key: cord-1020026-ac2o4zvo authors: Donnarumma, Marianna; Nocerino, Mariateresa; Lauro, Wanda; Annunziata, Maria Carmela; Marasca, Claudio; Fabbrocini, Gabriella title: Isotretinoin in acne treatment during the coronavirus disease 2019 (COVID‐19): A retrospective analysis of adherence to therapy and side effects date: 2020-12-22 journal: Dermatol Ther DOI: 10.1111/dth.14677 sha: 768ba6e4c2aba4b1a87494de1c1ab0a2feb381d3 doc_id: 1020026 cord_uid: ac2o4zvo nan We read with great interest the letter by Abdelmaksoud et al 1 Isotretinoin is an oral retinoid approved for the management of severe cases of acne vulgaris, and recently utilized for mild to moderate acne. 2 COVID-19, is a respiratory disease caused by the SARS-CoV-2 virus and it was stated a pandemic on 11 March 2020. Advanced age is recognized as a risk factor for a severe infection, however those of any age may suffer from severe disease from COVID-19. 3 According to the British Association of Dermatologists isotretinoin could theoretically increase the risk of COVID-19 viral load because of its drying effect on the mucous membranes (https://www. bad.org.uk/shared/get-file.ashx?itemtype=document&id=6661). Most isotretinoin side effects are skin related and associated with xerosis. Dry nasal membrane was also observed in two-thirds of patients. Isotretinoin treatment modifies nasal mucociliary clearance considerably, reduces normal and regenerated mucosal thickness, triggering severe inflammation. 4 Angiotensin-converting enzyme 2 (ACE2) is the host receptor for SARS-CoV-2 entrance. As reported by Abdelmaksoud ACE2 receptor expression was found in the basal layer of the epithelium in nasal mucosa. Disruption of nasal mucosa, uncovering the basal layer, perhaps could increase nasal mucosa invasion by coronavirus. 1 However, data are still sparse and controversial. Sinha et al evaluated the ACE2 expression levels in control and drug-treated groups for the top significant drugs (vorinostat, panobinostat, and isotretinoin) among the 672 clinically approved drugs. According to their data the top ACE2 downregulator is isotretinoin. 5 In the wake of these evidences, we retrospectively reviewed 34 patients in treatment with isotretinoin from March to August 2020 in our outpatient clinic in Naples (11 males and 23 females; median age 22.5 years, range 18 to 38; medium duration of isotretinoin treatment 5 months, range 2 to 8 months; medium dosage 22.7 mg/die). Female patients did not present any sign of hyper-androgenism. We observed that 14.7% of patients prematurely interrupted the therapy in the months of Italian lockdown (March to May 2020) because of the fear of COVID-19. The lockdown period in fact has been characterized by a drastic reduction in the number of accesses in dermatological departments and different measures, such as the implementation of teledermatology, have been applied in order to limit coronavirus infection spread. 6 Moreover, it is likely that there is an inclination of the patients to overestimate the incidence and severity of side effects of oral isotretinoin. 7 According to our survey 47% of the patients reported nasal dryness. In the light of this data, we believe that a nasal moisturizer should be recommended during the treatment. Our sample is mostly composed of non-hyperandrogenic females. This data could justify that patients do not report serious signs of disease. In fact, according to Cadegiani et al the frequency of several common clinical symptoms of COVID-19 is significantly more pronounced in males and hyperandrogenic females than their nonhyperandrogenic counterparts. 8 Finally, although the correlation between isotretinoin and the pathogenesis of COVID-19 infection is not clear, we believe is essen- Systemic isotretinoin therapy in the era of COVID-19 Comparison of guidelines and consensus articles on the management of patients with acne with oral isotretinoin Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the coronavirus disease 2019 (COVID-19), a comprehensive literature review Effect of systemic isotretinoin therapy on mucociliary clearance and nasal surface mucosa in acne patients In vitro and in vivo identification of clinically approved drugs that modify ACE2 expression Teledermatology for acne during COVID-19: high patients' satisfaction in spite of the emergency Challenges and solutions in oral isotretinoin in acne: reflections on 35 years of experience Clinical symptoms of hyperandrogenic women diagnosed with COVID-19 How to increase adherence and compliance in acne treatment? A combined strategy of SMS and visual instruction leaflet