Periorbital edema as the presenting sign of dermatomyositis.

BACKGROUND: Periorbital edema can occur in dermatomyositis, which is characterized by symmetric macular erythema, Gottron's papules, Gottron's sign, periungual telangiectasia, heliotrope rash, and poikilodermatous macules on the shoulders, arms, or upper back (shawl sign). CASE REPORT: We report the case of an 81-year-old man with dramatic periorbital edema. It was not until he was hospitalized with dysphagia 6 months after developing the edema that the diagnosis of dermatomyositis was considered. RESULTS: Laboratory tests, skin biopsy, and electromyography resulted in a diagnosis of dermatomyositis. CONCLUSIONS: Periorbital edema may appear as the presenting cutaneous manifestation of dermatomyositis.

Soluble HLA-I in rheumatic diseases.

OBJECTIVE: To study serum levels of Class I soluble HLA (sHLA-I) in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis or dermatomyositis (PM/DM) or scleroderma and to assess the possible influence of ethnic factors on concentration in each disease group. METHODS: Solid-phase enzyme linked immunoassay was used to measure sHLA-I in the serum of 385 patients with varied ethnic backgrounds (American-Caucasians, African-Americans, Georgian-Caucasians) with rheumatic diseases. Studies on patients were compared to similar measurements of 189 healthy individuals. RESULTS: Mean sHLA-I levels were significantly higher in patients with SLE than those observed in healthy individuals or other rheumatic diseases. Highest concentrations were present in Georgian-Caucasian patients with SLE. American-Caucasian patients with RA or scleroderma had higher sHLA-I levels than normal Caucasian individuals. The majority of patients with PM/DM in all ethnic subgroups were low secretors of sHLA-I. CONCLUSION: Mechanisms underlying the secretion of sHLA-I appear to differ among the rheumatic diseases studied and various ethnic groups. These genetic differences in sHLA-I secretion could be associated with ethnic and pathophysiologic differences among these rheumatic diseases.

Effects of tenidap and nonsteroidal antiinflammatory drugs on the response of cultured human T cells to interleukin 2 in rheumatoid arthritis.

OBJECTIVE: To assess the effects of tenidap, a new oxindole class antiinflammatory compound, on the proliferative response of cultured T cells to interleukin 2 (IL-2); and to compare these effects with the antiinflammatory drugs ibuprofen, naproxen, indomethacin, piroxicam, and sulindac. METHODS: T cells were cultured with either tenidap, ibuprofen, indomethacin, naproxen, piroxicam, or sulindac in the presence of IL-2, then assayed for incorporation of tritiated thymidine. RESULTS: Tenidap, ibuprofen, and naproxen, at therapeutically attainable concentrations, significantly inhibited the proliferative response of T cells to IL-2. In contrast, indomethacin, piroxicam, and sulindac did not alter this response. Tenidap had a direct inhibitory effect on the response of activated T cells to IL-2. Both ibuprofen and naproxen interfered with the binding of IL-2 to T cells. CONCLUSION: These results suggest variable effects of different antiinflammatory drugs on lymphocyte function that may relate to the differential effectiveness of these drugs in patients with rheumatoid arthritis.

Correlation of serum interleukin-8 and cell surface lysosome-associated membrane protein expression with clinical disease activity in systemic lupus erythematosus.

Cell surface expression of lysosome-associated membrane proteins (LAMPs) correlates with serum interleukin-8 (IL-8) levels, shorter disease duration, greater functional impairment from disease-related symptoms and soluble IL-2 receptor levels (sIL-2R) in patients with scleroderma. In this study of 46 patients with systemic lupus erythematosus (SLE), the relationship of serum IL-8 and cell surface LAMP to two clinical measures of disease activity, the SLEDAI and SLAM scales, was evaluated. IL-8 levels were determined on serum samples by the immunometric sandwich enzyme immunoassay technique. Cell surface LAMP expression was determined by flow cytometric quantitation of peripheral blood mononuclear cells with monoclonal antibodies directed against two of the major LAMP proteins, lamp1 and lamp2. The clinical disease activity scales correlated significantly with each other, with C3 levels, serum IL-8, C4, dsDNA and sIL-2R. Lamp1 and lamp2 expression correlated with the SLAM but not the SLEDAI scale. Serum IL-8 levels were elevated in 49 of 51 samples tested (44 of 46 patients) and had a stronger correlation with disease activity than C4, dsDNA and sIL-2R levels. Significantly higher levels of IL-8 were seen in patients with evidence of renal involvement. Serum IL-8 and cell surface LAMP expression may be useful indicators of disease activity in patients with SLE. The possible role of IL-8 in the pathogenesis of SLE requires further investigation.

Cell surface expression of lysosome-associated membrane proteins (LAMPs) in scleroderma: relationship of lamp2 to disease duration, anti-Sc170 antibodies, serum interleukin-8, and soluble interleukin-2 receptor levels.

Lysosome-associated membrane proteins (LAMPs) are integral transmembrane proteins densely expressed on lysosomes which can be shuttled to the plasma membrane during cell activation. The objective of this study was to examine the expression of LAMPs on the cell surface of peripheral blood mononuclear cells (PBMCs) derived from patients with scleroderma. Heparinized blood was obtained from 23 patients with scleroderma and 15 healthy controls and PBMCs were isolated via a Ficoll gradient. Cells were stained with monoclonal antibodies directed against two of the major LAMPs, lamp1 and lamp2, and after subsequent staining with a fluorescent second antibody, were analyzed by flow cytometry. Two -and three-color immunofluorescence was utilized to define the phenotype of LAMP+ cells. The proportion of PBMCs expressing lamp2 on the cell surface was significantly elevated in patients with scleroderma (2.21 +/- 0.38%) compared to controls (1.14 +/- 0.27%; P < 0.05). Multivariate analysis of patient subgroups indicated that the significant factors contributing to higher levels in patients were shorter duration of disease (P < 0.01) and greater functional disability related to disease manifestations (P < 0.01). Patients with anti-Scl70 antibodies had the highest levels of cell surface lamp2 expression (4.19 +/- 0.90%; P < 0.0005). The degree of cell surface lamp2 expression correlated with the level of sIL2R in 19 scleroderma patients (r = 0.48; P < 0.05). Serum IL4 and IL6 did not correlate with cell surface LAMPs or sIL2R. Five of 19 patients had detectable serum levels of interleukin-8 (IL8). These patients had significantly higher cell surface lamp2 expression than those with no detectable IL8 (3.76 +/- 0.48% vs 1.44 +/- 0.39%; P < 0.01). Extended phenotyping revealed that > 85% of lamp2+ cells expressed the B-cell antigen CD19. Cell surface lamp2 expression correlates with clinical and laboratory parameters in scleroderma patients and may reflect immune system activation. Additionally, this is the first report describing an elevation of serum IL8 in an autoimmune or collagen-vascular disease.

Cytokines and soluble interleukin 2 receptors in rheumatoid arthritis.

Cytokines (IL-1 alpha and IL-2) and soluble interleukin 2 receptors (sIL-2r) were evaluated in patients with rheumatoid arthritis (RA) and controls. In RA, serum sIL-2r and IL-1 alpha were increased, and sIL-2r were significantly higher in synovial fluid than in serum. Serum levels of sIL-1r but not IL-1 alpha were increased in patients with acute infections, suggesting additional discriminatory specificity for IL-1 alpha. Both tender and swollen joint scores were higher for patients with RA with serum sIL-2r levels greater than or equal to 700 U/ml. Quantitation of immune mediators may be useful in the clinical assessment of RA in addition to their implication regarding the pathogenesis of the disease.

Inhibition of in vitro proliferative response of cultured T lymphocytes to interleukin-2 by gold sodium thiomalate.

Gold sodium thiomalate (GST), in concentrations attainable during chrysotherapy for rheumatoid arthritis, significantly inhibited the proliferative responses of cultured T cells stimulated by interleukin-2 (IL-2). The observed suppression was not related to altered kinetics, cell death, or interference with the binding of IL-2 to cell surface receptors. It appeared that GST affected an early step in the proliferative process, since maximum inhibition was obtained by the addition of GST within 4 hours of stimulation; progressive reduction of suppression was observed when GST was added later. Significant inhibition occurred when cultured T cells were preincubated for 24 hours with GST and washed prior to IL-2 stimulation, although the degree of suppression was decreased. Thus, inhibitory activity was not dependent on the continued presence of GST throughout culture. These findings suggest that there is a direct inhibition of T lymphocytes by GST, which may be important in immunomodulation by gold compounds.

Interleukin-2 production and effect of thymosin fraction 5 on interleukin-2 production in rheumatoid arthritis.

Interleukin-2 (IL-2) production and effects of thymosin fraction 5 (F5) on IL-2 production by peripheral blood mononuclear cells from patients with active rheumatoid arthritis (RA) were studied. Three patients with RA had elevated IL-2 production which was which was suppressed by F5. IL-2 production by peripheral blood mononuclear cells from 17 other patients with RA was similar to controls and was not affected by F5. Our results are consistent with hyperproduction of IL-2 by some patients with RA which is suppressed by F5.