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Histology and immunopathology of systemic lupus erythematosus affecting the conjunctiva.

Systemic lupus erythematosus (SLE) is an autoimmune disease occasionally involving the conjunctiva, sclera or cornea. The immunopathology of the active epibulbar lesions has not been studied in detail. Conjunctival biopsies from 11 SLE patients with active epibulbar lesions and from 12 age-matched individuals undergoing cataract surgery were analysed by light microscopy, immunofluorescence and immunoperoxidase techniques. SLE patients presented with scleritis (3 cases), peripheral ulcerative keratitis (5 cases) or progressive cicatrising conjunctivitis (5 cases). Histologically, SLE specimens showed moderate subepithelial and perivascular mononuclear cell infiltration or granuloma formation in the substantia propria, and squamous metaplasia; thrombosis was not seen. Immunoreactant deposition was present at the epithelial basement membrane in 4 of 5 cases with cicatrising conjunctivitis. Vascular immunodeposits wer detected in 4 cases. The epithelium showed increased T helper cells (CD4+), granulocytes and natural killer cells (CD67+), dendritic cells (CD1+), and an increase in HLA-DR expression compared with normal tissue. In the substantia propria, B cells (CD22+), macrophages (CD14+), dendritic cells, activated T cells (CD25+, CD3+), the T helper (CD4+)/T suppressor (CD8+) ratio and HLA-DR expression were all increased. These observations suggest that the rare epibulbar manifestations in SLE result from immune-complex-mediated reactions.

Adolescent↗

Efficacy of topical tacrolimus for treating the malar rash of systemic lupus erythematosus.

The rash of systemic lupus erythematosus (SLE) is usually treated with topical corticosteroids, but prolonged use causes adverse cutaneous side-effects. We assessed the efficacy of topical tacrolimus for treating the skin lesions of SLE. Three patients with SLE affecting their facial skin applied 0.1% tacrolimus ointment on one side of their face twice daily for 3 weeks, in conjunction with a sunscreen cream. After 3 weeks, erythema on the treated side was ameliorated in all three patients compared with the untreated side. Although the study is preliminary, the results demonstrate that topical tacrolimus may be useful for treating the malar rash of SLE.

Adult↗

Placental pathology in systemic lupus erythematosus with antiphospholipid antibodies.

Systemic lupus erythematosus (SLE) is associated with a poor pregnancy outcome. Antiphospholipid antibodies (APL), which include lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL), are frequently found in patients with SLE, and their presence has been associated with fetal loss. To examine placental pathologic features of SLE patients with APL, we performed a pathologic study on 47 placental tissue samples from 47 pregnant SLE patients with APL (15 patients; four LAC single-positive patients, seven aCL single-positive patients, four LAC and aCL double-positive patients) and without APL (32 LAC and aCL double-negative patients). The incidence of extensive infarction, decidual vasculopathy, decidual thrombosis and perivillous fibrinoid change, which have been thought to be characteristic lesions of APL placenta, was significantly higher in the LAC and aCL double-positive patients than in the patients without APL. Conversely, the above-mentioned lesions between the LAC or aCL single-positive patients and the APL negative patients did not differ significantly. Among the 15 patients with APL, two of the three patients with both decidual vasculopathy and thrombosis had extensive infarction associated with fetal death. Moreover, the patients having fetal death showed LAC and aCL double-positivity. In conclusion, this study indicated that the LAC and aCL double-positivity is an important factor for extensive infarction resulting from decidual vasculopathy and decidual thrombosis in the SLE placenta. Moreover, it was indicated that LAC and aCL double-positivity is an important risk factor for fetal death in the SLE patient.

Adult↗

Multiple myeloma associated with systemic lupus erythematosus.

A case of systemic lupus erythematosus (SLE) complicated by multiple myeloma is presented; the lupus diagnosis was put together with the diagnosis of myeloma but the symptoms had commenced a few years before. The putative mechanisms underlying this unusual combination are discussed.

Aged↗

Multiple myeloma associated with systemic lupus erythematosus.

A case of systemic lupus erythematosus (SLE) complicated by multiple myeloma is presented. The lupus diagnosis was established together with the diagnosis of myeloma but the symptoms had commenced a few years before. The putative mechanisms underlying this unusual combination are discussed.

Aged↗

Balancing diversity and tolerance: lessons from patients with systemic lupus erythematosus.

The autoimmune disease systemic lupus erythematosus (SLE) is caused by a failure of B cell tolerance. Recent studies in mouse models of SLE have identified several distinct tolerance checkpoints that must each function appropriately to protect against disease. However, studies of B cell repertoire selection in humans are essential to understand which checkpoints are defective in human autoimmune diseases.

Animals↗

Gout and hyperuricaemia in systemic lupus erythematosus.

Coexistent gout and systemic lupus erythematosus (SLE) have received increasing attention. An additional case is reported and published cases reviewed. Common clinical features of this group include nephritis, diuretic and corticosteroid therapy and a tendency to be older and more frequently male. Prevalence of hyperuricaemia (HU) was assessed in 38 patients with SLE. HU was found in 29% and was closely associated with renal involvement particularly proteinuria and diuretic therapy. The presentation of gout in SLE may be modified or suppressed by anti-inflammatory therapy and may be misinterpreted as SLE arthritis.

Adolescent↗

Treponemal infection coexisting with systemic lupus erythematosus.

A patient with systemic lupus erythematosus (SLE)/erosive arthritis overlap is described who was also shown to have late latent treponemal infection. The possibility of serological reactivation is discussed. Since antiphospholipid antibodies are the basis of the reagin tests for syphilis as well as being present in patients with SLE, difficulties with diagnosis may ensue.

Female↗

SLICC/ACR Damage Index is valid, and renal and pulmonary organ scores are predictors of severe outcome in patients with systemic lupus erythematosus.

We investigated the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index as a predictor of severe outcome and an indicator of morbidity in different ethnic groups, and in regard to its validity. We retrospectively studied disease course within 10 yr of diagnosis in an inception cohort of 80 patients with systemic lupus erythematosus (SLE). The mean renal damage score (DS) at 1 yr after diagnosis was a significant predictor of endstage renal failure and the mean pulmonary DS at 1 yr significantly predicted death within 10 yr of diagnosis. Compared to Caucasians, Afro-Caribbeans and Asians had significantly higher mean total DS at 5 and 10 yr, and higher mean renal DS at 10 yr. At 5 yr, the mean renal DS in Afro-Caribbeans and the mean neuropsychiatric DS in Asians were significantly higher than in Caucasians. The rate of endstage renal failure in Caucasians was significantly lower than in the other ethnic groups. Our results confirm the validity of the SLICC/ACR Damage Index.

Adult↗

Genome-wide methylation profiling identifies signatures of pain, fatigue and health scores in women with systemic lupus erythematosus.

OBJECTIVES: People with systemic lupus erythematosus (SLE) experience high levels of pain and fatigue with poor overall health, which persist in those with low disease activity. By performing epigenome-wide DNA methylation analysis, this study aims to identify epigenetic alterations associated with self-reported scores for pain, fatigue and health in women with SLE. METHODS: Forty-eight women with SLE from the SLEGOT cohort were included. Study participants exhibited low disease activity (median SLEDAI-2K = 0) and minimal damage (median SLICC damage index = 0). An epigenome-wide DNA methylation analysis in whole blood identified 704 237 CpG loci, with 511 673 annotated to known genes. RESULTS: We identified 485, 591 and 577 differentially methylated CpGs linked to pain, fatigue and poor health, respectively. The association of reported pain with CpGs in GPR107, SPHK2, HBA1 and RERE genes suggested a potential role for neuromodulation in pain perception in SLE. For fatigue, enrichment analysis highlighted pathways related to neuronal development, morphogenesis and synaptic signalling. Nine genes, including BDNF and TGIF1, showed strong correlations with all three scores, suggesting a shared epigenetic influence that may underlie pain, fatigue and poor health in SLE. Specific microRNA genes were differentially methylated in relation to pain and fatigue. CONCLUSION: By studying a cohort of women with well-controlled SLE, we identified several CpGs and genes associated with pain, fatigue and general health. Our findings suggest that epigenetic changes in genes involved in neuronal modulation, rather than inflammatory pathways, could be involved in the development of these symptoms in patients with SLE.

Humans↗

Risk of coronary heart disease and stroke in a large British cohort of patients with systemic lupus erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are at increased risk of myocardial infarction and stroke. We sought to determine how much of this risk was dependent on recognized cardiovascular risk factors. METHODS: Initially a software package 'Cardio-Risk-Manager', which utilizes Framingham data, was used to calculate a 10-yr risk of coronary heart disease (CHD) and stroke for 202 patients with SLE (Group 1) in comparison with hypothetical age- and sex-matched comparators. Subsequently 47 patients who had been followed since 1991 (Group 2) were studied to compare their predicted risks in 1991 with the actual number of cardiovascular events that occurred during the subsequent decade. RESULTS: Patients in Group 1 had a higher predicted 10-yr risk of stroke (P<0.0001), but not of CHD, than their comparators. However, following age stratification, traditional risk factors predicted a higher risk of CHD (P<0.0001) and of stroke (P<0.0001) in patients under 40 with SLE compared with age-matched comparators. The predicted 10-yr risks of CHD and stroke for patients aged 40 and above were not significantly different from those of their comparators. Predicted risks, however, were lower than the true 10-yr event rate for CHD and stroke in patients in Group 2. In this group, during the 10 yr of follow-up four patients (8.5%) suffered a CHD event and five patients (10.6%) had a stroke, significantly more than were predicted by the presence of conventional risk factors (P<0.001 for CHD and P<0.001 for stroke, respectively). CONCLUSIONS: Conventional risk factors predicted an increased risk of stroke and CHD in younger patients. They do not, however, fully explain the high risk of cardiovascular disease in patients with SLE. Although it is important to address the management of orthodox risk factors for cardiovascular disease in patients with SLE, other causes must be sought to explain the increased incidence of CHD and stroke, especially in those aged over 40.

Adult↗

Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are susceptible to opportunistic infections. To examine the clinical manifestations of non-tuberculous mycobacterial (NTM) infections with those of Mycobacterium tuberculosis (MTB) infections in SLE patients. METHODS: Medical records of a cohort of 725 SLE patients were reviewed for previous NTM infections. Demographic characteristics, predisposing factors and clinical outcomes were compared with patients who had previous MTB infections (n = 39). RESULTS: Eleven (nine female and two male) cases were identified (prevalence 1.5%). The mean +/- S.D. age at the time of infection was 42.8 +/- 13.9 yrs, 9.3 +/- 5.8 yrs after the onset of SLE. The mean +/- S.D. time taken from onset of symptoms to the diagnosis of NTM infection was 5.7 +/- 7.2 months. Sites of involvement included skin and soft tissue (n = 8), chest (n = 2) and disseminated infection (n = 1). NTM infections were more likely to involve extrapulmonary sites (P = 0.006), presented in patients with longer lupus disease duration (P < 0.001), occurred in older patients (P < 0.001) and in those who had a higher cumulative dose of prednisolone (P = 0.01) than MTB infections. Using a stepwise logistic regression, disease duration was found to be the only independent predictive factor (P = 0.005) for NTM infections. Ten (25.6%) patients with MTB infections but none of the patients with NTM infections presented concomitantly at the onset of SLE (P = 0.09). There were no differences in the recurrence rate (P = 0.64) and frequency of disseminated infections (P = 0.40) between NTM and MTB infections. CONCLUSIONS: NTM infections tended to develop in SLE patients later in their disease course than MTB infections. A high index of suspicion is required for its diagnosis.

Adult↗

Role of viruses in systemic lupus erythematosus and Sjögren syndrome.

Systemic lupus erythematosus and Sjögren syndrome remain elusive in the description of their underlying etiologic causes and pathogenic mechanisms. Although underlying genetic predisposition appears to contribute to both diseases based on twin and other genetic studies, additional factors must play a role. Over the decades additional factors, such as hormonal influence, UV light, environmental exposures (e.g., silica, solvents), and infectious agents have been postulated to play a role. Over the past few years additional information has been published concerning roles of various infectious agents in both lupus and Sjögren syndrome. Although the understanding of this field is still incomplete, significant advances are being made.

Humans↗

Acute sarcoidosis occurring during the course of systemic lupus erythematosus.

A diagnosis of systemic lupus erythematosus (SLE) was established in a 54-year-old woman with a compatible history, as well as patchy alopecia, anemia, arthralgias, and a positive LE cell preparation. Sixteen months later bilateral hilar and mediastinal lymph nodes appeared on chest roentgenogram. Sarcoidosis was diagnosed when hypercalcemia and noninfectious, noncaseating epithelioid granulomas were found in the skin and liver. The sarcoidosis remitted with corticosteroid therapy, but slowly advancing renal failure ultimately resulted in the patient's death. We believe the concurrence of SLE and sarcoidosis had not been previously reported in the English literature. Immune mechanisms are discussed.

Female↗

Cutaneous bullae following acute steroid withdrawal in systemic lupus erythematosus.

A patient with systemic lupus erythematosus developed severe widespread bullae following sudden steroid withdrawal. Histologically the lesion was suggestive of leukocytoclastic vasculitis with a regenerating subepidermal bulla, but immunofluorescence on non-lesional skin was typical of lupus erythematosus. Treatment led to resolution of the bullous eruption, and despite exacerbations of the patient's lupus nephropathy, the blisters have not recurred. The differential diagnosis of bullous LE is discussed.

Blister↗

Autoantibodies to histone, DNA and nucleosome antigens in canine systemic lupus erythematosus.

Dogs can develop systemic lupus erythematosus syndromes that are clinically similar to those seen in humans. In contrast, previous observations suggest differences in their autoantibody reactivity patterns against histones and DNA which are components of the nucleosome in chromatin. The objective of this study was to assess comprehensively the levels of autoantibodies against histone, DNA and nucleosome antigens in a population of lupus dogs. The specificities of antibodies in lupus and control dog sera were determined using IgM- and IgG-specific reagents in an ELISA against a variety of chromatin antigens. When compared with control sera, IgG antibodies to individual histones H1, H2A, H3 and H4 were significantly higher in the lupus group. In contrast, we did not detect IgG antibodies specific for H2B, H2A-H2B, DNA, H2A-H2B-DNA or nucleosome in lupus dogs. There was no significant increase in any of the IgM specificities tested. Therefore, the reactivity pattern to nucleosome antigens in canine lupus is restricted to IgG antibodies against individual histones H1, H2A, H3 and H4. This stands in contrast with human and murine lupus, where autoantibodies are directed against a wide variety of nucleosomal determinants, suggesting that unique mechanisms lead to the expansion of anti-histone antibody clones in canine lupus. The high incidence of glomerulonephritis in dog lupus suggests that anti-DNA antibodies are not required for the development of this complication, whereas IgG anti-histone antibodies may be relevant to its pathogenesis.

Animals↗

Protein-losing enteropathy in systemic lupus erythematosus.

Two patients with systemic lupus erythematosus (SLE) presented with anasarca, pleural effusions and severe hypoalbuminema. Both were demonstrated to have protein-losing enteropathy, a rare complication of SLE. Other causes of gastrointestinal protein loss were excluded. There were marked similarities in both cases including circulating ANF with speckled staining, anti-(U1)RNP antibodies and low serum complement levels. Complete remission was achieved in both with prednisolone. Anti-(U1)RNP may be a marker for a subset of SLE in which protein-losing enteropathy is a major manifestation.

Adult↗