Letter to the Editor: Oral Isotretinoin

Dear Editor:

In the article titled, “Face to Face with Oral Isotretinoin,” in the November 2012 issue of JCAD, James Q. Del Rosso examined why some patients need repeated courses. I would like to offer my input on the matter. My comments rely on a cursory appreciation of the acne biofilm. A biofilm is a complex aggregation of micro-organisms marked by the excretion of a protective and adhesive matrix. Within a biofilm, multiple microenvironments exist, allowing for the same species of bacteria to live in diverse niches with varying rates of metabolism, replication, and responsiveness to antibiotic therapy. Micro-organisms within biofilms are 50 to 500 times more resistant to antimicrobial therapies than free-floating (planktonic) bacteria. Bacteria in a biofilm have a natural antibiotic resistance not apparent on agar plates. Once a biofilm is established, there is a change in behavior by the bacteria that is triggered by many factors, including quorum sensing, as well as other mechanisms that vary between species. When a cell switches modes, it undergoes a phenotypic shift in behavior in which large suites of genes are up- and down-regulated. For example, incriminating studies, such as API 20A systems, 16sRNA sequencing, DNA-DNA hybridization, XTT reduction method, and scanning electron microscopy, have suggested that the Propionibacterium acnes biofilm is the inciting factor for acne.[1] 

The complete P. acnes genome supports the existence of the P. acnes biofilm. In short, the P. acnes genome contains clusters of genes involved in polysaccharide capsule biosynthesis of a glycocalyx polymer, which account for adherence to a surface in biofilm formation secreted by the organisms.[2] For example, there are several sequences granting the genomic machinery necessary to make biofilm, such as UDP-N-acetylglucosamine 2 epimerase and glycosyl transferases. Indeed, these substances assisting adherence of the bacteria to the follicular wall are likely the incriminating cause of comedones as well.[3]

We propose that the microbiological principle of biofilms might apply to isotretinoin in which alteration of the physical, biological, and chemical environment of the pilosebaceous unit may be the primary function of the drug as the bacterial biofilm is greatly altered by the absence of the oil gland. The alteration in sebum composition clinically improves acne as the biofilm is no longer functional. Nevertheless, there always remains some P. acnes in the sebaceous unit, and if they are able to reform a functional acne biofilm, then clinical acne may well return.  

Certainly, the manipulation of the acne biofilm via antibiotics, isotretinoin, and other methods certainly warrants further investigation.
1.    Burkhart CN, Burkhart CG. Micro-biology’s principle of biofilms as a major factor in the pathogenesis of acne vulgaris. Int J Dermatol. 2003; 42:925–927.
2.    Burkhart CN, Burkhart CG. Genome sequence of Propionibacterium acnes reveals immunogenic and surface-associated genes confirming existence of the acne biofilm. Int J Dermatol. 2006;45:872.
3.    Burkhart CG, Burkhart CN. Expanding the microcomedone theory and acne therapeutics: Propionibacterium acnes biofilm produces glue that holds corneocytes together to form plug. J Am Acad Dermatol. 2007;57:722–724.

Craig G. Burkhart, MD, MPH
Clinical Professor, University of Toledo College of Medicine; Clinical Assistant Professor, Ohio University College of Osteopathic Medicine

Author’s reply:
Thank you for your letter. I appreciate the scientific explanation of the P. acnes biofilm. I am aware of the presence and potential clinical relevance of the biofilm, and certainly there have been publications on the P. acnes biofilm and its correlation with the P. acnes genome.

I agree that further research is needed in this area and also the relationship with oral isotretinoin.

James Q. Del Rosso, DO
Clinical Editor, The Journal of Clinical and Aesthetic Dermatology

Address correspondence to:
James Q. Del Rosso, DO
E-mail: kchesky@matrixmedcom.com