Fatal hepatitis and renal failure during treatment with nimesulide.

A healthy 70-year-old woman who took nimesulide for 5 days, presented 2 weeks later with jaundice for which no other cause was found. Laboratory evidence of coagulopathy, hypoalbuminaemia and hypoglycaemia were present on admission, and liver biopsy showed massive necrosis of hepatocytes and severe inflammatory infiltrate. Despite supportive and corticosteroid treatment, her jaundice deepened and progressive acute renal failure developed, characterized by a 'prerenal' profile changing into irreversible acute tubular necrosis pattern, coma, occult Gram-negative sepsis and death. Although rare, nimesulide-associated hepatotoxicity and nephrotoxicity may occur and should be recognized as early as possible, to ensure immediate drug withdrawal and treatment.

Nitrofurantoin-induced immune-mediated lung and liver disease.

A 60-year-old woman with multiple sclerosis and recurrent urinary tract infections (UTI) was evaluated for the recent onset of a dry cough, dyspnea on exertion, and jaundice. Investigation demonstrated interstitial lung disease with bilateral infiltrates and unilateral effusion, as well as a severe chronic active hepatitis with marked fibrosis. Other notable features were positive antinuclear antibodies and anti-smooth-muscle antibodies and the absence of any possible cause except for nitrofurantoin treatment (Macrodantin, 100 mg/day), which the patient had been taking for the previous 3 years as a prophylactic measure against UTI. The patient died of pneumococcal septicemia less than 30 days after presentation. Pulmonary or hepatic injury caused by nitrofurantoin treatment is rare; their combined occurrence is hardly ever described. Combined drug-induced pulmonary and hepatic toxicity is reviewed and should be considered early in the differential diagnosis to allow reversibility and avoid serious outcomes.

Fatty liver--an additional and treatable feature of the insulin resistance syndrome.

To test the hypothesis that fatty liver coexists with other metabolic abnormalities of the insulin resistance syndrome, and responds to their amelioration, we prospectively studied 48 consecutive patients with chronically elevated liver enzymes and clinical, ultrasound and histological findings consistent with fatty infiltration of the liver. Most of the patients were overweight or obese (64%) with increased waist circumference which closely relates to visceral fat. Only 10% of the patients had normal glucose tolerance: 44% had diabetes mellitus, 29% impaired glucose tolerance, and 17% were hyperinsulinaemic. The most common dyslipidaemia found was hypertriglyceridaemia and/or low HDL-C (86%). Dietary intervention and follow-up (median 24 months), supplemented by oral hypoglycaemic or lipid-lowering drugs as needed, resulted not only in weight loss (mean 3.7 kg), decreased fasting blood glucose (p < 0.005) and improvement in serum lipid profile (p < 0.02 for both triglycerides or HDL-C) but also in an improvement of serum liver enzymes in 96%, which became normal in more than half of the patients. Thus, fatty liver was strongly associated with many features of the insulin resistance syndrome, and follow-up revealed a high potential for reversibility and a benign course.

Primary intestinal T-cell lymphoma and sclerosing cholangitis: a cytokine-mediated association?

A 63-year-old woman with a 1-year history of abdominal pain and intrahepatic cholestasis developed anorexia, weight loss, lassitude and diarrhoea. Studies led to a diagnosis of primary intestinal T-cell lymphoma involving especially the proximal small intestine and infiltrating the mesenteric lymph nodes, bone marrow and skin. An associated severe hypoalbuminaemia (1.3 g dL-1) was most probably the result of protein-losing enteropathy. Liver biopsy demonstrated concentric fibrosis of the bile ducts ('onion skin' lesions, with an inflammatory cell infiltrate and lymphoid aggregates) and was considered almost pathognomonic of primary sclerosing cholangitis. Sudden death due to pulmonary embolism occurred and a limited autopsy confirmed the diagnosis. Other associated diseases such as coeliac disease or inflammatory bowel disease were not found. This first report of the simultaneous occurrence of two rare diseases - primary sclerosing cholangitis and intestinal T-cell lymphoma - may indicate an intriguing association, possibly mediated by the effect of cytokines released by the infiltrating T-cells into the portal circulation.

In-vitro activity of dirithromycin against Chlamydia pneumoniae.

The in-vitro susceptibilities of 12 strains of Chlamydia pneumoniae were determined for dirithromycin, a new macrolide antibiotic, erythromycyclamine, its active metabolite, and erythromycin. Both dirithromycin and erythromycyclamine had an MIC90 of 2 mg/L, as compared with 0.062 mg/L for erythromycin. The combination of dirithromycin and erythromycyclamine appeared to be additive. Determination of the role of dirithromycin for the treatment of C. pneumoniae infection will depend on the results of prospective, controlled studies utilizing culture.

Detection of anti-Chlamydia pneumoniae IgE in children with reactive airway disease.

An association of Chlamydia pneumoniae infection and reactive airway disease has been demonstrated in children. To determine if C. pneumoniae infection triggers production of C. pneumoniae-specific IgE, sera were examined from 45 children with and without C. pneumoniae infection. Anti-C. pneumoniae IgE was demonstrated by immunoblotting in 12 (85.7%) of 14 culture-positive asthmatic patients with wheezing compared with only 1 (9.1%) of 11 culture-positive patients with pneumonia, 2 (18.2%) of 11 culture-negative asthmatic children with wheezing, and 2 (22.2%) of 9 culture-negative asymptomatic patients. The most commonly recognized proteins were at 98 (82.4%), 78 (58.8%), 58-60 (70.6%), and 36 kDa (64.7%). The presence of anti-C. pneumoniae IgE by immunoblotting was not associated with the presence of anti-C. pneumoniae IgG and IgM by microimmunofluorescence. These results suggest that production of specific IgE may be an underlying mechanism leading to reactive airway disease in some patients with C. pneumoniae infection.