key: cord-0945403-eq35v32j authors: Aram, Khashayar; Patil, Anant; Goldust, Mohamad; Rajabi, Fateme title: COVID‐19 and exacerbation of dermatological diseases: A review of the available literature date: 2021-09-07 journal: Dermatol Ther DOI: 10.1111/dth.15113 sha: 5b8d6b102c8635359534be2041502fe95bb8ed49 doc_id: 945403 cord_uid: eq35v32j Since the emergence of the new coronavirus disease 19 (COVID‐19) pandemic, there has been a concern for the patients with chronic autoimmune diseases including dermatological conditions over the potential exacerbation of these underlying conditions after infection with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV2). We performed a systematic review to evaluate presentations, postinfection change in the manifestation, diagnosis, and management of flare‐ups of underlying dermatologic disease in patients with COVID‐19. A total of 17 articles were recovered reporting on flare‐ups of dermatological disease including pemphigus vulgaris, psoriasis, subacute cutaneous lupus erythematosus, acrodermatitis continua of Hallopeau, systemic sclerosis sine scleroderma, and Sézary syndrome (SS). Out of these, psoriasis and alopecia areata were the most common conditions. However, most cases of psoriasis could have been attributed to either antimalarial agents that were initially used for the treatment of COVID‐19 or discontinuation of treatment following SARS‐CoV2 infection. Aside from the fact that coronavirus diseases 2019 (COVID- 19) can present with cutaneous manifestations, there is a growing concern about the potential exacerbation of preexisting dermatological conditions following COVID-19. Though several case reports have been published on this issue, it remains one of the least studied aspects of dermatology-COVID-19 intersection. Viral infections are well-known triggers for induction and exacerbation of autoimmune conditions. Several mechanisms have been proposed for this phenomenon including antigen mimicry, epitope spreading, cytokine imbalance, and the overwhelming of clearance mechanisms by amplified tissue destruction that increases the selfantigens availability. Infection with the SARS-CoV2 virus is associated with an exaggerated immune response that could derail the vulnerable immune balance in autoimmune diseases. Though other factors related to the pandemic such as social isolation, loss-of-income, and non-adherence to treatment could greatly influence disease severity, in this review, we only focus on the changes directly related to SARS-CoV2 infection. We searched the PubMed, Scopus, and Google Scholar database with various combinations of three sets of keywords: COVID, SARS-COV-2, and coronavirus; flare-up, exacerbation, magnification, worsening, and aggravation; and cutaneous, dermatologic, and the Mesh term for several specific dermatological diseases ( Figure 1 ). The reference lists of selected studies were also explored. Databases were searched up to July 13, 2021. A final search was also done before paper submission. A total of 14 case reports were found. Nine patients had a history of psoriasis, and the others were diagnosed with pemphigus vulgaris, acrodermatitis continua of Hallopeau (ACH), systemic sclerosis sine scleroderma, SS, and cutaneous lupus erythematosus (CLE; Table 1 ). Of the nine patients with psoriasis, the flare-ups in five cases could be attributed to either hydroxychloroquine or systemic corticosteroids that were initially used in the treatment of COVID-19 and are wellknown causes of drug-induced psoriasis. [1] [2] [3] 6, 9 The exacerbation of psoriasis in two cases could have resulted from the discontinuation of treatments (secukinumab and cyclosporine). 5, 8 In one case the COVID-19 treatment was not mentioned. 7 Thus the exacerbation of psoriasis in only one case could be confidently linked to Various treatments were proposed to combat these exacerbations. For patients suffering from an exacerbation of psoriasis, these strategies included discontinuation of hydroxychloroquine and tapering of steroids accompanied by the initiation of topical steroids, oral acitretin, and cyclosporine and readministration of secukinumab (Table 1 ). The patient with pemphigus vulgaris was successfully treated with intravenous immunoglobulin (IVIG). 12 The patient with SS began a failed chemotherapy with gemcitabine. 14 The patient with ACH was initially started on oral acitretin and intravenous hydrocortisone which yielded unsatisfactory results. Intravenous infliximab was added to the treatment plan leading to improved lesions. 10 Aside from these case reports, several studies with larger sample sizes were able to assess the effect of COVID-19 infection on the disease course. One questionnaire-based study in the Netherlands assessed 1132 adult patients with atopic dermatitis and psoriasis and found 26% of the patients experienced worsening of their condition during symptomatic infection with SARS-CoV2. However, they did not mention whether these patients received antimalarials and steroids or not. 15 Another study assessed 21 adults with atopic dermatitis who had also been infected with COVID-19 and found out that 43% of these patients experienced disease exacerbation that did not require systemic intervention. The patients with severe atopic dermatitis who were receiving immunosuppressive therapy had milder exacerbations. 16 In a questionnaire-based survey in Italy, the investigators contacted 475 patients previously diagnosed with alopecia areata (AA) to follow up on their conditions after COVID-19. 42.5% of their participants who had been infected with SARS-CoV2 experienced a relapse that occurred about 2 months after COVID-19 (median of 2.14 months). Since only 12.5% of participants reported AA relapse in the absence of COVID-19, the association between AA exacerbation and COVID-19 seems to be significant. The production of IL-36 was reported to be enhanced after stimulation with polyinosinic-polycytidylic acid, a TLR3 agonist that mimics RNA of respiratory viruses. 20 There is a substantial paucity of literature on COVID-19 and flare-up of dermatological disease. We hope that the present review would inspire further larger epidemiological studies to assess the impacts of SARS-CoV2 infection on the course of chronic dermatological diseases. This data could greatly benefit the risk assessment and management of patients with proper prophylactic and treatment strategies. Pustular psoriasis exacerbated by COVID-19 in a patient with the history of psoriasis Generalized pustular psoriasis following COVID-19 COVID-19 infection revealed by a flare-up of psoriasis in an elderly Cameroonian: about a case Guttate psoriasis secondary to COVID-19 Coronavirus disease 2019 (COVID-19) rash in a psoriatic patient treated with Secukinumab: is there a role for interleukin 17? Covid-19 and exacerbation of psoriasis COVID-19 Infection Cause Moderate-Severe Psoriasis Flare Up A case of severe psoriatic erythroderma with COVID-19 A challenging case of psoriasis flare-up after COVID-19 infection Acrodermatitis continua of hallopeau evolving into generalized pustular psoriasis following covid-19: a case report of a successful treatment with infliximab in combination with acitretin COVID-19-associated cutaneous manifestations: does human herpesvirus 6 play an aetiological role? Aggressive course of pemphigus vulgaris following COVID-19 infection COVID-19 overlapping with systemic sclerosis COVID-19 infection in patients with Sézary syndrome: report of two cases COVID-19 in patients with cutaneous immune-mediated diseases in The Netherlands: real-world observational data The effect of sars-cov-2 virus infection on the course of atopic dermatitis in patients Targeting the NLRP3 inflammasome in severe COVID-19 Alopecia areata: a review of disease pathogenesis Evaluation of the relationship between alopecia areata and viral antigen exposure Respiratory virus infection triggers acute psoriasis flares across different clinical subtypes and genetic backgrounds COVID-19 and exacerbation of dermatological diseases: A review of the available literature The authors have no conflict of interest to declare. The article has never been presented anywhere else. All authors contributed to the study's conception and design. Not applicable. As this review does not directly involve human or animal subjects it did not require institutional board approval. Data sharing is not applicable to this article as no new data were created or analyzed in this study. https://orcid.org/0000-0002-9455-4025Fateme Rajabi https://orcid.org/0000-0001-5994-1997