Acne—New Thoughts on Inflammation

Isotretinoin normalized Toll receptor 2 (TLR-2) responses, a measure of innate immunity, as reported by Thiboutot and colleagues in the September JID. Both circulating cytokines and cytokines from P. acnes-stimulated macrophages were measured. TLR-2 levels from stimulated macrophages were increased in untreated acne patients; after one week of therapy, these levels decreased. More interestingly, TLR-2 levels remained decreased for six months after stopping  therapy. Il-10, usually considered an anti-inflammatory cytokine, was increased in the patients, and was not affected by isotretinoin.  These studies focused on two of the key elements in acne pathogenesis: P.acnes and inflammation. Innate immunity, a topic of interest as far back as the time of Ilya Ilyich Metchnikoff (1845-1916), is an active focus of acne vulgaris and acne rosacea investigations in several laboratories currently. Hormones are an active area of acne studies , while the morphology of the hair follicle relative to acne, diet, and blood lipids seems dormant. An article in 2005 by Zouboulis et al (including your blogger) explored the pathogenesis of acne in a broad based fashion (2005).

While musing on inflammation and acne, I remembered medical school pathology, where I learned that young servicemen killed during the Korean war were found to have significant amounts of atherosclerosis. Today, fries and burgers would be the immediate culprit assigned by armchair scientists, but could inflammation from acne be implicated?  The role of the inflammation associated with psoriasis and periodontal disease in inducing cardiovascular disease has been a topic of active investigation – and debate —  for over a decade.  In addition, the metabolic syndrome has been documented recently in acne’s first cousin, hidradenitis suppuritiva (acne inversa in the European literature) by Sabat et al (2012).

Galobardes et al reported a study acne and heart disease, including long-term follow-up of male graduates of Glasgow university (followed up in 1968, twenty years after graduation) (2005). Acne was documented by history in the student health service.  All of the issues related to such retrospective studies, including confounding, incomplete data, and antibiotic use, were discussed in a commentary by Ford and Liu (2005). The diagnosis, severity, and duration of acne may be the most important variables in this study.  Alas, the data suggested that acne was a protective factor for death from cardiovascular diseases and coronary artery disease. The studies were undertaken because of the possible androgen effects in acne. Further longitudinal studies may be available, and many of the drug therapies for acne, including isotretinoin, are documented in administrative databases.  In the next few decades, with proper data collection, it may be possible to determine if acne and its treatments influence cardiovascular disease. There may be an effect, but the extent and direction of the effect is yet to be determined.

 

REFERENCES

Dispenza MC, Wolpert EB, Gilliland KL, et al (2012) Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients. J Invest Dermatol doi:10.1038/jid.2012.111

Ford, ES et al Invited commentary: Acne in adolescence—protecting the heart but damaging the prostate late in life? Am J. Epidemiology 161:1102-1006, 2005.

Galobardes, B.  Acne in adolescence and cause-specific mortality: Lower coronary heart disease but higher prostate cancer mortality Am J. Epidemiology 161:1094-1101, 2005.

Sabat R, Chanwangpong A, Schneider-Burrus S, et al. (2012) Increased Prevalence of Metabolic Syndrome in Patients with Acne Inversa. (2012) PLOS One 7:e31810. 2012

Zouboulis CC, Eady A, Philpott M, et al (2005) What is the pathogenesis of acne  Exp Dermatol. 14:143-132

Credit: Image by Karl Harrison (http://www.3dchem.com/molecules.asp?ID=17#); used with permission. 3-D Model of Isotretinoin Structure

One thought on “Acne—New Thoughts on Inflammation

  1. This is a very interesting summary which I really enjoyed reading. I strongly believe that any disease that leads to systemic inflammation for long periods of time, does increase cardiovascular risk. Because almost all the studies done on acne and cardiovascular risks are retrospective it is difficult to make solid conclusions. We need more prospective, controlled studies to decipher the role acne and the inflammation induced by acne plays in cardiovascular disease. I suspect that moderate to severe acne might even place patients with congenital heart valve disease at high risk of endocarditis. Does anyone know if this has been studied before?

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