Early Systemic Lupus Erythematosus Research Articles

Early versus later onset childhood-onset systemic lupus erythematosus: Clinical features, treatment and outcome

The objective of the study was to compare clinical features, treatment and disease outcome in patients with early versus later onset of childhood-onset systemic lupus erythematosus (cSLE). A retrospective matched cohort study of cSLE patients diagnosed between 1988 and 2008 and followed for a minimum of one year was conducted. Thirty-four pre-pubertal cSLE patients with disease onset prior to their 12th birthday were matched by ethnicity and year of diagnosis to 34 pubertal cSLE patients. The most common criteria at diagnosis in both groups were malar rash, arthritis, hematologic manifestations, and renal disease. After a mean follow-up of more than six years, a similar proportion of patients in the two groups were still prescribed corticosteroids (47% and 41%); patients in the early onset group required a significantly higher daily dose (0.6 mg/kg prednisone-equivalent versus 0.2 mg/kg, p < 0.05). There were no significant differences in organ involvement, disease activity and disease damage between the two groups, and severe complications occurred at similar rates. There were a greater number of admissions to the pediatric intensive care unit (PICU) in the early onset group (18 versus 5, p = 0.01), with time-to-event analysis demonstrating a significantly shorter disease duration from diagnosis to first PICU admission in the early onset group (p < 0.001). While a similar proportion of patients in the early and later onset groups required treatment with cyclophosphamide, patients in the early onset group received treatment earlier in their disease course (mean 13.7 versus 19.9 months, p < 0.001). Early onset cSLE leads to earlier and more frequent PICU admission, earlier use of cyclophosphamide, and higher corticosteroid dose at long-term follow-up.

Differential association of juvenile and adult systemic lupus erythematosus with genetic variants of oestrogen receptors alpha and beta

Oestrogens acting via nuclear receptors (encoded by ESR1 or ESR2) are important for pathogenesis of systemic lupus erythematosus (SLE). rs2234693 and rs4986938 are two single nucleotide polymorphisms (SNPs) whose C and A variants increase transcription of ESR1 and ESR2, respectively. The T allele of rs2234693 was associated with early onset SLE, whereas the role of rs4986938 in SLE was not reported. Our aim was to examine the role of rs2234693 and rs4986938 in conferring susceptibility to juvenile and adult SLE (jSLE and aSLE). Genotype distribution of both SNPs was analysed in 84 jSLE, 112 aSLE patients and 1001 controls. Allele C of rs2234693 was associated with jSLE (OR = 1.87, p = 0.006, p(corrected) = 0.02), whereas allele A of rs4986938 showed an association with aSLE (OR = 1.46, p = 0.008, p(corrected) = 0.03). In jSLE, rs2234693 C had lower frequency in patients with central nervous system involvement (OR = 0.39, p = 0.005, p(corrected) = 0.04) and showed a trend for increase among males, patients with renal involvement and those without DR2/3 (p < 0.05, p(corrected) > 0.05). Whereas our results are consistent with a role of ESR1 variation in jSLE, more studies are needed since the direction of association was the opposite of that reported previously. The association between rs4986938 (ESR2) and aSLE is a novel finding, consistent with our recent report associating this variant with Graves' disease.

Early onset systemic lupus erythematosus: differential diagnoses, clinical presentation, and treatment options

Juvenile systemic lupus erythematosus is a rare multisystemic autoimmune disease with variable clinical manifestations, and disease onset before 16years of age. Patients younger than 5years are rarely affected and the age of onset may contribute to the course of disease in terms of clinical presentation, organ involvement, and serological findings. Here, we report two exemplary early-onset SLE patients, a 28-month-old patient with WHO class IIB kidney disease, arthritis, and a typical antibody constellation and an 11-month-old infant that presented with microcytic anemia, leukocytosis, arthritis, fasciitis, fatty liver disease, protein losing enteropathy, edema, and minimal change glomerulonephritis. Epidemiologic and clinical features of early-onset SLE compared to other forms of SLE are given and differential diagnoses and treatment options are discussed.

Evaluation of the Internet for Finding Persons With Undiagnosed Rheumatoid Arthritis and Systemic Lupus Erythematosus

The internet is used by many new rheumatology patients before visiting a health care provider, and is also used for health education, for recruiting study participants, administering surveys, conducting clinical trials, data entry and management of multicenter trials, and providing a forum for patients to share experiences in chat rooms. The internet has not been used for nor evaluated for public health applications. We evaluated the internet for early detection and referral of individuals with "typical" early symptoms of undiagnosed rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The websites and selected links identified by search terms of typical symptoms were evaluated for health information quality, readability, and whether or not the sites prioritized possibilities and suggested actions. None of the websites examined were completely suitable for finding undiagnosed persons with early RA or SLE. Although the websites had accurate information, their reading levels were too high for the average reader, and were generally poor in terms of giving a differential diagnosis, prioritizing the possibilities and none provided an algorithm for action. Internet sites could be enhanced for early detection and referral. The internet has become an important factor in clinical practice and physicians are increasingly explaining or responding to the information that their patients find on the internet. Our study shows that the information available to individuals with undiagnosed RA and SLE is likely to be of little help to them and could delay their seeking appropriate attention.

Compound heterozygosity for two MSH6 mutations in a patient with early onset colorectal cancer, vitiligo and systemic lupus erythematosus

Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is an autosomal dominant condition caused by heterozygous germline mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. Rare cases have been reported of an inherited bi-allelic deficiency of MMR genes, associated with multiple café-au-lait spots, early onset CNS tumors, hematological malignancies, and early onset gastrointestinal neoplasia. We report on a patient with vitiligo in segments of the integument who developed systemic lupus erythematosus (SLE) at the age of 16, and four synchronous colorectal cancers at age 17 years. Examination of the colorectal cancer tissue showed high microsatellite instability (MSI-H) and an exclusive loss of expression of the MSH6 protein. Immunohistochemical analysis of normal colon tissue also showed loss of MSH6, pointing to a bi-allelic MSH6 mutation. Sequencing of the MSH6 gene showed the two germline mutations; c.1806_1809delAAAG;p.Glu604LeufsX5 and c.3226C > T;p.Arg1076Cys. We confirmed that the two mutations are on two different alleles by allele-specific PCR. To our knowledge, neither parent is clinically affected. They did not wish to be tested for the mutations identified in their daughter. These data suggest that bi-allelic mutations of one of the MMR genes should be considered in patients who develop early-onset multiple HNPCC-associated tumors and autoimmune disorders, even in absence of either hematological malignancies or brain tumors.

The clinical impact of neuropsychiatric manifestations in early systemic lupus erythematosus

The clinical impact of neuropsychiatric manifestations in early systemic lupus erythematosus

Disease activity as a major risk factor for osteonecrosis in early systemic lupus erythematosus

This study Identifies the possible risk factors for osteonecrosis (ON) in a homogenous group of early system lupus erythematosus (SLE). Forty-six consecutive SLE patients (<5 years duration) followed at the Lupus Clinic, were enrolled between 2004 and 2005. An extensive clinical and laboratory evaluation using a standard electronic protocol established since 1999, including osteonecrosis symptoms and appropriate magnetic resonance imaging (MRI), were carried out at 1-6 months intervals. All other asymptomatic for osteonecrosis patients at study entry underwent MRI. ON confirmed by MRI was found in 10 of 46 patients (22%). Age, disease duration, clinical vascular features, frequency of thrombophilia and hypofibrinolysis factors and the lipoprotein profile were comparable in patients with and without osteonecrosis (P > 0.05). Remarkably, the frequency of patients with system lupus erythematosus disease activity index (SLEDAI) > or =8 in the previous year of osteonecrosis clinical diagnosis was significantly higher when compared to patients without this manifestation (60.0% versus 19.4%, P = 0.011), supported by the higher glucocorticoid cumulative dose in the same period (P = 0.045). In contrast, these two parameters evaluated in 13th-24th months preceding osteonecrosis diagnosis were similar in patients with and without osteonecrosis (P > 0.05). In the logistic regression analysis only SLEDAI remained as an independent risk factor for ON (OR = 6.78, CI = 1.05-43.55, P = 0.04). Disease activity in the previous year of ON clinical diagnosis is the main predictor factor for the development of this complication in early SLE.

Autoantibodies to RNA helicase A: A new serologic marker of early lupus

To investigate the clinical and immunologic significance of autoantibodies to RNA helicase A (RHA) in patients with systemic rheumatic diseases. The study group comprised 1,119 individuals enrolled in the University of Florida Center for Autoimmune Diseases registry from 2000 to 2005. Diagnoses were based on standard criteria. Autoantibodies were analyzed by immunoprecipitation and Western blot assays. Anti-RHA was observed in 17 (6.2%) of 276 patients with systemic lupus erythematosus (SLE), 2 patients with antiphospholipid antibodies, and 3 other patients, but anti-RHA was not observed in any patient with polymyositis/dermatomyositis, systemic sclerosis, rheumatoid arthritis, or Sjögren's syndrome. Anti-RHA was present in only 2.9% of African American patients, compared with 6.0% of white patients and 12-25% of patients of other races; this was in striking contrast to the frequency of anti-Sm in African American patients (27.2%). Among patients with SLE, anti-RHA was common in young patients (26% of those whose initial visit was at an age younger than 20 years versus 3-4% of those who were initially seen at ages 20-49 years) and at an early stage of disease (23% of those whose first clinic visit was within 1 year of disease onset versus 2-8% of those whose first visit was at least 1 year after disease onset). In 9 of 11 patients, levels of anti-RHA decreased to <10% of the initial value within 9-37 months, while levels of coexisting anti-Ro or anti-Su remained the same. New specificities developed in 2 patients (anti-nuclear RNP and anti-Sm, and anti-ribosomal P, respectively). These data suggest that the level of anti-RHA diminishes over time, and that anti-RHA is regulated via a mechanism different from that for other lupus-related autoantibodies. Anti-RHA is a new serologic marker for SLE. It is produced mainly in young non-African Americans at an early stage of their disease. Anti-RHA has a unique tendency to diminish over time. The production of anti-RHA may depend on a process restricted to early SLE, or it may be highly sensitive to treatment.

Clinical significance of antinucleosome antibodies in patients with “early” systemic lupus erythematosus

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Ig λ and Heavy Chain Gene Usage in Early Untreated Systemic Lupus Erythematosus Suggests Intensive B Cell Stimulation

AbstractTo determine the distribution of Vλ and Jλ as well as VH and JH gene usage in a patient with systemic lupus erythematosus (SLE), productive and nonproductive VJ and V(D)J rearrangements were amplified from individual peripheral CD19+ B cells and were analyzed. No differences in the Vλ and Jλ or the VH and JH gene usage in the nonproductive gene repertoire of this SLE patient were found compared with the distribution of genes found in normal adults, whereas marked skewing of both Vλ and VH was noted among the productive rearrangements. The distribution of productive Vλ rearrangements was skewed, with significantly greater representation of the Jλ distal cluster C Vλ genes and the Vλ distal Jλ7 element, consistent with the possibility that there was receptor editing of the Vλ locus in this patient. Significant bias in VH gene usage was also noted with VH3 family members dominating the peripheral B cell repertoire of the SLE patient (83%) compared with that found in normal subjects (55%; p &amp;lt; 0.001). Notably, a clone of B cells employing the VH3-11 gene for the heavy chain and the Vλ1G segment for the light chain was detected. These data are most consistent with the conclusion that extreme B cell overactivity drives the initial stages of SLE leading to remarkable changes in the peripheral V gene usage that may underlie on fail to prevent the emergence of autoimmunity.

Decreased production of interleukin-12 and other Th1-type cytokines in patients with recent-onset systemic lupus erythematosus.

To determine the profile of Th1-type and Th2-type cytokines produced by mononuclear cells from patients with recent-onset systemic lupus erythematosus (SLE), prior to the initiation of treatment with corticosteroids. Using sensitive radioimmunoassays, interleukin-4 (IL-4), IL-10, IL-12 p40, tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) released into the culture supernatants of various unstimulated and stimulated blood mononuclear cell populations from 10 SLE patients was assessed in comparison with 10 matched healthy controls studied in parallel. In early SLE, monocyte-enriched cells constitutively produced increased amounts of IL-10 and decreased amounts of IL-12 following stimulation. Lymphocyte-enriched cells in SLE produced decreased amounts of IFN gamma and TNF alpha following stimulation. In "rested" cells, these defects were accentuated and a defect in IL-12 production was suggested. Depletion studies suggested that CD8+ cells were a major source of TNF alpha and IFN gamma in controls, but not in SLE patients. Increased IL-4 production or abnormalities in GM-CSF production were not observed. This study suggests that even early in the course of SLE, monocyte production of IL-10 is increased and that of IL-12 is decreased. Decreased production of Th1-type cytokines in SLE may be secondary to this imbalance between IL-10 and IL-12. A contributory role of dysfunctional CD8+ cells is suggested.

Systemic lupus erythematosus: Recognition and management by the primary care physician

Systemic lupus erythematosus (SLE) is a disorder that primarily affects young to middle-aged women. It is a complex multisystem disease that can have very varied presentations. Typical manifestations of SLE include rash, oral ulcers, arthritis, Raynaud's phenomenon, alopecia, pleuropericarditis, and renal and central nervous system disease. However, the entire constellation of symptoms often is not present, and definitive diagnosis in early or atypical SLE can sometimes be difficult. Although the diagnosis of SLE is primarily clinical, it is often supported by the presence of specific autoantibodies. Recognition of the various signs and symptoms of SLE will allow the primary care physician to order appropriate screening tests and more specific serologies to help confirm the diagnosis. The antinuclear antibody is a useful screening test as it is found in more than 95 percent of patients with SLE, but its use is limited by its lack of specificity. Anti-double stranded DNA and anti-Smith antibodies are highly specific for SLE but are not found in all patients. Treatment and prognosis depend on the specific manifestations of the disease, with renal and central nervous system involvement generally being the most severe manifestations and requiring aggressive therapy.

Rheumatoid and lupus-erythematosus-like syndromes; complications of hydralazine (apresoline) therapy for hypertension.

During the past two years hydralazine hydrochloride (1-hydrazinophthalazine hydrochloride; Apresoline) has been used extensively in the treatment of hypertension. Its reputed ability to reduce arterial pressure through its central action 1 and to increase renal circulation 2 accounts in part for its usefulness as an antihypertensive agent. A syndrome, however, appeared among patients using hydralazine, with symptoms which ranged from mild migratory arthralgic pains to symptoms resembling early acute rheumatoid arthritis or acute systemic lupus erythematosus, according to Dustan and his group * and to Perry and Schroeder.† Other isolated cases reported in the recent literature include those of Manter, 7 Feder, 8 Reinhardt and Waldron, 9 and Shackman and associates. 10 Kaufman 11 reported a case of pancytopenia due to hydralazine. This report is an analysis of the late reactions in a group of patients treated with oral administrations of hydralazine