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43-year-old Caucasian female presented with progressive weakness and dyspnea. She was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:640 and positive antibodies to SSA and SSB. Schirmer's test was normal. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy and corticosteroids. Primary SS should be a differential in premenopausal women with acute weakness and hypokalemia.

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OBJECTIVES: To study the prevalence of connective tissue diseases (CTD) in patients with autoimmune hepatitis (AIH). METHODS: We identified 11 cases of AIH over the past 7 years at our institution, through a systematic chart review of patients with this diagnosis. Their charts were reviewed for the development of systemic CTD. RESULTS: Three of the 11 patients with a definitive diagnosis of AIH developed systemic CTD. All were white: 2 women and 1 man, with an age range of 33 to 62 years, and with disease duration of 1 to 7 years. One patient developed systemic lupus erythematosus (SLE) with vasculitis and peripheral neuropathy. The second developed limited scleroderma and the third developed undifferentiated connective tissue disease (UCTD) and interstitial lung disease. There appear to be shared susceptibility alleles for AIH and CTD in addition to the shared positive autoantibodies. CONCLUSIONS: Patients with AIH may be at increased risk for developing systemic CTD. Conversely, a review of the literature reveals that patients with systemic CTD may be at increased risk of developing AIH. Patients with either AIH or CTD should be monitored for further development of concurrent autoimmune diseases.

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OBJECTIVE: We have previously demonstrated the presence of IgG aggregates modified by oxygen radicals (chlorinated IgG [Cl-IgG]) and peroxynitrite (nitrated IgG [N-IgG]) in synovial fluid of patients with rheumatoid arthritis (RA). A possible explanation for the longstanding chronic inflammatory process in RA is the establishment of an immune response to autoantigens. This study was undertaken to examine whether a T cell response to oxidatively modified IgG contributes to the inflammation in RA. METHODS: We studied in vitro lymphocyte proliferation and interleukin 2 (IL-2) secretion in response to a common antigen (mumps), N-IgG, Cl-IgG, and heat-aggregated IgG (H-IgG) (control) in 15 normal blood donors and 16 RA patients not receiving immunosuppressive drugs. RESULTS: The responses of RA lymphocytes to mumps antigen were significantly lower that those in controls (mean +/- SEM 2,577 +/- 217 versus 6,367 +/- 365 counts per minute/well; P < 0.02). However, whereas in normal donors the cell responses to N-IgG and Cl-IgG were not significantly different than responses to H-IgG (N-IgG/H-IgG ratio 1.2 +/- 0.2, Cl-IgG/H-IgG 1.5 +/- 0.2), the RA lymphocyte responses to N-IgG and Cl-IgG were significantly higher than the responses to H-IgG (N-IgG/H-IgG 7.4 +/- 2.5, Cl-IgG/H-IgG 4.8 +/- 1.2). When ratios in RA cells were compared with normal cell responses as a group, there was a significant difference for both N-IgG (P < 0.017) and Cl-IgG (P < 0.014). When selected normal and RA lymphocyte culture supernatants were assayed for IL-2 secretion, the increase in IL-2 never exceeded 2-fold in normal cell cultures incubated with any of the IgG compared with unstimulated cultures, whereas responses of RA cells, particularly those incubated with N-IgG, were increased (range 2.6-15.7-fold) compared with unstimulated controls. CONCLUSION: These results suggest that in RA there are circulating T cells that are responsive to oxidatively modified IgG, a possible pathogenic mechanism contributing to the chronic inflammatory process within the inflamed joint.

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Calciphylaxis, a rare condition seen in association with endstage renal disease, is characterized by the appearance of painful, indurated plaques, ecchymosis, ulceration, and eschar formation. We describe a patient with systemic lupus erythematosus, endstage renal disease, and skin lesions first diagnosed as lupus profundus with vasculitis. Further investigation confirmed the diagnosis of extensive calciphylaxis.

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OBJECTIVE: To assess expression and individual functional relevance of tumor necrosis factor receptor 55 (TNF-R55) and TNF-R75 in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts (SFB). METHODS: Seventh to 9th passage RA SFB and OA SFB were analyzed for TNF-R expression by FACS. The SFB were then stimulated with TNF-a (1-10 ng/ml) or agonistic anti-TNF-R55 (HTR-9) and anti-TNF-R75 (UTR-1) monoclonal antibodies (1-25 micro g/ml each). Matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), interleukin 6 (IL-6), and prostaglandin E(2) (PGE(2)) in culture supernatants were quantified by ELISA, and DNA fragmentation by TUNEL assay. RESULTS: RA SFB variably expressed TNF-R55 (7.2 +/- 2.2% positive cells, mean +/- SEM) and TNF-R75 (0.6 +/- 0.3%), similarly to OA SFB (6.8 +/- 2.1% and 1.6 +/- 0.8%, respectively). RA SFB constitutively secreted large amounts of TIMP-1 (1700 ng/ml), but only small amounts of MMP-1 (23.7 ng/ml), IL-6 (4.4 ng/ml), and PGE(2) (0.34 ng/ml). OA SFB secreted comparable amounts of TIMP-1 (2470 ng/ml), MMP-1 (37 ng/ml), and IL-6 (5.0 ng/ml), but significantly higher amounts of PGE(2) (0.58 ng/ml; p RA) and by separate stimulation of both TNF receptors. TNF-a-induced PGE(2) release by RA SFB (92-fold) and OA SFB (56-fold) was mediated by both TNF receptors; however, predominantly by TNF-R55. DNA fragmentation was induced exclusively by high concentrations of anti-TNF-R55 Mab and only in RA SFB. CONCLUSION: These results indicate preferential induction of prodestructive and proinflammatory mediators in RA SFB by the TNF-R55, with potential implications for understanding the pathogenesis of RA and the development of more specific therapeutic strategies.

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BACKGROUND: Skeletal muscle involvement has been well documented in patients with polyarteritis nodosa (PAN), and symptoms referable to skeletal muscle are not uncommon. However, polymyositis as a mode of presentation of PAN is uncommon. This unusual presentation of PAN has been reported only once previously in the English literature. OBJECTIVE: This study describes a patient who had diffuse weakness, myalgias, and markedly elevated serum creatinine phosphokinase, mimicking polymyositis. The literature dealing with the clinical aspects of muscle involvement in PAN is reviewed. RESULTS: A 24-year-old man was admitted to the hospital with a 1-month history of fever, myalgia, and muscle weakness. Necrotizing vasculitis was shown on subsequent muscle biopsy, consistent with PAN. Literature review indicated that muscle involvement is common in PAN, as has been shown by the frequency of muscular symptoms and by histologic evidence obtained from both clinical and autopsy studies. Nineteen percent of patients with PAN had documented myopathy, and autopsy series have shown skeletal muscle involvement in 30% to 48% of cases. However, polymyositis as a mode of presentation of PAN is rare. We found only 1 other patient with PAN who had elevated creatinine phosphokinase and diffuse myopathy suggestive of polymyositis. CONCLUSIONS: PAN should be suspected in cases of focal or diffuse myopathy, especially in the context of a systemic disease. Biopsy of symptomatic muscles or EMG-directed biopsies can be helpful in establishing a diagnosis of PAN to allow the physician to provide early treatment.

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