INTRODUCTION
Acne vulgaris is a common skin disease affecting up to 70% of the population during their lifetime.1 Cutibacterium acnes is the primary target of acne pathogenesis, and oral antibiotics, namely oral tetracyclines, have been the mainstay of systemic acne treatment for decades. In addition, oral tetracyclines possess an indirect anti-inflammatory effect against acne.2,3 Oral tetracyclines are an important part of the acne treatment regimen, and substantial evidence exists for their efficacy and safety for use in inflammatory acne.4
Oral tetracyclines demonstrate bacteriostatic (inhibiting bacterial growth) effects against C. acnes; however, some tetracyclines also exhibit bacteriostatic effects on beneficial commensal organisms of the gut. This broad-spectrum effect can lead to a less diverse gut microbiome. Disruptions in the symbiotic relationship between the gut microbiome and the host have been associated with chronic diseases, such as obesity and inflammatory bowel disease (IBD).5,6 Although a compositional definition of an ideal gut microbiome does not exist, greater microbial diversity is important for protection from pathogens, nutrient supply, and vitamin production.7
While oral tetracyclines are widely prescribed for acne, a gap exists in synthesizing the most recent data on the efficacy and safety of these agents. We conducted a systematic review of the efficacy and safety of common oral tetracyclines (sarecycline, doxycycline, minocycline, and tetracycline) used for acne.
Oral tetracyclines demonstrate bacteriostatic (inhibiting bacterial growth) effects against C. acnes; however, some tetracyclines also exhibit bacteriostatic effects on beneficial commensal organisms of the gut. This broad-spectrum effect can lead to a less diverse gut microbiome. Disruptions in the symbiotic relationship between the gut microbiome and the host have been associated with chronic diseases, such as obesity and inflammatory bowel disease (IBD).5,6 Although a compositional definition of an ideal gut microbiome does not exist, greater microbial diversity is important for protection from pathogens, nutrient supply, and vitamin production.7
While oral tetracyclines are widely prescribed for acne, a gap exists in synthesizing the most recent data on the efficacy and safety of these agents. We conducted a systematic review of the efficacy and safety of common oral tetracyclines (sarecycline, doxycycline, minocycline, and tetracycline) used for acne.
METHODS
To determine the efficacy and safety of oral tetracyclines for acne, we followed the Preferred Reporting Items for Systematic Reviews guidelines and performed a systematic review using PubMed and Embase. Our search included published articles from January 1960 to April 2020, and our search criteria included the following: ("Acne"[MeSH] OR "Acne Vulgaris"[MeSH]) OR "acne vulgaris/drug therapy"[MeSH Major Topic]) AND tetracyclines [MeSH Terms]. This initial search identified 653 articles (Figure 1).
To include adequately powered studies for efficacy and safety assessments, we then applied the following inclusion criteria: large interventional (controlled and uncontrolled) and observational studies utilizing tetracycline antibiotics (N ≥ 200); acne indication; outcomes included acne severity assessments and/or rates of adverse events (AE). We excluded non-English articles and combination treatments. Lymecycline and oxytetracycline were not included due to their limited use in the U.S.
Two authors (JH and AWA) evaluated titles and abstracts of identified articles to determine eligibility based on inclusion and exclusion criteria. Selected articles underwent full-text review, and subsequently, two authors (JH and AWA) independently extracted the data. We performed quality assessment using the Cochrane Risk of Bias Tool for randomized interventional studies and the Newcastle-Ottawa scale for observational studies. The review protocol was registered with PROSPERO.
To include adequately powered studies for efficacy and safety assessments, we then applied the following inclusion criteria: large interventional (controlled and uncontrolled) and observational studies utilizing tetracycline antibiotics (N ≥ 200); acne indication; outcomes included acne severity assessments and/or rates of adverse events (AE). We excluded non-English articles and combination treatments. Lymecycline and oxytetracycline were not included due to their limited use in the U.S.
Two authors (JH and AWA) evaluated titles and abstracts of identified articles to determine eligibility based on inclusion and exclusion criteria. Selected articles underwent full-text review, and subsequently, two authors (JH and AWA) independently extracted the data. We performed quality assessment using the Cochrane Risk of Bias Tool for randomized interventional studies and the Newcastle-Ottawa scale for observational studies. The review protocol was registered with PROSPERO.
