key: cord-263882-s5oxr6es
authors: Najar Nobar, Niloufar; Goodarzi, Azadeh
title: Patients with specific skin disorders who are affected by COVID‐19: what do experiences say about management strategies? : A systematic review
date: 2020-06-18
journal: Dermatol Ther
DOI: 10.1111/dth.13867
sha: 
doc_id: 263882
cord_uid: s5oxr6es

BACKGROUND AND AIM: In patients with dermatologic disorders who are affected by new corona virus, we know little about course (underlying disease and new onset‐infection) and the most proper management strategies include both issues that are what this systematic review targets. METHOD: Databases of PubMed, Scopus, Google Scholar, Medscape and CEBD coronavirus dermatology resource of Nottingham University searched completely and initial 237 articles selected to further review and finally nine articles (including 12 patients) entered to this study. RESULT: from 12 patients with chronic underlying dermatologic disease treated with systemic therapies, only one patient required ICU admission, the others have been treated for mild‐ moderate symptoms with conventional therapies. The biologic or immunosuppressive/ Immunomodulator agents has been ceased during the course of disease. The course of COVID‐19 its management was as similar as normal populations. Their underlying dermatologic disease was exacerbating from mild to moderate. Their treatment has been continued as before, after the symptoms improved. CONCLUSION: Exacerbation of patients underlying dermatologic disease is mild‐ moderate. Discontinuing the treatment in the acute period of COVID and the restart after recovery may prevent severe recurrence in these patients. This article is protected by copyright. All rights reserved.

manifestations. There are growing reports of dermatologic manifestation among children like morbiliform or urticarial rash and conjunctivitis (33, 34) or non-specific exanthematous, urticarial rashes and facial ulceration in affected infants may born from infected mothers (33, 35) . Hydroxychloroquine-induced rashes solely or in combination with other therapies, are responsible for the main cutaneous drug reactions especially generalized pustular eruptions (36) (37) (38) .

There are some secondary COVID-19 related dermatoses like incidence of an acute new dermatologic entity for a limited time period that could be stress-related (e.g. Herpes Simplex, Herpes Zoster, alopecia areata ad etc…) or physical-environmental-related (e.g. contact dermatitis, acute urticaria…) or presence of a new dermatoses which have tendency to become chronic, like telogen-effluvium, various types of dermatitis, neurocutaneous or psychocutaneous disorders. In the pandemic, some preexisting chronic dermatoses may become poorly-controlled or aggravated by the stress, irregular visits, treatment interruptions, delayed therapies, physical and environmental situations like wearing masks and latex gloves, frequent washing and disinfectants, excessive sweating and etc (11) . Dermatologic visits and cosmetic or elective surgical procedure have been affected largely by a decreasing manner during pandemic (39) . Adherence to personal and social hygiene strategies, social isolation and distance are the rules of pandemic for better controlling any situations and the role of Teledermatology is really important in this area regarding educational and therapeutic issues (40) .

In dermatology, one of the most important concerns in the pandemic setting is the manner of disease management especially in the case of patients under treatment with immunosuppressive Immunomodulators. Non-infected non-at risk patients do not need to any change in their therapeutic protocols but at-risk patients or who suspected to being infected (like having suggestive symptoms) need altering drug regimen as dose reduction, increase dose interval or transient stop of drug usage for at least 2 weeks. It is not any doubt that, every patient with an active corona virus infection should discontinue systemic biologic or non-biologic immunosuppressive for at least 1 month or completely being symptom-free. A more severe Covid-19 course is usually predictable in the setting of dermatologic diseases which are treating by systemic Immunomodulators. Presence of any comorbidities related to underlying dermatologic disorder (like older age, metabolic syndrome and vital organ dysfunctions especially respiratory and cardiovascular involvements that may be seen in psoriatic or atopic patients or who with hidradenitis suppurativa, immunobullous or collagen vascular disorders), is associated with poorer outcomes in the case of being infected by COVID-19. Some studies suggested that more sever skin conditions are at risk for higher rate of pneumonia and symptomatic respiratory involvement. In future vaccination of these groups of patients is one of priority issues. It seems that in patients with any severe and serious dermatologic disorders, under treatment with systemic agents, if there is not any suspicion about concurrent infection or any high risk exposures, not only it is not recommend to cessation therapy but only emphasize that these drugs could prevent disease flare-up and control cytokine storm that both in a negative direction, affect the COVID-19 course (41) (42) (43) (44) (45) (46) (47) (48) .

One of the most important perspectives in the field of dermatology is to approach patients with any documented skin or mucosal disorders especially who are using Immunomodulators and now are affected by COVID-19. For consensus and more exact expert recommendations in this group of patients, we need data gathering about people who were in this situation and know more about what experience say about dermatologic disease course, COVID-19 course and manner of managing both conditions in the best possible way? So in this systematic review we focused on specific patient groups with a dermatologic disorder (usually under therapy) that concomitantly have been infected by the new corona virus and summed up their data in all aspects of underlying and infectious disease course and management.

This study is implemented according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement.

Inclusion criteria comprised all studies about patients with any documented skin or mucosal disorders especially who were using immunomoduators and now were affected by COVID-19. The exclusion criteria consisted of all publications not meeting the above contents and non-English literature.

We searched Databases of PubMed, Scopus, Google Scholar, Medscape and CEBD coronavirus dermatology resource of Nottingham University (https://www.nottingham.ac.uk/). Our key words were ( "COVID-19" ) OR ( "severe acute respiratory syndrome coronavirus 2" ) AND ( "Skin" ) OR ( "Skin Diseases" ) OR ( "Skin Manifestations" ) OR ( "Dermatology" ) OR ("Skin and Connective Tissue Diseases" ) OR ( "Eczematous" ) OR ( "Eczema" ) OR ( "eczematous dermatitis" ) OR ( "eczematous eruption" ) OR ( "eczematous skin" ) OR ( "Dermatitis, Atopic" ) OR ( "Papulosquamous" ) OR ( "Psoriasis" ) OR ( "Hidradenitis, Suppurativa" ) OR ("Alopecia" ) OR ( "Pemphigus" ) OR ( "Pemphigoid" ) OR ( "Immunobullous" ) OR ( "Skin Cancer" ) OR ( "Dermatologic Agents") OR (" Immunomodulator") OR ( " Systemic Drugs" ) OR ( "Biologics" ) OR (" Immunomodulator") OR ( "Immunospress" ) OR ( "Immunospressive" ). In the search of CEBD coronavirus dermatology resource of Nottingham University we focused on the link of Skin manifestations of coronavirus and Coronavirus and specific patient groups. We finally complete our search up to May/15/2020.

In the first screening 237 articles assigned to the inclusion and exclusion groups and then the titles and abstracts of articles were review by two expert dermatologists and acceptable articles (23) searched to find their full text and finally 9 articles (including 12 patients) selected to data entry for this systematic review (37, (49) (50) (51) (52) (53) (54) (55) (56) .

After researching, we have found nine related articles and the information of these articles are prepared as a table. Of the 12 patients reviewed in these articles, ten had psoriasis/ psoriatic arthritis and two had immunobullous disease included pemphigus and mucous membrane pemphigoid. Their underlying disease was treated with the following drugs:

 From patients with psoriasis/psoriatic arthritis, eight patients were treated with biologic agents (Guselkumab: three patients, Secukinumab: two patients, Apremilast: one patient, Adalimumab: one patient, Ustekinumab: one patient); two patients were on other immunosuppressive/Immunomodulators agents include Cyclosporine and Methotrexate.  One patient with mucous membrane pemphigoid was treated with Prednisolone, Rituximab, Mycophenolate mofetil and high dose IVIg  One patient with pemphigus was treated with Mycophenolate mofetil This article is protected by copyright. All rights reserved. 

At the time of the pandemic, many patients were diagnosed with various dermatoses treated with biological agents or immunosuppressive/ Immunomodulators (57) . Although, there is still no strong evidence of a higher risk of infection with COVID-19 in these patients, and clinicians emphasizes that the symptoms and management of disease in these patients are similar to those in the general population (26) . In addition, for many dermatoses, any mental or physical stress, such as infection or anxiety, may exacerbate the disease (61-62) . This study has evaluated nine case reports of patients with chronic dermatologic diseases treated with systemic agents. Of the 12 patients reported, the two patients did not show any symptoms despite close contact with people with confirmed cases of COVID-19; at the time of quarantine, these patients showed no signs of the disease and their treatment continued as before. Of the remaining ten patients, only one required hospitalization in the intensive care unit. Five patients were treated with conventional therapies such as hydroxychloroquine, oseltamivir, lopinavir/ritonavir, antibiotics. Other patients were treated with supportive/symptomatic therapies. At the time of the COVID-19, the biologic agents were discontinued except for one case (which was treated with Guselkumab) but the patients did not report any severe exacerbation of their underlying dermatologic disease despite treatment discontinuation. There was only one case of severe relapse of psoriasis after COVID-19, in which the patient was previously treated with cyclosporine and methotrexate.

Investigation of these articles showed that the severity of COVID-19 in patients with underlying dermatologic disease treated with biological agents was not more than in the general population. The management of these patients was in the form of discontinuation of the biological agents or immunosuppressive/ Immunomodulators and the use of routine and conventional treatments. After the symptoms have improved, treatment of the underlying dermatologic disease can be recommenced as before.

Our knowledge about managing patients with dermatologic disorders (especially chronic disorders under treatment with systemic immunomodulators) who are affected by COVID-19 in the pandemic is really scarce so for better controlling and managing both underlying dermatoses and concurrent corona virus infections, we need to sum up current relevant data that we did in this systematic review so far. We found that the severity of the disease or the need for hospitalization in these patients was not greater than in normal population. The treatment of the disease in confirmed cases with COVID-19 were similar to that of normal population, with the difference that it is better to stop the patient's previous medications until the symptoms improve. In patients who have already been treated with biological drugs, recurrence of underlying dermatologic disease was mild. After the symptoms of the disease have improved, the patient's treatment could be continued as before.

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The authors would like to thank Rasoul Akram Hospital Clinical research development Center (RCRDC) for its technical and editorial assists.

The authors contribute equally to all stages of this study. The team has reviewed the manuscript and the data, and all contributors were in full agreement.

The authors declare there is no conflict of interest in this study.

This study had no funding.
