C4 concentrations and C4 deficiency alleles in systemic lupus erythematosus.

In a study of 66 patients with systemic lupus erythematosus (SLE) and 80 controls it was found that the presence of two deficiency (null) alleles of C4 had a significant effect on mean C4 concentrations in serum. In six controls who each had two C4 null alleles the mean C4 concentration in serum was 56% lower than in 43 controls without C4 null alleles; the nadir of the C4 concentration in four patients with SLE with two null alleles was also lower by a mean of 55% than in 32 patients who did not have null alleles. Reduced production of C4 allotypes in subjects with two null alleles may be an important determinant of total C4 concentration in patients with SLE. For optimal interpretation of C4 concentrations in SLE, C4 allotyping appears to be indicated, particularly to identify patients who have two null alleles of C4.     

Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome

Systemic lupus erythematosus (SLE) is the autoimmune disease that most commonly compromises pregnancy. Moreover, the relationship between SLE and pregnancy is in both directions. However, the current experience indicates that pregnancy in patients with SLE should not be regarded as an unacceptable high risk condition for the mother or her baby provided that careful planning of conception and multidisciplinary monitoring and treatment are carried out.     

Selective C4 deficiency, systemic lupus erythematosus, and Whipple''s disease.

A 45-year-old female with selective deficiency of C4 and systemic lupus erythematosus developed puzzling gastrointestinal and systemic symptoms in the last 6 months of her life. Extensive investigation of the gastrointestinal tract did not yield any diagnosis, and the patient died shortly afterwards. Autopsy revealed evidence of a typical Whipple's disease of the jejunum and lymph nodes. This association has not been previously described. The disease is reviewed with emphasis on its being an opportunistic infection in an immunosuppressed host with a complement deficiency and SLE.     

Dengue fever evolving into systemic lupus erythematosus and lupus nephritis: a case report

Dengue viremia may be the trigger for immune complex formation in patients who are predisposed to developing autoimmune disease. We report a rare case of dengue virus infection evolving into systemic lupus erythematosus (SLE) and lupus nephritis. To the best of our knowledge this is the first case of dengue fever evolving into lupus nephritis. A 22 year old female presented with having had high grade fever, skin rash, breathlessness, retro-orbital pain, abdominal pain, arthralgias and myalgias for 10 days. She tested positive for dengue immunoglobulin M (IgM). She was given supportive treatment and was subsequently discharged. Four weeks later she developed recurrent fever, arthralgia, rash and anasarca. She was suspected as having SLE with active lupus nephritis. Antinuclear antibody (ANA), and anti double stranded deoxyribonucleic acid (anti dsDNA) titers were positive and complements were low. Renal biopsy showed diffuse proliferative glomerulonephritis grade IV. She was treated with steroids and immunosuppressants to which she responded. Dengue viremia incites antibody production, which if excessive causes deposition of viral antigen-antibody immune complexes. This could possibly lead to renal tubular damage and glomerulonephritis in susceptible individuals. Dengue fever leading to development of glomerulonephritis is rarely seen. Our patient developed dengue fever and after a month presented with manifestations of SLE and lupus nephritis. Both dengue fever and SLE have common manifestations of fever, arthralgia, rash, leucopenia with thrombocytopenia and serositis. Bacterial and viral infections may act as a 'trigger' for starting or relapsing lupus activity in genetically predetermined individuals. In our case it may be possible that dengue virus could have triggered a dysfunctional immune response, resulting in the developing of autoimmunity and SLE with lupus nephritis.     

Cognitive dysfunction and antiphospholipid antibodies in systemic lupus erythematosus

Nervous system involvement in systemic lupus erythematosus (SLE) is typically diagnosed on the basis of clinical psychiatric and/or neurologic syndromes (NPSLE). Neuropsychological tests can be used to assess nervous system integrity even in the absence of major NP syndromes. Their application has uncovered significant cognitive dysfunction, ranging from mild to severe, in a sizeable proportion of SLE patients irrespective of clinical NP status. Cognitive dysfunction has now been accepted as a bona fide manifestation of NPSLE. The heterogeneity of clinical NPSLE manifestations is paralleled by the diversity of cognitive deficits reported in different studies and within different patients. The success of attempts to explain these deficits on the basis of potential pathogenetic mechanisms, such as antibrain antibodies and proinflammatory cytokines, has been uneven. To date, the most robust findings have emerged in relation to antiphospholipid antibodies, which carry with them important therapeutic implications.     

Cerebral vasculitis in a patient with hereditary complete C4 deficiency and systemic lupus erythematosus

We describe the case of a female patient with hereditary complete C4 deficiency and systemic lupus erythematosus. She had suffered from lupus nephritis in early childhood. At the age of 23 years she developed severe lupus with skin disease and life-threatening cerebral vasculitis. Her cerebral disease was unresponsive to high-dose steroids, intravenous immunoglobulin, fresh frozen plasma and plasma exchange. Improvement was achieved with immunoadsorption in combination with mycophenolate mofetil. The patient made a complete recovery and is maintained in complete remission on mycophenolate and low-dose steroids.     

Systemic lupus erythematosus evolving into rheumatoid arthritis

We describe 3 patients who presented with clinical and serological evidence of systemic lupus erythematosus (SLE) and 10 or more years later developed for the first time clinical and serological manifestations of rheumatoid arthritis (RA). Each patient now meets the American College of Rheumatology criteria for both SLE and RA.     

Anetoderma associated with antiphospholipid syndrome and systemic lupus erythematosus

Anetoderma is an uncommon disorder characterized by the loss of elastic fibres in the dermis histologically and herniation of subcutaneous tissue clinically. Recent studies indicate that immunologic mechanisms may play a role in this process. Here we report a 33-year-old woman with numerous well-circumscribed, asymptomatic skin lesions in whom clinical and histopathologic features were consistent with anetoderma. Additionally, history and investigations revealed antiphospholipid syndrome and systemic lupus erythematosus. It has been speculated that immune deposits in the dermis or within the capillary walls may lead to ischaemia and subsequent degeneration of the elastic fibres.     

Hemocytopenia in systemic lupus erythematosus. Relationship to antiphospholipid antibodies

We studied 500 consecutive patients with systemic lupus erythematosus (SLE) for antibodies to phospholipids (APLA) by an ELISA method using cardiolipin as antigen and antiimmunoglobulins G, M and A to determine their isotype. Once entered into this prospective study the patients were followed for up to 16 months (mean 7.7 +/- 4.72 SD) with periodic determinations of APLA. Of the 500 patients with SLE, 88 had had thrombocytopenia, 25 had had hemolytic anemia, 25 had had both, and 362 had no history of these hemocytopenias. If we considered the odds ratio of these 362 patients for having high titer APLA as 1, patients with a history of thrombocytopenia, hemolytic anemia or both had significantly higher odds ratios of having APLA than did those without hemocytopenia. Patients with thrombocytopenia had significantly higher levels of IgG APLA, those with hemolytic anemia had significantly higher titers of IgM APLA and patients with both had significantly higher titers of both of these APLA isotypes, than did patients without hemocytopenias. A correlation between positive direct Coombs' tests and IgM APLA was also found. We conclude that APLA is associated with these hemocytopenias in SLE. This might be due to their interaction with negatively charged phospholipids in the cell walls of the respective cells.     

Anetoderma in systemic lupus erythematosus: relationship to antiphospholipid antibodies

Anetoderma is an elastolytic disorder where multiple patches of slack skin are formed. Twelve patients with anetoderma associated with systemic lupus erythematous have been described, all in the dermatological literature. Recently, a role for antiphospholipid antibodies has been proposed with microthromboses as its pathogenic mechanism. We present herein a 20-year-old female patient who developed anetoderma soon after sun exposure. She was found to have a false positive VDRL and gradually developed other manifestations of SLE, including interstitial cystitis. She has had repeatedly positive antiphospholipid antibodies. Although there are patients who may have a primary form, diagnosis of anetoderma should trigger a search for SLE and/or antiphospholipid antibodies.     

Critical illness in systemic lupus erythematosus and the antiphospholipid syndrome

OBJECTIVES: To investigate the causes, course, and outcome of critical illness requiring emergency admission to the intensive care unit (ICU) in patients with systemic lupus erythematosus (SLE) or the antiphospholipid syndrome (APS), or both. METHODS: Critically ill patients with SLE or APS, or both, admitted to a London teaching hospital ICU over a 15 year period were studied. Demographic, diagnostic, physiological, laboratory, and survival data were analysed. Kaplan-Meier survival curves were constructed by age, time from first diagnosis of SLE, and time from first ICU admission. The log rank test and a backwards stepwise Cox regression were used to identify factors associated with reduced survival. RESULTS: Sixty one patients with SLE alone (39%) and/or APS (61%) required 76 emergency admissions to the ICU. Patients had high severity of illness scores (median APACHE II 22 (range 8-45)) and multiorgan dysfunction. The primary diagnoses for patients admitted were infection in 31/76 (41%), renal disease in 16/76 (21%), cardiovascular disease in 12/76 (16%), and coagulopathies in 11/76 (14%). The commonest secondary diagnosis was renal dysfunction (49%). Factors associated with an increased risk of death were cyclophosphamide before admission, low white cell count, and high severity of illness score. Before adjustment for these factors renal disease had a strong adverse effect on long term survival (analysis by age at diagnosis p=0.005, analysis by time since first ICU admission, p=0.07). After adjustment, infection at admission to ICU was associated with an increased ICU mortality (p=0.02) and was the cause of death in 13/17 patients who died in the ICU. Similarly, after adjustment, APS was associated with reduced ICU survival (p=0.1) and reduced long term (p=0.03) survival. Seventeen patients (28%) died in the ICU, and 31 patients (51%) had died by the last follow up. Median time from ICU admission to death was four years. Overall five year survival from the first ICU admission was 43%. CONCLUSION: Critical illness requiring ICU admission may occur in patients with SLE and APS. In this study, ICU survival was better than previously described, but long term survival was poor. Cyclophosphamide administration, low white cell count, and high severity of illness score were associated with reduced survival. Before adjustment for these factors, only renal disease had an adverse effect on outcome but after adjustment, infection and APS reduced survival.     

Devic's syndrome in systemic lupus erythematosus and probable antiphospholipid syndrome

Neuropsychiatric lupus is common and results in significantmorbidity [1, 2]. Antiphospholipid antibodies (aPL) may playa major role and are associated with transverse myelitis [2–4],often with a significant response to anticoagulation [4, 5].Devic's syndrome is described in multiple sclerosis (MS) [6]and has rarely been associated with systemic lupus erythematosus(SLE) [5, 7–9]. We present a 44-yr-old woman with SLEwho developed neuromyelitis optica and probable antiphospholipidsyndrome (APS). She was healthy until 1990 when schizophrenia was     

Partial C4A deficiency is associated with susceptibility to systemic lupus erythematosus in black Americans

In a study of 59 black American patients with systemic lupus erythematosus (SLE), we found that partial C4A deficiency occurred twice as frequently as in 59 control subjects (32.3% versus 15.3%; P = 0.02). Complete C4A deficiency, however, occurred in only 1 patient and in no controls. Partial C4A deficiency is a risk factor for SLE in black, as well as in white, SLE populations studied to date. In contrast with white patients, complete C4A deficiency occurs relatively infrequently in black patients with SLE.