Can isotretinoin worsen the symptoms of ulcerative colitis?/nA young woman with ulcerative colitis

Fråga: Can isotretinoin worsen the symptoms of ulcerative colitis? A young woman with ulcerative colitis and acne has been treated with isotretinoin 50 mg daily for two months. Her acne is better, but her colitis is worse, despite budesonide treatment (administered rectally as needed).

Sammanfattning: There are a few well described cases of inflammatory bowel disease in connection with isotretinoin treatment in the literature. In the present case it is possible that isotretinoin is the cause of increased symptoms of colitis.

Svar: Inflammatory bowel disease (IBD), including regional ileitis, is mentioned as a possible side-effect to isotretinoin in (1). Some authors have been sceptic to this information: in (2) it is suggested that treatment with isotretinoin, if warranted, could be given to an IBD-patient, as the author and his collegues have never seen a case of isotretinoin-induced IBD. A 19-year-old man with ulcerative colitis and acne was successfully treated with isotretinoin for 18 weeks (3). The authors report that they have treated one hundred patients with isotretinoin without any signs of gastrointestinal adverse reactions (3).

However, several cases of gastrointestinal disease in connection with isotretinoin have been reported: a young woman with acne and previous complaints of frequent diarrhea experienced abdominal pain and rectal bleeding nine days after starting isotretinoin treatment. Sigmoidoscopy showed severe proctitis (4). A 17-year-old boy developed acute proctosigmoiditis a few days after institution of isotretinoin treatment. He promptly recovered on drug withdrawal. Rechallenge with isotretinoin induced a second attack (5). A 47-year-old woman with psoriasis, arthritis, anemia and liver cirrhosis (caused by alcohol abuse) was diagnosed with Crohn´s disease after ten months of isotretinoin treatment. She had then had gastric symptoms for half a year. She was treated with corticosteroids and the bowel disease stabilised despite continued isotretinoin treatment. However, a year later she died from acute necrotising colitis (6).

During a phase II trial of isotretinoin to evaluate its ability to reverse Barrett´s esophagus, two of ten patients developed esophageal ulcerations that resolved after drug withdrawal (7).

Finally, there is a report concerning four IBD patients with severe acne treated with isotretinoin. Two of these had no gastrointestinal side-effects and one patient had two episodes of rectal bleeding, probably from pre-existing hemorrhoids. The fourth patient, a 20-year-old man, got worse in his Crohn´s disease on three occasions within 2-6 weeks of starting isotretinoin treatment (8).

The Swedish Adverse Drug Reactions Advisory Committee (SADRAC) has not received any reports of isotretinoin-induced IBD.

We suggest that this case be reported to the regional centre of SADRAC and that isotretinoin treatment is withdrawn, as two months of treatment may well be sufficient to induce a long term effect on the skin disease.