New-onset Systemic Lupus Erythematosus Research Articles

Severe paediatric systemic lupus erythematosus nephritis--a single-centre experience

Paediatric patients with systemic lupus erythematosus (SLE) often have severe presentations including lupus nephritis (LN). Few paediatric studies have evaluated the anticardiolipin antibody (aCL) and renal histology. The purpose of this study was to evaluate clinicopathologic features, including aCL, short-term clinical and renal histologic outcomes of paediatric patients with new-onset SLE nephritis. We conducted a single centre, retrospective inception cohort study. Charts were reviewed at presentation (initial renal biopsy), 6-month (follow-up biopsy) and 12-month follow-up. The population consisted of 21 patients (median age, 14.5 years): 19/21 were female, 6/21 African American, 3/21 Asian, 9/21 Caucasian and 3/21 Hispanic. At presentation, 19/21 had elevated aCL, 15/21 hypertensive, 12/21 nephrotic and 7/21 required haemodialysis (HD)-2/7 HD patients had thrombotic microangiopathy, 1/7 crescentic glomerulonephritis. Two patients had thromboembolism: both had aCL, were taking oral contraceptives and required HD, one was nephrotic and the other had elevated lupus anticoagulant. Initial biopsies revealed 6/21 ISN/RPS class II nephritis, 3/21 class III, 7/21 class IV and 5/21 class V. Treatment consisted of methylprednisolone, corticosteroids, cyclophosphamide or mycophenolate mofetil. Follow-up biopsies revealed 12/13 to have improved histology. Indication for a follow-up biopsy was severe illness at presentation. At 12-month follow-up, no patients were nephrotic (P < 0.001) or required HD (P < 0.001), and 3/14 had elevated aCL (P < 0.001). Elevated aCL, hypertension, nephrotic syndrome and need for HD were common presentations among our paediatric SLE nephritis population. Renal histology and aCL were helpful in the therapeutic management.

Sweet Syndrome Associated With New-Onset Systemic Lupus Erythematosus in a 25-Year-Old Man

Sweet syndrome (SS) is a reactive neutrophilic process characterized by tender, erythematous papules and plaques, fever, and leukocytosis and is associated with underlying infections, inflammatory diseases, and malignant neoplasms. To our knowledge, only 2 cases of SS associated with new-onset systemic lupus erythematosus (SLE) have been reported—one in an adult woman and the other in a 14-year-old girl.1,2 We report the first case in an adult man.

Anti-α-actinin antibodies in relation to new-onset systemic lupus erythematosus and lupus nephritis

The aim of this study is to investigate the role of anti-alpha-actinin antibodies in patients with new-onset systemic lupus erythematosus (SLE). Thirty-six patients with SLE, 16 of whom had lupus nephritis (LN), and 53 healthy controls were included. The clinical and laboratory parameters of patients were collected from medical records or by questionnaire. Serum anti-alpha-actinin Abs was measured by competitive enzyme linked immunosorbent assay (ELISA). Our results show that the OD value of serum anti-alpha-actinin Abs in SLE patients was significantly lower than that in normal controls (1.212 +/- 0.244 vs. 1.364 +/- 0.202, P = 0.002); seven of 36 SLE patients were seropositive for anti-alpha-actinin Abs, which was significantly higher than in normal controls (19.4 vs. 3.8%, P = 0.028). There were no significant differences of clinical parameters between the anti-alpha-actinin Abs-positive patients and the negative patients. The positive rate of the term urine casts, elevated IgM and IgA in anti-alpha-actinin Abs-positive patients were higher than that in the negative patients. The OD values of serum anti-alpha-actinin Abs negatively correlated with disease activity (R(s) = -0.352, P = 0.035). Anti-alpha-actinin Abs may be a useful marker of the disease activity of SLE; in addition, it may be used as a complementary parameter to differentiate LN from SLE without nephritis.

Acute Viral Infections in Patients With Systemic Lupus Erythematosus

Few studies have evaluated the impact of viral infections on the daily management of patients with systemic lupus erythematosus (SLE). We analyzed the etiology and clinical features of acute viral infections arising in patients with SLE and their influence on the diagnosis, prognosis, and treatment of SLE. Cases occurring within the last 5 years were selected from the databases of 3 large teaching hospitals. Acute viral infections were confirmed by the identification of specific antiviral IgM antibodies and subsequent seroconversion with detection of specific IgG antibodies. In autopsy studies, macroscopic findings suggestive of viral infection were confirmed by direct identification of the virus or viruses in tissue samples. We performed a MEDLINE search for additional cases reported between January 1985 and March 2008. We included 88 cases (23 from our clinics and 65 from the literature review) of acute viral infections in patients with SLE. Twenty-five patients were diagnosed with new-onset SLE (fulfillment of the 1997 SLE criteria) associated with infection by human parvovirus B19 (n = 15), cytomegalovirus (CMV; n = 6), Epstein-Barr virus (EBV; n = 3), and hepatitis A virus (n = 1). The remaining 63 cases of acute viral infections arose in patients already diagnosed with SLE: in 18 patients, symptoms related to infection mimicked a lupus flare, 36 patients, including 1 patient from the former group who presented with both conditions, presented organ-specific viral infections (mainly pneumonitis, colitis, retinitis, and hepatitis), and 10 patients presented a severe, multiorgan process similar to that described in catastrophic antiphospholipid syndrome-the final diagnosis was hemophagocytic syndrome in 5 cases and disseminated viral infection in 5. Twelve patients died due to infection caused by CMV (n = 5), herpes simplex virus (n = 4), EBV (n = 2), and varicella zoster virus (n = 1). Autopsies were performed in 9 patients and disclosed disseminated herpetic infection in 6 patients (caused by herpes simplex in 4 cases, varicella in 1, and CMV in 1) and hemophagocytic syndrome in 3. A higher frequency of renal failure (54% vs. 19%, p = 0.024), antiphospholipid syndrome (33% vs. 6%, p = 0.023), treatment with cyclophosphamide (82% vs. 37%, p = 0.008), and multisystemic involvement at presentation (58% vs. 8%, p < 0.001); and a lower frequency of antiviral therapy (18% vs. 76%, p < 0.001) were found in patients who died, compared with survivors. The most common viral infections in patients with SLE are parvovirus B19 (predominantly mimicking SLE presentation) and CMV (predominantly presenting in severely immunosuppressed patients). CMV infection may mimic a lupus flare or present with specific organ involvement such as gastrointestinal bleeding or pulmonary infiltrates. Other herpesviruses are common in immunosuppressed SLE patients and may produce a wide range of manifestations. Physicians should examine the pharynx, eyes, skin, and genitalia and should conduct serologic and molecular studies to improve early detection of viral infection in patients with SLE.

Anti-neutrophil Cytoplasmic Antibodies in New-onset Systemic Lupus Erythematosus and Lupus Nephritis

This study aims to investigate the role of Antineutrophil cytoplasmic antibodies (ANCA) in patients with new-onset systemic lupus erythematosus (SLE). Sixty SLE patients, 28 of whom had lupus nephritis (LN), and 60 normal controls were enrolled; Serum ANCA was measured by enzyme linked immunosorbent assay (ELISA). The clinical and laboratory parameters of the patients were also recorded. Results show that twenty SLE patients were seropositive for ANCA, which was significantly higher than in normal controls. LN patients had significantly higher positive rate of ANCA than patients without nephritis. Compared with ANCA-negative patients, the ANCA-positive patients had significantly higher incidence of nerves system disorder, myocarditis, renal involvement and serositis. The positive rate of gamma-globulin, anti-dsDNA and anti-Sm antibodies were significantly higher in ANCA-positive patients. Elevated IgG and ESR, decreased serum C3/C4 appeared more often in ANCA-positive patients. In addition, serum ANCA level correlated positively with disease activity. Taken together, ANCA might be used as a potential complementary parameter to differentiate LN from SLE without nephritis. In addition, ANCA may serve as a useful marker of the disease activity of SLE.

Reduction of forkhead box P3 levels in CD4+CD25high T cells in patients with new-onset systemic lupus erythematosus

The aim of this study was to quantify and evaluate the forkhead box P3 (FoxP3) expression regulatory T cells in new-onset systemic lupus erythematosus (SLE) patients before and after treatment. Forty-four newly diagnosed and untreated SLE patients, including 24 with active disease (SLEDAI > or = 10) and 20 with inactive disease (SLEDAI < 5), were enrolled in this study. Twenty-one age- and sex-matched healthy volunteers were also included as controls. Peripheral blood samples were collected and mononuclear cells isolated. The expression of CD25 and FoxP3 in CD4(+) T cells were analysed with flow cytometry. CD4(+)CD25(+) (3.95-13.04%) and CD4(+)CD25(high) (0.04-1.34%) T cells in peripheral blood in untreated patients with new-onset active lupus were significantly lower than that in the patients with inactive lupus (7.27-24.48%, P < 0.05 and 0.14-3.07% P < 0.01 respectively) and that in healthy controls (5.84-14.84%, P < 0.05). Interestingly, the decrease in CD4(+)CD25(high) T cells was restored significantly in patients with active lupus after corticosteroid treatment. There was, however, a significantly higher percentage of CD4(+)FoxP3(+) T cells in patients with active (5.30-23.00%) and inactive (7.46-17.38%) new-onset lupus patients compared with healthy control subjects (2.51-12.94%) (P < 0.01). Intriguingly, CD25 expression in CD4(+)FoxP3(+) T cells in patients with active lupus (25.24-62.47%) was significantly lower than that in those patients with inactive lupus (30.35-75.25%, P < 0.05) and healthy controls (54.83-86.38%, P < 0.01). Most strikingly, the levels of FoxP3 expression determined by mean fluorescence intensity in CD4(+)CD25(high) cells in patients with active SLE were significantly down-regulated compared with healthy subjects (130 +/- 22 versus 162 +/- 21, P = 0.012). CD4(+)CD25(high) T cells are low in new-onset patients with active SLE and restored after treatment. Despite that the percentage of CD4(+)FoxP3(+) T cells appear high, the levels of FoxP3 expression in CD4(+)CD25(high) T cells are down-regulated in untreated lupus patients. There is a disproportional expression between CD25(high) and FoxP3(+) in new-onset patients with active SLE.

Clinical significance of increased CD4+CD25−Foxp3+ T cells in patients with new-onset systemic lupus erythematosus

Objective:To investigate the expressions of Foxp3 and CD25 on CD4+ T cells from patients with new-onset systemic lupus erythematosus (SLE) and assess their clinical significance.Methods:10 patients with active (systemic lupus...

Nephrogenic Fibrosing Dermopathy in a Patient with Systemic Lupus Erythematosus and Acute Lupus Nephritis

Nephrogenic fibrosing dermopathy is a recently recognized skin disorder similar in appearance to scleromyxedema but without the systemic involvement. We describe a 14-year-old girl with new-onset systemic lupus erythematosus and acute lupus nephritis who developed on the lower extremities confluent hyperpigmented, woody, indurated plaques that contained groups of coalescing erythematous papules. Nephrogenic fibrosing dermopathy was diagnosed histologically. Possible etiologies are discussed.

Long-term Survival of Southern Chinese Patients With Systemic Lupus Erythematosus

We conducted the current study to determine the clinical determinants of survival and the survival rates in an unselected cohort of Chinese patients with new-onset systemic lupus erythematosus (SLE), including all age-groups. Patients were those newly diagnosed as having SLE or referred within 6 months of diagnosis to the departments of medicine, geriatrics, and pediatrics at Tuen Mun Hospital, Hong Kong, between 1991 and 2003. Patients under the care of all specialists were included for analysis. We obtained demographic data, presenting and cumulative clinical features, disease activity, and serial damage scores. For patients who died or were lost to follow-up, data were censored at the last clinic visit. Survival over time was studied by the Kaplan-Meier method, and factors predictive of mortality were evaluated by the Cox proportional hazard model. We studied 285 new-onset SLE patients (92% women). All were ethnic Chinese and fulfilled at least 4 of the American College of Rheumatology criteria for SLE. The mean age of SLE onset was 30.0 +/- 13.5 years. Fifty (18%) patients had first onset of SLE before the age of 16 years (childhood onset), and 22 (8%) had disease onset after the age of 50 years (late onset); 213 (75%) patients had disease onset between the ages of 16 and 50 years (adult onset). Twenty-nine (10%) patients died (4 from the childhood-onset group, 6 from the late-onset group, and 19 from the adult-onset group) and 18 (6%) patients were lost to follow-up. The overall 5-, 10-, and 15-year survival rates were 92%, 83%, and 80%, respectively. Survival was significantly worse in late-onset patients: 5-, 10-, and 15-year survival rates were 66%, 44%, and 44%, respectively; p < 0.0001. Infection was the main cause of death (55%), followed by cardiovascular (17%) and cerebrovascular complications (14%). Unfavorable factors for survival on univariate analysis were increasing age, damage scores at 1 year, and the use of high-dose corticosteroids. Cox regression revealed that damage scores at 1 year and hematologic manifestations were independent predictors of mortality. Long-term survival of Chinese SLE patients is comparable to that reported for white patients in the 1990s. Late-onset SLE patients have the worst prognosis. Early damage predicts mortality.

SLE nephritis is associated with an oligoclonal expansion of intrarenal T cells

Autoimmune systemic lupus erythematosus (SLE) nephritis is characterized by the influx of mononuclear inflammatory cell infiltrates within the glomeruli and renal interstitium. To evaluate the possibility that intrarenal T cells result from the expansion of lymphocytes using limited T-cell receptor (TCR) genes, we analyzed the TCR Vbeta gene expression among infiltrating lymphocytes in renal tissue compared with simultaneous peripheral blood lymphocytes of four children with new-onset SLE nephritis. The TCR Vbeta gene expression in peripheral blood T cells from patients with SLE nephritis, when compared with normal controls, showed no preferential expansion or deletion of select Vbeta gene families. In contrast, when paired peripheral blood and renal tissue were analyzed, intrarenal lymphocytes in SLE nephritis demonstrated evidence of expansion of select Vbeta gene families. Sequence analysis of the V(D)J joining regions of the TCRbeta with the expanded families demonstrated a striking oligoclonality. These observations suggest that infiltrating T cells within renal tissue may use TCR Vbeta genes targeted toward nephritogenic antigens. (Am J Kidney Dis 1998 Mar;31(3):418-26)

New-Onset Systemic Lupus Erythematosus During Chronic Dialysis and After Transplantation for Idiopathic Renal Failure

The onset of end-stage renal disease typically leads to quiescence of systemic lupus erythematosus clinical and serologic activity. We report two cases of systemic lupus erythematosus diagnosed for the first time years after dialysis and transplantation, respectively, for idiopathic end-stage renal disease. The transplant patient developed SLE despite ongoing treatment with prednisone and cyclosporine. New onset SLE can occasionally occur despite dialysis or transplantation.