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To determine the prevalence of alpha 1-antitrypsin deficiency in patients with cirrhosis or chronic active hepatitis, we performed a five-year prospective study of liver-biopsy specimens from 1055 adults. Thirty-four patients whose specimens contained hepatocyte inclusions characteristic of the deficiency were phenotyped, and 25 had phenotype MZ (2.4 per cent). The distribution of patients with this phenotype among the 185 patients with cirrhosis diagnosed histologically was three of 84 patients with alcoholic cirrhosis (3.5 per cent), seven of 34 with non-B chronic active hepatitis (20.5 per cent), six of 28 with cryptogenic cirrhosis (21 per cent), and one of 39 with other kinds of cirrhosis (2.6 per cent). The increased prevalence of MZ in patients with cryptogenic cirrhosis and with chronic active hepatitis is highly significant (P < 0.001). Because serum levels of alpha 1-antitrypsin may be unreliable for identification of the subgroup of patients with chronic active hepatitis or cryptogenic cirrhosis, analysis of serum for the MZ phenotype and meticulous examination of biopsy specimens may be necessary.

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Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease.

All patients taking methotrexate for treatment of psoriasis over the past 5 yr have been reviewed. Thirty-eight patients have had pretreatment liver biopsies and at least 1 repeat liver biopsy. Of the 38, nine (24%) have developed significant liver fibrosis or cirrhosis, and have stopped treatment. The high incidence of fibrosis is attributed to synergism between methotrexate and other hepatotoxic factors, particularly alcohol, the use of a baseline biopsy to identify subsequent changes, and the early detection of fibrosis by sensitive histological techniques.

Fumarate hydratase (fumarase, EC 4.2.1.2) has a key role in cellular energy production: in the mitochondria it is a component of the tricarboxylic acid cycle; in the cytoplasm it is presumably a source of malate for the malate-aspartate shuttle, with an important source of fumarate being the urea cycle. Three cases of proven fumarase deficiency (McKusick 13686) have been reported (Zinn et al., 1986;Christensen et al., 1986;Petrova-Benedict et al., 1987).The second child of consanguineous Asian parents was delivered at 42 weeks, weight 3640 g. Hydramnios occurred in the third trimester. The female infant had dysmorphic facial features. On ultrasound and CT scans, the brain was malformed with agenesis of the corpus callosum, moderate communicating hydrocephalus affecting all four ventricles, and a small cyst in the right occipital horn. Chromosomes appeared normal. There was no apparent cardiomyopathy. She was clearly neurologically impaired from birth, fed poorly, and failed to thrive. She did not receive parenteral nutrition at any time. By 20weeks, vomiting, irritability and spasticity were problems. Her liver was consistently palpable to 2cm. She had conjugated hyperbilirubinaemia in the first 2months (plasma bilirubin t22-226~tmol/L) with a moderately raised plasma aspartate aminotransferase (AST) (63-87IU/L; normal 5-42) and ammonium (63~tmol/L). The jaundice abated, but AST remained elevated. Plasma and urinary amino acids, non-fasting plasma lactate and serum et-antitrypsin were normal. Blood pyruvate was raised (206 and 226 gmol/L). She did not have a metabolic acidosis.The bile duct and gall bladder appeared normal on ultrasound examination at 3 and 7 weeks. At open liver biopsy at 7 weeks, the liver was firm and green-tinged. Histology showed portal tract expansion by fibrosis, with focal degenerative changes in the bile ducts and peripheral bile ductular proliferation. Mild hepatocellular damage consistent with marked cholestasis was also present. Appearances were similar to changes associated with prolonged parenteral nutrition, but Kupffer cells only contained bile and lipochrome pigments. A quadriceps muscle biopsy appeared normal. She died aged 24weeks with an overwhelming varicella infection.Five urine samples, collected from 4 to 22weeks, analysed for organic acids showed grossly elevated fumaric acid at 2972-3829mmol/mol creatinine ~University

Cbrysiasis is a distinctive and permanent pigmentation of light-exposed skin resulting from the administration of parentera! gold salts. We report a study of 40 Caucasian patients with rheumatoid arthritis, treated with intramuscular sodium aurothiomalate. of whom 31 bad chrysiasis. Visible changes develop above a threshold, equivalent to 20 mg/kg gold content, and tbeir severity depends upon cumulative dose. Focal aggregates of particulate gold are deposited in the reticular and papillary dermis in amounts tbat correlate witb the degree of pigmentation. Characteristically, initially tbe periorbital region is affected hy a mauve discoloration, which intensifies and deepens into a blue/slate-grey colour, wbile extending to involve the face, neck and upper limbs. Altbough cbrysiasis develops insidiously and patients may he unaware ofthe changes, positive identification is important in order to avoid misdiagnosis and medical mismanagement, and afford appropriate reassurance. Prevention is difficult, but measures to reduce sunlight exposure may he helpful.