isotretinoin and Colitis

In vitro and in vivo data have shown that retinoid treatment promotes an anti-inflammatory milieu with few adverse effects toward the gastrointestinal tract. The in vivo studies reported here further evaluate retinoid effects in 2 mouse models of inflammatory bowel disease.. Chronic dextran sulfate sodium colitis was induced in age- and weight-matched C57Bl/6 mice by 4 cycles of dextran sulfate sodium administration (6-8 animals/group). At cycle 4, animals were administered 13-cis-retinoic acid (isotretinoin, 30 mg/kg) or vehicle (oral gavage) or 4-oxo-13-cis-retinoic acid (15 mg/kg, intraperitoneal) daily. T-cell transfer colitis was induced in CB17 SCID mice by transfer of naive CD4CD62L T cells and treated by transfer of regulatory CD4CD25 T cells (4-6 animals/group); isolated from BALB/c mice after treatment with isotretinoin or vehicle, as above, for 2 weeks. Assessments included endoscopic and histological scores, myeloperoxidase activity, serum cytokines, and plasma isotretinoin levels.. Retinoid-treated animals with colitis showed comparable changes in myeloperoxidase activity, and endoscopic and histological scores, versus untreated animals with colitis. Modest and comparable changes were seen in body weight and colon length in animals injected with naive T cells from isotretinoin-treated donors versus those injected with T cells from vehicle-treated donors. Retinoid treatment was consistently associated with lower interleukin-12 levels, which, after the transfer of naive T cells from isotretinoin-treated donors, supported isotretinoin-mediated predisposition of naive T cells toward reduced proinflammatory cytokine expression. Colitis had no effect on isotretinoin exposure.. Retinoids attenuate the proinflammatory cytokine response in vivo, with only modest effects on body weight and parameters of gastrointestinal morphology.

Topics: Animals; CD4-Positive T-Lymphocytes; Colitis; Cytokines; Dermatologic Agents; Dextran Sulfate; Disease Models, Animal; Female; Flow Cytometry; Gastrointestinal Tract; Isotretinoin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; Peroxidase; T-Lymphocytes, Regulatory

(1) Isotretinoin, a vitamin A derivative, is marketed as an oral treatment for refractory severe acne. It is known to carry a risk of severe birth defects. The skin tends to become dry and fragile during isotretinoin treatment; (2) Some adverse effects of isotretinoin are caused by damage to the intestinal mucosae. These effects include bloody and mucousy diarrhoea, colitis, ileitis (sometimes severe and necessitating surgery), and aggravation of inflammatory bowel disease such as Crohn's disease; (3) Isotretinoin can affect all mucous membranes, causing multiple disorders of varying severity, affecting: the eyes (conjunctivitis); ear, nose and throat (epistaxis); respiratory tract; gastrointestinal tract (colitis); and urinary tract; (4) Patients must be informed of the risk of mucosal damage and especially of intestinal disorders associated with isotretinoin therapy. Isotretinoin should be borne in mind as a possible cause when a young patient presents with gastrointestinal disorders, and its withdrawal should be envisaged. Isotretinoin is an additional risk factor in patients with a personal or familial history of inflammatory bowel disease.

Topics: Acne Vulgaris; Adolescent; Adult; Colitis; Crohn Disease; Diarrhea; France; Humans; Inflammatory Bowel Diseases; Intestinal Diseases; Intestines; Isotretinoin; Mucous Membrane; United States; Young Adult

Topics: Aged; Carcinoma, Basal Cell; Child, Preschool; Colitis; Combined Modality Therapy; Eyelid Neoplasms; Female; Homeopathy; Humans; Isotretinoin; Mistletoe; Patient Compliance; Phytotherapy; Plant Extracts; Recurrence; Xeroderma Pigmentosum

A 17-yr-old boy developed acute proctosigmoiditis after the institution of isotretinoin for the treatment of cystic acne vulgaris. Painless diarrhea, accompanied by mucus and eventually blood, began within days of commencing treatment and persisted while the drug was administered. At sigmoidoscopy patchy mucosal inflammation associated with numerous discrete aphthous ulcers was seen, apparently restricted to the rectosigmoid. Histologic examination of the affected mucosa revealed an acute focal superficial inflammatory infiltrate. Withdrawal of the drug resulted in prompt resolution of symptoms and a reduction in the severity of the inflammation. Rechallenge with isotretinoin induced a second, almost identical, attack of proctosigmoiditis. Withdrawal was again followed by disappearance of symptoms, and a subsequent sigmoidoscopy and mucosal biopsy were normal. The patient has remained clinically well for 16 mo after his initial presentation. Although the pathogenesis of the colonic mucosal inflammation remains unknown, the relationship of the bouts of proctosigmoiditis to the administration of isotretinoin strongly suggests that the drug was directly responsible.

Topics: Adolescent; Colitis; Humans; Intestinal Mucosa; Isotretinoin; Male; Proctocolitis; Rectum; Tretinoin