Longterm efficacy of interferon-alpha for extrahepatic disease associated with hepatitis C virus infection.

OBJECTIVE: To investigate longterm responsiveness to interferon-alpha (lFN-alpha) of patients with extrahepatic manifestations of hepatitis C virus (HCV) in a nonendemic area. METHODS: We prospectively evaluated 11 patients with extrahepatic manifestations of HCV infection, including 10 with Type II cryoglobulins, treated with IFN-alpha--9 had cutaneous vasculitis, 6 arthralgias, 7 neuropathy, and 4 glomerulonephritis. Liver biopsies were performed on all patients, although 6/11 had normal liver function tests. All received 3 M units IFN-alpha tiw, with total length of treatment ranging from 3 mo to 5 yrs. Periodic assessments were made of clinical activity, biochemical variables, cryoglobulin quantitation, and HCV copy number. RESULTS: Three patients were withdrawn because of toxicity. Three were nonresponders at 6, 16, and 17 mo of therapy, based on persistence of HCV RNA in blood, cryoprecipitates, and peripheral blood mononuclear cells. One patient was a partial responder at 3 yrs, with 2 major flares of cutaneous vasculitis occurring on separate attempts to withdraw IFN-alpha. Three patients (27.2%) were complete responders based on resolution of symptoms (purpura, neuropathy) and disappearance of cryoprecipitates and HCV RNA, but only one successfully tapered IFN-alpha after 3 yrs of treatment, with sustained resolution at followup 15 mo later. CONCLUSION: IFN-alpha is safely tolerated for prolonged periods in patients with extrahepatic HCV infection, and is particularly effective for treatment of cutaneous vasculitis. Careful monitoring is needed for evolution of liver pathology to cirrhosis, or for progression of renal or neurologic disease.

Dramatic improvement of left ventricular function after cytotoxic therapy in lupus patients with acute cardiomyopathy: report of 6 cases.

Although lupus cardiomyopathy is thought to be clinically uncommon, we encountered 6 patients with systemic lupus erythematosus (SLE) over a 10 year period who had severe left ventricular dysfunction and showed remarkable improvement in their cardiac function after cytotoxic therapy. All patients met the American College of Rheumatology criteria for classification of SLE and presented with signs of severe biventricular failure relatively early in their disease. Concurrent manifestations of SLE at the time of cardiomyopathy included rash, arthritis, myalgias, pleuritis, pericarditis, and nephritis. Four of the 6 patients were taking prednisone 20 mg/day at the time heart failure developed. In all cases the CPK were normal. Evaluation of cardiac function by echocardiogram and/or radionuclide gated blood pool scintigraphy revealed a severe depression of ventricular function with initial left ventricular ejection fraction (LVEF) ranging from 11 to 34% (mean 19%). Within 6 months of initiation of cytotoxic treatment all patients showed a dramatic response: the post-treatment LVEF ranged from 25 to 55%. This series of patients suggests that cardiomyopathy may be a more common complication of SLE than previously reported. Cardiomyopathy occurs relatively early in the course of SLE, may lead to severe cardiac dysfunction despite corticosteroid therapy, and appears to be responsive to cytotoxic therapy.

Sudden sensorineural hearing loss in patients with systemic lupus erythematosus or lupus-like syndromes and antiphospholipid antibodies.

Although the pathogenesis of sudden sensorineural hearing loss (SNHL) in patients with systemic lupus erythematosus (SLE) is not clear, several reports suggest an association with the antiphospholipid antibody (aPL). We describe 6 patients with SLE or a lupus-like syndrome, who had sudden SNHL and had elevated levels of anticardiolipin antibodies (aCL) or the lupus anticoagulant. In a literature search, of 5 additional reported cases, 2 were not tested for aPL; the remaining 3 had elevated aCL levels. Thus, acute SNHL in patients with SLE who have aPL may be a manifestation of the antiphospholipid syndrome. We recommend anticoagulation treatment of these patients.