Lupus

Pulmonary hypertension (PH) is a serious form of pulmonary complication that occurs less frequently in lupus than in other connective tissue diseases like scleroderma; however, it is likely that it is under-recognized in lupus. The symptoms of PH in lupus are non-specific (dyspnea, fatigue, impaired exercise tolerance) and can also be caused by other factors such as pleural or pericardial effusions, interstitial lung disease and many more, making it possible to miss the diagnosis. There are several potential causes of PH in lupus including thromboembolic disease, pulmonary vasculitis, and hypoxia and fibrosis from interstitial lung disease. Endothelin-1 is elevated in lupus and may be associated with PAH. In some studies, pulmonary arterial hypertension (PAH) has been found to be a major cause of mortality in lupus patients. Echocardiograms are a screening tool, but may yield false positives, and a right heart catheterization must be performed to confirm PAH. Early identification is important and can alter the natural history of this dangerous complication of lupus. Treatment of PAH associated with lupus includes standard PAH treatment as well as immunosuppression.

The aim of this study was to analyze the effect of exposure to antimalarial drugs at diagnosis of lupus nephritis on the outcome of the disease, especially renal failure, comorbid processes, and survival. We analyzed a cohort of 206 consecutive patients with biopsy-proven lupus nephritis. Renal biopsies were categorized according to the classification proposed by the ISN/RPS in 2003. Exposure to antimalarial drugs (chloroquine and hydroxychloroquine) was defined as the use of these drugs before the diagnosis of lupus nephritis independent of dose and duration. Fifty-six (27%) patients had received antimalarials before the diagnosis of lupus nephritis. During the follow-up, these patients had a lower frequency of creatinine values >4 mg/dL (2% vs 11%, P = 0.029) and end-stage renal failure (2% vs 11%, P = 0.044) in comparison with those never treated with antimalarials. Patients exposed to antimalarials also had a lower frequency of hypertension (32% vs 50%, P = 0.027), infections (11% vs 29%, P = 0.006), and thrombotic events (5% vs 17%, P = 0.039). Twenty patients (10%) died during the study period. Patients exposed to antimalarials had a lower mortality rate at the end of the follow-up (2% vs 13% for those not exposed to antimalarials, P = 0.029). Multivariate analysis identified thrombosis and infections as statistically significant independent variables. Kaplan–Meier plots showed a lower rate of end-stage renal failure (log rank = 0.04) in patients exposed to antimalarials. In conclusion, exposure to antimalarials before the diagnosis of lupus nephritis was negatively associated with the development of renal failure, hypertension, thrombosis and infection, and with a better survival rate at the end of the follow-up. This, together with other published data, suggests that antimalarials should be considered a mandatory therapeutic option in all patients diagnosed with systemic lupus erythematosus.

Previous reports have suggested that regulatory T cells (Treg) are abnormal in patients with systemic lupus erythematosus (SLE). In the present work, we quantified CD4⁺FOXP3⁺ Treg cells in patients with SLE and found no quantitative alterations. However, we found a clear defect in suppression assays. Surprisingly, SLE-derived Treg cells exhibited a normal phenotype and functional capacity. Conversely, SLE-derived CD4⁺CD25⁻ effector T cells resisted suppression by autologous and allogeneic regulatory cells. Our findings strongly suggest that the defect in T-cell suppression observed in SLE is because of effector cell resistance and not because of an abnormal regulatory function.

The main objective of this study is to describe the presence of infections in patients with pulmonary haemorrhage and systemic lupus erythematosus. Patients with systemic lupus erythematosus and pulmonary haemorrhage were thoroughly evaluated in the first 48 hours with imaging plus bronchoscopy and bronchoalveolar fluid analysis. If needed, videoassisted thoracoscopy and lung biopsy were performed too. In all, search for bacterial, mycobacterial and fungal infections proceeded. Appropriate blood, bronchoalveolar fluid and tissue cultures were taken. Patients were treated with antibiotics and corticosteroids in case of infection. Otherwise, they received initial intravenous methylprednsiolone pulses for 3 days as standard therapy for pulmonary haemorrhage in systemic lupus erythematosus. Additional treatment with immunosuppressives was further decided by the treating physicians. Fourteen events in 13 patients were evaluated. In eight events (57%), an infection was demonstrated. Aetiological agents included Pseudomonas sp. and Aspergillus fumigatus. Four patients died, three of them because of the pulmonary infection and one because of cerebral haemorrhage secondary to severe systemic hypertension, 48 hours after methylprednisolone treatment. Patients with systemic lupus erythematosus and pulmonary haemorrhage have a high prevalence of infections. The influence of pulmonary haemorrhage in the setting of systemic lupus erythematosus needs further study to establish adequate treatment and to reduce the high mortality of this complication.

The objective was to study the association of antibodies against cyclic citrullinated peptides (anti-CCP) in patients with lupus articular damage. We studied 34 systemic lupus erythematosus patients (30 women) with (n = 14) or without (n = 20) deforming arthropathy. Anti-DNA and arthritis were mandatory inclusion criteria for both groups. As controls, 34 patients with rheumatoid arthritis and nine patients with rheumatoid arthritis and systemic lupus erythematosus (rhupus) were included. Anti-CCP and rheumatoid factor were determined by ELISA and nephelometry respectively. All patients had recent x-ray films of the hands that were evaluated according to Sharp’s method. Systemic lupus erythematosus patients had a mean 6.50 ± 0.86 (SD, range 5–8) American College of Rheumatology (ACR) criteria, rheumatoid arthritis patients met 5.38 ± 0.60 (range 4–6) ACR criteria for rheumatoid arthritis and rhupus patients had 5.78 ± 0.44 (range 5–6) criteria for rheumatoid arthritis and 5.11 ± 0.78 (range 4–6) for systemic lupus erythematosus. Systemic lupus erythematosus patients, with or without deforming arthropathy, had normal serum anti-CCP concentrations. In contrast, rheumatoid arthritis and rhupus patients had 30- and 23-fold higher than normal amounts of anti-CCP (p < 0.001, both comparisons). Rheumatoid arthritis (97%) and rhupus (100%) patients were more frequently positive for anti-CCP than SLE patients with (7%) or without (5%) deforming arthropathy (p < 0.001, both comparisons). Patients with lupus deforming arthropathy were more frequently positive for rheumatoid factor (65%) than patients with non-deforming arthritis (15%) (p = 0.005). Patients with lupus deforming arthropathy had similar frequency of erosions and mean Sharp’s score than rhupus patients. Anti-CCP antibodies do not associate with lupus arthropathy, whether deforming, non-deforming or erosive.

Rapamycin is a potent immunosuppressive drug currently used mainly for rejection prophylaxis in renal transplantation. The aim of this study was to determine the effect of rapamycin treatment on the development of nephritis in lupus-prone New Zealand Black/White F₁ (NZB/W F₁) mice. Twelve-week-old female NZB/W F₁ mice were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 20 weeks. The severity of nephritis was assessed by clinical and biochemical parameters, renal histology, immunohistochemistry and gene expression studies. Rapamycin treatment markedly reduced proteinuria, improved renal function, decreased serum anti–double stranded DNA antibody levels and diminished splenomegaly. Kidney sections from saline-treated mice showed marked mesangial proliferation, tubular dilation with protein cast deposition and interstitial inflammatory cell infiltration. Rapamycin-treated mice had near normal renal histology, with marked reduction in glomerular immune deposition and the infiltration by T cells, B cells and macrophages. Rapamycin treatment was associated with down-regulation of intra-renal expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein. We conclude that rapamycin is highly effective in preventing the development of nephritis in NZB/W F₁ mice. The beneficial effects of rapamycin are mediated through inhibition of lymphoproliferation and reduced MCP-1 expression.

The objective of this study is to examine the clinical features and outcomes of patients with systemic lupus erythematosus (SLE) whose disease began in adolescence [juvenile-onset SLE (jSLE)] compared with adult-onset patients [adult-onset SLE (aSLE)] from a large multiethnic cohort. Systemic lupus erythematosus patients of African-American, Caucasian, or Hispanic ethnicity and ≥1 year follow-up were studied in two groups: jSLE (diagnosed at ≤18 years); aSLE (diagnosed at 19–50 years; matched for gender and disease duration at enrolment). Sociodemographic data, SLE manifestations, disease activity, damage accrual, SLE-related hospitalizations or emergency room visits, drug utilization, mortality and psychosocial characteristics and quality of life were compared. Data were analysed by univariable and multivariable analyses. Seventy-nine patients were studied (31 jSLE, 48 aSLE); 90% were women. Mean (SD) total disease duration was 6.8 (2.7) years in jSLE and 5.6 (3.3) years in aSLE (p = 0.077). Mean age at cohort entry was 18.4 (1.8) and 33.9 (9.2) years in jSLE and aSLE respectively. By univariable analysis, jSLE patients were more commonly of African-American descent, were more likely to have renal and neurological involvements, and to accrue renal damage; jSLE patients had lower levels of helplessness and scored higher in the physical component measure of the SF-36 than aSLE patients. Renal involvement [OR = 1.549, 95% CI (1.397–15.856)] and neurological involvement [OR = 1.642, 95% CI (1.689–15.786)] were independently associated with jSLE by multivariable analysis. There was a larger proportion of African-Americans within the jSLE group. After adjusting for ethnicity and follow-up time, jSLE patients experienced more renal and neurological manifestations, with more renal damage. There was a two-fold higher mortality rate in the jSLE group.

Myelopathy is a rare but severe neurological manifestation of systemic lupus erythematosus (SLE) with a high morbidity. The factors that contribute to prognosis are unknown. In this study, 14 patients with lupus myelopathy (LM) from our centre were retrospectively studied. Another 23 patients with other neuropsychiatric SLE (NPSLE) features were enrolled as a comparison group. The morbidity of LM was evaluated by the ASIA Impairment Scale. The clinical and serological characteristics and prognostic factors for LM were investigated. The age, gender, duration of SLE, non-CNS disease activity and autoantibody profile in patients with LM was not different in the NPSLE cohort. A relatively low prevalence of anti–phospholipid antibodies (aPL) in LM sera compared to NPSLE (28.6% vs 52.2%, P = 0.19) was observed. Longitudinal lesion detected by magnetic resonance imaging (MRI) was identified in 33.3% of patients with LM, whereas 50% showed focal speckle-like lesions. The morbidity of LM is 50%. Muscle strength of grade 3 or higher on admission was a strong indicator for a better prognosis (P = 0.006), whereas other parameters including longitudinal lesion, sensory deficit level, disease activity and aPL did not discriminate good from poor outcome in LM. Early aggressive immunosuppressive therapy (within 2 weeks of onset of myelopathy) tend to associate with a favourable outcome (P = 0.07).

Leflunomide is an immunosuppressive agent that acts by inhibiting pyrimidine synthesis in lymphocytes and other rapidly proliferating cells, as well as by suppressing tumor necrosis factor-α–induced cellular responses. A number of leflunomide-related adverse events have been reported. Among cutaneous side effects, a few cases of subacute cutaneous lupus erythematosus have been described. We report a previously undocumented reaction to leflunomide, manifesting as subacute cutaneous lupus erythematosus and erythema multiforme-like lesions, in a young woman treated with this drug for ankylosing spondylitis. Withdrawal of leflunomide combined with a short cycle of systemic corticosteroid led to the resolution of the patient’s rash, indicating this drug as being responsible for the development of the disease. We conclude that leflunomide might have triggered the occurrence of both subacute cutaneous lupus erythematosus and erythema multiforme in a patient with pre-existing autoimmune diathesis. The suppressive effect of this drug on tumor necrosis factor-α–related mechanisms might have played a role in the induction of such a unique reaction to leflunomide.

A healthy boy developed subacutely progressive quadriparesis, complicated by sudden paraplegia, fever, and meningeal signs, diagnosed as longitudinal myelitis, aseptic meningitis, and conus medullaris infarction and identified as the presenting manifestations of neuropsychiatric systemic lupus erythematosus. Rapid expansion of the conus on serial neuroimaging led to emergent decompressive laminectomy and cord biopsy showing vasculitis and cord infarction. The patient had partial recovery after treatment with high-dose steroids. Increased vigilance is required when pediatric patients develop a similar subacute presentation on the ground of active systemic lupus erythematosus because it may herald the onset of a catastrophic neurological syndrome.

Our objective was to characterize clinical features, laboratory findings, concomitant autoimmune diseases, and smoking habits of lupus erythematosus subgroups in genetically homogeneous patients from two Dermatology Departments of Finnish University hospitals. One hundred and seventy eight discoid lupus erythematosus, 55 subacute cutaneous lupus erythematosus, and 77 systemic lupus erythematosus patients were enrolled using patients’ charts from institutional database (1995–2006) and during routine control visits. Clustering analysis was performed to reveal natural groupings. Smoking at the onset of disease was significantly more common in all subgroups (57% for discoid lupus erythematosus, 35% for subacute cutaneous lupus erythematosus, and 34% for systemic lupus erythematosus) compared with the age/gender-matched prevalence in the Finnish population, suggesting smoking to be a trigger factor for cutaneous lupus. Leukopenia (38%) and lymphopenia (52%) were observed more often in patients with systemic lupus erythematosus than reported previously. Photosensitivity characterized all groups, especially patients with subacute cutaneous lupus erythematosus (87%). Of the autoimmune diseases, Sjögren’s syndrome was the most common (22% of patients with systemic lupus erythematosus), followed by autoimmune thyroid disease (13% of patients with subacute cutaneous lupus erythematosus). The clustering analysis showed environmental factors (smoking) to be more involved in disease development in discoid lupus erythematosus, whereas immunological factors were more significant in initiating systemic lupus erythematosus. The high prevalence of autoimmune thyroid disease, together with photosensitivity, and the clustering profiles suggest that lupus erythematosus subtypes, especially discoid lupus erythematosus, are heterogeneic in their pathomechanisms.

The aim of this study was to determine the factors associated with metabolic syndrome in patients with systemic lupus erythematosus from Puerto Rico. A total of 204 patients with systemic lupus erythematosus (per the American College of Rheumatology classification criteria) were evaluated. Metabolic syndrome was assessed using the American Heart Association and the National Heart, Lung, and Blood Institute classification. Socioeconomic–demographic parameters, health-related behaviours, clinical manifestations, autoantibodies, pharmacological treatments, disease activity (per the Systemic Lupus Activity Measure—Revised), and damage accrual (per the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were determined at study visit. Factors associated with metabolic syndrome were examined by univariable analyses and multivariable logistic regression models. A total of 196 (96.2%) were women. The mean age at study visit was 43.6 ± 13.0 years, and the mean disease duration was 8.7 ± 7.7 years. Seventy-eight patients (38.2%) had metabolic syndrome. In the multivariable analysis, age (odds ratio [OR] = 1.05; 95% confidence interval [CI] 1.02–1.09), government health insurance (OR = 2.06; 95% CI 1.07–4.22), exercise (OR = 0.33; 95% CI 0.14–0.92), thrombocytopenia (OR = 4.19; 95% CI 1.54–11.37), erythrocyte sedimentation rate (OR = 1.64; 95% CI 1.03–2.63), disease activity (OR = 1.14; 95% CI 1.00–1.30), and prednisone >10 mg/day (OR = 3.69; 95% CI 1.22–11.11) were associated with metabolic syndrome. In conclusion, older age, low socioeconomic status, lack of exercise, thrombocytopenia, increased erythrocyte sedimentation rate , higher disease activity, and prednisone >10 mg/day were independently associated with metabolic syndrome in patients with systemic lupus erythematosus from Puerto Rico.