– Isotretinoin, the go-to guy for severe acne, may not be so much a local cop as a community organizer, Kenneth B. Gordon, MD, said at the meeting provided by Global Academy for Medical Education.

Dr. Kenneth B. Gordon Bruce Jancin/Frontline Medical News

Dr. Kenneth B. Gordon

“It now appears that with isotretinoin treatment, the diversity of the skin microbiome, and the diversity of P. [Propionibacterium] acnes in particular, is increased, and that the microbial community is replenished with the types associated with healthy skin,” said Dr. Gordon, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee. When these new bacteria move in, they push pathogenic species out of the neighborhood “and create a new skin microbial community. Maybe this is the real reason our patients tend to stay better, once we get them better with isotretinoin.”

Dr. Gordon discussed new data published last October in the Journal of Investigative Dermatology (J Invest Dermatol. 2018 Oct 24. doi: 10.1016/j.jid.2018.09.023). In a letter to the editor, William H. McCoy, IV, MD, PhD, of Washington University, St. Louis, and his associates suggest that isotretinoin induces a “sebaceous drought,” which shifts the skin microbiome from pathogenic to normophysiological.

Isotretinoin is the gold standard treatment for severe acne, but its method of action has never been fully elucidated, Dr. Gordon said. It clearly targets the sebaceous gland – decreasing sebocyte proliferation and suppressing sebum production – but an emerging body of research suggests that the drug also markedly affects dermal microbial colonization.

The entire concept of a skin microbiome is nearly as new as this new concept of isotretinoin’s effect upon it. Only in the last few years have researchers begun to characterize the complex microbial film that keeps skin healthy and resistant to infection. Dermal dysbiosis has now been associated with acne, psoriasis and psoriatic arthritis, and atopic dermatitis.

The 2-year pilot study compared the dermal microbiome of isotretinoin-treated acne patients with that of patients with untreated acne and normal skin. Skin samples underwent genomic analysis before isotretinoin treatment, at several periods during treatment, and about 5 months after treatment stopped. Untreated controls were evaluated at baseline and at 2, 5, and 10 months.

Not surprisingly, before treatment the microbiome was similar in both acne groups, but markedly different from that seen in normal skin. As isotretinoin’s “oil drought” dragged on, levels of Cutibacterium acnes (the new appellation for P. acnes) declined. Staphylococcus species initially increased, but then declined as well. Simultaneously, four new taxa (Rothia, Flavobacterium, Enterobacter, and Micrococcus) increased. Most patients had a restructuring of their Propionibacterium community, populated largely by the less-pathogenic strains found on normal skin.

“We suggest that isotretinoin creates a Propionibacterium ‘population bottleneck’ that selects for ‘healthy’ Propionibacterium communities and other sebaceous skin taxa that persist after treatment, resulting in long-term acne remission [i.e., normal skin],” the investigators wrote.

This is a new and very exciting finding, Dr. Gordon commented. “It appears that the reason our isotretinoin patients stay better once they get better is not from targeting the sebaceous gland itself, but by repairing the skin’s microbiome and getting it back to normal.”

Dr. Gordon reported financial relationships with numerous pharmaceutical companies. Global Academy and this news organization are owned by the same parent company.