Acne vulgaris is a prevalent dermatological condition worldwide but is especially challenging to treat in individuals with skin of colour (SOC). Corresponding to Fitzpatrick skin phototypes III-VI, people of African, Asian, Middle Eastern and Hispanic ethnicity are considered to have SOC. With the additional risk of postinflammatory hyperpigmentation (PIH) as a consequence of inflammatory acne or its respective treatment, managing acne in this population holds significant importance. PIH adversely impacts self-esteem and quality of life and, thus, is usually the patient's priority of treatment. Available acne treatments are similar for all skin types. However, some are more beneficial for individuals with SOC, in particular by targeting both active acne lesions and PIH. The acne treatment literature was searched for topical and systemic treatments that were specifically studied in the SOC population. These treatments included topical agents, such as retinoids and azelaic acid, in addition to topical antibiotics and benzoyl peroxide. Newer formulations and combined regimens reported effective in reducing lesions are less likely to induce PIH and may treat pre-existing PIH. Moisturiser use, titrating doses and patient education are strategies to minimize irritation and improve adherence. In addition, systemic therapies, including oral antibiotics, isotretinoin, oral contraceptives and spironolactone, are efficacious for refractory acne or more severe cases but specific studies in SOC are lacking. Chemical peels may improve acne and target PIH directly. Overall, based on limited evidence, topical and systemic therapies are well tolerated in the SOC population but efficacy should be balanced with the risk of adverse effects. This narrative review aims to highlight formulations and combination therapies that are effective and safe for treating acne and PIH in patients with SOC.

Darier's disease (also known as keratosis follicularis or dyskeratosis follicularis) is an autosomal dominant inherited disorder which manifests as hyperkeratotic greasy papules in the first or second decade of life. Aside from symptom management and behavioral modifications to avoid triggers, there are currently no validated treatments for Darier's disease (DD). However, a variety of treatments have been proposed in the literature including retinoids, steroids, vitamin D analogs, photodynamic therapy, and surgical excision. The purpose of this review article is to identify therapeutic options for treating DD and to outline the evidence underlying these interventions. A search was conducted in Medline for English language articles from inception to July 4, 2020. Our search identified a total of 474 nonduplicate studies, which were screened by title and abstract. Of these, 155 full text articles were screened against inclusion/exclusion criteria, and 113 studies were included in our review. We identified Grade B evidence for the following treatments of DD: oral acitretin, oral isotretinoin, systemic Vitamin A, topical tretinoin, topical isotretinoin, topical adapalene gel, topical 5-flououracil, topical calciptriol and tacalcitol (with sunscreen), grenz ray radiation, and x-ray radiation. All other evidence for treatments of DD consisted of case reports or case series, which is considered grade C evidence. Considering the quality and quantity of evidence, clinicians may consider initiating a trial of select topical or oral retinoids first in patients with localized or generalized DD, respectively.

Acne vulgaris affects more than 80% of adolescents and young adults and forms a substantial proportion of the dermatologist's and general practitioner's caseload. Severity of symptoms varies but may result in facial scarring and psychological repercussions. Oral isotretinoin is highly effective but can only be prescribed by specialists. Side effects are recognized and mostly predictable, ranging from cosmetic effects to teratogenicity. These can affect patients' quality of life and treatment adherence. This article provides a commentary on 4 key areas: the use of oral isotretinoin vs oral antibiotics, including the importance of early recognition of nonresponse to treatment, the psychological effects of acne and isotretinoin treatment, the side effects of isotretinoin therapy, and cosmetic treatment options that can help alleviate predictable side effects. The authors, who have all participated in various international expert groups, draw on relevant literature and their extensive professional experience with oral isotretinoin in the treatment of acne. The aim of this article is to provide an informative and practical approach to managing oral isotretinoin treatment in patients with acne, to help optimize treatment of this skin disease.

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.

With Roche's withdrawl of Accutane from the U.S. market in 2009, isotretinoin has only been available in its generic form. Many clinicians fail to realize that for approval by the U.S. Food and Drug Administration, a generic medication must have a bioequivalence between 80 percent and 125 percent of that of the innovator product. This potential variability in bioavailability between branded and generic medications is important to keep in mind with isotretinoin, given the implications for achieving a sustained remission in acne patients.

Limited evidence suggests that isotretinoin may be associated with inflammatory bowel disease (IBD). To explore this association, we conducted a retrospective population-based cohort study in British Columbia, Canada, among participants who were newly treated with isotretinoin or topical acne medications. The entire population of untreated provincial residents aged 12-29 years served as the reference group. During the 12-year study period, we identified 46,922 participants treated with isotretinoin, 184,824 treated with a topical acne medication, and 1,526,946 untreated individuals. Compared with untreated individuals, we observed no significant association between isotretinoin use and IBD (rate ratio (RR) 1.14; 95% confidence interval (CI) 0.92-1.41). As expected, we found no association with topical acne medications (RR 1.11; 95% CI 0.99-1.24). In prespecified secondary analyses, isotretinoin was associated with IBD among individuals aged 12-19 years (RR 1.39; 95% CI 1.03-1.87) and topical acne medications were associated with ulcerative colitis (RR 1.19; 95% CI 1.00-1.42). Our primary analyses found no association between isotretinoin and IBD. In prespecified secondary analyses, some evidence was found of associations with isotretinoin as well as topical acne medications, suggesting a possible association between IBD and acne itself. Additional research is needed to explore this possibility.

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.

Oral isotretinoin is currently the most effective therapy for acne, but is associated with numerous adverse effects. To investigate the cardiac effects of isotretinoin, acne patients receiving isotretinoin for 6 months were studied. Methods Twenty-six patients with acne vulgaris were enrolled in the study. The patients were treated with a dose of 0.8 mg/kg/day of isotretinoin (Roaccutane, Hoffman-La Roche, Basle, Switzerland) for 6 months. All participants were assessed pretreatment and at the third month of therapy with 24-h Holter monitoring of electrocardiography. Results Twenty-two patients completed the study (19 females and three males). Initial 24-h Holter monitoring showed normal sinus rhythm in all patients, with a mean heart rate of 79 beats/min (lowest, 63 beats/min; highest, 97 beats/min). At the third month of therapy, 24-h Holter monitoring showed normal sinus rhythm in all patients, with a mean heart rate of 81 beats/min (lowest, 67 beats/min; highest, 91 beats/min). All patients were in sinus rhythm throughout the recording period. None of the patients had supraventricular tachycardia or atrial arrhythmia. Conclusion In this study, 6 months of isotretinoin therapy significantly improved acne and did not cause any cardiac adverse effects at a dose of 0.8 mg/kg/day.

Isotretinoin (Accutane) is a drug closely related to the chemical structure of Vitamin A. The pharmacology and toxicology of these two retinoids is similar enough to warrant comparison. Accutane is a powerful drug which its manufacturer, Roche, indicates is limited for severe recalcitrant nodular acne. This potency is also reflected in Accutane's well-known ability to produce severe birth defects if taken during pregnancy. Less well-known is the risk of this lipid soluble chemical to affect the Central Nervous System. Reports of intracranial hypertension, depression, and suicidal indeation with Accutane use have prompted an examination of this serious and life threatening potential. Though Roche has added a warning to its product label for signs of depression and suicidal ideation, this product is being overprescribed for all forms of acne, including mild cases and moderate acne that have not been treated with alternative medications, which have a lesser risk of depression and suicide. There is no contesting that this drug is effective at clearing up the most severe forms of acne, but the public must be informed of its proper, limited indication for use; depression and suicide can follow in patients with no prior history of psychiatric symptoms or suicide attempts.

The growing number of reported cases of depression and suicide associated with isotretinoin (a retinoid receptor agonist) use in patients with acne has prompted concern among dermatologists, patients, and their relatives and has triggered new warnings from regulators including depression-related, patient-informed consent forms. In establishing a cause-effect relationship, it is useful to judiciously consider whether there is an association, what is the nature of that association, if there is a plausible biological mechanism of action, the validity and reliability of measures used and the strength of study designs. Hoffmann-La Roche estimates that by April 2001 approximately 12 million patients worldwide have used isotretinoin, with 5 million patients in the US.A MEDLINE search between January 1966 and May 14 2003 of the published medical literature found 24 documented cases of isotretinoin-associated depression, with 3 suicides. One additional patient committed suicide during the fourth month of isotretinoin treatment and 3 further patients attempted suicide by taking an overdose of isotretinoin. The US FDA's Adverse Event Reporting System (AERS) contains almost 23,000 reports for isotretinoin from its approval in 1982 to December 2002. As of November 30, 2002, AERS contained 3,104 reports (US and foreign) with at least one reported psychiatric event. The FDA is aware of 173 reports of suicide (both US and foreign) in association with isotretinoin. Reports of positive dechallenge and rechallenge present a strong signal pointing to an association between isotretinoin and depression. A Hoffmann-La Roche sponsored epidemiological study failed to find any evidence of an association between isotretinoin and depression or suicide. However, the design of the study was flawed and the evidence was deemed inconclusive. Further studies using strong study designs, reliable and valid measures, and adequate sample sizes may bring us closer to the answer. The evidence suggesting a relationship between isotretinoin and depression needs to be weighed against the increasing prevalence of depression among adolescents and young adults and the psychological impact of acne. The literature contains credible evidence that isotretinoin treatment may reduce the psychosocial impact of acne in some patients. At the present time, there is no known pharmacological mechanism that would account for psychiatric symptomatology as a result of isotretinoin treatment; however, retinoid receptors are widely distributed in the brain and more research is needed to ascertain whether they have a role in depression. In the meantime, for the practitioner, the obvious benefit of isotretinoin in treating acne should encourage continued use. However, patients and their relatives must be informed and depressive symptoms should be actively assessed at each visit and, if necessary, referral to a psychiatrist, antidepressant therapy or discontinuation of isotretinoin should be considered.