Isotretinoin-induced inflammatory bowel disease in an adolescent.

OBJECTIVE: To report a case of inflammatory bowel disease (IBD) associated with use of isotretinoin. CASE SUMMARY: 17-year-old boy presented with new-onset rectal bleeding after completion of a five-month course of isotretinoin. A diagnosis of ulcerative colitis was made. His condition worsened despite therapy with 5-aminosalicylic acid, steroid retention enema, iron supplement, and prednisone. Five months after the onset of rectal bleeding, he had lost 11.4 kgand developed bilateral pitting edema of the hips and profound anemia. A subtotal colectomy and ileostomy was performed. DISCUSSION: Rectal bleeding has been reported to occur during or up to several years after treatment with isotretinoin. The mechanism by which isotretinoin may induce IBD is unknown. Proposed mechanisms include inhibition of epithelial cell growth resulting in ulceration and inflammation of the gut mucosa, inhibition of glycoprotein synthesis affecting the integrity of the mucosal wall, and stimulation of kiler T cells, leading to epithelial cell injury and a resultant inflammatory response. CONCLUSION: This case of probable isotretinoin-induced IBD suggests that patients with suspected IBD should be asked about current or past use of isotretinoin to improve documentation of this serious adverse event.

Erythromycin interaction with risperidone or clomipramine in an adolescent.

An adverse event is described which appeared when the macrolide antibiotic erythromycin was added to a regimen of risperidone 0.5 mg bid and clomipramine 50 mg tid in a 15-year-old male being treated for Tourette's, obsessive-compulsive, and attention-deficit hyperactivity disorders. An acute onset of behavioral symptoms, including agitation, labile mood, incessant talking, and argumentativeness, began within 24 h of starting the erythromycin and persisted for 9 days after its discontinuation. It was followed by a return to stable functioning on the prior risperidone-clomipramine regimen. Erythromycin, risperidone, and clomipramine are all metabolized by the hepatic cytochrome P450 system. It is postulated that the addition of erythromycin, a known inhibitor of CYP3A and CYP1A2, resulted in alterations in the metabolism of clomipramine and risperidone. Clomipramine metabolism is dependent upon the isoenzymes CYP2D6 and CYP1A2, and risperidone is a substrate for CYP2D6. Erythromycin would inhibit demethylation of clomipramine at the 1A2 isoenzyme and lead to a dual interaction between risperidone and clomipramine at the CYP2D6 isoenzyme. The subsequent increases in plasma levels of clomipramine, risperidone, their metabolites, or a combination of these agents could explain the adverse effects noted in this patient. In the absence of risperidone, clomipramine could have been metabolically cleared by CYP2D6. In the absence of clomipramine, risperidone clearance would not be affected by erythromycin. So the proposed mechanism requires an interaction involving all three agents: erythromycin, clomipramine, and risperidone. Alterations in plasma protein binding may also have played a role, because all three agents are extensively protein bound. Caution is urged when prescribing erythromycin with psychotropic drugs that are highly protein bound and/or are metabolized by the same P450 isoenzymes.