key: cord-281703-6xwcxe8l
authors: Di Altobrando, Ambra; Patrizi, Annalisa; Bardazzi, Federico
title: Should SARS‐CoV‐2 influence immunosuppressive therapy for autoimmune blistering diseases?
date: 2020-04-17
journal: J Eur Acad Dermatol Venereol
DOI: 10.1111/jdv.16491
sha: 
doc_id: 281703
cord_uid: 6xwcxe8l

In this dramatic period where the whole world is affected by the outbreak of coronavirus disease 19 (COVID‐19), scientific data relating to the causative virus SARS‐CoV‐2 as well as the subsequent therapeutic repercussions on the management of other diseases should be divulged in order to share as much information as possible among experts in a timely manner.

subsequent therapeutic repercussions on the management of other diseases should be divulged in order to share as much information as possible among experts in a timely manner.

Regarding autoimmune blistering diseases, it is already widely acknowledged that physicians should search for triggers in all newly identified patients before starting any therapy, including infectious agents. But what about patients already in immunosuppressive therapy for these potentially life-threatening disorders?

Given the current lack of scientific evidence on the basis of which official recommendations with a high degree of reliability are possible, some indications have been proposed by the International Pemphigus and Pemphigoid Foundation, as the result of expertise and clinical common sense, inspired by a principle of prudence. 2 However, no clear and comprehensive data have been provided on the management of ongoing immunosuppressive therapies in these patients.

Regarding other inflammatory diseases, the indications of the major scientific Societies of Dermatologists, Rheumatologists and Gastroenterologists in Italy 3-5 , but also the American Academy of Dermatology Association, 6 suggest that if the patient is stable or in good health, the stop of the ongoing biologic therapy is not reasonable/indicated, as the risk of reactivation of the underlying pathology could add an additional risk factor to infections, including COVID-19.

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Here we report our experience of around 380 patients suffering from autoimmune bullous diseases and in treatment with immunosuppressive drugs currently referring to our Bullous Diseases Outpatient Service, Sant'Orsola-Malpighi University Hospital, Bologna, Italy. About 20 patients are visited per week in the space of one day. Since 9 th March 2020, in accordance with the Sant'Orsola-Malpighi Hospital directives made following the last Decree of the President of the Council of Ministers (DPCM) of march 9, 2020 (GU Serie Generale n.62 del 09-03-2020), all the outpatient services, of any priority, first visits or control visits, have been temporary suspended and in place telephone calls have been made to all patients who were scheduled to be visited in our Outpatient Service in the following weeks to prevent them from leaving their home and crowding the hospital, given that social distancing is one of the most effective safeguards in order to limit the spread of the virus. We therefore held a telephone consultation, checking the health of patients over the last month. In particular, we asked whether patients in immunosuppressive therapy Among possible trigger factors of autoimmune blistering diseases, immunization and viral infections are mentioned in the literature, although the underlying immunological mechanism is still unclear. [7] [8] [9] The most acceptable hypothesis involves the possible molecular mimicry existing between viral and epidermal proteins, and over activation of the immune system as a consequence of the viral attack. 9 Indeed, in autoimmune blistering disorders, once the autoantibodies bind to

This article is protected by copyright. All rights reserved their targets, namely self-structural proteins, several pathways are activated, including complement activation and deposition, and neutrophilic chemotaxis, with the release of proteases and elastases that lead to blister formation and of cytokines such as IL-6 and IL-8, which recruit additional immune cells. 1 To the best of our knowledge, no studies regarding previous viral outbreaks and the effects of these viruses on autoimmune blistering disease patients have been reported in the literature so far.

Moreover, the pathogenesis of SARS-CoV-2 infection in humans is still unclear, although massive and prolonged chemokine response known as 'cytokine storm' correlating with high morbidity and mortality has been observed in these patients. 10 We hypothesize that the interruption of immunosuppressive therapy in autoimmune blistering disease patients may determine a dysregulation of inflammatory cytokines that not only exacerbates the bullous disease itself but may also be involved in the pathogenesis of the viral infection. Therefore, it is likely that the management of the inflammatory processes guaranteed by immunosuppressive therapies not only controls blistering, but also contributes to a less aggressive organic response to SARS-CoV-2.

In conclusion, to date there is a lack of direct scientific evidence to support the continuation of immunosuppressive therapies in patients infected with SARS-CoV-2. Therefore, it will be crucial for our community to learn of more cases of autoimmune bullous disease patients under immunosuppressive treatment who have developed COVID-19, in order to better quantify the risk of infection under immunosuppressive therapy. Moreover, now more than ever, research into autoimmune blistering diseases should focus attention on emerging safer therapeutic options that decrease the rate of mortality and morbidity as well as the risks connected to the therapy itself.

What is novel in the clinical management of pemphigus

Information for Pemphigus and Pemphigoid Patients Related to Coronavirus Disease

2° Comunicazione del Presidente SIR: infezione da Covid-19

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Infezione da Coronavirus: Vademecum per i pazienti affetti da psoriasi cutanea e/o artropatia psoriasica

Italian Group for the study of Inflammatory Bowel Disease, Avviso per I pazienti con MICI

Guidance on the use of biologic agents during COVID-19 outbreak

Three case reports of post immunization and post viral Bullous Pemphigoid: looking for the right trigger

Bullous pemphigoid

Viruses and pemphigus: an intriguing never-ending story

Hypothesis for potential pathogenesis of SARS-CoV-2 infection--a review of immune changes in patients with viral pneumonia

Acknowledgments: The patients in this manuscript have given written informed consent to publication of their case details.

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