Acute rheumatic fever in adults--understanding the disease.
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Acute Disease↗
Biomedical subjects
R D Inman
Publications and source records attributed to R D Inman.
Clinical and microbial features of prosthetic joint infection.
A one-year experience with prosthetic joint infection, in which 63 cases were identified, is reviewed. Thirty cases (48 percent) were early infections, in the first postoperative year, and 33 cases (52 percent) were late, occurring more than one year after implantation. Pain was the predominant symptom, but clinical clues suggesting infection were frequently absent, with fever in 43 percent and leukocytosis in only 10 percent. The radiographic appearance was more frequently abnormal in late infections (67 versus 37 percent, p less than 0.02). Staphylococci were predominant organisms, constituting 59 percent of prosthetic joint infections, and S. epidermidis was the predominant species in both early and later infections. Of the hematogenous infections, 11 of 13 occurred in the group with late infections; these were mostly nonstaphylococcal . Antigenic proteins of S. epidermidis were characterized by gel electrophoresis, but no infection-specific antigens could be identified when patient serum was compared with normal samples. Precipitating antibodies to the extracellular proteins of S. epidermidis were present in 50 percent of patients with S. epidermidis prosthetic joint infections, 27 percent of patients with nonstaphylococcal infections, 20 percent of patients with S. aureus infections, and 11 percent of normal subjects. In view of the increasing importance of prosthetic joint infection, further study of the pathogenesis of the infection and the host immune response is warranted.
Adult↗
Modulation of mononuclear phagocyte system function and circulating immune complexes by lyophilized concentrates in patients with classic hemophilia.
Infusions of lyophilized antihemophilic factor concentrates in patients with hemophilia were found to affect both circulating immune complexes and in vivo mononuclear phagocyte system function. Following infusion nine patients had simultaneous assessment of serial immune complex levels and mononuclear phagocyte system clearance of IgG-sensitized autologous erythrocytes relative to a previously established baseline. Nine patients also had a separate second sequence, and two a third sequence, of serial immune complex measurements in relation to infusions. The net change in immune complexes over the 2- to 4-hr interval following infusion was consistent in 10 of 11 study pairs (P less than 0.01) despite different antihemophilic factor preparations for each study and different individual patient responses. This change could not be explained by immunochemical rearrangement in infusate and serum since in vitro mixing experiments showed no relationship to in vivo results. Change in mononuclear phagocyte system function showed a strong correlation with change in complexes (r = 0.70; P less than 0.05). It is suggested that infusions of antihemophilic factor can modulate the mononuclear phagocyte system which in turn alters immune complex levels. Both of these effects could potentially influence immune regulation which has been shown to be abnormal in other hemophiliac patient groups.
Adolescent↗
Characterization of sequential immune complexes in infective endocarditis by Western blot analysis.
A patient with cutaneous vasculitis during infective endocarditis due to Lactobacillus casei was studied. Immune complexes (IC) were isolated from serum at the time of diagnosis and after 4 wk of therapy. Purification of IC used differential polyethylene glycol precipitation and competitive binding to staphylococcal protein A. In situ radioiodination of IC was performed, followed by SDS-polyacrylamide gel electrophoresis (PAGE). Anti-IC antisera were raised in rabbits by immunization with purified IC. IC were characterized by SDS-PAGE followed by electrophoretic transfer to nitrocellulose, incubation with antiserum and then with 125I protein A, and autoradiography. Although early and late IC differed quantitatively, there were no differentiating immunochemical features. Both IC contained a 60,000 dalton component that did not react with preimmune serum nor with anti-normal human serum. This component reacted with antiserum rendered specific for L. casei by affinity chromatography. The restricted antigen-antibody representation in IC contrasted with a wider panel of antibody activity in patient serum. The Western blot analysis proves to be an ideal method for the characterization of IC because of its sensitivity, dissociative capability, and preservation of immunoreactivity. IC isolated at a time removed from the original antigenic challenge may provide insight into the nature of the inciting antigen.
Animals↗
Induction of polymeric IgA rheumatoid factors in infective endocarditis.
IgA and IgM rheumatoid factor activity, circulating immune complex levels, and antinuclear antibodies were measured in 17 patients with subacute or chronic infective endocarditis. Approximately three fourths of these patients had both IgA and IgM rheumatoid factors detectable by radioimmunoassay, and IgA and IgM rheumatoid factor activity was strongly correlated (p less than 0.01). In three patients studied, IgA rheumatoid factor activity was predominantly polymeric as assessed by sucrose density ultracentrifugation (55 to 92 percent of total rheumatoid factor activity) and could bind radiolabeled secretory component. No correlations between rheumatoid factor activity and circulating immune complex levels or antibodies to nuclear antigens were observed. These observations indicate that circulating polymeric IgA antibodies do not necessarily signify a mucosal stimulus for IgA production and also demonstrate differences in the intensity and spectrum of autoantibody production when compared with autoimmune diseases.
Adult↗
Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura.
High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.
Adolescent↗
Serial circulating immune complexes and mononuclear phagocyte system function in infective endocarditis.
Twenty patients with infective endocarditis were followed prospectively and all had elevated levels of circulating immune complexes (CICs) detected by staphylococcal binding assay. Mean CIC levels declined for the group as a whole (193 micrograms/ml +/- 24 to 100 +/- 17, p less than 0.05) and became undetectable in eight patients (47%) who were cured. Patients who died or had complicated courses had higher mean CIC levels at the start and finish (254 micrograms/ml +/- 24 and 145 +/- 37) of antibiotic therapy than patients with uncomplicated courses (178 micrograms/ml +/- 19 and 38 +/- 24), p less than 0.05. CIC levels did not decline significantly in patients with glomerulonephritis or arthritis, in contrast to patients without these features. Despite elevated CIC levels, 10 patients had enhanced mononuclear phagocyte system (MPS) function as assessed by Fc-dependent IgG-coated red blood cell clearance. These data suggest that CICs probably are pathogenic in endocarditis and may contribute to the development of arthritis and glomerulonephritis. Elevated CICs in infective endocarditis do not appear to be directly related to defective MPS function.
Adult↗
C1 inactivator-C1s complexes in inflammatory joint disease.
A newly developed enzyme linked immunosorbent assay for the quantitation of C1 inhibitor (C1In)-C1s complexes was used to study activation of the classical pathway of complement in inflammatory joint diseases. Synovial fluid (SF) specimens were obtained from patients with rheumatoid arthritis (RA), other arthritides and non-inflammatory joint effusions. Paired serum (S) samples were obtained in 17 cases. Immune complexes (IC) were measured by the staphylococcal binding assay. C1In-C1s were higher in RA SF samples than in paired RAS samples (P less than 0.01). IC were higher in RA SF than non-RA SF. There was a significant inverse correlation between SF C1In-C1s complexes and SF total haemolytic complement. For all SF samples there was a correlation between IC and C1In-C1s complexes, but for RA SF alone there was no significant correlation between these parameters. There was no correlation between titre of rheumatoid factor and C1In-C1s complexes. These results demonstrate that activation of the classical pathway of complement is the hallmark of rheumatoid synovitis, yet also suggest functional heterogeneity of both circulating and intra-articular IC.
Antigen-Antibody Complex↗
Dynamics of mononuclear phagocyte system Fc receptor function in systemic lupus erythematosus. Relation to disease activity and circulating immune complexes.
Seventeen pairs of longitudinal studies of mononuclear phagocyte system (MPS) Fc receptor function in 15 patients with systemic lupus were performed to explore the dynamic range of Fc receptor dysfunction in lupus and to establish the relationships between MPS function, clinical disease activity and circulating immune complexes (CIC). Fc receptor function was measured by the clearance of IgG sensitized autologous erythrocytes. At the time of first study the degree of MPS dysfunction was correlated with both clinical activity (P less than 0.05) and CIC (P less than 0.05). At follow-up patients with a change in clinical status show significantly larger changes in clearance function compared to clinically stable patients (206 min vs 7 min; P less than 0.001). MPS function changed concordantly with a change in clinical status in all cases (P = 0.002). Longitudinal assessments did not demonstrate concordance of changes in MPS function and CIC, measured by three different assays. The MPS Fc receptor defect in systemic lupus is dynamic and closely associated with disease activity. The lack of concordance of the defect with changes in CIC suggests that either CIC does not adequately reflect receptor site saturation or that other factors may also contribute to the magnitude of MPS dysfunction.
Adult↗
Adult-onset Still's disease. Twenty-year followup and further studies of patients with active disease.
Eleven female patients with adult-onset Still's disease were followed for 7-36 years (mean 20.2 years) after the onset of their illness. Ten of these patients had a chronic course characterized by remissions and exacerbations of arthritis associated with fever and rash. Five patients had terminal interphalangeal involvement, and carpal ankylosis was demonstrated on x-ray film in 10. Two patients developed a widespread polyarthritis, and renal amyloidosis was diagnosed 10 years after disease onset in the most severely affected patient. In 4 patients studied during an exacerbation of the disease, circulating immune complexes were detected by the staphylococcal A binding assay, but not by the C1q binding assay. Synovial fluid analysis in 1 patient revealed a low C3 level and total hemolytic complement (CH50) together with immune complexes and IgG rheumatoid factor. Immune complexes were not identified in the characteristic Still's rash by immunofluorescence or electron microscopy, although mast cell degranulation, neutrophil lysis, and perivascular fibrin deposition were reminiscent of immune complex--mediated vascular injury. The clinical and laboratory features as well as the long-term course of adult- and juvenile-onset systemic Still's disease are similar, but further studies of genetic markers and immunopathology are required to establish a common pathophysiology.
Adult↗
Rheumatic manifestations of hepatitis B virus infection.
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Adolescent↗
Acute pancreatitis in systemic lupus erythematosus: report of twenty cases and a review of the literature.
A retrospective study was undertaken of patients with systemic lupus erythematosus in whom serum amylase had been determined. Sixty-three patients were identified, and of these 53 had abdominal pain at the time of the amylase measurement. Twenty-seven (51 percent) had a normal serum amylase, and 12 of this group had defined reasons for the abdominal pain. Of the 26 patients with hyperamylasemia, 6 had extrapancreatic causes for the elevated amylase. In 20 patients (37 percent of those with abdominal pain) the clinical diagnosis of pancreatitis was made. The amylase levels showed no correlation with renal function nor with dose of corticosteroid. Four patients with pancreatitis were identified in whom no contributing factor other than SLE could be ascertained. No serious complication of the pancreatitis was seen, and recovery occurred despite continued steroid therapy. Pancreatitis is not a rare occurrence in SLE, and may be related in part to the vasculitis seen during periods of disease activity.
Acute Disease↗
Identification of bacterial antigens in circulating immune complexes of infective endocarditis.
The presence of circulating immune complexes (IC) in patients with infective endocarditis has been well documented but the contributions of host and bacterial components to these IC have not been defined. To study this question, IC were isolated from serum of a patient with Streptococcus faecalis endocarditis by differential polyethylene glycol precipitation and competitive binding to staphylococcal protein A. A rabbit antiserum raised against the purified IC had reactivity by crossed immunoelectrophoresis primarily with an antigen derived from the cytoplasm of the infective organism. The antigen was a protein with a 12,000-dalton molecular mass. In situ radiolabeling of the IC bound to the protein A demonstrated a component of the same molecular mass as the bacterial antigen recognized by the antiserum. The patient serum had multiple antibody specificities reactive with bacterial antigens, including the antigen recognized by the rabbit anti-IC antiserum. These techniques for isolation and characterization of circulating IC may have value in the study of IC diseases in which the inciting antigens are not known.
Animals↗
Defective Fc receptor-mediated function of the mononuclear phagocyte system in lupus nephritis.
To determine whether patients with systemic lupus erythematosus and nephritis have more profound defects in mononuclear phagocyte system clearance than their counterparts without renal disease, we studed Fc receptor-mediated splenic clearance function in 32 patients. Clearance half-times were prolonged in patients with lupus erythematosus compared with those in normal controls (p less than 0.0001) and longer in patients with renal disease than in those without (p less than 0.025). Both renal (tau = 0.45, p less than 0.0002) and nonrenal (tau = 0.35, p less than 0.003) disease activity were significantly but independently associated with clearance half-times. When matched for nonrenal activity, patients with nephritis had greater clearance dysfunction than their counterparts without renal disease. Circulating immune complexes did not correlate with clearance for all patients. Neither B8 nor DR3 histocompatibility antigen markers differentiated the renal and nonrenal disease subgroups. The greater Fc receptor-mediated clearance dysfunction, which occurs in patients with lupus erythematosus and nephritis, could lead to enhanced glomerular deposition of immune complexes as a primary event, or as a secondary event amplifying previously established lesions.
Adult↗
Systemic lupus erythematosus in men. Genetic and endocrine features.
Sixteen men with systemic lupus erythematosus (SLE) were examined to assess their genetic and hormonal status. The results of buccal smears in 13 patients examined were normal. Hormonal profiling was done in eight patients receiving no steroid therapy. Four patients had elevated plasma estradiol levels (30, 35, 55, and 103 pg/mL; normal, 12 to 23 pg/mL) and elevated plasma estrone levels (115, 150, 155, and 160 pg/mL; normal, 48 to 100 pg/mL). One patient had a decreased serum testosterone level (134 ng/dL; normal, 300 to 1,000 ng/dL), with an elevated luteinizing hormone (LH) level (4.2 ng/mL; normal, 1.6 to 4.0 ng/mL). One patient had an elevation in both levels of serum follicle-stimulating hormone (17.6 ng/mL; normal, 1 to 5 ng/mL) and LH (10.0 ng/mL). Two patients given infusions of 3H-androstenedione and 14C-testosterone had normal findings from kinetic studies of these hormones. Hyperestrogenemia and hypoandrogenemia observed in some men with SLE suggest that female sex hormones may create an immunologic milieu that facilitates the autoimmune phenomena.
Adolescent↗
Effect of high-dose methylprednisolone infusion on polymorphonuclear leukocyte function in patients with systemic lupus erythematosus.
We have studied the effect of high-dose (1 gm) methylprednisolone infusion on polymorphonuclear leukocyte (PMN) function in 11 patients with active systemic lupus erythematosus (SLE). The only alteration of polymorphonuclear leukocyte function produced consistently by methylprednisolone was decreased adherence to plastic surfaces when tested 2 hours after infusion. This steroid-induced abnormality, however, was transient. Cells obtained from patients 24 hours after a single dose of drug exhibited normal adhesiveness. These results indicate that single, large doses of methylprednisolone do not produce long-lasting abnormalities of PMN function in patients with lupus.
Adolescent↗
High-dose intravenous methylprednisolone pulse therapy in systemic lupus erythematosus.
To determine guidelines for treatment with high-dose intravenous methylprednisolone in lupus nephritis, we prospectively assessed the response to pulse therapy in 34 patients. In 12 of them, serum creatinine decreased by at least 20 percent within two months of treatment whereas in the remaining 22 there was no such response. Patients who responded were characterized by recent deterioration in function whereas nonresponders had had a more stable antecedent course (p = 0.003). Responders also had more diffuse lesions on renal biopsy (p = 0.028), had higher levels of anti-DNA antibodies (p less than 0.05), and tended to have higher titers of immune complexes and lower total hemolytic complement. High-dose intravenous methylprednisolone therapy may lead to striking improvement in renal function in lupus nephritis, especially in the subset of patients with recent antecedent functional deterioration. This improvement was maintained in 60 percent of the patients who responded for at least six months.
Adolescent↗