Isotretinoin has been considered a unique drug for acne treatment. However, it is associated with numerous adverse effects. Isotretinoin can trigger premature ventricular contractions. This report describes a 33-year-old-woman who presented with palpitations for 1 week while undergoing 1-month isotretinoin treatment for mild-moderate facial acne. An electrocardiogram and Holter monitoring showed premature ventricular contractions during isotretinoin (Roaccutane, Roche) treatment. Isotretinoin-related premature ventricular contractions were strongly suggested in this case due to the existence of documented premature ventricular contractions on electrocardiograms and the disappearance of these premature ventricular contractions two weeks after termination of the treatment To the authors' knowledge, there has been 1 reported case of premature ventricular contractions linked to isotretinoin use; this report describes a second such case.

Inflammatory bowel disease (IBD) may develop due to an inflammatory response to commensal gut microbiota triggered by environmental factors in a genetically susceptible host. Isotretinoin (acne therapy) has been inconsistently associated with IBD onset and flares but prior treatment with antibiotics, also associated with IBD development, complicates the confirmation of this association. Here we studied in mice whether doxycycline, metronidazole or isotretinoin induce epigenetic modifications, and consequently change T-cell mRNA expression and/or function directly after treatment and after a 4 week recovery period. Isotretinoin induced IL-10 signaling in Tregs and naive T-cells directly after treatment and reduced effector T-cell proliferation alone and in co-culture with Tregs. Metronidazole activated processes associated with anti-inflammatory pathways in both T-cell subsets directly after the treatment period whereas doxycycline induced an immediate pro-inflammatory expression profile that resolved after the recovery period. Long-term changes indicated an inhibition of proliferation by doxycycline and induction of beneficial immune and metabolic pathways by metronidazole. Persistent alterations in microRNA and mRNA expression profiles after the recovery period indicate that all three medications may induce long-term epigenetic modifications in both T-cell subsets. Yet, our data do not support the induction of a long-term pro-inflammatory phenotype in murine Tregs and naive T-cells.

Rosacea is a chronic inflammatory disease that can manifest as a spectrum of symptoms including erythema, inflammatory lesions, edema, and telangiectasia. Treatment decisions need to be adapted to reflect the nature and severity of the different symptoms present. In this report, we discuss the case of a female patient diagnosed with severe, inflamed papulopustular rosacea (PPR) presenting with a large number of inflammatory lesions and severe background erythema. This patient responded well to a treatment regimen consisting of a short course of antibiotics in combination with a corticosteroid, followed by monotherapy with isotretinoin to reduce the inflammation. Brimonidine gel, used as needed, was then added to isotretinoin to target the remaining background erythema. This case of severe PPR required a combinatorial treatment regimen to effectively target all symptoms present. The patient continued to apply topical metronidazole throughout the different treatment regimens prescribed over the course of almost 1 year. Use of topical metronidazole helped to repair and protect the skin barrier, which minimized the occurrence of dermatological adverse events when topical treatments were used. We conclude that in patients with severe disease and an important inflammatory component, a rapid response can be obtained with a multimodal, tailored approach that also includes treatment to repair and protect the skin barrier.

Since it was introduced to the market by Hoffman-La Roche (Roche) in 1982, isotretinoin has remained the most effective treatment for severe and recalcitrant acne. However, it has also been surrounded by controversy due to its teratogenicity and inconsistent associations with depression, suicidality, inflammatory bowel disease, increases in lipid levels, and elevated transaminases. Areas covered: In this article, we reviewed data regarding safety of isotretinoin and its association with these conditions. A thorough and comprehensive search on the topics was performed using pubmed and google scholar. Expert commentary: Despite common misperceptions, there is weak evidence for increased incidence of depression, suicidality, or inflammatory bowel disease with isotretinoin use. Furthermore, data indicates that transient increases in transaminases and lipid levels do not typically necessitate discontinuation of therapy. We hope to provide clinicians with information necessary to have meaningful discussions with patients regarding the safety and efficacy of isotretinoin.

Based on the Food and Drug Administration Adverse Event Reporting System (FAERS), the FDA and Hoffman La Roche issued warnings of a possible causal association between isotretinoin and inflammatory bowel disease. While scientists studied the association, trial lawyers used the courts to award large sums of money to plaintiffs despite the absence of clear scientific evidence of a causal effect. In this Issue of the Journal, a well-designed, large pharmaco-epidemiologic study shows no association. The story of isotretinoin highlights the problems that occur when the FAERS is used in litigation prior to further study and scientific analysis.

Summary Isotretinoin (13-cis retinoic acid) is the most potent known inhibitor of sebum production. The multiple modes of action for isotretinoin, including suppression of sebaceous gland activity, normalization of the pattern of keratinization within the sebaceous gland follicle, inhibition of inflammation, reduction of growth of Propionibacterium acnes in a secondary manner and, as currently shown, normalization of the expression of matrix tissue metalloproteinases and their inhibitors make this compound the single most effective in the treatment of severe recalcitrant nodulocystic acne, and in the prevention of acne scarring. Several generic formulations for oral use have recently been introduced, in addition to the brand formulations Roaccutane and Accutane (Roche). This development, considering the high risk of teratogenicity associated with oral isotretinoin use, has led the European Commission and the European Medicines Agency (EMEA) to release a directive towards the harmonization of the Summary of Product Characteristics (SPC). This has similarities to US FDA regulations, a matter that caused the reaction of the Forum for the Improvement of Clinical Trials in Acne. Physician's experience, coupled with proper patient selection, dose adjustment or discontinuation of treatment, and routine monitoring for potential toxicity, has allowed the successful prevention and management of most adverse effects associated with isotretinoin.

Isotretinoin (13-cis-retinoic acid), a synthetic vitamin A derivative, is used to treat a wide variety of dermatologic conditions including severe acne. Isotretinoin can trigger premature ventricular contractions (PVCs). We describe a 17-year-old boy who presented with PVCs on electrocardiogram during isotretinoin (Roaccutane, Roche) treatment for nodular facial acne. Presence of documented PVCs -on electrocardiogram and Holter monitoring- and the disappearance of these PVCs after cessation of the treatment strongly suggest isotretinoin-related PVCs in our case. The impact of isotretinoin on ventricular rhythm can not be ruled out in our case as we have revealed the presence of the temporal association of isotretinoin and documented PVCs. Thus, clinicians should be aware of possible arrhythmogenic effect(s) of isotretinoin.