Brasileiro, A; Fonseca Oliveira, J; Pinheiro, S; Paiva-Lopes, M J
The therapeutic efficacy of high-dose intravenous immunoglobulin in systemic lupus erythematosus (SLE) patients is well established. However, side effects might limit its use and lead to the consideration of therapeutic alternatives, such as the subcutaneous formulation of immunoglobulin, which has been used in some patients with other autoimmune diseases. We report a case of SLE refractory to classical therapies. High-dose intravenous immunoglobulin was effective, but gave rise to significant side effects. The patient was successfully treated with subcutaneous human immunoglobulin, achieving and maintaining clinical and laboratory remission. A lower immunoglobulin dose was needed and no side effects were observed, compared to the intravenous administration. Subcutaneous immunoglobulin could be a better-tolerated and cost-saving therapeutic option for select SLE patients.
Lupus erythematosus (LE) is a multisystem disease. Genetic predisposition, altered immunity, hormones, drugs, viruses, and ultraviolet light all may play a role in etiology. A wide range of cutaneous lesions occur, and variants such as subacute cutaneous LE, complement-deficient LE, and neonatal LE have recently been emphasized. Management of the LE patient, including appropriate diagnostic studies and therapy relevant to the dermatologist, is discussed in the review.
... Name: Category: Share: Yes No, Keep Private Discoid Lupus Erythematosus Share | Discoid lupus erythematosus (DLE) is a chronic skin condition of ... occur. A small percentage of patients with discoid lupus can develop disease of the internal organs, which ...
de Macedo, José Fernando; de Macedo, Gustavo Capinzaiki; Campos, Luciana Aparecida; Baltatu, Ovidiu Constantin
Patients with systemic lupus erythematosus have a poor prognosis of pregnancy, since it is associated with significant maternal and fetal morbidity, including spontaneous miscarriage, pre-eclampsia, intrauterine growth restriction, fetal death and pre-term delivery. We report a case with successful pregnancy in a patient with systemic lupus erythematosus and hypertension. A 39-year-old nulliparous woman presented with systemic lupus erythematosus with antinuclear and antiphospholipid antibodies, hypertension and recurrent pregnancy loss presented for assisted reproduction. The patient responded well to enoxaparin and prednisone during both assisted reproduction and prenatal treatment. This case report indicates that prescription of immunosuppressant and blood thinners can be safely recommended throughout the whole prenatal period in patients with systemic lupus erythematosus. Enoxaparin and prednisone may be prescribed concurrently during pregnancy.
... Causes Drug-induced lupus erythematosus is similar to systemic lupus erythematosus (SLE). It is an autoimmune disorder. This means ... 2015:chap 132. Wright B, Bharadwaj S, Abelson A. Systemic lupus erythematosus. In: Carey WD, ed. Cleveland Clinic: Current Clinical ...
Celhar, Teja; Fairhurst, Anna-Marie
Mouse models of SLE have been indispensable tools to study disease pathogenesis, to identify genetic susceptibility loci and targets for drug development, and for preclinical testing of novel therapeutics. Recent insights into immunological mechanisms of disease progression have boosted a revival in SLE drug development. Despite promising results in mouse studies, many novel drugs have failed to meet clinical end points. This is probably because of the complexity of the disease, which is driven by polygenic predisposition and diverse environmental factors, resulting in a heterogeneous clinical presentation. Each mouse model recapitulates limited aspects of lupus, especially in terms of the mechanism underlying disease progression. The main mouse models have been fairly successful for the evaluation of broad-acting immunosuppressants. However, the advent of targeted therapeutics calls for a selection of the most appropriate model(s) for testing and, ultimately, identification of patients who will be most likely to respond.
Jiang, S; Lei, T-C; Xu, S-Z
Patients with systemic lupus erythematosus (SLE) have an increased susceptibility to bacterial, viral, fungal and parasitic infections. Cryptococcal infection of the central nervous system (CNS) is a rare but often fatal complication of SLE. Here, we describe a case of cryptococcal meningitis in a female patient with active SLE, who was successfully treated with amphotericin B. This case suggests that the clinical findings of SLE patients with cryptococcal meningitis are non-specific and misleading, and early use of amphotericin B has a good response.
Kalińska-Bienias, Agnieszka; Kowalewski, Cezary; Woźniak, Katarzyna
So far in the literature there have been reported only 5 patients with a recognized and well-documented history of systemic lupus erythematosus (SLE) who developed SCLE after terbinafine introduction. Here we report two women suffering from SLE who developed SCLE after initiation of oral terbinafine for onychomycosis. Skin lesions in both of them were extensive, located on the trunk, and upper and lower extremities. No exacerbation of SLE symptoms was observed at that time. Despite severe skin lesions, patients revealed good response to topical corticosteroids within a few weeks. The systemic review of the literature and our experience on terbinafine-induced SCLE developing in patients with SLE allowed to create a description for this special subset: a) terbinafine-induced SCLE usually develop in 1-8 weeks after terbinafine introduction, b) skin lesions are usually severe, disseminated including lower extremities, c) patients present Ro/SS-A La/SS-B antibodies, but anti-histone antibodies are rarely observed, d) exacerbation of SLE symptoms is rather not observed, e) eruptions clear within 2-8 weeks, f) withdrawal of terbinafine and topical corticosteroids should be considered as a first-line therapy in these cases, g) terbinafine should be carefully used in patients suffering from SLE.
Sams, Wiley M.
Cutaneous disorders which manifest themselves on the exposed parts are more likely than are hidden lesions to cause the patient to seek professional services promptly. Usually he consults his family physician or the community dermatologist. The physician who first sees the patient is dependent upon his own resources for management and diagnosis. A background of experience, a measure of energy and an inquisitive attitude are the necessary ingredients for successful management. The difficulties involved in differentiating early lupus erythematosus and polymorphic light eruptions cannot be invariably resolved even with the most complete review. The course of the disorder and the response to environmental factors supply important clues. Investigative work, especially in the field of immunology, offers hope for the solution of some of our problems. PMID:5909872
Hammami, Sonia; Bdioui, Fethia; Ouaz, Afef; Loghmari, Hichem; Mahjoub, Sylvia; Saffar, Hamouda
Systemic lupus erythematous (SLE) is an auto-immune disease with multiple organ involvements that occurs mainly in young women. Literature data suggest that serositis is more frequent in late-onset SLE. However, peritoneal serositis with massive ascites is an extremely rare manifestation. We report a case of old-onset lupus peritonitis treated successfully by Hydroxychloroquine. A 77-year-old Tunisian woman was hospitalized because of massive painful ascites. Her family history did not include any autoimmune disease. She was explored 4 years prior to admission for exudative pleuritis of the right lung without any established diagnosis. Physical examination showed only massive ascites. Laboratory investigations showed leucopenia: 3100/mm3, lymphopenia: 840/mm3 and trace protein (0.03 g/24 h). Ascitic fluid contained 170 cells mm(3) (67% lymphocytes), 46 g/L protein, but no malignant cells. The main etiologies of exudative ascites were excluded. She had markedly elevated anti-nuclear antibody (ANA) titer of 1/1600 and a significantly elevated titer of antibody to double-stranded DNA (83 IU/mL) with hypo-complementemia (C3 levl was at 67 mg/dL). Antibody against the Smith antigen was also positive. Relying on these findings, the patient was diagnosed with SLE and treated with Hydroxychloroquine 200 mg daily in combination with diuretics. One month later, there was no detectable ascitic fluid and no pleural effusions. Five months later she remained free from symptoms while continuing to take chloroquine. This case was characterized by old age of onset of SLE, the extremely rare initial presentation with lupus peritonitis and massive painful ascites with dramatic response to only hydroxychloroquine treatment.
Pinazo, María-Jesús; Espinosa, Gerard; Gállego, Montserrat; López-Chejade, Paulo Luis; Urbina, Julio A.; Gascón, Joaquim
American Trypanosomiasis or Chagas disease (CD) is a neglected disease that affects Latin American people worldwide. Two old antiparasitic drugs, benznidazole and nifurtimox, are currently used for specific CD treatment with limited efficacy in chronic infections and frequent side effects. New drugs are needed for patients with chronic CD as well as for immunosuppressed patients, for whom the risk of reactivation is life-threatening. We describe a case of chronic CD and systemic lupus erythematosus (SLE) that required immunosuppression to control the autoimmune process. It was found that benznidazole induced a reduction, but not an elimination, of circulating Trypanosoma cruzi levels, whereas subsequent treatment with posaconazole led to a successful resolution of the infection, despite the maintenance of immunosuppressive therapy. PMID:20348503
Arce-Salinas, C A; Pérez-Silva, E
This case involved a 75-year-old woman with systemic lupus erythematosus. Two months previously, she had a flare that was treated successfully by increasing the dosages of prednisone and azathioprine. A sudden onset of ocular pain, diplopia, and loss of vision suggestive of optical neuritis or vascular involvement confused the issue, and rhinocerebral zygomycosis was demonstrated later. We review the presentations of this fungal infection in patients with systemic lupus erythematosus with emphasis on its initial features.
Jasmin, R; Sockalingam, S; Shahrizaila, N; Cheah, T-E; Zain, A A; Goh, K-J
Peripheral neuropathy is a known manifestation of systemic lupus erythematosus. However, the association of primary autoimmune inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) with SLE is uncommon. We report a 26-year-old man who simultaneously presented with severe CIDP and photosensitive rash, but was unresponsive to intravenous immunoglobulin infusion and continued to progress. He was found to have underlying SLE and improved with combined corticosteroid and immunosuppressive therapy with oral cyclophosphamide. CIDP with underlying SLE may be more resistant to conventional therapy with IVIG, requiring the addition of other immunosuppressive agents.
Gatto, Mariele; Saccon, Francesca; Zen, Margherita; Bettio, Silvano; Iaccarino, Luca; Punzi, Leonardo; Doria, Andrea
Patients affected with systemic lupus erythematosus (SLE) still display increased mortality and decreased quality of life in respect to general population. The major determinant of poor long term prognosis is organ damage, which is predictive of more damage and death. Damage is in turn triggered by uncontrolled disease activity and especially by the long-standing corticosteroid use which often accompanies SLE patients over their disease course, owing both to the need of reaching disease remission and to the habit of keeping patients on a small steroid dose for an indefinite period of time. Hence, the need for new drugs and therapeutic strategies aiming at minimizing damage accrual through a better control of disease activity and a steroid-sparing potential is paramount. So far, however, the therapeutic strategy in SLE requires a multitarget approach which is not devoid of widespread immunesuppression. In fact, several studies have been carried out in recent years targeting both the adaptive and the innate immune system, the majority of which did not achieve their primary endpoint, being often divergent from successful clinical experience and thereby committing physician to off-label use of targeted therapies in face of refractory SLE manifestations. The study designs and the chosen endpoints were often blamed for inadequacy, being at least in part responsible for study failures. In this review, we go over major clinical trials conducted in SLE by analyzing any critical aspects related to study design, predefined endpoints and biological activity of novel compounds that may have hampered study outcome, despite the great effort of providing less toxic drugs within a targeted, pathogenic-based approach.
Shaikh, Maliha F; Jordan, Natasha; D'Cruz, David P
Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease that is highly heterogeneous in its presentation. This can pose significant challenges for physicians responsible for the diagnosis and treatment of such patients. SLE arises from a combination of genetic, epigenetic and environmental factors. Pathologically, the disease is primarily driven by loss of immune tolerance and abnormal B- and T-cell function. Major organ involvement may lead to significant morbidity and mortality. Classification criteria for SLE have been developed largely for research purposes; however, these are also widely used in clinical practice. Antinuclear antibodies are the hallmark serological feature, occurring in over 95% of patients with SLE at some point during their disease. The mainstay of treatment is antimalarial drugs such as hydroxychloroquine, combined with corticosteroids and conventional immunosuppressive drugs. An increasing understanding of pathogenesis has facilitated a move towards the development of targeted biologic therapies, with the introduction of rituximab and belimumab into clinical practice.
Skin ulcers are a dangerous and uncommon complication of vasculitis. We describe the case of a teenager suffering from Systemic Lupus Erythematosus with digital ulcer resistant to conventional therapy, treated successfully with Hyperbaric Oxygen Therapy. The application of hyperbaric oxygen, which is used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. Further studies are needed to evaluate its role as primary therapy for this group of patients. PMID:21040521
French, M A; Hughes, P
A case of Klinefelter's syndrome presenting with systemic lupus erythematosus while receiving androgen replacement therapy is described. The association of systemic lupus erythematosus with Klinefelter's syndrome is discussed, particularly in terms of the effect of sex hormones. PMID:6882046
Kim, Grace K.; Del Rosso, James Q.
The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice. PMID:23320123
Kaul, Arvind; Gordon, Caroline; Crow, Mary K; Touma, Zahi; Urowitz, Murray B; van Vollenhoven, Ronald; Ruiz-Irastorza, Guillermo; Hughes, Graham
Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.
Ahearn, Joseph M; Liu, Chau-Ching; Kao, Amy H; Manzi, Susan
The urgent need for lupus biomarkers was demonstrated in September 2011 during a Workshop sponsored by the Food and Drug Administration: Potential Biomarkers Predictive of Disease Flare. After 2 days of discussion and more than 2 dozen presentations from thought leaders in both industry and academia, it became apparent that highly sought biomarkers to predict lupus flare have not yet been identified. Even short of the elusive biomarker of flare, few biomarkers for systemic lupus erythematosus (SLE) diagnosis, monitoring, and stratification have been validated and employed for making clinical decisions. This lack of reliable, specific biomarkers for SLE hampers proper clinical management of patients with SLE and impedes development of new lupus therapeutics. As such, the intensity of investigation to identify lupus biomarkers is climbing a steep trajectory, lending cautious optimism that a validated panel of biomarkers for lupus diagnosis, monitoring, stratification, and prediction of flare may soon be in hand.
Gondane, Swati; Kothiwala, Rajkumar; Dangi, Sapna; Meherda, Ashok
A case of lupus erythematosus (LE) panniculitis in pregnancy without any lesions of discoid LE or systemic LE is being reported. There were no systemic symptoms. Her ANA, anti-dsDNA, anti-Ro/SSA, and anti-La/SSB antibodies were within normal limits. Diagnosis of lupus panniculitis was considered on clinical and histopathological grounds. The condition responded favorably to systemic steroid therapy. PMID:26677307
Sokalski, D G; Copsey Spring, T R; Roberts, W N
A 23-year-old African-American woman with a history of recurrent pneumonias presented to the hospital with 2 weeks of shortness of breath, chest pain, fevers, and lightheadedness. The histologic diagnosis proved to be lupus aortitis. Optimal Framingham risk factor management by itself may not be a completely successful approach in diminishing the extra risk of atherosclerosis conferred by systemic lupus erythematosus (SLE). Therefore it remains possible that important modifiable cardiovascular risk factors may include low-grade SLE disease activity in medium-sized vessels. The implication of the idea that subclinical vessel inflammation is widespread in patients with lupus-and that this inflammation confers a significant part of the patients' risk of accelerated atherosclerosis-might be a lowering of the threshold for aggressive disease-modifying treatment of lupus, essentially a "treat-to-target" approach to systemic lupus.
Mallavarapu, Ravi K; Grimsley, Edwin W
This article explores the history of lupus erythematosus from the origins of the name to the most modern therapeutic advances. The review includes information about the origin of the name "lupus," the first clear description of the skin lesions, the discovery of the systemic and discoid forms, and further advances which define our current view of this illness. The classical descriptions of Hippocrates, Paracelsus, Manardi, Rudolph Virchow, Cazenave, Robert Willan, and Moritz Kaposi are chronologically described. Later, the contributions of Sir William Osler, Jonathan Hutchinson, Sequira and Balean, Kraus and Bohac, Libman and Sacks, Malcolm Hargraves, and Edmund L. Dubois are highlighted. The major breakthroughs of the modern period, including the diagnostic tests, animal models, and genetics, are briefly described. The article ends with the history of drug-induced lupus, diagnostic criteria, and the history of the therapy of lupus erythematosus. With modern therapeutic advances, the mortality rate from lupus erythematosus has decreased substantially. It is hoped that current research will further improve the prognosis of this disease in the near future.
Sjöwall, C; Hjorth, M; Eriksson, P
Although the putative therapeutic options for patients with systemic lupus erythematosus (SLE) are steadily increasing, refractory disease is indeed a major challenge to many clinicians and patients. The proteasome inhibitor bortezomib - approved for the treatment of multiple myeloma since the beginning of this century - was recently reported successful in twelve cases of refractory SLE by German colleagues. Herein, we describe two Swedish SLE cases with refractory renal and pulmonary manifestations that were rescued by bortezomib as induction of remission followed by monthly doses of belimumab. The patients were carefully monitored with regard to disease activity and renal function. Anti-dsDNA and anti-C1q antibodies, complement proteins and lymphocyte subsets were analysed in consecutive samples. In December 2016, the patients had been in clinical remission post bortezomib administration for a period of 28 and 22 months, respectively. Potential benefits of using belimumab as maintenance therapy to prevent regeneration of autoreactive B cell clones are discussed.
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Ahn, Grace E; Ramsey-Goldman, Rosalind
Systemic lupus erythematosus is a chronic inflammatory autoimmune disease often characterized by fatigue, with significant effects on physical functioning and wellbeing. The definition, prevalence and factors associated with fatigue, including physical activity, obesity, sleep, depression, anxiety, mood, cognitive dysfunction, vitamin D deficiency/insufficiency, pain, effects of medications and comorbidities, as well as potential therapeutic options of fatigue in the systemic lupus erythematosus population are reviewed. Due to variability in the reliability and validity of various fatigue measures used in clinical studies, clinical trial data have been challenging to interpret. Further investigation into the relationships between these risk factors and fatigue, and improved measures of fatigue, may lead to an improvement in the management of this chronic inflammatory disease.
Propper, D J; Bucknall, R C
A sixteen year old girl with systemic lupus erythematosus developed acute transverse myelopathy. She was treated with high dose steroids, cyclophosphamide, and plasma exchange and regained partial neurological function. Previous descriptions of transverse myelopathy complicating systemic lupus erythematosus are reviewed, with particular reference to the efficacy of high dose steroid treatment. PMID:2662918
A 39-year-old man presented with a 4-month history of unilateral blepharitis that did not respond to conventional treatment. Punch biopsy confirmed the diagnosis of discoid lupus erythematosus. Unilateral blepharitis as the only presenting sign of discoid lupus erythematosus is uncommon but should be considered in the differential diagnosis in patients with asymmetric blepharitis.
Callen, J P
Subacute cutaneous lupus erythematosus (SCLE) is a subset of cutaneous lupus erythematosus with unique immunologic and clinical features. The first description dates back to 1985 when a series of five patients were found to have hydrochlorothiazide-induced SCLE. Since that time, at least 40 other drugs have been implicated in the induction of SCLE.
Pai, Varadraj V; Naveen, KN; Athanikar, SB; Dinesh, US; Reshme, Priyanka; Divyashree, RA
Subacute cutaneous lupus erythematosus (SCLE) is a type of lupus erythematosus having distinct characteristic clinical, serologic, and genetic features. Other than the commonly occurring papulosquamous and annular polycyclic lesion, rarely it may present as erythema multiformae, toxic epidermo necrolysis like lesion (Rowell syndrome), erythroderma, and generalized poikiloderma. Herein, we report a case of SCLE presenting as erythroderma. PMID:25484433
Skare, Thelma Larocca; Dagostini, Jéssica Scherer; Zanardi, Patricia Imai; Nisihara, Renato Mitsunori
ABSTRACT Objective To determine the incidence of infections in a population of systemic lupus erythematosus individuals and the characteristics of infections regarding original site, as well as to study the possible associations between infections and treatment. Methods An analytical retrospective study using data from medical charts of systemic lupus erythematosus patients from a single university hospital. A total of 144 patients followed up for five years were included. Data collected comprised age of patients and age at onset of lupus, sex and ethnicity, disease duration before the study period, medications, cumulative dose of prednisone, occurrence of infections and their original site. Results The most frequent infections were urinary tract infections (correlated to use of prednisone − p<0.0001 and cyclophosphamide − p=0.045), upper airways infections (correlated to use of prednisone − p=0.0004, mycophenolate mofetil − p=0.0005, and cyclosporine − p=0.025), and pneumonia (associated to prednisone − p=0.017). Conclusion Prednisone was the drug more often associated with presence of infections, pointing to the need for a more judicious management of this drug. PMID:27074234
Ayán, C; Martín, V
Systemic lupus erythematosus (SLE) is a rheumatic disease characterized by a variety of symptoms, especially fatigue, pain and reduced quality of life. Physical exercise is a useful tool for improving cardiovascular fitness, reducing metabolic abnormalities and fatigue and improving quality of life. However, very few studies have focused on the relationship between SLE and physical exercise. This paper reviews the main SLE symptoms that can be alleviated by exercising, as well as the results of studies seeking to analyse the exercise capacity and physical training possibilities of SLE patients. Considerations for future research are also discussed.
Belimumab is the only approved biological agent for the treatment of systemic lupus erythematosus (SLE). It is a fully humanized IgG1γ monoclonal antibody directed against soluble B lymphocyte stimulator (BLyS). It is indicated as an add-on therapy for the treatment of adult patients with active, autoantibody-positive SLE, who are receiving standard therapy. Belimumab is generally well-tolerated, common adverse effects include infections, infusion reactions, hypersensitivity, headache, nausea, and fatigue. Psychiatric events including suicidal tendency, progressive multifocal leukoencephalopathy and malignancies too have been reported. Apart from SLE, the drug is also being tried for other autoimmune disorders. PMID:27688447
COJOCARU, Manole; COJOCARU, Inimioara Mihaela; SILOSI, Isabela; VRABIE, Camelia Doina
ABSTRACT Systemic lupus erythematosus (SLE) is a chronic, multifaceted autoimmune inflammatory disease that can affect any part of the body. SLE is a disease of unknown aetiology with a variety of presenting features and manifestations. Interest in the disease has been stimulated in recent years, and improved methods of diagnosis have resulted in a significant increase in the number of cases recognized. It is apparent that it can no longer be regarded as a rare disease. The majority of the pathology in SLE is related to deposits of immune complexes in various organs, which triggers complement and other mediators of inflammation. Symptoms vary from person to person, and may come and go, depend on what part of the body is affected, can be mild, moderate, or severe. Diagnosis can be difficult because lupus mimics many other diseases; it requires clinical and serologic criteria. PMID:22879850
Szabó, Melinda Zsuzsanna; Szodoray, Peter; Kiss, Emese
Cardiovascular disease is one of the major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Accelerated atherosclerosis is related to traditional (age, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, and positive family history) and non-traditional, disease-related factors. Traditional risk factors are still more prominent in patients with lupus, as both hypertension and hypercholesterinemia were independently associated with premature atherosclerosis in several SLE cohorts. In this work, the authors summarize the epidemiology of dyslipidemia in lupus patients and review the latest results in the pathogenesis of lipid abnormalities. The prevalence of dyslipidemia, with elevations in total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), and apolipoprotein B (ApoB), and a reduction in low-density lipoprotein (LDL) levels are about 30% at the diagnosis of SLE rising to 60% after 3 years. Multiple pathogenetic mechanism is included, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) can suppress HDL and increase TG, auto-antibodies can cause the injury of the endothelium, lipoprotein lipase (LPL) activity can be reduced by circulating inflammatory mediators and antibodies, and increased oxidative stress may trigger a wide range of pro-atherogenic lipid modifications. As a major risk factor, dyslipidemia should be treated aggressively to minimize the risk of atherosclerosis and cardiovascular events. Randomized controlled trials with statins are controversial in the detention of atherosclerosis progression, but can be favorable by inhibiting immune activation that is the arterial wall and by decreasing lupus activity.
Cava, Antonio La
The dysfunctional immune response that characterizes systemic lupus erythematosus (SLE) associates with an unbalanced production of soluble mediators that are crucial in promoting and sustaining chronic inflammation. The successful use of biologics in several autoimmune diseases has led to studies in SLE aimed at contrasting the proinflammatory responses that contribute to tissue and organ damage in the disease. Several approaches have been developed and tested as potential therapeutic agents in SLE in preclinical studies and in clinical trials. This article provides an overview on antibody-based approaches in SLE that, although preliminary, have the potential to expand the current therapeutic possibilities in the disease. PMID:20636010
Aringer, M; Schneider, M
In the last few decades a number of small, often largely unrecognized steps have fundamentally changed the management of systemic lupus erythematosus (SLE). The current goal is to stop all disease activity without long-term use of more than 5 mg prednisolone per day. Remission, i.e. absence of activity in the SLE activity score of choice, is the defined target in the treat to target approach. The essential basic measures include life-long hydroxychloroquine as well as protection from sunlight (UV) and vitamin D substitution. Patients suffering from SLE need more vaccinations than the healthy population and control of risk factors for atherosclerosis is critical for long-term survival. Methotrexate is on par with azathioprine. If disease activity cannot be controlled in this way, belimumab is an approved therapeutic option. Cyclophosphamide is still used but only in life-threatening situations, such as lupus nephritis or central nervous system (CNS) vasculitis and in drastically reduced doses. Alternatively, off-label mycophenolate mofetil (MMF) can be used particularly for lupus nephritis and off-label rituximab in refractory disease courses. Numerous novel approaches are being tested in controlled trials and it is hoped that new drugs will be available for SLE patients within a few years.
Tagawa, Y; Saito, T; Takada, K; Kawahata, K; Kohsaka, H
Systemic lupus erythematosus-related hepatitis, known as lupus hepatitis, is a rare manifestation of systemic lupus erythematosus, and is usually subclinical with mild abnormalities of serum liver enzymes. While cases with clinically significant and refractory lupus hepatitis are uncommon, treatment options for lupus hepatitis are to be established. Here, we report the case of a 45-year-old man with progressive lupus hepatitis accompanied by autoimmune haemolytic anaemia. Lupus hepatitis of this patient was refractory to tacrolimus, azathioprine and cyclophosphamide, but was successfully treated by mycophenolate mofetil. Mycophenolate mofetil might be an effective therapeutic option for refractory lupus hepatitis.
Chanprapaph, K; Sawatwarakul, S; Vachiramon, V
Objective The aim of this study was to investigate the clinical features, laboratory findings, systemic manifestations, treatment and outcome of patients with bullous systemic lupus erythematosus in a tertiary care center in Thailand. Methods We performed a retrospective review from 2002 to 2014 of all patients who fulfilled the diagnostic criteria for bullous systemic lupus erythematosus to evaluate for the clinical characteristics, extracutaneous involvement, histopathologic features, immunofluorescence pattern, serological abnormalities, internal organ involvement, treatments and outcome. Results Among 5149 patients with cutaneous lupus erythematosus and/or systemic lupus erythematosus, 15 developed vesiculobullous lesions. Ten patients had validation of the diagnosis of bullous systemic lupus erythematosus, accounting for 0.19%. Bullous systemic lupus erythematosus occurred after the diagnosis of systemic lupus erythematosus in six patients with a median onset of 2.5 months (0-89). Four out of 10 patients developed bullous systemic lupus erythematosus simultaneously with systemic lupus erythematosus. Hematologic abnormalities and renal involvement were found in 100% and 90%, respectively. Polyarthritis (40%) and serositis (40%) were less frequently seen. Systemic corticosteroids, immunosuppressants, antimalarials and dapsone offered resolution of cutaneous lesions. Conclusion Bullous systemic lupus erythematosus is an uncommon presentation of systemic lupus erythematosus. Blistering can occur following or simultaneously with established systemic lupus erythematosus. We propose that clinicians should carefully search for systemic involvement, especially hematologic and renal impairment, in patients presenting with bullous systemic lupus erythematosus.
Okon, L G; Werth, V P
Cutaneous lupus erythematosus (CLE) encompasses a wide range of dermatologic manifestations, which may or may not be associated with the development of systemic disease. Cutaneous lupus is divided into several sub-types, including acute CLE (ACLE), sub-acute CLE (SCLE) and chronic CLE (CCLE). CCLE includes discoid lupus erythematosus (DLE), LE profundus (LEP), chilblain cutaneous lupus and lupus tumidus. The diagnosis of these diseases requires proper classification of the sub-type, through a combination of physical examination, laboratory studies, histology, antibody serology and occasionally direct immunofluorescence, while ensuring to exclude systemic disease. The treatment of cutaneous lupus consists of patient education on proper sun protection along with appropriate topical and systemic agents. Systemic agents are indicated in cases of widespread, scarring or treatment-refractory disease. In this chapter, we discuss issues in classification and diagnosis of the various sub-types of CLE, as well as provide an update on therapeutic management.
Lourenço, D M R; Gomes, R Cunha; Aikawa, N E; Campos, L M A; Romiti, R; Silva, C A
Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childreńs Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30-60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14-24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations.
Méndez-Flores, Silvia; Tinoco-Fragoso, Fátima; Hernández-Molina, Gabriela
Skin lesions caused by systemic lupus erythematosus are among the most frequent manifestations of this disease. These lesions show great variability in both their clinical and histological expression, making their understanding and study difficult. Patients presenting with cutaneous lupus do not necessarily have serious systemic complications, but they do have significant morbidity from impact on quality of life given the extent of the lesions, chronic tendency, and the risk of scarring; hence the importance of establishing a fast and effective treatment. This paper addresses the different varieties of specific injuries attributed to lupus erythematosus, correlation with systemic activity, quality of life, and the treatments available.
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Sete, Manuela Rubim Camara; Figueredo, Carlos Marcelo da Silva; Sztajnbok, Flavio
A large number of studies have shown a potential association between periodontal and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE). Similar mechanisms of tissue destruction concerning periodontitis and other autoimmune diseases have stimulated the study of a possible relationship between these conditions. This study aims to review the literature about this potential association and their different pathogenic mechanisms. Considering that periodontal disease is a disease characterized by inflammation influenced by infectious factors, such as SLE, it is plausible to suggest that SLE would influence periodontal disease and vice versa. However, this issue is not yet fully elucidated and several mechanisms have been proposed to explain this association, as deregulation mainly in innate immune system, with action of phagocytic cells and proinflammatory cytokines such as IL-1β and IL-18 in both conditions' pathogenesis, leading to tissue destruction. However, studies assessing the relationship between these diseases are scarce, and more studies focused on common immunological mechanisms should be conducted to further understanding.
Grönhagen, Carina M; Nyberg, Filippa
Lupus erythematosus (LE) is a chronic, autoimmune, multisystem disease that displays many diverse symptoms in which localized cutaneous LE (CLE) is on one end of the spectrum and severe systemic LE (SLE) on the other end. The underlying cause of LE is unknown but the etiology is thought to be multifactorial and polygenic. CLE is a disfiguring, chronic skin disease, with a significant impact on the patients’ everyday life. CLE are further divided into three main subsets: Acute CLE (ACLE), subacute CLE (SCLE) and chronic CLE (CCLE), where classic discoid LE (DLE) is the most common form. These subsets are defined by clinical symptoms, average duration of symptoms and histological and serological findings, although, the three subtypes can have overlapping clinical features. CLE patients display well-defined skin lesions, often in sun-exposed areas. The disease often has a chronic and relapsing course that can be induced or aggravated by UV light. It is important to confirm a CLE diagnosis histopathologically by a biopsy and in that there are several differential diagnoses and because CLE is a chronic disease in which regular follow-up is important and systemic treatment is sometimes indicated. PMID:24616847
Nozile, Wallace; Adgerson, Cheri N; Cohen, George F
Cutaneous Lupus Erythematosus (CLE) is a common manifestation in patients with Systemic Lupus Erythematosus. In a significant population of patients, CLE is the predominant feature and, in some cases, patients suffer from cutaneous disease alone. Chronic Cutaneous Lupus Erythematosus (CCLE) is a scarring subtype, more prevalent in blacks. Patients with skin of color may pose a challenge to physicians due to exaggerated cutaneous findings and increased risk of post-inflammatory hyperpigmentation and hypertrophic scarring. With the demographics of the United States rapidly shifting towards a greater population of non-Caucasian racial and ethnic groups, it is imperative that we expand on the limited research into molecular variation, clinical presentation, and therapeutic efficacy in CLE. The purpose of this review is to bring attention to the unique and severe aspects of CLE in persons of color, which calls for early and aggressive treatment.
Simeon-Aznar, C P; Cuenca-Luque, R; Fonollosa-Pla, V; Bosch-Gil, J A
The case of a patient admitted with thrombotic thrombocytopenic purpura nine years after developing systemic lupus erythematosus (SLE) is reported. Thrombotic thrombocytopenic purpura associated with SLE has been described on other occasions, but in most patients the diagnosis of SLE precedes that of thrombotic thrombocytopenic purpura. The unusual sequence and the chronological separation of the two diseases is emphasised. PMID:1575591
Sáenz-Corral, Claudia Ileana; Vega-Memíje, María Elisa; Martínez-Luna, Eduwiges; Cuevas-González, Juan Carlos; Rodríguez-Carreón, Alma Angélica; de la Rosa, Juan José Bollain-y-Goytia; del Muro, Felipe de Jesús Torres; Avalos-Díaz, Esperanza
Introduction: Lupus erythematosus is a multisystemic disease that is characterized by autoantibody production and immune complex deposition in such tissues as the mucosa, joints, the central nervous system, and skin. Cutaneous lupus erythematosus is categorized as acute, subacute, and chronic. Chronic cutaneous lupus erythematosus comprises discoid lupus erythematosus (DLE) and lupus profundus (LP). Aim: To analyze the expression of proapoptotic molecules in patients with lupus erythematosus discoid and lupus profundus. Material and methods: Descriptive study, the study groups comprised 10 cases of LP and 10 cases of DLE, and a control. Skin samples of cases and controls were processed for immunohistochemistry and by TUNEL technique. The database and statistical analysis was performed (statistical test X2) SPSS (Chicago, IL, USA). Results: Apoptotic features were broadly distributed along the skin biopsies in epidermal keratinocytes as well as at dermis. By immunohistochemistry the expression of Fas receptor and Fas-L was higher in the skin of lupus patients compared with controls. We also noted differences in Fas-L, -Fas, and -Bax proteins expression intensity in discoid lupus erythematosus patients in the epidermis, and hair follicles. Conclusions: Fas and Fas-L are expressed similarly in LP and DLE. PMID:26261624
Paramalingam, Shereen; Wong, Daniel D; Dogra, Gursharan K; Nossent, Johannes C
Podocytopathy in systemic lupus erythematosus is characterised by diffuse foot process effacement without significant peripheral capillary wall immune deposits as seen on electron microscopy. Lupus podocytopathy falls outside the scope of the current International Society of Nephrology and the Renal Pathology Society classification of lupus nephritis. We present a case of relapsing podocytopathy with nephrotic syndrome occurring simultaneously with two extra-renal and serological disease flares, which makes it likely that podocytopathy was related to systemic lupus erythematosus activity. This case adds to the growing body of evidence that lupus podocytopathy must be considered in the differential diagnosis of systemic lupus erythematosus patients presenting with nephrotic syndrome.
Paramalingam, Shereen; Wong, Daniel D; Dogra, Gursharan K; Nossent, Johannes C
Podocytopathy in systemic lupus erythematosus is characterised by diffuse foot process effacement without significant peripheral capillary wall immune deposits as seen on electron microscopy. Lupus podocytopathy falls outside the scope of the current International Society of Nephrology and the Renal Pathology Society classification of lupus nephritis. We present a case of relapsing podocytopathy with nephrotic syndrome occurring simultaneously with two extra-renal and serological disease flares, which makes it likely that podocytopathy was related to systemic lupus erythematosus activity. This case adds to the growing body of evidence that lupus podocytopathy must be considered in the differential diagnosis of systemic lupus erythematosus patients presenting with nephrotic syndrome. PMID:28321309
Yoon, Jimi; Kim, Hwa Mi; Kim, Tae-Heung; Kim, Chung-Won; Sun, Young-Woo; Yoon, Tae-Jin
Lupus erythematosus profundus, a form of chronic cutaneous lupus erythematosus, is a rare inflammatory disease involving in the lower dermis and subcutaneous tissues. It primarily affects the head, proximal upper arms, trunk, thighs, and presents as firm nodules, 1 to 3 cm in diameter. The overlying skin often becomes attached to the subcutaneous nodules and is drawn inward to produce deep, saucerized depressions. We present a rare case of lupus erythematosus profundus treated with autologous fat transfer. PMID:23139658
Ahmad, Zahida P; Johnstone, Lilian M; Walker, Amanda M
A 14-year-old boy with known stable cystinosis, treated with cysteamine since infancy, presented with a deterioration of renal function with haematuria in conjunction with a nodular rash, arthralgia, leucopenia, hypocomplementaemia and raised antinuclear antibodies. He was diagnosed with spontaneous onset of systemic lupus erythematosus (SLE), and his renal biopsy was consistent with lupus nephritis. It is unusual for patients with one severe disease to develop another disease process completely unrelated to their original condition, but it can occur. However, other distinct variants of lupus have been described, including drug-induced lupus (DIL), which have features that over-lap with SLE. The potential differential diagnosis of the SLE as a form of DIL in association with cysteamine is discussed.
Pérez-Pastor, G; Valcuende, F; Tomás, G; Moreno, M
Lupus erythematosus panniculitis or lupus erythematosus profundus is characterized by inflammation of the deep dermis and subcutaneous tissue. It can occur in isolation or associated with chronic systemic or discoid lupus erythematosus. It usually consists of nodules and hardened subcutaneous plaques on the forehead, cheeks, proximal extremities, and buttocks. Periorbital and parotid involvement are rare and can lead to misdiagnosis. We present the case of a patient with lupus erythematosus panniculitis who presented with palpebral edema and involvement of the periocular fat and parotid gland.
Benson, C.H.; Pennebaker, J.B.; Harisdangkul, V.; Songcharoen, S.
A patient with known systemic lupus erythematosus had fever and symptoms of a lower urinary tract infection. Bone scintigraphy showed left ureteral perforation and necrosis with no demonstrable nephrolithiasis. It is speculated that this episode was due to lupus vasculitis.
Rivas-Larrauri, Francisco; Yamazaki-Nakashimada, Marco Antonio
Systemic lupus erythematosus (SLE) is a multisystemic disease with a variety of clinical presentations. Monogenic predisposing conditions to the development of this disease have been described. As examples, an impaired expression of interferon-α regulated genes or complement deficiencies have been reported in patients with SLE, with particular clinical presentations. Those defects present particular presentations and a different severity, making an argument that lupus is not a single disease but many. Treatment could be individualized depending on the underlying defect generating the subtype of the disease.
Fisher, Juliya; Patel, Mital; Miller, Michael; Burris, Katy
Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with numerous drugs, but there are limited reports of its association with aromatase inhibitor anastrozole. We report the case of a patient undergoing treatment with anastrozole for breast cancer who presented with clinical, serological, and histological evidence consistent with DI-SCLE. Her condition quickly began to improve after the use of anastrozole was discontinued and hydroxychloroquine therapy was initiated. Cases such as ours as well as several others that implicate antiestrogen drugs in association with DI-SCLE seem to be contradictory to studies looking at the usefulness of treating systemic lupus erythematosus (SLE) with antiestrogen therapy. Further research on this relationship is warranted.
de Jesus, G R; Rodrigues, B C; Lacerda, M I; Dos Santos, F C; de Jesus, N R; Klumb, E M; Levy, R A
This study analyzed maternal and fetal outcomes of pregnancies of neuropsychiatric systemic lupus erythematosus patients followed in a reference unit. This retrospective cohort study included 26 pregnancies of patients seen between 2011 and 2015 included with history and/or active neuropsychiatric systemic lupus erythematosus among 135 pregnancies. Three patients had active neuropsychiatric systemic lupus erythematosus at conception, but only one remained with neurological activity during gestation, characteristically related to the inadvertent suspension of medications. Twenty six percent of the newborns were small for gestational age and 40% of live births were premature, with no neonatal death or early complications of prematurity. Preeclampsia was diagnosed in nine pregnancies, with two cases of early severe form that resulted in intrauterine fetal death. Patients with neuropsychiatric systemic lupus erythematosus had more prematurity and preeclampsia compared to patients without neuropsychiatric disease. However, when concomitant lupus nephritis was excluded, the gestational results of neuropsychiatric systemic lupus erythematosus patients were more favorable.
Rúa-Figueroa Fernández de Larrinoa, Iñigo
Systemic lupus erythematosus is a heterogeneous rheumatic systemic disease with extremely varied clinical manifestations and a diverse pathogenesis, as illustrated in this review on the most relevant new knowledge related to the disease. Topics such as anemia, pathogenesis, cardiovascular risk assessment, antiphospholipid syndrome, prediction of damage and recent advances in treatment, including tolerogenic and biological agents, are discussed. Relevant contributions regarding classical therapies such as corticosteroid and antimalarials and their optimal use, as well as the roll of vitamin D, are also referred.
Olivieri, I; Gemignani, G; Balagi, M; Pasquariello, A; Gremignai, G; Pasero, G
The case is reported of a 42 year old white woman meeting currently used diagnostic criteria for both ankylosing spondylitis and systemic lupus erythematosus (SLE). As found in a previously described similar case of a black man, HLA typing showed antigens associated with both SLE and seronegative spondyloarthropathy. This case thus supports the hypothesis that the two diseases occur together only when this rare combination of HLA antigens is present. Images PMID:2344214
Szczęch, Justyna; Rutka, Maja; Samotij, Dominik; Zalewska, Agnieszka
Introduction Lupus erythematosus (LE) shows a wide variety of clinical manifestations, skin involvement being one of the most important. Aim To analyze the clinical presentation of cutaneous variants of lupus erythematosus in terms of skin lesion spectrum and extracutaneous involvement. Material and methods A total of 64 patients with cutaneous LE (CLE) were included. The study was based on the “Core Set Questionnaire” developed by the European Society of Cutaneous Lupus Erythematosus (EUSCLE). Clinical severity of skin lesions was evaluated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). All results were subjected to statistical analysis. Results Fifteen (23.4%) patients had an acute CLE (ACLE), 26 (40.6%) subacute CLE (SCLE) and 21 (32.8%) chronic CLE (CCLE). Two (3.2%) individuals only demonstrated urticarial vasculitis as a cutaneous manifestation of LE and these patients were excluded. Patients with ACLE were characterized by the earliest onset of the disease (mean age of 31.9 ±15.0 years; p < 0.001). On average, 4.8 ±1.8 criteria of systemic LE were found in the ACLE group compared to 2.7 ±1.3 criteria in SCLE and 2.5 ±1.5 criteria in CCLE (p < 0.001). The highest activity of skin lesions according to CLASI was found in the SCLE group (p = 0.002). On the other hand, the most severe skin damage was observed in CCLE (p < 0.01). Conclusions Each variant of CLE differs significantly from the others in respect of various aspects of clinical manifestations. Due to a number of different variants of LE skin lesions, a unified classification of CLE still remains a challenge. PMID:26985173
Carrion, Diego M; Carrion, Andres F
Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment.
da Cunha Bang, F; Lange Wantzin, G; Dahl Christensen, J
A 24-year-old woman with discoid lupus erythematosus developed systemic lupus erythematosus after 6 years. One of the clinical features was Raynaud's phenomenon in the fingers and toes, and furthermore Raynaud's phenomenon appeared in the tongue when exposed to cold and windy weather.
Callen, Jeffrey P
SUMMARY Skin disease in patients with lupus erythematosus may be subdivided into two broad categories - those lesions that when biopsied demonstrate interface dermatitis and those that do not demonstrate interface dermatitis. The skin lesions that are represented by the interface dermatitis include discoid lupus erythematosus, subacute cutaneous lupus erythematosus and acute cutaneous lupus erythematosus. Patients with these 'specific' manifestations have varying degrees of systemic involvement from rare systemic disease in patients with localized discoid lupus erythematosus to common and often severe involvement in patients with acute cutaneous lupus erythematosus. Patients who do not demonstrate interface dermatitis also may have systemic disease and in some instances the skin manifestations are linked to some of the more severe systemic manifestations. Many patients with cutaneous lesions characterized by the interface dermatitis can be controlled with 'standard' therapies including sunscreens, protective clothing and behavioural alteration, and topical corticosteroids with or without an oral antimalarial agent. This review presents a brief summary of each common cutaneous manifestation of lupus erythematosus, its relationship to systemic involvement and treatment issues to effectively deal with the lupus erythematosus patient who has skin disease.
Koh, J H; Ko, H S; Kwok, S-K; Ju, J H; Park, S-H
We investigated the clinical and laboratory characteristics of pregnancies with systemic lupus erythematosus (SLE) and identified lupus flare predictors during pregnancy. Additionally, we examined lupus activity and pregnancy outcomes in SLE patients who continued, discontinued or underwent no hydroxychloroquine (HCQ) treatment during pregnancy. We retrospectively analyzed 179 pregnancies in 128 SLE patients at Seoul St. Mary's Hospital, Korea, between 1998 and 2012 and then assessed the clinical profiles and maternal and fetal outcomes. Overall, 90.5% of pregnancies resulted in a successful delivery and were divided into two groups: those who experienced lupus flares (80 pregnancies, 44.7%) and those who did not (99 pregnancies, 55.3%). Increased preeclampsia, preterm births, low birth weight, intrauterine growth restriction (IUGR), and low 1-minute Apgar scores occurred in pregnancies with lupus flares compared to pregnancies in quiescent disease. Lupus flares were predicted by HCQ discontinuation, a history of lupus nephritis, high pre-pregnancy serum uric acid and low C4 levels. Our study indicates that achieving pre-pregnancy remission and continuing HCQ treatment during pregnancy are important for preventing lupus flares.
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This text covers questions related to the history, etiology, pathogenesis, clinical aspects and therapy of systematic lupus erythematosus (SLE). Both animal models and human SLE are considered. With regard to basic science, concise information on cellular immunology, autoantibodies, viral aspects and molecular biology in SLE is provided. Clinical topics then deal with medical, dermatologic, neurologic, radiologic, pathologic, and therapeutic aspects. The book not only presents the most recent information on clinical and experimental insights, but also looks at future aspects related to the diagnosis and therapy of SLE.
Abadeer, Kerolos; Alsaad, Ali A; Geiger, Xochiquetzal J; Porter, Ivan E
Collapsing glomerulopathy (CG) is a rare disease that can be associated with multiple other disorders. It usually leads to poor prognosis with a high percentage of patients progressing to end-stage renal disease. In this article, we illustrate a clinical case of CG associated with systemic lupus erythematosus that had a prompt response to mycophenolate and prednisone. The condition started after sudden cessation of the already established mycophenolate treatment regimen. The patient then presented with acute kidney injury due to kidney biopsy-proven CG. In that circumstance, we hypothesised that mycophenolate may play a role in prevention and development of CG.
Katz, S M; Korn, S; Umlas, S L; DeHoratius, R J
In the past, necrotizing vasculitis has been considered to be one of the dominant intrarenal vascular abnormalities in systemic lupus erythematosus (SLE). To test the validity of this statement, 70 consecutive renal biopsies from patients with SLE were reviewed. Light microscopy (LM) and immunofluorescence (IF) studies documented abnormalities, including thrombosis and nephrosclerosis, in 30 patients (43 percent), but no cellular infiltration of the vessel walls or other evidence of acute necrotizing vasculitis was seen. It is concluded that while intrarenal vasculopathy with thrombosis and nephrosclerosis is a common finding in SLE, our data and recently published studies suggest that acute necrotizing vasculitis occurs rarely, if at all, in SLE nephritis.
Garza-Mayers, Anna Cristina; McClurkin, Michael; Smith, Gideon P
Discoid lupus erythematosus (DLE) is a chronic cutaneous disease characterized by inflammatory plaques that, in the absence of prompt diagnosis and treatment, may lead to disfiguring scarring and skin atrophy. However, there is limited evidence for which treatments are most effective. Currently, no medications have been approved specifically for the treatment of DLE. Many of the drugs described in the literature were developed for use in other immune disorders. This review will summarize current therapeutic options for DLE and their supporting evidence with discussion of prevention, topical measures, physical modalities, and systemic therapies, including newer potential therapies.
Park, K R; Seo, M R; Ryu, H J; Chi, M J; Baek, H J; Choi, H J
Ocular involvement sometimes occurs with systemic lupus erythematosus (SLE) but enophthalmos with SLE is rare. We report a case of enophthalmos with SLE. A 25-year-old male was admitted for two weeks of fever, sore throat, arthralgia, chest pain and right arm weakness with pain. We diagnosed him with SLE with malar rash, arthritis, pleural effusion, proteinuria, leukopenia, positive antinuclear antibody, anti-dsDNA, and lupus anticoagulant. The patient was prescribed high-dose prednisolone and hydroxychloroquine 400 mg. One week after discharge, he complained about a sensation of a sunken right eye. CT showed right enophthalmos, a post-inflammatory change and chronic inflammation. Proteinuria increased to 3.8 g/day after the patient stopped taking prednisolone. Cyclophosphamide therapy was administered for three months without improvement. We decided to restart prednisolone and change cyclophosphamide to mycophenolate mofetil. Proteinuria decreased but enophthalmos remains as of this reporting.
Barbhaiya, M; Costenbader, K H
Exposure to ultraviolet (UV) radiation is among the environmental factors that have been proposed and studied in association with systemic lupus erythematosus (SLE). While it is known that UV radiation exposure may exacerbate pre-existing lupus, it remains unclear whether UV exposure is a risk factor for the development of SLE. Experimental studies show a significant immunomodulatory role for UV radiation, but strong epidemiologic data regarding its role in triggering SLE onset are lacking. Further studies are needed to assess the role of UV radiation in relation to development of incident SLE, yet they are challenging to design due to difficulties in accurate exposure assessment, the heterogeneous nature of SLE, and the challenge of assessing photosensitivity, a feature of SLE, which often precedes its diagnosis.
Uva, Luís; Miguel, Diana; Pinheiro, Catarina; Freitas, João Pedro; Marques Gomes, Manuel; Filipe, Paulo
Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. The skin is one of the target organs most variably affected by the disease. The American College of Rheumatology (ACR) established 11 criteria as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. Cutaneous lesions account for four of these 11 revised criteria of SLE. Skin lesions in patients with lupus may be specific or nonspecific. This paper covers the SLE-specific cutaneous changes: malar rash, discoid rash, photosensitivity, and oral mucosal lesions as well as SLE nonspecific skin manifestations, their pathophysiology, and management. A deeper thorough understanding of the cutaneous manifestations of SLE is essential for diagnosis, prognosis, and efficient management. Thus, dermatologists should cooperate with other specialties to provide optimal care of SLE patient. PMID:22888407
Kafle, M P; Lee, Vws
Nepal is a small country that is landlocked between India and China. Several ethnic groups live within the 147,181 km(2) of this country. Geographic diversity ranges from the high Himalayas to the flatlands of the Ganges plains. Lupus nephritis (LN), a complication of systemic lupus erythematosus (SLE), is a common kidney problem in Nepal; but the real incidence and prevalence of SLE in Nepal is largely not known. Here, it more commonly affects people (mostly women) living in the southern flatlands, but SLE is reported to be uncommon further south in India. Even though the disease appears to be common, good quality research is uncommon in Nepali literature. This article was written to provide a review of the articles published to date about SLE in Nepal and to discuss the gaps in knowledge that require further evaluation.
Gescuk, Bryan D; Davis, John C
The last significant breakthrough in the treatment of systemic lupus erythematosus (SLE) was the use of cyclophosphamide and methylprednisolone in the treatment of lupus nephritis. Recent advances in immunology, oncology, and endocrinology have resulted in many potential therapies for SLE. These therapies include new immunosuppressants, biologic medications, tolerizing agents, immunoablation techniques, and hormonal medications. Each of these approaches will be discussed in this review. Some therapies are currently in use in clinical rheumatology practice (mycophenolate mofetil) and others are entering phase I trials (anti-BLyS monoclonal antibody). While some of these new therapies target specific inflammatory mechanisms in SLE (anti-CD40L monoclonal antibody), others work by nonspecific inhibition of the immune system (immunoablation).
Daugas, Eric; Nochy, Dominique; Huong, Du Le Thi; Duhaut, Pierre; Beaufils, Hélène; Caudwell, Valérie; Bariety, Jean; Piette, Jean-Charles; Hill, Gary
In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.
Diniz, J C; Almeida, R T; Aikawa, N E; Sallum, A M E; Sakane, P T; Silva, C A
Kawasaki disease (KD) is a common vasculitis in childhood. To the authors' knowledge, only one case of juvenile systemic lupus erythematosus (JSLE)-like onset mimicking KD and another case of KD and JSLE association have previously been described. However, the prevalence of this association of the two diseases was not reported. Therefore, over 27 consecutive years, 5419 patients were followed at the Pediatric Rheumatology Unit and 271 (5%) of them met the ACR classification criteria for JSLE. Two (0.7%) of them were female. These also had KD according to European League against Rheumatism / Paediatric Rheumatology European Society (EULAR/PReS) consensus criteria and are described in this report. One case was a 13-year-old who presented all six KD criteria. Echocardiogram showed pericardial effusion, dilatation and tortuosity of right and left coronary, and her symptoms promptly improved after treatment with intravenous immunoglobulin (IVIG). Lupus diagnosis was established a few days later. Another case was a 4-year-old who had also met all six KD criteria, with improvement after IVIG, and lupus diagnosis was made 1 year later. In conclusion, the frequency of the association between these two autoimmune diseases was rare. The occurrence of a second autoimmune systemic disease in a patient with a history of KD should also be considered. Furthermore, the initial presentation of lupus may mimic KD.
de Holanda, Bruna A.; Barreto, Isabela G. Menna; de Araujo, Isadora S. Gomes
Alveolar hemorrhage (AH) is a rare syndrome that can often occur in autoimmune diseases, blood clotting disorders, infection or by acute inhalation injury, presenting rapid evolution and high mortality, especially with late diagnosis and treatment. Among the autoimmune diseases, there are reported cases in patients with primary antiphospholipid syndrome (PAPS), vasculitis and systemic lupus erythematosus (SLE). An early diagnosis is an essential tool in the successful management of this complication, requiring aggressive treatment based on vigorous immunosuppression and broad-spectrum antibiotic. We describe here a case of alveolar hemorrhage associated with glomerulonephritis as the open presentation in a patient with SLE. PMID:27994272
de Holanda, Bruna A; Barreto, Isabela G Menna; de Araujo, Isadora S Gomes; de Araujo, Daniel B
Alveolar hemorrhage (AH) is a rare syndrome that can often occur in autoimmune diseases, blood clotting disorders, infection or by acute inhalation injury, presenting rapid evolution and high mortality, especially with late diagnosis and treatment. Among the autoimmune diseases, there are reported cases in patients with primary antiphospholipid syndrome (PAPS), vasculitis and systemic lupus erythematosus (SLE). An early diagnosis is an essential tool in the successful management of this complication, requiring aggressive treatment based on vigorous immunosuppression and broad-spectrum antibiotic. We describe here a case of alveolar hemorrhage associated with glomerulonephritis as the open presentation in a patient with SLE.
Ishikawa, T; Tsukamoto, N; Suto, M; Uchiumi, H; Mitsuhashi, H; Yokohama, A; Maesawa, A; Nojima, Y; Naruse, T
A patient with systemic lupus erythematosus (SLE) developed acquired hemophilia A. The patient, a 24-year-old Japanese woman, was referred to our hospital because of uncontrollable bleeding following a tooth extraction. Laboratory examination revealed prolonged APTT (116 seconds), reduced factor VIII activity (2.8 %) and the presence of factor VIII inhibitor at a titer of 46.5 Bethesda units/ml. Transfusion of prothrombin complex concentrate and activated prothrombin complex concentrate followed by administration of prednisolone and cyclophosphamide successfully arrested bleeding and reduced the factor VIII inhibitor level. Acquired hemophilia A is a rare but lethal condition. Rapid diagnosis and introduction of adequate therapies are critical.
Borrell, Helena; Narváez, Javier; Alegre, Juan José; Castellví, Ivan; Mitjavila, Francesca; Aparicio, María; Armengol, Eulàlia; Molina-Molina, María; Nolla, Joan M.
Abstract Shrinking lung syndrome (SLS) is a rare and less known complication mainly associated with systemic lupus erythematosus (SLE). In this study, we analyze the clinical features, investigation findings, approaches to management, and outcome in a case series of 9 adult patients with SLE and SLS diagnosed during a 35-year period in 3 referral tertiary care hospitals in Spain. Additionally, we reviewed 80 additional cases previously reported (PubMed 1965–2015). These 80 cases, together with our 9 patients, form the basis of the present analysis. The overall SLS prevalence in our SLE population was 1.1% (9/829). SLS may complicate SLE at any time over its course, and it usually occurs in patients without previous or concomitant major organ involvement. More than half of the patients had inactive lupus according to SELENA-systemic lupus erythematosus disease activity index (SLEDAI) scores. Typically, it presents with progressive exertional dyspnea of variable severity, accompanied by pleuritic chest pain in 76% of the cases. An important diagnostic delay is common. The diagnostic tools that showed better yield for SLS detection are the imaging techniques (chest x-ray and high-resolution computed tomography) along with pulmonary and diaphragmatic function tests. Evaluation of diaphragm dome motion by M-mode ultrasonography and phrenic nerve conduction studies are less useful. There are no standardized guidelines for the treatment of SLS in SLE. The majority of patients were treated with medium or high doses of glucocorticoids. Several immunosuppressive agents have been used in conjunction with steroids either if the patient fails to improve or since the beginning of the treatment. Theophylline and beta-agonists, alone or in combination with glucocorticoids, have been suggested with the intent to increase diaphragmatic strength. The overall long-term prognosis was good. The great majority of patients had significant clinical improvement and stabilization, or mild
De Smet, A.A.; Mahmood, T.; Robinson, R.G.; Lindsley, H.B.
Sacroiliac joint radiographs and radionuclide sacroiliac joint uptake ratios were obtained on 14 patients with active systemic lupus erythematosus. Elevated joint ratios were found unilaterally in two patients and bilaterally in seven patients when their lupus was active. In patients whose disease became quiescent, the uptake ratios returned to normal. Two patients had persistently elevated ratios with continued clinical and laboratory evidence of active lupus. Mild sacroiliac joint sclerosis and erosions were detected on pelvic radiographs in these same two patients. Elevated quantitative sacroiliac joint uptake ratios may occur as a manifestation of active systemic lupus erythematosus.
Askanase, Anca D
Given the female preponderance of systemic lupus erythematosus (SLE) in humans, the adverse effects of female gender and sex hormones in murine lupus, and numerous reports (retrospective, often anecdotal and uncontrolled) that describe a temporal association between estrogen exposure and development or exacerbation of SLE, it is tempting to accept that estrogens and SLE simply do not mix. While there are valid concerns regarding the use of exogenous estrogens in women with SLE, there are also potential health benefits to be considered. Oral contraceptives (OCs) offer effective birth control and may be bone protective in corticosteroid-treated patients. Recent studies, albeit retrospective, suggest that OCs are well tolerated in patients with SLE. Several salutary effects of postmenopausal estrogens assume particular importance in SLE where the risks of osteoporosis, exaggerated by menopause (natural or cyclophosphamide-induced) and corticosteroids, are substantial. However, the results of the Women's Health Initiative trial significantly limit the use of hormone replacement therapy in the general population, and raise particular concern for SLE patients. Other exogenous hormones (clomifene, gonadotropins, gonadotropin-releasing hormones) may be used to elevate levels of endogenous estrogen and to stimulate ovulation in patients with diminished fertility. Patients with inactive or stable/moderate disease and at low risk for thrombosis may benefit from OCs and other hormonal therapies without a change in lupus activity. Large prospective, double-blind, placebo-controlled studies inclusive of all ethnic groups should provide the basis for more definitive recommendations.
Shrestha, Nabin K; Khanal, Basudha; Sharma, Sanjib K; Dhakal, Subodh S; Kanungo, Reba
This report describes a case of primary amoebic meningoencephalitis in a patient with systemic lupus erythematosus. No specific exposure was identified. Treatment with intravenous amphotericin B was associated with marked clinical improvement, but subsequent fatal relapse while still on therapy.
Callen, Jeffrey P
Skin disease in patients with lupus erythematosus can be subdivided into two broad categories-those lesions that, when biopsied, demonstrate an interface dermatitis and those that do not demonstrate an interface dermatitis. The skin lesions that are represented by the interface dermatitis include discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus. Many patients with these cutaneous lesions can be managed with "standard" therapies, including sunscreens, protective clothing and behavioral alteration, and topical corticosteroids with or without an oral antimalarial agent. These standard therapies are often not used appropriately, resulting in a situation in which the patient is felt to have refractory disease. This chapter discusses these therapies and defines what is meant by refractory disease and how the author approaches these patients.
Taşdemir, Mehmet; Hasan, Chiar; Ağbaş, Ayşe; Kasapçopur, Özgür; Canpolat, Nur; Sever, Lale; Çalışkan, Salim
Systemic lupus erythematosus and Sjögren's syndrome are chronic auto- inflammatory disorders which can lead to serious organ damage. Although systemic lupus erythematosus and Sjögren's syndrome were previously considered two forms of the same disease because of presence of clinical coexistence of these two conditions, the view that they are two different conditions with mutual characteristics has become prominent in recent years. In this paper, we reported a 16 year-old girl who was followed up with a diagnosis of Sjögren's syndrome for six years and then was observed to have overlap of systemic lupus erythematosus. In the baseline, she did not have any clinical or serological evidence for systemic lupus erythematosus. After six year, massive proteinuria and serological findings developed and systemic lupus erythematosus nephritis was diagnosed by kidney biopsy. Currently, systemic lupus erythematosus and Sjögren's syndrome cannot be differentiated definetely. We need more valuable diagnostic and classification criteria to differentiate these two important conditions.
Moura Filho, Jucélio Pereira; Peixoto, Raiza Luna; Martins, Lívia Gomes; de Melo, Sillas Duarte; de Carvalho, Ligiana Leite; Pereira, Ana Karine F. da Trindade C.; Freire, Eutilia Andrade Medeiros
Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial etiology. Although clinical manifestations are varied, the skin is an important target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17 new criteria for the diagnosis of the disease, according to the Systemic Lupus International Collaborating Clinics. The cutaneous manifestations of lupus are pleomorphic. Depending on their clinical characteristics, they can be classified into Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus. Treatment is based on preventive measures, reversal of inflammation, prevention of damage to target organs and relief of adverse events due to pharmacological therapy. The most commonly used treatment options are topical, systemic and surgical treatment, as well as phototherapy. The correct handling of the cases depends on a careful evaluation of the morphology of the lesions and the patient's general status, always taking into consideration not only the benefits but also the side effects of each therapeutic proposal. PMID:24626656
Agarwal, Surabhi; Elliott, Jennifer R; Manzi, Susan
Cardiovascular disease (CVD) has emerged as a leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Growing evidence suggests that inflammation plays a key role in the pathogenesis of atherosclerosis from initial endothelial dysfunction to rupture of atheromatous plaques. The increased frequency of atherosclerosis in SLE is likely due to a complex interplay among traditional risk factors, disease-related factors such as medications and disease activity, and inflammatory and immunogenic factors. Identification of these novel risk factors will lead to a better understanding of CVD pathogenesis and may also provide targets for potential treatment strategies. When caring for SLE patients, clinicians should be aware of the increased CVD risk and treat the known modifiable risk factors in addition to controlling disease activity and inflammation.
Joseph, Vivek; Anil, Rahul; Aristy, Sary
A 70-year-old man presented with complaints of rapid cognitive decline and new onset leukopenia. The patient had a 17-year history of refractory seizures. Detailed review of symptoms and investigations revealed the patient met American College of Rheumatology (ACR) diagnostic criteria for systemic lupus erythematosus (SLE). The patient had high titer ANA with a strongly positive dsDNA. Immunosuppressive therapy with hydroxychloroquine and mycophenolate mofetil led to significant improvement in cognition and seizures. Neuropsychiatric SLE should be considered a potential differential diagnosis for patients presenting with seizures or cognitive decline. Moreover, neuropsychiatric manifestations especially seizures are an early event in the disease course of SLE. Hence, we believe that early diagnosis of SLE by neuropsychiatric manifestations will not only lead to better control of CNS symptoms but early immunosuppressive therapy could control the progression of the underlying autoimmune disease. PMID:27635183
Silpa-archa, Sukhum; Lee, Joan J; Foster, C Stephen
Systemic lupus erythematosus (SLE) can involve many parts of the eye, including the eyelid, ocular adnexa, sclera, cornea, uvea, retina and optic nerve. Ocular manifestations of SLE are common and may lead to permanent blindness from the underlying disease or therapeutic side effects. Keratoconjunctivitis sicca is the most common manifestation. However, vision loss may result from involvement of the retina, choroid and optic nerve. Ocular symptoms are correlated to systemic disease activity and can present as an initial manifestation of SLE. The established treatment includes prompt systemic corticosteroids, steroid-sparing immunosuppressive drugs and biological agents. Local ocular therapies are options with promising efficacy. The early recognition of disease and treatment provides reduction of visual morbidity and mortality.
Isenberg, David; Rahman, Anisur
We are about to enter a new era in the treatment of patients with systemic lupus erythematosus (SLE). For the past 40 years hydroxychloroquine sulfate and corticosteroids, together with varying combinations of immunosuppressive drugs, have been the main treatments for SLE. Although effective for many patients, some patients fail to respond to these drugs and even more suffer from major side effects due to the generalized nature of the immunosuppression. In this article we review the remarkable confluence of new therapies ranging from newer immunosuppressive drugs with fewer side effects, such as mycophenolate mofetil, to the more targeted approaches offered by biological agents. These agents have been designed to block molecules such as CD20, CD22 and interleukin-10 that are thought to have an integral part in the development of SLE. This wolf might not yet be about to become extinct but its survival is increasingly under threat!
Goldblatt, F; Isenberg, D A
In the past 40 years, prognosis for patients with systemic lupus erythematosus (SLE) has improved, with 10-year survival now approximately 90%. This is due probably to a combination of earlier disease diagnosis and diagnosis of milder disease, due in part to availability of multiple serological tests for SLE, use of steroids and other immunosuppressive agents, and availability of renal dialysis and transplantation. Despite this, however, the potential for significant morbidity and mortality remains in the group of patients with partially responsive or treatment resistant disease. More recently, advancements in the understanding of molecular mechanisms involved in the pathogenesis of SLE have translated to the development of novel therapies, offering possible alternatives to this patient cohort. Discussion of these pharmacological options and ongoing research forms the basis of this review. PMID:15807843
Shidara, Kumi; Soejima, Makoto; Shiseki, Mariko; Ohta, Syuji; Nishinarita, Makoto
A 49-years-old female admitted to our hospital because of skin eruptions on the extremities in 1985. She had suffered from polyarthralgia, skin eruptions since 1983. Physical examinations revealed discoid lesion, central nervous system involvement, and polyarthritis. Laboratory tests revealed leukopenia, thrombocytopenia, and hypocomplementemia. Antinuclear antibody, ant-DNA antibody, LE test were positive. From these findings, she was diagnosed as systemic lupus erythematosus (SLE). She developed lupus peritonitis in 1990 and 1994, which was successfully treated by steroid pulse therapy. Since then, the activity of SLE was in good control under administration of prednisolone 10 mg/day. Chilblain lupus was seen from 1993, Raynaud's phenomenon from 1996, and she further developed subcutaneous induration on her chest, back and upper extremities in 1999. Skin biopsy findings were compatible with lupus panniculitis. In 2002, erythematous patches with scales were observed on her right hand and left knee, and these skin lesions were histologically diagnosed as psoriasis vulgaris. An autoimmune response similar to SLE is speculated in psoriasis. We describe a rare case of SLE with various skin lesions including psoriasis vulgaris.
Loescher, A; Edmondson, H D
A case is reported of acute facial swelling following tooth extraction that failed to respond in a normal manner. The patient developed systemic signs and symptoms ultimately revealing the diagnosis of lupus erythematosus. The possibility of soft tissue lesions arising in some forms of lupus is emphasised by this report.
Basiaga, M; Sherry, D
Toe walking is a previously unreported presentation of systemic lupus erythematosus (SLE). We describe a patient who presented with profound multisystem involvement that was preceded by one month of toe walking and multiple flexion contractures without arthritis. Her lupus is now under control after aggressive therapy, yet she continues to struggle with tendinopathy despite continued physical and occupational therapy. Lupus should be considered in the appropriate clinical context in children who have new-onset contractures due to tight tendons.
Martín Nares, Eduardo; López Iñiguez, Alvaro; Ontiveros Mercado, Heriberto
Systemic lupus erythematosus is a chronic autoimmune disease with a relapsing and remitting course characterized by disease flares. Flares are a major cause of hospitalization, morbidity and mortality in patients with systemic lupus erythematosus. Some triggers for these exacerbations have been identified, including infections, vaccines, pregnancy, environmental factors such as weather, stress and drugs. We report a patient who presented with a lupus flare with predominantly mucocutaneous, serosal and cardiac involvement after being bitten by a spider and we present the possible mechanisms by which the venom elicited such a reaction. To the best of our knowledge, this is the first such case reported in the literature.
Bardana, Emil J.; Pirofsky, Bernard
Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disease having definite etiologic associations with ethnic, genetic, viral and immunologic factors. Its pathologic hallmark, vasculitis, is currently felt to be the end result of an immune-complex mechanism. Several clinical and serologic variants of SLE are recognized including discoid lupus erythematosus (DLE), mixed connective tissue disease (MCTD) and drug-induced equivalents—such as procainamide-induced lupus (PIL). The distinguishing features of these variants as well as their prognosis and therapy are discussed in relation to recent developments in the immunopathogenesis of SLE. PMID:46657
Cakici, Ozgur; Karadag, Remzi; Bayramlar, Huseyin; Ozkanli, Seyma; Uzuncakmak, Tugba Kevser; Karadag, Ayse Serap
A 40-year-old female patient with a 5-year history of systemic lupus erythematosus was referred to our policlinic with complaints of erythema, atrophy, and telangiectasia on the upper eyelids for 8 months. No associated mucocutaneous lesion was present. Biopsy taken by our ophthalmology department revealed discoid lupus erythematosus. Topical tacrolimus was augmented to the systemic therapeutic regimen of the patient, which consisted of continuous antimalarial treatment and intermittent corticosteroid drugs. We observed no remission in spite of the 6-month supervised therapy. Periorbital discoid lupus erythematosus is very unusual and should be considered in the differential diagnosis of erythematous lesions of the periorbital area.. PMID:28300917
Cakici, Ozgur; Karadag, Remzi; Bayramlar, Huseyin; Ozkanli, Seyma; Uzuncakmak, Tugba Kevser; Karadag, Ayse Serap
A 40-year-old female patient with a 5-year history of systemic lupus erythematosus was referred to our policlinic with complaints of erythema, atrophy, and telangiectasia on the upper eyelids for 8 months. No associated mucocutaneous lesion was present. Biopsy taken by our ophthalmology department revealed discoid lupus erythematosus. Topical tacrolimus was augmented to the systemic therapeutic regimen of the patient, which consisted of continuous antimalarial treatment and intermittent corticosteroid drugs. We observed no remission in spite of the 6-month supervised therapy. Periorbital discoid lupus erythematosus is very unusual and should be considered in the differential diagnosis of erythematous lesions of the periorbital area..
Gusdorf, Laurence; Bessis, Didier; Lipsker, Dan
Abstract Neutrophilic urticarial dermatosis (NUD) resembles urticaria clinically but is a neutrophilic dermatosis histopathologically. The majority of patients with NUD have an underlying systemic condition, mainly, autoinflammatory disorders such as cryopyrin-associated periodic syndromes, Schnitzler syndrome, and adult-onset Still disease, but a few also have systemic lupus erythematosus (LE). Here, we confirm these data and we report relevant clinical and histopathological data of 7 patients with LE and NUD. We retrospectively retrieved the medical records of all patients with LE in whom skin biopsy showed NUD in registers of Strasbourg and Montpellier University hospitals since 2000. All were female and aged between 13 and 45 years. Skin lesions were typically rose or red macules or slightly elevated papules occurring in a wide distribution. Individual lesions resolved within 24 hours and were not or only slightly itchy. Every patient had associated signs, most of the time polyarthritis and/or fever. NUD was the presenting mode of LE in 2 patients. NUD was misdiagnosed as a classic lupus flare and led to therapeutic intensification with the introduction of immunosuppressive drugs in 4 patients. Histopathological findings consisted of intense neutrophilic interstitial and perivascular infiltrate with leukocytoclasia and without fibrinoid necrosis of vessel walls. Direct immunofluorescence testing showed a lupus band in 4 patients. Antinuclear antibodies were always positive, anti-dsDNA antibodies were positive in 5 patients, and anti-Ro/SSA antibodies in 6 patients. Immunosuppressive drugs such as prednisone, hydroxychloroquine, mycophenolate mofetil, and methotrexate were never effective to treat NUD. Antihistamines were effective in 1 patient and dapsone or colchicine was effective in 5 patients. NUD is not exceptional in patients with systemic LE and is easily misdiagnosed as an acute LE flare. Furthermore, we show that conventional immunosuppressive LE
Reich, Adam; Marcinow, Katarzyna; Bialynicki-Birula, Rafal
The lupus band test (LBT) is a diagnostic procedure that is used to detect deposits of immunoglobulins and complement components along the dermoepidermal junction in patients with lupus erythematosus (LE). The LBT is positive in about 70%–80% of sun-exposed non-lesional skin specimens obtained from patients with systemic LE (SLE), and in about 55% of SLE cases if sun-protected nonlesional skin is analyzed. In patients with cutaneous LE only, the lesional skin usually shows a positive LBT. The LBT helps in differentiating LE from other similar skin conditions and may also be helpful in making the diagnosis of SLE in subjects with no specific cutaneous lesions. Furthermore, a positive LBT may be applied as a prognostic parameter for LE patients. However, the correct interpretation of this test requires detailed knowledge of the site of the biopsy, deposit components, morphology and brightness of the immunofluorescent band, and other associated serologic findings, as well as the response to treatment. It must be emphasized that LBT is a laboratory procedure that should always be interpreted in conjunction with clinical findings and other serological and immunopathological parameters. PMID:21339940
Revier, J; Kienzler, J L; Blanc, D; Coulon, G; Saint-Hillier, Y; Laurent, R
A 36-year-old woman presented with a widespread papulonodular eruption followed by cutaneous and systemic manifestations of lupus erythematosus. Both conditions, papular mucinosis and lupus erythematosus were investigated by histopathology, immunofluorescence and electron microscopy. Referring to seven other cases reported in the literature, the possible relationship between lupus erythematosus and cutaneous mucinosis is discussed. It seemed that the cutaneous deposits of mucine were secondary to lupus erythematosus and not a simultaneous occurrence of the two diseases.
Guettrot-Imbert, G; Morel, N; Le Guern, V; Plu-Bureau, G; Frances, C; Costedoat-Chalumeau, N
A causal link has long been described between estrogen and systemic lupus erythematosus activity. Contraceptive and pregnancy management is now common for lupus patients, but pregnancy continues to be associated with higher maternal and fetal mortality/morbidity in systemic lupus erythematosus patients than among the general population. Potential complications include lupus flares, obstetric complications (fetal loss, in utero growth retardation, premature birth) and neonatal lupus syndrome. Association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetric complications. Anti-SSA and/or anti-SSB antibodies put fetuses at risk for neonatal lupus. Improving the outcome of such pregnancies depends upon optimal systematic planning of pregnancy at a preconception counseling visit coupled with a multidisciplinary approach. Absence of lupus activity, use of appropriate medication during pregnancy based on the patient's medical history and risk factors, and regular monitoring constitute the best tools for achieving a favorable outcome in such high-risk pregnancies. The aim of this review is to provide an update on the management of contraception and pregnancy in systemic lupus erythematosus, cutaneous lupus and/or antiphospholipid syndrome in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis.
Howell, David N
Kidney biopsy is a mainstay in the diagnosis and management of renal disease in patients with systemic lupus erythematosus. Though biopsies from patients with lupus typically show various forms of immune complex glomerulonephritis, other pathologies are occasionally encountered, including unusual lupus-related nephropathies, other forms of autoimmune disease, and occasional renal disorders without any direct connection with lupus or autoimmunity. Electron microscopy is a powerful tool for detecting and classifying these unusual conditions, which frequently have important therapeutic and prognostic implications.
... Systemic Lupus Erythematosus--Developing Medical Products for Treatment; Availability AGENCY: Food and Drug... availability of a guidance for industry entitled ``Systemic Lupus Erythematosus--Developing Medical Products..., therapeutic biological products, and medical devices for the treatment of systemic lupus erythematosus...
Zhang, Sigong; Wang, Guochun; Wang, Jinping
Type B insulin resistance syndrome is characterized by the formation of autoantibodies against insulin receptors, which can cause severe hyperglycemia and insulin resistance. Systemic lupus erythematosus is the most common underlying diseases of the syndrome. This report details our study of a case involving a Chinese female with type B insulin resistance syndrome as well as systemic lupus erythematosus who completely recovered after undergoing immunosuppressive therapy, specifically pulse therapy utilizing intravenous immunoglobulin. We also conducted search in MEDLINE and Chinese BioMedicine database to identify relevant literatures published in the past 46 years. From our searches, six case reports in Chinese, 15 case reports, and a 28-year perspective article in English met our criteria; a total of 67 cases were included in our report. The mean age of subjects at presentation for groups A, B, and C were 42.95, 44.10, and 41.68 years, respectively, yielding no significant difference between these groups. African Americans were the most susceptible group to type B insulin resistance syndrome, followed by Asians representing 20.90 % of all cases. Comparisons between the three main racial groups surveyed indicated that the mean age of subjects at presentation were very contiguous for African Americans and Asians, and mean age of white people was remarkably higher than either of the first two groups. The syndrome appeared most common among Asian males, and white males were relatively less likely to suffer from type B insulin resistance syndrome. Hypoglycemia was most commonly observed in white people than in other racial groups. Hypoalbuminemia, elevated serum immunoglobulin G, and elevated sedimentation rates were more common in African Americans; Asian cases were more likely to show low serum C3 or C4 and nephritis. Two cases received intravenous immunoglobulin therapy, which has a remarkably rapid effect on insulin resistance.
Guettrot-Imbert, G; Le Guern, V; Morel, N; Vauthier, D; Tsatsaris, V; Pannier, E; Piette, J-C; Costedoat-Chalumeau, N
Pregnancy in systemic lupus erythematosus patients is a common situation that remains associated with higher maternal and fetal mortality/morbidity than in the general population. Complications include lupus flares, obstetrical complications (fetal loss, in utero growth retardation, prematurity) and neonatal lupus syndrome. The association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetrical complications. Improving the care of these pregnancies depends upon a systematic pregnancy planning, ideally during a preconception counseling visit and a multidisciplinary approach (internist/rheumatologist, obstetrician and anesthetist). The absence of lupus activity, the use of appropriate medications during pregnancy adjusted to the patient's medical history and risk factors, and a regular monitoring are the best tools for a favorable outcome for these high-risk pregnancies. The aim of this review article is to perform an update on the medical care of pregnancy in systemic lupus erythematosus or antiphospholipid syndrome to reduce the risk of complications and to ensure the best maternal and fetal prognosis.
Petrin, J; Rozman, B; Dolenc, P; Logar, D; Bozic, B; Vizjak, A; Ferluga, D; Jezersek, P
In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.
Mendeleev, I M; Miasnikov, A A; Polezhaev, Iu N; Berliner, G B
The authors describe three comparatively rare cases of extremely severe symptomatic autoimmune thrombocytopenia associated with systemic lupus erythematosus. The use of glucocorticoids in large doses and in two cases of splenectomy turned out ineffective. The next therapeutic measures are suggested in the following succession: glucocorticoids----cytostatic drugs (vincristine)----splenectomy to be performed only in special cases.
Americans with Systemic Lupus Erythematosus PRINCIPAL INVESTIGATOR: John Harley, M.D., Ph.D...September 2012 – 31 August 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Genome-Wide Association Study in African-Americans with Systemic Lupus ...SUPPLEMENTARY NOTES 14. ABSTRACT Systemic lupus erythematosus ( lupus ) is a potentially deadly systemic autoimmune disease that disproportionately
Gayed, Mary; Gordon, Caroline
Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with the production of autoantibodies, and with considerable morbidity and mortality. There has been much interest in developing more specific therapies for this disease, which is currently managed with immunosuppressive drugs, predominantly corticosteroids, azathioprine, methotrexate and cyclophosphamide, in combination with hydroxychloroquine. Mycophenolate mofetil has been demonstrated to be as efficacious as cyclophosphamide in patients with lupus nephritis, and is being used increasingly in the clinic despite not being licensed for this indication. Novel methods of reducing autoantibody formation in SLE include the use of mAbs that modulate and/or deplete B-cells (anti-CD22 and anti-CD20 antibodies, respectively), or that interfere with the stimulatory effects of the soluble factor B-lymphocyte stimulator (anti-BLys antibodies). Alternative approaches include the use of atacicept (Merck Serono), a transmembrane activator and calcium modulator ligand interactor (TACI)-Ig fusion protein, which inhibits B-cell stimulation by binding to BLys and a profileration-inducing ligand (APRIL), or toleragens such as abetimus. Blocking costimulatory molecule interactions, such as the CD40-CD40 ligand interaction with mAbs and the CD28-B7 interaction with a soluble cytotoxic T-lymphocyte antigen 4 (CTLA-4)-IgG1 construct (abatacept), has also been attempted as a therapeutic strategy for SLE. The most promising strategy for a new drug for SLE is belimumab (Human Genome Sciences/GlaxoSmithKline), an anti-BLys antibody, as two phase III clinical trials with this drug recently met their primary endpoints. In this review, these novel approaches to the treatment of SLE, including the potential of targeting cytokine pathways involved in autoimmunity, are discussed.
Wu, Tianfu; Xie, Chun; Han, Jie; Ye, Yujin; Weiel, Jim; Li, Quan; Blanco, Irene; Ahn, Chul; Olsen, Nancy; Putterman, Chaim; Saxena, Ramesh; Mohan, Chandra
The metabolic disturbances that underlie systemic lupus erythematosus are currently unknown. A metabolomic study was executed, comparing the sera of 20 SLE patients against that of healthy controls, using LC/MS and GC/MS platforms. Validation of key differences was performed using an independent cohort of 38 SLE patients and orthogonal assays. SLE sera showed evidence of profoundly dampened glycolysis, Krebs cycle, fatty acid β oxidation and amino acid metabolism, alluding to reduced energy biogenesis from all sources. Whereas long-chain fatty acids, including the n3 and n6 essential fatty acids, were significantly reduced, medium chain fatty acids and serum free fatty acids were elevated. The SLE metabolome exhibited profound lipid peroxidation, reflective of oxidative damage. Deficiencies were noted in the cellular anti-oxidant, glutathione, and all methyl group donors, including cysteine, methionine, and choline, as well as phosphocholines. The best discriminators of SLE included elevated lipid peroxidation products, MDA, gamma-glutamyl peptides, GGT, leukotriene B4 and 5-HETE. Importantly, similar elevations were not observed in another chronic inflammatory autoimmune disease, rheumatoid arthritis. To sum, comprehensive profiling of the SLE metabolome reveals evidence of heightened oxidative stress, inflammation, reduced energy generation, altered lipid profiles and a pro-thrombotic state. Resetting the SLE metabolome, either by targeting selected molecules or by supplementing the diet with essential fatty acids, vitamins and methyl group donors offers novel opportunities for disease modulation in this disabling systemic autoimmune ailment. PMID:22723834
Orme, Jacob; Mohan, Chandra
Systemic lupus erythematosus (SLE) is a heterogeneous group of autoimmune disorders defined by a consensus of clinical and laboratory criteria. Much of the pathophysiology and therapy of SLE has focused on autoimmune B and T cells of the adaptive immune system. Recently, the role of macrophages, part of the innate immune system, in SLE pathogenesis has gained attention. The field of immunology in general has recently changed in the way that it approaches macrophages. Rather than viewing them as a single, concrete whole, it has become clear that different subpopulations of macrophages contribute to various immune and non-immune processes. Such a nomenclature may provide an ideal framework from which to study macrophage pathogenesis in SLE. Studies suggest that M1 subtype macrophages play an important inflammatory role in SLE pathogenesis. Further, apparently reduced populations of M2a and M2c subtype macrophages may contribute to the lack of anti-inflammatory activity apparent in the disease. M2b subtype macrophages may actually have a role in causing disease directly. Regulatory macrophages have yet to be explored thoroughly in SLE, though the presence of a few of their markers may mean that they are active in suppressing SLE-related inflammation.
Systemic lupus erythematosus (SLE) is an autoimmune disease of diverse manifestations, with onset usually in young women in the third to fourth decade of life. The chronic nature of this relapsing remitting disease leads to organ damage accrual over time. Mortality and morbidity are increased in patients with SLE compared with the general population. Therapeutic advances over the last few decades have led to significant improvements in patient outcomes. Five-year survival has improved to over 90% from a low of 50% in the 1950s. However, multiple aspects of the management of SLE patients are still far from optimal. Early diagnosis remains a challenge; diagnostic delays leading to delay in definitive treatment are common. Monitoring treatment remains problematic due to the paucity of sensitive biomarkers. Current treatment regimens rely heavily on corticosteroids, even though corticosteroids are well known to cause organ damage. Treatment of refractory disease manifestations such as nephritis, recalcitrant cutaneous lesions and neurological involvement require new approaches with greater efficacy. Cognitive dysfunction is common in SLE patients, but early recognition and adequate treatment are yet to be established. Premature accelerated atherosclerosis remains a leading cause of morbidity and mortality. Fatigue is one of the most disabling symptoms, and contributes to the poor quality of life in patients with SLE. Ongoing research in SLE faces many challenges, including enrollment of homogeneous patient populations, use of reliable outcome measures and a standard control arm. The current review will highlight some of the outstanding unmet challenges in the management of this complex disease. PMID:23281889
Hevia, Arancha; Milani, Christian; López, Patricia; Cuervo, Adriana; Arboleya, Silvia; Duranti, Sabrina; Turroni, Francesca; González, Sonia; Suárez, Ana; Gueimonde, Miguel; Ventura, Marco
ABSTRACT Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease in humans and is characterized by the presence of hyperactive immune cells and aberrant antibody responses to nuclear and cytoplasmic antigens, including characteristic anti–double-stranded DNA antibodies. We performed a cross-sectional study in order to determine if an SLE-associated gut dysbiosis exists in patients without active disease. A group of 20 SLE patients in remission, for which there was strict inclusion and exclusion criteria, was recruited, and we used an optimized Ion Torrent 16S rRNA gene-based analysis protocol to decipher the fecal microbial profiles of these patients and compare them with those of 20 age- and sex-matched healthy control subjects. We found diversity to be comparable based on Shannon’s index. However, we saw a significantly lower Firmicutes/Bacteroidetes ratio in SLE individuals (median ratio, 1.97) than in healthy subjects (median ratio, 4.86; P < 0.002). A lower Firmicutes/Bacteroidetes ratio in SLE individuals was corroborated by quantitative PCR analysis. Notably, a decrease of some Firmicutes families was also detected. This dysbiosis is reflected, based on in silico functional inference, in an overrepresentation of oxidative phosphorylation and glycan utilization pathways in SLE patient microbiota. PMID:25271284
Adelowo, O O; Olaosebikan, B H; Animashaun, B A; Akintayo, R O
Juvenile systemic lupus erythematosus (JSLE) is a complex multisystemic autoimmune disorder of unknown cause. It accounts for about one in five cases of SLE. The tendency for SLE to run a fulminant course when it starts in childhood has made JSLE a potentially more severe disease than adult SLE. Reports of JSLE from sub-Saharan Africa are scanty in spite of the increasing reports of adult SLE. We conducted a 4-year retrospective study of JSLE cases seen at the Lagos State University Teaching Hospital between January 2010 and December 2014. Out of the 12 patients studied, eight were girls and four were boys. All patients had positive antinuclear antibody and extractable nuclear antibody tests. Anti-dsDNA antibody was positive in 10 patients. Eight patients had renal disease while four patients had neuropsychiatric manifestations. Haematological abnormalities and constitutional symptoms were present in all patients. Patients were treated with pulse methylprednisolone, oral prednisolone, hydroxychloroquine and azathioprine. Three patients also received rituximab. In conclusion, JSLE exists in Nigeria and exhibits clinical and immunological characteristics similar to its pattern in other parts of the world. It is, however, diagnosed late and is possibly being underdiagnosed as there is no paediatric rheumatologist in the country.
Lazaro, Estibaliz; Scherlinger, Marc; Truchetet, Marie-Elise; Chiche, Laurent; Schaeverbeke, Thierry; Blanco, Patrick; Richez, Christophe
Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challenging to develop. Several biotherapies targeting different pathophysiological pathways have been developed over the past 15 years. The results of Phase II trials were encouraging but rarely borne out by Phase III trials. Recent data, which are discussed in detail in this review, allowed belimumab - a monoclonal antibody against BLyS (B-lymphocyte stimulator) - to become the first biotherapy approved for use in SLE. Other molecules targeting B cells include the two anti-BLyS antibodies tabalumab and blisibimod; atacicept, which targets both BLyS and APRIL (a proliferation-inducing ligand); and the monoclonal antibody to CD22 epratuzumab. The rekindling of interest in the B-cell pathway has also driven new clinical research into rituximab, a monoclonal antibody targeting CD20 with evaluations of new strategies. A new and promising approach is the use of inhibitors of the type 1 interferon (IFN) pathway, of which the most promising is anifrolumab, a monoclonal antibody targeting the type 1 IFN receptor. In this review, we discuss study findings and their clinical relevance, present the most promising targets, and analyze possible explanations to negative results, such as inappropriate patient selection and treatment response criteria or the erratic use of high-dose glucocorticoid therapy.
Wu, E Y; Schanberg, L E; Wershba, E C; Rabinovich, C E
Objective Cutaneous manifestations of pediatric systemic lupus erythematosus cause significant morbidity. Lenalidomide, a thalidomide analogue, has shown promise treating cutaneous lupus erythematosus in adults. Our objective was to evaluate lenalidomide's efficacy and safety in treating refractory cutaneous manifestations of pediatric systemic lupus erythematosus. Methods We performed a retrospective chart review of 10 adolescents who received lenalidomide for recalcitrant cutaneous lupus erythematosus. Information was gathered at drug initiation and 6-month follow-up. The Wilcoxon matched-pairs signed-rank test was used to assess change in quantitative parameters of disease activity. Results Nine subjects were girls and six were African-American. Indications for lenalidomide treatment included alopecia, nasal and oral ulcers, extensive malar rash, discoid lesions, bullous lesions, panniculitis, cutaneous vasculitis, and Raynaud's phenomenon with digital ulcerations. Within 6 months, all patients demonstrated complete or near resolution based on physician report. Prednisone dose decreased from a mean 23.5 mg (SD± 13.3) to 12.25 mg (SD± 9.2) ( P= 0.008). Sedimentation rate decreased from a mean 29 mm/hour (SD± 31.5) to 17 mm/hour (SD± 18.1) ( P= 0.004). Lenalidomide was well tolerated. Conclusion Lenalidomide is an effective and safe treatment for a spectrum of dermatological conditions in pediatric systemic lupus erythematosus. Its use may allow a reduction in prednisone dose and decreased disfigurement. Prospective study is needed to clarify lenalidomide's role in treating cutaneous manifestations of systemic lupus erythematosus.
Wang, Y; Da, G; Yu, Y; Han, J; Li, H
Psoriasis vulgaris is an autoimmune chronic inflammatory skin disease, but its association with other typical autoimmune disease such as systemic lupus erythematosus has only occasionally been reported. We presented a 25-year-old female who developed systemic lupus erythematosus associated with psoriasis vulgaris. Her conditions were in good control after she got administration of prednisolone (5 mg/day) and Tripterygium Wilfordii Hook (20 mg/day). It is necessary to integrate past history and physical examination to diagnose coincident SLE and psoriasis, and combined treatment with prednisolone and Tripterygium Wilfordii Hook proves effective.
Baenas, Diego F; Diehl, Fernando A; Haye Salinas, María J; Riva, Verónica; Diller, Ana; Lemos, Pablo A
Kikuchi–Fujimoto disease, or histiocytic necrotizing lymphadenitis, is an infrequent idiopathic disorder. It has been associated with autoimmune disorders, of which systemic lupus erythematosus is the most outstanding. The basis of its diagnosis relies on the histological examination of lymph nodes, which typically reveals necrosis surrounded by histiocytes with crescentic nucleus, immunoblasts and plasma cells, and absence of neutrophils. We report the case of a 27-year-old Argentinian female patient without any relevant past medical history to demonstrate the correlation between Kikuchi–Fujimoto disease and systemic lupus erythematosus. PMID:27418858
Sánchez, A; Robaina, R; Pérez, G; Cairoli, E
Necrotizing fasciitis is a rapidly progressive destructive soft tissue infection with high mortality. Streptococcus pneumoniae as etiologic agent of necrotizing fasciitis is extremely unusual. The increased susceptibility to Streptococcus pneumoniae infection in patients with systemic lupus erythematosus is probably a multifactorial phenomenon. We report a case of a patient, a 36-year-old Caucasian female with 8-year history of systemic lupus erythematosus who presented a fatal Streptococcus pneumoniae necrotizing fasciitis. The role of computed tomography and the high performance of blood cultures for isolation of the causative microorganism are emphasized. Once diagnosis is suspected, empiric antibiotic treatment must be prescribed and prompt surgical exploration is mandatory.
Francis, Lisa; Perl, Andras
Infectious agents have long been implicated in the pathogenesis of systemic lupus erythematosus. Common viruses, such as the Epstein-Barr virus, transfusion transmitted virus, parvovirus and cytomegalovirus, have an increased prevalence in patients with systemic lupus erythematosus. They may contribute to disease pathogenesis through triggering autoimmunity via structural or functional molecular mimicry, encoding proteins that induce cross-reactive immune responses to self antigens or modulate antigen processing, activation, or apoptosis of B and T cells, macrophages or dendritic cells. Alternatively, some infectious agents, such as malaria, Toxoplasma gondii and Helicobacter pylori, may have a protective effect. Vaccinations may play dual roles by protecting against friend and foe alike. PMID:20209114
Jaimes-Hernandez, J; Aranda-Peirera, P; Melendez-Mercado, C I
Eosinophilic gastroenteritis (EGE) is an uncommon disease and has rarely been reported in association with connective tissue diseases as systemic lupus erythematosus. We report a 36-year-old woman who developed recurrent episodes of abdominal pain, nausea, vomiting and melena. Complete blood counts showed elevated eosinophil counts. Ultrasound and CT-scan images studies were significant for bowel wall thickening and ascites. The patient underwent an exploratory laparotomy with a mesenteric biopsy and appendectomy that showed eosinophil infiltration in the muscularis propria, establishing the diagnosis of EGE. The patient developed pleural effusions, with laboratory studies showing haemolytic anaemia, thrombocytopenia, positive antinuclear antibody and anticardiolipin antibodies. The patient was treated with high-dose systemic corticosteroid therapy, with successful resolution of symptoms. Three months later, she developed a new episode of abdominal pain defined as intestinal pseudo-obstruction that was resolved without complications.
GU, YUQING; ZHU, TAO; WANG, YIQING; XU, HONGXING
Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease, which can affect almost all systems and organs. Gastrointestinal disorder is one of the most noteworthy complications of patients with SLE. However, gastrointestinal disorder with intestinal perforation is rare, but potentially life-threatening if not treated promptly. The present study reported a case of SLE with intestinal perforation, where surgical intervention was performed and a crevasse (~3 cm in diameter) was detected in the ileum, ~60 cm from the ileocecal valve. Following surgery, the patient suffered from difficult ventilator weaning, septic shock and intestinal obstruction. The patient was successfully treated and discharged from the hospital after ~4 months of treatment. Intestinal perforation in SLE patients is potentially life-threatening; early diagnosis and prompt treatment are crucial to the management of this rare complication of SLE. PMID:26622471
Elliott, Jennifer R; Manzi, Susan
With improved treatment modalities and survival rates, patients with systemic lupus erythematosus live longer and their co-morbidities have become more apparent. Of great concern is cardiovascular disease, which has become a leading cause of death. Lupus patients prematurely develop atherosclerosis, which likely arises from an interaction among traditional cardiovascular risk factors, factors specific to lupus itself and inflammatory mediators. Despite these findings, lupus patients are not always adequately evaluated for traditional risk factors, many of which are treatable and reversible. We propose that lupus patients be assessed and managed regarding cardiovascular risk factors in the same manner as patients with known cardiovascular disease. As a result, preventive cardiology should be considered an essential component of the care for patients with lupus.
Düzgün, N; Duman, M; Sonel, B; Peksari, Y; Erdem, C; Tokgöz, G
We present the case of a patient with juvenile onset systemic lupus erythematosus (SLE) who developed a persistent, acquired hypogammaglobulinaemia with IgG deficiency. The hypogammaglobulinaemia was probably a complication of high dose corticosteroid treatment. The serum IgG level remained subnormal despite intravenous immunoglobulin therapy. Lupus vulgaris, which developed on the nasal cartilage in this patient with SLE, is not an expected finding. This patient is probably the first reported case of SLE associated with lupus vulgaris.
Kaye, B R; Neuwelt, C M; London, S S; DeArmond, S J
The case is reported of a patient with central nervous system systemic lupus erythematosus (SLE) with features of progressive multifocal leucoencephalopathy (PML) seen clinically and by magnetic resonance imaging. A brain biopsy sample showed microinfarcts. The use of magnetic resonance imaging and IgG synthesis rates in evaluating central nervous system lupus, the co-occurrence of SLE and PML, and the differentiation of these entities by magnetic resonance imaging and by histology are considered. Images PMID:1444628
Zandman-Goddard, Gisele; Orbach, Hedi; Shoenfeld, Yehuda
This review covers the major advances in the therapeutic potentials related to systemic lupus erythematosus published in Medline between 2000 and February 2005. Controlled, open and Phase I-III trials were included. Anecdotal reports were excluded. Several trials have defined the role of cyclophosphamide, methotrexate, antimalarials, hormonal treatment and mycophenolate mofetil (Cellcept) in the management of systemic lupus erythematosus. The aims of novel biologics for systemic lupus erythematosus are to target the autoimmune disease at different points: B-cell depletion (rituximab [Rituxan], anti-BLys antibodies [Lymphostat-B]), inhibition of T-B interaction (rituximab), blockade of cytokines (anti-interleukin-10 antibodies), manipulation of idiotypes (intravenous immunoglobulin), tolerance induction to DNA and immunoglobulin-peptides and peptide therapy (abetimus sodium [Riquent]). Low-dose intravenous cyclophosphamide (Euro-Lupus protocol) is as effective as the conventional National Institutes of Health protocol and is also associated with less toxicity. Stem cell transplantation for severe disease induces remission in most patients, however, the relapse rate in a third of patients and the associated morbity and mortality restricts its use to selected patients with life-threatening disease. Intravenous immunoglobulin, although utilized in open trials, is effective and safe for various manifestations of systemic lupus erythematosus. Major advances have been associated with mycophenolate mofetil and rituximab. Mycophenolate mofetil is effective for induction and maintenance therapy of lupus proliferative glomerulonephritis and is associated with fewer adverse events than monthly intravenous cyclophosphamide. Rituximab is a promising agent, and although its utilization is presently limited, it appears to be effective for lupus patients with severe disease.
Khamashta, M A; Gil, A; Anciones, B; Lavilla, P; Valencia, M E; Pintado, V; Vázquez, J J
Chorea is a rare manifestation of systemic lupus erythematosus (SLE). In this report the clinical features of two cases of chorea associated with SLE are presented. Of special interest were the raised titres of antiphospholipid antibodies in both cases. The possible pathogenic role of these antibodies is briefly discussed. PMID:3415367
Modi, Gunjan M; Maender, Jennifer L; Coleman, Neil; Hsu, Sylvia
Few papers discuss the potential challenge of differentiating dermatophytosis from subacute cutaneous lupus erythematosus. This masquerade, most often manifest on the face, is of both clinical and therapeutic importance. We report a patient whose extensive tinea corporis very closely mimicked SCLE. The threshold for biopsy should be low in cases that exhibit atypical features for either of these entities.
Although the etiology of systemic lupus erythematosus (SLE) remains to be fully elucidated, it is now apparent that multiple genetic and environmental factors are at play. Because lupus has a strong female preponderance, several studies have examined the role of female hormones in disease etiology. Yet this knowledge has not helped to explain lupus etiology or to prevent it. Estrogens exist not only as natural or drug compounds, but also as environmental chemical contaminant and women are highly exposed to all of them. Estrogenic activity has been found in a number of pesticides including pyrethroids that are largely used in the household. Although there is only a small amount of published data examining a possible causal relationship between lupus and pesticides it can be hypothesized that pesticides, in particular insecticides, through their estrogenic activity and capacity to induce oxidative stress provoke autoimmune reaction influencing lupus development.
Hosenpud, J.D.; Montanaro, A.; Hart, M.V.; Haines, J.E.; Specht, H.D.; Bennett, R.M.; Kloster, F.E.
Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment, major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.
Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.
In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.
Fernández-Nebro, Antonio; Rúa-Figueroa, Íñigo; López-Longo, Francisco J.; Galindo-Izquierdo, María; Calvo-Alén, Jaime; Olivé-Marqués, Alejandro; Ordóñez-Cañizares, Carmen; Martín-Martínez, María A.; Blanco, Ricardo; Melero-González, Rafael; Ibáñez-Rúan, Jesús; Bernal-Vidal, José Antonio; Tomero-Muriel, Eva; Uriarte-Isacelaya, Esther; Horcada-Rubio, Loreto; Freire-González, Mercedes; Narváez, Javier; Boteanu, Alina L.; Santos-Soler, Gregorio; Andreu, José L.; Pego-Reigosa, José M.
Abstract This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2–66.1], and SLE duration of 212.0 months [120.8–289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02–1.04]), hypertension (1.71 [1.20–2.44]), smoking (1.48 [1.06–2.07]), diabetes (2.2 [1.32–3.74]), dyslipidemia (2.18 [1.54–3.09]), neurolupus (2.42 [1.56–3.75]), valvulopathy (2.44 [1.34–4.26]), serositis (1.54 [1.09–2.18]), antiphospholipid antibodies (1.57 [1.13–2.17]), low complement (1.81 [1.12–2.93]), and azathioprine (1.47 [1.04–2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows—for the first time—an association between diabetes and CV events in SLE patients. PMID:26200625
Jarrett, P; Thornley, S; Scragg, R
Background The prevalence and variation by ethnicity of cutaneous lupus in New Zealand is not known. Therefore, a cross-sectional study to determine the prevalence and variation by ethnicity of cutaneous lupus in the ethnically diverse community of South Auckland, New Zealand, was undertaken. Methods Multiple sources were examined to determine the prevalence of acute cutaneous lupus erythematosus, subacute cutaneous erythematosus and discoid lupus erythematosus. Ethnicities examined were European, Māori/Pacific and Indian/Asian. Capture-recapture was used to determine the overall population prevalence of cutaneous lupus. Results A total of 145 cases of cutaneous lupus were identified. There were 22 men and 123 women, with an average age (standard deviation), respectively, of 46.4 (±21.5) and 43.1 (±14.8) years. There were 53 cases of acute cutaneous lupus erythematosus, 19 cases of subacute cutaneous erythematosus and 66 cases of discoid lupus erythematosus. The age and sex adjusted relative risk (95% confidence interval; CI) of Māori/Pacific compared to the European population was 2.47 (95% CI 1.67-3.67) for all types of cutaneous lupus, 1.60 (95% CI 0.84-3.18) for acute cutaneous lupus erythematosus, 0.09 (95% CI 0.01-1.1) for subacute cutaneous erythematosus and 5.96 (95% CI 3.06-11.6) for discoid lupus erythematosus. The overall prevalence of cutaneous lupus was 30.1 (95% CI 25.5-35.4) per 100,000. However, capture-recapture estimated the unadjusted prevalence of cutaneous lupus to be 86.0 (95% CI 78.1-94.7) per 100,000. Conclusion Māori and Pacific people in Auckland, New Zealand, have a greater relative risk of all types of cutaneous lupus compared to the European population and a particularly high risk of discoid lupus erythematosus.
Americans with Systemic Lupus Erythematosus PRINCIPAL INVESTIGATOR: John Harley, M.D., Ph.D... Systemic Lupus Erythematosus 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER John Harley, M.D., Ph.D. 5e. TASK...SUPPLEMENTARY NOTES 14. ABSTRACT Systemic lupus erythematosus is a potentially deadly systemic autoimmune disease that disproportionately afflicts women
Calderaro, Débora Cerqueira; Ferreira, Gilda Aparecida; Corrêa, Jôice Dias; Mendonça, Santuza Maria Souza; Silva, Tarcília Aparecida; Costa, Fernando Oliveira; Lúcio Teixeira, Antônio
The aim of this study was to compare the frequency and severity of chronic periodontitis (CP) in systemic lupus erythematosus (SLE) patients with individuals without rheumatic diseases. Seventy-five patients with SLE were compared to 75 individuals without rheumatic diseases (control group) matched for age, educational level, and income. The activity of SLE was assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus evaluated SLE-related damage. Dental evaluation included measuring plaque index and parameters of periodontal disease (probing depth, clinical attachment level, and bleeding on probing). Fifty-one (68 %) SLE patients and 42 (56 %) control individuals had CP (p = 0.13). Periodontal status was similar in both groups. Considering only individuals with CP, SLE patients were younger than controls (40.7 ± 9.8 versus 46.14 ± 12.5 years of age, p = 0.02). CP was not associated with activity or therapeutics in SLE patients. Severity of periodontal parameters was similar in SLE patients and control subjects; however, CP occurred earlier in SLE patients.
Chung, Sharon A.; Brown, Elizabeth E.; Williams, Adrienne H.; Ramos, Paula S.; Berthier, Celine C.; Bhangale, Tushar; Alarcon-Riquelme, Marta E.; Behrens, Timothy W.; Criswell, Lindsey A.; Graham, Deborah Cunninghame; Demirci, F. Yesim; Edberg, Jeffrey C.; Gaffney, Patrick M.; Harley, John B.; Jacob, Chaim O.; Kamboh, M. Ilyas; Kelly, Jennifer A.; Manzi, Susan; Moser-Sivils, Kathy L.; Russell, Laurie P.; Petri, Michelle; Tsao, Betty P.; Vyse, Tim J.; Zidovetzki, Raphael; Kretzler, Matthias; Kimberly, Robert P.; Freedman, Barry I.; Graham, Robert R.
Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis–predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10−7), 16p12 (SLC5A11; P=5.1×10−7), 6p22 (ID4; P=7.4×10−7), and 8q24.12 (HAS2, SNTB1; P=1.1×10−6). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10−5, respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10−6). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci. PMID:24925725
Schwartz, S; Esseltine, D W
A case of a 13-year-old boy with prolonged bleeding after tooth extraction is reported. This was the first manifestation of systemic lupus erythematosus found to be associated with circulating anticoagulants, including the "lupus anticoagulant," and possible hypoprothrombinemia.
Yaghoobi, Reza; Feily, Amir; Behrooz, Bahar; Yaghoobi, Elena; Mokhtarzadeh, Shabnam
A 28-year-old woman presented with a 2-year history of idiopathic, chronic blepharitis unresponsive to several courses treatment of corticosteroid eye drops. Physical examination was notable for edematous, erythematous plaques of the lower eyelids with madarosis in the absence of preceding skin scarring. Biopsy specimen was obtained and diagnosis of discoid lupus erythematosus (DLE) was made. DLE is a chronic, cutaneous disease that is clinically characterized by a malar rash, acute erythema, and discoid lesions. Localized DLE occurs when the head and neck only are affected, while widespread DLE occurs when other areas are affected, regardless of whether disease of the head and neck is seen. Patients with widespread involvement often have hematologic and serologic abnormalities, are more likely to develop systemic lupus erythematosus, and are more difficult to treat. A number of skin diseases may be confused with DLE, such as psoriasis, seborrheic dermatitis, acne, rosacea, lupus vulgaris, sarcoidosis, Bowen's disease, polymorphous light eruption, lichen planopilaris, dermatomyositis, granuloma annulare, and granuloma faciale. Palpebral lesions may rarely be the presenting or sole manifestation of the disease and lower eyelid involvement is seen in 6% of patients with chronic, cutaneous lupus erythematosus. DLE should therefore be considered as a differential diagnosis in chronic blepharitis or madarosis that persists despite usual medical management and eyelid hygiene. The patient was treated successfully with hydroxychloroquine. The skin lesions resolved with minimal scarring.
Prasad, D.; Agarwal, D.; Malhotra, V.; Beniwal, P.
We report recurrent hypokalemic periodic quadriparesis in a 30-year-old woman. Patient had also symptoms of multiple large and small joint pain, recurrent oral ulceration, photosensitivity and hair loss that were persisting since last 6 months and investigations revealed systemic lupus erythematosus (SLE) with distal tubular acidosis. Our patient was successfully treated with oral potassium chloride, sodium bicarbonate, hydroxychloroquine and a short course of steroids. Thus, tubular dysfunction should be carefully assessed in patients with SLE. PMID:25249723
Mete, Bilgul; Saltoglu, Nese; Vanli, Ersin; Ozkara, Cigdem; Arslan, Ferhat; Mert, Ali; Ozaras, Resat; Tabak, Fehmi; Ozturk, Recep
Simultaneous central nervous system (CNS) infection with Cryptococcus and tuberculosis (TB) is very rare. Despite improved therapeutic options, treatment of CNS cryptococcosis is still difficult and needs invasive treatment modalities, such as intrathecal or intraventricular amphotericin B, in refractory cases. We describe a patient with systemic lupus erythematosus diagnosed with simultaneous cryptococcal and TB meningitis who had a poor response to intravenous liposomal amphotericin B and fluconazole, but was successfully treated with intraventricular amphotericin B, in addition to anti-TB therapy.
Mosca, Marta; Tani, Chiara; Filice, Maria Elena; Carli, Linda; Delle Sedie, Andrea; Vagnani, Sabrina; Della Rossa, Alessandra; Baldini, Chiara; Bombardieri, Stefano
Joint involvement is a common manifestation of systemic lupus erythematosus (SLE) and is described as a non-erosive mild synovitis. However some SLE patients may present a more severe joint involvement requiring aggressive therapy. We describe the case of a SLE patient with a severe arthritis unresponsive to methotrexate, successfully treated with anti-TNF-alpha drug as induction therapy and we report the results of a systematic literature review on the use of TNF-alpha inhibitors in SLE.
Ugarte, A; Villar, I; Ruiz-Irastorza, G
Patients with systemic lupus erythematosus are exposed to a remarkably high number of maternal-fetal complications during pregnancy. Knowledge regarding the reciprocal influence between lupus and pregnancy is the starting point to assure that these patients are correctly monitored. It is also important to carry out comprehensive preconception evaluation to individually evaluate the risk of each patient. The immunological profile, history of nephritis, presence of chronic damage and disease activity are the basic data that will determine the specific individual risk profile. Finally, correct drug management must be assured during this period, based on the safety profile of the different treatments during pregnancy and lactation.
Zapor, M; Murphy, F T; Enzenauer, R
"That tongue of yours, by which I have been tricked, shall have its power curtailed and enjoy the briefest use of speech." With these words, Hera, of Greek mythology, deprived the nymph Echo of spontaneous speech, constraining her instead to merely repeating the words of others. Echolalia, which derives from the word "echo," is disordered speech in which an individual persistently repeats what is heard. Echolalia has been described in patients with a number of neuropsychiatric illnesses including autism and Tourette's syndrome. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a heterogeneous disease with protean manifestations that may occur in approximately 25% to 50% of patients with systemic lupus erythematosus (SLE). Although the most common manifestations include cognitive dysfunction (50%) and seizures (20%), NPSLE may also present as peripheral neuropathy (15%), psychosis (10%), or other central nervous system abnormalities. We report the case of a 57-year-old woman with SLE and echolalia.
Wardhana; Datau, E A
Morphea is an uncommon connective tissue disease with the most prominent feature being thickening or fibrosis of the dermal without internal organ involvement. It is also known as a part of localized scleroderma. Based on clinical presentation and depth of tissue involvement, morphea is classified into several forms, and about two thirds of adults with morphea have plaque type. Overproduction of collagen production by fibroblast is the cause of abnormality in morphea, and the hyperactivity mechanism of fibroblast is still unknown, although there are several mechanisms already proposed. Plaque type morphea is actually a benign and self limited. Plaque type morphea that mimicking systemic lupus erythematosus in clinical appearance, such as alopecia and oral mucosal ulcers, is uncommon. A case of plaque type morphea mimicking systemic lupus erythematosus in a 20 year old woman was discussed. The patient was treated with local and systemic immunosuppressant and antioxydant. The patient's condition is improved without any significant side effects.
Antón Vázquez, Vanesa; Pascual, Luis; Corominas, Héctor; Giménez Torrecilla, Isabel
Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine.
Kansara, Bhuvnesh; Singh, Ajmer; Karlekar, Anil; Mishra, Yugal K
Valvular heart disease in systemic lupus erythematosus (SLE) is associated with substantial morbidity and mortality. Current therapy includes symptomatic measures and valve replacement. SLE can present major challenges because of accrued organ damage, coagulation defects and complex management regimes. The peri-operative goals are to maintain strict asepsis, avoid use of nephrotoxic drugs and thereby renal insult, and to promote early ambulation post-operatively. PMID:23878452
Delmonte, S; Massone, C; Parodi, A; Rebora, A
A 34-year-old woman presented with a right winged scapula 8 months after developing systemic lupus erythematosus (SLE) with subacute cutaneous manifestations. The patient experienced severe shoulder pain followed by weakness of the right arm in the typically winged scapula fashion. Electromyography of the serratus anterior showed long thoracic nerve palsy. Clinical and laboratory signs did not reveal any associated disease. Paralysis of the long thoracic nerve has never been described before in SLE.
Richer, O; Ulinski, T; Lemelle, I; Ranchin, B; Loirat, C; Piette, J C; Pillet, P; Quartier, P; Salomon, R; Bader‐Meunier, B
Background Childhood‐onset lupus erythematosus is a rare disorder of unknown origin. Objectives To describe the frequency of gastrointestinal manifestations at presentation of systemic lupus erythematosus SLE and at follow‐up, and discuss the specific causes of these manifestations. Methods Medical records of 201 patients with childhood‐onset SLE followed up in French paediatric nephrological, haematological and rheumatological centres were reviewed and abstracted for gastrointestinal manifestations. Results Gastrointestinal involvement was recorded in 39 (19%) children. The median (range) age at the time of initial gastrointestinal manifestations was 11.3 (4.5–16) years. Gastrointestinal symptoms were present at or occurred within 1 month after diagnosis in 32% patients. Abdominal pain was the most frequent symptom, present in 34 (87%) patients. It was mostly related to lupus involvement, especially ascites (n = 14) and pancreatitis (n = 12), more rarely to treatment‐induced events (n = 1) or infection (n = 1) and never to events unrelated to SLE. Three children with surgical abdomen underwent a laparotomy before SLE was diagnosed, with a final diagnosis of lupus peritonitis and lupus acalculous cholecystitis. C reactive protein values were <40 mg/l in all but two patients who had surgical abdomen. Abdominal ultrasonography and computed tomography scans were abnormal in 58% and 83% of the evaluated patients, respectively. Corticosteroids, associated with intravenous cyclophospamide in eight patients, led to complete remission of gastrointestinal involvement in 30 of 31 treated patients. Conclusion Gastrointestinal involvement is common in children with SLE, and is mainly due to primary lupus involvement. Corticoidsteroid treatment should be promptly considered in children with lupus presenting with abdominal pain after infectious disease; side effects of treatment and intestinal perforation have been excluded. PMID:16818463
Lu, Chun-Chi; Chen, Chen-Hung; Yeh, Song-Feng; Lai, Jenn-Haung; Chang, Deh-Ming
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can lead to damage to several vital organs. Antiphospholipid syndrome (APS), manifesting as vascular thromboembolic events and morbidities of pregnancy in the presence of antiphospholipid antibodies (aPL), has been described in patients with SLE. Catastrophic antiphospholipid syndrome (CAPS), in contradistinction to APS, is defined as three or more organs affected by thrombotic microangiopathy in patients demonstrating aPL and can result in mortality up to 50%. We describe a unique SLE patient who was diagnosed with recurrent APS presented with axillary venous thrombosis and subsequent superficial edema and compartment syndrome. The CAPS followed and revealed thromboses over liver, spleen, and acute pancreatitis. The spontaneous hemorrhage of left fourth intercostal artery (ICA) and left axillary artery occured at the same time without vasculitis or severe trauma. Though emergency transcatheter arterial embolization (TAE) of the left fourth ICA was successfully accomplished by the radiologist. The repeated computed tomography angiogram of chest demonstrated remission of ruptured ICA. Nevertheless, the patient died of diffuse alveolar hemorrhage and respiratory failure and shock. Both disseminated intravascular coagulation (DIC) and CAPS share similar characteristics encompassing thrombotic microangiopathy, bleeding, thromboembolism, and multiple organ dysfunction. It is difficult to distinguish between them, especially in cases such as our uremic SLE patient with a calamitous disease progression. The emphasis of treatment for DIC is on platelet and fresh plasma transfusion, in contrast with anti-coagulant for CAPS. To the best of our knowledge, this is the first report describing ICA hemorrhage in an SLE patient without vasculitis or aneurysm. The lupus flare initiated a pathological immunological cascade and resulted in the CAPS and the vascular damage.
Andreoli, Laura; Fredi, Micaela; Nalli, Cecilia; Reggia, Rossella; Lojacono, Andrea; Motta, Mario; Tincani, Angela
Multidisciplinary approach and patient counselling have been the key points in the improvement of the management of pregnancy in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Most of these women can have successful pregnancy when thoroughly informed and instructed on several different issues. Disease activity should be in stable remission prior to pregnancy in order to reduce the chance for flare during pregnancy. To this purpose, medications must be modulated: "safe" drugs should be continued throughout pregnancy, embryotoxic/foetotoxic drugs should be withdrawn timely, and beneficial drugs such as low dose aspirin and heparin should be added for prophylaxis of maternal and foetal outcome, especially in the presence of antiphospholipid antibodies. The safety profile of anti-rheumatic drugs during pregnancy and breastfeeding should be kept constantly updated, as new data from inadvertent exposure accumulates and new drugs (especially biological agents) are available. Patients may carry autoantibodies that can negatively affect the baby, being neonatal lupus the prototypical case of passively acquired autoimmunity. Research has been greatly active in this field and more information on risk stratification and management are now available for counselling. The effect of both autoantibodies and drug exposure has been evaluated in the offspring: some concerns about learning disabilities have been raised, but these are treatable conditions that are likely to be overcome. To counsel a woman with SLE/APS during childbearing age means also to deal with contraception. Despite the "preferred choice" - combined oral contraceptive - may not be suitable for most of the patients, other options are available and should be offered and discussed with the patient. Fertility is not generally affected in SLE/APS patients, but those cases who require assisted reproduction techniques should be carefully evaluated and managed.
Kuhn, Annegret; Landmann, Aysche
Lupus erythematosus (LE) is an inflammatory connective tissue disease of generalized autoimmunity characterized by pathogenic autoantibodies and immune complexes, attributed to loss of immune tolerance. Cutaneous involvement, which appears in the majority of patients with the disease, can present as LE-specific or LE-nonspecific manifestations. The LE-nonspecific manifestations include e.g. vascular skin changes and may be associated with systemic organ manifestations or other autoimmune diseases. In contrast, the LE-specific manifestations encompass the various subtypes of cutaneous lupus erythematosus (CLE), which are classified as separate entities without or with less severe systemic organ involvement. In the "Duesseldorf Classification", CLE is subdivided into four different categories: acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). Differentiation between these subtypes is based on clinical features and average duration of the cutaneous lesions, but can also consider histological changes of skin biopsy specimens and laboratory abnormalities. In addition, direct immunofluorescence and photoprovocation may be applied to confirm the diagnosis in specific cases. Further investigations should be considered dependent on the clinical symptoms of the CLE patient and the results of the laboratory tests. A revised scoring system, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) has recently been validated to assess disease activity and damage in CLE. In this review, we focus on the classification of CLE and the diagnostic procedures to identify and confirm the different subtypes of the disease.
Kuhn, A; Landmann, A; Wenzel, J
Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE.
Merklen-Djafri, Carine; Bessis, Didier; Frances, Camille; Poulalhon, Nicolas; Debarbieux, Sébastien; Cordel, Nadège; Lipsker, Dan
Abstract The nosology of bullous lesions or equivalents (vesicles, erosions, and crusts) in patients with lupus erythematosus (LE) is rarely addressed. The primary aim of this study was to draw up a precise phenotypic inventory of such skin lesions; the secondary objective was to assess a potential relationship between the different types of loss of epidermis and extracutaneous lupus manifestations. We conducted a retrospective multicenter study including 22 patients with definite LE and bullous lesions or equivalents. All biopsies were reviewed. Patients were recruited in the dermatology departments of 6 centers. Patients were included if they met the diagnosis of systemic LE according to American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics criteria or diagnosis of cutaneous LE based on classic clinical criteria and/or histological ascertainment of LE. Patients were recruited through clinician's memory and photographic collections. Three clinico-pathological patterns could be individualized. First, toxic epidermal necrolysis (TEN)-like, sheet-like, skin detachment; sun-exposure, mild mucosal involvement, and dermal mucin deposition allow differential diagnosis with classical Lyell syndrome. Second, vesiculo-bullae and/or crusting occurring on typical lesions of subacute cutaneous lupus erythematosus or chronic cutaneous lupus erythematosus. Third, tense vesicles and/or blisters with an underlying neutrophilic dermatosis and a usual response to dapsone. A careful analysis of 22 LE patients with epidermal detachment reveals 2 main pathomechanisms: a classic LE interface dermatitis, which can be hyperacute and lead to TEN-like skin detachment; and a neutrophilic dermatosis, with tense vesicles and/or blisters, including classic bullous LE. PMID:26579826
Wan, S A; Teh, C L; Jobli, A T
Objective The aim of this study was to examine the clinical features, treatment and outcome of systemic lupus erythematosus (SLE) patients in our centre who presented with lupus pneumonitis as the initial manifestation. Methods We performed a retrospective review of all patients who presented with lupus pneumonitis during the initial SLE manifestation from March 2006 to March 2015. Results There were a total of five patients in our study who presented with fever and cough as the main clinical features. All patients had pulmonary infiltrates on chest radiographs. High-resolution computed tomography, which was performed in two patients, showed ground glass opacities with patchy consolidations bilaterally. All patients received high-dose steroids, 80% received intravenous cyclophosphamide and 60% received intravenous immunoglobulin. Two patients died from severe lupus pneumonitis within 2 weeks of admission despite treatment with ventilation, steroids, cyclophosphamide and intravenous immunoglobulin. Conclusions Acute lupus pneumonitis is an uncommon presentation of SLE. Mortality in this case series is 40%.
Blay, Gabriela; Ferriani, Mariana P L; Buscatti, Izabel M; França, Camila M P; Campos, Lucia M A; Silva, Clovis A
Pyomyositis is a pyogenic infection of skeletal muscle that arises from hematogenous spread and usually presents with localized abscess. This muscle infection has been rarely reported in adult-onset systemic lupus erythematous and, to the best of our knowledge, has not been diagnosed in pediatric lupus population. Among our childhood-onset systemic lupus erythematous population, including 289 patients, one presented pyomyositis. This patient was diagnosed with childhood-onset systemic lupus erythematous at the age of 10 years-old. After six years, while being treated with prednisone, azathioprine and hydroxychloroquine, she was hospitalized due to a 30-day history of insidious pain in the left thigh and no apparent trauma or fever were reported. Her physical examination showed muscle tenderness and woody induration. Laboratory tests revealed anemia, increased acute phase reactants and normal muscle enzymes. Computer tomography of the left thigh showed collection on the middle third of the vastus intermedius, suggesting purulent stage of pyomyositis. Treatment with broad-spectrum antibiotic was initiated, leading to a complete clinical resolution. In conclusion, we described the first case of pyomyositis during childhood in pediatric lupus population. This report reinforces that the presence of localized muscle pain in immunocompromised patients, even without elevation of muscle enzymes, should raise the suspicion of pyomyositis. A prompt antibiotic therapy is strongly recommended.
Cojocaru, Doina-Clementina; Costin, Melania; Bădeanu, Lucia Elena; Negru, R D; Aursulesei, Viviana
Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disorder that occurs primarily in women of childbearing age, immunologic abnormalities being a prominent feature of the disease. Psychiatric disorders frequently coexist, depression being the most common mood disorder in neuropsychiatric lupus. This literature review was performed through searching MEDLINE database for full-text English-language articles--original research, systematic review and updates published in the last five years (2010-2015), using the keywords "depression and systemic lupus erythematosus". The main outcomes identified were prevalence and predictors of depression in various cultural and ethnic groups, depression-related clinical issues (suicidal ideation, cognitive impairment, altered body image, sleep and sexual disturbances, influence of SLE treatment), and influence on quality of life. A multidisciplinary approach that takes into account the polymorphism and individual variability of the SLE clinical manifestations helps to improve early detection of depression, which is responsible for the increased risk of comorbidities, suicidal attempts, decreased treatment adherence, and impaired quality of life. Physicians across all specialties involved in the care for lupus patients should be aware of the major prevalence of this condition, while helping patients to cope with their disabling disease.
Lee-Kirsch, Min Ae; Gong, Maolian; Schulz, Herbert; Rüschendorf, Franz; Stein, Annette; Pfeiffer, Christiane; Ballarini, Annalisa; Gahr, Manfred; Hubner, Norbert; Linné, Maja
Systemic lupus erythematosus is a prototypic autoimmune disease. Apart from rare monogenic deficiencies of complement factors, where lupuslike disease may occur in association with other autoimmune diseases or high susceptibility to bacterial infections, its etiology is multifactorial in nature. Cutaneous findings are a hallmark of the disease and manifest either alone or in association with internal-organ disease. We describe a novel genodermatosis characterized by painful bluish-red inflammatory papular or nodular lesions in acral locations such as fingers, toes, nose, cheeks, and ears. The lesions sometimes appear plaquelike and tend to ulcerate. Manifestation usually begins in early childhood and is precipitated by cold and wet exposure. Apart from arthralgias, there is no evidence for internal-organ disease or an increased susceptibility to infection. Histological findings include a deep inflammatory infiltrate with perivascular distribution and granular deposits of immunoglobulins and complement along the basement membrane. Some affected individuals show antinuclear antibodies or immune complex formation, whereas cryoglobulins or cold agglutinins are absent. Thus, the findings are consistent with chilblain lupus, a rare form of cutaneous lupus erythematosus. Investigation of a large German kindred with 18 affected members suggests a highly penetrant trait with autosomal dominant inheritance. By single-nucleotide-polymorphism–based genomewide linkage analysis, the locus was mapped to chromosome 3p. Haplotype analysis defined the locus to a 13.8-cM interval with a LOD score of 5.04. This is the first description of a monogenic form of cutaneous lupus erythematosus. Identification of the gene responsible for familial chilblain lupus may shed light on the pathogenesis of common forms of connective-tissue disease such as systemic lupus erythematosus. PMID:16960810
Lee, D H; Lee, S C; Kim, M
Acute macular neuroretinopathy (AMN) is a rare disorder that presents with abrupt visual change with wedge-shaped or flower-like lesions pointing towards the fovea. Ischemic insults to the retinal capillary plexus may be important for development of this disease. While many case reports have been published on AMN, none have described AMN in association with systemic lupus erythematosus (SLE). Here, we report a case of AMN associated with newly-diagnosed SLE. We speculate that in patients with lupus flares, immune complex-mediated vascular injury and microvascular thrombosis may disrupt the deep retinal capillary network, causing ischemic damages to the outer retina and leading to the development of AMN. AMN can develop in patients with lupus flares, and must be considered as an SLE-associated ophthalmologic complication. To the best of our knowledge, this is the first case report of AMN associated with SLE.
Braunstein, E.M.; Weissman, B.N.; Sosman, J.L.; Schur, P.H.
Systemic lupus erythematosus in the elderly has a different clinical and serologic course from that in young patients. Radiographic findings in patients in whom the diagnosis was made after age 50 were compared with findings in younger patients to see if the radiologic patterns are also different. The only significant radiographic difference between the two groups was that the older group had a greater incidence of soft-tissue swelling of the hands and wrists (p < 0.001). There was no significant difference in osteopenia, erosion, soft-tissue calcification, alignment abnormalities, or intrathoracic findings. Of 24 patients over age 50, two developed lymphoma and another developed multiple myeloma. The data agree with clinical observations that there is a higher incidence of arthritis in late-onset lupus, but clinical findings of increased incidence of pleuropericardial disease are not confirmed radiographically. The coincidence of hematologic malignancy with late-onset lupus in this series is noteworthy.
Kurosawa, Rumiko; Miyamae, Takako; Imagawa, Tomoyuki; Katakura, Shigeki; Mori, Masaaki; Aihara, Yuhkoh; Yokota, Shumpei
The patient was a 13-year-old girl. In August 2000, she presented with a fever, together with diarrhea, vomiting, arthralgia, nasal bleeding and malaise, and was examined by another physician. Because her platelet count was low, and there were positive reactions for anti-nuclear antibodies, anti-DNA antibodies and platelet-associated IgG, idiopathic thrombopenic purpura, and systemic lupus erythematosus (SLE) was suspected. From January 2001, when she caught measles, she reported abdominal pain, and urinalysis indicated urinary protein and occult blood, and the left kidney was found hydronephrotic. At the same time left ureter stenosis and dilatation were demonstrated. Symptoms were disappeared by hydration and treatment with NSAIDs, but 2 months later fever and erythematous patches seen on both cheeks led to the proper diagnosis of SLE, and she was admitted to our hospital. Intravenous pyelography revealed hydronephrosis on left kidney, constriction and dilatation of the left ureter, and intracystic endoscopy showed erythema at the orifice of the left ureter. The pathological examination indicated the presence of vasculitis, and finally lupus cystitis was diagnosed. Intravenous cyclophosphamide (IVCY)-pulse therapy was introduced to a total of 8 times over the period of a year, and maintenance therapy with predonisolone and azathioprin was also used. After completion of the IVCY-pulse therapy, the hydronephrosis and constriction of the ureter were disappeared. No side effects of IVCY-pulses were observed, and the patient is now in remission. We reported a case of childhood SLE complicated with lupus cystitis and successfully treated by IVCY-pulse therapy and maintenance predonisolone and azathioprin.
Macêdo, Danielle Patrícia Cerqueira; Neves, Rejane Pereira; Lopes, Flávia Cadengue
Mycosis is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus and frequent exposition to an infectious source could enhance the development of dermatophytic infections. A case of disseminated dermatophytosis by Microsporum gypseum is reported in a systemic lupus erythematosus (SLE) patient. PMID:24031171
Elçioglu, N; Hall, C M
Two sibs with chondrodysplasia punctata in whom the mother was suffering from systemic lupus erythematosus are presented and the radiological features described. Comparison with other forms of chondrodysplasia punctata with a review of the relevant publications is presented and the possible association with maternal systemic lupus erythematosus is highlighted. Images PMID:9719382
Shulman, S; Shorer, R; Wollman, J; Dotan, G; Paran, D
Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy
Vinet, É; Pineau, C A; Clarke, A E; Fombonne, É; Platt, R W; Bernatsky, S
Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring.
Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C; Freedman, Barry I; Kaufman, Kenneth M; Kelly, Jennifer A; Niewold, Timothy B; Kamen, Diane L; Gilkeson, Gary S; Ziegler, Julie T; Langefeld, Carl D; Alarcón, Graciela S; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Brown, Elizabeth E; Kimberly, Robert P; Reveille, John D; Vilá, Luis M; Merrill, Joan T; Anaya, Juan-Manuel; James, Judith A; Pons-Estel, Bernardo A; Martin, Javier; Park, So-Yeon; Bang, So-Young; Bae, Sang-Cheol; Moser, Kathy L; Vyse, Timothy J; Criswell, Lindsey A; Gaffney, Patrick M; Tsao, Betty P; Jacob, Chaim O; Harley, John B; Alarcón-Riquelme, Marta E; Sawalha, Amr H
Objective Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods 4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0×10−6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of <0.05 and pass the significance threshold using Bonferroni correction for multiple testing. Conclusion Significant associations were found between lupus clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future. PMID:21719445
Contin, Letícia Arsie; Martins da Costa Marques, Elisa Raquel; Noriega, Leandro
Lupus erythematosus, especially the discoid form, and lichen planopilaris may be associated and can occur in different topographies (coexistence) or in the same lesion (lupus eythematosus/lichen planus overlap syndrome). Frontal fibrosing alopecia is considered a variant form of lichen planopilaris and is characterized by frontotemporal hairline and eyebrow involvement. Of the association with lupus erythematosus we have only a few descriptions. Hydroxychloroquine and chloroquine diphosphate are antimalarial drugs described as viable treatment options for both diseases, due to an antilymphocytic effect. The association between frontal fibrosing alopecia and lupus erythematosus (discoid or systemic) is reported in this article, showing a progressive alopecia in the frontotemporal hairline despite treatment with hydroxychloroquine.
Jara, Luis J; Medina, Gabriela; Saavedra, Miguel A; Vera-Lastra, Olga; Torres-Aguilar, Honorio; Navarro, Carmen; Vazquez Del Mercado, Monica; Espinoza, Luis R
Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.
Mohammed, Abdel GaffarA; Alghamdi, Abdulaziz A; ALjahlan, Mohammad A; Al-Homood, Ibrahim A
The aim of this study is to use transthoracic echocardiographic (TTE) imaging methods to identify cardiac dysfunction in asymptomatic systemic lupus erythematosus (SLE) patients and to determine the association between echocardiographic findings and serology. This is a prospective cross-sectional study where 50 patients with confirmed diagnoses of SLE were recruited from rheumatology outpatient clinics. Clinical and serological evaluation to confirm the diagnosis of lupus was done in all patients. Fifty SLE patients, 46 (92%) females and 4 (8%) males, were recruited. Anti-double-stranded DNA (Anti-dsDNA), anticardiolipin, lupus anticoagulant, and anti-β2-glycoproteins were positive in 52.1, 32.6, 13.3, and 15.6%, respectively. Transthoracic echocardiogram revealed mitral regurgitation in 16 patients (32%), pericardial effusion in16 patients (32%), aortic regurgitation in five patients (10%), and tricuspid regurgitation in 10 patients (20%). Eleven patients had left ventricular hypertrophy (22%), and eight patients had ventricular systolic dysfunction (16%). Only four patients had ventricular diastolic dysfunction (8%). A significant association between mitral and tricuspid valve regurgitation and positive anti-dsDNA (p < 0.018, p < 0.006, respectively) was found. Positive anticardiolipin antibodies, lupus anticoagulant, and anti-β 2 glycoprotein antibodies were also associated with mitral valve regurgitation (p values 0.044, 0.006, and 0.023), respectively. Active disease assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was found to be associated with increased risk of mitral valvular leaflet thickening (p value 0.028). Performing regular transthoracic echocardiogram in asymptomatic SLE patients is important for early detection and appropriate treatment of cardiac lesions. Clinically quiescent but serologically active disease and presence of antiphospholipid antibodies were associated with structural heart abnormalities.
Pastor Tomás, E; Guillén Antón, J; Vaquerizo Gareta, A; Lirola Grajales, P; Martínez García, R; Cuartero Lobera, J
A 28-year-old woman with systemic lupus erythematosus and a history of aseptic meningitis, digestive bleeding due to thrombopenia and deep venous thrombosis underwent elective cesarean for transverse presentation at 35 weeks. Preoperative blood work-up showed an antinuclear antibody titre that was slightly positive and steroid treatment was started. Surgery operation was performed with general anesthesia. The outcome was satisfactory even though serious complications can develop during the management of anesthesia in such patients. Systemic lupus erythematosus is a chronic, multisystemic disease that mainly affects women of childbearing age. Antibodies and immunocomplexes play a fundamental role. Given the multiorgan involvement in this disease, preoperative study of the lupus patient should assess all such involvement, including maternal-fetal risk, as well as consider the drug and anesthetic management to be applied. Among the clinical signs that can affect management of anesthesia are the following: aseptic meningitis, high blood pressure, pericarditis, pneumonitis and recurrent venous thrombosis. Anemia, thrombopenia and significantly altered coagulation events are common.
Krishnan, E; Hubert, H B
Objective To study ethnic differences in mortality from systemic lupus erythematosus (lupus) in two large, population‐based datasets. Methods We analysed the national death data (1979–98) from the National Center for Health Statistics (Hyattsville, Maryland, USA) and hospitalisation data (1993–2002) from the Nationwide Inpatient Sample (NIS), the largest hospitalisation database in the US. Results The overall, unadjusted, lupus mortality in the National Center for Health Statistics data was 4.6 per million, whereas the proportion of in‐hospital mortality from the NIS was 2.9%. African‐Americans had disproportionately higher mortality risk than Caucasians (all‐cause mortality relative risk adjusted for age = 1.24 (women), 1.36 (men); lupus mortality relative risk = 3.91 (women), 2.40 (men)). Excess risk was found among in‐hospital deaths (odds ratio adjusted for age = 1.4 (women), 1.3 (men)). Lupus death rates increased overall from 1979 to 98 (p<0.001). The proportional increase was greatest among African‐Americans. Among Caucasian men, death rates declined significantly (p<0.001), but rates did not change substantially for African‐American men. The African‐American:Caucasian mortality ratio rose with time among men, but there was little change among women. In analyses of the NIS data adjusted for age, the in‐hospital mortality risk decreased with time among Caucasian women (p<0.001). Conclusions African‐Americans with lupus have 2–3‐fold higher lupus mortality risk than Caucasians. The magnitude of the risk disparity is disproportionately higher than the disparity in all‐cause mortality. A lupus‐specific biological factor, as opposed to socioeconomic and access‐to‐care factors, may be responsible for this phenomenon. PMID:16627544
Tselios, Konstantinos; Yap, Kristy Su-Ying; Pakchotanon, Rattapol; Polachek, Ari; Su, Jiandong; Urowitz, Murray B; Gladman, Dafna D
The coexistence of psoriasis with systemic lupus erythematosus (SLE) has been reported in limited case series, raising hypotheses about shared pathogenetic mechanisms. Nevertheless, important differences regarding treatment do exist. The aim of the present study was to determine the prevalence and characteristics of psoriasis in a defined cohort of lupus patients. Patients with psoriasis were retrieved from the University of Toronto Lupus Clinic from its inception in 1970 up to 2015. Charts were hand-searched to collect information concerning demographic, clinical, and therapeutic variables. Patients were matched with non-psoriasis lupus patients to identify the impact of supervening psoriasis on lupus activity, damage accrual, and venous thromboembolic (VTEs) and cardiovascular events (CVEs). Psoriasis was diagnosed in 63 patients (49 females, 14 males) for a prevalence of 3.46% (63/1823). The male-to-female ratio was significantly higher in non-psoriasis patients (0.286 vs. 0.138, p = 0.017). Plaque psoriasis was the most prominent type (55/63, 87.3%) whereas three patients had pustular disease; one had psoriatic arthritis. Nine patients (14.3%) were administered systemic treatment with methotrexate (n = 5), azathioprine (n = 1), ustekinumab (n = 3), and etanercept (n = 1). Psoriasis was definitely deteriorated by hydroxychloroquine in one patient. There was no significant impact of psoriasis on disease activity, damage accrual, VTEs, and CVEs. The prevalence of psoriasis was twice as high as that of the general Canadian population in this lupus cohort. Plaque psoriasis was the most prominent subtype, and topical treatment was adequate in the majority of patients. Supervening psoriasis had no significant impact on lupus activity and damage accrual.
Lamichhane, D; Weinstein, A
Complement activation is a key feature of systemic lupus erythematosus (SLE). Detection of cell-bound complement activation products (CB-CAPS) occurs more frequently than serum hypocomplementemia in definite lupus. We describe a patient with normocomplementemic probable SLE who did not fulfill ACR classification criteria for lupus, but the diagnosis was supported by the presence of CB-CAPS.
Koh, J H; Lee, J; Jung, S M; Ju, J H; Park, S-H; Kim, H-Y; Kwok, S-K
This study was performed to investigate the clinical characteristics of lupus cystitis and determine the risk factors and clinical outcomes of lupus cystitis in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed 1064 patients at Seoul St. Mary's Hospital in Seoul, Korea, from 1998 to 2013. Twenty-four patients had lupus cystitis. Lupus cystitis was defined as unexplained ureteritis and/or cystitis as detected by imaging studies, cystoscopy, or bladder histopathology without urinary microorganisms or stones. Three-fourths of patients with lupus cystitis had concurrent lupus mesenteric vasculitis (LMV). The initial symptoms were gastrointestinal in nature for most patients (79.2%). High-dose methylprednisolone was initially administered to most patients (91.7%) with lupus cystitis. Two patients (8.3%) died of urinary tract infections. Sixty-five age- and sex-matched patients with SLE who were admitted with other manifestations were included as the control group. Patients with lupus cystitis showed a lower C3 level (p = 0.031), higher SLE Disease Activity Index score (p = 0.006), and higher ESR (p = 0.05) upon admission; more frequently had a history of LMV prior to admission (p < 0.001); and less frequently had a history of neuropsychiatric lupus (p = 0.031) than did patients with SLE but without lupus cystitis. The occurrence of lupus cystitis was associated with a history of LMV (OR, 21.794; 95% CI, 4.061-116.963). The median follow-up period was 3.4 years, and the cumulative one-year mortality rate was 20%. Complications developed in 33.3% of patients with lupus cystitis and were related to survival (log-rank p = 0.021). Our results suggest that the possibility of lupus cystitis should be considered when a patient with SLE and history of LMV presents with gastrointestinal symptoms or lower urinary tract symptoms. Development of complications in patients with lupus cystitis can be fatal. Thus, intensive treatment
Aluoch, Aloice O; Farbman, Mathew; Gladue, Heather
We present a case of a 47 year-old African American female with 15 pack-years of tobacco use and heavy alcohol use who presented with arthritis and was found to have a positive antinuclear antibodies (ANA), anti double stranded DNA antibodies (anti-dsDNA), and anti-Sjogren’s syndrome-related antigen A and antigen B (anti-SSA and anti-SSB). She was subsequently found to have a lung adenocarcinoma associated with hypertrophic pulmonary osteoarthropathy (HPO). This demonstrates a case of positive antinuclear antibodies and arthritis in a patient with lung adenocarcinoma, which can be falsely diagnosed as systemic lupus erythematosus. PMID:26106457
Yeap, S S; Chow, S K; Manivasagar, M; Veerapen, K; Wang, F
A retrospective analysis of the case records of 494 systemic lupus erythematosus (SLE) patients under follow-up at University Hospital, Kuala Lumpur during 1976-1990 was performed. Overall mortality was 20.2% (100 patients). The causes of death were infection (30%), renal (15%), respiratory (14%), neurological (5%), cardiovascular (7%), other causes (2%) and unknown (27%). Active SLE was a contributing factor in 19% of the deaths. The patients who died had significantly more renal disease, neurological disease, serositis or thrombocytopenia by the end of the first year of disease compared to the survivors. As in other series, infection and active SLE remain important causes of death.
Esscher, E; Scott, J S
The association between infants with congenital heart block (CHB) and the presence or later development of maternal systemic lupus erythematosus or other connective-tissue disease (CTD) was reviewed in 67 cases. In 24 cases CHB was diagnosed at or before birth. Of nine necropsies on affected infants, seven showed endomyocardial fibrosis. The results suggest that one in three mothers who deliver babies with CHB have or will develop CTD. The association is probably explained by placental transfer of a maternal antibody. Awareness of the association may lead to prevention of the birth of children with CHB and better neonatal care of affected children. PMID:455010
Moraes-Fontes, Maria Francisca; Antunes, Ana Margarida; Gruner, Heidi; Riso, Nuno
In the wake of the Portuguese vaccination program 50th anniversary it seems appropriate to review vaccination in patients with systemic lupus erythematosus. Controversial issues as regards the association between autoimmune diseases, infections, and vaccines are discussed as well as vaccine safety and efficacy issues as regards chronic immunosuppressant (IS) drug therapy. After a brief overview of national policies, specific recommendations are made as regards vaccination for adult patients with SLE with a particular focus on current IS therapy and unmet needs. PMID:27069477
Li, Tao; Gao, Liang; Chen, Peng; Bu, Si-Yuan; Cao, De-Hong; Yang, Lu; Wei, Qiang
A 26-year-old woman, with a six-year history of well-controlled systemic lupus erythematosus (SLE), complained of urinary frequency and urgency. After failure of commonly-used antibiotic therapy, mycobacterium tuberculosis was cultured from her urine and renal tuberculosis (TB) was diagnosed. However, she underwent right nephrectomy after the combination therapies of prednisone for SLE and anti-tuberculosis treatment for renal TB failed. To our knowledge, SLE accompanying renal TB is rare, and such a rapid deterioration in renal function has never been reported. PMID:26221395
Webster, Philip; Nelson-Piercy, Catherine; Lightstone, Liz
We report a case of systemic lupus erythematosus (SLE) in a young woman who became pregnant amid a severe flare. She continued to have active disease in the face of aggressive treatments complicated by several side effects of immunosuppressive drugs including recurrent sepsis and gestational diabetes. Her fetus was at risk for congenital heart block during the second and third trimesters. Despite an extremely guarded prognosis, she delivered a healthy baby girl. This case highlights the complexities of SLE management during pregnancy. We discuss the therapeutic options available in pregnancy, and highlight the importance of cross-specialty multidisciplinary care in these women.
Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production and inflammatory cell infiltration in target organs, such as the kidneys and brain. T cells are critical players in SLE pathophysiology as they regulate B cell responses and also infiltrate target tissues, leading to tissue damage. Abnormal signaling events link to defective gene transcription and altered cytokine production, contributing to the aberrant phenotype of T cells in SLE. Study of signaling and gene transcription abnormalities in SLE T cells has led to the identification of novel targets for therapy. PMID:21457530
Fatovic-Ferencic, Stella; Holubar, Karl
In analyzing the history of a certain disease, not only must the particular disease be investigated, but related pathological conditions that exist in a population at a given time must also be addressed. Also, the prevalence of other diseases should be explored, which may have a bearing on the problem under discussion. The history of medicine can help in this respect, revealing the circumstances or the environment when certain diseases (dis)appeared. Terminology must also be explored, and is the point with which we will begin. With regard to lupus, this again is the case (Latin for wolf; lykos ___ in Greek). Taboo and fantasy border semantics because in the naming of the wolf, the image of "tearing apart" or "pulling or ripping off" (a destructive phenomenon) comes into play. Even the Sanskrit word allows such a relation (v_ik, varkate, v_íkah [symbols: see text]). As a consequence, processes of various origin but characterized by ulceration or necrosis (neoplastic, infectious, traumatic, etc), were labeled lupus before the mid-19th century, and no specific pathogenesis was implied. This resulted in considerable confusion, as the books of Willan, Alibert, Cazenave, Schedeland, Hebra, and others prove. We see no purpose in delving further into the history of ulcerative lesions and what was understood early on to be their presumed cause, eg, back to Paracelsus and to the Old Testament ("shekhin" [see text] Hebrew, meaning "ulcer"); or, "cancer," another such descriptive term relating to destruction, taken from the Greek).
Maddison, P J
Nowhere across the spectrum of rheumatic and dermatological disease is the interaction of nature and nurture more relevant than in the connective tissue diseases such as SLE. While genetic and environmental factors are clearly involved in both the triggering of the disease and its expression, the interaction is complex with different combinations of factors contributing in different patients. For example, while genetic factors contribute substantially to susceptibility to lupus, this does not follow a simple Mendelian pattern of inheritance and mathematical models suggest that there may be varying contribution from at least four genes with differing inheritances. A variety of candidate genes and environmental factors have been highlighted in SLE but to dissect out the complexity of how these might interact requires the study of patient groups with a better defined clinical and serological phenotype. For example, studies of patients with subacute cutaneous lupus (SCLE) have shown associations with various genes in the MHC region (including HLA, complement and TNF) and suggest that the biological effect of inheriting an extended MHC region may be greater than its individual parts. One can now speculate on how interaction with an environmental factor such as UV light explains pathogenesis.
Rampudda, M; Marson, P; Pasero, G
Systemic lupus erythematosus can be considered the most characteristic and important among the connective tissue diseases. In this short review the main stages of its history are sketched, from the introduction of the term "lupus", traditionally attributed to Roger Frugardi, in 1230 (but in fact already documented in the 10th century) to the actual knowledge of its clinical and laboratory aspects. Initially considered exclusively of dermatological interest, the first to describe a systemic form with visceral involvement were Moriz Kohn Kaposi and William Osler. Significant contribution was also given by serological diagnosis, and in particular, by the identification of specific markers of disease, such as anti-native DNA and anti-Sm antibodies, allowing early diagnosis and the establishment of an adequate therapy.
Jawaid, Ambreen; Almas, Aysha
Systemic Lupus Erythematosus (SLE) is one of the many diseases known as 'the great imitators' because it can have diverse presentations and so is misunderstood for other illnesses. This case illustrates a 19 years old girl with SLE who presented as cardiac tamponade which is a rare feature of lupus pericarditis requiring medical and surgical treatment. Even after pericardiocentesis and steroid therapy there was a re-accumulation of the pericardial fluid resulting in cardiac tamponade which led to pericardial window formation. This case draws attention to the need to consider the diagnosis of tamponade in patients with connective tissue disease and dyspnea or hemodynamic compromise. It also outlines the treatment options available so that surgical referral, if needed, can be done timely for this rare but life threatening manifestation of SLE.
Murdaca, Giuseppe; Orsi, Andrea; Spanò, Francesca; Faccio, Valeria; Puppo, Francesco; Durando, Paolo; Icardi, Giancarlo; Ansaldi, Filippo
Systemic Lupus Erythematosus (SLE) is characterized by abnormal autoantibody production and clearance. Infections are among the most important causes of morbidity and mortality in SLE patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. In addition, infectious agents can switch on lupus disease expression and activity. Among the strategies to reduce the risk of infection, vaccination can be considered the most reliable option. Most vaccines are effective and safe in SLE patients, although in certain cases immunogenicity may be sub-optimal and vaccination can trigger a flare. Although these issues are currently unresolved, the risk benefit balance is in favor for vaccination to reduce the risk of infection in SLE patients. In the present review we discuss the preventive strategies currently recommended to reduce bacterial and viral infections in SLE. PMID:26750996
Alarcón-Segovia, D.; Fishbein, Eugenia; Díaz-Jouanen, E.
Presence of hepatitis-associated antigen (HAA) was investigated in 504 sera from 116 patients with SLE and was found in 41% of them. HAA was present in at least one serum in 75% of the patients but there were variations in presence and titres in the same patient at different times. Except for a tendency of HAA to appear or rise in titre with lupusi nactivation following corticosteroid or immunosuppresive therapy, there was no correlation between its presence and disease activity, specific organ involvement, antinuclear antibodies or immunoglobulin levels. All but one of twelve lupus patients with recurrent bacterial infections had HAA at high titres. HAA appeared in the serum of a patient upon development of IgA deficiency. HAA antigenaemia in systemic lupus erythematosus seems a consequence rather than a cause of the immunological derangement in this disease. PMID:4538860
Dalili, Amir Reza; Lotfi, Reza; Mousavi, Seyedeh Maryam
Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown pathogenesis. The frequency of SLE with cavitary lesion manifestation is very rare and is thought to be due to infection or pulmonary embolism. A 19-year-old female diagnosed with SLE complicated by lupus nephritis and cavitary pulmonary lesion is presented in this case report. Other diseases that can lead to such lesions were ruled out in the patient. The patient improved briefly after the initiation of immunosuppressive therapy, but was unresponsive to supportive treatment due to pneumothorax. Pneumothorax is caused by cavitary lesions and possibly bronchopleural fistulas - these later caused respiratory distress and death. The patient did not show any improvement in the lesions after the initiation of immunosuppressive therapy. This case report suggests that the differential diagnosis of cavitary lung lesions should include SLE.
Dalili, Amir Reza; Lotfi, Reza; Mousavi, Seyedeh Maryam
Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown pathogenesis. The frequency of SLE with cavitary lesion manifestation is very rare and is thought to be due to infection or pulmonary embolism. A 19-year-old female diagnosed with SLE complicated by lupus nephritis and cavitary pulmonary lesion is presented in this case report. Other diseases that can lead to such lesions were ruled out in the patient. The patient improved briefly after the initiation of immunosuppressive therapy, but was unresponsive to supportive treatment due to pneumothorax. Pneumothorax is caused by cavitary lesions and possibly bronchopleural fistulas – these later caused respiratory distress and death. The patient did not show any improvement in the lesions after the initiation of immunosuppressive therapy. This case report suggests that the differential diagnosis of cavitary lung lesions should include SLE. PMID:25763160
Sharmeen, Saika; Hussain, Nazia
Hemophagocytic syndrome (HS) or hemophagocytic lymphohistiocytosis (HLH) is an immune mediated phenomenon that can occur in the setting of an autoimmune disease, chronic immunosuppression, malignancy, or infection. It has been more commonly described in the pediatric population and less commonly in adults. We describe a case of a 52-year-old male who presented with a rash. He simultaneously met the Systemic Lupus International Collaborating Clinics (SLICC) criteria for the diagnosis of systemic lupus erythematosus (SLE) and the diagnostic criteria of HS as described in the hemophagocytic lymphohistiocytosis (HLH) 2004 trial. The bone marrow on autopsy showed the presence of abundant hemosiderophages with focal hemophagocytosis. SLE-associated HS might be underdiagnosed due to the overlap in clinical findings. This case represents the importance of prompt diagnosis and treatment of such a potentially fatal clinical syndrome. PMID:26981305
Liu, Yaoyang; La Cava, Antonio
Systemic lupus erythematosus (SLE) is a chronic disabling autoimmune disease that significantly impacts the quality of life of patients, and can associate with several complications including end-stage renal disease and shortened lifespan. A central component in the pathogenesis of SLE is the B-cell production of autoantibodies to multiple self-antigens. Since, B lymphocyte stimulator (BLyS) plays a key role in the selection, differentiation and survival of most B cells, it has been studied as a therapeutic target in SLE. After a gap of more than fifty years without new drugs being approved for this disease, the human neutralizing anti-BLyS monoclonal antibody belimumab has recently been approved by the FDA for SLE therapy. This review provides an overview on the targeting of BLyS in lupus animal models, the use of belimumab in human SLE, and relevant patents.
Pellefigues, Christophe; Charles, Nicolas
Systemic lupus erythematosus is a complex autoimmune disease of multifactorial origins. All compartments of the immune system appear to be affected, at least in some way, and to contribute to disease pathogenesis. Due to an escape from negative selection autoreactive T and B cells accumulate in SLE patients leading to the production of autoantibodies mainly raised against nuclear components and their subsequent deposition into target organs. We recently showed that basophils, in an IgE and IL-4 dependent manner, contribute to SLE pathogenesis by amplifying autoantibody production. Here, we summarize what we have learned about the deleterious role of basophils in lupus both in a mouse model and in SLE patients. We discuss which possible pathways could be involved in basophil activation and recruitment to secondary lymphoid organs during SLE, and how basophils may amplify autoantibody production. PMID:24209595
Aringer, M; Leuchten, N; Fischer-Betz, R
Similar to patients with other rheumatic diseases, patients with systemic lupus erythematosus (SLE) nowadays can also have the desire to terminate immunosuppressive and immunomodulatory medications. In order to provide appropriate advice to patients, the two main issues are the risk of severe adverse events under long-term therapy with any drug and the perceived risk of a flare, in particular of severe flares. The risks of long-term therapy vary greatly between drugs, ranging from severe unacceptable risks with cyclophosphamide and higher dose glucocorticoids to low risks usually outweighed by long-term benefits with hydroxychloroquine. The individual risk of flares is often difficult to estimate but clinical remission and at least 3 years of immunosuppression are recommended for lupus nephritis. The duration of remission can also be shorter in cases of milder forms of disease. This review article tries to put the available evidence into a clinical perspective and to derive concrete recommendations.
Chalayer, Émilie; Ffrench, Martine; Cathébras, Pascal
Peripheral cytopenias are common in systemic lupus erythematosus, but bone marrow involvement is rarely reported. Aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and characterized by an empty bone marrow. This rare but serious disease has been described as an unusual manifestation of systemic lupus erythematosus. We reviewed the 25 cases published in the English language literature and discuss the clinical presentation, outcome, treatment, and pathophysiology of aplastic anemia as a complication of systemic lupus erythematosus. We report here the first case of aplastic anemia associated with systemic lupus erythematosus treated with an allogeneic hematopoietic stem cell transplant. Over one half of patients received concomitantly the diagnoses of systemic lupus erythematosus and aplastic anemia. No clinical or histological features can distinguish primary aplastic anemia from aplastic anemia occurring in systemic lupus erythematosus patients. The overall mortality is about 15% and corticosteroid-based therapy alone or in combination with other immunomodulatory drugs can restore bone marrow function. Systemic lupus erythematosus may be complicated by bone marrow involvement. The diagnosis of peripheral cytopenias should be confirmed by bone marrow aspiration. All these patients should receive cortisone as a first treatment. Plasma exchanges seem to have some efficacy. Other different immunomodulatory therapies were used with variable results.
Knight, Caroline L; Nelson-Piercy, Catherine
Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease predominantly affecting women, particularly those of childbearing age. SLE provides challenges in the prepregnancy, antenatal, intrapartum, and postpartum periods for these women, and for the medical, obstetric, and midwifery teams who provide their care. As with many medical conditions in pregnancy, the best maternal and fetal–neonatal outcomes are obtained with a planned pregnancy and a cohesive multidisciplinary approach. Effective prepregnancy risk assessment and counseling includes exploration of factors for poor pregnancy outcome, discussion of risks, and appropriate planning for pregnancy, with consideration of discussion of relative contraindications to pregnancy. In pregnancy, early referral for hospital-coordinated care, involvement of obstetricians and rheumatologists (and other specialists as required), an individual management plan, regular reviews, and early recognition of flares and complications are all important. Women are at risk of lupus flares, worsening renal impairment, onset of or worsening hypertension, preeclampsia, and/or venous thromboembolism, and miscarriage, intrauterine growth restriction, preterm delivery, and/or neonatal lupus syndrome (congenital heart block or neonatal lupus erythematosus). A cesarean section may be required in certain obstetric contexts (such as urgent preterm delivery for maternal and/or fetal well-being), but vaginal birth should be the aim for the majority of women. Postnatally, an ongoing individual management plan remains important, with neonatal management where necessary and rheumatology followup. This article explores the challenges at each stage of pregnancy, discusses the effect of SLE on pregnancy and vice versa, and reviews antirheumatic medications with the latest guidance about their use and safety in pregnancy. Such information is required to effectively and safely manage each stage of pregnancy in women with SLE
Knight, Caroline L; Nelson-Piercy, Catherine
Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease predominantly affecting women, particularly those of childbearing age. SLE provides challenges in the prepregnancy, antenatal, intrapartum, and postpartum periods for these women, and for the medical, obstetric, and midwifery teams who provide their care. As with many medical conditions in pregnancy, the best maternal and fetal-neonatal outcomes are obtained with a planned pregnancy and a cohesive multidisciplinary approach. Effective prepregnancy risk assessment and counseling includes exploration of factors for poor pregnancy outcome, discussion of risks, and appropriate planning for pregnancy, with consideration of discussion of relative contraindications to pregnancy. In pregnancy, early referral for hospital-coordinated care, involvement of obstetricians and rheumatologists (and other specialists as required), an individual management plan, regular reviews, and early recognition of flares and complications are all important. Women are at risk of lupus flares, worsening renal impairment, onset of or worsening hypertension, preeclampsia, and/or venous thromboembolism, and miscarriage, intrauterine growth restriction, preterm delivery, and/or neonatal lupus syndrome (congenital heart block or neonatal lupus erythematosus). A cesarean section may be required in certain obstetric contexts (such as urgent preterm delivery for maternal and/or fetal well-being), but vaginal birth should be the aim for the majority of women. Postnatally, an ongoing individual management plan remains important, with neonatal management where necessary and rheumatology followup. This article explores the challenges at each stage of pregnancy, discusses the effect of SLE on pregnancy and vice versa, and reviews antirheumatic medications with the latest guidance about their use and safety in pregnancy. Such information is required to effectively and safely manage each stage of pregnancy in women with SLE.
Hanly, John G.; Su, Li; Urowitz, Murray B.; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; Bernatsky, Sasha; Clarke, Ann E.; Wallace, Daniel J.; Merrill, Joan T.; Isenberg, David A.; Rahman, Anisur; Ginzler, Ellen M.; Petri, Michelle; Bruce, Ian N.; Dooley, M. A.; Fortin, Paul; Gladman, Dafna D.; Sanchez-Guerrero, Jorge; Steinsson, Kristjan; Ramsey-Goldman, Rosalind; Khamashta, Munther A.; Aranow, Cynthia; Alarcón, Graciela S.; Fessler, Barri J.; Manzi, Susan; Nived, Ola; Sturfelt, Gunnar K.; Zoma, Asad A.; van Vollenhoven, Ronald F.; Ramos-Casals, Manuel; Ruiz-Irastorza, Guillermo; Lim, S. Sam; Kalunian, Kenneth C.; Inanc, Murat; Kamen, Diane L.; Peschken, Christine A.; Jacobsen, Soren; Askanase, Anca; Theriault, Chris; Thompson, Kara; Farewell, Vernon
Objective To determine the frequency, clinical and autoantibody associations and outcome of mood disorders in a multi-ethnic/racial, prospective, inception cohort of SLE patients. Methods Patients were assessed annually for mood disorders (4 types as per DSM-IV) and 18 other neuropsychiatric (NP) events. Global disease activity (SLEDAI-2K), SLICC/ACR damage index (SDI) and SF-36 subscale, mental (MCS) and physical (PCS) component summary scores were collected. Time to event, linear and ordinal regressions and multi-state models were used as appropriate. Results Of 1,827 SLE patients, 88.9% were female, 48.9% Caucasian, mean ± SD age 35.1±13.3 years, disease duration 5.6±4.8 months and follow-up 4.73±3.45 years. Over the study 863 (47.2%) patients had 1,627 NP events. Mood disorders occurred in 232/1827 (12.7%) patients and 98/256 (38.3%) events were attributed to SLE. The estimated cumulative incidence of any mood disorder after 10 years was 17.7% (95%CI=[15.1%,20.2%]). There was a greater risk of mood disorder in patients with concurrent NP events (p ≤ 0.01) and lower risk with Asian race/ethnicity (p=0.01) and immunosuppressive drugs (p=0.003). Mood disorders were associated with lower mental health subscale and MCS scores but not with SLEDAI-2K, SDI scores or lupus autoantibodies. Antidepressants were used in 168/232 (72.4%) patients with depression. 126/256 (49.2%) mood disorders resolved in 117/232 (50.4%) patients. Conclusion Mood disorders, the second most frequent NP event in SLE patients, have a negative impact on HRQoL and improve over time. The lack of association with global SLE disease activity, cumulative organ damage and lupus autoantibodies emphasize their multifactorial etiology and a role for non-lupus specific therapies. PMID:25778456
Van de Voorde, K; De Raeve, H; De Block, C E; Van Regenmortel, N; Van Offel, J F; De Clerck, L S; Stevens, W J
Collagen vascular diseases and malignancies have common systemic and immune features. We report a case of a 21 year old female patient with constitutional symptoms, polyserositis, spontaneous rupture of the spleen, leukocytoclastic vasculitis and acute renal failure. The tentative diagnosis of SLE was made because she developed a positive antinuclear factor (1/640), with anti-SSA antibodies and a positive lupus anticoagulans. Two months later a cervical lymphadenopathy occurred while recieving treatment with prednisolone. A lymph node biopsy revealed morphologic features of a SLE, similar to those observed in multicentric Castleman's disease (MCD). MCD is a distinct type of a lymphoproliferative disorder of unknown etiology. The difficulties in differential diagnosis of these two diseases are discussed.
Bade, D M; Lovasko, J H; Montana, J; Waide, F L
Collagen failure has been shown to result in synovitis, joint adhesions, and internal joint derangement. This case report illustrates the similarities between patients with systemic lupus erythematosus and an internally deranged temporomandibular joint and patients with internal derangement with no lupus erythematosus. If abnormalities in intra-articular collagen tissue lead to adhesion formation and restrict normal mobility during translatory movements, joint mechanics would be compromised. Arthritic changes, vasculitis, and synovitis of systemic lupus erythematosus appear to be contributory factors in this pathophysiologic process. Diagnostic and therapeutic arthroscopic surgery was performed. Acute and chronic signs of synovitis were observed during surgery, and tissue samples were obtained for histologic interpretation.
Choi, B Y; Yoon, M J; Shin, K; Lee, Y J; Song, Y W
We investigated the clinical characteristics of pleural effusion in systemic lupus erythematosus (SLE). A prospective analysis of 17 SLE patients with pleural effusion (seven lupus pleuritis, eight transudative effusions and two parapneumonic effusions) was performed. Thirty non-SLE patients with pleural effusion were recruited as controls. A pleural fluid ANA titer ≥1:160 was found in 8/17 (47.1%) SLE patients and none of the 30 non-SLE patients (p = 0.0001). Pleural fluid to serum C3 ratios were significantly lower in SLE than in non-SLE (median (minimum-maximum) 0.29 (0.03-0.43) versus 0.52 (0.26-0.73), p = 0.0002). Among SLE patients, pleural fluid ANA titers ≥1:160 were more frequently found in patients with lupus pleuritis than in those with pleural effusion from causes other than lupus itself (85.7% versus 20.0%, p = 0.0152). Serum CRP levels were significantly increased in patients with lupus pleuritis compared with SLE patients with transudative pleural effusion (2.30 (0.30-5.66) versus 0.7 (0.12-1.47) mg/dl, p = 0.0062). In conclusion, pleural fluid ANA titer and serum CRP levels are significantly increased in lupus pleuritis.
Hanly, John G.; Urowitz, Murray B.; Su, Li; Gordon, Caroline; Bae, Sang-Cheol; Sanchez-Guerrero, Jorge; Romero-Diaz, Juanita; Wallace, Daniel J; Clarke, Ann E.; Ginzler, E.M.; Merrill, Joan T.; Isenberg, David A.; Rahman, Anisur; Petri, M.; Fortin, Paul R.; Gladman, D. D.; Bruce, Ian N.; Steinsson, Kristjan; Dooley, M.A.; Khamashta, Munther A.; Alarcón, Graciela S.; Fessler, Barri J.; Ramsey-Goldman, Rosalind; Manzi, Susan; Zoma, Asad A.; Sturfelt, Gunnar K.; Nived, Ola; Aranow, Cynthia; Mackay, Meggan; Ramos-Casals, Manuel; van Vollenhoven, R.F.; Kalunian, Kenneth C.; Ruiz-Irastorza, Guillermo; Lim, Sam; Kamen, Diane L.; Peschken, Christine A.; Inanc, Murat; Theriault, Chris; Thompson, Kara; Farewell, Vernon
Objective To describe the frequency, attribution, outcome and predictors of seizures in SLE Methods The Systemic Lupus International Collaborating Clinics (SLICC) performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLEDAI-2K), cumulative organ damage (SLICC/ACR Damage Index (SDI)) and neuropsychiatric events were recorded at enrollment and annually. Lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrollment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 mental (MCS) and physical (PCS) component summary scores. Statistical analyses included Cox and linear regressions. Results The cohort was 89.4% female with a mean follow up of 3.5±2.9 years. 75/1631 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR(CI):1.97 (1.07–3.63); p=0.03) and lower education status (1.97 (1.21–3.19); p<0.01). Higher damage scores (without NP variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46–10.55)); SDI=2 or 3:1.57 (0.32–7.65); SDI≥4:7.86 (0.89–69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78(76%)) in the absence of anti-seizure drugs. There was no significant impact on the MCS or PCS scores. Anti-malarial drugs in absence of immunosuppressive agents were associated with reduced seizure risk (0.07(0.01–0.66); p=0.03). Conclusion Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Anti-malarial drugs were associated with a protective effect. PMID:22492779
Lewandowicz, Edward; Zieliński, Tomasz; Iljin, Aleksandra; Fijałkowska, Marta; Kasielska-Trojan, Anna
Lipodystrophies are a wide group of diseases with various etiology, mainly genetic, metabolic or autoimmune. The treatment of these diseases is chronic and not always effective. Major concerns for patients with lipodystrophies are also esthetic defects, especially deformities in the face, neck and upper limbs. There are many surgical methods that can be used to improve patient's appearance like fillers, autologous fat transfer and skin flaps. The aim of this paper is to present and discuss surgical techniques used for correction of lipoatrophy and other skin lesions present in lupus erythematosus. In the first presented patient, lipodermal grafts were performed in two stages (first – to both zygomatic areas, the second – to both nasolabial folds). Moreover, the patient was qualified for arm scar plasty. Deepithelialized skin in the affected area was covered with advanced local skin flaps. In the second patient, an extensive scarring lesion on the scalp was excised and the defect was closed with an expanded scalp flap. Patients with lipodystrophies may require aesthetic surgical procedures to improve their appearance. In patients with lupus erythematosus, autologous fat graft in the face area seems to be a safe and effective method of refilling the volume of atrophic tissues. On the basis of our experience, it is worth emphasizing that the process of fat graft resorption is typical. In patients with scalp scars, an effective method of their removal and hairline restoring is usage of the tissue expander. PMID:25610357
Hod, Tami; Zandman-Goddard, Giselle; Langevitz, Pnina; Rudnic, Hagit; Grossman, Zehava; Rotman-Pikielny, Pnina; Levy, Yair
We sought to evaluate a possible link between parvovirus B19 infection and the clinical and laboratory expression of systemic lupus erythematosus (SLE). SLE patients were examined to evaluate their clinical status and disease activity. A complete Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was obtained for each patient. In addition, we determined the level of systemic involvement throughout the course of the disease. Blood levels of IgM and IgG antibodies to parvovirus B19, levels of anti-dsDNA, C3, and C4 were measured. A PCR real-time assay was used to determine the presence of parvovirus B19 genetic material. The viral genome was found in sera of 2 of 51(3.9%) patients with SLE. There was no correlation between viral serology and the clinical and serological parameters of the disease. More SLE patients with secondary antiphospholipid syndrome (APS) had IgG and IgM antibodies to the virus (p < 0.029 and p < 0.018, respectively). These patients also had a higher titer of IgG antibodies to parvovirus B19 compared to SLE patients without APS. In this group of SLE patients, no association was found between parvovirus infection and the presence or activity of SLE. The results of the study suggest an association between parvovirus infection and antibody production directed against phospholipids.
Kapoor, T M; Mahadeshwar, P; Nguyen, S; Li, J; Kapoor, S; Bathon, J; Giles, J; Askanase, A
Objective In the era of powerful immunosuppression, opportunistic infections are an increasing concern in systemic lupus erythematosus. One of the best-studied opportunistic infections is Pneumocystis pneumonia; however, the prevalence of Pneumocystis pneumonia in systemic lupus erythematosus is not clearly defined. This study evaluates the prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, with a focus on validating the Pneumocystis pneumonia and systemic lupus erythematosus diagnoses with clinical information. Methods This retrospective cohort study evaluates the prevalence of Pneumocystis pneumonia in all systemic lupus erythematosus patients treated at Columbia University Medical Center-New York Presbyterian Hospital between January 2000 and September 2014, using electronic medical record data. Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and patients with renal transplants (including both early and late post-transplant patients) represented immunocompromised control groups. Patients with systemic lupus erythematosus, Pneumocystis pneumonia, HIV/AIDS, or renal transplant were identified using diagnostic codes from the International Classification of Diseases, Ninth Revision (ICD-9). Results Out of 2013 hospitalized systemic lupus erythematosus patients, nine had presumed Pneumocystis pneumonia, yielding a low prevalence of Pneumocystis pneumonia in systemic lupus erythematosus of 0.45%. Three of the nine Pneumocystis pneumonia cases were patients with concomitant systemic lupus erythematosus and HIV/AIDS. Only one of these nine cases was histologically confirmed as Pneumocystis pneumonia, in a patient with concomitant systemic lupus erythematosus and HIV/AIDS and a CD4 count of 13 cells/mm(3). The prevalence of Pneumocystis pneumonia in renal transplant patients and HIV/AIDS patients was 0.61% and 5.98%, respectively. Conclusion Given the reported high rate of adverse effects
Federmann, M; Morell, B; Graetz, G; Wyss, M; Elsner, P; von Thiessen, R; Wüthrich, B; Grob, D
After implantation of two metal plates a 24 year old woman developed fever of unknown origin and successively more symptoms of an ANA-negative systemic lupus erythematosus (SLE). These symptoms resolved after removal of the plates and recurred during patch testing of the metal components, which showed a reaction to molybdenum. A lymphocyte transformation test indicated a delayed-type hypersensitivity to molybdenum. Subsequent progressive flare ups of SLE appeared without molybdenum reexposure. This is the first report suggesting the existence of a hypersensitivity to molybdenum, which may act as another environmental trigger for SLE. PMID:8037499
Guerreiro Castro, Sara; Isenberg, David A.
Systemic lupus erythematosus (SLE) is a complex autoimmune rheumatic disease with multiple presentations, whose management presents many challenges. Many disease modifying or immunosuppressive drugs have been used with limited success, especially in patients with more severe disease activity. Belimumab is the first drug to be approved specifically for the treatment of SLE in more than 50 years. By blocking the B-cell activating factor, it interferes in B-cell differentiation and survival. Here we consider the results of the clinical trials that led to its approval, as well as the post-hoc analyses, follow-up studies and the current trials. PMID:28344669
Maggio, Maria Cristina; Corsello, Giovanni; Prinzi, Eugenia; Cimaz, Rolando
Patient: Female, 11 Final Diagnosis: Bullous pemphigoid in systemic lupus erythematosus Symptoms: Bullous lupus • photosensitive rash • synovitis Medication:— Clinical Procedure: Pharmacological treatment Specialty: Rheumatology Objective: Unusual clinical course Background: Bullous pemphigoid is an autoimmune blistering disease, with relapses, isolated or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Joint manifestations rapidly respond to small or moderate doses of corticosteroids, whereas skin manifestations usually respond to antimalarial drugs. Case Report: We describe the clinical case of an 11-year-old girl with SLE. She showed bullous skin lesions with arthralgia, mild proteinuria, resolved after steroid treatment. At the tapering of her prednisone dose, the patient had new skin lesions requiring an increased dose of prednisone. She started dapsone at the dosage of 1 mg/kg/day, maintaining low dose prednisone; this treatment was successfully followed by the dramatic disappearance of skin lesions and limb pain. Conclusions: Bullous skin lesions can represent the first clinical presentation of pediatric SLE and could influence the treatment and the outcome of these patients. This case showed an atypical course as both skin manifestations and arthritis promptly and persistently resolved with dapsone without the use of high-dose glucocorticoids. Only a few cases of patients with SLE associated with bullous pemphigoid have been reported in the literature, and very few in the pediatric population. PMID:28352068
Hesselvig, J Halskou; Ahlehoff, O; Dreyer, L; Gislason, G; Kofoed, K
Systemic lupus erythematosus (SLE) is a well-known cardiovascular risk factor. Less is known about cutaneous lupus erythematosus (CLE) and the risk of developing cardiovascular disease (CVD). Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients diagnosed with SLE and CLE. We conducted a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular endpoint and all-cause mortality, for patients with SLE and CLE. A total of 3282 patients with CLE and 3747 patients with SLE were identified and compared with 5,513,739 controls. The overall HR for the composite CVD endpoint was 1.31 (95% CI 1.16-1.49) for CLE and 2.05 (95% CI 1.15-3.44) for SLE. The corresponding HRs for all-cause mortality were 1.32 (95% CI 1.20-1.45) for CLE and 2.21 (95% CI 2.03-2.41) for SLE. CLE and SLE were associated with a significantly increased risk of CVD and all-cause mortality. Local and chronic inflammation may be the driver of low-grade systemic inflammation.
Systemic lupus erythematosus (SLE) is a multi-systemic immune-complex mediated autoimmune condition which chiefly affects women during their prime year. While the management of the condition falls into the specialty of internal medicine, patients with SLE often present with signs and symptoms pertaining to the territory of orthopedic surgery such as tendon rupture, carpal tunnel syndrome, osteonecrosis, osteoporotic fracture and infection including septic arthritis, osteomyelitis and spondylodiscitis. While these orthopedic-related conditions are often debilitating in patients with SLE which necessitate management by orthopedic specialists, a high index of suspicion is necessary in diagnosing these conditions early because lupus patients with potentially severe orthopedic conditions such as osteomyelitis frequently present with mild symptoms and subtle signs such as low grade fever, mild hip pain and back tenderness. Additionally, even if these orthopedic conditions can be recognized, complications as a result of surgical procedures are indeed not uncommon. SLE per se and its various associated pharmacological treatments may pose lupus patients to certain surgical risks if they are not properly attended to and managed prior to, during and after surgery. Concerted effort of management and effective communication among orthopedic specialists and rheumatologists play an integral part in enhancing favorable outcome and reduction in postoperative complications for patients with SLE through thorough pre-operative evaluation, careful peri-operative monitoring and treatment, as well as judicious postoperative care. PMID:24653977
Sönmez, Hafize Emine; Karhan, Asuman Nur; Batu, Ezgi Deniz; Bilginer, Yelda; Gümüş, Ersin; Demir, Hülya; Yüce, Aysel; Özen, Seza
Systemic lupus erythematosus (SLE) is an autoimmune disease which may involve gastrointestinal system (GIS). The aim of this study was to present GIS manifestations of pediatric SLE patients. The medical files of 69 children with SLE followed between January 2011 and January 2016 were reviewed. All fulfilled the Systemic Lupus International Collaborating Clinics criteria. All patients (≤18 years of age) with GIS manifestations were included. GIS manifestations were observed in 19 (27.5%) out of 69 SLE patients and present at the time of SLE diagnosis in 13 (68.4%). The GIS manifestations due to SLE were autoimmune hepatitis (AIH) (n = 8) and lupus enteritis (n = 1). Manifestations associated with SLE were hepatomegaly and hypertransaminasemia due to macrophage activation syndrome (MAS) (n = 3) and hepatic steatosis (n = 1). GIS manifestations as a result of the adverse events of drugs were as follows: toxic hepatitis (n = 3; associated with methotrexate and nonsteroidal anti-inflammatory drugs in one, methotrexate in another, and azathioprine in another patient), azathioprine-induced cholestatic hepatitis (n = 1), and gastritis associated with corticosteroid (n = 1). In one patient, acute appendicitis occurred as a coincidence. In this study, one of every five pediatric SLE patients had GIS-related manifestations. GIS involvement may occur as an initial manifestation of the disease.
Ponticelli, Claudio; Moroni, Gabriella
A number of monoclonal antibodies (mAb) are now under investigation in clinical trials to assess their potential role in Systemic Lupus Erythematosus (SLE). The most frequently used mAb is rituximab, which is directed against CD20, a membrane protein expressed on B lymphocytes. Uncontrolled trials reported an improvement of SLE activity in non-renal patients and other studies even reported an improvement of severe lupus nephritis unresponsive to conventional treatments. However two randomized trials failed to show the superiority of rituximab over conventional treatment in non renal SLE and in lupus nephritis. Preliminary trials reported promising results with epratuzumab, a humanized mAb directed against CD22, and with belimumab, a human mAb that specifically recognizes and inhibits the biological activity of BLyS a cytokine of the tumor-necrosis-factor (TNF) ligand superfamily. Other clinical trials with mAb directed against TNF-alpha, interleukin-10 (Il-10), Il-6, CD154, CD40 ligand, IL-18 or complement component C5 are under way. At present, however, in spite of good results reported by some studies, no firm conclusion on the risk-benefit profile of these mAbs in patients with SLE can be drawn from the available studies. PMID:27713252
McAlindon, T; Giannotta, L; Taub, N; D'Cruz, D; Hughes, G
OBJECTIVES--To evaluate social class, ethnic origin, and various endocrine variables as potential risk factors in the development of nephritis in patients with systemic lupus erythematosus (SLE). METHODS--A cross-sectional survey was carried out of all outpatients with SLE attending the lupus Clinic of St Thomas's Hospital from March to October 1992 using retrospective survival data. The main outcome measure was the duration of SLE before the onset of nephritis. RESULTS--Two hundred and ninety six women and 11 men were studied; the male patients were excluded from the analysis. Univariate analysis showed an increased risk of nephritis in patients with SLE of West Indian origin with 54 v 19% with nephritis at five years, in patients of lower social class, in patients who did not drink alcohol, and in those with a history of fetal loss after the onset of lupus. No significant effect of the age of onset of SLE, use of oral contraceptives, normal pregnancy, or smoking was seen. Multivariate analysis showed that ethnic origin did not influence the risk of nephritis independently of social class. CONCLUSIONS--Factors associated with socioeconomic deprivation may increase disease severity in patients with SLE. PMID:8257208
Manuel, Valdano; Pedro, Gertrudes Maria; Cordeiro, Lemuel Bornelli; de Miranda, Sandra Maria da Rocha Neto
Acute acalculous cholecystitis is a very rare gastrointestinal manifestation in systemic lupus erythematosus and becomes rarer as an initial manifestation. There are only two cases reported. The authors report a 20-year-old black woman that presented acute acalculous cholecystitis revealed by abdominal computed tomography. During hospitalization, she was diagnosed systemic lupus erythematosus. Conservative treatment with antibiotics was performed with complete remission of the symptoms. Corticosteroid was started in ambulatory. Cholecystectomy has been the treatment of choice in acute acalculous cholecystitis as a complication of systemic lupus erythematosus. The patient responded well to conservative treatment, and surgery was not required. This case is unique in the way that corticosteroid was started in ambulatory care. We should not forget that the acute acalculous cholecystitis can be the initial presentation of systemic lupus erythematosus although its occurrence is very rare. Conservative treatment should be considered. Abdominal computed tomography was a determinant exam for better assessment of acute acalculous cholecystitis.
Postal, M; Lapa, A Tamires; Reis, F; Rittner, L; Appenzeller, S
Systemic lupus erythematosus is a chronic, inflammatory, immune-mediated disease affecting 0.1% of the general population. Neuropsychiatric manifestations in systemic lupus erythematosus have been more frequently recognized and reported in recent years, occurring in up to 75% of patients during the disease course. Magnetic resonance imaging is known to be a useful tool for the detection of structural brain abnormalities in neuropsychiatric systemic lupus erythematosus patients because of the excellent soft-tissue contrast observed with MRI and the ability to acquire multiplanar images. In addition to conventional magnetic resonance imaging techniques to evaluate the presence of atrophy and white matter lesions, several different magnetic resonance imaging techniques have been used to identify microstructural or functional abnormalities. This review will highlight different magnetic resonance imaging techniques, including the advanced magnetic resonance imaging methods used to determine central nervous system involvement in systemic lupus erythematosus.
Miller, M H
I report the case of a woman with systemic lupus erythematosus who had pulmonary hypertension unassociated with chronic interstitial lung disease or pulmonary emboli. She had started taking the contraceptive pill seven months previously.
Introduction The occurrence of systemic lupus erythematosus has been only rarely reported in patients with sickle-cell disease. Case presentation We describe the case of a 23-year-old North-African woman with sickle-cell disease and systemic lupus erythematosus, and discuss the pointers to the diagnosis of this combination of conditions and also present a review of literature. The diagnosis of systemic lupus erythematosus was delayed because our patient’s symptoms were initially attributed to sickle-cell disease. Conclusions Physicians should be alerted to the possible association of sickle-cell disease and systemic lupus erythematosus so as not to delay correct diagnosis and initiation of appropriate treatment. PMID:23101910
Mon, T; L'ecuyer, S; Farber, N B; White, A J; Baszis, K W; Hearn, J K; Spiegel, T E; French, A R; Kitcharoensakkul, M
Catatonia is a rare manifestation in patients with systemic lupus erythematosus (SLE). As catatonia can be associated with both psychiatric and organic conditions, this could create a diagnostic dilemma once this occurs in SLE patients. The report describes a 15-year-old female with SLE who developed catatonia three days after the diagnosis of SLE was made. Her catatonia was refractory to the treatment with immunosuppressive therapy, which included pulse methylprednisolone, intravenous cyclophosphamide, rituximab, intravenous immunoglobulin (IVIG) and plasmapheresis. Given her persistent catatonia, electroconvulsive therapy (ECT) was initiated three months after the onset of her symptoms. After the third ECT treatment, her mental status dramatically improved and returned nearly to baseline while she was continued on the immunosuppression. This is the first report of a successful ECT therapy in catatonic lupus in children.
Momen, Tooba; Madihi, Yahya
Bullous systemic lupus erythematosus (BSLE) is an autoimmune blistering disease occurring in patients with systemic lupus erythematosus (SLE). It is a rare disease, especially in children. A 14-year-old girl initially presented with fatigue, generalized vesiculobullous skin lesions, and ulcers over the hard palate and oral mucosa. Clinical investigations revealed hematuria and proteinuria, a high erythrocyte sedimentation rate and titer of antinuclear antibody, and anti-double-stranded DNA. Skin biopsy findings were suggestive of BSLE. A renal biopsy confirmed the features of class V lupus nephritis. Based on the clinical features and investigations, a diagnosis of BSLE with nephritis was made. She received methylprednisolone pulse therapy and hydroxychloroquine; however, it did not alleviate the vesiculobullous eruption, so treatment with dapsone started and resulted in the dramatic disappearance of the lesions. Interruption of dapsone due to hemolysis did not aggravate the bullous disease. During follow-up, she had multiple flare-ups of disease and nephritis without rebound of bullous lesions. BSLE is a rare presentation of SLE in children. Differentiating it from other skin bullous diseases and SLE with blister is important for the correct management. The unusual presentation of this disease may delay the diagnosis and therefore requires a high index of clinical suspicion. PMID:27974963
Taşdemir, Mehmet; Hasan, Chiar; Ağbaş, Ayşe; Kasapçopur, Özgür; Canpolat, Nur; Sever, Lale; Çalışkan, Salim
Systemic lupus erythematosus and Sjögren’s syndrome are chronic auto- inflammatory disorders which can lead to serious organ damage. Although systemic lupus erythematosus and Sjögren’s syndrome were previously considered two forms of the same disease because of presence of clinical coexistence of these two conditions, the view that they are two different conditions with mutual characteristics has become prominent in recent years. In this paper, we reported a 16 year-old girl who was followed up with a diagnosis of Sjögren’s syndrome for six years and then was observed to have overlap of systemic lupus erythematosus. In the baseline, she did not have any clinical or serological evidence for systemic lupus erythematosus. After six year, massive proteinuria and serological findings developed and systemic lupus erythematosus nephritis was diagnosed by kidney biopsy. Currently, systemic lupus erythematosus and Sjögren’s syndrome cannot be differentiated definetely. We need more valuable diagnostic and classification criteria to differentiate these two important conditions. PMID:27738403
Yamamoto, Yuriko; Aoki, Shigeru
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with a high prevalence in females of childbearing age. Thus, reproduction in SLE patients is a major concern for clinicians. In the past, SLE patients were advised to defer pregnancy because of poor pregnancy outcomes and fear of SLE flares during pregnancy. Investigations to date show that maternal and fetal risks are higher in females with SLE than in the general population. However, with appropriate management of the disease, sufferers may have a relatively uncomplicated pregnancy course. Factors such as appropriate preconception counseling and medication adjustment, strict disease control prior to pregnancy, intensive surveillance during and after pregnancy by both the obstetrician and rheumatologist, and appropriate interventions when necessary play a key role. This review describes the strategies to improve pregnancy outcomes in SLE patients at different time points in the reproduction cycle (preconception, during pregnancy, and postpartum period) and also details the neonatal concerns. PMID:27468250
Ghannouchi Jaafoura, N; Khalifa, M; Atig, A; Ben Jazia, E; Alaoua, A; Braham Krifa, A; Letaief, A; Bahri, F
Intestinal pseudo-obstruction (IPO) is an uncommon and severe complication of systemic lupus erythematosus (SLE). We report a 24-year-old female with a 2 year SLE duration who presented with abdominal pain, vomiting, constipation and abdominal distention. Plain abdominal radiograph showed multiple air-fluid levels of the small bowel. Computed tomographic scan of the abdomen revealed dilated small bowel loops without mechanical obstruction. Urinary tract involvement was also demonstrated. IPO was diagnosed and the patient responded well to immunosuppressive treatment. IPO is a recently recognized manifestation of SLE that may be the presenting manifestation of the systemic disease or occur more commonly during disease course. Early recognition of IPO is necessary to institute appropriate medical treatment and to avoid inappropriate surgical intervention.
Arenas Miras, María del Mar; Hidalgo Tenorio, Carmen; Jimenez Alonso, Juan
There has recently been an increase in the incidence of patients with systemic lupus erythematosus (SLE) due mainly to earlier diagnosis, and increased survival. Tuberculosis in our country is one of the most prevalent infectious diseases, and one of the underlying causes would be HIV infection and increased immigration from areas with high tuberculosis prevalence; this phenomenon is truly important in patients with autoimmune diseases, as clinical presentation, severity and prognosis of tuberculosis are often different to that of immunocompetent patients. Studies of tuberculosis in patients with SLE are scarce and inconclusive, with many doubts existing about the performance or non-tuberculous prophylaxis in this population and the absence of a protocol due to lack of conclusive studies. New techniques for diagnosis of tuberculosis (IGRAs) may be useful in this population due to higher sensitivity than Mantoux, helping avoid false negatives.
Guleria, Vivek S; Singh, Pradeep K; Saxena, Puneet; Subramanian, Shankar
Shrinking lung syndrome (SLS) is a infrequently reported manifestation of systemic lupus erythematosus (SLE). Reported prevalence of SLS is about 0.5% in SLE patients. Pathogenesis is not fully understood and different therapeutic modalities have been employed with variable results, as only 77 cases of SLS have been documented in literature. SLS in SLE-Scleroderma overlap has not been reported yet. We report a patient of SLE - scleroderma overlap presenting with dyspnea, intermittent orthopnea and pleuritic chest pain. Evaluation revealed elevated hemidiaphragms and severe restrictive defect. She was eventually diagnosed as a case of SLS. This case report is a reminder to the medical fraternity that SLS although a rare complication must be thought of in the special subset of patients of SLE having respiratory symptoms.
Smolen, Josef S
The prognosis for patients with systemic lupus erythematosus has greatly improved over the past two decades. However, therapies that are more effective and that have fewer sequelae are needed to rescue patients from organ failure and further reduce mortality. Research under way, including that into induction of tolerance to self-antigens, prevention of the consequences of pathogenic autoantibody production, interference with the cytokine network and signal transduction, the identification and treatment of any infectious triggers, and stem cell therapy, offers hope of improved remedies or even of cure. Given the fact that a number of biological therapies for rheumatologic disease are already in use or are in the development stage, such progress may come soon.
Lupus erythematosus (LE) is an important dermatologic autoimmune disease and in many aspects, including epidemiology, genetics, immunology, diagnostics and treatment, may be regarded as model for many other autoimmune diseases. Constant efforts in the past years have unraveled important new aspects of LE pathogenesis. Among these are the genetic associations with immunoregulatory signaling pathways such as TNF-, NF-κB-, IL23/IL17- and interferon pathway as well as new insights into the relevance of the innate immune system. Here Toll-like receptors and neutrophils play a central role. The knowledge about immune and autoimmune interactions in LE pathogenesis and the contributing cell types is steadily increasing and has led to new therapeutic approaches using antibodies directed against the B-cell activating factor BLyS. In the first part of this review article, the current knowledge about epidemiology, genetics and immunology is summarized. A second article will deal with diagnostics, clinical picture and different treatment modalities.
Franklyn, Kate; Hoi, Alberta; Nikpour, Mandana; Morand, Eric F
In the current therapeutic climate, mortality rates from systemic lupus erythematosus (SLE) remain unacceptably high. Although new therapies are on the horizon, pending their emergence and availability, optimization of the currently available therapies is potentially achievable. A 'treat-to-target' approach is now considered routine for many diseases, including rheumatoid arthritis, for which it has substantially improved patient outcomes. The heterogeneity of SLE, as well as lack of universal agreement over methods to measure disease activity and treatment responses, has impeded the development of such an approach for this disease. In this article, the potential benefits of a treatment-target definition are explored, obstacles to the development of a treatment target in SLE are identified, and possible strategies to achieve this goal are discussed.
Sammaritano, L R
Contraceptive choice in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) is challenging but important. Long-acting forms of contraception such as the progesterone intrauterine device (IUD) or subdermal implant are preferable for most patients. Estrogen-containing hormonal contraceptives may be used in stable, inactive SLE patients but are contraindicated in patients with positive antiphospholipid antibodies (aPL). The levonorgestrel IUD is a good alternative for many APS patients and often decreases menstrual blood loss. It is prudent to avoid depot medroxyprogesterone acetate (DMPA) in corticosteroid-treated or other patients at risk for osteoporosis because of the inhibition of ovulation. Effective and safe contraception in patients with SLE and APS permits planning for pregnancy during inactive disease and while on pregnancy-compatible medications, preventing a poorly timed pregnancy that may jeopardize maternal and/or fetal health.
Koarada, Syuichi; Tada, Yoshifumi
Systemic lupus erythematosus (SLE) is a multisystem disease characterized by B cells producing autoantibodies against nuclear proteins and DNA, especially anti-double-strand DNA (dsDNA) antibodies. RP105 (CD180), the toll-like receptor- (TLR-) associated molecule, is expressed on normal B cells. However, RP105-negative B cells increase in peripheral blood from patients with active SLE. RP105 may regulate B-cell activation, and RP105-negative B cells produce autoantibodies and take part in pathophysiology of SLE. It is possible that targeting RP105-negative B cells is one of the treatments of SLE. In this paper, we discuss the RP105 biology and clinical significance in SLE. PMID:21941580
Spinozzi, F; Capodicasa, E; Gerli, R; Bertotto, A; Rambotti, P; Grignani, F
A case of a 63-year old man, who developed systemic lupus erythematosus three years after an initial diagnosis of small-cleaved centrofollicular lymphoma is described. The diagnosis of SLE was made on the basis of the accepted "1982 revised criteria for the classification of SLE". The autoimmune disease arose after a cycle of total body irradiation, despite the treatment with combination chemotherapeutic doses such a CVP or COAP or Cyclophosphamide, Vincristine, VM-26 and Prednisone. Genetic, immunological and exogenous environmental factors may co-exist and might equally be implicated in the pathogenesis of SLE and malignant lymphoma. However, the onset of SLE after total body irradiation could have been caused by the inactivation of suppressor T lymphocytes, which are known to be sensitive to radiations in vitro.
Basnyat, Shristi; Eid, Hala; Kuzyshyn, Halyna; Feinstein, David
The clinical presentation of Systemic Lupus Erythematosus (SLE) is diverse and vasculitis can be a potential manifestation. Cutaneous lesions involving small vessels are the most frequent presentation. However, medium and large vessel vasculitis may present with life-threatening visceral manifestations. We present a unique case of pelvic vasculitis mimicking a pelvic mass as an initial presentation of SLE. There are case reports of systemic vasculitis involving the female genital tract with giant cell arteritis (GCA), polyarteritis nodosa (PAN), and granulomatous with polyangiitis and microscopic polyangiitis (GPA/MPA), among others, but only a few cases attributed to SLE. Awareness of this condition and a prompt diagnosis are warranted as this is a severe and potentially life-threatening condition. PMID:28127489
Gladman, D D; Urowitz, M B
Deep vein thrombophlebitis (DVT) and pulmonary emboli (PE) have been uncommonly reported manifestations of systemic lupus erythematosus (SLE). This may be partly due to their being masked by other more familiar lesions of the lungs and extremities in SLE. We have identified 17 patients with SLE from a population of 180 being followed up prospectively who had 21 attacks of DVT and/or PE. Of the total of 21 episodes the SLE was considered to be active in 14, inactive in 6, and variable in a patient with recurring phlebitis. The incidence of hyperlipidaemia, smoking history, and use of birth control medication or corticosteroids was not higher in these patients. These clinical findings thus constitute additional features of SLE occurring in about 9% of patients and may be significance for morbidity and mortality.
Conventional immunosuppressive therapies have radically transformed patient survival in systemic lupus erythematosus (SLE), but their use is associated with considerable toxicity and a substantial proportion of patients remain refractory to treatment. A more comprehensive understanding of the complexity of SLE immunopathogenesis has evolved over the past decade and has led to the testing of several biologic agents in clinical trials. There is a clear need for new therapeutic agents that overcome these issues, and biologic agents offer exciting prospects as future SLE therapies. An array of promising new therapies are currently emerging or are under development including B-cell depletion therapies, agents targeting B-cell survival factors, blockade of T-cell co-stimulation and anti-cytokine therapies, such as monoclonal antibodies against interleukin-6 and interferon-α. PMID:23642011
Aringer, M; Dörner, T; Leuchten, N; Johnson, S R
While clearly different in their aims and means, classification and diagnosis both try to accurately label the disease patients are suffering from. For systemic lupus erythematosus (SLE), this is complicated by the multi-organ nature of the disease and by our incomplete understanding of its pathophysiology. Hallmarks of SLE are the presence of antinuclear antibodies (ANA), and multiple immune-mediated organ symptoms that are largely independent. In an attempt to overcome limitations of the current sets of SLE classification criteria, a new four-phase approach is being developed, which is jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). This review attempts to delineate the performance of the current sets of criteria, the reasons for the decision for classification, and not diagnostic, criteria, and to provide a background of the current approach taken.
Chen, Junwei; Wu, Meng; Wang, Jing; Li, Xiaofeng
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with different variety of clinical manifestations. Natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during broad range of immune responses. A number of studies demonstrated that the quantity and quality of invariant NKT (iNKT) cells showed marked defects in SLE patients in comparison to healthy controls. This finding suggests that iNKT cells may play a regulatory role in the occurrence and development of this disease. In this review, we mainly summarized the most recent findings about the behavior of NKT cells in SLE patients and mouse models, as well as how NKT cells affect the proportion of T helper cells and the production of autoreactive antibodies in the progress of SLE. This will help people better understand the role of NKT cells in the development of SLE and improve the therapy strategy. PMID:26819956
Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel
The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab.
Thong, Bernard; Olsen, Nancy J
SLE presents many challenges for clinicians. The onset of disease may be insidious, with many different symptoms and signs, making early and accurate diagnosis challenging. Tests for SLE in the early stages lack specificity; those that are useful later often appear only after organ damage is manifest. Disease patterns are highly variable; flares are not predictable and not always associated with biomarkers. Children with SLE may have severe disease and present special management issues. Older SLE patients have complicating co-morbid conditions. Therapeutic interventions have improved over recent decades, but available drugs do not adequately control disease in many patients, and successful outcomes are limited by off-target effects; some of these become manifest with longer duration of treatment, now in part revealed by improved rates of survival. Despite all of these challenges, advances in understanding the biological basis of SLE have translated into more effective approaches to patient care. This review considers the current state of SLE diagnosis and management, with a focus on new approaches and anticipated advances.
High, Whitney A; Costner, Melissa I
Neonatal lupus erythematosus is an uncommon autoimmune disease with distinctive cutaneous findings. Descriptions of chronic cutaneous sequelae are rare. We describe a 12-year-old girl with persistent dyspigmentation, scarring, and atrophy as a result of neonatal lupus occurring during infancy.
Ghodke-Puranik, Yogita; Niewold, Timothy B.
Summary Our understanding of the genetic basis of systemic lupus erythematosus has progressed rapidly in recent years. While many genetic polymorphisms have been associated with disease susceptibility, the next major step involves integrating these genetic polymorphisms into the molecular mechanisms and cellular immunology of the human disease. In this review, we summarize some recent work in this area, including the genetics of the type I IFN response in SLE, including polygenic and monogenic factors, as well as epigenetic influences. Contributions of both HLA and non-HLA polymorphisms to the complex genetics of SLE are reviewed. We also review recent reports of specific gene deficits leading to monogenic SLE-like syndromes. The molecular functions of common SLE-risk variants are reviewed in depth, including regulatory variations in promoter and enhancer elements and coding-change polymorphisms, and studies which are beginning to define the molecular and cellular functions of these polymorphisms in the immune system. We discuss epigenetic influences on lupus, with an emphasis on micro-RNA expression and binding, as well as epigenetic modifications that regulate the expression levels of various genes involved in SLE pathogenesis and the ways epigenetic marks modify SLE susceptibility genes. The work summarized in this review provides a fascinating window into the biology and molecular mechanisms of human SLE. Understanding the functional mechanisms of causal genetic variants underlying the human disease greatly facilitates our ability to translate genetic associations toward personalized care, and may identify new therapeutic targets relevant to human SLE disease mechanisms. PMID:26324017
Di Matteo, A; Satulu, I; Di Carlo, M; Lato, V; Filippucci, E; Grassi, W
Background Musculoskeletal involvement is extremely common in patients with systemic lupus erythematosus (SLE). Continuing the research initiated in patients with inflammatory arthritis, recent studies have shown the potential role of musculoskeletal ultrasound (MSUS) in the evaluation of clinical and subclinical lupus synovitis. The inflammatory process in SLE is traditionally considered to be localized at synovial tissue areas while enthesis is not included among the possible targets of the disease. Patients and methods Entheses included in the Glasgow Ultrasound Enthesitis Scoring System were scanned in a cohort of 20 SLE patients serving as disease controls in an MSUS study aimed at assessing enthesitis in patients with psoriatic arthritis. We describe in detail four cases with unexpected and unequivocal expressions of MSUS enthesitis according to the OMERACT definition. Three out of four patients had no predisposing factors for enthesopathy. Case no. 2 was treated with a variable-dose prednisone regimen. Results In the four cases MSUS examination revealed relevant grey-scale and power Doppler abnormalities at the entheseal level, most commonly at the distal insertion of the patellar tendon. Signs of clinical enthesitis were detected in only one patient. Conclusions This case series shows for the first time the presence of clearly evident MSUS findings indicative of enthesitis in four out of 20 SLE patients (20%), raising the hypothesis that enthesis could be a missing target in the clinical evaluation of SLE patients. Our case series justifies further investigations for a better evaluation of the prevalence, characteristics and clinical relevance of entheseal involvement in SLE.
Gómez, Jesús; Suárez, Ana; López, Patricia; Mozo, Lourdes; Díaz, José Bernardino; Gutiérrez, Carmen
Asturias is an autonomous region in the north of Spain with historical and anthropologic peculiarities. In the current report, we examine the main clinical and immunologic features of 363 patients with systemic lupus erythematosus (SLE), virtually the entire population of SLE patients in Asturias. We constructed a database with the clinical and immunologic features of all patients fulfilling the American College of Rheumatology criteria, based on the review of hospital records corresponding to blood samples received for antinuclear antibodies testing since 1992. Arthritis was the most frequently observed main clinical feature and neuropathy was the rarest. Male patients had a disease more frequently characterized by serositis (p<0.05) and neurologic disorder (p<0.01) than females, while children presented malar rash (p<0.05), fever (p<0.05), and kidney involvement (p<0.01) more often than adults. Late-onset patients were characterized by lower frequencies of malar rash (p<0.01), neurologic disorder (p<0.05), alopecia (p<0.01), and lymphadenopathy (p<0.05) than young adults. Numerous direct and inverse significant associations were found among clinical and immunologic features. The most relevant significant associations were neurologic disorder with lupus anticoagulant (p<0.01); kidney involvement with serositis (p<0.01) and DNA antibodies (p<0.05); and thrombosis with DNA antibodies (p<0.05), cardiolipin antibodies (p<0.01), and lupus anticoagulant (p<0.01). A low mortality was found in our series, although kidney involvement (p<0.05) and cardiolipin antibodies (p<0.05) are factors associated with poor survival.
Ruiz-Irastorza, Guillermo; Danza, Alvaro; Khamashta, Munther
Systemic lupus erythematosus (SLE) is a complex disease with different clinical forms of presentation, including a wide range of severity and organic involvement. Such circumstance, along with the fact of the uncommon nature of the disease and the absence of clinically representative response criteria, make it difficult to design controlled clinical trials in SLE patients. As a result, observational studies have a special relevance, being a source of valuable information of SLE prognosis and outcome as well as of the efficacy and adverse effects of the different therapies. Herein we update some of the main treatments used in SLE. Steroids may have more risks than benefits if used at high doses. New mechanisms of action have been described, supporting the use of lower doses, possibly with the same efficacy and less adverse effects. Intravenous pulses of cyclophosphamide still have a role in the treatment of proliferative lupus nephritis and other serious SLE manifestations. Mycophenolate mofetil has shown its efficacy both as induction and maintenance therapy of selected cases of lupus nephritis. Biological therapies have emerged as new promising options. Although clinical trials have not confirmed a clear superiority of rituximab in SLE, observational studies have shown good response rates in severe SLE manifestations or refractory forms. Belimumab has recently been added to the therapeutic armamentarium of SLE; although its place in clinical practice is not well-defined, it may be recommended in active patients with no response or good tolerance to standard therapies. Hydroxichloroquine improves survival, decreases the risk of thrombosis and flares and is safe in pregnancy, and should be considered the baseline therapy in most SLE patients.
Shah, Asha; Albrecht, Joerg; Bonilla-Martinez, Zuleika; Okawa, Joyce; Rose, Mathew; Rosenbach, Misha; Werth, Victoria P.
Background Discoid Lupus Erthematosus (DLE) is a chronic, disfiguring disease characterized by scaly, erythematous disk-shaped patches and plaques followed by atrophy, scarring, and dyspigmentation. A small population of patients suffer from disease that is refractory to standard therapies. We investigated the use of lenalidomide, a thalidomide analogue, as a novel alternative therapy on two cases of refractory DLE and report our results. Observations Two patients with chronic, severe DLE were treated with low dose lenalidomide. One patient demonstrated improvement within 1 month on 5 mg and was maintained for 10 months before her dose was doubled to 10 mg for 12 months because of a slight worsening of symptoms. Clinical improvement was demonstrated by a sustained reduction in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score with no change in the CLASI damage score. Within five months, the patient was tapered off of oral prednisone 60 mg daily; however, she was restarted and maintained on a low dose of prednisone 5 mg daily for management of SLE symptoms. Of note, the patient experienced mild neutropenia after being on 10 mg. Lenalidomide carries a black box warning of neutropenia, and it is recommended to monitor complete blood cell count (CBC) weekly for the first 2 months and then monthly. The second patient failed to show clinical improvement and lenalidomide was discontinued after six months. Conclusions Lenalidomide is a potential alternative or adjunctive treatment for patients with severe, chronic DLE that is refractory to standard therapies. A larger study is needed to clarify its role in the treatment of DLE and other forms of cutaneous lupus. PMID:19289762
Thorbinson, Colin; Oni, Louise; Smith, Eve; Midgley, Angela; Beresford, Michael W
Systemic lupus erythematosus (SLE) is a rare, severe, multisystem autoimmune disorder. Childhood-onset SLE (cSLE) follows a more aggressive course with greater associated morbidity and mortality than adult-onset SLE. Its aetiology is yet to be fully elucidated. It is recognised to be the archetypal systemic autoimmune disease, arising from a complex interaction between the innate and adaptive immune systems. Its complexity is reflected by the fact that there has been only one new drug licensed for use in SLE in the last 50 years. However, biologic agents that specifically target aspects of the immune system are emerging. Immunosuppression remains the cornerstone of medical management, with glucocorticoids still playing a leading role. Treatment choices are led by disease severity. Immunosuppressants, including azathioprine and methotrexate, are used in mild to moderate manifestations. Mycophenolate mofetil is widely used for lupus nephritis. Cyclophosphamide remains the first-line treatment for patients with severe organ disease. No biologic therapies have yet been approved for cSLE, although they are being used increasingly as part of routine care of patients with severe lupus nephritis or with neurological and/or haematological involvement. Drugs influencing B cell survival, including belimumab and rituximab, are currently undergoing clinical trials in cSLE. Hydroxychloroquine is indicated for disease manifestations of all severities and can be used as monotherapy in mild disease. However, the management of cSLE is hampered by the lack of a robust evidence base. To date, it has been principally guided by best-practice guidelines, retrospective case series and adapted adult protocols. In this pharmacological review, we provide an overview of current practice for the management of cSLE, together with recent advances in new therapies, including biologic agents.
Lee, J W; Park, D J; Kang, J H; Choi, S E; Yim, Y R; Kim, J E; Lee, K E; Wen, L; Kim, T J; Park, Y W; Sung, Y K; Lee, S S
Objectives The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus. Methods Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined "frequent hospitalization" as hospitalization more than once per year. Results Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8-year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjögren's syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. Conclusions Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and
Kawai, Takako; Tominaga, Sizuo; Okouchi, Akiko; Kudo, Makoto; Katoh, Kiyoshi; Shoda, Masataka; Fujino, Masayuki A
A 27-year-old Japanese woman was referred to our hospital for acute hepatitis in April 2002. She had been suffering from low grade fever and fatigue for a week. She also presented with dyspnea. On admission, ALT and AST were 857 U/l and 473 U/l respectively. Urine protein was 2 g/day. Chest radiograph showed bilateral infiltrative shadow and pleural effusion. She developed jaundice and her level of total bilirubin was increased to 9.6 mg/dl on May 9. Antibodies to hepatitis viruses were not detected. Testing for antimitochondrial antibodies, antismooth muscle antibodies, and antiribosomal P antibodies showed all negative. However, antinuclear antibodies were positive at titer 1:160 and anti-double stranded DNA antibodies were 130 U/ml. A diagnosis of systemic lupus erythematosus was made and oral administration of 60 mg/day prednisolon was started on May 10. Serum levels of ALT, AST and bilirubin were reduced to within normal range and pulmonary lesions were also improved. We conclude that this is a rare case of systemic lupus erythematosus presenting with acute hepatitis and jaundice.
Contin, Letícia Arsie; Martins da Costa Marques, Elisa Raquel; Noriega, Leandro
Lupus erythematosus, especially the discoid form, and lichen planopilaris may be associated and can occur in different topographies (coexistence) or in the same lesion (lupus eythematosus/lichen planus overlap syndrome). Frontal fibrosing alopecia is considered a variant form of lichen planopilaris and is characterized by frontotemporal hairline and eyebrow involvement. Of the association with lupus erythematosus we have only a few descriptions. Hydroxychloroquine and chloroquine diphosphate are antimalarial drugs described as viable treatment options for both diseases, due to an antilymphocytic effect. The association between frontal fibrosing alopecia and lupus erythematosus (discoid or systemic) is reported in this article, showing a progressive alopecia in the frontotemporal hairline despite treatment with hydroxychloroquine. PMID:28232926
Magro-Checa, C; Beaart-van de Voorde, L J J; Middelkoop, H A M; Dane, M L; van der Wee, N J; van Buchem, M A; Huizinga, T W J; Steup-Beekman, G M
Objective The objective of this study was to assess whether clinical and patient's reported outcomes are associated with a different pathophysiological origin of neuropsychiatric events presenting in systemic lupus erythematosus. Methods A total of 232 neuropsychiatric events presenting in 131 systemic lupus erythematosus patients were included. Neuropsychiatric systemic lupus erythematosus diagnosis was established per event by multidisciplinary evaluation. All neuropsychiatric events were divided according to a suspected underlying pathophysiological process into one of the following: non-neuropsychiatric systemic lupus erythematosus related, inflammatory and ischaemic neuropsychiatric systemic lupus erythematosus. The clinical outcome of all neuropsychiatric events was determined by a physician-completed four-point Likert scale. Health-related quality of life was measured with the subscales of the patient-generated Short Form 36 (SF-36) health survey questionnaire. The change between scores at paired visits of all domain scores, mental component summary (SF-36 MCS) and physical component summary (SF-36 PCS) scores were retrospectively calculated and used as patient-reported outcome. The association among these outcomes and the different origin of neuropsychiatric events was obtained using multiple logistic regression analysis. Results The clinical status of 26.8% non-neuropsychiatric systemic lupus erythematosus events, 15.8% ischaemic neuropsychiatric systemic lupus erythematosus and 51.6% inflammatory neuropsychiatric systemic lupus erythematosus improved after re-assessment. Almost all SF-36 domains had a positive change at re-assessment in all groups independently of the origin of neuropsychiatric events. Neuropsychiatric systemic lupus erythematosus ( B = 0.502; p < 0.001) and especially inflammatory neuropsychiatric systemic lupus erythematosus ( B = 0.827; p < 0.001) had better clinical outcome, with change in disease activity being the
Sato, J O; Corrente, J E; Saad-Magalhães, C
Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p < 0.001). Similarly, Spearman correlation between the activity indices was also high ( rs > 0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.
Devilliers, H; Bonithon-Kopp, C; Jolly, M
Objective The lupus impact tracker (LIT) is a 10-item patient reported outcome tool to measure the impact of systemic lupus erythematosus or its treatment on patients' daily lives. Herein, we describe the responsiveness of the LIT and LupusQoL to changes in disease activity, using the systemic lupus erythematosus responder index (SRI). Methods A total of 325 adult systemic lupus erythematosus patients were enrolled in an observational, longitudinal, multicentre study, conducted across the USA and Canada. Data (demographics, LIT, LupusQoL, BILAG, SELENA-SLEDAI) were obtained three months apart. Modified SRI was defined as: a decrease in SELENA-SLEDAI (4 points); no new BILAG A, and no greater than one new BILAG B; and no increase in the physician global assessment. Standardised response mean and effect size for LIT and LupusQoL domains were calculated among SRI responders and non-responders. Wilcoxon's test was used to compare the LIT and LupusQoL variation by SRI responder status. Results Of the participants 90% were women, 53% were white, 33% were of African descendant and 17% were Hispanic. Mean (SD) age and SELENA-SLEDAI at baseline were 42.3 (16.2) years and 4.3 (3.8), respectively. Mean (SD) LIT score at baseline was 39.4 (22.9). LIT standardised response mean (effect size) among SRI responders and non-responders were -0.69 (-0.36) and -0.20 (-0.12), respectively ( P = 0.02). For LupusQoL, two domains were responsive to SRI: standardised response mean (effect size) for physical health and pain domains were 0.42 (0.23) and 0.65 (0.44), respectively. Conclusions LIT is moderately responsive to SRI in patients with systemic lupus erythematosus. Inclusion of this tool in clinical care and clinical trials may provide further insights into its responsiveness. This is the first systemic lupus erythematosus patient reported outcome tool to be evaluated against composite responder index (SRI) used in clinical trials.
de Oliveira, Leonardo Rodrigues; Ferreira, Thaís Camargos; Neves, Fernando de Freitas; Meneses, Antônio Carlos de Oliveira
Aplastic anemia is a bone marrow failure syndrome characterized by peripheral cytopenias and hypocellular bone marrow. Although aplastic anemia is idiopathic in most cases, rheumatic diseases such as systemic lupus erythematosus are recognized as causes of aplastic anemia, with their possible etiological mechanisms being T and B lymphocyte dysfunction and pro-inflammatory cytokines and autoantibody production directed against bone marrow components. In the course of the human immunodeficiency virus infection/acquired immunodeficiency syndrome, the identification of autoantibodies and the occurrence of rheumatic events, in addition to the natural course of systemic lupus erythematosus which is modified by immune changes that are characteristic of human immunodeficiency virus infection/acquired immunodeficiency syndrome, make the diagnosis of systemic lupus erythematosus challenging. This study reports the case of a woman with acquired immunodeficiency syndrome treated with a highly active antiretroviral therapy, who had prolonged cytopenias and hypocellular bone marrow consistent with aplastic anemia. The clinical picture, high autoantibodies titers, and sustained remission of the patient's hematological status through immunosuppression supported the diagnosis of systemic lupus erythematosus-associated aplastic anemia. This is the first report of aplastic anemia concurrent with systemic lupus erythematosus and acquired immunodeficiency syndrome, providing additional evidence that immune dysfunction is a key part of the pathophysiological mechanism of aplastic anemia.
Lopes, V A P; Lourenço, D M R; Guariento, A; Trindade, M A; Avancini, J; Silva, C A
Leprosy is a contagious and chronic systemic granulomatous disease caused by the bacillus Mycobacterium leprae. To our knowledge, no case of leprosy in a childhood-onset systemic lupus erythematosus (c-SLE) patient has been reported. For a period of 31 years, 312 c-SLE patients were followed at the Pediatric Rheumatology Unit of our University Hospital. One of them (0.3%) had tuberculoid leprosy skin lesions during the disease course and is here reported. A 10-year-old boy from Northwest of Brazil was diagnosed with c-SLE based on malar rash, photosensitivity, oral ulcers, lymphopenia, proteinuria, positive antinuclear antibodies, anti-double-stranded DNA, anti-Sm and anti-Ro/SSA autoantibodies. He was treated with prednisone, hydroxychloroquine and intravenous cyclophosphamide, followed by mycophenolate mofetil. At 12-years-old, he presented asymmetric skin lesions characterized by erythematous plaques with elevated external borders and hypochromic center with sensory loss. Peripheral nerve involvement was not evidenced. No history of familial cases of leprosy was reported, although the region where the patient resides is considered to be endemic for leprosy. Skin biopsy revealed a well-defined tuberculoid form. A marked thickening of nerves was observed, often destroyed by granulomas, without evidence of Mycobacterium leprae bacilli. At that time, the SLEDAI-2K score was 4 and he had been receiving prednisone 15 mg/day, hydroxychloroquine 200 mg/day and mycophenolate mofetil 3 g/day. Paucibacillary treatment for leprosy with dapsone and rifampicine was also introduced. In conclusion, we have reported a rare case of leprosy in the course of c-SLE. Leprosy should always be considered in children and adolescents with lupus who present skin abnormalities, particularly with hypoesthesic or anesthesic cutaneous lesions.
Sinicato, Nailú Angélica; Postal, Mariana; Peres, Fernando Augusto; Peliçari, Karina de Oliveira; Marini, Roberto; dos Santos, Allan de Oliveira; Ramos, Celso Dario; Appenzeller, Simone
Background. In systemic lupus erythematosus (SLE), atherosclerosis is attributed to traditional and lupus related risk factors, including metabolic syndrome (MetS), obesity, and inflammation. Objective. To evaluate the association between obesity, measures of body fat content, serum tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6 and -10 levels in childhood-onset SLE (cSLE). Methods. We screened consecutive cSLE patients followed up in the Pediatric Rheumatology Outpatient Clinic of the State University of Campinas. cSLE patients were assessed for disease and damage. Obesity was definite as body mass index (BMI) ≥30 kg/m2. Serum TNF-α, IL-6, and IL-10 levels were measured by ELISA. Dual-energy X-ray absorptiometry was used to determine total fat mass, lean mass, and percent of body fat. Results. We included 52 cSLE patients and 52 controls. cSLE patients had higher serum TNF-α (P = 0.004), IL-6 (P = 0.002), and IL-10 (P < 0.001) levels compared to controls. We observed higher serum TNF-α (P = 0.036) levels in cSLE patients with obesity. An association between serum TNF-α levels and body fat percent (P = 0.046) and total fat mass on trunk region (P = 0.035) was observed. Conclusion. Serum TNF-α levels were associated with obesity and body fat content in cSLE. Our finding suggests that obesity may contribute to the increase of serum TNF-α levels in cSLE. PMID:24741576
Quintanilla-Flores, D L; Hernández-Coria, M I; Elizondo-Riojas, G; Galarza-Delgado, D A; González-González, J; Tamez-Pérez, H E
A thyroid nodule (TN) is a discrete lesion in the thyroid gland radiologically distinct from the adjacent parenchyma, with a prevalence variable depending on the diagnostic method used and the study population. Thyroid disorders have been identified in more than 50% of patients with systemic lupus erythematosus (SLE); however, the prevalence of TN has not been frequently studied. We identified a prevalence of 27% TN in 55 SLE patients > 16 years of age. One-third of TN were >1 cm with radiological features of malignancy. The mean age of patients with TN was 39 ± 11 years, 93% women, and SLE duration 10 ± 6 years. Among patients, we reported family history of cancer in three cases (20%), thyroid disease in one (7%), and autoimmune disease in six (40%). Regarding treatment, 50% of patients with TN were treated with azathioprine vs. 23% of patients without TN (p = 0.02), with an OR of 3.94 (95% CI 1.12-13.84, p = 0.03). As a conclusion a high prevalence of TN in SLE patients was found. Prevalence of TN correlated only with history of azathioprine use. We don't know the long-term implications of our findings; however, a functional and morphological evaluation of the thyroid gland is warranted in all patients with SLE.
Sabharwal, U K; Fong, S; Hoch, S; Cook, R D; Vaughan, J H; Curd, J G
An enzyme linked immunosorbent assay was developed to quantitate antibodies to Sm (anti-Sm) and to measure complement activation by anti-Sm in vitro. Anti-Sm in plasma of patients with systemic lupus erythematosus (SLE) were bound to purified Sm bound to polyvinyl chloride microtitre plates and assayed for bound IgG or IgM using enzyme linked anti-gamma or anti-mu. The activation of C4 by anti-Sm was measured by adding diluted normal human serum (complement) to the wells and quantitating the amount of C4 bound to the well surface using (Fab')2 goat anti-C4 followed by enzyme linked rabbit anti-goat IgG. The plasmas of 12 of 36 patients with SLE contained anti-Sm and all 12 activated complement (complement activating anti-Sm). Twenty-eight plasmas containing anti-Sm from 12 patients with SLE were studied. Ten of the 12 patients had anti-Sm of the IgG class whereas two had anti-Sm of both IgG and IgM classes. The amount of C4 activating anti-Sm correlated significantly with the in vivo activation of C4 measured by rocket immunoelectrophoresis for C4d and C4, suggesting that complement activation by anti-Sm is important in vivo.
Ogawa, Yayoi; Mukai, Masaya; Gotoh, Hideki; Tanaka, Satoshi; Takada, Akio; Takenouchi, Toshinao
We described a case of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE). A-60-year old woman was admitted to our hospital because of fever, disconsciousness, and general fatigue. 32 years ago, she was diagnosed as SLE with Raynaud's phenomenon, rash, photosensitivity, arthritis, lymphocytopenia, and ANA. Her SLE was well controlled with 10 mg predonisolone as a maintance dose until several weeks ago. On admission, severe thrombocytopenia (0.7x10(4)/microl) and other laboratory data revealed microangiopathic hemolytic anemia and renal dysfunction, Immediately after diagnosed as TTP, plasma exchange and corticosteroid therapy started. In spite of the treatment, disconsciousness progressed and systemic convulsion occurred and died 4 days after admission. Autopsied examination revealed diffuse microvascular hyalinized thrombi in heart, kidney, liver, spleen, and pancreas. Some microvascular thrombi were detected in lymph nodes, bone marrow, intestine. Pathological diagnosis of TTP was made on microvascular hyalinized platelet thrombi in organs. Von Willebrand factor-cleaving protease (VWF-CP) activity in plasma on set is less than 0.5 percent of normal and inhibitor for VWF-CP was detected. We here report a valuable case for analysis of pathogenesis in SLE-TTP.
van Vollenhoven, Ronald F
The adrenal steroidal hormone dehydroepiandrosterone (DHEA) has been studied as a potential pharmacological agent in the treatment of the autoimmune disease systemic lupus erythematosus (SLE). Both the endocrine effects (the ability to be converted peripherally to androgenic and oestrogenic sex steroids) and the immunomodulatory effects of DHEA (the production of the Th(1) cytokines, such as IL-2) suggest that this hormone could be of benefit for patients with SLE. During the past decade, five controlled clinical trials and a number of additional observational studies have been performed investigating these possibilities. The results from these studies suggest that 200 mg/day of DHEA for 7 - 12 months decreases corticosteroid requirement for the patients, the frequency of disease flares, has an anti-osteoporotic effect and has an overall beneficial effect on SLE disease activity in female patients. A small study suggested benefits for cognitive function in such patients. The side effects acne and hirsutism were seen relatively frequently (30 - 40% and 10 - 12% of patients, respectively) but in most instances were deemed mild. DHEA treatment resulted in changes in lipid profile and may have endocrine effects, the consequences of which will need to be ascertained through longer-term follow-up studies.
Pons-Estel, Guillermo J; Andreoli, Laura; Scanzi, Francesco; Cervera, Ricard; Tincani, Angela
The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis and pregnancy morbidity in the presence of pathogenic autoantibodies known as antiphospholipid antibodies (aPL). APS may be associated with other diseases, mainly systemic lupus erythematosus (SLE). The presence or absence of SLE might modify the clinical or serological expression of APS. Apart from the classical manifestations, APS patients with associated SLE more frequently display a clinical profile with arthralgias, arthritis, autoimmune hemolytic anemia, livedo reticularis, epilepsy, glomerular thrombosis, and myocardial infarction. The management of patients with SLE and APS/aPL should include an accurate stratification of vascular risk factors. Low dose aspirin and hydroxychloroquine should be considered as primary prophylaxis. In high risk situations, such as surgery, prolonged immobilization, and puerperium, the prophylaxis should be potentiated with low molecular weight heparin. The challenge of treating patients with a previous vascular event (secondary prophylaxis) is the choice of treatment (anti-platelet agents, anticoagulation with vitamin K antagonists or combined therapy) and its duration, based on individual risk stratification and the site of vascular presentation. The role of novel anticoagulants in APS patients is still to be clearly defined. Novel approaches are needed since the prognosis of SLE patients with APS/aPL is still worse than that of SLE patients with negative aPL. The goal for the future is to improve the outcome of these patients by means of early recognition and optimal preventative treatment.
Jones, H W; Ireland, R; Senaldi, G; Wang, F; Khamashta, M; Bellingham, A J; Veerapan, K; Hughes, G R; Vergani, D
Systemic lupus erythematosus (SLE) is highly prevalent in Malaysia, which has a mixed population of Malays, Chinese, and Indians. A quantitative enzyme linked immunosorbent assay (ELISA) was used to determine anticardiolipin antibody (aCL) levels (total immunoglobulin, IgG, and IgM) in 200 patients with SLE (164 Chinese, 26 Malay, and 10 Indian) attending the University Hospital of Kuala Lumpur, Malaysia, and 103 matched controls. Only 33 (16.5%) of the patients had raised aCL levels; 26 had raised IgG aCL, five IgM aCL, and two both IgG and IgM aCL. There was a low prevalence of raised levels of aCL in the population studied, which was seen in conjunction with a rare occurrence of thrombosis. The classical association of high aCL levels with thrombocytopenia and recurrent abortions was noted, though not with cerebral disease. The low prevalence of aCL in this study population of mixed racial origin contrasts with findings in European patients with SLE and lends support to the influence of local factors, be they genetic or environmental, on the clinical manifestations of this disease.
Jang, Min Soo; Park, Jong Bin; Yang, Myeong Hyeon; Jang, Ji Yun; Kim, Joon Hee; Lee, Kang Hoon; Kim, Geun Tae; Hwangbo, Hyun
Degos disease, also referred to as malignant atrophic papulosis, was first described in 1941 by Köhlmeier and was independently described by Degos in 1942. Degos disease is characterized by diffuse, papular skin eruptions with porcelain-white centers and slightly raised erythematous telangiectatic rims associated with bowel infarction. Although the etiology of Degos disease is unknown, autoimmune diseases, coagulation disorders, and vasculitis have all been considered as underlying pathogenic mechanisms. Approximately 15% of Degos disease have a benign course limited to the skin and no history of gastrointestinal or central nervous system (CNS) involvement. A 29-year-old female with history of systemic lupus erythematosus (SLE) presented with a 2-year history of asymptomatic lesions on the dorsum of all fingers and both knees. The patient had only skin lesions and no gastrointestinal or CNS vasculitis symptoms. Her skin lesions were umbilicated, atrophic porcelain-white lesions with a rim of erythema. On the basis of clinical, histologic, and laboratory findings, a diagnosis of Degos-like lesions associated with SLE was made. The patient had been treated for SLE for 7 years. Her treatment regimen was maintained over a 2 month follow-up period, and the skin lesions improved slightly with no development of new lesions. PMID:28392651
Berntsson, Shala Ghaderi; Katsarogiannis, Evangelos; Lourenço, Filipa; Moraes-Fontes, Maria Francisca
Progressive multifocal leukoencephalopathy (PML) caused by reactivation of the JC virus (JCV), a human polyomavirus, occurs in autoimmune disorders, most frequently in systemic lupus erythematosus (SLE). We describe a HIV-negative 34-year-old female with SLE who had been treated with immunosuppressant therapy (IST; steroids and azathioprine) since 2004. In 2011, she developed decreased sensation and weakness of the right hand, followed by vertigo and gait instability. The diagnosis of PML was made on the basis of brain MRI findings (posterior fossa lesions) and JCV isolation from the cerebrospinal fluid (700 copies/ml). IST was immediately discontinued. Cidofovir, mirtazapine, mefloquine and cycles of cytarabine were sequentially added, but there was progressive deterioration with a fatal outcome 1 year after disease onset. This report discusses current therapeutic choices for PML and the importance of early infection screening when SLE patients present with neurological symptoms. In the light of recent reports of PML in SLE patients treated with rituximab or belimumab, we highlight that other IST may just as well be implicated. We conclude that severe lymphopenia was most likely responsible for JCV reactivation in this patient and discuss how effective management of lymphopenia in SLE and PML therapy remains an unmet need.
Kampylafka, E I; Alexopoulos, H; Fouka, P; Moutsopoulos, H M; Dalakas, M C; Tzioufas, A G
We investigated systemic lupus erythematosus (SLE) patients with epilepsy, a major and organic neurological symptom. Our aim was to test patients for the autoimmune epilepsy-associated antibodies anti-GAD, anti-NMDAR, anti-AMPAR1/2, anti-GABABR and anti-VGKC. We tested sera from ten SLE patients with current or previous episodes of epileptic seizures. In addition, sera were tested for staining on primary hippocampal neurons. The patients' clinical and neuroimaging profile, disease activity and accumulated damage scores and therapeutic regimens administered were recorded, and correlations were evaluated. Patients were negative for all anti-neuronal autoantibodies tested, and showed no staining on primary hippocampal cells, which suggests the absence of autoantibodies against neuronal cell surface antigens. Epileptic seizures were all tonic-clonic, and all patients had high disease activity (mean SLE Damage Acticity Index score 19.3 ± 7.3). Six patients had minor or no brain magnetic resonance imaging findings, and three had major findings. 9/10 patients received immunosuppression for 5 ± 4 months, while anti-convulsive treatment was administered to all patients (4.2 ± 3 years). Our results suggest that the majority of SLE-related epileptic seizures cannot be attributed to the action of a single antibody against neuronal antigens. Studies with larger neuropsychiatric SLE populations and stricter inclusion criteria are necessary to verify these findings.
Calebotta, A; Cirocco, A; Giansante, E; Reyes, O
Few cases have been published relating systemic lupus erythematosus (SLE) and pemphigus vulgaris (PV). We describe a patient with this association. A 35-year old woman who started to develop persistent pain and morning stiffness of proximal inter and metacarpo-phalangeal joints. During the following year, the patient recalled the onset of blisters on both legs, face, arms and thorax, as well as erosions appearing on oral mucous membranes. We observed generalized multiple erosions on her trunk and legs, flaccid bullae located on her right thigh and multiple erosions on oral mucous membranes. A skin biopsy reported PV Direct immunofluorescence on the perilesional skin specimen, showed beehive intercellular IgG deposits in the epidermis (+++), suggesting PV; granular discontinuous IgM and C3 deposits in the dermal-epidermal union (+++), suggesting SLE. Direct immunofluorescence of the healthy unexposed skin specimen, reported granular discontinuous IgG deposits in the dermal-epidermal union and beehive intercellular IgG deposits in the lower levels of the epidermis (+++); granular continuous IgM deposits in the dermal-epidermal union (+++). The results of rheumatic studies were obtained as follows: ANA :3 +, Anti-DNA, Anti-Sm, Anti-Ro and Anti-La :4 + . The definite diagnosis was PVand SLE. Treatment with 50 mg of prednisone daily with good evolution.
Andrade, C; Mendonça, T; Farinha, F; Correia, J; Marinho, A; Almeida, I; Vasconcelos, C
Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%.
Arnaud, L; Mathian, A; Bruckert, E; Amoura, Z
Multiple factors contribute to the increased cardiovascular risk observed in patients with systemic lupus erythematosus (SLE). Among these are the so-called classical cardiovascular risk factors, the disease itself through its activity, treatments, and complications, and the thrombotic risk due to antiphospholipid antibodies (aPL). Observational studies suggest that most classical cardiovascular risk factors are observed more frequently in SLE patients than in the general population, and that these are insufficient to explain the increased cardiovascular risk observed in most studies. Given this high risk, adequate management of cardiovascular risk factors should be recommended in SLE patients. Paradoxically, the benefit due to the anti-inflammatory properties of treatments such as corticosteroids may exceed, in certain cases, their pro-atherogenic effect. Importantly, the tools that were developed for the estimation of cardiovascular risk at the individual level among the general population cannot be used reliably in SLE patients, as these tools appear to underestimate the true cardiovascular risk. The adequate indications and targets of cardiovascular treatments are therefore not fully known in SLE. A better understanding of the determinants of the cardiovascular risk in SLE will allow the identification and more tailored management of these high-risk patients.
Lang, Tali; Foote, Andrew; Lee, Jacinta P W; Morand, Eric F; Harris, James
Macrophage migration Inhibitory factor (MIF) was one of the earliest pro-inflammatory cytokines to be identified. Increasing interest in this cytokine in recent decades has followed the cloning of human MIF and the generation of Mif(-/-) mice. Deepening understanding of signaling pathways utilized by MIF and putative receptor mechanisms have followed. MIF is distinct from all other cytokines by virtue of its unique induction by and counter regulation of glucocorticoids (GCs). MIF is further differentiated from other cytokines by its structural homology to specific tautomerase and isomerase enzymes and correlative in vitro enzymatic functions. The role of MIF in immune and inflammatory states, including a range of human autoimmune diseases, is now well established, as are the relationships between MIF polymorphisms and a number of inflammatory diseases. Here, we review the known pleiotropic activities of MIF, in addition to novel functions of MIF in processes including autophagy and autophagic cell death. In addition, recent developments in the understanding of the role of MIF in systemic lupus erythematosus (SLE) are reviewed. Finally, we discuss the potential application of anti-MIF strategies to treat human diseases such as SLE, which will require a comprehensive understanding of the unique and complex activities of this ubiquitously expressed cytokine.
Weidenbusch, Marc; Kulkarni, Onkar P; Anders, Hans-Joachim
Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease. This is why targeting the innate immune system offers an additional means of treating SLE. First trials assessing the efficacy of anti-type I interferon (IFN) therapy or modulators of pattern recognition receptor (PRR) signalling have been attempted. In this review, we summarize the available evidence on the role of several distinct innate immune elements, especially neutrophils and dendritic cells as well as the IFN system, as well as specific innate PRRs along with their signalling pathways. Finally, we highlight recent clinical trials in SLE addressing one or more of the aforementioned components of the innate immune system.
Alarcón-Segovia, D; Abud-Mendoza, C; Diaz-Jouanen, E; Iglesias, A; De los Reyes, V; Hernández-Ortiz, J
Forty-one of 858 patients with systemic lupus erythematosus (SLE) developed clinical deformity of their hands. This deformity was clinically and radiologically different from that found in 40 patients with classical or definite rheumatoid arthritis (RA), and tended to appear early in the course of disease. Characteristics of this arthropathy included nonerosive carpal collapse; exceptional erosion of the styloid processes; Z deformity of the thumb; nonerosive ulnar deviation and subluxation of MCP joints; parametacarpophalangeal joint hook formation; scant and asymmetric joint erosions; and swan neck deformity of the fingers. Most of these changes seemed to be due to involvement of the ligaments rather than to the destructive effect of synovitis. Patients with SLE with deforming arthropathy had a higher frequency of rheumatoid factor positivity, sicca symptoms and antibodies to native DNA, whereas they had lower incidence of facial rash and photosensitivity than did those without. Other manifestations did not differ. We propose that most patients with SLE with deforming arthropathy belong to a subset of SLE rather than representing the coexistence of SLE and RA.
Han, Fei; Zhong, Ding-Rong; Hao, Hong-Lin; Kong, Wei-Ze; Zhu, Yi-Cheng; Guan, Hong-Zhi; Cui, Li-Ying
Abstract Background: Hypertrophic pachymeningitis (HP) is a chronic disease characterized by inflammatory hypertrophy and fibrosis of dura mater. It can be divided into cranial and spinal forms depending on the location of the lesion. HP involving 2 separate sites simultaneously is quite uncommon. Case summary: This study presents a case of a 49-year-old woman with pathologically confirmed cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus (SLE), which is a rare etiology of HP. She experienced persistent numbness and pain of the left lower limb, followed by headache and seizures. In laboratory tests, levels of erythrocyte sedimentation rate and C-reactive protein were elevated, and antinuclear antibodies and anti–double-strand deoxyribonucleic acid (DNA) antibodies were detected. Magnetic resonance imaging revealed dural thickening with homogenous gadolinium enhancement both at lumbosacral level and over cerebral convexities. Histology suggested chronic inflammation in spinal dura mater with extensive fibrosis, dense lymphoplasmacytic infiltrate, and focal vasculitis. Treatment with corticosteroids and cyclophosphamide was started with significant clinical and radiological improvement. Conclusion: HP is etiologically heterogeneous. Despite its rarity, SLE should be considered in the differential diagnosis of HP. Early recognition and therapy may provide an optimal outcome. PMID:27684799
Shimizu, T; Nishinarita, S; Son, K; Tomita, Y; Yoshihiro; Matsukawa; Kitamura, N; Horie, T; Baba, M; Hiranuma, M
We described a 37-year-old man with Crohn's disease (CD) resembling systemic lupus erythematosus (SLE) at his disease onset. He was admitted to the municiple Akiru Hospital in October 1986 by fever, aphtous oral ulcerations, sore throat and polyarthralgia. Hematologic examination showed leukocytopenia, lymphocytopenia, positive tests for antinuclear antibody, anti-DNA antibody and LE cell phenomenon. He has had episodes of convulsion and conciousness loss of unknown etiology when he was 17 years old. The diagnosis of SLE was made, and oral medication of prednisolone was started. Several weeks later, most of symptoms and autoantibodies disappeared, although the oral aphtous ulcerations and leukocytopenia remained. In May 1987, he admitted to the other hospital because of bloody vomiting. Endoscopic examination showed the esophagial ulceration, and histology of biopsied-specimen was nonspecific esophagitis. The combination of prednisolone and oral cyclophosphamide or methotrexate was employed thereafter. However, the leukocytopenia, oral aphtous ulceration and esophagial ulceration continued in spite of these treatments. All the immunosuppressive treatment was stopped at March 1992. In October 1995, he admitted to our hospital because of body weight loss and continuous diarrhea with occasional bloody stool. Barium enema and endoscopic examination of the colon revealed the findings compatible with CD. The patient responded favorably to methylprednisolone pulse therapy followed by oral sulphasalazine. This case indicated that cases with inflammatory bowel diseases like CD could show similar clinical signs and symptoms to SLE, and in some cases of CD might satisfied the classification of criteria for SLE.
Martin, M; Guffroy, A; Argemi, X; Martin, T
Lymphopenia is frequent in systemic lupus erythematosus (SLE) and profound (<500/mm(3)) in 10% of cases. T lymphocytes, especially CD4+, are more affected than B cells. The pathophysiological mechanisms are complex, involving lymphocytotoxic antibodies, excess of apoptosis, increased susceptibility of T cells to complement mediated cytolysis, as well as lymphopoiesis impairment and lymphocyte sequestration. Lymphopenia in SLE is independent from other cytopenia and immunosuppressive drug regiments, and associated with disease activity, risk of flare and damage scores. Infectious risk is mostly bacterial, and lymphopenia <1 G/L is an independent risk factor for severe bacterial infections occurrence. The T cellular deficiency is associated with less control of viral replication, but severe and symptomatic infections are scarce. Although exceptional in SLE, pneumocystis is more severe than in HIV+ patients, and risk of progressive multifocal leukoencephalopathy seems increased compared to other rheumatic diseases. To date, there are no specific recommendations for management of SLE with lymphopenia. Infectious prophylaxis should remain exceptional and discussed on a case by case basis. Further studies are needed to assess the clinical characteristics and outcomes of patients with SLE and profound lymphopenia (<500/mm(3)), which are probably a subset of SLE with primary immunodeficiency and require specific management.
Moori, M; Ghafoori, H; Sariri, R
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody-directed self-antigens, immune complex formation and immune deregulation, resulting in damage to essentially all the organs. SLE is associated with the increased production of free radicals. Increase in free radicals or impaired antioxidant defense system in SLE causes oxidative stress. Considering that saliva could be a reflection of the state of health, the purpose of this study was to evaluate some antioxidants in the saliva and serum of patients with SLE and compare these with healthy individuals. This could help us in obtaining a possible marker in saliva in the future. During the course of the practical part of the project, 30 patients with SLE and 30 healthy controls were investigated. After centrifugation of un-stimulated saliva and blood samples, they were examined using spectrophotometric methods and the results were analyzed by statistical software. According to the results, concentrations of malondialdehyde, uric acid and total antioxidants were significantly increased but the level of reduced glutathion was reduced significantly in the saliva and serum of SLE patients as compared to controls. It is therefore suggested that antioxidant power is impaired in saliva and serum of SLE patients. As there was a positive correlation between the antioxidant level of saliva and blood serum, the antioxidant status of saliva could be an indicator of serum antioxidants.
Napirei, Markus; Gültekin, Aykut; Kloeckl, Thomas; Möröy, Tarik; Frostegård, Johan; Mannherz, Hans Georg
Systemic lupus-erythematosus is an auto-immune-disease characterized by pathogenic anti-nuclear auto-antibodies. These form immune-complexes that after deposition at basal membranes at various locations initiate inflammatory reactions. There is a clear genetic and gender predisposition (females are affected 10 times more frequently), but also infectious agents and further environmental factors have been shown to be causative for the initiation of the disease. It has been suggested that the auto-antibodies arise after release and/or inefficient removal of nuclear components during cell death (defective cellular "waste disposal" theory). So far, increased apoptotic cell death has been made responsible, but recent data suggest that defective cellular waste disposal during/after necrosis may also lead to the release and prolonged exposure of nuclear components. Here, we concentrate on chromatin disposal during necrosis and the involvement of Deoxyribonuclease 1 in this process with respect to its possible role in the prevention of anti-nuclear auto-immunity.
Vo, An; Volpe, Bruce T; Tang, Chris C; Schiffer, Wynne K; Kowal, Czeslawa; Huerta, Patricio T; Uluğ, Aziz M; Dewey, Stephen L; Eidelberg, David; Diamond, Betty
Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb- mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb- mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects.
Haze, Masaya; Kobayashi, Takatoshi; Kakurai, Keigo; Shoda, Hiromi; Takai, Nanae; Takeda, Sayako; Tada, Rei; Maruyama, Kouichi; Kida, Teruyo; Ikeda, Tsunehiko
Purpose The purpose of this study was to report the case of a patient who underwent vitrectomy for bilateral rhegmatogenous retinal detachment caused by cytomegalovirus (CMV) retinitis while undergoing steroid and immunosuppressant therapy for systemic lupus erythematosus (SLE). Case Report We report on a 29-year-old female who was undergoing steroids and immunosuppressants treatment for SLE at Osaka Medical College Hospital, Takatsuki City, Japan. Examination of the patient due to prolonged and worsening diarrhea revealed positive test results for C7-HRP, and she was diagnosed with CMV colitis. She was subsequently admitted to the hospital and started on intravenous ganciclovir for treatment. Approximately 1.5 months later, her primary complaint was deterioration of the upper visual field in her left eye, and she was then referred to the Department of Ophthalmology. Numerous granular exudative spots were found around the lower retinal area of her left eye with retinal breaks that had developed in an area of retinal necrosis that resulted in retinal detachment. After time was allowed for the patient's general condition to improve, a vitrectomy was performed on that eye. The patient subsequently developed a similar retinal detachment in her right eye, for which she underwent a vitrectomy. Although the patient required multiple surgeries on both eyes, her retinas currently remain reattached and the inflammation has subsided. Conclusion The findings of this study show that strict attention must be paid to SLE patients on immunosuppressive therapy due to the possible association of CMV retinitis. PMID:27462259
Vo, An; Volpe, Bruce T; Tang, Chris C; Schiffer, Wynne K; Kowal, Czeslawa; Huerta, Patricio T; Uluğ, Aziz M; Dewey, Stephen L; Eidelberg, David; Diamond, Betty
Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood–brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb− mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb− mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects. PMID:24824914
Bhari, N; Khaitan, B K; Gupta, P; Kumar, T; Srivastava, A
Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus erythematosus that runs an indolent course. The rare complications of DLE include scarring, mutilation, non-healing ulceration, cicatricial alopecia and malignancy. DLE progresses to systemic lupus erythematosus (SLE) in around 5% of localized cases and 22% of generalized cases. We report a case of DLE, presenting with a six-month history of ulcerated fungating plaques and small crusted nodules superimposed on DLE plaques over both the forearms. Two weeks prior to the presentation, maggots were also noticed on these plaques. Skin biopsies from these lesions were suggestive of squamous cell carcinoma (SCC) and keratoacanthoma. A wide surgical excision of the tumor followed by partial split-thickness skin grafting was performed with complete healing of the lesions. No recurrence has been noted 18 months from follow-up.
Calderaro, Débora Cerqueira; Ferreira, Gilda Aparecida
Systemic lupus erythematosus is an autoimmune systemic disease that commonly affects the respiratory system. Shrinking lung syndrome is a rare respiratory complication associated with systemic lupus erythematosus. Patients present with dyspnea alone or associated with chest pain and orthopnea, lung volume reduction with no parenchymal abnormalities and a restrictive ventilatory defect on pulmonary function tests. The pathogenesis, treatment, and prognosis of shrinking lung syndrome remain controversial. This study describes the clinical features, investigations, and outcome of a series of four patients with systemic lupus erythematosus and shrinking lung syndrome regularly followed on Rheumatology Service of the Clinics Hospital of the Federal University of Minas Gerais, Brazil, with a brief review of literature. It emphasizes that, despite prognosis of shrinking lung syndrome has been reported as good, it may cause severe functional pulmonary abnormalities and must be treated promptly and aggressively in order to, at least, stabilize pulmonary function tests.
Kopsachilis, Nikolaos; Tsaousis, Konstantinos T; Tourtas, Theofilos; Tsinopoulos, Ioannis T
Discoid lupus erythematosus is a common form of chronic cutaneous lupus erythematosus, an autoimmune inflammatory disease that affects most of the human organs, including the skin, kidneys, joints, heart and lungs. We describe a 45-year-old Caucasian woman with a 21-year history of eyelid redness and irritation. She had been treated with antibiotics, steroids and eyelid hygiene, a therapy that resulted to brief periods of relief of symptoms. In the last 12 months, her symptoms seemed to have exacerbated, despite the administration of a local therapy. Following biopsy, a diagnosis of discoid lupus erythematosus was confirmed and the patient was placed on a systemic therapy with hydroxychloroquine. The eyelid inflammation decreased but severe scarring of the marginal eyelids persisted, resulting in cicatricial ectropion.
Sinicato, N A; Peres, F A; de Oliveira Peliçari, K; de Oliveira Santos, A; Ramos, C D; Marini, R; Appenzeller, S
Objective We aimed to compare estimates of body fat content with respect to their ability to predict the percentage of body fat, confirmed by dual-energy X-ray absorptiometry scans in childhood-onset systemic lupus erythematosus. Methods We included 64 consecutive childhood-onset systemic lupus erythematosus patients and 64 healthy age and sex-matched controls in a cross-sectional study. Anthropometric data, body mass index and body adiposity index were calculated for all subjects. Childhood-onset systemic lupus erythematosus patients were further assessed for clinical and laboratory childhood-onset systemic lupus erythematosus manifestations and fat mass, lean mass and percentage of body fat evaluated by dual-energy X-ray absorptiometry. Results Elevated waist/hip ratio was observed in childhood-onset systemic lupus erythematosus patients when compared to controls ( p < 0.001). We did not find differences between body mass index and body adiposity index classification in childhood-onset systemic lupus erythematosus patients and controls. Using dual-energy X-ray absorptiometry as gold standard we observed that all indirect estimates of body fat were correlated with whole body fat mass. We observed a correlation between height and cumulative corticosteroid dose adjusted by weight ( r = 0.429, p = 0.005) in childhood-onset systemic lupus erythematosus. On whole body analysis we observed a correlation between lean mass and ACR Damage Index scores ( r = -0.395; p = 0.019); percentage of body fat and adjusted Systemic Lupus Erythematosus Disease Activity Index ( r = 0.402; p = 0.008), disease duration ( r = -0.370; p = 0.012). On trunk analysis we observed a correlation between lean mass and ACR Damage Index ( r = -0.319; p = 0.042); percentage of body fat with adjusted Systemic Lupus Erythematosus Disease Activity Index ( r = 0.402; p = 0.005), disease duration ( r = -0.408; p = 0.005). Conclusions This is the
Chawki, Sylvain; Aouizerate, Jessie; Trad, Selim; Prinseau, Jacques; Hanslik, Thomas
Abstract Introduction: Sudden sensorineural hearing loss is an unusual presenting clinical feature of systemic lupus erythematosus. Case report: We report the case of a young woman who was admitted to hospital for sudden sensorineural hearing loss and hemophagocytic syndrome which was attributed to systemic lupus erythematosus on the basis of specific renal involvement, thrombocytopenia, and consistent autoantibodies. Favorable outcome was obtained on high-dose corticosteroids, and the hearing fully recovered. Discussion: Sudden sensorineural hearing loss in systemic lupus erythematosus is seemingly more frequently associated with severe systemic involvement and antiphospholipid antibodies may be present. Although management remains empirical, the high risk of permanent hearing impairment seems to justify emergency treatment with high-dose corticosteroids. When the clinical and laboratory criteria of antiphospholipid syndrome are met, antiplatelets agents or anticoagulation therapy shall be considered. PMID:27603334
Dasgupta, Subhajit; Dasgupta, Shaoni
Systemic lupus erythematosus (lupus) is a female predominant autoimmune disease. The auto reactive B cells and T helper cells together are known to develop self-reactive immune responses in different tissues like kidney, bone, cardiovascular and central nervous system. Progression of disease is associated with deposition of immune complex which initiates tissue damage. The therapy for lupus still includes corticosteroids to reduce allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit in lupus therapy. The prospect of B cell depletion by CD20 targeted monoclonal antibody Rituximab has been demonstrated in lupus patients. The CD52 specific monoclonal antibody Alemtuzumab is another proposition for lupus therapy. The drug Belimumab inhibits B cell activation by altering BAFF/APRIL signal cascade. Recent discovery of the CD22 targeted Epratuzumab also shows therapeutic prospect. The researches on new generation drugs for autoimmune lupus include search for inhibitors of CD40-CD40Ligand interactions, CD86 activation, selective modulation of complement cascades. The choice of inhibitors of transcription factor NF-κBp65 and selective modulators for estrogen receptor alpha are proposed areas of lupus drug discovery research. Keeping a close eye on the mechanisms of disease onset, a comprehensive view is provided on recent therapy of systemic lupus erythematosus.
Hidalgo-Tenorio, C; Sabio-Sánchez, J M; Tercedor-Sánchez, J; León-Ruíz, L; Pérez-Alvarez, F; Jiménez-Alonso, J
Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many organs in the body. Skin manifestations are frequent and sometimes vesiculobullous lesions may apper such as in bullous lupus erythematosus. SLE may also be exceptionally associated with other blistering diseases such as pemphigus vulgaris (PV). We describe the case of a male diagnosed as having SLE, who one year later developed PV. Only three cases (all in women) of SLE associated with PV have been reported in the literature. Our case is noteworthy in that this exceptional association developed in a middle-aged male.
Criscov, Geanina Irina; Rugină, Aurica; Stana, A B; Azoicăi, Alice Nicoleta; Moraru, Eovelina
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by auto antibodies directed against self-antigens, immune complex formation and immune deregulations and may affect joints, skin, kidneys, heart, lungs, nervous system, and immune system. The onset can be variable and the symptoms can occur for many years. Parotitis as the initial manifestation of systemic lupus erythematosus (SLE) is a rare condition and can be associated with Sjogren's syndrome. In this article we present the case of a young patient who was diagnosed with Sjogren's syndrome retrospectively, after she met the criteria for SLE.
The Author remarks the interstitial lung involvement in systemic lupus erythematosus. This secondary respiratory manifestation is infrequent as well as the consequent pulmonary hypertension making it possible to miss or delay the diagnosis. Therefore the interdisciplinary evaluation of the multisystemic disease lupus erythematosus needs. In this context the role of the pneumologists is relevant for the global treatment of the patients with LES in particular as concerns the early detection of the clinical and functional respiratory symptoms as well as the appropriate treatment plan within their specialistic competence.
Calderaro, Débora Cerqueira; Ferreira, Gilda Aparecida; de Mendonça, Santuza Maria Souza; Corrêa, Jôice Dias; Santos, Fabrícia Xavier; Sanção, João Guilherme Capinam; da Silva, Tarcília Aparecida; Teixeira, Antônio Lúcio
Periodontal disease results from the interaction between pathogenic bacteria that colonize supragingival and subgingival biofilms and the host, triggering an inflammatory response, with systemic effects leading to immune-mediated destruction of the attachment apparatus and loss of supporting alveolar bone. Immunological pathways and predisposing genetic factors common to periodontal disease and rheumatic diseases, including systemic lupus erythematosus, have been described. Case reports have suggested greater severity of periodontal disease in patients with systemic lupus erythematosus. However, studies evaluating the influence of the treatment of one disease on the clinical and laboratory manifestations of the other have yielded conflicting results.
Panchenko, O N; Miagkova, M A; Kiselev, I P; Abramenko, T V
Serum levels of autoantibodies to endogenous bioregulators (prostaglandin F2 alpha, angiotensin II, epinephrine, bovine serum albumin, dinitrophenol) were measured in patients with systemic and integumental lupus erythematosus and donors and the diagnostic significance of deviations of these levels from the norm was evaluated. A total of 75 patients with lupus erythematosus aged 19-54 years with disease lasting for 0.5 to 18 months were examined. Significant differences between patients and donors were observed as regards virtually all parameters except IgG to angiotensin II.
Sarkar, Piyabi; Basu, Keya; Mallick (Sinha), Mamata Guha
Histoplasmosis is a systemic fungal infection caused by dimorphic fungus, Histoplasma capsulatum. Immunocompetent individuals usually have self-limiting or localized disease whereas immunocompromised individuals develop disseminated disease. The occurrence of progressive disseminated histoplasmosis in juvenile systemic lupus erythematosus is extremely rare with only one reported case in literature showing such association. Therefore, we report a case of severe opportunistic fungal infection caused by Histoplasma in a 13-year-old girl who was diagnosed with juvenile lupus erythematosus, subsequently developed septic shock and died of the disease despite of aggressive antifungal therapy. PMID:27904204
Reyes, Hans A; Cativo, Eder H; Sy, Alexander M
Hepatitis C infection and its treatment have been associated with extrahepatic manifestations, including different skin conditions. Over the past decades, a greater number of drugs have been implicated as triggers for drug-induced subacute cutaneous lupus erythematosus. We report a case of a 42-year-old Hispanic man who developed a forehead violaceous rash during treatment with pegylated interferon alpha-2a as part of his therapy against hepatitis C infection that subsequently resulted to be subacute cutaneous lupus erythematosus. The skin lesion improved with discontinuation of medication and some topic therapy.
Ghodke-Puranik, Yogita; Niewold, Timothy B
Genetic studies of systemic lupus erythematosus (SLE) have been successful, identifying numerous risk factors for human disease. While the list is not yet complete, it is clear that important immune system pathways are represented, one of which being type I interferon (IFN). Circulating type I IFN levels are high in SLE patients and this IFN pathway activation is heritable in families with SLE. We summarize our current understanding of the genetics of the type I IFN pathway in SLE, with an emphasis on studies that demonstrate an impact of the SLE-risk alleles upon type I IFN pathway activation in SLE patients. These studies illustrate that variations in type I IFN pathway genes represent a common genetic feature of SLE. By understanding the genetic regulation of type I IFN, we may be able to intervene in a more personalized fashion, based upon the molecular dysregulation present in a given individual. PMID:24416080
Tse, J R; Schwab, K E; McMahon, M; Simon, W
Diffuse alveolar hemorrhage (DAH) is a rare manifestation of systemic lupus erythematosus (SLE) and is associated with high mortality rates. Treatment typically consists of aggressive immunosuppression with pulse-dose steroids, cyclophosphamide, and plasma exchange therapy. Mortality rates remain high despite use of multiple medical therapies. We present a case of recurrent DAH in a 52-year-old female with SLE after a deceased donor renal transplant who was successfully treated with rituximab. Our report highlights the pathophysiologic importance of B-cell-mediated immunosuppression in SLE-associated DAH and suggests that rituximab may represent a viable alternative to cyclophosphamide in the treatment of this disease. We also review eight other reported cases of rituximab use in SLE-associated DAH.
Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to be effective in transplant patients. It is also efficacious in the management of lupus nephritis and useful in the treatment of autoimmune conditions because its mechanisms of action target T- and B- lymphocytes, leading to suppression of the cell-mediated immune response and antibody formation. MMF has been used successfully to treat immune-mediated conditions like myasthenia gravis, autoimmune hepatitis and immune cytopenias. However, the conditions for its optimal use for non-renal manifestations (e.g., hematological, neuropsychiatric, myocardial, pulmonary or cutaneous symptoms) in lupus patients are unclear. There have yet to be any randomized, controlled trials to guide the optimal dose and duration of MMF treatment in such situations. MMF is well tolerated and safe to use, although there are reports of serious adverse effects including urticaria, myopathy, Epstein-Barr virus-associated B-cell lymphoma, cytomegalovirus infection and disseminated varicella zoster infection. Immunosuppressive treatment with MMF and supportive care over the past few decades have led to improved clinical outcomes in patients with severe lupus nephritis. A favorable long-term prognosis can be ensured provided that effective treatment is instituted early, before irreversible renal parenchymal damage occurs. Another area of concern for patients is the increased cost of long-term MMF use.
JI, CAIHONG; YU, XING; WANG, YONG; SHI, LUFENG
Intestinal pseudo-obstruction (IpsO) and acute lupus pneumonitis (ALP) are uncommon severe complications of systemic lupus erythematosus (SLE). The present study reports the case of a 26-year-old female who presented with abdominal pain, nausea and vomiting as initial symptoms. Computed tomography (CT) scanning revealed the jejunal wall was thickened and streaky, mimicking the presentation of intestinal obstruction. Following emergency surgery, the patient's general condition was aggravated, with evident limb erythematous rashes. A series of laboratory examinations revealed SLE, and combined with patient's medical history IpsO was diagnosed, with a disease Activity Index score of 10. During the therapeutic period, high fever, dyspnea and oxygen saturation (SaO2) reductions were detected, and CT scans indicated lung infiltration, excluding other causes through a comprehensive infectious work-up and a bronchoalveolar lavage examination. ALP was confirmed and treated with high-dose methylprednisolone and gamma globulin supplement. The patient responded well and was discharged in 2 weeks. In the one-year tapering period and after stopping corticosteroids, the patient recovered well with no relapse detected. In conclusion, the manifestation of IpsO in SLE is rare and represents a challenge for the surgeon to establish the correct diagnosis and avoid inappropriate surgical intervention. ALP may be the consequence of emergency surgery, and immediate high-dose glucocorticoid therapy is recommended. PMID:27347044
Rubin, R L; Teodorescu, M; Beutner, E H; Plunkett, R W
The immunofluorescence antinuclear antibody (ANA) test has been widely used to monitor autoimmune disease, but its value for diagnostic purposes is compromised by low specificity and high prevalence in disease-free individuals. The capacity of autoantibodies to fix serum complement proteins when bound to antigen is an important effector function because this property is associated with acute and chronic inflammatory processes. The current study evaluates the complement-fixing properties of antinuclear antibodies (CANA) in three well-defined and clinically-related patient groups: systemic lupus erythematosus (SLE), drug-induced lupus (DIL) and drug-induced autoimmunity (DIA). Of 20 patients diagnosed with SLE, 90% displayed complement-fixing ANA while this feature was present in only two of 18 patients with DIL and no patients with DIA without associated disease even though the mean ANA titres were similar among these patient groups. CANA was significantly correlated with anti-Sm activity. Because SLE but not DIL or DIA can be a life-threatening disease associated with complement consumption in vivo, these results demonstrate that measurement of CANA is a diagnostically useful tool and may have immunopathologic implications.
Xue, Jing; Yang, Jiali; Yang, Lijuan; Zhou, Shaolan; Ji, Chen; Wang, Xuemei; Yu, Nan
An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p < 0.0001); in particular the serum DKK-1 concentration was even higher in LN-SLE patients relative to non-LN SLE subjects (p < 0.0001). Intriguingly, concentrations of above examined proteins in SLE patients showed no correlation between serum and urine. Moreover, a combination of DKK-1 with anti-dsDNA and/or levels of complement C3 and C4 could not increase the specificity and/or sensitivity for identification of patients with LN diseases, but both ROC curve and multiple-factor nonconditional logistic regression analysis showed that serum DKK-1 was considered better positive biomarker for identification of LN in SLE patients. These results imply that serum and/or urine DKK-1 may be a valuable and independent biomarker for identification of SLE patients with LN. PMID:28373995
González, Luis A; Muñoz, Carolina; Restrepo, Mauricio; Vanegas, Adriana Lucía; Vásquez, Gloria
Patients with systemic lupus erythematosus (SLE) have a higher incidence rate of tuberculosis and a more frequent extrapulmonary involvement than the general population. We present 2 SLE patients who developed gastrointestinal tuberculosis complicated with intestinal perforation, a rare but serious complication that could be confused with lupus-associated intestinal vasculitis. Opportunistic infections such as tuberculosis must be suspected in SLE patients with abdominal symptoms on immunosuppressive therapy because its early recognition could prevent catastrophic complications such as intestinal perforation and subsequent peritonitis.
Mozaffarian, Neelufar; Lobosco, Steve; Lu, Peng; Roughley, Adam; Alperovich, Gabriela
Purpose Patient satisfaction with disease control of systemic lupus erythematosus (SLE) is an important component of medical management. This analysis evaluated patient and physician satisfaction with disease control of SLE, factors associated with satisfaction/dissatisfaction, and the degree of physician–patient concordance of these parameters. Patients and methods Data were extracted from the US Adelphi Real World Lupus Disease Specific Programme®, a cross-sectional survey of 50 rheumatologists, 25 nephrologists, and their patients with non-nephritis SLE (NNSLE) or lupus nephritis (LN). Results Physicians reported moderate or severe disease activity in 25.0% of patients with NNSLE and in 50.5% of patients with LN, and were satisfied with disease control in 78.6% (132/168) and 73.8% (152/206) of patients, respectively. For patients, 75.8% (75/99) with NNSLE were satisfied with their current treatment, compared with 65.5% (74/113) with LN. Physician–patient agreement (70.7%) on the level of satisfaction was “slight” (kappa =0.1445) for NNSLE; patients were more frequently dissatisfied than physicians with regard to joint tenderness, fatigue, anxiety, pain on movement, malar rash, and photosensitivity. Physician–patient agreement (71.4%) on the level of satisfaction was “fair” (kappa =0.3695) for LN; patients expressed greater dissatisfaction than physicians for headache, photosensitivity, and anxiety, whereas physicians were more dissatisfied with regard to joint swelling, kidney function, and blood pressure control. In general, patients with NNSLE or LN who were dissatisfied (or whose physicians were dissatisfied) were more likely to have joint swelling, joint stiffness, malar rash, hair loss, depression, and fatigue, have moderate or severe disease, or to be currently experiencing disease flare. Conclusion These data highlight the patient and physician dissatisfaction with real-world disease control of SLE. PMID:27784995
Monov, Simeon; Hristova, Ruska; Dacheva, Rositza; Toncheva, Reni; Shumnalieva, Russka; Shoumnalieva-Ivanova, Viara; Monova, Daniela
Abstract Rationale: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production, complement activation, and deposition of immune complexes in tissues and organs. SLE can involve any region of the visual system. Although ocular manifestations are not part of the classification criteria for SLE, they can be observed in up to one-third of the patients with SLE. They are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with active generalized disease. Due to its low frequency, we report a case of acute necrotizing retinal vasculitis as onset of SLE. Patient concerns and diagnosis: A 25-year-old white female was referred to the rheumatology clinic with gradually and rapid deterioration of the vision due to abnormal vessel permeability in the right fundus with edema along the vessels, occlusion of arterial branches in the middle periphery with leakage of the dye in these areas and indentical but less prominent changes with cotton wool spots in the papillomacular area and extensive hemorrhages in the left eye. The onset of malar rash, arthralgias and positive antinuclear, anti-double stranded DNA, anti-ribosomal P and anti-β2 glycoprotein I antibodies with decreased C4 complement levels, as well as the positive lupus-band test confirmed the diagnosis of SLE. Interventions: Aggressive immunomodulating therapy with high-dose methylprednisolone, intravenous immunoglobulin, and cyclophosphamide was used for suppression of the disease activity followed by azathioprine as maintaince therapy. Outcomes: Substantial improvement and partial resorption of the vasculitic changes, including central retinal artery and vein, was achieved prominently in the left eye. The study was conducted in accordance with the Declaration of Helsinki and written informed consent was obtained from the patient. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary
Xianbin, Wang; Mingyu, Wang; Dong, Xu; Huiying, Li; Yan, Xu; Fengchun, Zhang; Xiaofeng, Zeng
Abstract This article aims to analyze the frequency and clinical characteristics of peripheral neuropathy (PN) in patients with systemic lupus erythematosus (SLE). A total of 4924 SLE patients admitted to the Peking Union Medical College Hospital, Beijing, China, from January 1995 to September 2013 were included in this retrospective analysis. The individuals designated as control patients were selected from the pool of SLE patients without PN using the systematic sampling method of 1:2 during the same time. The prevalence of SLE-associated PN (SLE-PN) in SLE patients was 1.5% (73/4924). Seventy-nine cases of PN affected 73 patients and 6 of these patients (8.2%) presented with 2 types of PN. Among the 7 types of PN, polyneuropathy was the most frequent and was diagnosed in 47 cases (59.5%); the remaining patients suffered from mononeuropathy (13.9%), cranial neuropathy (12.7%), myasthenia gravis (10.1%), autonomic neuropathy (2.5%), or acute inflammatory demyelinating polyradiculoneuropathy (1.3%). Five patients developed PN before the onset of SLE (3 out of 5 patients had myasthenia gravis). The most common PN-related symptoms were myasthenia and numbness (50.6%), followed by pain in affected regions (35.9%). PN symptoms were relieved in a majority of the patients (76.7%) after treatment. Compared with non-SLE-PN patients, patients with SLE-PN had a higher frequency of fever (65.8% vs 45.9%, P < 0.01), mucocutaneous involvement (73.9% vs 36.3%, P < 0.01), arthritis (42.5% vs 28.1%, P < 0.05), myositis (17.8% vs 5.5%, P < 0.01), and central nervous system involvement (38.4% vs 21.9%, P < 0.05) as well as being positive for the anti-Sm antibody (31.4% vs 18.8%), immunoglobulin G (IgG) elevation (53.6% vs 37.1%, P < 0.01), and reduction in complement 3 (54.8% vs 36.9%, P < 0.05). A statistically significant difference was found between the Systemic Lupus Erythematosus Disease Activity Index scores in SLE-PN patients compared with the non
Victorio-Navarra, S T; Dy, E E; Arroyo, C G; Torralba, T P
A retrospective review of the clinical records of 54 patients with systemic lupus erythematosus (SLE) and documented tuberculosis (TB) infection seen at the University of Santo Tomas Hospital was accomplished. There were 53 women and one man, with a mean age of 32.2 +/- 10 years and a total of 57 TB occurrences. Pulmonary involvement was recorded in 42 (74%): upper lungfield in 25, mid to lower lungfield in 7, and miliary pattern or diffuse infiltrates in 10. TB arthritis was noted in 8, osteomyelitis in 4, and soft tissue abscesses in 4. Central nervous system involvement consisted of brain abscesses (tuberculomas) in two and meningitis in one. Two patients each had TB lymphadenitis, genitourinary TB, ileocecal TB, and TB peritonitis. Hepatobiliary and cutaneous TB occurred in one patient each. Eight of 10 patients with disseminated or miliary TB died primarily of respiratory failure; six of these eight patients also had some form of extrapulmonary involvement. Using the Wilcoxon rank-sum test, there were significant differences in the mean SLE Disease Activity Index (SLEDAI) and Severity of Disease Index (SDI) scores between those with limited TB (SLEDAI 24 +/- 7 SD; SDI 19 +/- 18 SD) versus those with extensive TB (SLEDAI 41 +/- 16 SD; SDI 36 +/- 21 SD), P < .05. There was no significant difference in the average daily prednisone dose (mg) between those with limited TB (25 +/- 17 SD) versus those with extensive TB (31 +/- 16 SD). The contributory role of tuberculous infection in the morbidity and mortality of patients with SLE must be emphasized, especially in areas endemic for TB.
Introduction Serum interleukin (IL)-17 concentrations have been reported to be increased in systemic lupus erythematosus (SLE), but associations with clinical characteristics are not well understood. We characterized clinical associations of serum IL-17 in SLE. Methods We quantified IL-17 in serum samples from 98 SLE patients studied cross-sectionally, and in 246 samples from 75 of these patients followed longitudinally over two years. Disease activity was recorded using the SLE Disease Activity Index (SLEDAI)-2k. Serum IL-6, migration inhibitory factor (MIF), and B cell activating factor of the tumour necrosis factor family (BAFF) were also measured in these samples. Results Serum IL-17 levels were significantly higher in SLE patients compared to healthy donors (P <0.0001). No correlation was observed between serum IL-17 and SLEDAI-2k, at baseline or during longitudinal follow-up. However, we observed that SLEDAI-2k was positively correlated with IL-17/IL-6 ratio. Serum IL-17 was significantly increased in SLE patients with central nervous system (CNS) disease (P = 0.0298). A strong correlation was observed between serum IL-17 and IL-6 (r = 0.62, P <0.0001), and this relationship was observed regardless of disease activity and persisted when integrating cytokine levels over the period observed (r = 0.66, P <0.0001). A strong correlation of serum IL-17 was also observed with serum BAFF (r = 0.64, P <0.0001), and MIF (r = 0.36, P = 0.0016). Conclusions Serum IL-17 concentration correlates poorly with SLE disease activity but is significantly elevated in patients with CNS disease. IL-17/IL-6 ratio may be more useful than IL-17 or IL-6 alone to characterize Th17-driven disease, such as SLE. The association of other cytokines with serum IL-17 suggests that IL-17 may drive activation of diverse immune pathways in SLE. PMID:23968496
Tektonidou, Maria G.; Wang, Zhong; Dasgupta, Abhijit; Ward, Michael M.
Objective To compare rates of hospitalizations for serious infections, trends in rates from 1996 to 2011, and in-hospital mortality between patients with systemic lupus erythematosus (SLE) and those without SLE in a national sample. Methods We analyzed hospitalizations for pneumonia, bacteremia/sepsis, urinary tract infections, skin infections, and opportunistic infections among adults in the Nationwide Inpatient Sample. We compared rates of hospitalizations yearly among patients with SLE and the general population. We also computed odds ratios for in-hospital mortality. Results In 1996, the estimated number of hospitalizations for pneumonia in patients with SLE was 4382, followed by sepsis (2305), skin infections (1422), urinary tract infections (643), and opportunistic infections (370). Rates were much higher in SLE than those without SLE, with age-adjusted relative risks ranging from 5.7 (95% confidence interval (CI) 5.5, 6.0) for pneumonia to 9.8 (95% CI 9.1, 10.7) for urinary tract infection in 1996. Risks increased over time, so that by 2011, all relative risks exceeded 12.0. Overall risk of in-hospital mortality was higher in SLE only for opportunistic infections (adjusted odds ratio 1.52; 95% CI 1.12, 2.07). However, in pneumonia and sepsis, mortality risks were higher in SLE among those that required mechanical ventilation. Conclusion Hospitalization rates for serious infections in SLE increased substantially between 1996 and 2011, reaching over 12 times higher than in patients without SLE in 2011. Reasons for this acceleration are unclear. In-hospital mortality was higher among patients with SLE and opportunistic infections, and those with pneumonia or sepsis who required mechanical ventilation. PMID:25732901
Hrycek, A; Cieślik, P; Tustanowski, J; Nowak, S; Jedynak, P
The objective of this study was to determine the effect of quinagolide (Norprolac) on serum level of cytokines in systemic lupus erythematosus (SLE) patients. In 20 SLE patients treated with a low dose of quinagolide, and in 17 healthy persons who constituted the control group, concentration of serum prolactin (PRL), interleukins (ILs), soluble tumor necrosis factor receptors (sTNF Rs) preceded by calculation of disease activity index (SLEDAI) were tested at entry and then after 3 months in 16 patients and after 6 months in 11 patients who completed the study. Serum PRL level was higher (though insignificantly) in the SLE group than in the controls and decreased significantly after 6 months of therapy. A raised SLEDAI score at entry was significantly reduced during therapy but a weak correlation with PRL level was revealed. A significant increase in IL-6 level in SLE group as compared to controls was observed (respectively 14.57 +/- 13.25 and 5.04 +/- 3.35 microg/ml) as well as a significantly decreased level after 6 months of treatment (4.30 +/- 2.51 pg/ml). There was a significant difference between sTNF RI concentration before and after 3 months of quinagolide treatment (respectively 1140.83 +/- 312.08 and 1454.58 +/- 465.54 pg/ml). After 6 months of treatment a statistically significant correlation between concentration of PRL and level of IL-6 and a negative correlation between PRL and sTNF RI was revealed. Quinagolide treatment may have a role in the management of SLE patients.
Faria, Daniella Antunes Pousa; Revoredo, Luciana Silva; Vilar, Maria José; Eulália Maria Chaves, Maia
Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune, rheumatic inflammatory disease that can cause significant morbidity with evident psychological impacts and obvious harm to quality-of-life that require the patient to adapt treatment. Objective: Assessment of resilience and the self-reported treatment adhesion behaviors of patients with SLE, investigating which of these factors are associated to resilience. Method: Cross-sectional study of 40 women with SLE. A questionnaire with social demographic data, health history and the Wagnild Young Resilience Scale were used. Results: 62.5% followed the medical treatment properly but 55% found it difficult. 27.5% of the patients presented low resilience, 57.5% medium and 15% high resilience. Resilience was associated in the chi-square test (p-value < 0.05) with the variables work, understanding SLE, trying to find out about SLE, following the treatment correctly, difficulty in following the treatment and stopping some activity because of the disease. In the correlation analysis, resilience was associated with age (-0.3960), number of working hours (0.5533), specialized treatment duration (-0.8103) and disease duration from diagnosis (-0.8014). Conclusion: Patients with high resilience tended to follow treatment correctly, tried to understand the disease and adhered more to the treatment to avoid risks and promote protection factors. Therefore knowledge of resilience in patients with SLE is necessary. It is important that the state takes necessary actions to facilitate access to treatment, to educational programs and to medical support. Awareness and counselling sessions must be initiated to develop and promote individual capacities to learn how to tackle with the disease for which psychological support of family and doctors can play a significant role. PMID:24665352
Ng, R; Bernatsky, S; Rahme, E
Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an array of organ manifestations that can appear during flares and disappear during remissions. The objectives of this study were: (i) to examine SLE manifestation groups longitudinally in an SLE cohort; and (ii) to assess the association between early antimalarial treatment and renal manifestations. Methods Seven SLE manifestation groups-cutaneous, hematologic, lung, musculoskeletal, neuropsychiatric, serositis, renal-were tracked using Kaplan-Meier survival curves in an incident SLE cohort from Quebec health administrative data ( n = 2010). A subgroup with provincial drug insurance coverage was followed over time to examine the association between early antimalarial treatment (within three months after SLE diagnosis) and renal manifestations using a Cox proportional hazards survival model. Results Cutaneous manifestations was the most common manifestation at SLE diagnosis (30.0%, 95% CI: 27.7-32.2%). About two-thirds (66.2%, 95% CI: 63.4-68.9%) of patients had evidence of at least one SLE manifestation at diagnosis, which increased to 87.2% (95% CI: 84.2-90.3%) by the end of follow-up. After adjusting for age, sex, early concomitant systemic steroid therapy, Charlson comorbidity index, primary care visits in the year prior and other SLE manifestations at baseline, no statistically significant association was established between antimalarial therapy and renal manifestations. Conclusion This study provides insight regarding organ manifestations within a population-based sample. Most patients identified with SLE had other diagnostic evidence that supports an underlying diagnosis of SLE. No protective effects for antimalarial agents against renal manifestations could be established in this population-based cohort.
Graffeo, Christopher S.; Tanweer, Omar; Nieves, Cesar Fors; Belmont, H. Michael; Izmirly, Peter M.; Becske, Tibor; Huang, Paul P.
Background: Subarachnoid hemorrhage (SAH) due to intracranial aneurysm rupture is a major neurosurgical emergency associated with significant morbidity and mortality. Rapid aneurysm growth is associated with rupture. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder whose complications can include cerebral vasculitis and vasculopathy. Intracranial aneurysms are not known to occur more frequently in SLE patients than the general population; however, aneurysm growth rates have not been studied in SLE. Case Description: We present a 43-year-old female with SLE on prednisone, hydroxychloroquine, and azathioprine with moderate disease activity who presented with severe, acute-onset headache and was found to have Hunt and Hess grade II SAH due to rupture of an 8 mm saccular anterior communicating artery (ACoA) aneurysm. The patient developed severe vasospasm, re-ruptured, and was taken for angiography and embolization, which was challenging due to a high degree of vasospasm and arterial stenosis. Review of imaging from less than 2 years prior demonstrated a normal ACoA complex without evidence of an aneurysm. Conclusion: We review the literature and discuss the risk factors and pathophysiology of rapid aneurysm growth and rupture, as well as the pathologic vascular changes associated with SLE. Although SLE patients do not develop intracranial aneurysm at an increased rate, these changes may predispose them to higher incidence of growth and rupture. This possibility-coupled with increased morbidity and mortality of SAH in SLE-suggests that SAH should be considered in SLE patients presenting with headache, and advocates for more aggressive treatment of SLE patients with unruptured aneurysms. PMID:25657862
Aydemir, M; Yazisiz, V; Basarici, I; Avci, A B; Erbasan, F; Belgi, A; Terzioglu, E
Neurological involvement is a well-documented issue in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, little is known about the involvement of the autonomic nervous system. This study was conducted to investigate autonomic nervous system dysfunction in patients with RA and SLE. Twenty-six RA patients, 38 SLE patients and 40 healthy controls were recruited from our in- and out-patient departments. Heart rate variability (HRV) parameters (the power of the high- [HF] and low-frequency [LF] band of haemodynamic time series, the ratio between low- and high-frequency components [LF/HF ratio], the power spectral density), baroreflex sensitivity (BRS) and beat-to-beat blood pressures were assessed by a novel non-invasive haemodynamic monitoring tool (Task Force Monitor [TFM], CNSystems Medizintechnik GmbH, Graz, Austria). Autonomic nervous system dysfunction was determined according to classical Ewing autonomic test battery. Furthermore, we implemented a secondary autonomic test score by modifying the Ewing test battery with additional criteria. Both the classical and modified Ewing test batteries have revealed that the frequencies of autonomic neuropathy were significantly higher in patient groups compared with controls (p < 0.001). Evaluation by TFM revealed that deterioration of sophisticated autonomic parameters (such as HRV and BRS) were more pronounced in the patient groups compared with controls. There was a significant association between BRS and Ewing test scores and abnormal BRS results were more frequent in patients with autonomic dysfunction according to Ewing test batteries. No relation was found between autonomic neuropathy and disease duration, disease activity and autoantibody positivity. Consequently, we believe that further large-scale studies investigating cardiovascular autonomic neuropathy in rheumatic diseases should be carried out to verify our findings and manifest clinical consequences beyond these results.
Weinstein, P J; Noyer, C M
Ascites in systemic lupus erythematosus (SLE) is rarely massive, and either accompanies the typical manifestations of active disease or results from nephrotic syndrome, protein-losing enteropathy, constrictive pericarditis, and conditions unrelated to lupus. Marked ascites has been attributed to chronic lupus peritonitis, characterized by the insidious onset of massive, painless ascites and unrelated to disease activity. Regardless of the etiology, ascites typically has a gradual onset and occurs after a diagnosis of SLE has been made. We describe a young woman presenting with the rapid development of massive ascites as the initial manifestation of SLE.
Monneaux, Fanny; Muller, Sylviane
The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this review article is to highlight emerging pharmacological options and new therapeutic avenues for lupus with a particular focus on non-antibody molecular strategies. PMID:19591653
Peñataro, Joaquín S; De Mingo, Ana; Del Río, Ana; Martínez, José A; Heras, Magda
Pericarditis is the most frequent cardiac manifestation of systemic lupus erythematosus (SLE). However, a large pericardial effusion as the initial manifestation of the disease is infrequent, especially when it is associated with myocardial damage. We describe an unusual case of a young female with pleuropericarditis and severe myocardial dysfunction as the initial manifestation of SLE. PMID:24062915
Braden, Carrie Jo; And Others
Data from 104 participants in the Systemic Lupus Erythematosus Self-Help Course showed that patients had significant increases in enabling skills and use of relaxation/exercise and decreases in depression. Amount of time spent in class was correlated with significant changes over time. (SK)
Finger, Eduardo; Romaldini, Helio; Lewi, David Salomão; Scheinberg, Morton Aaron
A patient with systemic lupus erythematosus developed interstitial lung disease initially felt to be a manifestation of the disease but that, on further workup, proved to be a manifestation of cytomegalic disease resistant to ganciclovir. Treatment with foscarnet was associated with prompt improvement.
Peñacoba Toribio, Patricia; Córica Albani, María Emilia; Mayos Pérez, Mercedes; Rodríguez de la Serna, Arturo
Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. We report the case of a patient with non-responding SLS (neither to glucocorticoids nor immunosupresors), who showed remarkable improvement after the onset of treatment with rituximab. Although there is a little evidence, treatment with rituximab could be proposed in SLS when classical treatment fails.
Sera from patients with systemic lupus erythematosus contain specific autoantibodies directed against different polypeptide components of the multicatalytic proteinase (also known as proteasome or prosome). These human autoantibodies, in contrast to polyclonal antibodies obtained in rabbits against the purified enzyme, recognize highly conserved epitopes of the multicatalytic proteinase polypeptides from yeast to human. PMID:1703207
Wu, Chan; Dong, Fang-tian; Chen, You-xin; Wang, Qian; Dai, Rong-ping; Zhang, Hua
Making accurate and timely diagnosis is often challenging when patients with a systemic disease first present with ocular manifestations. The possibility that vasculitis associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) can be misdiagnosed as cysticercosis has not been discussed in the literatures.
Rarely, systemic lupus erythematosus (SLE) presents with bullous lesions due to severe edema and hydropic degeneration of the basal layer, or as a subepidermal blistering disease. Here, we describe two Mexican teenagers, one with SLE with blisters and another with bullous SLE. We also discuss the mechanisms and clinical implications of lesion formation in patients with SLE and bullae. PMID:20615233
Mira-Avendano, Isabel C; Abril, Andy
Interstitial lung disease is a common and often life-threatening manifestation of different connective tissue disorders, often affecting its overall prognosis. Systemic lupus erythematosus, Sjögren syndrome, and mixed connective tissue disease, although all unique diseases, can have lung manifestations as an important part of these conditions. This article reviews the different pulmonary manifestations seen in these 3 systemic rheumatologic conditions.
Radis, C D; Callis, K P
This report describes a 29-year-old bodybuilder taking anabolic steroids who presented with urinary retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic steroid use and hyperprolactinemia, and their possible link to the development of SLE, are reviewed.
Alpert, Orna; Marwaha, Raman; Huang, Hsiang
Steroids may both be a cause of and treatment for pediatric patients with systemic lupus erythematosus (SLE) presenting with psychotic symptoms. We present two cases demonstrating that careful histories (including prior steroid exposure) and the use of biomarkers can help guide the management of children with SLE presenting with psychosis.
Gluhovschi, Cristina; Gluhovschi, Gheorghe; Petrica, Ligia; Velciov, Silvia; Gluhovschi, Adrian
Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE) is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg) cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. Other components of the immune system also participate to maintain maternal-fetal immune tolerance. If the immune system of pregnant women with SLE is not able to maintain maternal immune tolerance to the fetus, pregnancy complications (miscarriage, fetal hypotrophy, and preterm birth) or maternal complications (preeclampsia or activation of SLE, especially in conditions of lupus nephritis) may occur. In certain situations this can be responsible for neonatal lupus. At the same time, it must be noted that during pregnancy, the immune system is able to achieve immune tolerance while maintaining the anti-infectious immune capacity of the mother. Immunological monitoring of pregnancy during SLE, as well as of the mother's disease, is required. It is important to understand immune tolerance to grafts in transplant pathology.
Cardiel, Mario H; Almagro, Raúl Menor
Evaluation of: Tseng CE, Buyon JP, Kim M et al. The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 54, 3623-3632 (2006). Systemic lupus erythematosus is an autoimmune disease of unknown origin. Flares and remissions are commonly seen in clinical settings. These clinical flares can have several degrees of severity, some of which require intensive immunosuppressive treatment and/or hospitalization. Clinicians treating these patients have looked at different strategies for prevention, early detection and prompt treatment of a lupus flare. Clinical information and laboratory findings have been proposed to reach these goals and preventive steroid adjustment has even been used in some cases without convincing results. This paper presents results from a controlled, multicenter, double-blind clinical trial evaluating the effectiveness of short-term corticosteroid treatment for preventing severe flares in which elevations of C3a by 50% were accompanied by a 25% increase in the anti-double-stranded DNA titer in patients with inactive or stable/active systemic lupus erythematosus. Results suggest that this strategy can prevent severe lupus flares.
Fang, Wenjie; Chen, Min; Liu, Jia; Hagen, Ferry; Ms, Abdullah; Al-Hatmi; Zhang, Peilian; Guo, Yun; Boekhout, Teun; Deng, Danqi; Xu, Jianping; Pan, Weihua; Liao, Wanqing
Cryptococcal meningitis is an important fungal infection among systemic lupus erythematosus patients. We conducted a pooled analysis and systematic review to describe the epidemiological and clinical profile of cryptococcal meningitis in systemic lupus erythematosus patients. From two hospitals in China and nine literature databases, cases and prevalence data were collected for pooled analysis and meta-analysis, respectively. Categorical variables of cases were compared using a χ(2)-test on the statistical program of SAS. A multiple regression analysis was performed to ascertain independent predictors significantly correlated with prognosis. Meta-analysis was conducted by the statistical program of R. The prevalence of cryptococcal meningitis in systemic lupus erythematosus patients was 0.5%. Patients were predominantly females and adults. A prednisone equivalent of more than 30 mg/day before infection was associated with higher mortality (odds ratio (OR)=9.69 (1.54, 60.73)). In all, 36.8-38.9% patients showed low lupus activity when they developed the crytococcal infection. Moreover, 38.2% of the patients were misdiagnosed. The estimated case-fatality rate was 23.6%. Our results suggest that more emphasis should be placed to further understand lupus-related cryptococcal meningitis and to develop better prophylaxis and management strategies to combat this condition.
Fang, Wenjie; Chen, Min; Liu, Jia; Hagen, Ferry; MS, Abdullah; Al-Hatmi; Zhang, Peilian; Guo, Yun; Boekhout, Teun; Deng, Danqi; Xu, Jianping; Pan, Weihua; Liao, Wanqing
Cryptococcal meningitis is an important fungal infection among systemic lupus erythematosus patients. We conducted a pooled analysis and systematic review to describe the epidemiological and clinical profile of cryptococcal meningitis in systemic lupus erythematosus patients. From two hospitals in China and nine literature databases, cases and prevalence data were collected for pooled analysis and meta-analysis, respectively. Categorical variables of cases were compared using a χ2-test on the statistical program of SAS. A multiple regression analysis was performed to ascertain independent predictors significantly correlated with prognosis. Meta-analysis was conducted by the statistical program of R. The prevalence of cryptococcal meningitis in systemic lupus erythematosus patients was 0.5%. Patients were predominantly females and adults. A prednisone equivalent of more than 30 mg/day before infection was associated with higher mortality (odds ratio (OR)=9.69 (1.54, 60.73)). In all, 36.8–38.9% patients showed low lupus activity when they developed the crytococcal infection. Moreover, 38.2% of the patients were misdiagnosed. The estimated case-fatality rate was 23.6%. Our results suggest that more emphasis should be placed to further understand lupus-related cryptococcal meningitis and to develop better prophylaxis and management strategies to combat this condition. PMID:27599471
Stojan, G; Petri, M
C1q is the first component of the classical complement pathway. Both clinically validated in-house ELISA assays as well as commercial ELISA kits are used for detection of anti-C1q antibodies. Anti-C1q autoantibodies can be detected in a wide range of autoimmune diseases and are highly sensitive for hypocomplementemic uticarial vasculitis. In SLE, anti-C1q are strongly associated with proliferative lupus nephritis, and their absence carries a negative predictive value for development of lupus nephritis of close to 100%. Anti-C1q in combination with anti-dsDNA and low complement has the strongest serological association with renal involvement. The anti-C1q titers correlate with global disease activity scores in patients with renal involvement, and higher titers seem to precede renal flares. After the successful treatment of a renal flare, anti-C1q has the tendency to decrease or even become undetectable. The main obstacle to the inclusion of anti-C1q in the classification criteria and clinical management of SLE is the lack of standardized laboratory assays.
Farrugia, E; Torres, V E; Gastineau, D; Michet, C J; Holley, K E
Circulating lupus anticoagulant (LA) is associated with thrombosis in large and small vessels. To determine how often the presence of LA is associated with thrombosis within the renal microcirculation, 33 patients with systemic lupus erythematosus (SLE), renal dysfunction, and LA were identified over a 25-year period (LA group) and 32 patients with renal SLE but with normal gross coagulation screen were matched for age, sex, and biopsy timing (C group). Prevalences of serositis, neuropsychiatric illness, leukopenia, thrombocytopenia, hemolysis, anti-DS-DNA elevation, and complement reduction were similar. Arthritis was less and biologic false-positive (BFP) syphilis serology more common in LA. More LA patients had thrombotic events (LA 39% v C 13%; P = 0.014); bleeding episodes, including postbiopsy, were similar. At biopsy, hypertension (LA 55%, C 41%), serum creatinine (mean +/- SD: LA 186 +/- 168 mumol/L [2.1 +/- 1.9 mg/dL] v C 150 +/- 168 mumol/L [1.7 +/- 1.9 mg/dL]) and proteinuria (LA 2.6 +/- 3.1 g/24 h v C 3.1 +/- 2.7) were similar. Lesions by World Health Organization (WHO) class, activity, and chronicity indices, as well as immunofluorescence (IF) and electron microscopy (EM) findings, were not significantly different. Occlusive glomerular, arteriolar, and arterial fibrin thrombi, along with varying degrees of renal thrombotic microangiopathy, were seen in five of 33 patients with LA, but zero of 32 C patients (P = 0.053); three of these five patients died soon after biopsy. Overall, mortality was not different between LA and C. We conclude that the majority of patients with SLE, renal dysfunction, and LA exhibit renal morphologic findings indistinguishable from patients without LA. However, a significant minority of LA patients have thrombotic microangiopathy in their biopsy, which is accompanied by a worse prognosis.
Somers, Emily C.; Marder, Wendy; Cagnoli, Patricia; Lewis, Emily E.; DeGuire, Peter; Gordon, Caroline; Helmick, Charles G.; Wang, Lu; Wing, Jeffrey J.; Dhar, J. Patricia; Leisen, James; Shaltis, Diane; McCune, W. Joseph
Objective To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a sociodemographically diverse southeastern Michigan source population of 2.4 million people. Methods SLE cases fulfilling the American College of Rheumatology classification criteria (primary case definition) or meeting rheumatologist-judged SLE criteria (secondary definition) and residing in Wayne or Washtenaw Counties during 2002–2004 were included. Case finding was performed from 6 source types, including hospitals and private specialists. Age-standardized rates were computed, and capture–recapture was performed to estimate underascertainment of cases. Results The overall age-adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval [95% CI] 5.0–6.1) and 72.8 (95% CI 70.8–74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by capture–recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3-fold higher in black persons than in white persons, and 10-fold higher in females than in males. Among incident cases, the mean ± SD age at diagnosis was 39.3 ± 16.6 years. Black SLE patients had a higher proportion of renal disease and end-stage renal disease (ESRD) (40.5% and 15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%, respectively). Black patients with renal disease were diagnosed as having SLE at younger age than white patients with renal disease (mean ± SD 34.4 ± 14.9 years versus 41.9 ± 21.3 years; P = 0.05). Conclusion SLE prevalence was higher than has been described in most other population-based studies and reached 1 in 537 among black female persons. There were substantial racial disparities in the burden of SLE, with black patients experiencing earlier age at diagnosis, >2-fold increases in SLE incidence and prevalence, and increased
van Schaarenburg, Rosanne A.; Magro-Checa, César; Bakker, Jaap A.; Teng, Y. K. Onno; Bajema, Ingeborg M.; Huizinga, Tom W.; Steup-Beekman, Gerda M.; Trouw, Leendert A.
C1q deficiency is a rare immunodeficiency, which is strongly associated with the development of systemic lupus erythematosus (SLE). A mutation in one of the C1q genes can either lead to complete deficiency or to low C1q levels with C1q polypeptide in the form of low-molecular weight (LMW) C1q. Patients with C1q deficiency mainly present with cutaneous and renal involvement. Although less frequent, neuropsychiatric (NP) involvement has also been reported in 20% of the C1q-deficient patients. This involvement appears to be absent in other deficiencies of early components of the complement classical pathway (CP) (C1r/C1s, C2, or C4 deficiencies). We describe a new case with C1q deficiency with a homozygous G34R mutation in C1qC-producing LMW-C1q presenting with a severe SLE flare with NP involvement. The serum of this patient contained very low levels of a LMW variant of C1q polypeptides. Cell lysates contained the three chains of C1q, but no intact C1q was detected, consistent with the hypothesis of the existence of a LMW-C1q. Furthermore, we provide a literature overview of NP-SLE in C1q deficiency and hypothesize about the potential role of C1q in the pathogenesis of NP involvement in these patients. The onset of NP-SLE in C1q-deficient individuals is more severe when compared with complement competent NP-SLE patients. An important number of cases present with seizures and the most frequent findings in neuroimaging are changes in basal ganglia and cerebral vasculitis. A defective CP, because of non-functional C1q, does not protect against NP involvement in SLE. The absence of C1q and, subsequently, some of its biological functions may be associated with more severe NP-SLE. PMID:28082982
Resch, Miklós D.; Marsovszky, László; Németh, János; Bocskai, Márta; Kovács, László
Purpose. Investigation of dry eye and corneal Langerhans cells (LCs) in systemic lupus erythematosus (SLE). Methods. Prospective consecutive case series of 27 SLE patients and 27 control subjects. Dry eye was evaluated by lid-parallel conjunctival folds (LIPCOF), Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) questionnaire. In vivo investigation of corneal LCs density and morphology (LCM) was performed with confocal corneal microscopy (Heidelberg Retina Tomograph with Rostock Cornea Module). Results. Tear production and stability were pathological in SLE subjects compared to control (Schirmer: 8.45 ± 9.82 mm/5 min versus 11.67 ± 3.21 mm/5 min; TBUT: 6.86 ± 3.53 s versus 11.09 ± 3.37 s). OSDI was significantly greater in SLE patients (25.95 ± 17.92) than in controls (11.06 ± 7.18). Central LC density was greater in SLE patients (43.08 ± 48.67 cell/mm2) than in controls (20.57 ± 21.04 cell/mm2). There was no difference in the peripheral LC density (124.78 ± 165.39 versus 78.00 ± 39.51 cell/mm2). LCM was higher in SLE patients in the centre (1.43 ± 0.79) and in the periphery (2.89 ± 0.42) compared to controls (centre: 1.00 ± 0.69, periphery: 2.35 ± 0.54). Conclusions. Significant changes in dry eye parameters and marked increase of central LCs could be demonstrated in SLE patients. SLE alters not only the LC density but also the morphology, modifies corneal homeostasis, and might contribute to the development of dry eye. PMID:25893112
Cozzani, Emanuele; Drosera, Massimo; Parodi, Aurora
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the aberrant production of a broad and heterogenous group of autoantibodies. Even though the presence of autoantibodies in SLE has been known, for more than 60 years, still nowadays a great effort is being made to understand the pathogenetic, diagnostic, and prognostic meaning of such autoantibodies. Antibodies to ds-DNA are useful for the diagnosis of SLE, to monitor the disease activity, and correlate with renal and central nervous involvements. Anti-Sm antibodies are highly specific for SLE. Anti-nucleosome antibodies are an excellent marker for SLE and good predictors of flares in quiescent lupus. Anti-histone antibodies characterize drug-induced lupus, while anti-SSA/Ro and anti-SSB/La antibodies are associated with neonatal lupus erythematosus and photosensitivity. Anti-ribosomal P antibodies play a role in neuropsychiatric lupus, but their association with clinical manifestations is still unclear. Anti-phospholipid antibodies are associated with the anti-phospholipid syndrome, cerebral vascular disease, and neuropsychiatric lupus. Anti-C1q antibodies amplify glomerular injury, and the elevation of their titers may predict renal flares. Anti-RNP antibodies are a marker of Sharp's syndrome but can be found in SLE as well. Anti-PCNA antibodies are present in 5–10% of SLE patients especially those with arthritis and hypocomplementemia. PMID:24649358
Shibata, S; Sasaki, T; Hirabayashi, Y; Seino, J; Okamura, K; Yoshinaga, K; Morito, N; Kasukawa, R; Aotuka, S; Yokohari, R
Fetal wastage is still high in the pregnancies of patients with systemic lupus erythematosus (SLE). We examined retrospectively the cases of 38 patients with inactive SLE in whom pregnancy was either desired or had already been obtained. The prevalence of antiphospholipid antibodies in the group with fetal loss was high. The antibodies were, however, also detected in five of 14 patients who had had a live birth. It was noted that low levels of serum complement activity (CH50 less than 25 U/ml) occurred in five of six patients with fetal loss, but in only two of 22 with a live birth. Serial studies also confirmed a close association between decreased serum complement activity and poor fetal prognosis in lupus pregnancy. Treatment with increased doses of prednisolone may help to achieve successful live births. Thus hypocomplementaemia may be associated with a worse prognosis for the fetus in the pregnancies of some patients with SLE in remission. Images PMID:1616326
Castrejón, I; Tani, C; Jolly, M; Huang, A; Mosca, M
This review summarises most currently used indices to assess and monitor patients with systemic lupus erythematosus (SLE) in clinical trials, long-term observational studies, and clinical care. Six SLE disease activity indices include the British Isles Lupus Assessment Group Index (BILAG), European Consensus Lupus Activity Measurement (ECLAM), Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Lupus Activity Index (LAI), and Systemic Lupus Erythematosus Activity Questionnaire (SLAQ). Three SLE responder indices include Responder Index for Lupus Erythematosus (RIFLE), SLE Responder Index (SRI), and BILAG Based Combined Lupus Assessment (BICLA). Three SLE damage indices include the Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index (SLICC/ACE-DI), Lupus Damage Index Questionnaire (LDIQ), and Brief Index of Lupus Damage (BILD). The SLAQ, LDIQ and the BILD are patient self-report questionnaires, which appear to give similar information to physician-completed indices, but are pragmatically more easily completed as patients do almost all the work. Additional self-report indices which have been used to assess and monitor patients with in SLE include a generic general health short form 36 (SF36), a SLE-specific Lupus Patient Reported Outcome (LupusPRO), and a generic rheumatology index, Routine Assessment of Patient Index Data 3 (RAPID3). These activity, response, damage and patient self-report indices have been validated at different levels with no consensus about what it is the most appropriate for every setting. Sensitive and feasible assessment of SLE in clinical trials, observational studies, and busy clinical settings remains a challenge to the rheumatology community.
Dell'era, L; Boati, E; Nebbia, G; Corona, F
Systemic lupus erythematosus (SLE) has been reported to be associated to Wilson's disease, as a complication of treatment with penicillamine. Even though drug-induced lupus erythematosus (DILE) has some features in common with SLE, they are distinct entities. We report the case of a young girl who at the age of five had a diagnosis of Wilson's disease and she started therapy with penicillamine. Eight years after the beginning of therapy, she developed proteinuria, which was considered to be related to penicillamine. Two years later, she developed arthritis, malar rash and laboratory findings suggestive for lupus erythematosus. At the beginning her symptoms, due to the known association between penicillamine and DILE, were thought to be related to this treatment. In this hypothesis, she was referred to the Rheumatology Centre; zinc acetate was substituted for penicillamine and she started naproxen for the treatment of arthritis. Anyway, the subsequent clinical course and laboratory findings led us to a diagnosis of idiopathic SLE. A renal biopsy detected massive mesangiocapillary proliferation with subendothelial deposits (wire loops) and duplication of glomerular basement membrane (active diffuse global proliferative lupus nephritis, class IV G A). To our knowledge, this is the first report of an association between Wilson's disease and SLE.
Yokogawa, Naoto; Kato, Yukihiko; Sugii, Shoji; Inada, Shinichi
We evaluated the cutaneous lupus erythematosus disease area and severity index (CLASI) in Japanese patients with systemic lupus erythematosus (SLE) in order to design a clinical trial of hydroxychloroquine (HCQ) in Japan. Our prospective cohort study consisted of seven SLE patients with active skin disease who started HCQ at Tokyo Metropolitan Tama Medical Center. The therapeutic responses were assessed at 4 months. Patients were categorized as responders (improved) or non-responders (unchanged or worsened) using the criteria of a 4-point or 20% decrease in the CLASI activity score. We also assessed joint pain determined by patient visual analog scale (VAS), malaise (VAS), patient global assessment of SLE (VAS), and constitutional and musculoskeletal symptoms according to the British Isles Lupus Assessment Group (BILAG) disease activity index. Six patients (86%) were categorized as responders. The median (range) CLASI activity score of all patients at assessment had changed from 8.0 (2-22) to 4 (2-10). All five patients with joint pain and all five patients with malaise showed improvement in patient VAS but the BILAG findings failed to capture these improvements. In conclusion, the cutaneous aspects of SLE can be measured by the CLASI. The CLASI activity score may be a reasonable primary endpoint when performing a clinical trial of HCQ.
Kasturi, Shanthini; Goodman, Susan
Systemic lupus erythematosus (SLE) is a chronic debilitating condition with significant impact on the musculoskeletal system. Arthroplasty may be indicated for damage related to active lupus or its treatment. As therapies for SLE have advanced, morbidity and mortality have declined, while the rate of joint replacement has increased. The age of SLE patients undergoing arthroplasty is increasing, and the indication for surgery is evolving-while avascular necrosis was previously the predominant indication for arthroplasty, osteoarthritis now accounts for a larger proportion of surgeries. Pain and functional outcomes of arthroplasty in SLE patients are comparable to those of the general population with osteoarthritis, but lupus remains an independent risk factor for post-hip arthroplasty complications and mortality. Further research is needed to characterize the impact of lupus disease activity and severity on arthroplasty outcomes.
McElhone, Kathleen; Abbott, Janice; Sutton, Chris; Mullen, Montana; Lanyon, Peter; Rahman, Anisur; Yee, Chee‐Seng; Akil, Mohammed; Bruce, Ian N.; Ahmad, Yasmeen; Gordon, Caroline
Objective As a health‐related quality of life (HRQOL) measure, the LupusQoL is a reliable and valid measure for adults with systemic lupus erythematosus (SLE). This study evaluates the responsiveness and minimal important differences (MIDs) for the 8 LupusQoL domains. Methods Patients experiencing a flare were recruited from 9 UK centers. At each of the 10 monthly visits, HRQOL (LupusQoL, Short Form 36 health survey [SF‐36]), global rating of change (GRC), and disease activity using the British Isles Lupus Assessment Group 2004 index were assessed. The responsiveness of the LupusQoL and the SF‐36 was evaluated primarily when patients reported an improvement or deterioration on the GRC scale and additionally with changes in physician‐reported disease activity. MIDs were estimated as mean changes when minimal change was reported on the GRC scale. Results A total of 101 patients were recruited. For all LupusQoL domains, mean HRQOL worsened when patients reported deterioration and improved when patients reported an improvement in GRC; SF‐36 domains showed comparable responsiveness. Improvement in some domains of the LupusQoL/SF‐36 was observed with a decrease in disease activity, but when disease activity worsened, there was no significant change. LupusQoL MID estimates for deterioration ranged from −2.4 to −8.7, and for improvement from 3.5 to 7.3; for the SF‐36, the same MID estimates were −2.0 to −11.1 and 2.8 to 10.9, respectively. Conclusion All LupusQoL domains are sensitive to change with patient‐reported deterioration or improvement in health status. For disease activity, some LupusQoL domains showed responsiveness when there was improvement but none for deterioration. LupusQoL items were derived from SLE patients and provide the advantage of disease‐specific domains, important to the patients, not captured by the SF‐36. PMID:26816223
Gómez-Guzmán, Manuel; Jiménez, Rosario; Romero, Miguel; Sánchez, Manuel; Zarzuelo, María José; Gómez-Morales, Mercedes; O'Valle, Francisco; López-Farré, Antonio José; Algieri, Francesca; Gálvez, Julio; Pérez-Vizcaino, Francisco; Sabio, José Mario; Duarte, Juan
Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47(phox) were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti-double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications.
Levy, O; Maslakov, I; Vosco, S; Markov, A; Amit-Vazina, M; Tishler, M
A 35-year-old female with long standing aPL-positive lupus without history of thromboembolic events, who has developed critical peripheral ischemia (CPI) is described. An episode of severe Raynaud's phenomenon rapidly progressed to an extensive digit-threatening ischemia, involving bilateral hands and feet. She was successfully treated with corticosteroids, anticoagulation, iloprost, sildenafil, and nifedipine. Her serological studies were remarkable for the emergence of high titer anti-RNP seroconversion and an increase in aPL titer, suggesting that these autoantibodies played a role in the pathogenesis of CPI. It is important to note that such observation should herald this potentially devastating complication of systemic lupus erythematosus.
Orquevaux, P; Masseau, A; Le Guern, V; Gayet, V; Vauthier, D; Boutin, D; Wechsler, B; Morel, N; Guettrot-Imbert, G; Pennaforte, J-L; Piette, J-C; Costedoat-Chalumeau, N
Fertility is not impaired in systemic lupus erythematosus or antiphospholipid syndrome, but, similarly to the general population, these patients may undergo in vitro fertilization. This type of treatment increases the risk of lupus flare, thrombosis, and ovarian hyperstimulation syndrome. This review will focus on in vitro fertilization in systemic lupus erythematosus or antiphospholipid syndrome. Literature data are relatively scant with only 3 reported studies. The first one included 17 patients and 63 cycles of induction ovulation/in vitro fertilization leading to 25 % of lupus flare, no thrombosis, and 3 % of ovarian hyperstimulation syndrome. The second study included 10 patients and 40 cycles of in vitro fertilization showing 31 % of lupus flare, no thrombosis and no ovarian hyperstimulation syndrome. The last one included 34 patients and 83 procedures of in vitro fertilization leading to 8 % of flares, 5 % of thrombosis and no ovarian hyperstimulation syndrome. Interestingly, in this last study, half of the complications were explained by poor adherence to treatment. These data are reassuring but it is important to remember that in vitro fertilization should be scheduled and carefully supervised in the same way as the high-risk pregnancies occurring in these patients.
Sansinanea, Pierina; Carrica, Sebastián Augusto; Marcos, Josefina; García, Mercedes Argentina
A case is presented of a protein-losing enteropathy (PLE) as the initial manifestation of systemic lupus erythematosus (SLE) in a 17 year-old female patient, who presented with ascites, edema and hypoalbuminemia. The diagnosis of SLE was based on the presence of: malar rash, oral ulcers, thrombocytopenia, antinuclear antibodies, IgM anticardiolipin antibody, and lupus anticoagulant. Renal and liver diseases were ruled out. The PLE diagnosis was confirmed with fecal alpha 1-antitrypsin clearance. The PLE was refractory to different lines of immunosuppressive agents like glucocorticoids, cyclophosphamide, azathioprine, and cyclosporine, showing a satisfactory and sustained response with rituximab, allowing steroid sparing and long term remission.
Mackern-Oberti, J P; Obreque, J; Méndez, G P; Llanos, C; Kalergis, A M
Systemic lupus erythematosus is characterized by the presence of circulating anti-nuclear antibodies (ANA) and systemic damage that includes nephritis, haematological manifestations and pulmonary compromise, among others. Although major progress has been made in elucidating the molecular mechanisms responsible for autoimmunity, current therapies for lupus have not improved considerably. Because the exposure of carbon monoxide (CO) has been shown to display beneficial immunoregulatory properties in different immune-mediated diseases, we investigated whether CO therapy improves lupus-related kidney injury in lupus mice. MRL-Faslpr lupus mice were exposed to CO and disease progression was evaluated. ANA, leucocyte-infiltrating populations in spleen, kidney and lung and kidney lesions, were measured. CO therapy significantly decreased the frequency of activated B220+ CD4− CD8− T cells in kidneys and lungs, as well as serum levels of ANA. Furthermore, we observed that CO therapy reduced kidney injury by decreasing proliferative glomerular damage and immune complexes deposition, decreased proinflammatory cytokine production and finally delayed the impairment of kidney function. CO exposure ameliorates kidney and lung leucocyte infiltration and delays kidney disease in MRL-Faslpr lupus mice. Our data support the notion that CO could be explored as a potential new therapy for lupus nephritis. PMID:26095291
Wang, D Y; Chang, D B; Kuo, S H; Yang, S; Shiah, D C; Chou, H T; Luh, K T
Systemic lupus erythematosus (SLE) presenting as a pleural effusion in a young male is not common. This paper describes a 20-year-old man who was admitted to hospital with a spiking fever, chills and cough. A chest x-ray showed alveolar infiltration and a moderate right-sided pleural effusion. The patient was treated for parapneumonic effusion. Thoracentesis was performed and cytology of the aspirated fluid was initially interpreted as showing only numerous polymorphonuclear (PMN) leukocytes. However, in spite of antibiotic treatment the symptoms persisted. A careful review of the cytology specimen showed classic lupus erythematosus (LE) cells in addition to PMN cells. Subsequent investigation, including antinuclear antibodies titer, confirmed the diagnosis of LE pleurisy. Therapy with antibiotics was discontinued and treatment with prednisolone 20 mg daily was begun. There was a rapid clinical response including resolution of the fever and pleural effusion.
Leite, Cristhiane Almeida; Galera, Marcial Francis; Espinosa, Mariano Martínez; de Lima, Paulo Ricardo Teles; Fernandes, Vander; Borges, Álvaro Henrique; Dias, Eliane Pedra
Background. Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem, and autoimmune disease. Objective. The aim of this study was to describe the prevalence of hyposalivation in SLE patients and evaluate factors associated. Methods. This is a cross-sectional study developed at the Cuiaba University General Hospital (UNIC-HGU), Mato Grosso, Brazil. The study population consisted of female SLE patients treated at this hospital from 06/2010 to 12/2012. Unstimulated salivary flow rates (SFRs) were measured. Descriptive and inferential analyses were performed in all cases using a significance level P < 0.05. Results. The results showed that 79% of patients with systemic lupus erythematosus suffered from hyposalivation and that the disease activity and age in years were the factors that resulted in statistically significant differences. Conclusion. The activity of the disease, age >27 years, and the drugs used were factors associated with hyposalivation, resulting in a statistically significant decrease in saliva production. PMID:25649631
Wei, Wenxin; Zerfoss, Erica; Ashker, Lamees; Cantore, William A
The authors report a case of a 16-year-old girl with a history of systemic lupus erythematosus who developed bilateral acute optic neuritis. Systemic lupus erythematosus can present with a vast array of neurological and ophthalmic complications, with optic neuritis being a rare but devastating manifestation and the major cause of blindness in these patients. The patient presented with an acute unilateral visual deficit that progressed to bilateral visual loss with no light perception over the course of days. Treatment included high-dose steroids, cyclophosphamide, intravenous immunoglobulin, and eventually rituximab. Furthermore, the patient was also seropositive for both antiphospholipid and neuromyelitis optica antibodies, which can have implications on prognosis and treatment options.
Matta, Bassem N; Uthman, Imad; Taher, Ali T; Khamashta, Munther A
The antiphospholipid syndrome was first described in the early 1980s. The term was first coined to describe patients presenting with recurrent arterial and venous thrombosis or pregnancy complications. Antiphospholipid syndrome was first reported in systemic lupus erythematosus patients, but later on it became obvious that systemic lupus erythematosus is not a necessary condition for its occurrence. It has been shown that antibodies to phospholipids are the main causative agents of the disease, hence its name. The diagnosis of the disease has witnessed a remarkable evolution over the course of the past 25 years. With the observation that clinical parameters would not be enough to accurately diagnose the disease, antiphospholipid antibodies were recognized to play a central role in this regard. The main hindrance to an accurate diagnosis was the lack of standardization between different laboratory parameters that tested for the antiphospholipid antibodies. Lately, a combination of tests has been acknowledged to play a crucial role in diagnosis.
Lamond, N W D; Younis, T; Purdy, K; Dorreen, M S
Drug-induced lupus erythematosus (dile) syndromes are documented complications of chemotherapeutic agents, including paclitaxel. Subacute cutaneous lupus erythematosus (scle) is a distinct dile syndrome presenting with characteristic annular or papulosquamous skin lesions in a photosensitive distribution with associated high anti-ssa titres. Previously, dile syndromes complicating paclitaxel therapy have been attributed to polyethoxylated castor oil (Kolliphor EL: BASF, Ludwigshafen, Germany), the biologic solvent included in the drug's original formulation (Taxol: Bristol-Myers Squibb, Montreal, QC), rather than the parent chemotherapy molecule. Here, we report a characteristic case of drug-induced scle complicating treatment with nanoparticle albumin bound (nab)-paclitaxel (Abraxane: Celgene, Summit, NJ, U.S.A.), a solvent-free taxane formulation. The pertinent English-language literature is also discussed. This case report is the first to link solvent-free paclitaxel with scle, and it suggests that the parent molecule is responsible for the reaction.
Córdoba-Guijarro, S; Feal, C; Daudén, E; Fraga, J; García-Díez, A
Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease. Carrier status of CGD has been reported in association with lupus erythematosus-type lesions. A 35-year-old woman, mother of a child with X-linked CGD presented an 8-year history of erythematous plaques with an arciform pattern on the upper trunk, back and arms. The nitroblue tetrazolium test revealed the carrier status of the patient. Haematological, biochemical and immunological tests (including ANA, DNA, SSA-Ro, SSB-La, RNP, SM and Jo1 antibodies) were normal or negative except for a polyclonal hypergammaglobulinaemia with high serum IgA. Histological examination showed a papillary and perifollicular lymphohistiocytic infiltrate. Direct immunofluorescence was negative. We report a female carrier of X-linked CGD who developed clinical subacute lupus erythematosus-like lesions. We review the literature and discuss the pathogenetic mechanisms involved in the condition.
Fatani, Mohammad Ibrahim; Hussain, Waleed Mohd; Baltow, Badee; Alsharif, Sahar
A cutaneous horn is a rare clinical condition characterised by a conical projection of hyperkeratotic epidermis. Cutaneous horns most commonly arise from sun-exposed skin in elderly men, but may arise from any part of the body at any age in men and women. When a cutaneous horn forms, it is important to determine the underlying cause. Various skin diseases may present with cutaneous horns including viral warts, actinic keratosis, keratoacanthoma, seborrhoeic keratosis, pyogenic granuloma, discoid lupus erythematosus, verruca vulgaris, Bowen's disease, basal cell carcinoma and squamous cell carcinoma. The underlying pathology is benign in 61.1% of cases, premalignant in 23.2% of cases and malignant in 15.7% of cases. We report a patient with a cutaneous horn arising from an area of discoid lupus erythematosus on the scalp.
Fouad, El Asri; Hanane, Momen; Mounir, Belmalih; Rachid, Zarrouk; Karim, Reda; Abdelber, Oubaaz
Systemic lupus erythematosus (SLE) is a chronic, autoimmune, multisystem disease which may affect the eyes and/or visual system in up to a third of patients. Severe retinal vaso-occlusive diseases have been rarely reported as manifestation in patients with SLE. We report the case of a 35-year-old female treated for systemic lupus erythematosus for 6 months, presented a sudden loss of vision. Fundus examination and fluorescein angiography revealed severe retinal vascular occlusion. This has motivated the search for antiphospholipid antibody syndrome and this was confirmed without the presence of anticardiolipin antibodies. And the treatment consisted in a laser therapy. The purpose of this case report is to demonstrate that an ocular vascular event can reveal the disease and that its diagnosis is important because this disease generally affects young people and may endanger ocular and vital prognosis.
Winfield, J B; Winchester, R J; Wernet, P; Kunkel, H G
Antibodies to surface determinants of human lymphocytes, recognized both by cytotoxicity of fluorescent antibody analysis, were shown to be specifically enriched over the serum levels in cryoprecipitates from patients with systemic lupus erythematosus (SLE). The antilymphocyte antibody was shown to be cold reactive and was exclusively IgM. It was distinct from IgM anti-IgG, which was also variably concentrated in the cryoprecipitates. The question whether the antilymphocyte antibodies appear in the cryoprecipitates as complexes because of interaction with surface membrane antigens, or simply because of cold reactive properties, remains to be determined. The possible clinical relevance of the cryoprecipitation of these antibodies in systemic lupus erythematosus is discussed. PMID:1081927
Molina-Ruiz, Ana María; Lasanta, Begoña; Barcia, Ana; Pérez-Vega, Elisa; Requena, Luis
Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood.
Resources - lupus ... The following organizations are good resources for information on systemic lupus erythematosus : The Lupus Foundation of America -- www.lupus.org The National Institute of Arthritis and Musculoskeletal ...
Ungprasert, P; Chowdhary, V R; Davis, M D; Makol, A
Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil.
Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A
Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.
Vargas-Hitos, J A; Sabio, J M; Navarrete-Navarrete, N; Arenas-Miras, M del M; Zamora-Pasadas, M; Jiménez-Alonso, J
Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant.
Macêdo, Danielle Patrícia Cerqueira; Silva-Júnior, Heraldo Maia; de Souza-Motta, Cristina Maria; Milan, Eveline Pípolo; Neves, Rejane Pereira
Aspergillus is a ubiquitous fungus which can cause a variety of clinical syndromes. This fungus has emerged as agent of systemic infections and has therefore gained considerable public health importance. This paper describes two cases of invasive aspergillosis caused by A. fumigatus in immuno-suppressed patients and underscores the importance of early identification of Aspergillus infection associated with systemic lupus erythematosus and cardiac postoperative complications. PMID:24031340
Grover, S; Parakh, P; Sharma, A; Rao, P; Modi, M; Kumar, A
Although, neuropsychiatric morbidity is quite high in patients with systemic lupus erythematosus (SLE), catatonia has been rarely reported. We report a case of a 22-year-old female who presented with catatonic symptoms at the time of relapse of SLE and have discussed the presentation in the context of existing literature with regard to phenomenology of catatonia, psychiatric co-morbidity and treatment of catatonia in patients with SLE.
Mizuno, R; Fujimoto, S; Fujimoto, T; Nishino, T; Shiiki, H; Hashimoto, T; Nakamura, S; Dohi, K
Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome (APS) characterized by disseminated microangiopathy that results in multiorgan failure. CAPS mainly occurs in association with systemic lupus erythematosus (SLE). Clinically, CAPS mimics disseminated SLE vasculitis, intravascular coagulation (DIC), and particularly thrombotic thrombocytopenic purpura (TTP). We describe an autopsy case of young woman with CAPS in SLE, which is difficult to differentiate from TTP secondary to SLE.
A case of internal carotid artery dissection in a pregnant woman with Systemic Lupus Erythematosus (SLE) immediately following chiropractic treatment is presented. The literature regarding complications of neck manipulation during pregnancy, spontaneous dissection of craniocervical arteries in pregnancy and the postpartum period, and dissection of craniocervical arteries in SLE are reviewed. To the best of the author's knowledge, this is the first case of carotid artery dissection following chiropractic treatment in a pregnant woman published in the literature.
A case of internal carotid artery dissection in a pregnant woman with Systemic Lupus Erythematosus (SLE) immediately following chiropractic treatment is presented. The literature regarding complications of neck manipulation during pregnancy, spontaneous dissection of craniocervical arteries in pregnancy and the postpartum period, and dissection of craniocervical arteries in SLE are reviewed. To the best of the author’s knowledge, this is the first case of carotid artery dissection following chiropractic treatment in a pregnant woman published in the literature. PMID:23254252
Lin, Hsiu-Fen; Yeh, Yi-Chun; Chen, Chien-Fu; Chang, Wei-Chen; Chen, Cheng-Sheng
Kluver-Bucy syndrome (KBS) is a collection of neuropsychiatric symptoms, including visual agnosia (prosopagnosia), hypermetamorphosis, placidity, hypersexuality, and hyperorality. Although neuropsychiatric manifestation is prevalent in cases with systemic lupus erythematosus (SLE), only one literature reported a case with SLE that had KBS previously. In this article, a 37-year-old woman with SLE who developed KBS and other neuropsychiatric symptoms is presented. Brain imaging proved the relevant structural lesion. The possible explanation of pathogenesis of KBS in SLE is discussed.
Ting, Li Yu; Shrestha, Bikash; Lu, Yi Lu; Ping, Fu
Tuberculosis is a common infectious mycobacterial disease having a wide range of clinical and serological manifestations that are similar to rheumatic disease. Differential diagnosis is a crucial aspect in any rheumatic disease as many other infectious diseases portray clinical similarities and autoantibody positivity. Our case report illustrates of a young woman just after the delivery of a child presented an unusual case of extrapulmonary tuberculosis infection initially misdiagnosed as systemic lupus erythematosus (SLE).
Wright, Tracey B; Punaro, Marilynn
Investigations in paediatric SLE contributed significantly to the discovery of the association of type I IFNs with lupus and underscored the potential application of this knowledge by informing the use of glucocorticoid therapy. Recent, promising research reveals biomarkers that may yield more focused clinical monitoring and assessment of response to treatment. This article reviews unique features of paediatric SLE and details important developments in paediatric lupus research.
... bite or scratch of a wolf ("lupus" is Latin for wolf and "erythematosus" is Latin for red). SLE is the most serious form ... occurs more often in African-American, Asian-American, Latin-American, and Native-American women than in non- ...
Aliko, A; Ciancaglini, R; Alushi, A; Tafaj, A; Ruci, D
The aim of the present study was to estimate the prevalence of temporomandibular joint (TMJ) symptoms and clinical findings in Albanian patients with rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. The authors examined 124 consecutive hospitalized patients (88 with rheumatoid arthritis, 22 with systemic lupus erythematosus and 14 with systemic sclerosis) and 124 age- and gender-matched healthy controls using a questionnaire and an oro-facial clinical examination for assessing the presence of TMJ sounds, pain in the TMJ area, tenderness of masticatory muscles and limited mouth opening. Significantly more patients (67%) reported TMJ symptoms than controls (19%). A significantly higher proportion of patients (65%) exhibited clinical signs of temporomandibular dysfunction compared with controls (26%). The most frequent findings in rheumatoid arthritis were temporomandibular sounds and pain. Pain was found in a significantly higher proportion in patients with systemic lupus erythematosus compared with controls. Difficulty and limitation in mouth opening were observed in the majority of systemic sclerosis patients, and in only a minority of rheumatoid arthritis patients. This study supports the notion that TMJ examination should be encouraged in the rheumatology setting and clinicians should be able to provide pain management and patient support.
Wu, F-X; Wu, L-J; Luo, X-Y; Tang, Z; Yang, M-H; Xie, C-M; Liu, N-T; Zhou, J-G; Guan, J-L; Yuan, G-H
HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. A 14-bp insertion/deletion polymorphism in the HLA-G gene has been suggested to influence the expression of HLA-G and to associate with certain pathological conditions, including autoimmune diseases. We investigated the influence of the 14-bp insertion/deletion polymorphism in the HLA-G gene on disease susceptibility in systemic lupus erythematosus by genotyping this polymorphism in 231 patients with systemic lupus erythematosus and 367 healthy controls and analyzing the levels of soluble HLA-G in a subset of patients with systemic lupus erythematosus and healthy subjects from a Han Chinese population. No statistically significant differences were observed in the frequencies of the 14-bp insertion/deletion HLA-G alleles or genotypes between controls and patients with systemic lupus erythematosus. However, a significant increased expression of soluble HLA-G was noted in patients with systemic lupus erythematosus (mean value = 230.2 U/ml vs 118.3 U/ml in controls, p = 0.0001). Moreover, patients with high levels of soluble HLA-G presented with higher disease activity and had more neurological involvement. Our results do not support the HLA-G 14-bp insertion/deletion polymorphism as a genetic factor influencing systemic lupus erythematosus susceptibility. It is possible that the expression of soluble HLA-G in systemic lupus erythematosus is enhanced as part of a mechanism to try to restore the tolerance process towards auto-antigens and to counteract inflammation. However, the participation of this molecule in the pathological process of the disease also could not be excluded.
Harris, Julia G; Maletta, Kristyn I; Kuhn, Evelyn M; Olson, Judyann C
The aim of this study was to describe compliance with select quality indicators and assess organ-specific dysfunction in a childhood-onset systemic lupus erythematosus population by using a validated damage index and to evaluate associations between compliance with quality indicators and disease damage. A retrospective chart review was performed on patients diagnosed with systemic lupus erythematosus prior to age 18 followed at a single center in the USA from 1999 to 2012 (n = 75). Data regarding quality indicators and outcome variables, including the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, were collected. The median disease duration was 3.8 years. The proportion of patients or patient-years in which care complied with the proposed quality measures was 94.4% for hydroxychloroquine use, 84.3% for vitamin D recommendation,75.8% for influenza vaccination (patient-years), 67.2% for meningococcal vaccination, 49.0% for ophthalmologic examination (patient-years), 31.7% for pneumococcal vaccination, and 28.6% for bone mineral density evaluation. Disease damage was present in 41.3% of patients at last follow-up, with an average damage index score of 0.81. Disease damage at last follow-up was associated with minority race/ethnicity (p = 0.008), bone mineral density evaluation (p = 0.035), and vitamin D recommendation (p = 0.018). Adherence to quality indicators in a childhood-onset systemic lupus erythematosus population is varied, and disease damage is prevalent. This study highlights the importance of quality improvement initiatives aimed at optimizing care delivery to reduce disease damage in pediatric lupus patients.
Merklen-Djafri, Carine; Bessis, Didier; Frances, Camille; Poulalhon, Nicolas; Debarbieux, Sébastien; Cordel, Nadège; Lipsker, Dan
The nosology of bullous lesions or equivalents (vesicles, erosions, and crusts) in patients with lupus erythematosus (LE) is rarely addressed.The primary aim of this study was to draw up a precise phenotypic inventory of such skin lesions; the secondary objective was to assess a potential relationship between the different types of loss of epidermis and extracutaneous lupus manifestations.We conducted a retrospective multicenter study including 22 patients with definite LE and bullous lesions or equivalents. All biopsies were reviewed. Patients were recruited in the dermatology departments of 6 centers. Patients were included if they met the diagnosis of systemic LE according to American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics criteria or diagnosis of cutaneous LE based on classic clinical criteria and/or histological ascertainment of LE. Patients were recruited through clinician's memory and photographic collections.Three clinico-pathological patterns could be individualized. First, toxic epidermal necrolysis (TEN)-like, sheet-like, skin detachment; sun-exposure, mild mucosal involvement, and dermal mucin deposition allow differential diagnosis with classical Lyell syndrome. Second, vesiculo-bullae and/or crusting occurring on typical lesions of subacute cutaneous lupus erythematosus or chronic cutaneous lupus erythematosus. Third, tense vesicles and/or blisters with an underlying neutrophilic dermatosis and a usual response to dapsone.A careful analysis of 22 LE patients with epidermal detachment reveals 2 main pathomechanisms: a classic LE interface dermatitis, which can be hyperacute and lead to TEN-like skin detachment; and a neutrophilic dermatosis, with tense vesicles and/or blisters, including classic bullous LE.
Purpose of review Systemic lupus erythematosus (SLE) and Sjogren’s syndrome are chronic inflammatory diseases characterized by the dysfunction of T cells, B cells, and dendritic cells and the production of antinuclear autoantibodies. Here, we evaluate newly discovered molecular and cellular targets for the treatment of SLE and Sjogren’s syndrome. Recent findings The mammalian target of rapamycin in T and B cells has been successfully targeted for treatment of SLE with rapamycin or sirolimus both in patients and animal models. Inhibition of oxidative stress, nitric oxide production, interferon alpha, toll-like receptors 7 and 9, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, and the nuclear factor kappa B pathway showed efficacy in animal models of lupus. B-cell depletion and blockade of anti-DNA antibodies and T–B cell interaction have shown success in animal models, whereas human studies have so far failed to accomplish clinical endpoints, possibly due to inadequacies in study design. Summary Discovery of novel genes and signaling pathways in lupus pathogenesis offers novel biomarker-targeted approaches for treatment of SLE and Sjogren’s syndrome. PMID:19584730
Sibbitt, Wilmer L.; Brooks, William M.; Kornfeld, Mario; Hart, Blaine L.; Bankhurst, Arthur D.; Roldan, Carlos A.
Objective Magnetic resonance imaging (MRI) often demonstrates brain lesions in neuropsychiatric systemic lupus erythematosus (NPSL). The present study compared post-mortem histopathology with pre-mortem MRI in NPSL. Methods 200 subjects with NPSLE were studied prospectively with MRI over a 10-year period during which 22 subjects died. In 14 subjects, a brain autopsy with histopathology that permitted direct comparison with pre mortem MRI was successfully obtained. Surface anatomy was used to determine the approximate location of individual lesions. Results Pre mortem MRI findings in fatal NPSLE were small focal white matter lesions (100%), cortical atrophy (64%), ventricular dilation (57%), cerebral edema (50%), diffuse white matter abnormalities (43%), focal atrophy (36%), cerebral infarction (29%), acute leukoencephalopathy (25%), intracranial hemorrhage (21%), and calcifications (7%). Microscopic findings in fatal NPSLE included global ischemic changes (57%), parenchymal edema (50%), microhemorrhages (43%), glial hyperplasia (43%), diffuse neuronal/axonal loss (36%), resolved cerebral infarction (33%), microthomboemboli (29%), blood vessel remodeling (29%), acute cerebral infarction (14%), acute macrohemorrhages (14%), and resolved intracranial hemorrhages (7%). Cortical atrophy and ventricular dilation seen by MRI predicted brain mass at autopsy (r = -0.72, p = 0.01, and r = -0.77, p =0.01, respectively). Cerebral autopsy findings, including infarction, cerebral edema, intracranial hemorrhage, calcifications, cysts, and focal atrophy were also predicted accurately by pre mortem MRI. Conclusion Brain lesions in NPSLE detected by MRI accurately represent serious underlying cerebrovascular and parenchymal brain injury on pathology. PMID:19880162
Hawro, Tomasz; Krupińska-Kun, Maria; Rabe-Jabłońska, Jolanta; Sysa-Jędrzejowska, Anna; Robak, Ewa; Bogaczewicz, Jarosław; Woźniacka, Anna
Physicians' awareness about neuropsychiatric syndromes in systemic lupus erythematosus (SLE) is not rarely limited to seizures and psychoses included in the American College of Rheumatology (ACR) classification. Involvement of the central nervous system (CNS) with its rich symptomatology still belongs to the faintly recognised and understood aspects of lupus. The objective was to investigate prevalence and clinical correlations of psychiatric disorders in SLE patients. Fifty-two SLE patients were included. Disease duration and current and cumulative corticosteroid doses were calculated. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM). All subjects were examined by a psychiatrist. Psychiatric disorders were classified according to ACR criteria for neuropsychiatric systemic lupus erythematosus (NPSLE). Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) were used to screen for cognitive impairments. Mental disorders were diagnosed in 16 (30.77%), depressive disorder in 6 (11.54%), cognitive dysfunction in 5 (9.62%), anxiety disorder in 4 (7.69%) and psychosis in one patient (1.92%). SLE duration was shorter in patients diagnosed with anxiety disorder (P < 0.05), and cumulative dose of corticosteroids was lower in patients with anxiety disorder (P < 0.01). There was high positive correlation between SLE duration and cumulative dose of corticosteroids (r = 0.684, P < 0.001). Shorter SLE duration in patients with anxiety disorder seems to reflect its adaptative nature.
Ku, Ming; Guo, Shuiming; Shang, Weifeng; Li, Qing; Zeng, Rui; Han, Min; Ge, Shuwang; Xu, Gang
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects women during their reproductive years. The interaction between SLE and pregnancy remains debated. The objective of this study was to analyze the fetal and maternal outcomes of Chinese women with SLE. A total of 109 pregnancies in 83 SLE patients from June 2004 to June 2014 at a tertiary university hospital were reviewed retrospectively. Patients’ characteristics, clinical and laboratory data during pregnancy were obtained from electronic medical records. After exclusion of elective abortions, the live birth rate was 61.5%. Significantly, APS (antiphospholipid syndrome), disease activity, hypertension, hypocomplementemia, thrombocytopenia, and anemia during pregnancy were more commonly observed in fetal loss pregnancies than in live birth pregnancies. Compared to the 64 women with a history of SLE, 19 women with new-onset lupus during pregnancy had worse pregnancy outcome. Furthermore, the 64 patients with a history of SLE were divided into lupus nephritis group and SLE group (non-renal involvement). We found that the lupus nephritis group had worse maternal outcome than the SLE group. We conclude that new-onset lupus during pregnancy predicts both adverse maternal and fetal outcomes, while a history of lupus nephritis predicts adverse maternal outcomes. It is essential to provide SLE women with progestational counseling and regular multispecialty care during pregnancy. PMID:27442513
Inoue, M; Shiozawa, K; Yoshihara, R; Yamane, T; Shima, Y; Hirano, T; Makimoto, K
Sleep problems are common in patients with systemic lupus erythematosus (SLE). This study aimed to examine the following: (1) predictors of sleep quality and (2) fluctuations in sleep quality in patients with SLE. Patients with SLE were recruited from three rheumatology centers in Japan. We collected demographic and clinical data and data on sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI), the Medical Outcome Study Short Form-12, and the Lupus Patient Reported Outcome Tool (LupusPRO). Fluctuations in sleep quality were examined by administering the PSQI a second time after a 2-week interval. We used multiple linear regression analysis to predict sleep quality. Of 205 patients who completed the survey, 62.9% showed poor sleep quality. The largest fluctuation in sleep quality was for "waking in the middle of the night or early morning." "LupusPRO pain/vitality" was a major predictor of poor sleep. The other significant predictors were mostly LupusPRO subscales and clinical variables and SF-12 subscales were mostly non-predictive. The majority of the participants had poor sleep quality. A lupus-specific QoL scale is important for understanding poor sleep quality in SLE patients. Symptom management appeared to play a key role in improving sleep quality.
Duxbury, B; Combescure, C; Chizzolini, C
The wide spectrum of clinical manifestations and high relapse rate represent a therapeutic challenge in systemic lupus erythematosus (SLE). Observational studies suggested efficacy of rituximab (RTX), a B-cell-targeting antibody, to control the activity of SLE. Two randomized trials controlled by placebo did not prove the superiority of RTX when used in addition to conventional treatment in nonrenal (EXPLORER) and renal (LUNAR) lupus. A systematic review of studies exploring the efficacy of RTX in SLE patients was conducted. The pooled percentages of response were assessed. Thirty studies with 1243 patients were analyzed. In studies using the British Isles Lupus Assessment Group (BILAG), the complete response (CR) rate was 46.7% (95% CI 36.8%-56.8%) and the partial response (PR) was 37.9% (95% CI 30.6%-45.8%). With the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the CR was 56.6% (95% CI 32.4%-78.1%) and the PR was 30.9% (95% CI 8.9%-46%). In renal lupus the CR was 36.1% (95% CI 25.2%-48.6%); PR was 37.4% (95% CI 28.5%-47.3%). In EXPLORER, CR was 12.4% and PR was 17.2%; in LUNAR CR was 26.4% and PR was 30.6%, in both cases not different from controls. Assessment and standardization of SLE response to treatment remain a challenge. The discrepancy in the perceived efficacy of RTX between controlled and observational studies reflects the heterogeneity of lupus and stringency in criteria of response. Further randomized trials focusing on selected SLE manifestations and using composite response indices are warranted.
Bastian, H M; Roseman, J M; McGwin, G; Alarcón, G S; Friedman, A W; Fessler, B J; Baethge, B A; Reveille, J D
The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95
Ball, Elizabeth; Newburger, Amy; Ackerman, A Bernard
Degos' disease, known confusingly as malignant strophic papularis, is an uncommon condition of unknown cause characterized by distinctive infarctive lesions in the skin, gastrointestinal tract, and central nervous system; the lesions at the two latter sites often result in death. We deem Degos' disease to be analogous to lupus erythematosus in the sense that each is fundamentally a systemic pathologic process involving several organs, among them the skin, but, moreover, we regard Degos' disease, in most instances, to be an actual manifestation of lupus erythematosus. Histopathologically, the findings in sections of tissue of skin lesions of Degos' disease are indistinguishable from those of one expression of cutaneous lupus erythematosus; immunopathologically, some patients with morphologic findings stereotypical of Degos' disease display signs characteristic of lupus erythematosus. For these reasons, we consider Degos' disease to be a distinctive pattern of disease, rather than a specific disease per se, just as are erythema multiforme, erythema nodosum, leukocytoclastic vasculitis, Sweet's syndrome, and pyoderma gangrenosum, to name but five of scores of them. The singular pattern that is designated Degos' disease usually is an expression of lupus erythematosus, but, episodically, of conditions like dermatomyositis and rheumatoid arthritis.
Rodríguez-Rivera, Diana V; Rodríguez-Navedo, Yerania; Nieves-Plaza, Mariely; Vilá, Luis M
Objective: To determine patient-reported outcomes measures in indigent patients with systemic lupus erythematosus receiving their healthcare through the Puerto Rico government managed care system and compare these measures with non-indigent patients treated in a private fee-for-service setting. Methods: A cross-sectional study was conducted in a cohort of 98 Puerto Ricans with systemic lupus erythematosus. Patients from the public group (n = 40) were treated in a university-based specialized systemic lupus erythematosus clinic and the private group (n = 58) in a community-based rheumatology practice. Demographic and clinical features and patient-reported outcomes measures per LupusPRO instrument were determined. LupusPRO captures quality-of-life measures in 12 domains. Differences among study groups were examined using chi-square, Fisher’s exact, t-tests, and the Wilcoxon signed-rank test. Results: The mean (standard deviation) age of the study population was 44.9 (12.0) years; 94 (95.9%) were women. Patients in the public setting were younger and were more likely to have renal disease and elevated anti-double-stranded DNA antibodies, and being treated with azathioprine and cyclophosphamide. Patients from the public sector were more likely to have better quality-of-life measures in the LupusPRO domains of pain/vitality and coping. No significant differences were observed for the domains of lupus symptoms, physical health, emotional health, body image, cognition, procreation, lupus medications, desires/goals, social support, and satisfaction with medical care. Conclusion: Despite having a lower socioeconomic status and worse clinical status, systemic lupus erythematosus patients from the public sector had equal or better patient-reported outcomes measures than those treated in the private setting. This favorable outcome may be associated with the comprehensive healthcare received by these patients in a specialized lupus clinic. PMID:27721978
Jarukitsopa, Sudumpai; Hoganson, Deana D; Crowson, Cynthia S; Sokumbi, Olayemi; Davis, Mark D; Michet, Clement J; Matteson, Eric L; Maradit –Kremers, Hilal; Chowdhary, Vaidehi R
Objective Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993 to 2005. Methods SLE cases were identified from review of medical records and fulfilled the 1982 ACR classification criteria. CLE cases included patients with classic discoid LE (CDLE), subacute cutaneous LE (SCLE), lupus panniculitis and bullous LE. Age-and sex-adjusted incidence and prevalence were standardized to 2000 US white population. Results The age- and sex-adjusted incidence of SLE (2.9 per 100,000; 95% CI 2.0, 3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1, 5.2, p= 0.10). However, incidence of CLE was three times higher than SLE in males (2.4 versus 0.8 per 100,000, p=0.009). The age- and sex-adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; p<0.001). The prevalence of CLE and SLE in women were similar but the CLE prevalence was higher in men than in women (56.9 versus 1.6 per 100,000, p<0.001). The incidence of CLE rose steadily with age and peaked at 60-69 years. Conclusion The incidences of CLE and SLE are similar but CLE is more common than SLE in males and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE. PMID:25369985
Burns, Natalie S; Stevens, Anne M; Iyer, Ramesh S
Systemic lupus erythematosis (SLE) can affect the lungs and pleura, usually manifesting with pleural effusions or diffuse parenchymal disease. A rare manifestation of SLE is shrinking lung syndrome, a severe restrictive respiratory disorder. While pleuropulmonary complications of pediatric SLE are common, shrinking lung syndrome is exceedingly rare in children. We present a case of a 13-year-old girl previously diagnosed with lupus, who developed severe dyspnea on exertion and restrictive pulmonary physiology. Her chest radiographs on presentation demonstrated low lung volumes, and CT showed neither pleural nor parenchymal disease. Fluoroscopy demonstrated poor diaphragmatic excursion. While shrinking lung syndrome is described and studied in adults, there is only sparse reference to shrinking lung syndrome in children.
Sanchez, E; Webb, R; Rasmussen, A.; Kelly, J.A; Riba, L.; Kaufman, K.M.; Garcia-de la Torre, I.; Moctezuma, J.F.; Maradiaga-Ceceña, M.A.; Cardiel, M.; Acevedo, E.; Cucho-Venegas, M.; Garcia, M.A.; Gamron, S.; Pons-Estel, B.A.; Vasconcelos, C.; Martin, J.; Tusié-Luna, T.; Harley, J.B.; Richardson, B.; Sawalha, A.H.; Alarcón-Riquelme, M.E.
Objectives To analyze if genetically determined Amerindian ancestry predicts the increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus. Methods Single nucleotide polymorphisms within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo normal healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation of the presence of risk alleles with ancestry was done using linear regression. Results A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, PDCD1, ITGAM, and IRF5 were associated with lupus in a Hispanic-Mestizo cohort enriched for European and Amerindian ancestry. In addition, two SNPs within the MHC region, previously associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression we predict an average increase of 2.34 risk alleles when comparing a lupus patient with 100% Amerindian ancestry to an SLE patient with 0% American Indian Ancestry (p<0.0001). SLE patients with 43% more Amerindian ancestry are predicted to carry one additional risk allele. Conclusion Amerindian ancestry increased the number of risk alleles for lupus. PMID:20848568
Rojas, E; Orrea Solano, M
The central nervous system (CNS) manifestations of the chronic autoimmune disease systemic lupus erythematous (SLE) are reviewed. SLE-CNS dysfunction is broadly divided into neurologic and psychiatric clinical categories. The distinct clinical entities within these broad categories are fully described. Diagnostic criteria employed to verify the presence of SLE-CNS dysfunction, including laboratory serum and cerebral spinal fluid analyses as well as radiologic and other multimodality diagnostic tools, are compared and contrasted with respect to sensitivity and specificity.
Zhou, Yi; Chen, Huimei; Liu, Li; Yu, Xueqing; Sukhova, Galina K; Yang, Min; Zhang, Lijun; Kyttaris, Vasileios C; Tsokos, George C; Stillman, Isaac E; Ichimura, Takaharu; Bonventre, Joseph V; Libby, Peter; Shi, Guo-Ping
CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 Fas(lpr) mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro. The presence of kidney TECs from Fas(lpr) mice, rather than from wild-type mice, produced significantly stronger histones, dsDNA, and ribonucleoprotein-Smith Ag complex-induced CD4(+) T cell activation. Splenocytes from CD74-deficient Fas(lpr)Cd74(-/-) mice had muted responses in a MLR and to the autoantigen histones. Compared with Fas(lpr)Cd74(+/+) mice, Fas(lpr)Cd74(-/-) mice had reduced kidney and spleen sizes, splenic activated T cells and B cells, serum IgG and autoantibodies, urine albumin/creatinine ratio, kidney Periodic acid-Schiff score, IgG and C3 deposition, and serum IL-6 and IL-17A levels, but serum IL-2 and TGF-β levels were increased. Study of chronic graft-versus-host C57BL/6 mice that received donor splenocytes from B6.C-H2(bm12) /KhEg mice and those that received syngeneic donor splenocytes yielded similar observations. CD74 deficiency reduced lupus-like autoimmunity and kidney pathology in chronic graft-versus-host mice. This investigation establishes the direct participation of CD74 in autoimmunity and highlights a potential role for CD74 in kidney TECs, together with professional APCs in systemic lupus erythematosus.
Weening, Jan J; D'Agati, Vivette D; Schwartz, Melvin M; Seshan, Surya V; Alpers, Charles E; Appel, Gerald B; Balow, James E; Bruijn, Jan A; Cook, Terence; Ferrario, Franco; Fogo, Agnes B; Ginzler, Ellen M; Hebert, Lee; Hill, Gary; Hill, Prue; Jennette, J Charles; Kong, Norella C; Lesavre, Philippe; Lockshin, Michael; Looi, Lai-Meng; Makino, Hirofumi; Moura, Luiz A; Nagata, Michio
The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
Weening, Jan J; D'Agati, Vivette D; Schwartz, Melvin M; Seshan, Surya V; Alpers, Charles E; Appel, Gerald B; Balow, James E; Bruijn, Jan A; Cook, Terence; Ferrario, Franco; Fogo, Agnes B; Ginzler, Ellen M; Hebert, Lee; Hill, Gary; Hill, Prue; Jennette, J Charles; Kong, Norella C; Lesavre, Philippe; Lockshin, Michael; Looi, Lai-Meng; Makino, Hirofumi; Moura, Luiz A; Nagata, Michio
The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
Brunasso, A M G; Aberer, W; Massone, C
We report on a 52-year-old woman with a history of severe seronegative rheumatoid arthritis. Several conventional therapies and biological therapy with etanercept and infliximab had been unsuccessful. In 2010 she was given golimumab subcutaneously at a monthly dose of 50 mg. She had a negative ANA titre. After 16 months of uninterrupted therapy and sustained response, she developed skin lesions on the upper trunk, back and upper extremities, which worsened on exposure to the sun. The skin biopsy was compatible with subacute lupus erythematosus. Laboratory findings included an ANA titre 1:640, negative anti-Ro/SSA and anti-DNA antibodies. Topical corticosteroid therapy proved inadequate. The patient's condition improved only after discontinuation of golimumab. The causal relationship between subacute cutaneous lupus erythematosus and golimumab is not dose-related and occurs with some delay (a typical feature of immunological adverse reactions). The association is likely, but not confirmed (because re-challenge was not performed). However, a clear improvement was noted after withdrawal. Based on this case, we hypothesized the aetiological role of golimumab-associated immunogenicity. TNF-α antagonist-induced lupus-like syndrome (TAILS) is a well-known side effect of this class of substances. The British Society of Rheumatology recommends discontinuation of the causal anti-TNF-α treatment in patients with TAILS.
Márquez, Ana; Dávila-Fajardo, Cristina Lucía; Robledo, Gema; Rubio, José Luis Callejas; de Ramón Garrido, Enrique; García-Hernández, Francisco J; González-León, Rocío; Ríos-Fernández, Raquel; Barrera, José Cabeza; González-Escribano, Ma Francisca; García, Ma Teresa Camps; Palma, Ma Jesús Castillo; del Mar Ayala, Ma; Ortego-Centeno, Norberto; Martín, Javier
To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2-IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56%) and non-responder (45.45%) SLE patients (p=0.010, odds ratio (OR)=6.10 [1.28-29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p=0.024, OR=3.53 [1.06-11.64]). Our results show for a first time that IL2-IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.
Deng, Datong; Sun, Li; Xia, Tongjia; Xu, Min; Wang, Youmin; Zhang, Qiu
A case of a 42-year-old female with hyperthyroidism was subsequently diagnosed to have systemic lupus erythematosus with distal RTA. The clinical examination on admission showed swelling of the knee joints and the urinalysis showed pH 6.5, pro 3+. Her blood routine results were as follows: white blood cells 1.85×109/L, platelets 100×109/L, erythrocyte 3.06×1012/L. The serum potassium was 3.11 mmol/L, 24 hour urinary electrolyte: K 68.87 mmol/24 H, antinuclear antibodies (ANA) 1:1 000, speckled pattern. The anti-double stranded DNA antibody (anti-dsDNA), anti SS-A(52) antibody and anti SS-A(60) antibody were positive. The light microscopy and immunofluorescence showed diffuse proliferative lupus nephritis. These data were compatible with the diagnosis of systemic lupus erythematosus. The diagnosis of hyperthyroidism and distal RTA is clear. This report showed that other autoimmune disease in the diagnosis of hyperthyroidism should not be ignored.
Background The aim of this study was evaluate the late-onset repercussions of heart alterations of patients with systemic lupus erythematosus (SLE) after a 13-year follow up. Methods A historical prospective study was carried out involving the analysis of data from the charts of patients with a confirmed diagnosis of lupus in follow up since 1998. The 13-year evolution was systematically reviewed and tabulated to facilitate the interpretation of the data. Results Forty-eight patient charts were analyzed. Mean patient age was 34.5 ± 10.8 years at the time of diagnosis and 41.0 ± 10.3 years at the time of the study (45 women and 3 men). Eight deaths occurred in the follow-up period (two due to heart problems). Among the alterations found on the complementary exams, 46.2% of cases demonstrated worsening at reevaluation and four patients required a heart catheterization. In these cases, coronary angioplasty was performed due to the severity of the obstructions and one case required a further catheterization, culminating in the need for surgical myocardial revascularization. Conclusion The analysis demonstrated progressive heart impairment, with high rates of alterations on conventional complementary exams, including the need for angioplasty or revascularization surgery in four patients. These findings indicate the need for rigorous cardiac follow up in patients with systemic lupus erythematosus. PMID:23635330
Ruiz-Cerdá, M Leire; Irurzun-Arana, Itziar; González-Garcia, Ignacio; Hu, Chuanpu; Zhou, Honghui; Vermeulen, An; Trocóniz, Iñaki F; Gómez-Mantilla, José David
Drug development in Systemic Lupus Erythematosus (SLE) has been hindered by poor translation from successful preclinical experiments to clinical efficacy. This lack of success has been attributed to the high heterogeneity of SLE patients and to the lack of understanding of disease physiopathology. Modelling approaches could be useful for supporting the identification of targets, biomarkers and patient subpopulations with differential response to drugs. However, the use of traditional quantitative models based on differential equations is not justifiable in a sparse data situation. Boolean networks models are less demanding on the required data to be implemented and can provide insights into the dynamics of biological networks. This methodology allows the integration of all the available knowledge into a single framework to evaluate the behavior of the system under different conditions and test hypotheses about unknown aspects of the disease. In this proof-of-concept study, we explored the potential of a systems pharmacology model based on Boolean networks to support drug development in SLE. We focused the analysis on the antigen presentation by the antigen presenting cells (APC) to the T-cells to evaluate the scope of this methodology in a medium size network before full implementation of the whole SLE pathway. The heterogeneity of SLE patients was replicated using this methodology simulating subjects with distinct pathway alterations. A perturbation analysis of the network coupled with clustering analysis showed potential to identify drug targets, optimal combinatorial regimens and subpopulations of responders and non-responders to drug treatment. We propose this approach as a first step towards the development of more quantitative platforms to address the current challenges in drug development for complex diseases.
Ngaïdé, A A; Ly, F; Ly, K; Diao, M; Kane, Ad; Mbaye, A; Lèye, M; Aw, F; Sarr, S A; Dioum, M; Ndao, C T; Gaye, N D; Ndiaye, M B; Bodian, M; Bah, M B; Ndiaye, M; Cissé, A F; Kouamé, I; Tabane, A; Mingou, J S; Thiombiano, P; Kane, A; Bâ, S A
Systemic lupus erythematosus is a non-specific inflammatory disorder of an organ of unknown cause and autoimmune origin. Visceral injuries, including those cardiovascular, determine the prognosis of this disease primarily affecting women. The objectives of this study were to determine the frequency and describe the cardiovascular manifestations in systemic lupus erythematosus in a lupus population of the Dakar region. This is a multicenter prospective study descriptive and analytical conducted in the region of Dakar (Senegal) from 14 February 2011 to 2 July 2012. Patients were either hospitalized or monitored as outpatients. Included were all patients with lupus and meeting at least four criteria of the American College of Rheumatology of lupus disease classification 1997. All patients underwent physical examination, an electrocardiogram and an echocardiogram looking for cardiovascular damage. The collected data were entered into the Epi Info version 3.5.1 and processed with SPSS 16.0 software. Quantitative variables are described in the median and the qualitative workforce, percentage and frequency. We have included 50 patients. The average age of the population was 36.18 years. A female predominance is noted with a sex ratio man/woman of 0.09. Cardiovascular functional symptoms were dominated by dyspnea stage II to IV NYHA (26%) and palpitations (22%). The physical signs we have found were mainly tachycardia (40%), spontaneous turgor of the jugular veins (29%), a muffling of the heart sounds (29%) and a infandibulopulmonairy shock (18%). The frequency of cardiovascular events was 46%. Electrical cardiac events were dominated by sinus tachycardia (40%) of repolarization disorders (16.3%) type of ischemia, injury, ischemia injury, necrosis and hypertrophy with 18% atrial and left ventricular hypertrophy each. Furthermore, one case of BAV first degree at 280 ms was recorded. We found 19 cases of pericarditis including 2 tamponade, 3 cases of dilated cardiomyopathy
Furtado, João; Isenberg, David A
Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus.
Arce-Salinas, C A; Carmona-Escamilla, M A; Rodríguez-García, F
Only a few cases of complete atrioventricular block (AVB) in adult lupus patients have been previously described, but only one as the initial manifestation. A 19-year-old woman who presented with seizures and loss of consciousness, was diagnosed with complete ABV and underwent pacemaker placement. Over the next weeks she developed serositis, joint, cutaneous, and renal involvement; positive antinuclear antibodies and high anti-SSA/Ro titers. This is the second case with AVB as a feature of SLE at onset. A review of previous complete AVB cases of adult SLE patients is presented.
Otukesh, Hasan; Chalian, Majid; Hoseini, Rozita; Chalian, Hamid; Hooman, Nakysa; Bedayat, Arash; Yazdi, Reza Salman; Sabaghi, Saeed; Mahdavi, Saeed
We reported a series of ten patients with lupus nephritis (five patients in the relapse phase and five in the remission phase) and measured the macrophage migration inhibitory factor (MIF), an important pro-inflammatory cytokine with probable role in the pathogenesis of many inflammatory diseases, in their urine samples. MIF/creatinine (Cr) ratio directly correlated with disease activity and it does not have any significant difference between inactive disease and normal ones. We found that the urine MIF/Cr ratio not only differentiates active disease from inactive disease and normal ones but also correlates with the activity indices of renal pathology.
Sohns, Melanie; Friedrichs, Stefanie; Hung, Rayjean J.; Fehringer, Gord; McLaughlin, John; Amos, Christopher I.; Brennan, Paul; Risch, Angela; Brüske, Irene; Caporaso, Neil E.; Landi, Maria Teresa; Christiani, David C.; Wei, Yongyue; Bickeböller, Heike
Introduction Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease. Methods We performed a meta-analysis of seven GSAs for lung cancer, applying the method META-GSA. Overall, the information taken from 11,365 cases and 22,505 controls from within the TRICL/ILCCO consortia was used to investigate a total of 234 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results META-GSA reveals the systemic lupus erythematosus KEGG pathway hsa05322, driven by the gene region 6p21-22, as also implicated in lung cancer (p = 0.0306). This gene region is known to be associated with squamous cell lung carcinoma. The most important genes driving the significance of this pathway belong to the genomic areas HIST1-H4L, -1BN, -2BN, -H2AK, -H4K and C2/C4A/C4B. Within these areas, the markers most significantly associated with LC are rs13194781 (located within HIST12BN) and rs1270942 (located between C2 and C4A). Conclusions We have discovered a pathway currently marked as specific to systemic lupus erythematosus as being significantly implicated in lung cancer. The gene region 6p21-22 in this pathway appears to be more extensively associated with lung cancer than previously assumed. Given wide-stretched linkage disequilibrium to the area APOM/BAG6/MSH5, there is currently simply not enough information or evidence to conclude whether the potential pleiotropy of lung cancer and systemic lupus erythematosus is spurious, biological, or mediated. Further research into this pathway and gene region will be necessary. PMID:28273134
Kakati, Sanjeeb; Ahmed, Sobur U; Hussain, Masaraf
Introduction Neurological manifestations although common in Systemic Lupus Erythematosus (SLE), are often not recognized due to their diversed and varied presentation. Therefore, the study was planned to highlight the pattern of neurological involvement in SLE to help in early recognition. Aim To study the pattern of neurological involvement in SLE and its correlation with disease activity and different investigation. Materials and Methods This hospital based prospective observational study was carried out from August 2009 to July 2010. Diagnosed cases of SLE [based upon American Rheumatism Association (ARA) criteria] who presented with neurological manifestations at the time of diagnosis or develop during the course of the disease were included in the study. They were assessed clinically and investigated with neuroimaging and neurophysiological tests as applicable. Results In total, 52 consecutive patients with SLE were evaluated, 92% were female. The most common age group was 21 to 25 years. Nervous system involvement was found in 19 (36.54%) patients. Cognitive impairment was the most frequent manifestation, present in 11 (57.89%) patients followed by seizure disorder in eight patients (42.1%). Peripheral neuropathy was diagnosed in eight (42.1%), acute confusional state in six (31.57%) and headache and depression was diagnosed in five (26.31%) patients each. Less common manifestations were psychosis, movement disorder and aseptic meningitis. Percentage of neurological manifestations directly correlated with disease activity. A significant difference was found in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score between the patients with Neuro Psychiatric Systemic Lupus Erythematosus (NPSLE) and those without NPSLE (32.42±16.34 Vs 17.3±10.6). Conclusion Neurological involvement in SLE is seen relatively early in the course of the disease with cognitive impairment being the most common manifestation and correlate with disease activity. PMID
Nadri, Quaid; Althaf, Mohammed Mahdi
A number of neurological entities have been associated with systemic lupus erythematosus (SLE). Gullian-Barre syndrome (GBS) as a presenting feature of SLE remains uncommon with just 9 cases reported in the last half-century with the first case reported in 19641-9 (Table 1). We report a young female presenting with GBS in whom SLE and WHO class V lupus nephritis (LN) was subsequently diagnosed. The neurological symptoms partially responded to pulse methylprednisone, intravenous immunoglobulin (IVIG) and plasmapheresis.
Jiang, S; Lei, T-C; Xu, S-Z
Patients with systemic lupus erythematosus (SLE) have an increased susceptibility to bacterial, viral, fungal and parasitic infections. Cryptococcal infection of the central nervous system (CNS) is a rare but often fatal complication of SLE. Here we describe a case of cryptococcal meningitis in a female patient with active SLE, who was successfully treated with amphotericin B. This case suggests that the clinical findings of SLE patients with cryptococcal meningitis are non-specific and misleading, and early use of amphotericin B has a good response.
Mossell, James; Goldman, John A.; Barken, Derren; Alexander, Roberta Vezza
Background: Systemic lupus erythematosus (SLE) is a multifaceted disease, and its diagnosis may be challenging. A blood test for the diagnosis of SLE, the Avise Lupus test, has been recently commercialized and validated in clinical studies. Objectives: To evaluate the use of the Avise Lupus test by community rheumatologists. Methods: The study is a longitudinal, case-control, retrospective review of medical charts. Cases had a positive test result, and controls had a negative result; all patients were anti-nuclear antibodies (ANA) positive but negative for SLE-specific autoantibodies. Features of SLE, diagnosis, and medications at two time points were recorded. Results: Twenty of the 23 cases (87%) and 4 of the 23 controls (17%) were diagnosed with SLE (sensitivity=83%; specificity=86%). More cases than controls (43% vs. 17%) fulfilled 4 American College of Rheumatology (ACR) classification criteria of SLE. Sensitivity of the test was significantly higher than the ACR score (83% vs. 42%, p=0.006). A higher percentage of patients who met the classification criteria had elevated cell-bound complement activation products (CB-CAPs) compared to patients who did not. Anti-rheumatic medications were used in a higher percentage of cases than controls (83% vs. 35% at baseline, p=0.002), suggesting that cases were treated more aggressively early on. Conclusion: A positive Avise Lupus test result aids in formulating a SLE diagnosis when diagnosis based on standard-of-care tests and clinical features may be challenging, and impacts patient management. Prospective studies will be performed to better evaluate the clinical utility of the test and of CB-CAPs as biomarkers of SLE. PMID:27867431
Tani, Chiara; Trieste, Leopoldo; Lorenzoni, Valentina; Cannizzo, Sara; Turchetti, Giuseppe; Mosca, Marta
Recent advances in health information technologies (HIT) in systemic lupus erythematosus have included electronic databases and registries, computerised clinical charts for patient monitoring, computerised diagnostic tools, computerised prediction rules and, more recently, disease-specific applications for mobile devices for physicians, health care professionals, and patients. Traditionally, HIT development has been oriented primarily to physicians and public administrators. However, more recent development of patient-centered Apps could improve communication and empower patients in the daily management of their disease. Economic advantages could also result from the use of HIT, including these Apps by collecting real life data that could be used in both economic analyses and to improve patient care.
Malcangi, G; Fraticelli, P; Palmieri, C; Cappelli, M; Danieli, M G
We report on a case of a 17-year-old female with systemic lupus erythematosus (SLE), with a clinical history of complex partial seizure, who developed a tonicoclonic crisis after receiving hydroxychloroquine for 2 weeks at a dosage of 200 mg/day (5 mg/kg). The absence of previous similar episodes and of recurrences after withdrawal of the drug in subsequent months, the short latency after administration and the favourable short-term evolution raised suspicions for a potential role of the drug in the development of the isolated convulsive crisis. It is possible for hydroxychloroquine to be responsible for tonicoclonic seizures in predisposed subjects.
Martínez-Martínez, Marco Ulises; Abud-Mendoza, Carlos
Diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus is a rare but potentially fatal condition. Although the pathogenesis of this condition is unknown, high disease activity is the main characteristic; moreover, histopathology in some studies showed alveolar immune complex deposits and capillaritis. Clinical features of DAH include dyspnea, a drop in hemoglobin, and diffuse radiographic alveolar images, with or without hemoptysis. Factors associated with mortality include mechanical ventilation, renal failure, and infections. Bacterial infections have been reported frequently in patients with DAH, but also invasive fungal infections including aspergillosis. DAH treatment is based on high dose methylprednisolone; other accepted therapies include cyclophosphamide (controversial), plasmapheresis, immunoglobulin and rituximab.
Esteva, M H; Blasini, A M; Ogly, D; Rodríguez, M A
False positive results were obtained for HIV tests in two men with active systemic lupus erythematosus (SLE) who were suspected of being infected with HIV because of fever, weight loss, lymphadenopathy, and inflammatory myopathy. Enzyme linked immunosorbent assays (ELISAs) for HIV were twice positive when tested three times over a period of six months. Western blot analysis showed reactivity against the gp41 band in patient 1. False positive results for HIV tests can occur in patients with SLE, potentially leading to an erroneous diagnosis of HIV infection. PMID:1417140
Menor Almagro, Raúl; Ruiz Tudela, María del Mar; Girón Úbeda, Juan; Cardiel Rios, Mario H; Pérez Venegas, José Javier; García Guijo, Carmen
Transverse myelitis is a rare focal inflammation of the spinal cord. Multiple etiologies have been identified including autoimmune diseases, mainly systemic lupus erythematosus and Sjögren' syndrome. It can occur in an acute or subacute clinical onset, with the acute presentation having a worse prognosis. An early diagnosis and intensive treatment are important features recommended in these patients. We present three cases with transverse myelitis associated with autoimmune diseases. We discuss different clinical manifestations, association with autoantobodies, radiologic findings, and therapeutic and prognostic issues.
Pretorius, Etheresia; du Plooy, Jenny; Soma, Prashilla; Gasparyan, Armen Yuri
The study suggests that patients with systemic lupus erythematosus (SLE) present with distinct inflammatory ultrastructural changes such as platelets blebbing, generation of platelet-derived microparticles, spontaneous formation of massive fibrin network and fusion of the erythrocytes membranes. Lupoid platelets actively interact with other inflammatory cells, particularly with white blood cells (WBCs), and the massive fibrin network facilitates such an interaction. It is possible that the concerted actions of platelets, erythrocytes and WBC, caught in the inflammatory fibrin network, predispose to pro-thrombotic states in patients with SLE.
Nabors, Laura; Ige, Teminijesu John; Fevrier, Bradley
This paper reviews information on Systemic Lupus Erythematosus (SLE) in children. Children with this chronic illness often experience pain related to their condition. They also can experience social isolation. This paper reviews psychosocial information on peer support and cognitive behavioral pain management strategies. The information presented in this paper provides new insights for health professionals assisting children and families in coping with psychological facets of this disease. Research focusing on ways by which peers and friends can support the child's use of psychological pain management strategies will provide new information for the literature. PMID:26583153
Klein, Rachel S.; Sayre, Robert M.; Dowdy, John C.; Werth, Victoria P.
It is well known that ultraviolet radiation can exacerbate skin disease in patients with lupus erythematosus. While many patients are advised to avoid sunlight and artificial tanning, it is not clear how best to counsel patients regarding the use of indoor lamps. Indeed, many of the light bulbs commonly used in the home and workplace emit low-dose ultraviolet radiation. The irradiance is considerably lower than that of the sun, however the exposure time can last for hours and is typically repeated on a daily basis. Therefore, it is possible that this chronic exposure could ultimately result in a significant accumulation of damage. PMID:18992852
Utermohlen, Virginia; Winfield, John B.; Zabriskie, John B.; Kunkel, Henry G.
Using the direct migration inhibition test, response to measles antigen in patients with systemic lupus erythematosus (SLE) was found to be decreased when compared with that of normal subjects. No alteration was observed in similar experiments using parainfluenza type 1 and rubella antigens. The specific decrease in measles antigen effect showed no obvious correlation with activity of SLE or with the presence of lymphocytotoxic antibodies. Whether the specificity of the decrease in reactivity is due to some particular relationship between the measles virus or antigen and SLE, or to the possibility that measles reactivity is a more sensitive indicator of a generalized defect of cell-mediated immunity, remains unclear. PMID:4361242
Dai, Chao; Deng, Yun; Quinlan, Aaron; Gaskin, Felicia; Tsao, Betty P; Fu, Shu Man
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disorder. Considerable progress has been made to delineate the genetic control of this complex disorder. In this review, selected aspects of human and mouse genetics related to SLE are reviewed with emphasis on genes that contribute to both innate and adaptive immunity and to genes that contribute directly to susceptibility to end organ damage. It is concluded that the interactions among these two major pathways will provide further insight into the pathogenesis of SLE. An interactive model of the two major pathways is proposed without emphasis on the importance of breaking tolerance to autoantigens. PMID:25458999
Mandik-Nayak, Laura; Ridge, Natalie; Fields, Michele; Park, Audrey Y; Erikson, Jan
B cell tolerance to many self-proteins is actively maintained by either purging self-reactive B receptors through clonal deletion and receptor editing, or by functional silencing known as anergy. However, these processes are clearly incomplete as B cell driven autoimmune diseases still occur. The significance of B cells in two such diseases, rheumatoid arthritis and systemic lupus erythematosus, is highlighted by the ameliorative effects of B cell depletion. It remains to be determined, however, whether the key role of the B cell in autoimmune disease is autoantibody production or another antibody-independent function.
Cansu, Döndü Üsküdar; Teke, Hava Üsküdar; Korkmaz, Cengiz
Hematological abnormalities are very common in the course of systemic lupus erythematosus (SLE). Myelofibrosis is a bone marrow disorder in which there is excessive fibrous tissue formation in the bone marrow. Various benign and malignant disorders can cause or be associated with a diffuse increase in the bone marrow reticular tissue. Some diseases such as infections, neoplasms, and autoimmune diseases may also induce bone marrow fibrosis (secondary myelofibrosis). Cytopenia from autoimmune myelofibrosis (AIMF) in SLE is a rare condition. Here we present a case of AIMF associated with SLE and aim to emphasize on the other cause of cytopenia in SLE. PMID:28293461
Hegazi, M O; Saleh, F; Al Rashidi, A; Yaktien, M M
Rheumatologists are increasingly aware of the entity synovitis with pitting edema. The remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome has been reported with an array of conditions that include polymyalgia rheumatica, rheumatoid arthritis, Sjögren's syndrome and psoriatic arthropathy. Synovitis with pitting edema is now being increasingly recognized with systemic lupus erythematosus (SLE). We report a patient who presented with edema of hands and feet and was diagnosed eventually with definite SLE. With magnetic resonance imaging, joint effusions and tenosynovitis were confirmed to be associated with the otherwise-unexplained extremity edema.
Nozari, Neda; Divsalar, Parisa
This case report demonstrates fatal gastrointestinal vasculitis as a rare presentation of systemic lupus erythematosus. A 34-year-old woman presented with abdominal pain and diarrhea. Anti nuclear antibody was positive and high titre of anti-ds DNA antibody was also reported. Treatment with corticosteroid and supportive cares were started; however, her condition worsened. Eventually, she was considered as a candidate for diagnostic laparoscopy. Immediately after laparoscopy, she developed respiratory distress along with upper gastrointestinal bleeding. Soon after, the patient died because of disseminated intravascular coagulation . PMID:25093065
Suárez H, Felipe; Urrutia E, Daniela; Canales P, Felipe; Gutiérrez O, Camila
Neuromyelitis optica (NMO) is a severe demyelinating disease of the central nervous system, which preferentially attacks the optic nerve and spinal cord. It is associated with antibodies against aquaporin 4. Morbidity and mortality are higher than in multiple sclerosis and its treatment focuses on immunosuppressive drugs. Immunomodulators are contraindicated. We report a previously healthy 35-year-old man, presenting with NMO concomitantly with systemic lupus erythematosus. His evolution was torpid with three outbreaks in the 10 months after the diagnosis, requiring a first-line therapy with methylprednisolone and cyclophosphamide and then a second-line therapy with rituximab.
Rezaieyazdi, Zahra; Sharifi-Doloui, Davood; Hashemzadeh, Kamila; Shirdel, Abbas; Mansouritorghabeh, Hassan
Acquired haemophilia A, secondary to systemic lupus erythematosus (SLE) is a rare bleeding diathesis. Here we report a 37-year-old woman with autoimmune hepatitis who developed SLE and acquired haemophilia caused by factor VIII inhibitors. She presented with spontaneous ecchymosis and haematuria. There were a prolongation of the activated partial thromboplastin time, reduced factor VIII activity and a high titer of FVIII inhibitors. Therapeutic regimen was started with intravenous methylprednisolone pulse, continued with prednisolone, intravenous pulse cyclophosphamide and fresh frozen plasma. After 8 weeks, factor VIII inhibitor assay was negative.
Rezaieyazdi, Zahra; Sharifi-Doloui, Davood; Hashemzadeh, Kamila; Shirdel, Abbas; Mansouritorghabeh, Hassan
Acquired haemophilia A, secondary to systemic lupus erythematosus (SLE), is a rare bleeding diathesis. Here we report a 37-year-old woman with autoimmune hepatitis who developed SLE and acquired haemophilia caused by factor VIII (fVIII) inhibitors. She presented with spontaneous ecchymosis and haematuria. There were a prolongation of the activated partial thromboplastin time, reduced fVIII activity and a high titre of fVIII inhibitors. Therapeutic regimen was started with intravenous methylprednisolone pulse, continued with prednisolone, intravenous pulse cyclophosphamide and fresh frozen plasma. After 8 weeks, fVIII inhibitor assay was negative.
Zhang, L; Liu, J J; Li, M T
In this report we discuss a case of a patient with systemic lupus erythematosus who developed herpes simplex virus type 1(HSV-1) infection presenting with encephalitis as well as necrotic and non-necrotic retinitis. The patient presented with typical clinical symptoms and radiologic abnormalities consistent with HSV-1 encephalitis and HSV-1 retinitis in patients with HIV infection, but lacked cerebrospinal fluid pleocytosis and had bilateral retinitis with poor visual acuity. To the best of our knowledge, this is the first such case reported in the literature.
Perez, H.D.; Kramer, N.
Pulmonary hypertension has been reported rarely in patients with systemic lupus erythematosus (SLE). During the past 31/2 yr we have observed pulmonary hypertension as a major clinical manifestation of their disease in four of 43 patients with well-documented SLE followed at out institution. Pulmonary hypertension could be attributed to underlying lung disease in three and was considered to be primary in the remaining patient. Neither hydralazine nor prednisone administration had any effect on the course of the pulmonary hypertension in these patients. The presence of pulmonary hypertension in the course of active SLE may be more common than previously recognized.
Aguirre, Verónica; Alvo, Miriam; Ardiles, Leopoldo; Carpio, J Daniel; Foster, Carolina; Goecke, Annelise; Jalil, Roberto; Massardo, Loreto; Palma, Sergio; Roessler, Emilio; Wurgaft, Andrés
Renal involvement affects over one half of patients with Systemic Lupus Erythematosus increasing their mortality and morbidity, including chronic renal disease and the need of renal replacement therapies. Aiming to achieve a consensus in the most relevant topics on diagnosis, therapy and follow-up of patients with lupus renal disease, the Chilean Societies of Nephrology and Rheumatology constituted a workgroup that, based on a critical review of the available literature and their experience, raised and answered by consensus a set of relevant questions. This document includes aspects related to the clinical diagnosis, the importance of a suitable histological classification, therapeutic alternatives to induce and maintain disease remission, strategies for follow-up, additional therapies and gynecological-obstetric issues.
Crampton, Steve P.; Morawski, Peter A.; Bolland, Silvia
Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease. PMID:25147296
Abdel Galil, S M
Increased serum level of liver enzymes is a common finding in patients with systemic lupus erythematosus (SLE). Hepatotoxic drugs, viral hepatitis and fatty liver are thought to be the main causes of hepatic lesion in these patients. Our aim was to determine the cause of strikingly elevated liver enzymes in a case with systemic lupus presenting with acute abdomen. Liver enzyme abnormality was defined as a 10-fold or greater increase in aspartate aminotransferase and alanine aminotransferase. Acute toxic hepatitis was diagnosed, which rapidly returned to normal after cessation of the suspected causative medication, hydroxychloroquine, and subsequent administration of mycophenolate mofetil. Elevated liver enzymes are a major concern and should be well investigated in SLE patients.
Activation of the classical pathway complement system has long been implicated in stimulating immune complex mediated tissue destruction in systemic lupus erythematosus (SLE). C3 and C4 complement levels are utilized as part of SLE diagnosis and monitoring criteria. Recently, cell bound complement activation products (CBCAPs) have shown increased sensitivity in diagnosing and monitoring lupus activity, compared to traditional markers. CBCAPs are increasingly utilized in rheumatology practice as additional serological markers in evaluating SLE patients. We report a case of a patient diagnosed with SLE that had chronically low C3 and C4, along with negative CBCAPs. We surmise that the patient has an inherited complement deficiency as the etiology of her SLE and that CBCAPs could be used to predict such deficiency. PMID:28074166
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease and is usually diagnosed with the SLICC criteria. Here we report a case of SLE presenting as Herpes Zoster (HZ). She had presented with painful vesicular eruptions from 8th thoracic nerve to 10th thoracic nerve segments and oliguria. There were no clinical manifestations suggestive of SLE. However, on further workup, haematological and immunologic laboratory profiles were suggestive of SLE. A diagnosis of lupus nephropathy was confirmed by renal biopsy and final diagnosis of SLE as the underlying systemic illness associated with HZ was established. We report this case because this patient had none of the manifestations of SLE, as a result of which this would have been an incomplete diagnosis. PMID:27134921
Mosaad, Naglaa Abd Elrahman; Lotfy, Hala Mohamed; Farag, Yomna Mohamed; Mahfouz, Rasha Hossam El-Din; Shahin, Rasha Mohamad Hosny
The aim of the study was to assess the serum levels of Syndecan-1 in a group of Egyptian juvenile systemic lupus erythematosus (JSLE) patients and to study any possible associations with disease activity, renal activity and organ damage. Serum level of Syndecan-1 was assessed in 60 Egyptian JSLE patients and 30 apparently healthy age and gender matched children using ELISA. SLE Disease Activity Index-2000 (SLEDAI-2K), renal SLEDAI-2K, renal activity score and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index were assessed for all patients. Serum SDC-1 levels were higher in patients with JSLE than in healthy controls (p<0.001) and were positively correlated with SLEDAI-2K (p<0.001), with renal SLEDAI score (p=0.008) and renal activity score (p=0.04). So, Syndecan-1 might be used as a marker for disease activity and renal activity in JSLE patients.
Suzuki, Akitake; Shoji, Norikazu; Aoki, Naoko; Asazuma, Naoki; Machinami, Rikuo; Kojima, Masaru; Okai, Takahiro
Herein we report a case of the simultaneous occurrence of angioimmunoblastic T-cell lymphoma (AITL) and systemic lupus erythematosus (SLE) in a 76-year-old woman. She presented with fever, night sweats, and general malaise. A laboratory examination revealed leukopenia, anemia, polyclonal hypergammaglobulinemia, hypocomplementemia, positive results for anti-nuclear antibodies and anti-double strand DNA (anti-dsDNA) antibodies, and mild proteinuria. A computed tomography scan of the abdominal cavity showed multiple swollen intra-abdominal and intra-pelvic lymph nodes. A biopsy specimen obtained from the peri-iliac lymph node confirmed the diagnosis of AITL, while renal biopsy results were consistent with lupus nephritis, International Society of Nephrology and Renal Pathology Society class V. These results indicated that our patient developed SLE concomitantly with AITL. These findings will lead to further understanding of the pathogenic mechanism of SLE.
Carrasco Cubero, Carmen; Bejarano Moguel, Verónica; Fernández Gil, M Ángeles; Álvarez Vega, Jose Luis
Tuberous sclerosis, also called Bourneville Pringle disease, is a phakomatosis with potential dermal, nerve, kidney and lung damage. It is characterized by the development of benign proliferations in many organs, which result in different clinical manifestations. It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). MTOR activation signal has been recently described in systemic lupus erythematosus (SLE) and its inhibition could be beneficial in patients with lupus nephritis. We report the case of a patient who began with clinical manifestations of tuberous sclerosis complex (TSC) 30 years after the onset of SLE with severe renal disease (tipe IV nephritis) who improved after treatment with iv pulses of cyclophosphamide. We found only two similar cases in the literature, and hence considered the coexistence of these two entities of great interest.
Mathew, M; Cherian, A
An adolescent boy presented with headache, bilateral papilloedema, growth retardation and absent secondary sexual characteristics. The diagnosis of intracranial hypertension was confirmed by increased intracranial pressure and normal neuroimaging of the brain except for partial empty sella and prominent perioptic cerebrospinal fluid (CSF) spaces. Evaluation showed an erythrocyte sedimentation rate of 150 mm/hr, positive antinuclear antibody, anti-dsDNA and antiribosomal P protein. Renal biopsy revealed diffuse segmental proliferative lupus nephritis (LN) class IV-S (A), which confirmed the diagnosis of systemic lupus erythematosus (SLE). Treatment of LN with intravenous pulse methylprednisolone and cyclophosphamide normalised the patient's CSF pressure and symptoms. In cases of intracranial hypertension, SLE must be considered. Growth retardation and absence of secondary sexual characteristics could coexist and may be presenting features of SLE. These manifestations point to advanced grades of LN, which could be asymptomatic and may be missed without a renal biopsy.
Silva, Clovis Artur; Aikawa, Nadia Emi; Pereira, Rosa Maria Rodrigues; Campos, Lucia Maria Arruda
Childhood-onset systemic lupus erythematosus (cSLE) is a chronic inflammatory and autoimmune disease that may involve various organs and systems. This narrative review focuses on the recent evidence relating to cSLE management. The general management considerations of cSLE patients require the use of validated classification criteria, disease and health-related quality of life tools evaluation, as well as assessments of lupus nephritis biomarkers and cSLE quality indicators. The drug treatment for cSLE patients includes general supportive care and immunosuppressive therapy. Important implications on cSLE therapy are also updated such as infection, vaccination, infertility, pregnancy, contraception, dyslipidemia, physical activity, cancer, bone health, drug pharmacokinetics, adherence, academic outcomes, transition to adult care and cumulative organ damage.
... Twitter Facebook Pinterest Email Print Different types of lupus Lupus Foundation of America February 24, 2017 Resource ... lupus. Learn more about each type below. Systemic Lupus Erythematosus Systemic lupus is the most common form ...
Checa, A; Idborg, H; Zandian, A; Sar, D Garcia; Surowiec, I; Trygg, J; Svenungsson, E; Jakobsson, P-J; Nilsson, P; Gunnarsson, I; Wheelock, C E
Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C16:0- and C24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with
Wang, Hongxu; Cao, Ju; Lai, Xiaofei
Interleukin-34 (IL-34) was initially identified as an alternative ligand for the colony-stimulating factor-1 receptor (CSF-1R) to mediate the biology of mononuclear phagocytic cells. Recently, IL-34 was found to be associated with chronic inflammation, such as in rheumatoid arthritis (RA). Both RA and systemic lupus erythematosus (SLE) are multifactorial autoimmune diseases and are characterized by excessive immune and inflammatory responses. Thus, we investigated whether IL-34 is involved in the pathogenesis of SLE. In all, 78 SLE patients and 53 healthy controls were enrolled in the research. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the concentrations of serological IL-34. Then serum IL-34 levels between the SLE group and healthy controls were analyzed by the Mann-Whitney U test. Meanwhile, the correlations between the serum IL-34 levels and disease activity indexes and other established serum markers were assessed. Furthermore, the serum IL-34 levels of 20 active SLE patients were reevaluated when diseases were in the remission stage from corticosteroids or immunosuppressive drugs. Serum IL-34 levels were significantly higher in SLE patients compared to healthy controls. Their levels were remarkably associated with accumulation of the clinical features of SLE. Additionally, IL-34 titers were positively correlated with the SLE disease activity indexes, anti-double-stranded DNA antibody (anti-dsDNA) titers and C-reactive protein (CRP) levels, and inversely with complement3 (C3) levels. Moreover, serum IL-34 levels were significantly decreased after successful treatment of SLE. Serum IL-34 could be a candidate biomarker for SLE as there are elevated serum levels in treatment-naive SLE patients and we saw a significant decrease after effective treatment.
Martins, Sofia S; Buscatti, Izabel M; Freire, Pricilla S; Cavalcante, Erica G; Sallum, Adriana M; Campos, Lucia M A; Silva, Clovis A
Kikuchi-Fujimoto disease (KFD) is a self-limiting histiocytic necrotizing lymphadenitis of unknown origin. Of note, KFD was infrequently reported in adult systemic lupus erythematosus (SLE), with rare occurrence in childhood-SLE (C-SLE) patients. To our knowledge, the prevalence of KFD in the paediatric lupus population was not studied. Therefore, in a period of 29 consecutive years, 5,682 patients were followed at our institution and 289 (5%) met the American College of Rheumatology classification criteria for SLE, one had isolated KFD (0.03) and only one had KFD associated to C-SLE diagnoses, which case was reported herein. A 12 year-old female patient had high fever, fatigue and cervical and axillary lymphadenopathy. The antinuclear antibodies (ANA) were negative, with positive IgM and IgG herpes simplex virus type 1 and type 2 serologies. Fluorine-18-fluoro-deoxy-glucose positron emission tomography/computed tomography (PET/CT) imaging demonstrated diffuse lymphadenopathy. The axillary lymph node biopsy showed necrotizing lymphadenitis with histiocytes, without lymphoproliferative disease, compatible with KFD. After 30 days, she presented spontaneous regression and no therapy was required. Nine months later, she developed malar rash, photosensitivity, oral ulcers, lymphopenia and ANA 1:320 (homogeneous nuclear pattern). At that moment the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 and she was treated with prednisone (1.0mg/kg/day) and hidroxychloroquine showing progressive improvement of hers signs and symptoms. In conclusion, KFD is a benign and rare disease in our paediatric lupus population. We also would like to reinforce the relevance of autoimmune diseases diagnosis during the follow-up of patients with KFD.
Kao, Amy H.; Navratil, Jeannine S.; Ruffing, Margie J.; Liu, Chau-Ching; Hawkins, Douglas; McKinnon, Kathleen M.; Danchenko, Natalya; Ahearn, Joseph M.; Manzi, Susan
Objective Disease activity in systemic lupus erythematosus (SLE) is typically monitored by measuring serum C3 and C4. However, these proteins have limited utility as lupus biomarkers, because they are substrates rather than products of complement activation. The aim of this study was to evaluate the utility of measuring the erythrocyte-bound complement activation products, erythrocyte-bound C3d (E-C3d) and E-C4d, compared with that of serum C3 and C4 for monitoring disease activity in patients with SLE. Methods The levels of E-C3d and E-C4d were measured by flow cytometry in 157 patients with SLE, 290 patients with other diseases, and 256 healthy individuals. The patients with SLE were followed up longitudinally. Disease activity was measured at each visit, using the validated Systemic Lupus Activity Measure (SLAM) and the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results At baseline, patients with SLE had higher median levels of E-C3d and E-C4d (P < 0.0001) in addition to higher within-patient and between-patient variability in both E-C3d and E-C4d when compared with the 2 non-SLE groups. In a longitudinal analysis of patients with SLE, E-C3d, E-C4d, serum C3, and anti–double-stranded DNA (anti-dsDNA) antibodies were each significantly associated with the SLAM and SELENA–SLEDAI. In a multivariable analysis, E-C4d remained significantly associated with these SLE activity measures after adjusting for serum C3, C4, and anti-dsDNA antibodies; however, E-C3d was associated with the SLAM but not with the SELENA–SLEDAI. Conclusion Determining the levels of the erythrocyte-bound complement activation products, especially E-C4d, is an informative measure of SLE disease activity as compared with assessing serum C4 levels and should be considered for monitoring disease activity in patients with SLE. PMID:20187154
Jiménez-Alonso, J; Vargas-Hitos, J A; Navarrete-Navarrete, N; Zamora-Pasadas, M; Aguilar-Huergo, S; Jáimez, L; Sabio, J M
A series of measures in the management of patients with systemic lupus erythematosus (SLE) which usually are not found in the lupus guidelines are discussed. In the lupus patient who has been well-controlled in the long term, the dose of hydroxychloroquine should be progressively reduced, without decreasing more than approximately 600 mg per week. We recommend taking this drug in the morning in patients with insomnia, at night in those with dyspepsia and to separate the intake of the drug from the shower (and the water should be as cool as possible) in those patients with aquagenic pruritus. We do not use prednisone on alternate days and exceptionally divide the dose into ¾ before breakfast and ¼ before dinner. Twenty to 30 min should be used per patient in every scheduled visit to assure a good clinical and human practice. We analyzed the follow-up of 112 consecutive patients from our systemic disease unit and found that 71.4% of them had symptoms that were unexplained by lupus and we only referred 8.9% of them to other specialists, probably because of our general training as internal medicine doctors. We suggest that knowing the views of SLE specialists might be of interest since, well-designed studies that would allow to progress in the understanding of this disease could be performed based on their experience.
Wakaki, K; Koizumi, F; Fukase, M
An autopsy case with SLE suffering from Raynaud's phenomenon and pulmonary hypertension was reported. Histological examinations revealed systemically marked fibrous intimal thickening of arteries and arterioles with or without thrombus throughout the whole body, especially of the pulmonary arteries and arterioles. Pulmonary arterial changes in the present case were compared with those in 52 autopsied cases with SLE without pulmonary hypertension, but there were no cases with such marked arterial changes as the present case. In addition, the incidence of pulmonary thrombosis was significantly higher in the cases with Raynaud's phenomenon than the cases without this phenomenon. However, the relation between pulmonary hypertension and Raynaud's phenomenon, pulmonary thrombosis, fibrous pericarditis, or type of lupus nephritis in SLE could not be clarified with a significant difference.
Valor, Lara; López-Longo, Francisco Javier
Systemic lupus erythematosus is an autoimmune disease associated with an aberrant production of autoantibodies by self-reactive B lymphocytes. The study of the phenotypic characteristics of B lymphocytes and the identification of their surface receptors such as BAFF-R, TACI and BCMA, which are responsible of their survival and maturation, have contributed to the development of new therapeutic strategies in recent years.
Zvetina, J.R.; Rubinstein, H.; Demos, T.C.
Atypical mycobacterial infections of bone are rare. A patient with systemic lupus erythematosus treated with steroids developed an M. intracellulare infection of the shoulder and spine. These infections are insidious and diagnosis is difficult. Marked involvement of one joint, large effusion, or aspirated small synovial fragments suggest an atypical tuberculous joint infection.
Machado, Roberta Ismael Lacerda; Scheinberg, Morton Aaron; de Queiroz, Maria Yvone Carlos Formiga; de Brito, Danielle Christinne Soares Egypto; Guimarães, Maria Fernanda Brandao de Resende; Giovelli, Raquel Altoé; Freire, Eutilia Andrade Medeiros
ABSTRACT Objective: To report the experience in three Brazilian institutions with the use of rituximab in patients with different clinical forms of lupus erythematosus systemic in activity. Methods: The study consisted of a sample of 17 patients with LES, who were already being treated, but that at some stage of the disease showed refractory symptoms. The patients were subdivided into groups according to the clinical manifestation, and the responses for the use of rituximab were rated as complete, partial or no response. Data were collected through a spreadsheet, and used specific parameters for each group. The treatment was carried on by using therapeutic dose of 1g, and repeating the infusion within an interval of 15 days. Results: The clinical responses to rituximab of the group only hematological and of the group only osteoarticular were complete in all cases. In the renal group there was a clinical complete response, two partial and one absent. In the renal and hematological group complete response, there was one death and a missing response. The pulmonary group presented a complete response and two partial. Conclusion: The present study demonstrated that rituximab can bring benefits to patients with lupus erythematosus systemic, with good tolerability and mild side effects; it presented, however, variable response according to the system affected. PMID:24728244
Robak, E; Smolewski, P; Woźniacka, A; Sysa-Jedrzejowska, A; Robak, T
Dendritic cells are a complex group of mainly bone-marrow-derived leukocytes that play a role in autoimmune diseases. The total number of circulating dendritic cells (tDC), and their plasmacytoid dendritic cell (pDC) and myeloid dendritic cell (mDC1 and mDC2) subpopulations were assessed using flow cytometry. The number of tDC and their subsets were significantly lower in systemic lupus erythematosus patients than in the control group. The count of tDC and their subsets correlated with the number of T cells. The number of tDC and pDC subpopulation were lower in the patients with lymphopenia and leukopenia than in the patients without these symptoms. Our data suggest that fluctuations in blood dendritic cell count in systemic lupus erythematosus patients are much more significant in pDC than in mDC, what may be caused by their migration to the sites of inflammation including skin lesions. Positive correlation between dendritic cell number and TCD4+, TCD8+ and CD19+ B cells, testify of their interactions and influence on SLE pathogenesis. The association between dendritic cell number and clinical features seems to be less clear. PMID:15223608
Iannella, I; Candela, S; Di Libero, L; Argano, F; Tartaglia, E; Candela, G
Systemic Lupus Erythematosus (SLE) is a chronic inflammatory rheumatic disease which affects the connective tissue. Its etiology is as yet unknown, while its pathogenesis involves the immune system. Both genetic and environmental and hormonal factors play a key role in the impaired immune regulation. A correlation with estrogens is demonstrated by the fact that the greatest incidence is found in young women, when estrogen secretion is at its highest. The disease is also reported to worsen in women taking oral contraceptives. It is therefore believed that the components of oral contraceptives, estrogens (ethinyl estradiol) and progestins, can affect the immune profile. Of the various complications attributed to systemic lupus erythematosus, gastrointestinal disorders are less common but potentially by far the most serious. We report a case of ischemic necrosis with sigma perforation in a patient with SLE. Signs and symptoms of acute abdomen in patients with SLE are rare (0.2%), but serious. Most patients require an exploratory laparotomy, as the causes are often linked with vasculitis.
Plata-Menchaca, Erika P.; de Leon, V. M. De la Puente-Diaz; Peña-Romero, Adriana G.; Rivero-Sigarroa, Eduardo
Introduction. Pulmonary hemorrhage secondary to disseminated strongyloidiasis is an unusual, well-recognized entity in immunocompromised patients with autoimmune disease, which is associated with the hyperinfection syndrome, sepsis, and a high mortality rate. Case Presentation. We present a case of a 44-year-old Mexican woman with systemic lupus erythematosus and acute bacterial meningitis who developed pulmonary hemorrhage with acute respiratory failure requiring mechanical ventilation, treated with broad spectrum systemic antibiotics and high dose methylprednisolone, who subsequently developed a characteristic purpuric skin eruption and septic shock and died two days later of refractory hypoxemia caused by massive pulmonary bleeding. The postmortem examination reports filariform larvae of S. stercolaris in lung, skin, and other organs. Conclusion. This case highlights the importance of considering disseminated strongyloidiasis in the differential diagnosis of diffuse alveolar hemorrhage in systemic lupus erythematosus, and screening for S. stercolaris infection before initiation of immunosuppressive therapy should be considered, especially in endemic areas. Disseminated strongyloidiasis has a high mortality rate, explained in part by absence of clinical suspicion. PMID:26101672
Leszczynski, Piotr; Pawlak-Bus, Katarzyna
Vocal cords palsy is a rare complication in the course of systemic lupus erythematosus (SLE). A 38-year-old female patient with a history of SLE presented with chronic voice hoarseness resistant to standard treatment. High levels of antinuclear antibodies including dsDNA, Ro52, SSA, SSB were confirmed, while antiphospholipid antibodies were absent. While other causes of voice hoarseness were excluded, bilateral vocal cords palsy was diagnosed. Moreover, the patient revealed features of obvious Hashimoto thyroiditis with high levels of antithyroid antibodies and also developed a convergent squint as a result of fatigability of oculomotor muscles. Electrophysiology test of peripheral nerves detected myasthenic type nerve-muscle conduction impairment which was suspected as the cause of reported symptoms. Possible reasons for emerging signs and symptoms of neuropsychiatric systemic lupus erythematosus were discussed as well as the presence of vasculitis, neuropathy, significance of thyroiditis and coexistence of myasthenia. All that reasons of similar autoimmune background were also raised in this case report.
Wang, Yuanyuan; Lu, Yang; Chai, Jixia; Sun, Meiqun; Hu, Xiaodong; He, Wenxin; Ge, Min; Xie, Changhao
The purpose of the present study was to evaluate whether Rho-kinase inhibition (Y-27632) modulated the expressions of nuclear factor kappaB (NF-κB) in systemic lupus erythematosus. 20 wild type mice and 20 MRL/lpr mice were applied for the research. The animals were randomly assigned to wild type, wild type+Y-27632 group, MRL/lpr group and MRL/lpr+Y-27632 group. 5mg/kg Y-27632 was intravenously injected to inhibit the ROCK expressions.Y-27632 significantly decreased the serum levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and increased IL-10 level in serum of MRL/lpr mice. Flow cytometry (FCM) studies also showed that Y-27632 remarkably increased Regulatory cells(Treg) cell percentage in spleen cells. Western blot analysis demonstrated Y-27632 downregulated the expressions of ROCK1, ROCK2, upregulated the expression of forkhead/winged helix transcription factor(Foxp3), and inhibited the phosphorylations of NF-κBp65 and IκBα. The findings showed that the inhibition of ROCK was beneficial for the prevention of systemic lupus erythematosus, which possibly by suppressing NF-κB activation.
Huang, Liuye; Kuang, Yu; Wei, Dapeng; Li, Wanyi; Yin, Qin; Pang, Juan
Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease identified by a plethora of production of autoantibodies. Autoreactive T cells may play an important role in the process. Attenuated T cell vaccination (TCV) has proven to benefit some autoimmune diseases by deleting or suppressing pathogenic T cells. However, clinical evidence for TCV in SLE is still limited. Therefore, this self-controlled study concentrates on the clinical effects of TCV on SLE patients. Methods. 16 patients were enrolled in the study; they accepted TCV regularly. SLEDAI, clinical symptoms, blood parameters including complements 3 and 4 levels, ANA, and anti-ds-DNA antibodies were tested. In addition, the side effects and drug usage were observed during the patients' treatment and follow-up. Results. Remissions in clinical symptoms such as facial rash, vasculitis, and proteinuria were noted in most patients. There are also evident reductions in SLEDAI, anti-ds-DNA antibodies, and GC dose and increases in C3 and C4 levels, with no pathogenic side effects during treatment and follow-up. Conclusions. T cell vaccination is helpful in alleviating and regulating systemic lupus erythematosus manifestation. PMID:28044142
Ramachandran, Sarika M; Leventhal, Jonathan S; Franco, Loren G; Mir, Adnan; Walters, Ruth F; Franks, Andrew G
Subacute cutaneous lupus erythematosus (SCLE) is a well-defined subtype of lupus erythematosus, characterised by photosensitivity, annular and/or psoriasiform lesions, variable systemic involvement and presence of circulating SSA/anti-Ro antibodies. SCLE may be idiopathic or drug-induced. Both the idiopathic and drug-induced forms of SCLE are analogous in their clinical, serological and histological features. Drug-induced SCLE has been reported with various oral agents, but to our knowledge this is the first reported case due to a topical medication. A 34-year-old female foot masseuse presented with a 2-month history of scaly, erythematous lesions isolated to the dorsal hands and interdigital spaces. She had used topical terbinafine, a topical antifungal cream, to her clients’ feet for a number of years. ANA and anti-SSA/Ro antibodies were positive. Physical examination, serology and histopathology were consistent with SCLE. We propose that our patient's unique presentation of SCLE may be explained by a prolonged occupational exposure to topical terbinafine as a foot masseuse. While oral terbinafine is a drug known to cause drug-induced SCLE, to our knowledge, this is the first topically induced form of the disease. PMID:28331627
Szczęch, J; Samotij, D; Werth, V P; Reich, A
It is currently believed that autoimmune conditions are triggered and aggravated by a variety of environmental factors such as cigarette smoking, infections, ultraviolet light or chemicals, as well as certain medications and vaccines in genetically susceptible individuals. Recent scientific data have suggested a relevant role of these factors not only in systemic lupus erythematosus, but also in cutaneous lupus erythematosus (CLE). A variety of environmental factors have been proposed as initiators and exacerbators of this disease. In this review we focused on those with the most convincing evidence, emphasizing the role of drugs in CLE. Using a combined search strategy of the MEDLINE and CINAHL databases the following trigger factors and/or exacerbators of CLE have been identified and described: drugs, smoking, neoplasms, ultraviolet radiation and radiotherapy. In order to give a practical insight we emphasized the role of drugs from various groups and classes in CLE. We also aimed to present a short clinical profile of patients with lesions induced by various drug classes.
Katsanos, Konstantinos H; Voulgari, Paraskevi V; Goussia, Anna; Oikonomou, Panagiotis; Christodoulou, Dimitrios K; Drosos, Alexandros A; Tsianos, Epameinondas V
The concurrence of inflammatory bowel disease with systemic lupus erythematosus (SLE) is rare. The concomitant diagnosis of Crohn's disease and SLE is even more rare. The patient, a 40-year-old woman, was admitted to our hospital because of relapsing episodes of abdominal pain, diarrheas upper and lower extremities arthralgias, Raynaud's phenomenon with positive antinuclear antibodies, and fever for the last 2 years. The patient was diagnosed elsewhere with SLE and treated with hydroxychloroquine. Her medical history also included tonsillectomy and total hip replacement after a car accident. Family history was unremarkable. Physical examination was unremarkable except of very mild pain at lower left abdominal quadrant. Laboratory tests showed erythrocyte sedimentation rate at 32 mm/h, C-reactive protein at 36 mg/dl, positive rheumatoid factor, and increased C3, C4, positive antinuclear antibodies with the presence of anti-Sm and anti-RNP antibodies. Ileocolonoscopy revealed colonic inflammation with ulcers and pseudopolyps. Subsequent biopsies were diagnostic of Crohn's disease. Patient was diagnosed with Crohn's colitis concomitant to systemic lupus erythematosus and was started on therapy with azathioprine 2 mg/Kg, methylprednisolone 16 mg/d with slow tapering, mesalazine 1.5 g/day, and hydroxychloroquine. Patient is in excellent health status on the six-month follow-up.
Schiffer, L; Worthmann, K; Haller, H; Schiffer, M
Different studies over the last decade have linked the B cell-attracting chemokine CXC ligand 13 (CXCL13) to the autoimmune disease systemic lupus erythematosus (SLE). A pathogenetic role of this chemokine for disease manifestation in SLE was described initially in mouse models for SLE. Mechanisms of CXCL13 actions were also identified in SLE patients. Moreover, various clinical studies have identified CXCL13 serum levels as a useful biomarker in patients with SLE of different ethnicities for disease activity. In addition, CXCL13 seems to be a promising marker for the diagnosis of lupus nephritis, one of the most severe complications of SLE. However, its exact place within the mechanisms that lead to SLE remains to be defined. Further research is needed to resolve more details of the pathomechanism and the signalling pathway of CXCL13 in SLE. Blocking CXCL13 or the signal pathways of CXCL13 is seen as a promising therapeutic approach for SLE and will be addressed in the near future. This review summarizes all papers that linked CXCL13 to SLE and highlights its importance in the pathogenesis and diagnosis of SLE PMID:25138065
Reich, A; Werth, V P; Furukawa, F; Kuhn, A; Szczęch, J; Samotij, D; Szepietowski, J C
The treatment of cutaneous lupus erythematous (CLE) remains a challenge. Most of the therapeutic options used in CLE have not been tested in randomized controlled studies and to date no agent has been approved. Therefore, CLE treatment is mostly based on personal experience. To better characterize therapeutic habits among physicians treating CLE patients, a questionnaire-based study about various aspects of topical and systemic treatment for CLE has been performed. The questionnaire was distributed among CLE experts, mostly from Japan, the USA, and Europe. A total of 82 completed questionnaires were assessed. High-potent and potent corticosteroids as well as calcineurin inhibitors were the most often recommended topical treatment for all CLE subtypes. The most relevant factors for initiation of systemic therapy were severity of skin lesions, concomitant involvement of internal organs, CLE subtype and lack of response to topical therapies. Corticosteroids and antimalarials were considered as the most suitable and effective systemic drugs for CLE patients. However, significant differences were observed between various CLE subtypes and between different countries regarding the assessment of various topical and systemic treatment options. In conclusion, great variability of obtained answers underlines the need of development of CLE treatment guidelines suitable for different disease subtypes.
Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E
In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the
Teboul, Isaac; Littlefield, Michael J; Siegart, Nicolle M; Turi, George K; Fazzari, Melissa J; Carsons, Steven E; DeLeon, Joshua; Reiss, Allison B
Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Numerous investigations by our group and others have indicated cardioprotective and anti-inflammatory properties of resveratrol. The present study explored potential atheroprotective actions of resveratrol on cholesterol efflux in cultured human macrophages exposed to plasma from systemic lupus erythematosus (SLE) patients. These results were confirmed in ApoE−/−Fas−/− double knockout mice, displaying a lupus profile with accelerated atherosclerosis. Resveratrol treatment attenuated atherosclerosis in these mice. THP-1 human macrophages were exposed to 10% pooled or individual plasma from patients who met diagnostic criteria for SLE. Expression of multiple proteins involved in reverse cholesterol transport (ABCA1, ABCG1, SR-B1, and cytochrome P450 27-hydroxylase) was assessed using QRT-PCR and Western blotting techniques. Ten-week-old ApoE−/−Fas−/− double knockout mice (n = 30) were randomly divided into two equal groups of 15, one of which received 0.01% resveratrol for 10 consecutive weeks. Atherosclerosis progression was evaluated in murine aortas. Bone marrow-derived macrophages (BMDM) were cultured and expression of cholesterol efflux proteins was analyzed in each group of mice. Our data indicate that inhibition of cholesterol efflux by lupus plasma in THP-1 human macrophages is rescued by resveratrol. Similarly, administration of resveratrol in a lupus-like murine model reduces plaque formation in vivo and augments cholesterol efflux in BMDM. This study presents evidence for a beneficial role of resveratrol in atherosclerosis in the specific setting of SLE. Therefore, resveratrol may merit investigation as an additional resource available to reduce lipid deposition and atherosclerosis in humans, especially in such vulnerable populations as lupus patients. PMID:27190277
Min, Hong Ki; Lee, Jae Ho; Jung, Seung Min; Lee, Jennifer; Kang, Kwi Young; Kwok, Seung-Ki; Ju, Ji Hyeon; Park, Kyung-Su
Background/Aims We investigated whether transthoracic echocardiography-suspected pulmonary hypertension (PH) affects survival in systemic lupus erythematosus (SLE) patients and examined factors associated with PH occurrence and survival. Methods This retrospective single-center study included 154 Korean SLE patients fulfilling the American College of Rheumatology criteria (January 1995 to June 2013). Student t test, Mann-Whitney U test, Kaplan-Meier curves, and log-rank tests were used for comparisons. Results A total of 35 SLE patients with PH (SLE/PH+) and 119 without PH (SLE/PH-) were analyzed. Higher percentages of interstitial lung disease, Raynaud's phenomenon (RP), World Health Organization functional classification III/IV, and cardiomegaly were found in SLE/PH+ compared to SLE/PH-. Furthermore, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was significantly higher in SLE/PH+ (2.46 ± 1.245 vs. 1.00 ± 1.235), whereas survival rates were significantly higher in SLE/PH- in log-rank tests (p = 0.001). In multivariate analysis, the adjusted mortality hazard ratio (HR) for SLE/PH+ patients was 3.10. Subgroup analysis demonstrated a higher percentage of lupus nephritis in the SLE/PH+ patients who died (p = 0.039) and low complement-3 levels (p = 0.007). In univariate analysis, the mortality HR for SLE/PH+ patients with lupus nephritis was 4.62, whereas the presence of RP decreased the mortality risk in multivariate analysis; adjusted HR, 0.10. Conclusions PH is an independent factor predicting survival in SLE patients. The presence of lupus nephritis resulted in an increased trend for mortality, whereas coexistence of RP was associated with a better survival prognosis in SLE/PH+ patients. PMID:25750566
Freire, Paula Vieira; Watanabe, Elisa; dos Santos, Nelita Rocha; Bueno, Cleonice; Bonfá, Eloísa; de Carvalho, Jozélio Freire
We have performed a retrospective study to determine if patients with antiphospholipid syndrome that developed systemic lupus erythematosus (APS/SLE) had distinct clinical and/or serological features. All 80 primary APS (PAPS) patients followed up at our APS unit were included in the study and divided into two groups: 14 APS/SLE and 66 PAPS. Prior or at onset of lupus manifestations, six patients were uniformly negative for lupus and Sjögren autoantibodies, and the other eight patients had persistent positive. In the first year after diagnosis of SLE, three patients remained with negative antibodies, the other seven patients maintained the same antibodies, and four patients developed other antibodies. APS/SLE group had a significant lower mean age at PAPS diagnosis (26.0 ± 8.0 vs. 34.2 ± 11.9 years, p = 0.03) and a longer disease duration (14.0 ± 7.0 vs. 6.0 ± 5.0 years, p < 0.0001). The mean time for PAPS to develop SLE was 5.2 ± 4.3 years. The typical clinical and laboratorial findings of APS did not discriminate both groups of patients. At lupus onset, antinuclear antibodies were more frequently observed in those who evolved to SLE (100 vs. 51.5%, p = 0.0005). Anti-double-stranded DNA (dsDNA), anti-ribosomal P, anti-Ro/SS-A, anti-La/SS-B, and anti-U1RNP antibodies were exclusively found in the APS/SLE patients, whereas anti-Smith (Sm) antibodies were not detected in both groups. The detection of a distinct subgroup of lupus-associated autoantibody in PAPS patients seems to be a hint to overt SLE disease, particularly in those patients with young age at diagnosis.
Wang, Dandan; Chen, Haifeng; Wang, Shiying; Zou, Yaohong; Li, Jing; Pan, Jieping; Wang, Xiangdang; Ren, Tianli; Zhang, Yu; Chen, Zhiwei; Feng, Xuebing; Sun, Lingyun
Thalidomide is effective for treating severe cutaneous lupus patients. The aim of this study was to observe the optimum effective and maintenance doses of thalidomide to maximize clinical benefit and minimize side effects for patients with cutaneous lupus in China. Sixty-nine patients with lupus rash from eight hospitals in China were enrolled and treated with different doses of thalidomide. We started the dose of thalidomide at 25 mg daily and gradually increased administration dose once a week until erythema was markedly improved. The effective and maintenance doses were documented. The size of skin lesions was noted once a week. Systemic lupus erythematosus disease activity index (SLEDAI) score, levels of erythrocyte sedimentation rate (ESR), and serum TNF-α were measured before and after treatment. The remission rates were evaluated weekly until 8 weeks. Sixty-eight percent of patients showed an effective dose of 50 mg daily; another 13, 10, and 9 % of patients had an effective dose of 100, 75, and 25 mg daily, respectively. The maintenance dose was 50 mg daily for 71 % of the patients, and 100, 75, and 25 mg daily for 9, 14, and 6 % of the patients. SLEDAI score and serum ESR levels significantly decreased 4 weeks after thalidomide treatment. At the end of the fourth week, the rates of complete remission, partial remission, and no response were 56 % (n = 39), 41 % (n = 28), and 3 % (n = 2). At the eighth week, the rate of total remission rose up to 100 %. The most common side effects were drowsiness and constipation. No peripheral neuropathy was observed in these patients. Thalidomide at a dose of 50 mg daily may offer a better benefit to risk ratio in the treatment of Chinese cutaneous lupus patients.
Borrell, Helena; Narváez, Javier; Alegre, Juan José; Castellví, Ivan; Mitjavila, Francesca; Aparicio, María; Armengol, Eulàlia; Molina-Molina, María; Nolla, Joan M
Shrinking lung syndrome (SLS) is a rare and less known complication mainly associated with systemic lupus erythematosus (SLE). In this study, we analyze the clinical features, investigation findings, approaches to management, and outcome in a case series of 9 adult patients with SLE and SLS diagnosed during a 35-year period in 3 referral tertiary care hospitals in Spain. Additionally, we reviewed 80 additional cases previously reported (PubMed 1965-2015). These 80 cases, together with our 9 patients, form the basis of the present analysis.The overall SLS prevalence in our SLE population was 1.1% (9/829). SLS may complicate SLE at any time over its course, and it usually occurs in patients without previous or concomitant major organ involvement. More than half of the patients had inactive lupus according to SELENA-systemic lupus erythematosus disease activity index (SLEDAI) scores. Typically, it presents with progressive exertional dyspnea of variable severity, accompanied by pleuritic chest pain in 76% of the cases.An important diagnostic delay is common. The diagnostic tools that showed better yield for SLS detection are the imaging techniques (chest x-ray and high-resolution computed tomography) along with pulmonary and diaphragmatic function tests. Evaluation of diaphragm dome motion by M-mode ultrasonography and phrenic nerve conduction studies are less useful.There are no standardized guidelines for the treatment of SLS in SLE. The majority of patients were treated with medium or high doses of glucocorticoids. Several immunosuppressive agents have been used in conjunction with steroids either if the patient fails to improve or since the beginning of the treatment. Theophylline and beta-agonists, alone or in combination with glucocorticoids, have been suggested with the intent to increase diaphragmatic strength.The overall long-term prognosis was good. The great majority of patients had significant clinical improvement and stabilization, or mild to moderate
Murro, Diana; Novo, Jorge; Arvanitis, Leonidas
Classic cerebral toxoplasmosis typically presents with neurologic symptoms such as seizures and mental status changes and histological examination shows focal lesions with necrosis. However, in the diffuse "encephalitic" form, patients are asymptomatic with diffuse, inflammatory, non-necrotic lesions. Asymptomatic diffuse "encephalitic" toxoplasmosis has been reported only in four acquired immunodeficiency syndrome patients and one human immunodeficiency virus (HIV) negative patient with chronic lymphocytic leukemia. We present a 36-year-old HIV-negative woman with systemic lupus erythematosus and lupus nephritis who was on immunosuppression for 9years after cadaveric renal transplant and died from pulmonary hemorrhage and cytomegalovirus pneumonia. Brain autopsy findings revealed multifocal microglial nodules containing Toxoplasma bradyzoites and associated astrogliosis. These nodules were prominent in the cerebellum, midbrain and medulla and also present in the cortex and thalamus. No coagulative necrosis, necrotizing abscesses, or other opportunistic infections were present. The patient had previously exhibited no neurologic symptoms and there was no clinical suspicion for toxoplasmosis. To the best of our knowledge, this is the first case of diffuse, non-necrotizing, "encephalitic" cerebral toxoplasmosis reported in a lupus patient and also the first reported female case.
Davis, Laurie S; Hutcheson, Jack; Mohan, Chandra
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by a defect in immune tolerance and exacerbated by both the innate and adaptive arms of the immune response. SLE-associated immune hyperactivity can be detected systemically as elevations in levels of cytokines along with their upregulated receptors expressed by hematopoietic cells. Importantly, increased levels of cytokines and their receptors can be observed in target organs, and it is clear that they have important roles in disease pathogenesis. Recent therapeutic strategies have focused on proximal cytokines, such as interferon-α, interleukin (IL)-1, IL-6, and tumor necrosis factor as a result of the efficacious use of biologic agents for intervention in rheumatoid arthritis and other autoimmune diseases. Despite the recent advances in understanding the cytokine networks involved in autoimmune diseases and more specifically in SLE, the diagnosis and prognosis of lupus remain a challenge. Lupus is heterogeneous and unpredictable; moreover, the frequency and severity of flares can be difficult to determine and treat. A better understanding of the regulation of expression of key cytokines and their receptors can likely provide important clues to the pathogenic mechanisms underlying specific forms of SLE, and pave the way toward more effective therapeutics.
Savov, A; Andonova, S; Tanev, D; Robeva, R; Marincheva, Ts; Tomova, A; Kumanov, Ph; Rashkov, R; Kolarov, Zl
Systemic lupus erythematosus (SLE) is a connective tissue disease affecting predominantly women that has been widely associated with obstetric complications. Inherited thrombophilias are significant risk factors for pregnancy loss, but their role in patients with SLE, and especially in those without concomitant secondary antiphospholipid syndrome (APS) has not been clarified. The aim of the present study was to study PAI-1 5G/4G polymorphism in women with lupus. A total of 103 SLE patients as well as 69 healthy volunteers were genotyped for PAI-1 5G/4G (rs1799889). No significant differences in the PAI-1 5G/4G genotype prevalence between patients and controls were found. After exclusion of the women with secondary APS, the frequency of pregnancies and spontaneous abortions, as well as the number of live births were similar in the studied patients with different PAI-1 genotype (p> 0.05). PAI-1 5G/4G polymorphism was not significantly related to any of the lupus ACR criteria or disease activity (p > 0.05), but it could influence the platelet number in the studied patients (263.52 ± 91.10 [5G/5G genotype] versus 210.12 ± 71.79 [4G/4G genotype], p = 0.023). In conclusion, our results showed that PAI-1 4G/5G polymorphism did not worsen the reproductive outcome in SLE women without secondary APS.
Kronbichler, Andreas; Brezina, Biljana; Quintana, Luis F; Jayne, David R W
Extracorporeal treatments have been used since the 1970s in the management of systemic lupus erythematosus (SLE). A randomised controlled trial comparing the efficacy of standard of care (SOC) combined with plasma exchange against SOC alone in patients with lupus nephritis revealed no difference in terms of renal outcome. Subsequently, initial expectations have been dampened and further experience with plasma exchange is mainly limited to observational studies and single case reports. Beneficial effects have been reported in patients with refractory disease course or in pregnancy with prior complications due to SLE and antiphospholipid syndrome. A more specific form of extracorporeal treatment, immunoadsorption (IAS), has emerged as a valuable option in the treatment of SLE. In line with the plasma exchange experience, IAS seems to have beneficial effects in patients with refractory disease, contraindications to standard immunosuppression or during pregnancy. The mechanism IAS relates to autoantibody removal but for plasma exchange removal of activated complement components, coagulation factors, cytokines and microparticles may also be relevant. Both treatment forms have good safety profiles although reactions to blood product replacement in plasma exchange and procedure related complications such as bleeding or catheter-related infections have occurred. There is a need to more clearly define the clinical utility of plasma exchange and IAS in refractory lupus and APS subgroups.
Tsumagari, T; Fukumoto, S; Kinjo, M; Tanaka, K
A clinicopathologic autopsy study of the vascular changes in the kidneys of 100 patients with systemic lupus erythematosus was undertaken. Necrotizing arteritis was found in seven patients, mucinous intimal thickening in nine, onion-skin intimal thickening in two, and renal vein thrombosis in two. Active necrotizing arteritis was present most frequently in the arterioles and interlobular arteries, with healing necrotizing arteritis predominating in the arcuate and interlobar arteries. These events were closely related to the activity of glomerular lesions, and immunologic vascular injury seemed to be the causative factor. Rapidly progressive renal failure and severe hypertension had characterized the clinical courses of the patients. Mucinous intimal thickening, present in the arterioles and interlobular arteries, had been accompanied by accelerated hypertension. Although dialysis or accelerated hypertension may have been causes, other factors, including glucocorticoid therapy, must be considered. In one patient with class II lupus nephritis, renal vein thrombosis was considered the cause of the nephrotic syndrome. These vasculopathies, often detected in patients with lupus at autopsy, seem to alter the clinical course.
Crowe, William; Doherty, Leanne; Watson, Gene; Armstrong, David; Ball, Elisabeth; Magee, Pamela; Allsopp, Philip; Bell, Aubrey; Strain, J. J.; McSorley, Emeir
Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, and environmental factors are proposed to exacerbate existing symptoms. One such environmental factor is mercury. The aim of this study was to investigate the relationship between exposure to mercury (Hg) and disease activity and disease associated damage in Total Hg concentrations in hair and urine were measured in 52 SLE patients. Dental amalgams were quantified. Disease activity was assessed using three indexes including the British Isles Lupus Assessment Group Index (BILAG). Disease associated damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLICC/ACR Damage Index. Pearson’s correlation identified a significant negative correlation between hair Hg and BILAG (r = −0.323, p = 0.029) and SLICC/ACR (r = −0.377, p = 0.038). Multiple regression analysis identified hair Hg as a significant predictor of disease associated damage as determined by SLICC/ACR (β = −0.366, 95% confidence interval (CI): −1.769, −0.155 p = 0.019). Urinary Hg was not related to disease activity or damage. Fish consumption is the primary route of MeHg exposure in humans and the inverse association of hair Hg with disease activity observed here might be explained by the anti-inflammatory effects of n-3 long chain polyunsaturated fatty acids also found in fish. PMID:26703710
Pham, Anthony Q; Berz, David; Karwan, Patricia; Colvin, Gerald A
We report the first case of Cremophor EL-induced cutaneous lupus erythematosus-like reaction in a 40-year-old female undergoing treatment for breast cancer. There have been four reported cases of paclitaxel- and four cases of docetaxel-induced cutaneous lupus reactions in the published literature [Dasanu and Alexandrescu: South Med J 2008;101:1161-1162; Adachi and Horikawa: J Dermatol 2007;34:473-476; Lortholary et al: Presse Med 2007;36:1207-1208; Chen et al: J Rheumatol 2004;31:818-820]. Our patient developed findings of a cutaneous lupus-like reaction with administration of paclitaxel which was subsequently discontinued. She was re-challenged with albumin-bound paclitaxel which has no Cremophor EL compound in its formulation. This administration of albumin-bound paclitaxel did not induce further reaction. She did not develop a cutaneous lupus erythematosus-like reaction with three other subsequent administrations of albumin-bound paclitaxel. The diagnosis of lupus-like reaction in our patient was made based on the development of a malar butterfly rash sparing the nasolabial folds, the appearance of this rash in context of recently receiving treatments with paclitaxel, resolution of the rash after discontinuing the paclitaxel, and the presence of autoimmune antibodies in the patient's serum which resolved with discontinuation of the paclitaxel. This is the first case demonstrating that the cause of the cutaneous lupus erythematosus-like reaction is not likely due to the taxane component of paclitaxel but the chemical composition of Cremophor EL. If the chemotherapeutic agent was causing the reaction then the same reaction should be seen by albumin-bound paclitaxel. We propose that previously reported lupus reactions may actually be due to Cremophor EL, which consists of polyoxyethylated castor oil, and not the chemotherapeutic agent itself.
Klonizakis, P; Tselios, K; Sarantopoulos, A; Gougourellas, I; Rouka, E; Onufriadou, Z; Kapali, P; Kyriakou, D; Boura, P
To clarify the role of ADAMTS-13 in the pathogenesis of thrombotic microangiopathy in systemic lupus erythematosus (SLE) we evaluated ADAMTS-13 profile (metalloprotease antigen levels, anti-ADAMTS-13 autoantibody levels, activity) in distinct patient groups according to disease activity, extent of cumulative tissue damage and history of antiphospholipid syndrome or end-organ damage. Forty-one lupus patients were analysed. ADAMTS-13 metalloprotease antigen levels and anti-ADAMTS-13 autoantibodies were evaluated by ELISA. ADAMTS-13 activity was measured by Fluorescence resonance energy transfer (FRET) technique. ADAMTS-13 metalloprotease antigen levels were significantly decreased in patients with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) >1 (p<0.05). ADAMTS-13 metalloprotease antigen levels also exhibited a significant inverse correlation with anti-dsDNA levels (r= -0.60, p<0.05). Anti-ADAMTS-13 autoantibodies were marginally higher in patients with positive anti-dsDNA (p=0.08). Additionally, patients with positive anti-ADAMTS-13 autoantibodies exhibited the lowest activity levels (p<0.05). To our knowledge ADAMTS-13 profile in SLE has not been studied in regard to composite structured indices. The results of this study suggest that in patients with active SLE or considerable cumulative tissue damage, ADAMTS-13 levels may be decreased and anti-ADAMTS-13 autoantibodies may partially mediate this reduction. Further evaluation of ADAMTS-13 profile may explain its role in the pathogenesis of thrombotic microangiopathy in lupus patients and reveal a potential prognostic marker of microthrombotic manifestations in SLE.
Mendoza-Pinto, C; Méndez-Martínez, S; Soto-Santillán, P; Galindo Herrera, J; Pérez-Contreras, I; Macías-Díaz, S; Taboada-Cole, A; García-Carrasco, M
The objective of this cross-sectional study was to determine relationships between socioeconomic status and organ damage in Mexican systemic lupus erythematosus (SLE) patients. Demographic and clinical variables were assessed. Socioeconomic status was evaluated using the Graffar method and monthly household income. Lupus activity and organ damage were measured using the SLE disease activity scale, validated for the Mexican population (Mex-SLEDAI), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) scale. The 143 Mexican female SLE patients included (mean age 40.1 ± 8.9 years, mean disease duration 8.9 ± 6.3 years) had a mean monthly household income of $ 407.2 ± 326.5. According to the Graffar index, 18.9%, 52.5%, and 28.7% had high/medium-high, medium, and medium-low/low socioeconomic status, respectively. Organ damage was observed in 61 patients (42.7%). Patients with organ damage had lower monthly household incomes ($241.4 ± 152.4 vs. $354.8 ± 288.3) and were more frequently unemployed (57.3% vs. 35.3%; p = 0.01) than those without. Low monthly income was not associated with lupus activity or self-reported health status. In the adjusted multivariate analysis, low monthly income ( < $300) was associated with organ damage. In conclusion, low income may be associated with organ damage in Mexican SLE patients.
Juang, Y-T; Peoples, C; Kafri, R; Kyttaris, V C; Sunahori, K; Kis-Toth, K; Fitzgerald, L; Ergin, S; Finnell, M; Tsokos, G C
Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease diagnosed on the presence of a constellation of clinical and laboratory findings. At the pathogenetic level, multiple factors using diverse biochemical and molecular pathways have been recognized. Succinct recognition and classification of clinical disease subsets, as well as the availability of disease biomarkers, remains largely unsolved. Based on information produced by the present authors' and other laboratories, a lupus gene expression array consisting of 30 genes, previously claimed to contribute to aberrant function of T cells, was developed. An additional eight genes were included as controls. Peripheral blood was obtained from 10 patients (19 samples) with SLE and six patients with rheumatoid arthritis (RA) as well as 19 healthy controls. T cell mRNA was subjected to reverse transcription and PCR, and the gene expression levels were measured. Conventional statistical analysis was performed along with principal component analysis (PCA) to capture the contribution of all genes to disease diagnosis and clinical parameters. The lupus gene expression array faithfully informed on the expression levels of genes. The recorded changes in expression reflect those reported in the literature by using a relatively small (5 ml) amount of peripheral blood. PCA of gene expression levels placed SLE samples apart from normal and RA samples regardless of disease activity. Individual principal components tended to define specific disease manifestations such as arthritis and proteinuria. Thus, a lupus gene expression array based on genes previously claimed to contribute to immune pathogenesis of SLE may define the disease, and principal components of the expression of 30 genes may define patients with specific disease manifestations.
Mihaylova, Nikolina; Bradyanova, Silviya; Chipinski, Petroslav; Herbáth, Melinda; Chausheva, Stela; Kyurkchiev, Dobroslav; Prechl, József; Tchorbanov, Andrey I
Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production. Therefore, both factors promote the idea that a down-modulation of activated self-reactive T and B cells involved in the pathogenic immune response is a reasonable approach for SLE therapy. Annexin A1 (ANX A1) is expressed by many cell types and binds to phospholipids in a Ca(2+) dependent manner. Abnormal expression of ANX A1 was found on activated B and T cells in both murine and human autoimmunity, suggesting its potential role as a therapeutic target. While its role on T lymphocytes is through formyl peptide receptor-like molecules (FPRL), and the formed ANX A1/FPRL pathway modulates T cell receptor signalling, there is still no fool-proof data available for the role of ANX A1 in B cells. We employed a lupus model of Balb/c mice with pristane-induced SLE which very closely resembles human lupus. In the present study, we investigated the possibility to modulate the autoimmune response in a pristane-induced mouse model of SLE using an anti- ANX A1 antibody. Administration of this monoclonal antibody resulted in the inhibition of T-cell activation and proliferation, suppression of IgG anti-dsDNA antibody-secreting plasma cells and of proteinuria, decreased disease activity and prolonged survival compared to control group.
Hammad, A; Mossad, Y M; Nasef, N; Eid, R
Background Increased expression of interferon-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Interferon regulatory factor 5 (IRF5) is one of the transcription factors regulating interferon and was proved to be implicated in the pathogenesis of SLE in different populations. Objectives The objective of this study was to investigate the correlation between polymorphisms of the IRF5 gene and SLE susceptibility in a cohort of Egyptian children and to investigate their association with clinico-pathological features, especially lupus nephritis. Subjects and methods Typing of interferon regulatory factor 5 rs10954213, rs2004640 and rs2280714 polymorphisms were done using polymerase chain reaction-restriction fragment length polymorphism for 100 children with SLE and 100 matched healthy controls. Results Children with SLE had more frequent T allele and TT genotype of rs2004640 ( Pc = 0.003 and 0.024, respectively) compared to controls. Patients with nephritis had more frequent T allele of rs2004640 compared to controls ( Pc = 0.003). However the allele and genotype frequencies of the three studied polymorphisms did not show any difference in patients with nephritis in comparison to those without nephritis. Haplotype GTA of rs10954213, rs2004640 and rs2280714, respectively, was more frequent in lupus patients in comparison to controls ( p = 0.01) while the haplotype GGG was more frequent in controls than lupus patients ( p = 0.011). Conclusion The rs2004640 T allele and TT genotype and GTA haplotype of rs rs10954213, rs2004640, and rs2280714, respectively, can be considered as risk factors for the development of SLE. The presence of the rs2004640 T allele increases the risk of nephritis development in Egyptian children with SLE.
Hughson, M D; Nadasdy, T; McCarty, G A; Sholer, C; Min, K W; Silva, F
Current studies indicate that a thrombotic microangiopathy (TMA) identifies patients with systemic lupus erythematosus (SLE) who are at high risk of progressing to end-stage renal disease. We have observed two patients with SLE and one patient with a primary antiphospholipid syndrome (APS) who developed acute renal insufficiency with thrombocytopenia. Renal biopsies showed a TMA characterized by thrombi or by cellular and mucoid intimal hyperplasia of small arteries and arterioles. No arterial or arteriolar immune-complex deposits were detected by immunofluorescent or electron microscopy. Biopsies from one SLE patient and the APS patient showed no immune-complex glomerular disease. Both had serum antiphospholipid antibodies (aPL). aPL were not detected in the serum of the other SLE patient who had an active lupus nephritis. Acute renal failure and thrombocytopenia resolved in each case following treatment by plasmapheresis or prednisone and heparin. None of the patients were initially treated with cytotoxic drugs. As more knowledge is gained, the accurate identification of renal vascular lesions in SLE or related diseases could influence renal prognosis and choice of therapy. The cases reported here provide further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases.
Mina, Rina; Abulaban, Khalid; Klein-Gitelman, Marisa; Eberhard, Anne; Ardoin, Stacy; Singer, Nora; Onel, Karen; Tucker, Lori; O’Neil, Kathleen; Wright, Tracey; Brooks, Elizabeth; Rouster-Stevens, Kelly; Jung, Lawrence; Imundo, Lisa; Rovin, Brad; Witte, David; Ying, Jun; Brunner, Hermine I.
Objective To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. Methods In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score: ≤ 10 vs. > 10; Tubulointerstitial Activity Index (TIAI) score: ≤ 5 vs. > 5) or the absence vs. presence of LN chronicity [NIH Chronicity Index (NIH-CI) score: 0 vs. ≥ 1]. Results There were 10, 50 and 23 patients with class I/II, III/IV and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with LN-activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between LN-activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture LN chronicity was 23.5% and 91.7%, respectively. Despite designed to measure LN-activity, SLICC-RAS and SLEDAI-R scores significantly differed with LN chronicity status. Conclusion Current clinical indices of LN fail to discriminate ISN/RPS Class in children. Despite its shortcomings, the SLEDAI-R appears to best for measuring LN activity in a clinical setting. The SDI-R is a poor correlate of LN chronicity. PMID:26213987
Petri, Michelle; Orbai, Ana-Maria; Alarcón, Graciela S.; Gordon, Caroline; Merrill, Joan T.; Fortin, Paul R.; Bruce, Ian N.; Isenberg, David; Wallace, Daniel J.; Nived, Ola; Sturfelt, Gunnar; Ramsey-Goldman, Rosalind; Bae, Sang-Cheol; Hanly, John G.; Sanchez-Guerrero, Jorge; Clarke, Ann; Aranow, Cynthia; Manzi, Susan; Urowitz, Murray; Gladman, Dafna; Kalunian, Kenneth; Costner, Melissa; Werth, Victoria P.; Zoma, Asad; Bernatsky, Sasha; Ruiz-Irastorza, Guillermo; Khamashta, Munther A.; Jacobsen, Soren; Buyon, Jill P.; Maddison, Peter; Dooley, Mary Anne; van Vollenhoven, Ronald F.; Ginzler, Ellen; Stoll, Thomas; Peschken, Christine; Jorizzo, Joseph L.; Callen, Jeffrey P.; Lim, S. Sam; Fessler, Barri J.; Inanc, Murat; Kamen, Diane L.; Rahman, Anisur; Steinsson, Kristjan; Franks, Andrew G.; Sigler, Lisa; Hameed, Suhail; Fang, Hong; Pham, Ngoc; Brey, Robin; Weisman, Michael H.; McGwin, Gerald; Magder, Laurence S.
Objective The Systemic Lupus Collaborating Clinics (SLICC) revised and validated the American College of Rheumatology (ACR) SLE classification criteria in order to improve clinical relevance, meet stringent methodology requirements and incorporate new knowledge in SLE immunology. Methods The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. SLICC validated the classification criteria in a new validation sample of 690 SLE patients and controls. Results Seventeen criteria were identified. The SLICC criteria for SLE classification requires: 1) Fulfillment of at least four criteria, with at least one clinical criterion AND one immunologic criterion OR 2) Lupus nephritis as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications than the current ACR classification criteria (49 versus 70, p=0.0082), had greater sensitivity (94% versus 86%, p<0.0001) and equal specificity (92% versus 93%, p=0.39). In the validation set, the SLICC Classification criteria resulted in fewer misclassifications (62 versus 74, p=0.24), had greater sensitivity (97% versus 83%, p<0.0001) but less specificity (84% versus 96%, p<0.0001). Conclusions The new SLICC classification criteria performed well on a large set of patient scenarios rated by experts. They require that at least one clinical criterion and one immunologic criterion be present for a classification of SLE. Biopsy confirmed nephritis compatible with lupus (in the presence of SLE autoantibodies) is sufficient for classification. PMID:22553077
Stimmler, M M; Coletti, P M; Quismorio, F P
To determine the utility of magnetic resonance imaging (MRI) of the brain in diagnosing active neuropsychiatric disease in systemic lupus erythematosus (NP-SLE), a prospective study of 51 hospitalized systemic lupus erythematosus (SLE) patients during 64 separate episodes of suspected NP-SLE was initiated. In addition to standard hematology, chemistry, and serological tests, the workup included MRI in all patients. A computed tomographic scan of the brain was obtained in patients enrolled in the first year of the study. Of the 64 neuropsychiatric episodes, 42 were attributable to NP-SLE and 22 were attributed to causes other than SLE. Neuropsychiatric complaints unrelated to lupus included depression (n = 6), seizures (n = 5), headache (n = 3), altered mental status (n = 2), aseptic meningitis (n = 2), cardiovascular accident (n = 2), transient ischemic attack (n = 1), and vertigo (n = 1). The MRI was abnormal in 34 of 64 (53%) episodes. MRI abnormalities were more common in patients with focal neurological deficits (19/26) than in those without focal findings (15/38; P = .008) and in patients with nephritis (19/24) than in those without renal disease (15/40; P = .002). MRI abnormalities were as frequent in NP-SLE (25/42) as in cases with non-NP-SLE-related causes (9/22). Periventricular increased signal (PIS) was a frequent MRI finding (10/64). Enlargement of the prepontine cistern, an MRI finding not previously described in NP-SLE, was seen (14/64). Both findings were associated with the presence of hypertension and lupus nephritis. PIS similar to that seen in our patients has been described in otherwise healthy elderly individuals with risk factors for stroke, suggesting that vascular abnormalities may be important in the etiology of these lesions. In conclusion, abnormalities in brain MRI occur frequently in NP-SLE, especially in patients with focal neurological deficits. However, the presence of similar MRI abnormalities in SLE patients with neuropsychiatric
Hanly, J G; Urowitz, M B; Su, L; Bae, S-C; Gordon, C; Sanchez-Guerrero, J; Clarke, A; Bernatsky, S; Vasudevan, A; Isenberg, D; Rahman, A; Wallace, D J; Fortin, P R; Gladman, D; Dooley, M A; Bruce, I; Steinsson, K; Khamashta, M; Manzi, S; Ramsey-Goldman, R; Sturfelt, G; Nived, O; van Vollenhoven, R; Ramos-Casals, M; Aranow, C; Mackay, M; Kalunian, K; Alarcón, G S; Fessler, B J; Ruiz-Irastorza, G; Petri, M; Lim, S; Kamen, D; Peschken, C; Farewell, V; Thompson, K; Theriault, C; Merrill, J T
Objective Neuropsychiatric (NP) events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. We examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrollment predicted subsequent NP events. Methods Patients with recent SLE diagnosis were assessed prospectively for up to 10 years for NP events using ACR case definitions. Decision rules of graded stringency determined whether NP events were attributable to SLE. Associations between the first NP event and baseline autoantibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results Disease duration at enrollment was 5.4±4.2 months, followup was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed ≥1 NP event (total 917 events). NP events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrollment 21.9% of patients had lupus anticoagulant, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. Lupus anticoagulant at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (Hazard ratio, HR 2.54 (95% CI: 1.08–5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR: 3.92 (95% CI:1.23–12.5); p=0.02). Other autoantibodies did not predict NP events. Conclusion In a prospective study of 1047 recently diagnosed SLE patients, lupus anticoagulant and anti-ribosomal P antibodies are associated with an increased future risk for intracranial thrombosis and lupus psychosis respectively PMID:21893582
van Tuyll van Serooskerken, Anne-Moon; Habets, J M Werner; Badeloe, Sadhanna; Poblete-Gutiérrez, Pamela; Frank, Jorge
In lupus erythematosus (LE), vesicles and bullae are only rarely seen. However, in some instances such efflorescences might suggest an association with distinct cutaneous diseases, including erythema multiforme, toxic epidermal necrolysis or autoimmune blistering disorders such as bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis Duhring. Another blistering disease that has been described in association with cutaneous and systemic LE is porphyria cutanea tarda (PCT). PCT is a metabolic disorder caused by a deficiency of the fifth enzyme in heme biosynthesis, uroporphyrinogen decarboxylase. Here, we report on a 57-year-old Caucasian woman of Dutch origin with a medical history of mild cutaneous LE who developed skin fragility, blistering skin lesions, milia, and facial hypertrichosis. Subsequent porphyrin analysis in urine and feces confirmed the suspected simultaneous manifestation of LE and PCT.
Manolios, N; Schrieber, L
Systemic lupus erythematosus is an autoimmune disorder that occurs spontaneously in humans and mice. Genetic factors play an important role in the predisposition to and expression of disease. Environmental factors augment the expression of illness and in the absence of normal control mechanisms may provide the stimulus to autoimmunity. Sex hormones modulate the immune response and tend to modify disease expression. Disordered immune regulation may be due to a primary or secondary abnormality in cellular, cytokine, and/or humoral function. Therapy for SLE is directed towards suppression of exaggerated immunological and inflammatory activity. This review will re-evaluate current therapy and describe newer approaches including the use of pharmacological, hormonal, immunological, dietary, and physical modalities.
Marinho, Ayana Karla de Oliveira Ferreira; Ramos, Ticiana Batista; Barbosa, Deborah Maria de Castro; Kozmhinsky, Valter; Takano, Daniela Mayumi; Figueira, Marcella Maria de Souza Araújo
Chronic cutaneous lupus erythematosus in a linear configuration is rare, particularly in children, demonstrating similar incidence in both genders, no photo-sensitivity and lower probability of progression to systemic disease. We describe the case of a 9-year-old girl who presented erythematous papules with central atrophy on the upper and lower right limbs, asymptomatic and following the lines of Blaschko, since age four. Histological examination showed atrophy of the epidermis with aggression from epidermal-dermal interface and periadnexal and perivascular lymphocytic inflammatory infiltrate. Laboratory tests showed ANA in a titer of 1:320, in a dense and fine speckled pattern. Due to the rarity of presentation and location of the disease, this case is reported here. PMID:27579750
Xu, Changgang; Carlsson, Daniel O; Mihranyan, Albert
The goal of this project was to study the feasibility of using a DNA-immobilized nanocellulose-based immunoadsorbent for possible application in medical apheresis such as systemic lupus erythematosus (SLE) treatment. Calf thymus DNA was bound to high surface area nanocellulose membrane at varying concentrations using UV-irradiation. The DNA-immobilized samples were characterized with scanning electron microscopy, atomic force microscopy, and phosphorus elemental analysis. The anti-ds-DNA IgG binding was tested in vitro using ELISA. The produced sample showed high affinity in vitro to bind anti-ds-DNA-antibodies from mice, as much as 80% of added IgG was bound by the membrane. Furthermore, the binding efficiency was quantitatively dependent on the amount of immobilized DNA onto nanocellulose membrane. The described nanocellulose membranes are interesting immunoadsorbents for continued clinical studies.
Afzal, Wais; Arab, Talal; Ullah, Tofura; Teller, Katerina; Doshi, Kaushik J.
Lymphadenopathy could represent a vast spectrum of etiologies including infectious and non-infectious diseases. Besides proper history taking, physical examination, and laboratory investigations, a tissue diagnosis is often necessary to unmask the cause of generalized lymphadenopathy. Here we present a 23-year-old woman who was admitted for diffuse generalized lymphadenopathy, fatigue, malaise, weight loss, nausea, and bilateral lower extremity edema. She reported a history of seizures as well as stroke 2 years prior with no other medical conditions present. Although malignant and infectious etiologies were initially the primary targets for workup, her history of seizures and stroke remained a dilemma. Extensive workup for malignant and infectious diseases was unrevealing; however, rheumatologic workup was eventually positive for systemic lupus erythematosus (SLE). This case illustrates that extensive generalized diffuse lymphadenopathy may be a presenting feature of SLE and should be considered in the differential diagnosis of patients presenting with diffuse lymphadenopathy and constitutional symptoms. PMID:27738484
Nakajima, Claire; Manzi, Susan
It is estimated that over 50 % of patients with systemic lupus erythematosus (SLE) have utilized complementary and alternative medicine (CAM) treatments to reduce symptoms and manage their health. However, there are relatively few randomized controlled trials of CAM for SLE. This review describes recent studies of vitamins and supplements, acupuncture, and mind-body interventions in SLE patients. The recent trials of CAM treatments for SLE indicate that supplements such as vitamin D, omega 3 fatty acids, N-acetyl cysteine and turmeric show some promise for reducing SLE disease activity. In addition, mind-body methods such as cognitive-behavioral therapy and other counseling interventions may improve mood and quality of life in SLE. PMID:24078104
Khairullah, S; Jasmin, R; Yahya, F; Cheah, T E; Ng, C T; Sockalingam, S
Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome of ineffective intestinal motility characterised by clinical and radiological evidence of intestinal obstruction with no identifiable mechanical lesion. CIPO can either be idiopathic or secondary to a systemic disease, like systemic lupus erythematosus (SLE). Fewer than 30 cases of CIPO secondary to SLE have been reported so far. Here we describe a case of SLE with the initial presentation of CIPO. In SLE-related CIPO, treatment includes a combination of high-dose intravenous corticosteroids, immunosuppressants and supportive care. With awareness of this condition, unnecessary surgical intervention and repeated invasive procedures could be avoided. Early initiation of treatment would avoid complications and bring about resolution of symptoms.
López-López, Linnette; Rivera-Rodríguez, Noridza; Vilá, Luis M
Patients with systemic lupus erythematosus (SLE) may develop thrombotic thrombocytopaenic purpura (TTP) or TTP-like illness manifested by microangiopathic haemolytic anaemia (MAHA) and thrombocytopaenia. The distinction between active SLE and TTP is difficult because these entities share similar clinical features. Drug-induced TTP caused by an immune-mediated reaction have been documented for several drugs. Herein, we report a middle-aged Hispanic woman with long-standing SLE, who developed a TTP-like illness characterised by MAHA and thrombocytopaenia after exposure to nitrofurantoin. The patient responded well to plasmapheresis and immunosuppressive therapy and has remained clinically stable after 18 months of follow-up. To our knowledge, this is the first case that reports the association between nitrofurantoin and a TTP-like presentation.
Hahn, B H
Transfer of disease by bone marrow cells has been described in experimental models of systemic lupus erythematosus (SLE). In one experiment, marrow ablation followed by transfer of T depleted allogeneic marrow resulted in prolonged survival of animals with SLE. Some experimental studies suggest a rationale for autologous stem cell transplantation indicating this intervention might "reset the thermostat" so that normal immunoregulation can control disease, while others indicate it might not be beneficial. The pros and cons of offering patients with SLE autologous hematopoietic stem cell transplantation are considered. A profile of the patient with SLE who might be considered as a candidate for autologous stem cell transplantation can be constructed by evaluating causes of death and factors that increase mortality. This profile includes life threatening disease, inadequate response to aggressive immunosuppressive therapy, and adequate function of all major organs so that risks associated with stem cell transplantation can be minimized.
García-Reynoso, Marco Julio; Veramendi-Espinoza, Liz Eliana; Ruiz-Garcia, Henry Jeison
A 45 year-old man went to the emergency room due to disease duration of 15 days of insidious onset and progressive course. It began with symmetrical weakness and pain in feet and ankles that extends upward to the knees. Later, this progressed to paraparesis with Creatine phosphokinase levels of 44,270 U/L and respiratory failure that required mechanical ventilation. Electromyography and muscle biopsy of quadriceps were made. The patient responded to corticotherapy in pulses and supporting management. The presentation of ascending paresis suggested the diagnosis of Guillain-Barré syndrome. However, the degree of muscle involvement with rhabdomyolysis explains the neurological damage by itself. The biopsy revealed pathological criteria for necrotizing autoimmune myopathy (NAM), as well as other clinical and laboratory evidence. Patient disease continued and reached criteria for systemic lupus erythematosus (SLE). To our best knowledge, this is the first report of the NAM and SLE association.
Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.
High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.
Horta-Baas, G; Hernández-Cabrera, M F; Barile-Fabris, L A; Romero-Figueroa, M del S; Arenas-Guzmán, R
Leprosy is an infectious chronic disease with a wide range of clinical and serological manifestations. We report a case of a woman presenting with a malar rash, painless oral ulcers, photosensitivity, arthritis, positive antinuclear antibodies test and leuko-lymphopenia. Our case illustrates an unusual presentation of leprosy initially diagnosed as systemic lupus erythematosus (SLE). After the confirmation of multibacillary leprosy and multidrug therapy recommended by the World Health Organization, a good clinical response was observed. Recognition of rheumatic manifestations in leprosy is important as they may be confused with SLE. A literature review is presented to encourage clinicians to consider leprosy as a differential diagnosis. Specifically in patients with unusual rheumatic manifestations and persistent skin lesions, and when neurological symptoms are present. Leprosy has not been eradicated, so misdiagnosis can be frequent. It is necessary to increase medical practitioner awareness in order start proper treatment.
Fajardo-Hermosillo, Luis D; López-López, Linnette; Nadal, Anaida; Vilá, Luis M
Osteonecrosis is a relatively common comorbidity in systemic lupus erythematosus (SLE), but avascular necrosis in multiple sites is unusual. Multifocal osteonecrosis is defined as osteonecrotic lesions affecting three or more separate anatomic sites. We report a case of a 24-year-old woman diagnosed with SLE when she presented with mucocutaneous, haematological and mild renal manifestations. Initially, she was treated with prednisone and hydroxychloroquine and her condition remained stable. Two years later, she developed severe bilateral pretibial ulcers intractable to immunosuppressive therapy and broad-spectrum antibiotics. MRI of both legs disclosed osteonecrosis of the distal tibia, proximal tibia, distal fibula and talus bilaterally. She had elevated anticardiolipin antibodies for which she was treated with chronic anticoagulation resulting in complete healing of the leg ulcers and no further episodes of osteonecrosis. In addition to this case, we review the demographic, clinical and pharmacological features of 14 cases reported in the literature. PMID:23595183
O'Laughlin, John P.; Wong, Brian C.
We present a case of a syncopal episode resulting from significant QT interval prolongation in a patient on hydroxychloroquine for the treatment of systemic lupus erythematosus and end stage renal disease. The patient had been treated with hydroxychloroquine for two years prior to presentation. After thorough workup for secondary causes of QT interval prolongation hydroxychloroquine was discontinued and the patient's QT interval shortened. The patient was treated with mexiletine to prevent sudden ventricular arrhythmias, which was unique compared to other documented cases in which lidocaine was used. The patient was noted to have mild prolongation of the QT interval on electrocardiogram prior to initiation of hydroxychloroquine therapy which was exacerbated by its use and may have been caused due to toxicity from underlying renal failure. PMID:27478650
Meinicke, Holger; Heinzmann, Andrea; Geiger, Julia; Berner, Reinhard; Hufnagel, Markus
While pleuropulmonary involvement in systemic lupus erythematosus (SLE) is a common occurrence, shrinking lung syndrome (SLS) is a rare complication of SLE, particularly in children. We report on a teenager girl with a primary SLE diagnosis, which was based upon clinical, imaging, lung-function and histological findings ascertained to be compatible with SLS. Following a pneumonia, the patient developed inflammatory residues in the lower lobes, an event that probably caused diaphragmatic immobility and subsequently led to SLS. Treatment response to steroids, cyclophosphamide and hydroxychloroquine in this case was excellent, and efficacy was more profound than previously has been reported in the literature with respect to pediatric patients. This case report argues that prognosis of SLS in SLE is likely to be favorable when the diagnosis is made early and the disease is treated appropriately.
Cooper, Glinda S; Parks, Christine G
Although genetic susceptibility plays a strong role in the etiology of systemic lupus erythematosus (SLE), recent research has provided new evidence of the potential influence of environmental factors in the risk for this disease. This paper describes epidemiologic and experimental research pertaining to occupational and environmental sources of exposure to respirable crystalline silica, solvents and pesticides, and two "lifestyle" factors (smoking and hair dye use). As has been seen with other systemic autoimmune diseases (eg, systemic sclerosis and rheumatoid arthritis), a series of epidemiologic studies, using different designs in different settings, have demonstrated relatively strong and consistent associations between occupational silica exposure and SLE. The type and quality of exposure assessment is an important consideration in evaluating these studies. Recent experimental studies examined the effect of trichloroethylene exposure in MRL+/+ mice, but to date there have been few epidemiologic studies of solvents and SLE. There are numerous avenues with respect to environmental factors in SLE that need additional research.
Greco, Carol M; Nakajima, Claire; Manzi, Susan
It is estimated that over 50 % of patients with systemic lupus erythematosus (SLE) have utilized complementary and alternative medicine (CAM) treatments to reduce symptoms and manage their health. However, there are relatively few randomized controlled trials of CAM for SLE. This review describes recent studies of vitamins and supplements, acupuncture, and mind-body interventions in SLE patients. The recent trials of CAM treatments for SLE indicate that supplements such as vitamin D, omega 3 fatty acids, N-acetyl cysteine and turmeric show some promise for reducing SLE disease activity. In addition, mind-body methods such as cognitive-behavioral therapy and other counseling interventions may improve mood and quality of life in SLE.
Changcharoen, Bhisit; Bolger, Dennis Thomas
We report a female patient presenting with headache, fatigue, ecchymoses and recent, excessive vaginal bleeding. Prompt review of the peripheral blood smear showed evidence of microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange and corticosteroids were started urgently. The patient responded favourably to the treatment. Subsequently, positive serological markers returned and were compatible with systemic lupus erythematosus (SLE). A disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS 13) activity was remarkably low with a positive inhibitory ADAMTS 13 antibody. Mycophenolate and hydroxychloroquine were started along with a prolonged course and taper of corticosteroids. These medications have been maintained with an excellent response in 14 months of follow-up. PMID:25701834
Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. The pathogenic mechanisms that cause SLE remain unclear; however, it is well recognized that the immune balance is disturbed and that this imbalance contributes to the autoimmune symptoms of SLE. Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and the ability of the biological system to readily detoxify the reactive intermediates or to repair the resulting damage. In humans, oxidative stress is involved in many diseases, including atherosclerosis, myocardial infarction, and autoimmune diseases. Numerous studies have confirmed that oxidative stress plays an important role in the pathogenesis of SLE. This review mainly focuses on the recent research advances with respect to oxidative stress and regulatory T (Treg)/helper T 17 (Th17) cell dysfunction in the pathogenesis of SLE. PMID:27597882
Zhao, Jian; Wu, Hui; Langefeld, Carl D; Kaufman, Kenneth M; Kelly, Jennifer A; Bae, Sang-Cheol; Alarcón, Graciela S; Anaya, Juan-Manuel; Criswell, Lindsey A; Freedman, Barry I; Kamen, Diane L; Gilkeson, Gary S; Jacob, Chaim O; James, Judith A; Merrill, Joan T; Gaffney, Patrick M; Sivils, Kathy Moser; Niewold, Timothy B; Petri, Michelle A; Song, Seung Taek; Jeong, Hye-Jin; Ramsey-Goldman, Rosalind; Reveille, John D; Scofield, R Hal; Stevens, Anne M; Boackle, Susan A; Vilá, Luis M; Chang, Deh-Ming; Song, Yeong Wook; Vyse, Timothy J; Harley, John B; Brown, Elizabeth E; Edberg, Jeffrey C; Kimberly, Robert P; Hahn, Bevra H; Grossman, Jennifer M; Tsao, Betty P; La Cava, Antonio
Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE.
González-Moreno, J; Ruíz-Ruigomez, M; Callejas Rubio, J L; Ríos Fernández, R; Ortego Centeno, N
Pyoderma gangrenosum (PG) is an uncommon, distinctive cutaneous ulceration which is usually idiopathic, but may be associated with many systemic disorders. The etiopathogenesis of PG is still not well understood. PG is part of the spectrum of the neutrophilic dermatoses and it has been proposed as a prototype of cutaneous autoinflammatory disease. PG usually has a good outcome under immunosuppressive treatment. Although PG has been associated with several systemic diseases, it has rarely been reported in association with systemic lupus erythematosus (SLE). In this article we report five cases of SLE-related PG and review the literature. Our findings support the possible relationship between active SLE and PG, although the mechanism remains unclear. Clinical manifestations, used treatments and outcomes of SLE-related PG do not differ from the described for the general population.
Sabato, Leah A; Mendes, Lisa A; Cox, Zachary L
Hydroxychloroquine (HQ) is commonly prescribed for autoimmune diseases such as systemic lupus erythematosus. We report a case of a 75-year-old female presenting with de novo decompensated heart failure and restrictive cardiomyopathy (left ventricular ejection fraction: 40%-45%) after treatment with HQ for more than 11 years. Hydroxychloroquine was discontinued, and follow-up echocardiogram 57 days after discontinuation showed normalization of her left ventricular ejection fraction. A score of 7 on the Naranjo Adverse Drug Reaction Probability Scale indicates that HQ is a probable cause of this patient's cardiomyopathy. An adverse drug effect due to HQ should be considered in treated patients who present with restrictive cardiomyopathy. Discontinuation may allow for partial or complete reversal of the cardiomyopathy.
Wu, Meng; Yang, Jinhua; Li, Xiaofeng; Chen, Junwei
Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the overproduction of autoantibodies against an array of nuclear and cytoplasmic antigens and affects multiple organs, such as the skin, joints, kidneys, and neuronal tissues. T cells have been recognized as important players in the development of SLE due to their functions in cytokine secretion, antigen presentation, and supporting B cells for antibody production. γδ T cells are a minor population of T cells that play important roles in infection and tumor-associated disease. In recent years, the role of γδ T cells in autoimmune diseases has been investigated. In this review, we discussed the role of γδ T cells in the pathogenesis of SLE. PMID:26981547
Lee, Yongseung; Motomura, Goro; Yamamoto, Takuaki; Nakashima, Yasuharu; Ohishi, Masanobu; Hamai, Satoshi; Iura, Kunio; Iwamoto, Yukihide
A 37-year-old female had been treated with corticosteroids for systemic lupus erythematosus clinically diagnosed at age 10. She suddenly had right hip pain without any antecedent trauma. Four months after the onset of pain, she visited her primary care physician. On magnetic resonance imaging, joint space narrowing at the weight-bearing area was already seen with bone marrow edematous lesions in both the femoral head and acetabulum. She was treated non-operatively; however, her pain continued to worsen in severity. Thirteen months after the onset of pain, she was referred to our hospital. A plain radiograph showed subluxation of the collapsed femoral head accompanied by destruction of the acetabular rim. Because of her severe intractable pain, she underwent total hip arthroplasty 1 month after her first visit. Histological examination of the resected femoral head revealed pseudogranulomatous lesions along with prominent callus formation, suggesting rapid destruction of the femoral head.
Chen, Dongying; Yang, Zheng; Yang, Ying; Zhan, Zhongping; Yang, Xiuyan
Patients with systemic lupus erythematosus (SLE) are susceptible to tuberculosis (TB), especially in endemic areas such as China. The variable and nonspecific clinical features of disseminated TB often leads to an erroneous or misdiagnosis. When a patient presents with TB of the bone marrow, the clinical condition is more perplexing and the prognosis is typically poor. Till now, there is no case report after apatinib came in the market.Here, we report a case of TB of the bone marrow accompanied with SLE. The patient exhibited remarkable features, including widespread lesions in the lungs, spinal vertebrae, sacrum, and ilium that were found to be consistent with TB of the bone marrow after histopathological examination.This case highlights the importance of clinical suspicion for TB during the follow-up of SLE patients, especially in endemic areas. An aggressive diagnostic biopsy should be performed in suspected TB patients as early as possible.
Zhu, B; Iwata, H; Kong, D; Yu, Y; Kato, K; Ikada, Y
A new DNA-immobilized immunoadsorbent was prepared to remove the pathogenic anti-DNA antibody from the serum of systemic lupus erythematosus (SLE) patients. A non-woven poly(ethylene terephthalate) (PET) fabric made of 3.5-microm diameter fibers was used as the support of the immunoadsorbent. A cationic monomer, N,N-dimethylaminoethyl methacrylate (DAM), was graft polymerized onto the PET fiber surface by UV irradiation or with a chemical initiator. Polyion complexation between the cationic groups of the graft chains and DNA molecules was employed to immobilize DNA onto the fiber surface. No DNA leaching was observed when the DNA-immobilized fabrics were placed in 0.9 and 2.0 wt% NaCl solution at 37 degrees C overnight. In vitro evaluation of this DNA-immobilized immunoadsorbent demonstrated that this adsorbent could selectively adsorb anti-DNA antibody from the serum of SLE patients.
Boccuti, Viera; Perrone, Antonio; D'Introno, Alessia; Campobasso, Anna; Sangineto, Moris; Sabbà, Carlo
Autoimmune disorders are known to be more frequent in women and often associated each others, but it is rare to see multiple autoimmune diseases in a single patient. Recently, the concept of multiple autoimmune syndrome has been introduced to describe patients with at least three autoimmune diseases. We describe a case of a young man with a clinical history of psychiatric symptoms and celiac disease (CD) who was diagnosed to have other two autoimmune disorders: systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis. This case is unusual upon different patterns: the rare combination of the three autoimmune diseases, their appearance in a man and the atypical onset of the diseases with psychiatric symptoms likely to be related either to CD or to SLE.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease and occurs worldwide in both children and adults. The estimated annual incidence among children is 2.22/100,000 and among adults is 23.2/100,000 in the United States. There is increasing understanding about differences in disease manifestations, medication use, and disease severity between those with childhood-onset SLE as compared with adult-onset SLE. Children have a more fulminant disease onset and course than adults with SLE, resulting in two to three times higher mortality. In future years, we anticipate more insight into the genetics between childhood-onset SLE and adult-onset SLE to help delineate the best therapies for both subsets of patients. PMID:23998441
Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.
High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice. PMID:27279139
Lin, Heng-Kuei; Wang, Jiaan-Der; Fu, Lin-Shien
We report a rare case of diffuse systemic sclerosis (SSc) evolving into diffuse SSc/systemic lupus erythematosus (SLE) overlap syndrome. A 15-year-old boy was diagnosed as diffuse SSc with initial presentations of Raynaud's phenomenon and skin tightening. He underwent Chinese herbal treatment and clinical symptoms deteriorated in the following 3 years. On admission to our ward, serositis with pleural effusion, severe pulmonary fibrosis with moderate pulmonary hypertension, swallowing difficulty, and polyarthritis were observed. Autoantibody profiles revealed concurrence of anti-double-stranded DNA, anti-Smith, anti-topoisomerase I, and anti-ribonucleoprotein antibodies. The patient fulfills the criteria for both diffuse SSc and SLE. After drainage for pleural effusion accompanied by oral prednisolone and sildenafil, there were improvement of respiratory distress, swallowing difficulty, and pulmonary hypertension. In conclusion, connective tissue diseases may overlap with each other during the disease course. Serial follow-up for clinical symptoms as well as serological changes is recommended.
Petelin, Andrew; Johnson, Diane H; Cunha, Burke A
Fevers of unknown origin (FUOs) are classified according to the underlying disorder. The 4 main clinical categories of FUOs are infectious, malignant, rheumatic/inflammatory, and miscellaneous disorders. Although malignancy remains the most common cause of FUOs, rheumatic/inflammatory disorders remain important diagnostically and therapeutically. Rheumatic/inflammatory disorders, for example, systemic lupus erythematosus (SLE) presenting as FUO, have become uncommon in recent years because of better serologic diagnostic tests. However, SLE remains a rare but important cause of FUO in adults. SLE may be a difficult FUO diagnosis when a patient presents with fever without joint manifestations as the only symptoms of SLE. During the workup of the patient described in this article, the other causes of pericarditis were ruled out and SLE pericarditis was diagnosed. This is a rare case of an adult FUO with pericarditis as the only manifestation of SLE.