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Seven patients being treated for acute lymphoblastic leukaemia between March 1976 and March 1981, in accordance with Medical Research Council protocols, developed clinical malabsorption while on maintenance chemotherapy. All of them received weekly methotrexate and 6 of the 7 were given co-trimoxazole. Five patients had folate deficiency. Stopping the anti-leukaemic therapy led to a resolution of gastrointestinal symptoms. A combined effect of methotrexate and co-trimoxazole is postulated.

Serial small intestinal biopsies related to withdrawal and challenge with cows' milk are described in 5 infants with cows' milk protein intolerenace. On the basis of these serial observations the existence of a cows' milk-sensitive enteropathy in infancy is clearly established. The cows' milk-sensitive mucosal lesion varied in its severity ranging from a partly flat mucosa to a mild degree of partial villous atrophy. Intraepithelial lymphocyte counts rose after a positive milk challenge, but on only one occasion to a level outside the normal range. The technique of serial biopsies related to dietary milk enables a firm diagnosis of cows' milk intolerance to be made upon the basis of a single milk challenge. Clinically this appears to be a temporary condition which disappears by the age of 2 years.

Cows' milk protein enteropathy is recognised as a significant cause of persistent diarrhoea and malabsorption in young infants, but there are as yet no generally accepted diagnostic criteria. A combined clinical and histological approach to the diagnosis of cows' milk protein-sensitive enteropathy has been used in 15 patients, and the following set of criteria are proposed. (1) Clinical disease (diarrhoea with or without vomiting) while receiving cows' milk protein. (2) Clinical improvement on a diet free of cows' milk protein. (3) Normal or mildly abnormal histology of jejunal mucosa when taken 6-8 weeks after symptoms subside. (4) Histological relapse, with or without clinical relapse, after re-exposure to cows' milk protein.

Fifty-four infants with the malabsorption syndrome and cow's milk intolerence seen during 1962-1971 were investigated. All had diarrhoea and failed to thrive. Most had vomiting and about 20% had atopic eczema and recurrent respiratory infections. Laboratory investigations revealed malabsorption, raised serum IgA, and precipitins to cow's milk. Biopsies showed that the jejunal mucosa was damaged, and in about half the cases was flat. The patient did well on human milk but reacted clinically to cow's milk challenge, either in a few hours or gradually during 3-4 weeks. Some patients showed first a quick, but later a slow, reaction. Clinical symptoms of cow's milk intolerance disappeared at the age of about one year. At that time 81% had normal faecal fat, but only 29% had a normal proximal jejunal mucosa. Many of the patients developed intolerances to other food proteins, such as soya and wheat, if these were given during the sensitive period. Forty-two patients have been followed up for 2 years on a normal gluten-containing diet. Of these, 37 have a normal or nearly normal jejunal mucosa and 5 (12%) have subtotal villous atrophy indicative of coeliac disease. It is concluded that the malabsorption syndrome with cow's milk intolerance is a clear-cut clinical entity. However, the symptomatology, results of laboratory tests, and jejunal biopsy findings closely resemble those of other entities where damage to the intestinal mucosa causes a malabsorption snydrome. Follow-up studies showed that the disease is transient, but about 10% of the patients have coeliac disease, regarded in such cases as the primary disorder.