and fatigue and worse HRQOL. Efforts should be made to improve patient confidence to assess the impact on HRQOL.

Late-onset and rare far-advanced pulmonary involvement in patients with sarcoidosis in Taiwan.

PubMed

Hsieh, Chia-Wei; Chen, Der-Yuan; Lan, Joung-Liang

2006-04-01

Sarcoidosis is still considered a rare multisystem disorder in Taiwan, and data on the disease course and outcome are limited. We analyzed the clinical manifestations, disease course and complications in Taiwanese patients with sarcoidosis. A retrospective cohort design was used. Fifty-six patients with sarcoidosis diagnosed between 1985 and 2004 were included. Their clinical features, laboratory findings at initial presentation, disease course, and complications were analyzed. Forty-three patients (76.8%) were female. The mean age at symptom onset was 47 years. The most common clinical symptoms were pulmonary (82.1%), cutaneous (23.2%), ophthalmic (19.6%), and articular (17.8%). Only two patients presented with Löfgren's syndrome. There was a seasonal variation in disease onset, with higher incidence in winter and early spring. No advanced pulmonary involvement was noted. Elevated levels of serum angiotensin converting enzyme (sACE) were found in 72.5% (29/40) of patients with active sarcoidosis, and significantly higher levels of sACE were found in patients with lung involvement (27.98+/-1.71 IU/L vs. 18.2+/-2.76 IU/L; p<0.01). In 50% (20/40) of patients, sACE levels declined significantly in parallel with clinical remission (24.75+/-1.53 IU/L vs. 16.33+/-1.21 IU/L; p<0.05). Spontaneous complete remission was found in 20.7% of patients, whereas 39.6% of patients with multiple extrapulmonary involvement responded poorly to intensive corticosteroids plus various immunosuppressants. In this series, the mean age of disease onset was in middle age (mean, 47 years old), there was a low incidence of Löfgren's syndrome (3.6%), and no patients had advanced pulmonary syndrome. The results of this study also suggest that sACE might be a marker of pulmonary involvement that is also useful in monitoring disease activity.

Long-Term Outcomes of Catheter Ablation of Ventricular Tachycardia in Patients With Cardiac Sarcoidosis.

PubMed

Muser, Daniele; Santangeli, Pasquale; Pathak, Rajeev K; Castro, Simon A; Liang, Jackson J; Magnani, Silvia; Hayashi, Tatsuya; Garcia, Fermin C; Hutchinson, Mathew D; Supple, Gregory E; Frankel, David S; Riley, Michael P; Lin, David; Schaller, Robert D; Desjardins, Benoit; Dixit, Sanjay; Callans, David J; Zado, Erica S; Marchlinski, Francis E

2016-08-01

Catheter ablation (CA) of ventricular tachycardia (VT) in patients with cardiac sarcoidosis can be challenging because of the complex underlying substrate. We sought to determine the long-term outcome of CA of VT in patients with cardiac sarcoidosis. We enrolled 31 patients (age, 55±10 years) with diagnosis of cardiac sarcoidosis based on Heart Rhythm Society criteria and VT who underwent CA. In 23 (74%) patients, preprocedure cardiac magnetic resonance imaging and positron emission tomographic (PET) evaluation were performed. Preprocedure magnetic resonance imaging was positive for late gadolinium enhancement in 21 of 23 (91%) patients, whereas abnormal 18-fluorodeoxyglucose uptake was found in 15 of 23 (65%) cases. In 14 of 15 patients with positive PET at baseline, PET was repeated after 6.1±3.7-month follow-up. After a median follow-up of 2.5 (range, 0-10.5) years, 1 (3%) patient died and 4 (13%) underwent heart transplant. Overall VT-free survival was 55% at 2-year follow-up. Among the 16 (52%) patients with VT recurrences, CA resulted in a significant reduction of VT burden, with 8 (50%) having only isolated (1-3) VT episodes and only 1 patient with recurrent VT storm. The presence of late gadolinium enhancement at magnetic resonance imaging, a positive PET at baseline, and lack of PET improvement over follow-up were associated with increased risk of recurrent VT. In patients with cardiac sarcoidosis and VT, CA is effective in achieving long-term freedom from VT or improvement in VT burden in the majority of patients. The presence of late gadolinium enhancement at magnetic resonance imaging, a positive PET scan at baseline, or lack of improvement at repeat PET over follow-up predict worse arrhythmia-free survival. © 2016 American Heart Association, Inc.

Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nosal, A.; Schleissner, L.A.; Mishkin, F.S.

1979-03-01

Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. Itmore » was concluded that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis.« less

[Sarcoidosis: A Descriptive Approach to the Global Research Network and Recent Scientific Developments].

PubMed

Schöffel, N; Kirchdörfer, M; Brüggmann, D; Bundschuh, M; Ohlendorf, D; Groneberg, D A; Bendels, M H K

2016-01-01

Sarcoidosis continues to be an underestimated disease that can cause severe morbidity and mortality in individuals. There has, however, been an increasing awareness of this disease as shown by the increasing number of publications since the 1990  s. The large number of available publications makes it challenging for a single scientist to provide an overview of the topic. To quantify the global research activity in this field, a scientometric investigation was conducted. The total number of publications on sarcoidosis was determined in the Web of Science to obtain their bibliometric data for the period 1900-2008. According to the NewQIS-protocol, different visualisation techniques and scientometric methods were applied. A total of 14,190 published items were evaluated. The U.S. takes a leading position in terms of the overall number of publications and collaborations. Prolific institutions and authors are of U.S. origin. Only a relatively small number of international co-operations were identified. The most intensive network is between the "University of Colorado" and the "National Jewish Medical Research Center". "Semenzato, G" has the highest citation rate of all authors. The most productive co-operative author is "du Bois, RM". The scientific interest in the topic sarcoidosis is growing steadily. The influence of international co-operation on scientific progress in this area is of increasing importance. © Georg Thieme Verlag KG Stuttgart · New York.

[Coexistence of sarcoidosis and primary Sjögren syndrome: a clinical analysis and literature review].

PubMed

Song, X Y; Huang, H; Liu, Y Z; Zhao, Y Y; Li, S; Xu, Z J

2017-05-01

Four patients with coexistence of sarcoidosis and primary Sjögren syndrome (pSS) were retrospectively analyzed.All patients were female, who were referred to our department mainly because of respiratory symptoms.Positive antinuclear antibody(ANA) was detected in 2 patients and anti-Sjögrens syndrome A (SSA) antibody positive in 1 patient.All patients presented specific histologic patterns of both sarcoidosis and pSS.Publications related to coexistence of these two diseases were reviewed.Forty-one patients were finally included in the analysis, among whom 37 confirmed patients were from literature search.There were 37 women and 4 men.The main clinical features presentation were xerophthalmia in 40, xerostomia in 38, hilaradenopathies in 28, interstitial lung disease in 15, respiratory symptoms in 13.The main immunologic data were positive ANA in 23, SSA antibody in 19, anti-Sjögrens syndrome B antibody in 10 and rheumatoid factor in 12.All patients presented specific histologic patterns of both diseases.Patients with both sarcoidosis and pSS of ten represent multisystemic involvement and positive immunologic parameters, as well as the dual expression of specific histologic characteristics.

Changes in the prevalence and biofilm formation of Haemophilus influenzae and Haemophilus parainfluenzae from the respiratory microbiota of patients with sarcoidosis.

PubMed

Kosikowska, Urszula; Rybojad, Paweł; Stępień-Pyśniak, Dagmara; Żbikowska, Anna; Malm, Anna

2016-08-26

Healthy condition and chronic diseases may be associated with microbiota composition and its properties. The prevalence of respiratory haemophili with respect to their phenotypes including the ability to biofilm formation in patients with sarcoidosis was assayed. Nasopharynx and sputum specimens were taken in 31 patients with sarcoidosis (average age 42.6 ± 13), and nasopharynx specimens were taken in 37 healthy people (average age 44.6 ± 11.6). Haemophili were identified by API-NH microtest and by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system. Biofilm was visualised by crystal violet staining and confocal scanning laser microscopy (CSLM). The statistical analysis was performed with Statgraphics Plus for Windows. In total, 30/31 patients with sarcoidosis and 31/37 healthy people were colonized by Haemophilus influenzae (6/30 vs. 1/31) and Haemophilus parainfluenzae (28/30 vs. 31/31) in the nasopharynx. The overall number of nasopharyngeal haemophili isolates was 59 in patients with sarcoidosis and 67 in healthy volunteers (H. influenzae 6/59 vs. 1/67, P = 0.05; H. parainfluenzae 47/59 vs. 65/67, P = 0.0032). Moreover, the decreased number of H. parainfluenzae biofilm-producing isolates was shown in nasopharyngeal samples in patients with sarcoidosis as compared to healthy people (19/31 vs. 57/65, P = 0.006), especially with respect to isolates classified as strong and very strong biofilm-producers (8/31 vs. 39/65, P = 0.002). The obtained data suggest that the qualitative and quantitative changes within the respiratory microbiota concerning the overall prevalence of H. influenzae together with the decreased number of H. parainfluenzae strains and the decreased rate of H. parainfluenzae biofilm-producing isolates as compared to healthy people may be associated with sarcoidosis.

Role of serum immunoglobulins for predicting sarcoidosis outcome: A cohort study.

PubMed

Belhomme, Nicolas; Jouneau, Stéphane; Bouzillé, Guillaume; Decaux, Olivier; Lederlin, Mathieu; Guillot, Stéphanie; Perlat, Antoinette; Jégo, Patrick

2018-01-01

Sarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis. We conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients. Eighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01-1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4-24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years. There was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.

Custom-made ocular prosthesis.

PubMed

Gunaseelaraj, Rajkumar; Karthikeyan, Suma; Kumar, Mohan N; Balamurugan, T; Jagadeeshwaran, A R

2012-08-01

An ocular defect may affect a patient psychologically. An ocular prosthesis is given to uplift the patient psychologically and improve the confidence. Ocular prosthesis can be custom made or a stock shell. To improve the comfort and matching of the prosthesis with that of the adjacent natural eye an custom made ocular prosthesis is preferred. Different techniques are available to fabricate a custom ocular prosthesis, here we have used paper iris disk technique.

Risk of sarcoidosis and seropositive rheumatoid arthritis from occupational silica exposure in Swedish iron foundries: a retrospective cohort study.

PubMed

Vihlborg, Per; Bryngelsson, Ing-Liss; Andersson, Lena; Graff, Pål

2017-07-20

To study the impact of occupational silica exposure on the incidence rates of sarcoidosis and rheumatoid arthritis (RA) in a cohort of exposed workers in Swedish iron foundries. The prevalence of sarcoidosis and RA in a cohort of silica exposed workers was compared with the prevalence in the general Swedish population in this register study. A mixed model was used to calculate silica exposure, and individual silica exposures were used to compute dose responses. Personnel records from 10 iron foundries were used to identify workers whose employment began before 2005 which was then linked to the national non-primary outpatient visits register. The final cohort consisted of 2187 silica-exposed male workers who had been employed for at least 1 year and were still alive without having emigrated when the follow-up study began. The cohort's employment period covers 23 807 person-years at risk. The presented results indicate that moderate to high levels of silica exposure increase risks for sarcoidosis and seropositive RA. Mean levels of airborne silica dust in the foundries decreased significantly between the 1970s and 2000s. Incidence rates of sarcoidosis (3.94; 95% CI 1.07 to 10.08) and seropositive RA (2.59; 95% CI 1.24 to 4.76) were significantly higher among highly exposed individuals. Our results reveal increased risks for sarcoidosis and seropositive RA among individuals with high exposure to silica dust (>0.048 mg/m 3 ) compared with non-exposed and less-exposed groups. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sarcoidosis with high serum levels of vascular endothelial growth factor (VEGF), showing RS3PE-like symptoms in extremities.

PubMed

Matsuda, Masayuki; Sakurai, Kumi; Fushimi, Tomohisa; Yamamoto, Kanji; Rokuhara, Shiho; Hosaka, Naritoshi; Ikeda, Shu-ichi

2004-06-01

We report a patient with sarcoidosis who showed edema in the distal portion of all extremities, particularly the legs, as seen in remitting seronegative symmetrical synovitis with pitting edema (RS3PE). Magnetic resonance imaging demonstrated diffuse abnormal intensity in subcutaneous tissues of both legs, and skin biopsy led to a diagnosis of sarcoidosis. Vascular endothelial growth factor (VEGF) showed a high serum level, which decreased soon after starting oral prednisolone, in parallel with an improvement in the limb edema. In this patient VEGF as well as infiltration by sarcoid granuloma in the skin might have played an important role in the pathogenesis of RS3PE-like symptoms in the extremities. When painful pitting edema is seen predominantly in the distal portion of all extremities, sarcoidosis as well as RS3PE should be considered as a possible diagnosis.

Cluster bomb ocular injuries.

PubMed

Mansour, Ahmad M; Hamade, Haya; Ghaddar, Ayman; Mokadem, Ahmad Samih; El Hajj Ali, Mohamad; Awwad, Shady

2012-01-01

To present the visual outcomes and ocular sequelae of victims of cluster bombs. This retrospective, multicenter case series of ocular injury due to cluster bombs was conducted for 3 years after the war in South Lebanon (July 2006). Data were gathered from the reports to the Information Management System for Mine Action. There were 308 victims of clusters bombs; 36 individuals were killed, of which 2 received ocular lacerations and; 272 individuals were injured with 18 receiving ocular injury. These 18 surviving individuals were assessed by the authors. Ocular injury occurred in 6.5% (20/308) of cluster bomb victims. Trauma to multiple organs occurred in 12 of 18 cases (67%) with ocular injury. Ocular findings included corneal or scleral lacerations (16 eyes), corneal foreign bodies (9 eyes), corneal decompensation (2 eyes), ruptured cataract (6 eyes), and intravitreal foreign bodies (10 eyes). The corneas of one patient had extreme attenuation of the endothelium. Ocular injury occurred in 6.5% of cluster bomb victims and 67% of the patients with ocular injury sustained trauma to multiple organs. Visual morbidity in civilians is an additional reason for a global ban on the use of cluster bombs.

Prevalence and Correlates of Early Right Ventricular Dysfunction in Sarcoidosis and Its Association with Outcome.

PubMed

Joyce, Emer; Kamperidis, Vasileios; Ninaber, Maarten K; Katsanos, Spyridon; Debonnaire, Philippe; Schalij, Martin J; Taube, Christian; Bax, Jeroen J; Delgado, Victoria; Ajmone Marsan, Nina

2016-09-01

Right ventricular (RV) function has not been systematically assessed in sarcoidosis. The aim of this study was to assess the prevalence and associates of RV dysfunction in sarcoidosis using global longitudinal peak systolic strain (GLS). Furthermore, whether RV dysfunction was associated with clinical outcomes was investigated. A total of 88 patients with sarcoidosis (mean age, 54 ± 13 years; 51% men) without known sarcoid-related or other structural heart disease or alternative etiologies of pulmonary hypertension were retrospectively included. RV GLS was measured using two-dimensional speckle-tracking echocardiography, and patients were stratified (using a previously defined cutoff value) as having preserved (RV GLS < -19%) or impaired (RV GLS ≥ -19%) RV function. An age- and gender-matched control group (n = 50) was included. The main outcome was all-cause mortality or clinical heart failure (hospitalization or New York Heart Association functional class ≥ III and/or deterioration by one or more classes). RV GLS was significantly reduced (-20.1 ± 4.6 vs -24.6 ± 1.8%, P = .001) in patients compared with control subjects. Patients with impaired RV function (n = 41) were older and had worse pulmonary function, worse left ventricular diastolic function, and lower tricuspid annular plane systolic excursion compared with patients with preserved RV function (n = 47). Lower tricuspid annular plane systolic excursion and diabetes were independent correlates of RV GLS. Over a median follow-up period of 37 months, 19 clinical end points occurred. Patients with impaired RV function were more likely to experience the clinical end point (log-rank P = .003). RV contractile dysfunction, identified using RV GLS, is common in patients with sarcoidosis without manifest cardiac involvement or pulmonary hypertension and is associated with adverse outcome. RV GLS may therefore be useful to detect sarcoidosis-related RV dysfunction at an earlier and

The Assessment of Cough in a Sarcoidosis Clinic Using a Validated instrument and a Visual Analog Scale.

PubMed

Judson, Marc A; Chopra, Amit; Conuel, Edward; Koutroumpakis, Efstratios; Schafer, Christopher; Austin, Adam; Zhang, Robert; Cao, Kerry; Berry, Rani; Khan, Malik M H S; Modi, Aakash; Modi, Ritu; Jou, Stephanie; Ilyas, Furqan; Yucel, Recai M

2017-10-01

Cough is a common symptom of pulmonary sarcoidosis. We analyzed the severity of cough and factors associated with cough in a university sarcoidosis clinic cohort. Consecutive patients completed the Leicester Cough Questionnaire (LCQ) and a cough visual analog scale (VAS). Clinical and demographic data were collected. Means of the LCQ were analyzed in patients who had multiple visits in terms of constant variables (e.g., race, sex). 355 patients completed the LCQ and VAS at 874 visits. Cough was significantly worse in blacks than whites as determined by the LCQ-mean (16.5 ± 2.6 vs. 17.8 ± 3.0, p < 0.001) and VAS-mean (3.8 ± 3.0 vs. 2.0 ± 2.6, p < 0.0001). Cough was worse in women than men as measured by the VAS-mean (2.7 ± 2.9 vs. 2.2 ± 2.7, p = 0.002), one of the LCQ-mean domains (LCQ-Social-mean 5.4 ± 0.9 vs. 5.2 ± 1.0, p = 0.03), but not the total LCQ-mean score. Cough was not significantly different by either measure in terms of smoking status, age, or spirometric parameter (FVC % predicted, FEV1 % predicted, FEV1/FVC). In a multivariable linear regression analysis, cough was significantly worse in blacks than whites and in pulmonary sarcoidosis than non-pulmonary sarcoidosis with both cough measures, in women than men for the VAS only, and not for spirometric parameters, Scadding stage, or age. The LCQ and VAS were strongly correlated. In a large university outpatient sarcoidosis cohort, cough was worse in blacks than whites. Cough was not statistically significantly different in terms of age, spirometric measures, Scadding stage, or smoking status. The LCQ correlated strongly with a visual analog scale for cough.

Ocular Rosacea

MedlinePlus

... Signs and symptoms of ocular rosacea may include: Dry eyes Burning or stinging in the eyes Itchy eyes ... signs and symptoms of ocular rosacea, such as dry eyes, burning or itchy eyes, redness, or blurred vision. ...

Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates.

PubMed

Asbell, Penny A; Colby, Kathryn A; Deng, Sophie; McDonnell, Peter; Meisler, David M; Raizman, Michael B; Sheppard, John D; Sahm, Daniel F

2008-06-01

Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. Laboratory investigation. Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a

Genetic susceptibility to beryllium: a case-referent study of men and women of working age with sarcoidosis or other chronic lung disease.

PubMed

Cherry, Nicola; Beach, Jeremy; Burstyn, Igor; Parboosingh, Jillian; Schouchen, Janine; Senthilselvan, Ambikaipakan; Svenson, Larry; Tamminga, Jan; Yiannakoulias, Niko

2015-01-01

The study was designed to investigate whether beryllium exposure was related to illness diagnosed as sarcoidosis. Chronic beryllium disease (CBD) and sarcoidosis are clinically and pathologically indistinguishable, with only the presence of beryllium-specific T-lymphocytes identifying CBD. Testing for such cells is not feasible in community studies of sarcoidosis but a second characteristic of CBD, its much greater incidence in those with a glutamic acid residue at position 69 of the HLA-DPB1 gene (Glu69), provides an alternative approach to answering this question. Cases of sarcoidosis aged 18-60 years diagnosed in Alberta, Canada, from 1999 to 2005 were approached through their specialist physician, together with age-matched and sex-matched referents with other chronic lung disease. Referents were grouped into chronic obstructive pulmonary disease (COPD), asthma and other lung disease. Participants completed a telephone questionnaire, including industry-specific questionnaires. DNA was extracted from mailed-in mouthwash samples and genotyped for Glu69. Duration of employment in types of work with independently documented beryllium exposure was calculated. DNA was extracted for 655 cases (270 Glu69 positive) and 1382 referents (561 positive). No increase in sarcoidosis was seen with either Glu69 or beryllium exposure (none, <10, ≥10 years) as main effects: longer duration in possible beryllium jobs was related to COPD. In Glu69 positive men with exposure ≥10 years, the trend towards increasing rate of COPD was reversed, and a significant interaction of duration of exposure and Glu69 was detected (OR=4.51 95% CI 1.17 to 17.48). The gene-environment interaction supports the hypothesis that some cases diagnosed as sarcoidosis result from occupational beryllium exposure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cluster Bomb Ocular Injuries

PubMed Central

Mansour, Ahmad M.; Hamade, Haya; Ghaddar, Ayman; Mokadem, Ahmad Samih; El Hajj Ali, Mohamad; Awwad, Shady

2012-01-01

Purpose: To present the visual outcomes and ocular sequelae of victims of cluster bombs. Materials and Methods: This retrospective, multicenter case series of ocular injury due to cluster bombs was conducted for 3 years after the war in South Lebanon (July 2006). Data were gathered from the reports to the Information Management System for Mine Action. Results: There were 308 victims of clusters bombs; 36 individuals were killed, of which 2 received ocular lacerations and; 272 individuals were injured with 18 receiving ocular injury. These 18 surviving individuals were assessed by the authors. Ocular injury occurred in 6.5% (20/308) of cluster bomb victims. Trauma to multiple organs occurred in 12 of 18 cases (67%) with ocular injury. Ocular findings included corneal or scleral lacerations (16 eyes), corneal foreign bodies (9 eyes), corneal decompensation (2 eyes), ruptured cataract (6 eyes), and intravitreal foreign bodies (10 eyes). The corneas of one patient had extreme attenuation of the endothelium. Conclusions: Ocular injury occurred in 6.5% of cluster bomb victims and 67% of the patients with ocular injury sustained trauma to multiple organs. Visual morbidity in civilians is an additional reason for a global ban on the use of cluster bombs. PMID:22346132

Central Corneal Thickness and its Relationship to Intra-Ocular and Epidmiological Determinants.

PubMed

Tayyab, Ali; Masrur, Amena; Afzal, Farooq; Iqbal, Fyza; Naseem, Kamran

2016-06-01

To measure central corneal thickness in Pakistani population and determine its relationship to intra-ocular pressure, age, gender and ethnicity. Cross-sectional observation study. Pakistan Institute of Medical Sciences, Islamabad, Pakistan, between December 2013 and February 2015. The right eyes of 1000 cases (496 males and 504 females) were recruited for this study. Inclusion criteria were Pashtun or Punjabi ethnicity, intra-ocular pressure < 22 mmHg, gonioscopically open angles, cup-disk-ratio < 0.5, and age matched normal visual fields. Cases with prior ocular surgery, contact lens use, corneal pathologies, myopia or hypermetropia > ±3.0 diopters, astigmatism of > ±1.0 diopters were excluded. Central corneal thickness was measured using a TopCon non-contact specular microscope. Intra-ocular pressure was measured using Goldmann applanation tonometer. Frequency distribution, test of significance, and regression analysis was carried out using Statistical Package for Social Sciences version 20.0. Mean age was 47.31 ±11.78 years. Ethnic composition was 51.6% (n=516) Pashtun and 48.4% (n=484) Punjabi. The mean central corneal thickness was 503.96 (±12.47) µm, while the mean intra-ocular pressure was 15.61 (±2.68) mmHg. Regression analysis showed a significant association between central corneal thickness and intra-ocular pressure (p=0.00) and age (p=0.00). A±100 µchange in central corneal thickness was associated with change in IOPof ±3.30 mmHg, whereas central corneal thickness decreased by 0.12 µm per year. No significant association could be established between central corneal thickness and ethnicity (p=0.19). Central corneal thickness of the studied races was comparable to non-Caucasians which affects intra-ocular pressure measurements, and decreases with increasing age. No relationship was observed between central corneal thickness and ethnicity or gender.

Unusual presentation of a skull base mass lesion in sarcoidosis mimicking malignant neoplasm: a case report.

PubMed

Shijo, Katsunori; Moro, Nobuhiro; Sasano, Mari; Watanabe, Mitsuru; Yagasaki, Hiroshi; Takahashi, Shori; Homma, Taku; Yoshino, Atsuo

2018-05-29

Sarcoidosis is a multi-organ disease of unknown etiology characterised by the presence of epithelioid granulomas, without caseous necrosis. Systemic sarcoidosis is rare among children, while neurosarcoidosis in children is even rarer whether it is systemic or not. We described the case of a 12-year-old boy who presented with monocular vision loss accompanied by unusual MRI features of an extensive meningeal infiltrating mass lesion. The patient underwent surgical resection (biopsy) via a frontotemporal craniotomy to establish a definitive diagnosis based on the histopathology, since neurosarcoidosis remains a very difficult diagnosis to establish from neuroradiogenic imagings. Based on the histopathology of the resected mass lesion, neurosarcoidosis was diagnosed. On follow-up after 3 months of steroid therapy, the patient displayed a good response on the imaging studies. MRI revealed that the preexisting mass lesion had regressed extremely. We also conducted a small literature review on imaging studies, manifestations, appropriate treatments, etc., in particular neurosarcoidosis including children. Although extremely rare, neurosarcoidosis, even in children, should be considered in the differential diagnosis of skull base mass lesions to avoid unnecessary aggressive surgery and delay in treatment, since surgery may have little role in the treatment of sarcoidosis.

[Extensive interactions between eating and weight disorder, major depression, pain, and sarcoidosis - case 5/2012].

PubMed

Schäflein, Eva; Wettach, Irmtraud; Smolka, Robert; Kuprion, Jürgen; Zipfel, Stephan; Teufel, Martin

2012-06-01

We report on a 41-year-old female patient suffering from obesity, binge eating more than twice a week with loss of control, eating rapidly and feeling guilty after eating, dyspnoea and chronic pain in the whole body, especially in her arms, legs and in both ankles. Furthermore, subdued mood, loss of interest and pleasure, fatigue and impaired concentration could be recognized. In the past, weight increase had been observed when corticosteroids were given against exacerbations of sarcoidosis. In the case of our patient, the beginning of sarcoidosis and increase of weight and pain correlated with augmentation of depression and psychosocial stress. Dysfunctional behavioral features and multiple interactions between diseases could be observed. We diagnosed obesity, binge eating disorder, major depression, chronic pain disease with somatic and psychical components and sarcoidosis. The patient was treated in a multimodal therapy program including psychotherapy, pharmacotherapy and psychopharmacotherapy, nutritionist advice and therapeutic exercise. A weight loss of 7.9 kg (5.9 %), well-balanced diet, reduction of binge eating and of pain intensity, mood stabilization as well as perception and expression of emotions and coping strategies in chronic diseases were achieved. Interdisciplinary treatment of patients suffering from psychosomatic, somatic and mental diseases is crucial for a good outcome. © Georg Thieme Verlag KG Stuttgart · New York.

Prevalence of cardiac sarcoidosis in white population: a case-control study: Proposal for a novel risk index based on commonly available tests.

PubMed

Martusewicz-Boros, Magdalena M; Boros, Piotr W; Wiatr, Elżbieta; Zych, Jacek; Piotrowska-Kownacka, Dorota; Roszkowski-Śliż, Kazimierz

2016-08-01

Cardiac sarcoidosis (CS) is a life-threatening and underdiagnosed manifestation of the disease, which requires a complicated and expensive diagnostic pathway. There is a need for simple tool for practitioners to determine the risk of CS without access to specialized equipment.The aim of study was to determine the prevalence of CS in a group of patients diagnosed with or followed up because of sarcoidosis. A secondary objective was the search for factors associated with heart involvement.We performed a prospective case-control study (screening analysis) in consecutive sarcoidosis patients collected from October 2012 to September 2015. Cardiac magnetic resonance (CMR) imaging was performed to confirm or exclude cardiac involvement in all patients. The study was conducted in a hospital-based referral center for patients with sarcoidosis and other interstitial lung diseases.Analysis was performed in a group of 201 patients (all white) with biopsy-proven sarcoidosis, mean age 41.4 ± 10.2, 121 of them (60.2%) males. Four patients with previously recognized cardiac diseases, which make CMR imaging for CS inconclusive, were not included.Cardiac involvement was detected by CMR in 49 patients (24.4%). Factors associated with an increased risk of CS (univariate analyses) included male sex (odds ratio [OR]: 2.5; 1.21-5.16, P = 0.01), cardiac-related symptoms (OR: 3.53; 1.81-6.89, P = 0.0002), extrathoracic sarcoidosis (OR: 3.48; 1.77-6.84, P = 0.0003), elevated serum NT-proBNP (OR: 3.82; 1.55-9.42, P = 0.004), any electrocardiography abnormality (OR: 5.38; 2.48-11.67, P = 0.0001), and contemporary radiological progression sarcoidosis in the lungs (OR: 2.98; 1.52-5.84, P = 0.001). Abnormalities in echocardiography and Holter ECG were also risk factors, but not significant in multivariate analyses. A CS Risk Index was developed using a multivariate model to predict CS, achieving an accuracy of 82%, sensitivity of 50%, specificity of 94%, and

X-linked ocular albinism in Blacks. Ocular albinism cum pigmento.

PubMed

O'Donnell, F E; Green, W R; Fleischman, J A; Hambrick, G W

1978-07-01

X-linked ocular albinism can be an unsuspected cause of congenital nystagmus in blacks. In this study, eight of ten black ocular albinos from two kindreds had nonalbinotic, moderately pigmented fundi and no transillumination of the iris. We refer to this paradoxical condition as "ocular albinism cum pigmento." The only constant ophthalmoscopic feature was a foveal hypoplasia. Biopsy of clinically normal skin to demonstrate giant pigment granules is the most accurate means of diagnosis.

Post-inflammatory fatigue in sarcoidosis: personality profiles, psychological symptoms and stress hormones.

PubMed

Korenromp, Ingrid H E; Grutters, Jan C; van den Bosch, Jules M M; Heijnen, Cobi J

2012-02-01

Chronic fatigue following inflammatory diseases has been well documented. However, little is known about possible risk factors of chronic post-inflammatory fatigue. The aim of this study was to investigate whether chronic post-inflammatory fatigue after clinical remission of the disease sarcoidosis is associated with specific dimensions of personality, psychological symptoms and baseline levels of stress hormones. Thirty-seven non-fatigued and 33 fatigued patients in clinical remission of sarcoidosis were evaluated with the Temperament and Character Inventory-short form (TCI); the Symptom CheckList-90 (SCL), and the Checklist Individual Strength (CIS). Baseline levels of ACTH and cortisol were measured in plasma. Principal component analysis with orthogonal rotation (varimax) was conducted on all personality, psychological and stress hormone data in order to obtain a smaller set of components. Logistic regression was performed to associate these components with chronic post-inflammatory fatigue. Principal component analyses identified 5 components, of which two components were significantly associated with chronic post-inflammatory fatigue. The first component comprised the personality trait Harm Avoidance and all SCL-subscales except Sleep. The second component consisted of baseline levels ACTH and cortisol, and showed an inverse association with chronic post-inflammatory fatigue. The 3 other components, consisting of respectively SCL-Sleep, TCI-Novelty Seeking-Reward Dependence-Self Transcendence, and TCI-Persistence, were not significantly associated with chronic fatigue. Chronic post-inflammatory fatigue after clinical remission of sarcoidosis is associated with a triad of risk factors: a specific personality profile with profound neurotic characteristics in combination with high levels of psychological distress, and decreased baseline ACTH/cortisol levels. Copyright © 2011 Elsevier Inc. All rights reserved.

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis).

PubMed

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C; Sarantopoulos, Konstantinos D; Yosipovitch, Gil

2017-08-01

To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity.

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis)

PubMed Central

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C.; Sarantopoulos, Konstantinos D.; Yosipovitch, Gil

2017-01-01

Purpose To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. Methods A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. Results The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Conclusions Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity. PMID:29391860

Gallium-67 scintigraphy, bronchoalveolar lavage, and pathologic changes in patients with pulmonary sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abe, S.; Munakata, M.; Nishimura, M.

1984-05-01

The intensity of gallium-67 scintiscans, lymphocyte counts in bronchoalveolar lavage fluid, and pathologic changes were studied in 26 patients with untreated pulmonary sarcoidosis. Noncaseating granulomas were recognized with significantly greater frequency in stage 2 (80 percent; 8/10 cases) than in stage 1 (43 percent; 6/14 cases). Alveolitis showed little relation to the roentgenographic stage. There was a strong correlation between the intensity of gallium uptake in pulmonary parenchyma and the detection rate of granuloma; however, the detection rate of alveolitis was not statistically different from the intensity of gallium uptake. A highly significant correlation was revealed between the lymphocyte countsmore » in bronchoalveolar lavage fluid and the intensity of alveolitis. These observations suggest that the gallium uptake reflects mainly the presence of granuloma, and the lymphocyte count in bronchoalveolar lavage fluid reflects the intensity of alveolitis in patients with pulmonary sarcoidosis.« less

The problem of the treatment of sarcoidosis: Report of the Subcommittee on Therapy.

PubMed

Turiaf, J; Johns, C J; Terstein, A S; Tsuji, S; Wurm, K

1976-01-01

Stage I: Hilar Adenopathy With normal lung function observe, as it often resolves. With reduced lung function observe for 6-12 months. Treat if there is progression or persistence. With erythema nodosum use mild anti-inflammatory agents such as salicylates or like drugs. Stage II: Adenopathy + Pulmonar Infiltrates With normal or slightly reduced lung function observe; treat if it worsens. Treat if there is no remission in 6-12 months. With reduced lung function treat, possibly for many years or a lifetime. Stage III: Pulmonary Infiltrates +/- Fibrosis Without Adenopathy There is reduced lung function. Treat, demonstrate improvement, follow patients with serial measurements of vital capacity at least. Other Indications for Treatment Other indications for treatment include myocardial sarcoidosis, cerebral sarcoidosis (although the outcome is less certain), serious hepatic or renal sarcoidosis, hypercalcemia, persistent systemic symptoms, or other serious organ or functional impairment. Assess each patient individually and completely. Use good clinical judgement. It is clear that treatment that is too little or too late is of little benefit. Even the statistical results form a perfectly controlled study cannot provide absolute direction for the individual patient. As clinicians we are frequently called upon to apply considered judgements without hard data to predict the outcome. We also maintain the flexibility to change our therapeutic programs when circumstances change, either in the patient or in our knowledge. We can be grateful we have a treatment as good as corticosteroids and must try to exercise our best judgement as to when it should be instituted.

Clinical features of sarcoidosis associated pulmonary hypertension: Results of a multi-national registry.

PubMed

Baughman, Robert P; Shlobin, Oksana A; Wells, Athol U; Alhamad, Esam H; Culver, Daniel A; Barney, Joseph; Cordova, Francis C; Carmona, Eva M; Scholand, Mary Beth; Wijsenbeek, Marlies; Ganesh, Sivagini; Birring, Surinder S; Kouranos, Vasilis; O'Hare, Lanier; Baran, Joanne M; Cal, Joseph G; Lower, Elyse E; Engel, Peter J; Nathan, Steven D

2018-06-01

Pulmonary hypertension (PH) is a significant cause of morbidity and mortality in sarcoidosis. We established a multi-national registry of sarcoidosis associated PH (SAPH) patients. Sarcoidosis patients with PH confirmed by right heart catheterization (RHC) were studied. Patients with pulmonary artery wedge pressure (PAWP) of 15 mmHg or less and a mean pulmonary artery pressure (mPAP) ≥ 25 Hg were subsequently analyzed. Data collected included hemodynamics, forced vital capacity (FVC), diffusion capacity of carbon monoxide (DL CO ), chest x-ray, and 6-min walk distance (6MWD). A total of 176 patients were analyzed. This included 84 (48%) cases identified within a year of entry into the registry and 94 (53%) with moderate to severe PH. There was a significant correlation between DL CO percent predicted (% pred) andmPAP (Rho = -0.228, p = 0.0068) and pulmonary vascular resistance (PVR) (Rho = -0.362, p < 0.0001). PVR was significantly higher in stage 4 disease than in stage 0 or 1 disease (p < 0.05 for both comparisons). About two-thirds of the SAPH patients came from the United States (US). There was a significant difference in the rate of treatment between US (67.5%) versus non-US (86%) (Chi Square 11.26, p = 0.0008) sites. The clinical features of SAPH were similar across multiple centers in the US, Europe, and the Middle East. The severity of SAPH was related to reduced DLCO. There were treatment differences between the US and non-US centers. Copyright © 2018. Published by Elsevier Ltd.

Sarcoidosis: correlation of pulmonary parenchymal pattern at CT with results of pulmonary function tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergin, C.J.; Bell, D.Y.; Coblentz, C.L.

1989-06-01

The appearances of the lungs on radiographs and computed tomographic (CT) scans were correlated with degree of uptake on gallium scans and results of pulmonary function tests (PFTs) in 27 patients with sarcoidosis. CT scans were evaluated both qualitatively and quantitatively. Patients were divided into five categories on the basis of the pattern of abnormality at CT: 1 = normal (n = 4); 2 = segmental air-space disease (n = 4); 3 = spherical (alveolar) masslike opacities (n = 4); 4 = multiple, discrete, small nodules (n = 6); and 5 = distortion of parenchymal structures (fibrotic end-stage sarcoidosis) (nmore » = 9). The percentage of the volume judged to be abnormal (CT grade) was correlated with PFT results for each CT and radiographic category. CT grades were also correlated with gallium scanning results and percentage of lymphocytes recovered from bronchoalveolar lavage (BAL). Patients in CT categories 1 and 2 had normal lung function, those in category 3 had mild functional impairment, and those in categories 4 and 5 showed moderate to severe dysfunction. The overall CT grade correlated well with PFT results expressed as a percentage of the predicted value. In five patients, CT scans showed extensive parenchymal disease not seen on radiographs. CT grades did not correlate with the results of gallium scanning or BAL lymphocytes. The authors conclude that patterns of parenchymal sarcoidosis seen at CT correlate with the PFT results and can be used to indicate respiratory impairment.« less

Poor accumulation of technetium-99m glucoheptonate in sarcoidosis and other diffuse infiltrative lung diseases as compared with gallium-67 citrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vorne, M.; Sahlstroem, K.A.; Alanko, K.

1988-02-01

Forty-two patients with diffuse infiltrative lung diseases were imaged with Ga-67 citrate and Tc-99m glucoheptonate (GH). Twenty patients had sarcoidosis, six had fibrosis, six had tuberculosis, nine had lung infiltration, and one had pleural empyema. The main difference between Ga-67 and Tc-99m GH was the much greater uptake of Ga-67 in sarcoidosis than that of Tc-99m GH. Fifteen patients with sarcoidosis had positive Ga-67 scans but only six had positive Tc-99m GH scans. The results in other diffuse infiltrative lung diseases were almost equal with Ga-67 and Tc-99m GH. Although Tc-99m GH is less expensive and simpler to use, itmore » is not an adequate substitute for Ga-67 in diffuse infiltrative lung diseases.« less

Serum angiotensin-converting enzyme (SACE) activity as an indicator of total body granuloma load and prognosis in sarcoidosis.

PubMed

Muthuswamy, P P; Lopez-Majano, V; Ranginwala, M; Trainor, W D

1987-09-01

The relationship between the level of serum angiotensin converting enzyme (SACE) and the total body granuloma load in patients with sarcoidosis was studied in two groups using SACE levels and total body gallium67 scans. The study group consisted of 22 patients with SACE levels greater than or equal to 100 U/ml (EH-SACE group) and the control group consisted of 24 patients consecutively diagnosed to have sarcoidosis in a one year period with SACE level of less than 80 U/ml. The average number of organs involved in the EH-SACE group was 3.9 +/- 1 compared to 2.3 +/- 1 in the control group (p less than 0.0001). The incidence of extra pulmonary organ involvement in the EH-SACE group was 2.2 +/- 1 organs compared to 1.0 + 0.8 in the control group (p less than 0.0002). The SACE level was correlated with the number of organs involved for all patients with sarcoidosis (r = .55; p less than .0001). Following corticosteroid therapy for 39 +/- 41 weeks the SACE dropped to 64 +/- 45 units in the EH-SACE group. But it took only 13 +/- 10 weeks to normalize the SACE level to 27 +/- 9 units in the control group. The EH-SACE group patients were followed for 114 +/- 64 weeks and 73% of them still have active sarcoidosis requiring repeated cycles of corticosteroid therapy, while after 42 +/- 23 weeks of follow up only 10% of patients from the control group were still on therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Ocular disease and driving.

PubMed

Wood, Joanne M; Black, Alex A

2016-09-01

As the driving population ages, the number of drivers with visual impairment resulting from ocular disease will increase given the age-related prevalence of ocular disease. The increase in visual impairment in the driving population has a number of implications for driving outcomes. This review summarises current research regarding the impact of common ocular diseases on driving ability and safety, with particular focus on cataract, glaucoma, age-related macular degeneration, hemianopia and diabetic retinopathy. The evidence considered includes self-reported driving outcomes, driving performance (on-road and simulator-based) and various motor vehicle crash indices. Collectively, this review demonstrates that driving ability and safety are negatively affected by ocular disease; however, further research is needed in this area. Older drivers with ocular disease need to be aware of the negative consequences of their ocular condition and in the case where treatment options are available, encouraged to seek these earlier for optimum driving safety and quality of life benefits. © 2016 Optometry Australia.

Optimized angiotensin-converting enzyme activity assay for the accurate diagnosis of sarcoidosis.

PubMed

Csongrádi, Alexandra; Enyedi, Attila; Takács, István; Végh, Tamás; Mányiné, Ivetta S; Pólik, Zsófia; Altorjay, István Tibor; Balla, József; Balla, György; Édes, István; Kappelmayer, János; Tóth, Attila; Papp, Zoltán; Fagyas, Miklós

2018-06-27

Serum angiotensin-converting enzyme (ACE) activity determination can aid the early diagnosis of sarcoidosis. We aimed to optimize a fluorescent kinetic assay for ACE activity by screening the confounding effects of endogenous ACE inhibitors and interfering factors. Genotype-dependent and genotype-independent reference values of ACE activity were established, and their diagnostic accuracies were validated in a clinical study. Internally quenched fluorescent substrate, Abz-FRK(Dnp)P-OH was used for ACE-activity measurements. A total of 201 healthy individuals and 59 presumably sarcoidotic patients were enrolled into this study. ACE activity and insertion/deletion (I/D) genotype of the ACE gene were determined. Here we report that serum samples should be diluted at least 35-fold to eliminate the endogenous inhibitor effect of albumin. No significant interferences were detected: up to a triglyceride concentration of 16 mM, a hemoglobin concentration of 0.71 g/L and a bilirubin concentration of 150 μM. Genotype-dependent reference intervals were considered as 3.76-11.25 U/L, 5.22-11.59 U/L, 7.19-14.84 U/L for II, ID and DD genotypes, respectively. I/D genotype-independent reference interval was established as 4.85-13.79 U/L. An ACE activity value was considered positive for sarcoidosis when it exceeded the upper limit of the reference interval. The optimized assay with genotype-dependent reference ranges resulted in 42.5% sensitivity, 100% specificity, 100% positive predictive value and 32.4% negative predictive value in the clinical study, whereas the genotype-independent reference range proved to have inferior diagnostic efficiency. An optimized fluorescent kinetic assay of serum ACE activity combined with ACE I/D genotype determination is an alternative to invasive biopsy for confirming the diagnosis of sarcoidosis in a significant percentage of patients.

MRI in ocular drug delivery

PubMed Central

Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

2008-01-01

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

Assessment of activity in Sarcoidosis. Sensitivity and specificity of 67Gallium scintigraphy, serum ACE levels, chest roentgenography, and blood lymphocyte subpopulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klech, H.; Kohn, H.; Kummer, F.

1982-12-01

The value of different factors are examined to assess activity in 60 patients with biopsy-proven sarcoidosis. In patients with active sarcoidosis (n . 35), /sup 67/Ga scans proved to be the most sensitive method (94 percent sensitivity), followed by serum angiotensin I converting enzyme (S-ACE) levels, chest x-ray films, and lymphocyte assays. In patients with peripheral pulmonary lesions, chest x-ray films failed in 32 percent of cases to document activity (68 percent sensitivity) whereas /sup 67/Ga scans and S-ACE levels remained to give reliable results. Despite poor specificity, negative /sup 67/Ga scans together with normal ACE levels have a highmore » predictive value for exclusion of active sarcoidosis. In patients with peripheral pulmonary lesions, chest roentgenography is of doubtful value for staging lung involvement and assessment of activity including monitoring and control of therapy.« less

Ocular changes with oxaliplatin.

PubMed

O'Dea, Denise; Handy, Catherine M; Wexler, Ann

2006-04-01

Ocular toxicity, although uncommon, can occur with many chemotherapeutic agents. Platinum compounds have been documented to produce a variety of ocular side effects, and reports have been made of ocular toxicity with oxaliplatin. This article reports on four patients who experienced ocular symptoms while receiving oxaliplatin. The symptoms included tunnel vision and visual loss with postural changes. One patient had objective findings that included papilledema. All of the changes were reversible. Oxaliplatin will continue to be used widely, so clinicians treating patients with it must be alert for unusual toxicities such as those described in this article.

Gallium-68 DOTA-NOC PET/CT as an alternate predictor of disease activity in sarcoidosis.

PubMed

Sharma, Sanchit; Singh, Achintya D; Sharma, Surendra K; Tripathi, Madhavi; Das, Chandan J; Kumar, Rajeev

2018-05-30

We evaluated the role of gallium-68-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide (Ga-DOTA-NOC) PET/CT in assessing sarcoidosis disease activity. Patients diagnosed with sarcoidosis underwent Ga-DOTA-NOC-PET/CT. The maximum standardized uptake value (SUVmax) at the pathological site and in the descending thoracic aorta (reference standard, SUVmed) were assessed. A SUVmax/SUVmed ratio (disease activity score) of more than one was considered a marker of active disease and was compared with the clinical symptoms and serum angiotensin-converting enzyme and computed tomography (CT) scan. The primary outcome was to assess the efficacy of the scan in estimating disease activity. Of the 39 patients enrolled in the study, 27 patients were symptomatic and the rest were asymptomatic at enrollment. Increased disease activity was present in 25 (92%) of the 27 symptomatic patients and two (16%) of the 12 asymptomatic patients. The sensitivity and specificity of the test were 92.5% (95% confidence interval=75.7-99.0) and 83.3% (95% confidence interval=51.5-97.9), respectively. Seven out of nine patients who became asymptomatic after treatment showed a significant decrease in the mean disease activity score in post-treatment scans (3.38±1.05 vs 1.20±0.82, P<0.001). Ga-DOTA-NOC PET/CT emerged as a useful tool to assess the disease activity and treatment response in patients with sarcoidosis with thoracic involvement.

Efficacy and Tolerance of Anti-Tumor Necrosis Factor α Agents in Cutaneous Sarcoidosis: A French Study of 46 Cases.

PubMed

Heidelberger, Valentine; Ingen-Housz-Oro, Saskia; Marquet, Alicia; Mahevas, Matthieu; Bessis, Didier; Bouillet, Laurence; Caux, Frédéric; Chapelon-Abric, Catherine; Debarbieux, Sébastien; Delaporte, Emmanuel; Duval-Modeste, Anne-Bénédicte; Fain, Olivier; Joly, Pascal; Marchand-Adam, Sylvain; Monfort, Jean-Benoît; Noël, Nicolas; Passeron, Thierry; Ruivard, Marc; Sarrot-Reynauld, Françoise; Verrot, Denis; Bouvry, Diane; Fardet, Laurence; Chosidow, Olivier; Sève, Pascal; Valeyre, Dominique

2017-07-01

Evidence for the long-term efficacy and safety of anti-tumor necrosis factor α agents (anti-TNF) in treating cutaneous sarcoidosis is lacking. To determine the efficacy and safety of anti-TNF in treating cutaneous sarcoidosis in a large observational study. STAT (Sarcoidosis Treated with Anti-TNF) is a French retrospective and prospective multicenter observational database that receives data from teaching hospitals and referral centers, as well as several pneumology, dermatology, and internal medicine departments. Included patients had histologically proven sarcoidosis and received anti-TNF between January 2004 and January 2016. We extracted data for patients with skin involvement at anti-TNF initiation. Response to treatment was evaluated for skin and visceral involvement using the ePOST (extra-pulmonary Physician Organ Severity Tool) severity score (from 0 [not affected] to 6 [very severe involvement]). Epidemiological and cutaneous features at baseline, efficacy, steroid-sparing, safety, and relapses were recorded. The overall cutaneous response rate (OCRR) was defined as complete (final cutaneous ePOST score of 0 or 1) or partial response (ePOST drop ≥2 points from baseline but >1 at last follow-up). Among 140 patients in the STAT database, 46 had skin involvement. The most frequent lesions were lupus pernio (n = 21 [46%]) and nodules (n = 20 [43%]). The median cutaneous severity score was 5 and/or 6 at baseline. Twenty-one patients were treated for skin involvement and 25 patients for visceral involvement. Reasons for initiating anti-TNF were failure or adverse effects of previous therapy in 42 patients (93%). Most patients received infliximab (n = 40 [87%]), with systemic steroids in 28 cases (61%) and immunosuppressants in 32 cases (69.5%). The median (range) follow-up was 45 (3-103) months. Of the 46 patients with sarcoidosis and skin involvement who were treated with anti-TNF were included, median (range) age was 50 (14-78) years, and 33

Vertebral sarcoidosis: demonstration of bone involvement by computerized axial tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dinerstein, S.L.; Kovarsky, J.

1984-08-01

A report is given of a rare case of vertebral sarcoidosis with negative conventional spinal x-ray films, yet with typical cystic lesions of the spine found incidentally during abdominal computerized axial tomography (CAT). The patient was a 28-year-old black man, who was admitted for evaluation of a 1 1/2-year history of diffuse myalgias, intermittent fever to 102 F orally, bilateral hilar adenopathy, and leukopenia. A technetium polyphosphate bone scan revealed diffuse areas of increased uptake over the sternum, entire vertebral column, and pelvis. Conventional x-ray films of the cervical, thoracic, and lumbar spine, and an AP view of the pelvismore » were all normal. Chest x-ray film revealed only bilateral hilar adenopathy. During the course of an extensive negative evaluation for infection, an abdominal CAT scan was done, showing multiple, small, sclerotic-rimmed cysts at multiple levels of the lower thoracic and lumbar spine. Bone marrow biopsy revealed only changes consistent with anemia of chronic disease. Mediastinal lymph node biopsy revealed noncaseating granulomas. A tentative diagnosis of sarcoidosis was made, and treatment with prednisone, isoniazid and rifampin was begun. Within two weeks of initiation of prednisone therapy, the patient was symptom-free. A repeat technetium polyphosphate bone scan revealed only a small residual area of mildly increased uptake over the upper thoracic vertebrae.« less

Sudden death from systemic sarcoidosis: a case of legal medicine.

PubMed

Zoja, R; Andreola, S; Gentile, G; Rancati, A

2012-03-01

The sarcoid condition of vital organs such as heart, lungs, liver and brain, may constitute, though rarely, a dangerous situation for survival. In forensic pathology, sudden death related to such disease represents an unusual event occurring in subjects who die unexpectedly in spite of their previous good health, and whose autopsy reveals, mainly, the involvement of heart or the central nervous system (CNS). The Authors describe a case of sudden death due to systemic sarcoidosis with atypical presentation in a young South American nulliparous woman showing, as the only symptom, occasional episodes of spotting during the last two months of her life. The only noteworthy finding from the autopsy resulted in secondary obstructive hydrocephalus. The subsequent forensic toxicological examination was negative, whereas the histopathological examination, conducted by means of post-fixation techniques and standard coloring methods on the viscera removed during autopsy, revealed useful data to determine the cause of death, consisting of a diffuse inflammatory reaction with giant cells and epithelioid cells of sarcoid type localized in the CNS and in the genitourinary apparatus. The case presented, ranking among deaths occurred unexpectedly, is a useful opportunity both for clinical remarks, given its inherent diagnostic difficulties, especially in the presence of atypical symptoms, and for legal medicine ones, given the inclusion of sarcoidosis in cases of sudden death that can give rise to criminal investigations.

Infliximab therapy balances regulatory T cells, tumour necrosis factor receptor 2 (TNFR2) expression and soluble TNFR2 in sarcoidosis.

PubMed

Verwoerd, A; Hijdra, D; Vorselaars, A D M; Crommelin, H A; van Moorsel, C H M; Grutters, J C; Claessen, A M E

2016-08-01

Sarcoidosis is a systemic granulomatous disease of unknown aetiology that most commonly affects the lungs. Although elevated levels of regulatory T cells (Tregs ) have been reported, the extent to which they play a role in sarcoidosis pathogenesis remains unclear. Tumour necrosis factor (TNF) is thought to be one of the driving forces behind granuloma formation, illustrated by the efficacy of infliximab in severe sarcoidosis. Tregs express TNF receptor 2 (TNFR2) highly. Here, we examined the influence of infliximab therapy on Tregs and (soluble) TNFR2 levels in sarcoidosis, and correlated these with response to therapy. We observed that relative frequencies of Tregs were significantly higher in patients (n = 54) compared to healthy controls (n = 26; median 6·73 versus 4·36%; P < 0·001) and decreased following therapy (4·95; P < 0·001). Baseline TNFR2 expression on Tregs was increased significantly in patients versus controls (99·4 versus 96·2%; P = 0·031), and also in responders to therapy versus non-responders (99·6 versus 97·3%; P = 0·012). Furthermore, baseline soluble TNFR2 (sTNFR2) was higher in responders than in non-responders (mean 174 versus 107 pg/ml; P = 0·015). After treatment, responders showed a significant reduction in sTNFR2 levels in peripheral blood (-44·7 pg/ml; P < 0·001), in contrast to non-responders (+3·59 pg/ml). Our results demonstrated that Treg frequencies and TNFR2 expression on Tregs are increased in sarcoidosis, followed by a decline during infliximab therapy, suggesting a pathophysiological role of this T cell subset. Interestingly, sTNFR2 levels at baseline differed significantly between responders and non-responders, making it a potential marker in predicting which patients might benefit from infliximab. © 2016 British Society for Immunology.

ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy.

PubMed

Vorselaars, Adriane D M; van Moorsel, Coline H M; Zanen, Pieter; Ruven, Henk J T; Claessen, Anke M E; van Velzen-Blad, Heleen; Grutters, Jan C

2015-02-01

In sarcoidosis, the search for disease activity markers that correlate with treatment response is ongoing. The aim of this study was to investigate the pattern of two proposed markers, serum angiotensin-converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) during methotrexate (MTX) therapy in sarcoidosis patients. We analysed 114 sarcoidosis patients who used MTX for six months, consisting of a subgroup of 76 patients with a pulmonary indication for treatment and a subgroup of 38 patients with an extra-pulmonary indication. ACE and sIL-2R serum levels were measured at baseline and after six months of treatment. Correlation coefficients (R) and odds ratios (ORs) were calculated to study the correlation and predictive effect of serum ACE and sIL-2R levels for pulmonary improvement. High baseline levels of ACE correlated significantly with lung function improvement after treatment (R = 0.45, p < 0.0001; stronger in the pulmonary subgroup R 0.57, p < 0.0001). ACE baseline levels >90 U/l predicted a 10% improvement in overall lung function (OR 3.55; CI 1.34-9.38), with the highest prediction level for 10% improvement in DLCO (OR 4.63; CI 1.23-17.4). After six months of MTX, mean ACE decreased with 17.2 U/l (p < 0.0001) and sIL-2R with 1850 pg/ml (p < 0.0001). Decreases in both ACE and sIL-2R correlated with an increase in lung function. The strongest correlation was found with change in DLCO in the pulmonary subgroup (ACE R = 0.63, P < 0.0001; sIL-2R R = 0.56, P < 0.0001). Baseline and serial serum ACE and sIL-2R levels correlate well with lung function improvement during MTX treatment. Serial measurements of these biomarkers are helpful in monitoring treatment effects in sarcoidosis patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Th17 and Treg cell levels in patients with sarcoidosis and their relation to disease activation].

PubMed

Weng, Yue-song; Wang, Hua-ying; Lv, Ding-feng; Fu, Zhong-ming; Yu, Wan-jun

2015-03-01

To investigate the Th17 cell and Treg cell levels in patients with sarcoidosis, and their relation to disease activation and glucocorticoids treatment. Twenty-three sarcoidosis patients admitted in Yinzhou People's Hospital from January 2009 to December 2013 and 25 healthy subjects (controls) were included in this study. The blood samples and bronchoalveolar lavage fluid (BALF) samples were collected in all patients before and after glucocorticoids treatment. The serum angiotensin converting enzyme (SACE) levels were detected. The percentages of Th17 cells and Treg cells in peripheral blood and BALF were determined by flow cytometry, the concentrations of cytokines in serum and supernatants of BALF were measured by enzyme-linked immunosorbent assay (ELISA). The levels of ROR-γt and Foxp3 mRNA transcripts in peripheral blood mononuclear cells (PBMC) were determined by real-time quantitative PCR. The potential correlation between the percentages of Th17 or Treg cells and SACE levels was evaluated. Compared with healthy controls, significantly higher frequencies of Th17 cells (4.34%±0.89% vs 1.60% ± 0.42%), lower frequencies of Treg cells (1.28% ± 0.37% vs 3.39% ± 0.50%) in peripheral blood were observed. Higher level of ROR-γt mRNA (21.31 ± 3.55 vs 3.63 ± 1.00) and lower level of Foxp3 mRNA (1.60 ± 0.24 vs 3.12 ± 0.76) in peripheral blood were detected in sarcoidosis patients in active stage (before glucocorticoids treatment) (all P<0.01). After the treatment of glucocorticoids, these index in peripheral blood were significantly improved (Th17 cells 2.16% ± 0.68%，Treg cells 2.21% ± 0.42%, ROR-γt mRNA 10.15 ± 1.93, Foxp3 mRNA 2.44 ± 0.38) ( all P<0.05). The changing trends of Th17 and Treg cell cytokines levels in serum were consistent with two type cells. Meanwhile, the changing trends of above index in BALF of patients treated by glucocorticoids were consistent with those in sarcoidosis patients in active stage. The increased ratios of Th17 cells to

Imitating the Great Imitator The Intersection of Sarcoidosis and Hodgkin's Lymphoma A Report of Two Cases.

PubMed

Outlaw, Darryl; Mehta, Amitkumar; Dalvi, Sam R

2018-06-01

Sarcoidosis and Hodgkin's lymphoma represent two distinct diseases with different pathogenic mechanisms, therapeutic interventions, and prognoses. Nevertheless, both diseases can have overlapping presentations, thus blurring the line between successful identification and treatment. A propensity to develop one of these diseases following diagnosis of the other has long been appreciated. Here we review two cases of presumed sarcoidosis that were ultimately diagnosed as Hodgkin's lymphoma. Both patients initially presented with non-specific symptoms and underwent a thorough workup, including histological evaluation demonstrating non-caseating granulomas without evidence of malignancy. Both patients started sarcoid-directed therapies with relapse of symptoms. Repeat imaging and tissue biopsy eventually led to the diagnosis of stage IVB Hodgkin's lymphoma. After the initiation of Hodgkin's-directed therapies, both patients showed marked clinical responses, and entered complete remission.

In vitro gallium-67 lung index for the evaluation of sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braude, A.C.; Cohen, R.; Rahmani, R.

1984-11-01

In the evaluation of the active alveolitis of pulmonary sarcoidosis, both the proportional lymphocyte count obtained by bronchoalveolar lavage and state of activation of the alveolar macrophage by gallium scanning are required. We injected 6 mCi (200 MBq) of /sup 67/Ga intravenously on 24 occasions in 13 patients with biopsy-proved sarcoidosis. Forty-eight hours later, patients were scanned with a rectilinear scanner and the generated scintigrams were evaluated using the NIH index. Seventy-two hours after injection, bronchoalveolar lavage was performed, and venous blood was sampled. The harvested lavage fluid was analyzed for absolute and proportional cell counts, and radioactivity was measuredmore » in blood and BAL fluid. An in vitro /sup 67/Ga index was generated and expressed as counts/100,000 alveolar macrophages/ml blood (mean, 0.0146 +/- 0.0087 SD). There was a significant relationship between the in vitro index and proportional lymphocyte BAL counts (r . 0.79; p less than 0.002) that was comparable to that obtained using the NIH index (r . 0.74; p less than 0.005). These data suggest that the in vitro index might offer a more objective assessment of /sup 67/Ga uptake by the lung, but this would require validation against clinical parameters in a prospective study.« less

Importance of Early Diagnosis of Cardiac Sarcoidosis in Patients with Complete Atrioventricular Block.

PubMed

Kaida, Toyoji; Inomata, Takayuki; Minami, Yoshiyasu; Yazaki, Mayu; Fujita, Teppei; Iida, Yuichiro; Ikeda, Yuki; Nabeta, Takeru; Ishii, Shunsuke; Naruke, Takashi; Maekawa, Emi; Koitabashi, Toshimi; Ako, Junya

2018-05-23

Our aim is to clarify the factors for early diagnosis of cardiac sarcoidosis (CS) in patients with complete atrioventricular block (CAVB) and its impact on cardiac function after corticosteroid therapy.A total of 15 CS patients with CAVB who underwent corticosteroid therapy were retrospectively analyzed. Patients were divided into two groups according to the time from the first CAVB onset to the diagnosis of CS. Clinical characteristics and outcomes were compared between the early diagnosis group (within 1 year; group E, n = 10) and the late diagnosis group (over 1 year; group L, n = 5).The history of extracardiac sarcoidosis (60 versus 0%, P = 0.0440) and abnormal findings on echocardiography (70 versus 0%, P = 0.0256) at the CAVB onset were significantly more frequent in group E than in group L. The change of left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) levels was significantly better in group E than in group L (0.8 ± 2.8 versus -32.4 ± 3.9%, P < 0.0001; -11.1 ± 16.0 versus 161.8 ± 35.8 pg/mL, P = 0.0013, respectively). After corticosteroid therapy, the LVEF and BNP levels were also significantly better in group E than in group L (53.3 ± 10.7 versus 37.0 ± 9.3%, P = 0.0128; 63.0 ± 46.4 versus 458.8 ± 352.0 pg/mL, P = 0.0027).The diagnosis may be delayed in CS patients with CAVB without history of extracardiac sarcoidosis. Abnormal findings on echocardiography contributed to the early diagnosis of CS. Therefore, the diagnosis of CS may be missed or delayed in patients without them. Time delay from the CAVB onset to the CS diagnosis may exacerbate the cardiac function.

Association of TNF polymorphisms with sarcoidosis, its prognosis and tumour necrosis factor (TNF)-α levels in Asian Indians

PubMed Central

Sharma, S; Ghosh, B; Sharma, S K

2008-01-01

Tumour necrosis factor (TNF)-α, an important proinflammatory cytokine, has been implicated in the pathogenesis of sarcoidosis, a multi-systemic granulomatous disorder of unknown aetiology. Here, we report for the first time the association of TNF haplotypes and genotypes with sarcoidosis and its prognosis in the Indian population. Five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene were genotyped in a clinically well-defined cohort of North-Indian patients with sarcoidosis (n = 96) and their regional controls (n = 155). Serum TNF-α (sTNF-α) and serum angiotensin converting enzyme (SACE) levels were measured and correlated with genotypes and haplotypes. The TNFA_-1031 and TNFA_-863 polymorphisms were identified as markers for disease onset (FET P = 0·006 and 0·042 for TNFA_-1031 and TNFA_-863, respectively). Additionally, the allele A of LTA_NcoI polymorphism was shown to be prevalent in the ‘no treatment’ group (FET P = 0·005), while the G allele was associated with frequent relapses on drug withdrawal (P = 0·057). Furthermore, the TNFA-308G>A and the TNFA-238G>A polymorphisms were found to influence sTNF-α (P = 0·054 and 0·0005, respectively) and SACE levels (P = 0·0017 and 0·056, respectively). The haplotype frequencies were significantly different in the patients and the controls (P = 0·0067). The haplotype GTCCGG was identified as the major risk/susceptibility haplotype (P = 0·003) and was associated with increased SACE levels in the patient population. In conclusion, our study suggests an association of TNF polymorphisms with sarcoidosis. PMID:18062795

Magnetic Resonance Imaging as a Predictor of Survival Free of Life-Threatening Arrhythmias and Transplantation in Cardiac Sarcoidosis.

PubMed

Ekström, Kaj; Lehtonen, Jukka; Hänninen, Helena; Kandolin, Riina; Kivistö, Sari; Kupari, Markku

2016-05-02

Cardiac magnetic resonance imaging has a key role in today's diagnosis of cardiac sarcoidosis. We set out to investigate whether cardiac magnetic resonance imaging also helps predict outcome in cardiac sarcoidosis. Our work involved 59 patients with cardiac sarcoidosis (38 female, mean age 46±10 years) seen at our hospital since February 2004 and followed up after contrast-enhanced cardiac magnetic resonance imaging. The extent of myocardial late gadolinium enhancement (measured as percentage of left ventricular mass), the volumes and ejection fractions of the left and right ventricles, and the thickness of the basal interventricular septum were determined and analyzed for prognostic significance. By April 2015, 23 patients had reached the study's end point, consisting of a composite of cardiac death (n=3), cardiac transplantation (n=1), and occurrence of life-threatening ventricular tachyarrhythmias (n=19; ventricular fibrillation in 5 and sustained ventricular tachycardia in 14 patients). In univariate analysis, myocardial extent of late gadolinium enhancement predicted event-free survival, as did scar-like thinning (<4 mm) of the basal interventricular septum and the ejection fraction of the right ventricle (P<0.05 for all). In multivariate Cox regression analysis, extent of late gadolinium enhancement was the only independent predictor of outcome events on cardiac magnetic resonance imaging, with a hazard ratio of 2.22 per tertile (95% CI 1.07-4.59). An extent of late gadolinium enhancement >22% (third tertile) had positive and negative predictive values for serious cardiac events of 75% and 76%, respectively. Findings on cardiac magnetic resonance imaging and the extent of myocardial late gadolinium enhancement in particular help predict serious cardiac events in cardiac sarcoidosis. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The tear film and ocular mucins.

PubMed

Davidson, Harriet J; Kuonen, Vanessa J

2004-01-01

Abstract The trilaminar tear film, composed of the lipid, aqueous and mucin layers, has many functions including defending the ocular surface. The aqueous layer has several soluble antimicrobial factors that protect the ocular surface. Ocular mucins have recently been studied with regard to their role in the defense of the eye as well as in dry eye syndromes. To date, 15 mucin genes have been identified, and six of these mucin genes are localized to or secreted by ocular glands or epithelia. Understanding the production, secretion and function of ocular mucins will aid in the treatment of dry eye syndromes and ocular surface microbial infections.

The Effect Of Pixel Size On The Detection Rate Of Early Pulmonary Sarcoidosis In Digital Chest Radiographic Systems

NASA Astrophysics Data System (ADS)

MacMahon, Heber; Vyborny, Carl; Powell, Gregory; Doi, Kunio; Metz, Charles E.

1984-08-01

In digital radiography the pixel size used determines the potential spatial resolution of the system. The need for spatial resolution varies depending on the subject matter imaged. In many areas, including the chest, the minimum spatial resolution requirements have not been determined. Sarcoidosis is a disease which frequently causes subtle interstitial infiltrates in the lungs. As the initial step in an investigation designed to determine the minimum pixel size required in digital chest radiographic systems, we have studied 1 mm pixel digitized images on patients with early pulmonary sarcoidosis. The results of this preliminary study suggest that neither mild interstitial pulmonary infiltrates nor other abnormalities such as pneumothoraces may be detected reliably with 1 mm pixel digital images.

11C-4DST PET/CT Imaging of Cardiac Sarcoidosis: Comparison With 18F-FDG and Cardiac MRI.

PubMed

Hotta, Masatoshi; Minamimoto, Ryogo; Kubota, Shuji; Awaya, Toru; Hiroi, Yukio

2018-06-01

A 75-year-old woman with a history of sarcoidosis presenting with low cardiac output and complete right bundle-branch block underwent 4'-[methyl-C]-thiothymidine (4DST) PET/CT after cardiac MRI and FDG PET/CT for the evaluation of suspected cardiac sarcoidosis (CS) before treatment. Cardiac MRI revealed late gadolinium enhancement on the anterior-to-lateral and posterior wall, indicating CS. FDG uptake was shown on the anterior-to-lateral wall, but not on the posterior wall. In contrast, 4DST uptake was demonstrated on both anterior-to-lateral and posterior walls. Use of 4DST appears promising for detecting CS without dietary restriction, due to the lack of physiological uptake in myocardium.

A COMPREHENSIVE INSIGHT ON OCULAR PHARMACOKINETICS

PubMed Central

Agrahari, Vibhuti; Mandal, Abhirup; Agrahari, Vivek; Trinh, Hoang My; Joseph, Mary; Ray, Animikh; Hadji, Hicheme; Mitra, Ranjana; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment model of ocular drug delivery has been developed for describing the absorption, distribution and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems and routes of administration are discussed including factors affecting intraocular bioavailability. Factors such as pre-corneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, drug metabolism renders ocular delivery challenging and elaborated in this manuscript. Several compartment models are discussed those are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations. PMID:27798766

High mass (>18g) of late gadolinium enhancement on CMR imaging is associated with major cardiac events on long-term outcome in patients with biopsy-proven extracardiac sarcoidosis.

PubMed

Agoston-Coldea, Lucia; Kouaho, Sylvain; Sacre, Karim; Dossier, Antoine; Escoubet, Brigitte; Chillon, Sylvie; Laissy, Jean-Pierre; Rouzet, François; Kutty, Shelby; Extramiana, Fabrice; Leenhardt, Antoine; Borie, Raphael; Crestani, Bruno; Ou, Phalla

2016-11-01

Cardiac involvement is the most important cause of mortality in patients with systemic sarcoidosis. Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) has been shown to be a predictor of major cardiovascular adverse events (MACE) in the setting of systemic sarcoidosis. We sought to evaluate the relationship between LGE mass and adverse long-term outcome in patients with biopsy-proven extracardiac sarcoidosis. Between 2001 and 2013, 197 consecutive patients with suspected cardiac sarcoidosis were identified in our institution database. Of them, 56 patients have had biopsy-proven extracardiac sarcoidosis and represented our studied population. Patients were divided into two groups based on LGE mass by a median value (mild LGE<18g, high LGE>18g) for comparison of MACE. Twenty-eight patients had a high mass of LGE. Of them, 15 (54%) experienced MACE (OR=31.15, 95% CI 3.7-262). Except for 1 patient, no patient with mild LGE presented with any MACE during follow-up (median of 32months). Patients with high LGE had lower CMR-derived left (53.6±14.9 vs. 62.2±6.7, p<0.01) and right (49.1±11.5 vs. 56.4±9.2, p<0.05) ventricular ejection fractions. LGE mass of 18g discriminated patients with and without MACE (93% sensitivity, 88% specificity, AUC=0.972). LGE mass was the only independent predictor of MACE on multivariate Cox analysis adjusted (OR=1.7, 95% CI 1.06 to 2.72, p=0.03). In biopsy-proven extracardiac sarcoidosis patients, a high mass of LGE >18g was associated with MACE. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

The Kmif (Kveim-induced macrophage migration inhibition factor) test in sarcoidosis

PubMed Central

Williams, W. Jones; Pioli, E.; Jones, D. J.; Dighero, M.

1972-01-01

Circulating lymphocytes from 30 patients with sarcoidosis when stimulated in vitro with Kveim-induced macrophage migration factor, the Kmif test, produced a guinea-pig macrophage migration inhibition factor in 21 of 30 cases (70%). In those patients not on steroids the results showed a good correlation with the cutaneous Kveim test. One positive test was found in 16 normal subjects. Our results suggest that the Kmif test may prove a useful rapid alternative to the Kveim test. PMID:4675181

Short-Term Particulate Air Pollution Exposure is Associated with Increased Severity of Respiratory and Quality of Life Symptoms in Patients with Fibrotic Sarcoidosis.

PubMed

Pirozzi, Cheryl S; Mendoza, Daniel L; Xu, Yizhe; Zhang, Yue; Scholand, Mary Beth; Baughman, Robert P

2018-05-26

This study aimed to determine if short-term exposure to particulate matter (PM 2.5 ) and ozone (O₃) is associated with increased symptoms or lung function decline in fibrotic sarcoidosis. Sixteen patients with fibrotic sarcoidosis complicated by frequent exacerbations completed pulmonary function testing and questionnaires every three months for one year. We compared 7-, 10-, and 14-day average levels of PM 2.5 and O₃ estimated at patient residences to spirometry (forced expiratory volume in 1 s (FEV1), to forced vital capacity (FVC), episodes of FEV1 decline > 10%) and questionnaire outcomes (Leicester cough questionnaire (LCQ), Saint George Respiratory Questionnaire (SGRQ), and King's Sarcoidosis Questionnaire (KSQ)) using generalized linear mixed effect models. PM 2.5 level averaged over 14 days was associated with lower KSQ general health status (score change -6.60 per interquartile range (IQR) PM 2.5 increase). PM 2.5 level averaged over 10 and 14 days was associated with lower KSQ lung specific health status (score change -6.93 and -6.91, respectively). PM 2.5 levels were not associated with FEV₁, FVC, episodes of FEV₁ decline > 10%, or respiratory symptoms measured by SGRQ or LCQ. Ozone exposure was not associated with any health outcomes. In this small cohort of patients with fibrotic sarcoidosis, PM 2.5 exposure was associated with increased severity of respiratory and quality of life symptoms.

Anti-TNF-α therapy in refractory uveitis associated with sarcoidosis: Multicenter study of 17 patients.

PubMed

Riancho-Zarrabeitia, Leyre; Calvo-Río, Vanesa; Blanco, Ricardo; Mesquida, Marina; Adan, Alfredo M; Herreras, José M; Aparicio, Ángel; Peiteado-Lopez, Diana; Cordero-Coma, Miguel; García Serrano, José Luis; Ortego-Centeno, Norberto; Maíz, Olga; Blanco, Ana; Sánchez-Bursón, Juan; González-Suárez, Senén; Fonollosa, Alejandro; Santos-Gómez, Montserrat; González-Vela, Carmen; Loricera, Javier; Pina, Trinitario; González-Gay, Miguel A

2015-12-01

To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13-76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4-8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range-IQR) 0.5 (0-2) versus 0 (0-0) (p = 0.003), vitritis 0 (0-1.25) versus 0 (0-0) (p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) (p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0-30)mg at the onset of the anti-TNF-α therapy to 0 (0-0)mg at 2 years (p = 0.02). Significant reduction was

Cicatricial changes in ocular pemphigus

PubMed Central

Chirinos-Saldaña, P; Zuñiga-Gonzalez, I; Hernandez-Camarena, J C; Navas, A; Ramirez-Luquin, T; Robles-Contreras, A; Jimenez-Martinez, M C; Ramirez-Miranda, A; Bautista-de Lucio, V M; Graue-Hernandez, E O

2014-01-01

Purpose To describe the clinical characteristics of ocular involvement in patients with pemphigus at an ophthalmological referral center. Methods A retrospective review was conducted on patients with the immunopathological diagnosis of pemphigus examined between 1 January 2000 and 1 April 2010. Uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (BCVA), ocular symptoms, and ocular surface inflammatory and scarring changes were assessed. Results A total of 15 patients were identified, with a mean age of 68.27±14.35 years, and 80% (n=12) were female. Extraocular involvement was reported in one patient. All of the eyes showed cicatricial changes in the conjunctiva. In all, 6 eyes (20%) were classified as stage I; 12 eyes (40%) as stage II; 10 eyes (33%) as stage III; and 2 eyes (7%) as stage IV. A statistically significant association was found between BCVA and the severity of ocular involvement. The mean BCVA logMAR was 1.66 (20/914), with a range from logMAR 0 (20/20) to logMAR 4 (NLP). Other ocular diseases were found in 8 (53.3%), systemic diseases in 10 (66.7%), and the use of pemphigus-inducing drugs in 10 patients (66.7%). Conclusions The present report represents the largest series of ocular involvement in pemphigus confirmed by immunopathology. The clinical manifestations varied from conjunctival hyperemia to corneal scarring and perforation. There was a strong association between scarring changes and low BCVA. Ocular and systemic diseases as well as the use of pemphigus-inducing drugs may predispose to ocular cicatricial changes observed in this series. PMID:24480839

Ocular drug delivery systems: An overview

PubMed Central

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

2014-01-01

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

Ocular drug delivery systems: An overview.

PubMed

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

Sarcoidosis presenting as granulomatous myositis in a 16-year-old adolescent.

PubMed

Orandi, Amir B; Eutsler, Eric; Ferguson, Cole; White, Andrew J; Kitcharoensakkul, Maleewan

2016-11-10

Sarcoidosis is a multi-system disease characterized by the presence of non-caseating epithelioid granulomas in affected tissues, including skeletal muscle. These organized collections of immune cells have important pathophysiologic action including cytokine production leading to inflammation as well as enzymatic conversion of cholecalciferol to calcitriol via 1-α hydroxylase. There are limited reports of isolated granulomatous myositis causing hypercalcemia in pediatric patients. Our patient uniquely presented with symptoms from hypercalcemia and renal insufficiency caused by an overwhelming burden of granulomatous myositis in her lower extremities, but was otherwise asymptomatic. A 16 year old Caucasian female presented with protracted symptoms of fatigue, nausea and prominent weight loss with laboratory evidence of hypercalcemia and renal insufficiency. She lacked clinical and physical findings of arthritis, weakness, rash, uveitis, fever, lymphadenopathy or respiratory symptoms. After extensive negative investigations, re-examination yielded subtle soft tissue changes in her lower extremities, with striking MRI findings of extensive myositis without correlative weakness or serum enzyme elevation. Biopsy showed the presence of non-caseating epithelioid granulomas and calcium oxalate crystals. The patient responded well to prednisone and methotrexate but relapsed with weaning of steroids. She reachieved remission with addition of adalimumab. Sarcoidosis should be considered in patients presenting with symptomatic hypercalcemia with no apparent causes and negative routine workup. The absences of decreased muscle strength or elevated muscle enzymes do not preclude the diagnosis of granulomatous myositis.

Ocular emergencies presenting to Menelik II Hospital.

PubMed

Negussie, Dereje; Bejiga, Abebe

2011-01-01

Ocular conditions such as trauma, painful red eye of any cause, painless sudden visual loss and others are commonly seen as ocular emergencies, and can lead to ocular morbidity and visual loss. To determine types and causes of ocular emergencies seen at Menelik II hospital. A cross-sectional study was conducted from April to October, 2007. Consecutive patients who presented with ocular emergencies at any time of the day were prospectively evaluated and registered on a formatted questionnaire. Evaluation of the patients included history of presenting illness, visual acuity testing intraocular pressure measurement on non-perforated and non-infected eyes, and complete eye examination in order to arrive at the diagnosis. A total of 26,400 patients attended Menelik II hospital during the study period. Of these, 758 (3%) were persons with an ocular emergency. The majority of patients (n=551; 72.7%) were male, with a male to female ratio of 2.7:1. The age group of 16 to 30 years was the most affected (47.9%), followed by those aged 15 years or younger (27.3%). Ocular trauma and ocular infections accounted for 75.6% and 13.1% of cases, respectively. Of the total ocular emergencies, open globe injuries constituted 171 (22.6%), corneal foreign bodies and abrasion 125 (16.5%), and open adnexal injuries 119 (15.7%). Metal and wood were the commonest work-related causes of ocular injuries in adults, with both together accounting for 60% of all ocular injuries. Children, on the other hand, sustained ocular injury while playing with others in 128 (22.3%) of cases. This study was able to provide a more complete picture to improve understanding of the nature and circumstances of ocular emergencies in Ethiopia. Ocular emergencies were dominated by ocular trauma, particularly affecting males and working-age adults. Public education and use of protective safety measures are recommended to alleviate the problem.

[Application of Ocular Trauma Score in Mechanical Ocular Injury in Forensic Medicine].

PubMed

Xiang, Jian; Guo, Zhao-ming; Wang, Xu; Yu, Li-li; Liu, Hui

2015-10-01

To evaluate the application value for the prognosis of mechanical ocular injury cases using ocular trauma score (OTS). Four hundred and eleven cases of mechanical ocular trauma were retrospectively reviewed. Of the 449 eyes, there were 317 closed globe injury and 132 open globe injury. OTS variables included numerical values as initial visual acuity, rupture, endophthalmitis, perforat- ing or penetrating injury, retinal detachment and relative afferent pupillary block. The differences be- tween the distribution of the final visual acuity and the probability of standard final visual acuity were compared to analyze the correlation between OTS category and final visual acuity. The different types of ocular trauma were compared. Compared with the distribution of final visual acuity in standard OTS score, the ratio in OTS-3 category was statistically different in present study, and no differences were found in other categories. Final visual acuity showed a great linear correlation with OTS category (r = 0.71) and total score (r = 0.73). Compared with closed globe injury, open globe injury was generally associated with lower total score and poorer prognosis. Rupture injury had poorer prognosis compared with penetrating injury. The use of OTS for the patients with ocular trauma can provide re- liable information for the evaluation of prognosis in forensic medicine.

Ocular pulsation correlates with ocular tension: the choroid as piston for an aqueous pump?

PubMed

Phillips, C I; Tsukahara, S; Hosaka, O; Adams, W

1992-01-01

In 26 random out-patients, including 13 treated glaucoma patients and ocular hypertensives, the higher the ocular tension, the greater the pulse amplitude, by Alcon pneumotonometry, at a statistically significant level. In a single untreated hypertensive, when 2-hourly pneumotonometry was done for 24 h, the correlation was similar and significant. The higher the diastolic blood pressure, the higher the ocular pulsation, also significantly. Pulsation is suggested to be a pump, the choroid being the piston, contributing (1) to an increase in the outflow of aqueous humour and (2) to a homeostatic mechanism contributing to normalization of the intra-ocular pressure, wherein pulsation increases or decreases, as the intraocular pressure increases or decreases, respectively.

/sup 67/Ga citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

/sup 67/Ga citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n . 30) and in 71% of patients with inactive disease (n . 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r..436; p less than .005). The frequency of abnormalmore » /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical indentification of inactive sacoidosis.« less

Sarcoidosis-associated pulmonary hypertension.

PubMed

Cordova, Francis C; D'Alonzo, Gilbert

2013-09-01

Pulmonary hypertension is a serious complication of sarcoidosis. This review discusses clinical characteristics of patients with sarcoid-associated pulmonary hypertension (SAPH) and pitfalls in the diagnosis, and highlights potential therapies. SAPH is common in patients with advanced disease, but it can occur in patients with minimal disease burden. Risk factors for SAPH include restrictive lung physiology, hypoxemia, advanced Scadding chest X-ray stage, and low carbon monoxide diffusion capacity. Echocardiogram is a good initial screening tool in the diagnosis of pulmonary hypertension, but right heart catheterization is necessary to confirm the diagnosis. Treatment with pulmonary vasodilators, including endothelin antagonists, can lead to improvements in pulmonary hemodynamics in some patients but may not improve their exercise capacity. Forced vital capacity is an important predictor of exercise performance in patients with SAPH. Clinical observations and response to specific therapies for pulmonary hypertension suggest the presence of different SAPH phenotypes. Patients who complain of persistent dyspnea should be screened for the presence of pulmonary hypertension. The prognosis of SAPH is poor and it is prudent to consider referral of these patients for lung transplantation. In some patients with SAPH, treatment with anti-inflammatory agents and pulmonary vasodilators can lower pulmonary arterial pressures, improve dyspnea and functionality, and enhance overall quality of life.

A joint procedural position statement on imaging in cardiac sarcoidosis: from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology.

PubMed

2017-10-01

This joint position paper illustrates the role and the correct use of echocardiography, radionuclide imaging with 18F-fluorodeoxyglucose positron emission tomography, radionuclide myocardial perfusion imaging and cardiovascular magnetic resonance imaging for the evaluation and management of patients with known or suspected cardiac sarcoidosis. This position paper will aid in standardizing imaging for cardiac sarcoidosis and may facilitate clinical trials and pooling of multi-centre data on cardiac sarcoidosis. Proposed flow charts for the work up and management of cardiac sarcoidosis are included. Copyright © 2017 European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology.

Myocardial Blood Flow and Inflammatory Cardiac Sarcoidosis.

PubMed

Kruse, Matthew J; Kovell, Lara; Kasper, Edward K; Pomper, Martin G; Moller, David R; Solnes, Lilja; Chen, Edward S; Schindler, Thomas H

2017-02-01

This study sought to evaluate the effects of inflammatory sarcoid disease on coronary circulatory function and the response to immune-suppressive treatment. Although positron emission tomography assessment of myocardial inflammation is increasingly applied to identify active cardiac sarcoidosis, its effect on coronary flow and immune-suppressive treatment remains to be characterized. Thirty-two individuals, who were referred for positron emission tomography/computed tomography, were evaluated for known or suspected cardiac sarcoidosis applying 18 F-fluorodeoxyglucose to determine inflammation and 13 N-ammonia to assess for perfusion deficits following a high-fat/low-carbohydrate diet and fasting state >12 h to suppress myocardial glucose uptake. Inflammation was quantified with standardized uptake value and regional myocardial blood flow at rest and during regadenoson-stimulated hyperemia was determined in ml/g/min. Positron emission tomography studies were repeated in 18 cases with a median follow-up of 2.5 years (interquartile range [IQR]:1.3 to 3.4 years). Twenty-five exams had normal perfusion but evidence of regional inflammation (group 1), and 21 exams presented a regional perfusion deficit associated with inflammation (group 2). Median myocardial blood flow did not differ between inflamed and noninflamed myocardium in both groups (0.86 ml/g/min [IQR: 0.66 to 1.11 ml/g/min] vs. 0.83 ml/g/min [IQR: 0.64 to 1.12 ml/g/min] and 0.74 ml/g/min [IQR: 0.60 to 0.93 ml/g/min] vs. 0.77 ml/g/min [IQR: 0.59 to 0.95 ml/g/min], respectively). As regards median hyperemic myocardial blood flows, they were significantly lower in the inflamed than in the remote regions in group 1 and 2 (2.31 ml/g/min [IQR: 1.81 to 2.95 ml/g/min] vs. 2.70 ml/g/min [IQR: 2.07 to 3.30 ml/g/min] and 1.61 ml/g/min [IQR: 1.17 to 2.18 ml/g/min] vs. 1.94 ml/g/min [IQR: 1.49 to 2.39 ml/g/min]; p < 0.001, respectively). Immune-suppression-mediated decrease in inflammation was associated with

Ocular trauma.

PubMed

Cassen, J H

1997-10-01

A review of the literature was conducted to investigate recent articles about ocular trauma. Eye injuries may be divided into blunt and penetrating types. Males are more affected than females. Evaluation of eye injuries should start with visual acuity and continue with prompt referral to an ophthalmologist as indicated. Medlines search/American Academy of Ophthalmology. Ocular trauma is a frequent reason for emergency room visits. Most injuries stem from sports, recreation, military, occupational, or automotive. Patient education is highly recommended, as well as prevention by use of protective polycarbonate eyewear.

Epidemiology of ocular toxoplasmosis.

PubMed

Petersen, Eskild; Kijlstra, Aize; Stanford, Miles

2012-04-01

Retinal infection with Toxoplasma gondii is the most important cause of posterior uveitis, whereby prevalence and incidence of ocular symptoms after infection depend on socio-economic factors and the circulating parasite genotypes. Ocular toxoplasmosis is more common in South America, Central America, and the Caribbean and parts of tropical Africa as compared to Europe and Northern America, and is quite rare in China. Ocular disease in South America is more severe than in other continents due to the presence of extremely virulent genotypes of the parasite. Drinking untreated water is considered the major source of Toxoplasma infection in developing countries, whereas in the Western world the consumption of raw or undercooked meat (products) is the most important cause. Since acquired infection with T. gondii is currently a more important cause of ocular toxoplasmosis compared to congenital infection, prevention should be directed not only toward pregnant women but toward the general population.

[Descending ocular myopathy].

PubMed

de Freitas, M R; Nascimento, O J

1975-06-01

The case of a 23 years old female patient, with primary involvement of the extraocular and faringeal muscles without familiar history is reported. Electromyographic and muscular biopsy studies proved the myogenic nature of the process. A clinical comparison between the ocular myopathy and the descending ocular myopathy is made, the authors thinking that both of them would be variants of the same muscle disease.

Ocular Manifestations of Acquired Immunodeficiency Syndrome.

PubMed

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong; Lee, Sung Jin

2015-08-01

To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations versus anterior segment ocular

Elevated Serum Anti-GM-CSF Antibodies before the Onset of Autoimmune Pulmonary Alveolar Proteinosis in a Patient with Sarcoidosis and Systemic Sclerosis.

PubMed

Yamasue, Mari; Nureki, Shin-Ichi; Usagawa, Yuko; Ono, Tomoko; Matsumoto, Hiroyuki; Kan, Takamasa; Kadota, Jun-Ichi

2017-09-01

Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of periodic acid-schiff stain-positive lipoproteinaceous materials in the alveolar space due to impaired surfactant clearance by alveolar macrophage. Autoimmune PAP is the most common form of PAP, but rarely accompanies collagen disease or sarcoidosis. We report here a rare case of autoimmune PAP preceded by systemic sclerosis and sarcoidosis. A 64-year-old woman was admitted to our hospital for blurred vision, muscle weakness of extremities, Raynaud's phenomenon, and exertional dyspnea. We diagnosed her as having systemic sclerosis complicated with sarcoidosis. Chest computed tomography (CT) and transbronchial lung biopsy showed the findings of pulmonary fibrosis without PAP. We treated her with corticosteroid and intravenous cyclophosphamide therapy, followed by tacrolimus therapy. Thereafter, her symptoms improved except for exertional dyspnea, and she began to complain of productive cough thirteen months after corticosteroid and immunosuppressant therapy. On the second admission, a chest CT scan detected the emergence of crazy-paving pattern in bilateral upper lobes. Bronchoalveolar lavage (BAL) fluid with milky appearance and a lung biopsy specimen revealed acellular periodic acid-schiff stain-positive bodies. The serum titer of anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibodies was elevated on first admission and remained high on second admission. We thus diagnosed her as having autoimmune PAP. Reducing the dose of immunosuppressive agents and repeating the segmental BAL resulted in the improvement of her symptoms and radiological findings. Immunosuppressant therapy may trigger the onset of autoimmune PAP in a subset of patients with systemic sclerosis and/or sarcoidosis.

Efficacy of /sup 67/Ga-scintigraphy in predicting the diagnostic yield of transbronchial lung biopsy in pulmonary sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ackart, R.S.; Munzel, T.L.; Rodriguez, J.J.

1982-07-01

Nineteen consecutive patients with clinically suspected sarcoidosis underwent /sup 67/Ga-scintigraphy prior to transbronchial lung biopsy (TBLB) to determine if /sup 67/Ga uptake in lung parenchyma would increase the diagnostic yield of the biopsy procedure. Biopsies were obtained from the areas showing parenchymal uptake on the /sup 67/Ga scan in 13 of the 19 patients. In the six patients not demonstrating uptake of /sup 67/Ga in the lung parenchyma, biopsies were obtained at random from the right lower lobe. There was no correlation between /sup 67/Ga uptake in hilar nodes or pulmonary parenchyma tissue and the diagnostic yield from TBLB. Researchersmore » conclude that /sup 67/Ga scanning is neither efficacious nor cost-effective in predicting the diagnostic yield of TBLB in sarcoidosis.« less

Ga-67 positivity in sarcoidosis of the skin with coincident thyroid uptake of uncertain etiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreno, A.J.; Brown, J.M.; Salinas, J.A.

1984-03-01

Gallium-67 citrate scintigraphy of a 26-year-old woman with systemic sarcoidosis demonstrated abnormal radiotracer uptake within multiple biopsy-proven sarcoidal cutaneous lesions and within both lobes of the thyroid gland. The etiology of the thyroidal uptake of the Ga-67 was uncertain but it may represent sarcoidal involvement of the gland.

[Ocular surface system integrity].

PubMed

Safonova, T N; Pateyuk, L S

2015-01-01

The interplay of different structures belonging to either the anterior segment of the eye or its accessory visual apparatus, which all share common embryological, anatomical, functional, and physiological features, is discussed. Explanation of such terms, as ocular surface, lacrimal functional unit, and ocular surface system, is provided.

Challenging ocular image recognition

NASA Astrophysics Data System (ADS)

Pauca, V. Paúl; Forkin, Michael; Xu, Xiao; Plemmons, Robert; Ross, Arun A.

2011-06-01

Ocular recognition is a new area of biometric investigation targeted at overcoming the limitations of iris recognition performance in the presence of non-ideal data. There are several advantages for increasing the area beyond the iris, yet there are also key issues that must be addressed such as size of the ocular region, factors affecting performance, and appropriate corpora to study these factors in isolation. In this paper, we explore and identify some of these issues with the goal of better defining parameters for ocular recognition. An empirical study is performed where iris recognition methods are contrasted with texture and point operators on existing iris and face datasets. The experimental results show a dramatic recognition performance gain when additional features are considered in the presence of poor quality iris data, offering strong evidence for extending interest beyond the iris. The experiments also highlight the need for the direct collection of additional ocular imagery.

Cutaneous sarcoidosis in a patient with ulcerative colitis on infliximab.

PubMed

Fok, Kum C; Ng, Watson W S; Henderson, Christopher J A; Connor, Susan J

2012-07-01

The advance of anti-tumour necrosis factor (TNF) therapy had dramatically changed the treatment algorithm of inflammatory bowel disease (IBD). This had significantly improved the quality of life for patients with Crohn's disease (CD) and ulcerative colitis (UC).(1) However, side-effects of anti-TNF treatment were unavoidable with paradoxical inflammation (for example leucocytoclastic vasculitis and psoriasis) being well-known phenomena of anti-TNF therapy.(2) We report a case of infliximab induced cutaneous sarcoidosis in a patient with ulcerative colitis and review the literature. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Increases in Ocular Syphilis-North Carolina, 2014-2015.

PubMed

Oliver, Sara E; Cope, Anna Barry; Rinsky, Jessica L; Williams, Charnetta; Liu, Gui; Hawks, Stephanie; Peterman, Thomas A; Markowitz, Lauri; Fleischauer, Aaron T; Samoff, Erika

2017-10-30

Ocular syphilis is an inflammatory eye disease due to Treponema pallidum infection. In the United States, syphilis rates have increased since 2000; clusters of ocular syphilis were reported in 2015. We investigated ocular syphilis in North Carolina to describe the epidemiology and clinical course of disease. We reviewed syphilis cases reported to North Carolina during 2014-2015 and abstracted information from health department interviews for cases with ocular symptoms and no other defined etiology. To assess duration and severity of ocular symptoms, we also reviewed medical records and conducted structured interviews. We compared the prevalence of ocular manifestations among reported syphilis cases by demographic and clinical characteristics. Among 4232 syphilis patients, 63 (1.5%) had ocular syphilis: 21 in 2014 and 42 in 2015, a 100% increase. Total syphilis cases increased 35% through 2015. No patient with ocular syphilis named another ocular syphilis patient as a sex partner. Patients presented in all syphilis stages; 24 (38%) were diagnosed in primary or secondary syphilis. Ocular manifestations were more prevalent among syphilis patients who were male, aged ≥40 years, white, and infected with human immunodeficiency virus. No risk behaviors were associated with ocular syphilis. Among 39 interviewed patients, 34 (87%) reported reduced vision during infection; 12 (31%) reported residual visual symptoms posttreatment. In North Carolina, ocular syphilis increased from 2014 to 2015 and may be due to increased recognition of ocular manifestations, or a true increase in ocular syphilis. Many ocular syphilis patients experienced vision loss; however, most improved posttreatment. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Ocular complications of boxing

PubMed Central

Bianco, M; Vaiano, A; Colella, F; Coccimiglio, F; Moscetti, M; Palmieri, V; Focosi, F; Zeppilli, P; Vinger, P

2005-01-01

Objectives: To investigate the prevalence of ocular injuries in a large population of boxers over a period of 16 years, in particular, the most severe lesions that may be vision threatening. Methods: Clinical records of the medical archive of the Italian Boxing Federation were analysed. A total of 1032 boxers were examined from February 1982 to October 1998. A complete ophthalmological history was available for 956, who formed the study population (a total of 10 697 examinations). The following data were collected: age when started boxing; duration of competitive boxing career (from the date of the first bout); weight category; a thorough ocular history. The following investigations were carried out: measurement of visual acuity and visual fields, anterior segment inspection, applanation tonometry, gonioscopy, and examination of ocular fundus. Eighty age matched healthy subjects, who had never boxed, formed the control group. Results: Of the 956 boxers examined, 428 were amateur (44.8%) and 528 professional (55.2%). The median age at first examination was 23.1 (4.3) years (range 15–36). The prevalence of conjunctival, corneal, lenticular, vitreal, ocular papilla, and retinal alterations in the study population was 40.9% compared with 3.1% in the control group (p⩽0.0001). The prevalence of serious ocular findings (angle, lens, macula, and peripheral retina alterations) was 5.6% in boxers and 3.1% in controls (NS). Conclusions: Boxing does not result in a higher prevalence of severe ocular lesions than in the general population. However, the prevalence of milder lesions (in particular with regard to the conjunctiva and cornea) is noteworthy, justifying the need for adequate ophthalmological surveillance. PMID:15665199

Evaluating ocular blood flow

PubMed Central

Maram, Jyotsna; Srinivas, Sowmya; Sadda, Srinivas R

2017-01-01

Studies have shown that vascular impairment plays an important role in the etiology and pathogenesis of various ocular diseases including glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal venous occlusive disease. Thus, qualitative and quantitative assessment of ocular blood flow (BF) is a topic of interest for early disease detection, diagnosis, and management. Owing to the rapid improvement in technology, there are several invasive and noninvasive techniques available for evaluating ocular BF, with each of these techniques having their own limitations and advantages. This article reviews these important techniques, with a particular focus on Doppler Fourier domain optical coherence tomography (OCT) and OCT-angiography. PMID:28573987

Combat ocular trauma and systemic injury.

PubMed

Weichel, Eric D; Colyer, Marcus H

2008-11-01

To review the recent literature regarding combat ocular trauma during hostilities in Operations Iraqi Freedom and Enduring Freedom, describe the classification of combat ocular trauma, and offer strategies that may assist in the management of eye injuries. Several recent publications have highlighted features of combat ocular trauma from Operation Iraqi Freedom. The most common cause of today's combat ocular injuries is unconventional fragmentary munitions causing significant blast injuries. These explosive munitions cause high rates of concomitant nonocular injuries such as traumatic brain injury, amputation, and other organ injuries. The most frequent ocular injuries include open-globe and adnexal lacerations. The extreme severity of combat-related open-globe injuries leads to high rates of primary enucleation and retained intraocular foreign bodies. Visual outcomes of intraocular foreign body injuries are similar to other series despite delayed removal, and no cases of endophthalmitis have occurred. Despite these advances, however, significant vision loss persists in cases of perforating globe injuries as well as open and closed-globe trauma involving the posterior segment. This review summarizes the recent literature describing ocular and systemic injuries sustained during Operations Iraqi and Enduring Freedom. An emphasis on classification of ocular injuries as well as a discussion of main outcome measures and complications is discussed.

Ocular Manifestations of Acquired Immunodeficiency Syndrome

PubMed Central

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong

2015-01-01

Purpose To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). Methods This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Results Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. Conclusions The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations

Ocular diseases: immunological and molecular mechanisms.

PubMed

Song, Jing; Huang, Yi-Fei; Zhang, Wen-Jing; Chen, Xiao-Fei; Guo, Yu-Mian

2016-01-01

Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.

Immunohistochemical identification of Propionibacterium acnes in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients.

PubMed

Asakawa, Naoya; Uchida, Keisuke; Sakakibara, Mamoru; Omote, Kazunori; Noguchi, Keiji; Tokuda, Yusuke; Kamiya, Kiwamu; Hatanaka, Kanako C; Matsuno, Yoshihiro; Yamada, Shiro; Asakawa, Kyoko; Fukasawa, Yuichiro; Nagai, Toshiyuki; Anzai, Toshihisa; Ikeda, Yoshihiko; Ishibashi-Ueda, Hatsue; Hirota, Masanori; Orii, Makoto; Akasaka, Takashi; Uto, Kenta; Shingu, Yasushige; Matsui, Yoshiro; Morimoto, Shin-Ichiro; Tsutsui, Hiroyuki; Eishi, Yoshinobu

2017-01-01

Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect Propionibacterium acnes, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients. We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P. acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (≥14 inflammatory cells) and minimal (<14 inflammatory cells) inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS-group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18 (46%) of the CM-group samples. P. acnes-positive reactivity in granulomas, massive inflammatory foci, and minimal inflammatory foci were detected in 10 (63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none of the M-group and CM-group samples. Frequent identification of P. acnes in sarcoid granulomas of originally aseptic myocardial tissues suggests that this indigenous bacterium causes granuloma in many CS patients. IHC detection of P. acnes in massive or minimal inflammatory foci of myocardial biopsy samples without granulomas may be useful for differentiating sarcoidosis from myocarditis or other cardiomyopathies.

Plasticity of the human otolith-ocular reflex

NASA Technical Reports Server (NTRS)

Wall, C. 3rd; Smith, T. R.; Furman, J. M.

1992-01-01

The eye movement response to earth vertical axis rotation in the dark, a semicircular canal stimulus, can be altered by prior exposure to combined visual-vestibular stimuli. Such plasticity of the vestibulo-ocular reflex has not been described for earth horizontal axis rotation, a dynamic otolith stimulus. Twenty normal human subjects underwent one of two types of adaptation paradigms designed either to attenuate or enhance the gain of the semicircular canal-ocular reflex prior to undergoing otolith-ocular reflex testing with horizontal axis rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about a vertical axis with a 0.2 Hz optokinetic stripe pattern that was deliberately mismatched in peak velocity. Pre- and post-adaptation horizontal axis rotations were at 60 degrees/s in the dark and produced a modulation in the slow component velocity of nystagmus having a frequency of 0.17 Hz due to putative stimulation of the otolith organs. Results showed that the magnitude of this modulation component response was altered in a manner similar to the alteration in semicircular canal-ocular responses. These results suggest that physiologic alteration of the vestibulo-ocular reflex using deliberately mismatched visual and semicircular canal stimuli induces changes in both canal-ocular and otolith-ocular responses. We postulate, therefore, that central nervous system pathways responsible for controlling the gains of canal-ocular and otolith-ocular reflexes are shared.

Validity of mini-dose gallium for objective quantification of alveolitis in pulmonary sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vitti, R.; Maurer, A.H.; Siegel, J.A.

1985-05-01

Patents (pts) with pulmonary sarcoidosis will often have frequent gallium (Ga) studies to assess the response of alveolitis to corticosteroid therapy. Since many pts are young and the cumulative radiation burden significant the authors have evaluated the ability of computer based Ga lung imaging to reliably quantify Ga activity using a 0.5 mCi dose of Ga. Twelve pts with biopsy proven pulmonary sarcoidosis received 0.5 mCi of Ga-67 citrate intravenously and had a posterior view of the chest including a portion of the liver obtained at 24 hrs post injection. At 24 hrs the pts received an additional 2.5 mCimore » and were then imaged at 48 and 72 hrs. A gallium score (GS) was computer generated as follows: regions of interest (ROI's) were manually created for the lungs, liver and background. Following a 9 point spatial smooth and background subtraction, the images were scaled so that the liver activity was assigned an arbitrary value of 400 counts per pixel. The resulting average counts per pixel for the lungs were then summed for the GS. Using a paired T-test there was only a borderline significant difference (0.05« less

Etiologic Aspect of Sarcoidosis as an Allergic Endogenous Infection Caused by Propionibacterium acnes

PubMed Central

2013-01-01

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Propionibacterium acnes is the only microorganism that has been isolated from sarcoid lesions. Many P. acnes have been detected in sarcoid lymph nodes using quantitative PCR and in sarcoid granulomas by in situ hybridization. P. acnes trigger factor protein causes a cellular immune response only in sarcoid patients and induces pulmonary granulomas in mice sensitized with the protein and adjuvant, but only those with latent P. acnes infection in their lungs. Eradication of P. acnes by antibiotics prevents the development of granulomas in this experimental model. Although P. acnes is the most common commensal bacterium in the lungs and lymph nodes, P. acnes-specific antibody detected the bacterium within sarcoid granulomas of these organs. P. acnes can cause latent infection in the lung and lymph node and persist in a cell-wall-deficient form. The dormant form is activated endogenously under certain conditions and proliferates at the site of latent infection. In patients with P. acnes hypersensitivity, granulomatous inflammation is triggered by intracellular proliferation of the bacterium. Proliferating bacteria may escape granulomatous isolation, spreading to other organs. Latent P. acnes infection in systemic organs can be reactivated by another triggering event, leading to systemic sarcoidosis. PMID:23844371

What Is an Ocular Migraine?

MedlinePlus