Diagnostic conundra in the spondyloarthropathies: towards a base for revised nosology.
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Arthritis↗
Biomedical subjects
R D Inman
Publications and source records attributed to R D Inman.
Prevalence of tendinitis and related disorders of the upper extremity in a manufacturing workforce.
A cross sectional survey of a randomly selected population of 2,261 textile workers form an overall population of 8,539 eligible workers was performed to evaluate the prevalence of tendinitis in related upper extremity disorders. Of the sample, 2,047 respondents (91.3%) participated in a nurse screening history and examination: 1,091 (53%) had no upper extremity symptoms or abnormalities on examination; 959 (47%) with positive findings were examined by trained physicians. Of these, 347 (36.5%) were found to have no abnormality, whereas, 548 (57.3%) workers were assigned a diagnosis. Of these 227 were considered to fall into the categories of tendinitis (n = 69) or related disorders (n = 158). The projected prevalence of tendinitis and related disorders for the overall group was 11.6% (carpal tunnel syndrome 1.1%, epicondylitis 2.0%, tendinitis 3.5%, shoulder condition 2.3%, ganglion 2.3%, neck conditions 4.0%). Tendinitis was less frequent in the older age group and those employed for a longer time. The prevalence of tendinitis was found to be statistically higher in physically demanding job categories. Ninety-four percent of ailments were of mild or moderate severity. Although our study provides prevalence data for these conditions in a large manufacturing workforce across several job categories.
Adult↗
Eosinophilia-myalgia syndrome--old questions for a new syndrome.
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Biopsy↗
HLA class I-related impairment in IL-2 production and lymphocyte response to microbial antigens in reactive arthritis.
The contribution of certain Gram-negative bacteria and host HLA class I Ag to the development of reactive arthritis (ReA)3 has strong epidemiologic support but the pathogenesis of the arthritis is unknown. An outbreak of Salmonella typhimurium afforded the opportunity to compare the immune response to the organism between those who developed ReA (ReA+, n = 11) with those who did not (ReA-, n = 12). Of the 11 ReA+ patients, 4 were B27-positive and 6 were B7-positive; of the ReA- patients none was B27- or B7-positive. The causative pathogen S. typhimurium phage 22 was used to examine PBL proliferation by [3H]thymidine incorporation. Impairment in lymphocyte response to S. typhimurium in ReA+ compared with ReA- was demonstrated by: i) lower stimulation index (1.9 +/- 0.3 for ReA+, 5.7 +/- 0.6 for ReA-, p less than 0.01); ii) lower in vitro Ig production; and iii) lower Ag-induced IL-2 production. Mixing experiments did not demonstrate a soluble suppressor factor in ReA+ supernatants. Thus, after infection with S. typhimurium there is an impairment in cellular immunity that has correlates in immunogenetic and clinical features of the infected population.
Antibodies, Bacterial↗
Neuromodulation of synovitis: capsaicin effect on severity of experimental arthritis.
This study addresses the effect of capsaicin on the severity of inflammation in experimental arthritis in the cat. Animals were sensitized with methylated bovine serum albumin (mBSA) and sequential serum antibody levels measured by enzyme-linked immunosorbent assay (ELISA). Synovitis was induced by intra-articular injection of mBSA. Histopathology revealed marked inflammatory cell infiltration and synovial cell hypercellularity, in comparison with the saline-injected control joint which showed no synovitis. In animals given intra-articular capsaicin concurrently with mBSA, there was consistently a diminution in the severity of inflammation compared with contralateral joints receiving mBSA alone. In this experimental system capsaicin appears to moderate the severity of inflammation in feline antigen-induced arthritis.
Animals↗
Internuclear ophthalmoplegia in giant cell arteritis.
Ophthalmoplegia from ischemia to peripheral ocular motor nerves or muscles may complicate the course of giant cell arteritis (GCA). Although brainstem ischemia is known to occur in GCA, internuclear ophthalmoplegia has not been described. Two cases of biopsy-proven GCA are described in which internuclear ophthalmoplegia resulted from brainstem ischemia. Embolization from thrombosed extradural segments of inflammed vertebral arteries, or arteritis of brainstem perforating vessels may account for brainstem infarction. Rapid tapering of steroids was temporally related to brainstem infarction in both cases.
Aged↗
Postdysenteric reactive arthritis. A clinical and immunogenetic study following an outbreak of salmonellosis.
Following an outbreak of foodborne gastroenteritis caused by Salmonella typhimurium, questionnaires were sent to affected individuals and then to the family physicians of any who experienced extra-enteric complications. Of 260 individuals infected with S typhimurium for whom adequate data were obtained, 19 patients developed joint disease (7.3%). All were men; the mean age +/- SD was 39.3 +/- 1.6 years. Among the 16 patients for whom this information was available, the interval from the onset of diarrhea to the onset of joint pain was less than 7 days in 7, 8-21 days in 2, and greater than 21 days in 7. There was a significantly longer duration of diarrhea in those patients with joint disease (mean +/- SEM 15.2 +/- 2.6 days) than in those without complications (10.0 +/- 1.1 days) (P less than 0.01). The joint disease was monarticular in 3 patients and polyarticular in 16. The joints most commonly affected were the elbow (47%), wrist (47%), knee (42%), low back (32%), and shoulder (32%). Six of the 19 patients had at least 1 extraarticular feature: ocular (5 patients), mucosal (1 patient), urethral (2 patients), or cutaneous (1 patient). Of these 19 patients, 11 were located and agreed to HLA typing. Four were positive for HLA-B27, 6 were HLA-B7 positive, and 1 had HLA-Bw60. Of the 4 B27 positive patients, 3 were DR1 positive; of the 6 B7 positive patients, 5 were DR2 positive.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Immunogenetic aspects of host immune response.
The central role of histocompatibility leukocyte antigens (HLA) class II molecules in antigen presentation has received great attention in recent years, yet class I molecules have been defined as primarily functioning as a restriction element for cytotoxic T cell killing of virus-infected cells. Extensive clinical evidence, however, indicates that the HLA class I genes are strongly associated with nonseptic complications of enteric and genitourinary bacterial infections. Ninety percent of patients with Reiter's syndrome and reactive arthritis are positive for HLA-B27, yet the mechanism of disease susceptibility conferred by this gene remains obscure. Hypotheses concerning this interaction include (i) class I antigens functioning as receptors for microbial antigens; (ii) class I antigens expressing determinants that cross-react with microbial antigens; and (iii) class I genes controlling immunoregulatory functions that dictate qualitative differences in immune response to pathogenic organisms. These hypotheses await formal testing and hold great promise for understanding immunogenetic control of immune responses in general.
Genes, MHC Class I↗
Plasma substance P levels in fibrositis.
The mechanism of pain in the fibrositis syndrome is unknown. We measured plasma levels of substance P in 32 patients with fibrositis and 26 sex and age matched controls using a radioimmunoassay. The mean plasma level of substance P in the patients with fibrositis was 371 +/- 91 pg/ml and in controls 397 +/- 84 pg/ml (p = NS). We conclude that determination of plasma levels of substance P in fibrositis is of no diagnostic value. This does not exclude the possible role of substance P as a neurotransmitter in the fibrositis syndrome.
Adult↗
Analysis of immune complexes in rheumatoid arthritis for Epstein-Barr virus antigens reveals cross-reactivity of viral capsid antigen and human IgG.
We recently defined the immunochemical characteristics of immune complexes (IC) isolated from synovial fluid (SF) of patients with rheumatoid arthritis with the use of Western blot analysis. In the present study, we probe for exogenous antigens in the IC by examining the specificity of antisera raised against the IC. Anti-IC antisera demonstrated strong reactivity against the viral capsid antigen (VCA) of Epstein Barr virus (EBV), which was not explained by preimmune reactivity, polyclonal B cell activation, or Fc-mediated binding in the immunofluorescence or ELISA systems used to measure antibody titers. However, comparable anti-VCA reactivity was detected in antisera raised against non-rheumatoid SF. This phenomenon was not due to antigen since monoclonal anti-VCA antibody probing the IC by Western blot detected only IgG, nor to idiotype/anti-idiotype interaction since normal IgG absorbed out the anti-VCA reactivity. A monoclonal anti-VCA antibody competitively inhibited the binding of anti-IgG to IgG, and Fc fragment of IgG competitively inhibited the monoclonal antibody binding to VCA. No relationship between IgG anti-VCA antibody and IgG rheumatoid factor could be demonstrated. These data demonstrate an unexpected cross-reactivity of Fc fragment of IgG and VCA of EBV through the analysis of SF IC.
Antibodies, Monoclonal↗
Analysis of serum and synovial fluid IgA in Reiter's syndrome and reactive arthritis.
The presumed antecedent infection which precedes Reiter's syndrome and reactive arthritis is frequently across a mucosal surface, and IgA immune responses may play a role in this process. Twelve of 29 patients with these conditions demonstrated elevation in serum IgA levels, and serum IgA levels in the postdysentery group (mean 3.21 g/liter +/- 1.27) were higher (P less than 0.01) than those in the posturethritis group (mean 2.40 g/liter +/- 0.80). In 10 of the 12 patients, IgA was the only immunoglobulin increased. There was no evidence of activation of complement in serum or synovial fluid. Using a complement-dependent assay, we were unable to demonstrate circulating IgA immune complexes. Sucrose density gradient ultracentrifugation analysis was used to assess IgA immune complexes in a non-complement-dependent manner. IgA of 11s was in fact demonstrated by this technique but appeared to be polymeric IgA on the basis of specific binding of secretory component and resistance to acid dissociation. IgA rheumatoid factor was not present. Synovial fluid revealed levels of polymeric IgA higher (mean 56.7% +/- 12.9) than did serum (23.7% +/- 13.9, P less than 0.001) despite higher levels of total IgA in serum than in synovial fluid (synovial fluid:serum ratio of IgA, mean 0.53 +/- 0.11). Although elevation in serum IgA in postdysenteric arthropathies suggests mucosal acquisition of antigen, the study does not implicate IgA circulating immune complexes in the pathogenesis of these diseases.
Antigen-Antibody Complex↗
Arthritis and enteritis--an interface of protean manifestations.
We live in tenuous proximity to a vast array of microbial agents that inhabit the balanced ecosystem of the gut. When an alteration in that balance occurs our immune system can be challenged abruptly with pathogens expressing microbial antigens that may form immune complexes or that may induce autoimmunity by cross-reactivity with host endogenous antigens. Toxins and proteolytic enzymes, normally limited to bowel lumen, may evade local mucosal defences and effect systemic inflammatory responses. Understanding the pathogenic events behind arthritis related to GI pathology will provide insight not only into this important group of diseases but also into fundamental mechanisms underlying other forms of inflammatory joint disease which remain of unknown origin.
Arthritis↗
Immunochemical analysis of immune response to Chlamydia trachomatis in Reiter's syndrome and nonspecific urethritis.
Chlamydia trachomatis (Ct) has been proposed as a causative agent in Reiter's syndrome (RS) when an infection occurs in a susceptible host. To assess whether this susceptibility is reflected in a characteristic humoral immune response we compared patients with complicated (RS) and uncomplicated courses of nonspecific urethritis (NSU). Geometric mean titres of antibodies to C. trachomatis by immunofluorescence were 89.6 for RS, 80.0 for NSU and 16.0 for normals. 125I-Protein A probing of immunoblotted antigens of C. trachomatis revealed no band unique to RS. 125I-anti-IgA probing of immunoblots demonstrated reactivity with the 59,000 dalton antigen in 11/11 RS and 2/6 NSU. The major outer membrane protein of C. trachomatis (40,000 daltons) bound immunoglobulin nonspecifically. There was no clearly differentiating feature between HLA-B27-positive and B27-negative RS. One sequentially studied patient revealed an augmentation in synovial fluid IgA reactivity during the course of disease. No pattern of humoral immune response to C. trachomatis could be regarded as specific for RS nor for HLA B27-positivity. The study did not identify a Reiter's-specific antigen in C. trachomatis but demonstrates the usefulness of applying blotting techniques to population studies of HLA modulation of immune response to infectious agents.
Adult↗
Aseptic arthritis in a man with toxic shock syndrome.
Synovitis in toxic shock syndrome (TSS) is an unusual finding. A 31-year-old man presented with pain and swelling in both knees and was found to have TSS, secondary to a septic bursitis caused by Staphylococcus aureus. Immune complexes were not detected in serum or synovial fluid, and the S aureus was not recovered from the inflamed joints. Antibodies against the TSS toxin-1 were detected in serum and synovial fluid, but in lower levels than would be seen in a normal control serum. Complement studies implicated alternative pathway activation by a marked diminution in C3 levels compared with C4 levels, and by lower levels of factor B than would be found in other inflammatory joint diseases. The diagnostic dilemma posed by TSS in a man is discussed.
Adult↗
Arthritis, vasculitis, and cryoglobulinemia associated with relapsing hepatitis A virus infection.
Hepatitis A virus, unlike hepatitis B virus, has rarely been associated with extrahepatic features. Two patients developed relapsing hepatitis A complicated by arthritis in both cases and cutaneous vasculitis in one. Both patients had cryoglobulinemia, with cryocrit values of 4.3% and 8.6%. Serologic studies showed that the cryoglobulin consisted of polyclonal IgM and IgG. The washed cryoglobulin was analyzed by sucrose density gradient ultracentrifugation under neutral (pH 7.4) and acidic (pH 2.8) conditions. Enzyme-linked immunosorbent assay techniques were used to characterize the native and dissociated cryoglobulin. The cryoglobulin contained acid-dissociable IgG complexes greater than 19S, and high molecular weight rheumatoid factors of both IgG and IgM isotypes that could be dissociated to 7S and 19S forms, respectively. Dissociation of the cryoglobulin augmented 7S anti-hepatitis A virus IgG 2.27-fold, but augmented total 7S IgG only 1.12-fold, suggesting enrichment of antiviral antibody in the cryoglobulin.
Adult↗
Electrophoretic transfer blotting analysis of immune complexes in rheumatoid arthritis.
Immunochemical analysis of immune complexes (IC) derived from synovial fluid and serum of patients with rheumatoid arthritis (RA) was undertaken. IC were isolated by differential polyethylene glycol precipitation and competitive binding to staphylococcal Protein A. Anti-IC antisera were raised in rabbits by immunization with purified IC. IC were characterized by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), electrophoretic transfer to nitrocellulose sheets, reaction with either anti-IC antiserum or monospecific antiserum against putative components, then developed with 125I-Protein A and autoradiography. Synovial fluid IC from both RA and control inflammatory joint diseases contained immunoglobulin light chains, and mu and gamma heavy chains. IC from RA synovial fluid also contained alpha chain, and Clq. Cross-over studies of IC and antisera revealed cross-reactive antigens in IC of RA synovial fluid and that remained unidentified were of the following relative molecular masses: 26,000; 39,000; 40,000; and 43,000. Studies using early and late serum samples to probe the blotted IC failed to disclose serological autoreactivity. This sensitive analytical technique provides a means for detailed description of the constituents of IC in inflammatory joint diseases.
Antigen-Antibody Complex↗
Alpha 2-plasmin inhibitor-plasmin complexes in synovial fluid.
The role of the fibrinolytic enzyme system in inflammatory joint disease has been addressed by several experimental approaches. In our study we examined synovial fluid (SF) in several different diseases for alpha 2-plasmin inhibitor-plasmin complexes by an enzyme linked immunosorbent assay (ELISA). These complexes are present in both rheumatoid and nonrheumatoid SF, with highest levels seen in septic arthritis. Thus the plasminogen system is intact in inflammatory SF, and plasmin may play a role in the local inflammatory process.
Antifibrinolytic Agents↗
Molecular mimicry in Reiter's syndrome: cytotoxicity and ELISA studies of HLA-microbial relationships.
The pathogenic links between HLA antigens, certain bacterial infections and arthritis have not yet been characterized. The hypothesis of cross-reactivity between HLA B27, the marker of disease susceptibility for these disorders, and the provocative microorganism has been suggested by studies of Klebsiella and ankylosing spondylitis. The present study examines the possibility of molecular mimicry between HLA B27 and two organisms implicated more directly in reactive arthritis, Yersinia enterocolitica and Chlamydia trachomatis. Antibodies against these organisms were obtained both from patients and from antisera raised in rabbits. Neither source of antibacterial antibody was specifically cytotoxic for HLA B27-positive lymphocytes, even when the target cells were derived from patients with recent infections due to these organisms. In addition, monoclonal antibodies against HLA B27 (M1 and M2) showed no reactivity with antigens from these organisms in an ELISA system. These data do not support the notion of molecular mimicry as being the basis of immunogenetic susceptibility to reactive arthritis and Reiter's syndrome following infections with Y. enterocolitica and C. trachomatis.
Antigens, Bacterial↗