key: cord-0690581-oyu0e3rl
authors: Azimi, Seyyede Zeinab; Firooz, Alireza; Murrell, Dedee F.; Daneshpazhooh, Maryam
title: Treatment concerns for bullous pemphigoid in the COVID‐19 pandemic era
date: 2020-07-04
journal: Dermatol Ther
DOI: 10.1111/dth.13956
sha: 0806adecd9cbd03af312c9687bcc87fe36c4f856
doc_id: 690581
cord_uid: oyu0e3rl

Bullous pemphigoid (BP) is the most common autoimmune blistering disease with subepidermal involvement, typically affecting the elderly. It has spontaneous remissions and exacerbations with significant morbidity. A novel coronavirus called severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is responsible for the new universal coronavirus disease 2019 (COVID‐19) pandemic. The pandemic made concerns, especially about immunosuppressive therapy. In this article, we reviewed the management of BP in the COVID‐19 pandemic era. The data about the best management of autoimmune bullous diseases like BP, during the outbreak of COVID‐19, is evolving and updated every day. This article is protected by copyright. All rights reserved.

The 2019 novel coronavirus , also named as severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), has caused a serious pneumonia pandemic. Advanced age, male gender, and comorbidities such as immunosuppression are the main mortality risk factors. Mostly, individuals between 30 and 80 years old are involved. A low mortality rate has been reported in healthy individuals while COVID-19 can be life-threatening due to sepsis, multi-organ failure, and acute respiratory distress syndrome (ARDS). 1 Generally, autoimmune bullous disorders (AIBDs) such as BP patients who are under immunosuppressive treatment are at increased risk of developing opportunistic infections including viral infections, and microbial pathogens which may potentially trigger the bullous diseases. Of note, the risk of death in patients with BP is increased especially due to pneumonia. 2, 3 A higher risk of infection with corticosteroids during COVID-19 restricts its administration. 4 AIBD patients on immunomodulatory treatment, especially old age in the presence of co-morbidities, may be at higher risk of poor outcomes of COVID-19. 5 However, their suppressive effects on inflammation and the presence of pulmonary inflammation and over activation of the immune system induced by COVID-19 attracted the physicians during the COVID-19 outbreak. 1, 6 Data about the administration of steroidsparing immunosuppressive drugs during COVD-19 are scarce and inconclusive. 4 Patients should consult with their dermatologist before discontinuing any medications. Current guidelines for handling immunosuppression in autoimmune disease patients at risk for contracting COVID-19 advice for outpatients with known contact, who are under quarantine and for certain patients who are experiencing symptoms of COVID-19 and are under investigation for the disease, it may be prudent to hold maintenance immunosuppression for 2 weeks following contact or travel. But autoimmune diseases patients without obvious evidence of exposure should continue their treatments. 7, 8, 9 Some authors recommend that during COVID-19 pandemic, AIBD patients treated with immunomodulating therapy, keep immunomodulatory therapy as needed because unjustified withdrawal might lead to uncontrolled activity of AIBD which results in high morbidity and mortality. 2, 3, 9 Others suggest that the basic principle of treatment, including corticosteroids and immune suppressants, such as azathioprine and mycophenolate mofetil, should be reduced to the lowest effective dose. 10 For BP patients infected with COIVID-19 on immunomodulating therapy it is recommended that confirmed cases of COVID-19 should undergo risk evaluation at first and these drugs are only discontinued in proven cases of active COVID-19 after an individual risk-benefit analysis. 3, 8, 9 The immunomodulating medications which are considered to impose the highest risks in patients with COVID-19 are azathioprine, mycophenolate mofetil/sodium, cyclophosphamide, and methotrexate, while topical corticosteroids, prednisolone ≤10 mg/d, dapsone/sulfapyridine, doxycycline/tetracycline, colchicine, and IVIG can be continued. 5, 9 The anti-malarial drugs such as hydroxychloroquine, which had been suggested for COVID-19, do not seem to be effective in BP. 11 Prednisone >10 mg/d may be reduced depending on the activity/severity of the BP, age, co-morbidities, and severity of COVID-19. It is generally not safe to cease chronic corticosteroids abruptly because of adrenal suppression. Until now, there is little information specifically concerning COVID-19 and BP, despite these patients usually being very elderly and often in care homes.

Since IVIG is safe for long-term use in all age groups 12 , it has been suggested as a potential option for COVID-19. 33 In BP patients with COVID-19 who are unresponsive to low dose corticosteroids and/or antimicrobials and dapsone, this therapeutic option can be considered. Potential side effects, particularly thromboembolism, should be considered. 4 Since IVIG is helpful as adjuvant treatment in both BP and COVID-19 and supports immunity, it is likely to be valuable in this situation. 10 General precautions for the protection of the elderly and immunosuppressed should be strictly adhered to in BP patients, including social distancing, avoiding gatherings, application of teledermatology and screening the patients for symptoms of COVID-19 as well as evaluating the psychological tolerance of patients during quarantine, especially in those with high doses of corticosteroids should be considered as supportive strategies. 14 This article is protected by copyright. All rights reserved.

While evidence of plasmapheresis effectiveness is generally anecdotal in BP and COVID-19, it could also be considered. 10 Interestingly, here in Iran most of the patients with BP continued their treatment with no complication.

Most of them had been on topical clobetasol due to their old age and accompanied co-morbidities. In new cases and in a few cases of relapse, adding/ increasing clobetasol application and/ or adding doxycycline, and as a last resort oral corticosteroids up to 0.5 mg/kg were prescribed. We discontinued methotrexate if patients were taking it.In conclusion, low doses of oral corticosteroids and potent topical corticosteroids are effective in the acute and maintenance phases in most cases of BP. Topical corticosteroid therapy is much safer than oral corticosteroid therapy for extensive disease. 15 It is better not to use high-dose corticosteroids and limit them to the lowest effective doses. In unavoidable cases, minimally effective doses of immunosuppressive drugs or IVIG might be used.

Clinical course and risk factors for mortality of adults in patients with COVID-19 in Wuhan, China: a retrospective cohort study

Pemphigoid diseases

Management of Pemphigus in COVID-19 Pandemic Era; a Review Article

Expert recommendations for the management of autoimmune bullous diseases during the COVID-19 pandemic

Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

GUIDANCE ON THE USE OF IMMUNOSUPPRESSIVE AGENTS

Thoughts on COVID-19 and autoimmune diseases

Guidance from the EADV Task Force Autoimmune Blistering Diseases during the COVID-19 pandemic

Treatment considerations for patients with pemphigus during the COVID-19 pandemic

Treatment of bullous pemphigoid with adjuvant immunoadsorption: a case series

Potential interventions for novel coronavirus in China: A systematic review

A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence

Ethical outpatient dermatology care during the coronavirus (COVID-19) pandemic

A comparison of oral and topical corticosteroids in patients with bullous pemphigoid