Muscle involvement in polyarteritis nodosa: report of a patient presenting clinically as polymyositis and review of the literature.

Muscle symptoms, especially myalgias, appear to be common in patients with polyarteritis nodosa (PAN). We describe a patient who presented with a generalized myopathy and elevated creatine kinase (CK) suggestive of polymyositis. However, subsequent exploratory surgery for an acute abdomen revealed colonic perforation on the basis of PAN. A review of the literature suggests that generalized myopathy and elevated CK are uncommon features of PAN. A muscle biopsy can be a helpful procedure to secure the diagnosis in patients with PAN especially those with myopathies. Strategies for optimizing the choice of biopsy site are discussed.

Abnormal T-cell function in patients with psoriatic arthritis: evidence for decreased interleukin 2 production.

Psoriatic arthritis (PSA) is an inflammatory arthritis associated with psoriasis. Although not considered an autoimmune process, there is evidence for humoral and cellular immune abnormalities similar to autoimmune diseases such as rheumatoid arthritis and systemic lupus (SLE). We investigated mitogen-induced proliferation and interleukin 2 (IL-2) production by peripheral blood mononuclear cells in patients with PSA. Both IL-2 production and proliferation were significantly decreased in PSA patients when compared to controls. Increased arachidonic acid metabolism has been reported in skin and peripheral mononuclear cells of patients with psoriasis and PSA. We therefore also investigated the effect of indomethacin and prostaglandin E2 (PGE2) on IL-2 production. Addition of indomethacin to cultures did not significantly change IL-2 production in patients with PSA, but did so in controls. PGE2 produced a significant reduction in IL-2 production in PSA and in controls.

B cell surface marker analysis of synovial fluid cells in a patient with monoarthritis and chronic lymphocytic leukemia.

We describe a women with clinically quiescent chronic lymphocytic leukemia who developed monoarthritis consistent with her known diagnosis of osteoarthritis. Because of the concurrent chronic leukemia, we were concerned with the possibility of leukemic arthritis. Immunofluorescence of synovial fluid cells demonstrated an increase in B cells that failed to demonstrate monoclonality as determined by light chain class expression. However, biopsy of synovial tissue revealed leukemic infiltration. Local radiation therapy resolved the monoarthritis.

Colony stimulating factor occurs in both inflammatory and noninflammatory synovial fluids.

Synovial fluids (SF) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) and various other arthritides were examined for the presence of colony stimulating factors (CSF). CSF was found in 7 of 13 (54%) SF from OA patients and in 8 of 12 (67%) SF from RA patients. It was also found in SF from patients with other arthropathies including 5 of 5 samples from patients with septic arthritis. Inhibition studies employing monospecific antisera indicated that in both RA and OA, CSF was of the macrophage type (M-CSF). While CSF was found in both inflammatory and noninflammatory effusions, significantly greater numbers of colonies were stimulated by RA SF than by OA SF and in general greater numbers of colonies correlated with higher SF leukocyte counts. Our data suggest that CSF as well as other cytokines may be involved in the perpetuation of joint destruction that occurs in various rheumatological conditions.

Occurrence of interleukin-1 in human synovial fluid: detection by RIA, bioassay and presence of bioassay-inhibiting factors.

Synovial fluid (SF) from patients with osteoarthritis (OA), rheumatoid arthritis (RA), and various other arthridites was analyzed to assess the prevalence of interleukin-1 (IL-1) using both radioimmunoassay competitive inhibition specific for the beta form of IL-1 and the D10.G4.1 cell line bioassay which measures both alpha and beta forms of IL-1. Using radioimmunoassay competitive inhibition, IL-1 beta was found in 45% and 60% of individual samples from patients with OA and RA respectively. When RA and OA SF were examined in sequentially obtained samples, IL-1 beta occurred in one or more samples from 8 of 10 patients studied, suggesting the probability that it can be produced at some time in SF by all patients with these conditions. No correlation between SF leukocyte counts and the occurrence of IL-1 beta was noted and no effect of antiinflammatory drug treatment on the prevalence of IL-1 beta was found. When tested for the presence of IL-1 by the D10.G4-1 cell line, 66% and 50% of RA and OA patients respectively were found to contain IL-1. These were not in total concordance with results obtained by RIA. Of all SF tested, seven were negative by RIA but positive by D10.G4.1 and these are considered to contain IL-1 alpha. Seven samples which were RIA positive and D10.G4.1 negative were tested for their ability to inhibit IL-1 responses in the bioassay. Five of these contained inhibitor and one markedly enhanced the proliferative response of D10.G4.1 to a known amount of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of progressive necrotizing vasculitis with intravenous pulse cyclophosphamide and methylprednisolone.

We describe a patient with polyarteritis nodosa who, despite therapy with daily doses of oral prednisone and cyclophosphamide, developed acute renal failure. Renal histopathologic examination demonstrated crescentic glomerulonephritis. Treatment with intravenous pulse cyclophosphamide and methylprednisolone resulted in clinical improvement and significant recovery of renal function.

Intravenous cyclophosphamide and methylprednisolone for the treatment of bronchiolitis obliterans and interstitial fibrosis associated with crysotherapy.

A patient with rheumatoid arthritis receiving intramuscular gold developed severe pulmonary insufficiency. Histopathology revealed both bronchiolitis obliterans and interstitial fibrosis possibly related to gold therapy. The patient was successfully treated with IV cyclophosphamide and prednisone. During the course of therapy, hypogammaglobulinemia without detectable IgM developed.

Anticardiolipin antibodies in patients with rheumatic diseases.

Recent attention has focused on the presence of anticardiolipin (ACL) antibodies and their possible role in recurrent thrombosis and abortions in patients with systemic lupus erythematosus. We analyzed ACL antibodies in 243 consecutive patients to determine their frequency in patients with different rheumatic disorders. A significantly elevated frequency was found in patients with systemic lupus erythematosus (38%), rheumatoid arthritis (33%), and psoriatic arthritis (28%). No correlation could be found between ACL antibody levels and recurrent thrombosis. In patients with rheumatoid arthritis there was a significant correlation between ACL antibodies and a history of repeated abortions. No significant association was found between ACL antibodies and other autoantibodies except in patients with rheumatoid arthritis; ACL antibody-positive rheumatoid arthritis patients were much more likely to be antinuclear antibody-positive (P less than 0.0002).

Localized eosinophilic fasciitis in a patient with rheumatoid arthritis.

A case of eosinophilic fasciitis localized to the left thenar eminence in a patient with active rheumatoid arthritis is described for the first time. The clinical and pathologic similarities to localized forms of scleroderma, and the features that help to distinguish these conditions are discussed.

The specificity of antibodies to the F(ab')2 fragment of human IgG.

The specificity of IgG anti-F(ab')2 antibodies was examined by unfractionated sera of patients with rheumatoid arthritis and also with affinity-purified antibody preparations. Examination of the sera by an enzyme-linked immunosorbent assay, using pooled human F(ab')2 fragments absorbed to microtiter plates, revealed that IgG anti-F(ab')2 antibodies cross-react with human and rabbit IgG and rabbit F(ab')2. IgG anti-F(ab')2 antibodies were purified by affinity chromatography and, when tested by a fluid-phase inhibition enzyme-linked immunosorbent assay, were found to be of 2 types. One fraction, similar to pepsin agglutinator, reacted with human F(ab')2 fragment alone. The other fraction was cross-reactive with human IgG and yet failed to react with idiotopes on Fab or epitopes on Fc fragments. The IgG anti-F(ab')2 antibodies we purified had no reactivity toward a human immune complex prepared from tetanus toxoid and antitoxoid.

Analysis of immune complexes by two-dimensional gel electrophoresis.

High resolution two-dimensional (2D) gel electrophoresis is useful for analysis of constituents of immune complexes (IC) in serum, provided that the samples for the analysis are prepared by a standardized and effective purification protocol. The details of the protocol, which involve gel permeation chromatography and adsorption with protein A-Sepharose, were worked out with a model system of radiolabeled antigen bound to antibody. With this protocol one can attain an over 50% recovery of the antigen, in a protein preparation purified over 1000-fold with respect to starting amounts in an initial 0.5 ml serum. With silver staining of the 2D gel, the model antigen was detectable at levels of 100 ng initial input. The analysis of eight normal sera and eight sera of patients with systemic lupus erythematosus (SLE) showed no clearly demonstrable differences, suggesting that the latter sera did not contain homogeneous antigens exceeding 100 ng within IC. In addition to IgG, albumin was seen in all preparations, probably due to complexing with immunoglobulin. Trace amounts of other constituents of the samples appeared in some gels, and the presence of C3 related material was detectable only by Western blotting.

Specificity of IgM antibodies to pooled human F(ab')2 fragments.

An isotope specific immunoassay which minimizes interference by endogenous rheumatoid factors was used to determine the specificity of IgM anti-F(ab')2 antibodies in human serum. We underscore the heterogeneity of these antibodies. While one subset of IgM anti-F(ab')2 antibodies reacts only with intact F(ab')2, another recognizes determinants present following reduction and alkylation of F(ab')2 and separation of Fd' fragments from light chains. IgM anti-F(ab')2 antibodies in sera from rheumatoid arthritis patients do not react significantly with intact pooled IgG and, therefore, probably are not anti-idiotypic antibodies. Some sera, but not all, contain elevated levels of antibodies that are crossreactive with rabbit F(ab')2. Such crossreactive antibodies may interfere with assays which utilize F(ab')2 fragments of rabbit antibodies specific for antigens of clinical relevance.

IgM and IgG anti-F(ab')2 antibodies in rheumatoid arthritis and systemic lupus erythematosus.

Radioimmunoassays for anti-F(ab')2 antibodies, which feature the use of goat anti-human Fc antibody for correcting potentiation of IgM anti-F(ab')2 antibody titers by endogenous IgM anti-Fc antibodies (rheumatoid factors), are described. Individuals with classic rheumatoid arthritis had significantly more IgM anti-F(ab')2 antibody (P less than 0.001) and IgG anti-F(ab')2 antibody (P = 0.05) than did individuals with systemic lupus erythematosus or normal volunteers. There is some similarity in patterns of isotype distribution of anti-F(ab')2 antibodies and rheumatoid factors.

Agnogenic myeloid metaplasia with polyarteritis.

The 1st known case of agnogenic myeloid metaplasia and chronic polysynovitis is described. The arthritis, although disabling and clinically inflammatory, has not been locally invasive or destructive. The synovial fluid showed a mononuclear cell response, and the serum was hypocomplementemic and yielded cryoglobulins. The observations are consistent with an immune pathogenesis.

The detection of antigens in immune complexes.

A procedure is described for the purification of soluble immune complexes (IC) from biologica fluids and for the detection of antibody-bound antigen. A model IC, prepared with various amounts of human serum albumin (HSA) and constant amounts of anti-HSA, gave a 44% recovery after gel filtration on Sephacryl S-300, affinity chromatography on protein A--Sepharose, and concentration of eluates there from before analysis by sodium dodecyl sulphate--polyacrylamide gel electrophoresis. It was calculated that 20 ng of antibody-bound HSA should be detectable when polyacrylamide gels are subjected to a direct radioimmunoassay involving the use of rabbit anti-HSA, 125I-protein A, and autoradiography, thus defining the sensitivity of the procedure for detecting IC-bound antigen in a model system. The procedure has direct relevance to the examination of IC of unknown composition present in sera of individuals with various diseases.