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Biomedical subjects

E D Silverman

Publications and source records attributed to E D Silverman.

At least 91 records · Page 5Linked to original sources
PubMed1993

Localized scleroderma progressing to systemic disease. Case report and review of the literature.

We describe a 15-year-old girl with biopsy-proven morphea who developed progression to systemic disease 2 years after initial presentation. In contrast to other reported patients with localized scleroderma, some of whom have had mild, nonprogressive systemic involvement, this patient developed severe, debilitating disease, with skin tightness, sclerodactyly, esophageal involvement, restrictive pulmonary disease, and myopathy. From the time of her initial evaluation, the patient was positive for antinuclear antibodies (ANA), which were shown to be primarily directed against the Ku antigens. This observation suggests that ANA may be a prognostic indicator for progression to systemic disease.

Antibodies, Antinuclear↗
PubMed1993

Limiting dilution analysis of Epstein-Barr virus infectable B cells secreting anti-Ro/SSA and anti-La/SSB antibodies in neonatal lupus erythematosus and systemic lupus erythematosus.

Neonatal lupus erythematosus (NLE) is associated with the transplacental passage of maternal anti-Ro and anti-La antibodies. In order to better determine the risk of delivery of a child with NLE, we examined the frequency of anti-Ro and anti-La antibody secreting cells in mothers of children with NLE and in mothers at risk to deliver a child with NLE. We established limiting dilution experiments, using EBV-infected peripheral blood mononuclear cells, from 10 mothers following delivery of a child with NLE and from six mothers with anti-Ro and anti-La antibodies who delivered an unaffected child. Supernatants were assessed, by Poisson analysis, to determine the frequency of IgG and IgM anti-Ro and anti-La antibody-secreting B cells. We found that the frequency of anti-Ro and anti-La IgM antibody secreting B cells was greater than the frequency of IgG antibody secreting B cells of the same autoantibody specificity. We found no correlation between serum IgM and IgG anti-Ro or anti-La antibody titres and their respective precursor cell frequencies. We found that the mothers of children with NLE who later developed SLE tended to have higher anti-Ro and anti-La antibody-committed B cells than did the mothers who remained well. Although anti-Ro and anti-La antibody precursor frequencies were similar within a patient, they varied significantly from patient to patient. We found that most of the experiments with a precursor frequency of < 1 per million were from mothers of children with NLE rather than the mother with SLE who delivered normal children. Overall, we found that, in anti-Ro and anti-La antibody-positive women, a low anti-Ro or anti-La antibody B cell precursor frequency tended to be associated with the birth of a child with NLE.

Antibodies, Antinuclear↗
PubMed1993

Diagnostic use of B-cell alloantigen D8/17 in rheumatic chorea.

Two unrelated patients with a family history of rheumatic fever had isolated, acquired chorea. Both index cases, as well as affected family members, had increased expression of the rheumatic B-cell alloantigen D8/17. This test may help differentiate Sydenham chorea from lupus chorea.

B-Lymphocytes↗
PubMed1993

Synovial fluid cells in juvenile arthritis: evidence of selective T cell migration to inflamed tissue.

The perpetuation of chronic synovitis in juvenile arthritis (JA) is a complex interaction of local and systemic regulatory mechanism. We examined the cell surface phenotype of synovial fluid cells and peripheral blood lymphocytes from 15 patients with JA to better understand the mechanism of local inflammation. Synovial fluid and peripheral blood mononuclear cells were analysed for cell surface expression of CD2, CD3, CD4, CD8, CD19, CD25, CD29, CD45R and Ia using flow cytometry. We found a very low percentage of B cells with a concomitant increase of T cells in synovial fluid as compared with peripheral blood. A large percentage of the synovial fluid T cells were HLA-DR+, or activated T cells, and there was a relative decrease in CD4+ cells in synovial fluid as compared with peripheral blood. There was only a minimal increase in CD25+ synovial fluid cells. The synovial fluid CD4+ cells were mainly of the CD2high, CD29+, CD45RO phenotype. This CD4 phenotype found on synovial fluid cells from patients with JA and in particular the CD29 cell surface marker, which recognizes a common beta-chain of adhesion molecules, is associated with binding to extracellular matrix proteins and is also associated with 'primed' T cells. Our results demonstrated the presence of T cells which either selectively migrate to synovium and synovial fluid or are activated in situ in the joint.

Adolescent↗
PubMed1992

Evidence for clonal expansion of T cell receptor V gamma II+ T cells in the synovial fluid of patients with arthritis.

We have demonstrated among synovial fluid T cells a unique profile of V gamma II sequences likely arising from clonally expanded T cells. We have determined the junctional diversity associated with each expressed V gamma family by resolving amplified fragments of cDNA into component parts on large denaturing gels. Among synovial fluid T cells we frequently find dominant fragments of a unique size clearly smaller than the dominant band observed with peripheral blood T lymphocytes. In some cases the dominant bands are 12 or 15 nucleotides smaller than the corresponding most abundant band from peripheral blood T lymphocytes. Patterns of lower m.w. species not typical of a polyclonal population argues that clones of T cells expressing the V gamma II family are expanding in the joint and that a high proportion of these cells do not express the V gamma IIJP sequence typical of peripheral blood but rather express V gamma II in combination with a shorter J fragment, JP1, JP2, J1, or J2. In addition by examining joint effusions from the left and right knees from the same individual we have shown that the profiles of V gamma II sequences derived from the fluids are identical to each other but clearly distinct from that of peripheral blood. We have, in addition, quantitated with a series of synthetic internal standards the relative usage of each V gamma family expressed by T cells in the synovial fluid and peripheral blood of seven patients with arthritis including six patients who were either children or adolescents and one adult patient. All patients showed a reduction in the relative expression of V gamma II in synovial T cells relative to peripheral blood T lymphocytes and a corresponding increase in the expression of V gamma I or V gamma III or both. We did not detect expression of V gamma IV in either lymphocyte population.

Arthritis↗
PubMed1992

Prognostic indicators of joint destruction in systemic-onset juvenile rheumatoid arthritis.

We retrospectively reviewed the charts and radiographs of 38 patients with systemic-onset juvenile rheumatoid arthritis, attempting to identify early in the disease course the clinical and laboratory observations most predictive of the later development of destructive arthritis. In 12 of the patients, destructive arthritis developed within 2 years of disease onset. When first examined, these patients could not readily be differentiated from those in whom joint destruction did not develop, but they more commonly had hepatosplenomegaly (p less than 0.04), serositis (p less than 0.01), and a lower mean serum albumin concentration (26.7 vs 31.3 gm/L; p less than 0.02). However, by 6 months after onset, patients with destructive arthritis more frequently had persistent systemic symptoms (92% vs 12%; p less than 0.0001), polyarthritis (67% vs 19%; p less than 0.0005), a lower mean hemoglobin level (95 vs 114 gm/L; p less than 0.001), a higher mean leukocyte count (21.2 vs 10 x 10(9)/L; p less than 0.0003), a higher mean platelet count (794 vs 400 x 10(9)/L; p less than 0.0001), and a higher mean erythrocyte sedimentation rate (43 vs 24 mm/hr; p less than 0.05). Multivariate analysis of the results at 6 months revealed that persistent systemic symptoms and a platelet count greater than or equal to 600 x 10(9)/L were the variables most highly predictive of the later development of joint destruction. We conclude that patients at high risk for the development of destructive arthritis may be identified within 6 months of disease onset, thereby indicating the need for more aggressive early therapy.

Adolescent↗
PubMed1992

High synovial immunoglobulin E levels in eosinophilic synovitis.

Eosinophilic synovitis occurred in a 7-year-old boy. Synovial fluid leukocytes were mostly eosinophils; the peripheral blood showed only mild eosinophilia. The level of eosinophil-derived neurotoxin in the synovial fluid was higher than that in the serum, suggesting intraarticular eosinophil degranulation. The IgE level was also elevated in the synovial fluid (3854 ng/ml) but normal in the serum (408 ng/ml), suggesting a localized immediate hypersensitivity immune response.

Child↗
PubMed1992

DNA analysis of HLA-DR, DQ, and DP alleles in children with polyarticular juvenile rheumatoid arthritis.

HLA-DR, DQ and DP alleles were determined by restriction fragment length polymorphism analysis and oligonucleotide probe hybridization of polymerase chain reaction amplified genomic DNA in 94 Caucasian children with polyarticular juvenile rheumatoid arthritis (JRA) [13 rheumatoid factor (RF)+ and 81 RF-] and 100 healthy controls. HLA-DRw8, DQw4, DQA1*0401, DQB1*0402 were increased in frequency in those patients with RF seronegative disease, with highest frequencies seen in patients with young age at onset (< 5 years of age). These findings were similar to what we observed in children with pauciarticular JRA, especially those with young age at onset. DPB1*0301 was also found in increased frequency in the RF- group, and in particular those seronegative for antinuclear antibody. In contrast to what is observed in patients with pauciarticular JRA, the frequency of DPB1*0201 was not increased in any polyarticular JRA patient group. These data suggest that polyarticular JRA shares many genetic features with pauciarticular JRA.

Alleles↗
PubMed1992

Childhood linear scleroderma: a possible role of thermography for evaluation.

Linear scleroderma is a rare, at times debilitating, disease with an unpredictable course. Currently, there is no satisfactory objective method for assessment of disease activity upon which to base therapeutic decisions. We evaluated 11 children with 18 linear scleroderma lesions (mean age 11.7 years, mean duration of disease 5.1 years) for disease severity and the presence of immunologic abnormalities, and attempted to correlate these results with thermography. Positive thermography was defined as warmer than surrounding skin or opposite limb by 0.5 degrees C. Six patients were thermography positive. Mean age, sex, disease duration and the presence of hypergammaglobulinemia and autoantibodies were similar in thermography positive and thermography negative patients. Six of 18 linear scleroderma lesions were thermography positive. All 3 new or expanding lesions were thermography positive. All 3 lesions that were resolving clinically were thermography negative. Three of 12 lesions that were clinically unchanged over a 6-month period were also thermography positive. In summary, thermography is a noninvasive test that appears to demonstrate active lesions in linear scleroderma. It is not influenced by previous soft tissue damage induced by linear scleroderma and may enable better monitoring of the effectiveness of proposed therapies.

Adolescent↗
PubMed1992

Major histocompatibility complex class II alleles in Kawasaki syndrome--lack of consistent correlation with disease or cardiac involvement.

Recent refinements in molecular genetic typing have allowed the precise determination of the extensive polymorphism now recognized in class II major histocompatibility complex (MHC) genotypes. This could have important applications in Kawasaki syndrome (KS), where the relative contribution of genetic factors is now well known. Accordingly, 44 Caucasian, 13 Asian, and 5 American black patients, as well as 221 Caucasian controls were typed for HLA-DRB1, DRB3, DRB4, DQA1, DQB1, and DPB1 alleles by oligonucleotide probe hybridization of polymerase chain reaction amplified genomic DNA using probes and primers supplied by the 11th International Histocompatibility Testing Workshop. Among the 15 HLA-DRB1, 3 DRB3, 9 DQA1, 15 DQB1, and 19 DPB1 alleles examined, none were found to be significantly associated with KS, except for an increased frequency of HLA-DRB3*0301 in Houston Caucasian patients when compared to Houston Caucasian controls (38 vs 11%, pc = 0.012, RR = 5.0). Twelve patients developed coronary artery involvement of whom 7 had aneurysms and 5 had dilatation (8 Caucasians, 2 blacks, 2 Asians). No specific HLA class II allele was associated with this disease complication. Despite a regional association, our data fail to support a consistent role for MHC class II alleles in the pathogenesis of KS.

Alleles↗
PubMed1992

T cell receptor V beta usage in synovial fluid of children with arthritis.

We have examined synovial fluid (SF) T cells from 5 children with various types of juvenile arthritis. Using the polymerase chain reaction (PCR) to determine the expression of 20 individual T cell receptor (TCR) beta variable (V) region families, we have shown with each patient that the SF T cells are polyclonal. Nevertheless, expanded usage of some families by SF T cells relative to peripheral blood T cells was evident in some cases. We conclude that the pattern of T lymphocytes in the inflamed joint may be a consequence in part of a polyclonal expansion or nonspecific homing of T cells to the joint, and in part a more restricted expansion of T cells potentially driven by arthritogenic antigens.

Antibodies, Antinuclear↗
PubMed1992

Intravenous immunoglobulin therapy: magic or black magic.

Intravenous immunoglobulin (IVIG) therapy has been used not only as replacement treatment for immunodeficiency, but also as treatment of autoimmune diseases, specifically Kawasaki disease, systemic juvenile arthritis and juvenile dermatomyositis. In Kawasaki disease, IVIG reduces the incidence of coronary artery abnormalities, as well as rapidly improving clinical and laboratory variables such as fever and rash, platelet count, white blood cell count and serum albumin. Furthermore, a single high dose of 2 g/kg is as effective as 400 mg/kg x 4 days. In systemic juvenile arthritis, followup of at least one year demonstrated that monthly treatment with IVIG resulted in improvement of systemic disease in 10/11 patients, allowed for cessation of prednisone treatment in 7/8 patients and significant improvement of arthritis in 8 patients. In juvenile dermatomyositis, we report 2 uncontrolled trials of IVIG treatment that resulted in significant clinical improvement and steroid-sparing. In contrast, IVIG treatment of systemic lupus erythematosus (SLE) resulted in improvement in 3 patients, but exacerbation or new onset of renal disease in 3 patients. Overall, our report demonstrates that IVIG has been effective both in a controlled trial in Kawasaki disease and in uncontrolled trials in systemic juvenile arthritis and juvenile dermatomyositis. We suggest that IVIG should be used cautiously in SLE.

Arthritis, Juvenile↗
PubMed1991

Primary pulmonary hypertension in a patient with systemic-onset juvenile arthritis.

We describe a 16-year-old girl with systemic-onset juvenile arthritis who presented with pulmonary hypertension, without evidence of pleural or parenchymal involvement of the lung, pulmonary vasculitis, or immune deposition in the pulmonary vasculature. Pleuropulmonary involvement occurs occasionally in juvenile arthritis, but primary pulmonary hypertension has not, to our knowledge, been previously reported. Histocompatibility typing showed positivity for HLA-DR3 and DRw52, both of which are associated with idiopathic pulmonary hypertension in children, and with pulmonary hypertension among patients with systemic sclerosis. Treatment with cyclosporine and corticosteroids resulted in a marked improvement in the clinical findings and pulmonary function in our patient.

Adolescent↗
PubMed1991

Treatment of dermatomyositis with intravenous gammaglobulin.

PURPOSE: The mainstay of pharmacologic therapy in patients with dermatomyositis is corticosteroids. However, because patients sometimes become refractory to these drugs and because these drugs have potential short- and long-term toxicities, alternate therapy is highly desirable. Therefore, a pilot study was initiated using high-dose intravenous gammaglobulin (IVGG) in the treatment of dermatomyositis. PATIENTS AND METHODS: IVGG was administered to five patients with juvenile dermatomyositis. Prior to IVGG treatment, all patients had persistent muscle weakness despite daily corticosteroids and three patients had developed unacceptable steroid toxicity. Two of the patients had previously developed toxicity while receiving immunosuppressive therapy. RESULTS: IVGG therapy resulted in improved muscle strength and ameliorated skin rash in all patients. The percentage increase in muscle strength as measured by sphygmomanometry following the 9-month course of IVGG ranged from 56% to 606% in the proximal lower extremities and from 30% to 186% in the proximal upper extremities. Following IVGG therapy, prednisone could be discontinued or the dose reduced in all patients. CONCLUSION: This study suggests that IVGG may allow steroid sparing in dermatomyositis and may provide a safe alternative to cytotoxic therapy.

Adrenal Cortex Hormones↗