NEW ORLEANS - A recent large study associating tetracycline-class antibiotics for acne therapy with an increase in inflammatory bowel disease is one of the hottest topics at this year's annual meeting of the American Academy of Dermatology.
Doxycycline was the antimicrobial associated with the highest risk for inflammatory bowel disease (IBD) in this retrospective cohort study of 94,487 acne patients followed for more than 406,000 person-years in the very large U.K. general practice Health Improvement Network database. The 15,032 patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohn’s disease than did acne patients not exposed to antibiotics.
Dr. Ted Rosen
"Think about that the next time you have someone on doxycycline for acne for a year. This is a really scary paper to me," commented Dr. Ted Rosen, professor of dermatology at Baylor College of Medicine, Houston. "We need other studies with better controls, but I think it's a cautionary tale—and you don't ignore cautionary tales. You investigate them further."
The study, conducted by investigators at the University of Pennsylvania, Philadelphia, was the focus of at least three separate "what's new in dermatology" sessions on day 1 alone of the AAD conference.
The 38,603 British acne patients exposed to tetracycline had a 61% increased rate of Crohn’s disease relative to acne patients not receiving antibiotics, while the 24,085 who were prescribed minocycline had a 28% increase in risk (Am. J. Gastroenterol. 2010;105:2610-6).
The investigators noted that these findings further muddy the waters regarding a highly controversial possible association between exposure to isotretinoin and IBD, since most acne patients treated with isotretinoin have previously had an extended period of antibiotic therapy. They cautioned that attempts to determine whether treatment with isotretinoin is associated with the development of IBD should consider potential confounding by previous doxycycline exposure.
Dr. Diane M. Thiboutot observed that while the study of U.K. acne patients found a relationship between doxycycline and Crohn’s disease but not ulcerative colitis, a recent large case-control study paradoxically showed just the opposite for isotretinoin: an associated 4.4-fold increased risk of ulcerative colitis, but no increase in Crohn's disease, compared with matched acne patients not exposed to the retinoid. This study, drawn from a large insurance database, involved more than 8,000 patients with IBD and nearly 22,000 controls (Am. J. Gastroenterol. 2010;105:1986-93).
It's not possible to draw definitive conclusions from the tetracycline study or the various isotretinoin studies, said Dr. Thiboutot, professor of dermatology at Pennsylvania State University, Hershey. "We really can't point to a cause-and-effect relationship."
Dr. Rosen agreed. It's entirely possible, he said, that some patients who are predisposed to developing IBD are the same ones who require systemic therapy for their acne. But for Dr. Rosen, who calls antibiotic resistance one of the greatest and most underappreciated threats to humankind, there is one clear message to be drawn from the tetracycline study: Physicians need to become more resourceful in drawing on the many alternatives to the long-term use of antibiotics for acne and rosacea.
The tetracycline study comes at a time of pervasive advertisements by personal injury lawyers reaching out to "Accutane injury" victims.
"To the best of my knowledge there have been no dermatologists sued for treating a patient with isotretinoin, but you know lawyers: It's coming," said Dr. Mark G. Lebwohl, professor and chairman of dermatology at Mount Sinai School of Medicine, New York.
Dr. Lebwohl disclosed that he has assisted Hoffman-La Roche in its defense against isotretinoin lawsuits. Dr. Thiboutot declared she has received research grants from and served as a consultant to numerous pharmaceutical companies developing acne therapies. Dr. Rosen declared having no relevant financial interests.