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A child, L.B., born at term, the third child whose older sister has juvenile idiopathic arthritis successfully treated with azathioprine, presented at 3 months with 6 to 8 bloody diarrheal stools per day, resolving spontaneously within 1 week. She was breast-fed for 4 months, when solid food was started. Formula was introduced at 6 months. She was asymptomatic between 4 and 10 months, but then presented again with bloody diarrhea, up to 10 stools per day, with mucus and bright red blood in her diapers. Upper endoscopy and histology were normal. Lower endoscopy showed pancolitis with loss of colonic haustrations, friability, absent vascular pattern, and some small ulcerations ( Fig. 1). Histology was consistent with an ulcerative colitis (UC)-like phenotype; additionally, perinuclear anti-neutrophil cytoplasmic antibody was positive (1/160). Oral (50-60 mg Á kg À1 Á day À1 ) and rectal (333 mg/day) mesalamine was initiated. Following a good initial response, she relapsed 2 months later. At 13 months, azathioprine (2.0 mg Á kg À1 Á day À1 ) and prednisolone (2 mg Á kg À1 Á day À1 ) were initiated. Although she responded with decreased severity of symptom, stools remained frequent, bloody, and liquid. General condition, weight, and linear growth remained acceptable. The use of an amino acid-based formula for several months had no effect. Iron supplements failed to compensate for the rectal bleeding, and transfusion of packed red blood cells was needed every 3 to 4 weeks. Several probiotics, including VSL-3, proved unsuccessful. Infliximab treatment (5 mg/kg at 0-2-6-10 weeks) had no effect. An adverse reaction to sirolimus (Rapamune; Pfizer Pharmaceutical, New York, NY) made further administration impossible. Intravenous broad-spectrum antibiotics and total parental nutrition were administered for severe flares. Repeat biopsies with histology including electron microscopy did not reveal etiologies other than the ''UC-like image.'' Antigen detection for Clostridium difficile was negative. An immunodeficiency was suspected because of L.B.'s young age at onset. Lymphocyte numbers and subsets were normal. Immunoglobulin levels were within the normal range for age. B-cell subsets for common variable immunodeficiency were analyzed and showed no decrease in switched memory B cells. Vaccination response against tetanus was adequate. Normal

MethodsThe molecular basis of adult human "lactase deficiency" has long been a subject of controversy. To address this issue, small intestinal biopsies from oriental, black, and white patients were analyzed. Adjacent samples were assayed for lactase and sucrase specific activities and the sucrase/lactase ratio (high ratio signifies lactase deficiency), and the results were compared to lactase steady-state mRNA levels detected in Northern blots probed with a human lactase cDNA. All oriental patients had high ratios and no detectable lactase mRNA. Four black patients had a similar pattern; two with low ratios had detectable mRNA. The group of white patients displayed a range of findings, from high ratio/no mRNA to low ratio/considerable mRNA. Elevated levels of lactase mRNA always correlated with the presence of elevated levels of lactase enzyme activity, suggesting that the difference in levels of adult human intestinal lactase activity among racial groups may be regulated at the level of gene transcription. (J. Clin. Invest. 1992. 89:480-483.)

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6-Mercaptopurine (6-MP) maintains remission in pediatric Crohn's disease (CD). Azathioprine, a prodrug of 6-MP, is used for maintenance of remission of CD in Europe. We evaluated to what extent azathioprine is used in newly diagnosed pediatric CD patients and whether maintenance of remission differed between patients using azathioprine or not. Charts of children (diagnosed 1998Y2003, follow-up Q 18 mo) were reviewed. Active disease was defined as Pediatric Crohn's Disease Activity Index (PCDAI) greater than 10 or systemic corticosteroid use. Remission was defined as PCDAI 10 or less without use of corticosteroids. Eighty-eight children (55M/33F, age 12 T 3 yr) were included. Seventy-two (82%) patients received azathioprine during the follow-up period (38 T 17 mo). Patients diagnosed after 2000 received azathioprine significantly earlier during the course of disease compared with those diagnosed earlier (median, at 233 vs. 686 days; P G 0.05). At initial presentation, moderate-severe disease activity and prescription of corticosteroids were more prevalent in patients using azathioprine compared with nonazathioprine patients (75% vs. 52%; P G 0.05; and 89% vs. 58%; P G 0.005, respectively). Duration of corticosteroid use was longer in patients receiving azathioprine (232 vs. 168 days; P G 0.005). Median maintenance of first remission in patients who initially used corticosteroids, however, was longer in patients receiving azathioprine compared with nonazathioprine patients (PCDAI, 544 vs. 254 days, P = 0.08; corticosteroid free, 575 vs. 259 days, P G 0.05, respectively). We conclude that, since 2000, azathioprine is being introduced earlier in the treatment of newly diagnosed pediatric CD patients. The use of azathioprine is associated with prolonged maintenance of the first remission.