Updated international expert recommendations for the management of autoimmune bullous diseases during the COVID‐19 pandemic

Dear Editor,

The SARS‐CoV‐2 pandemic has worsened since the publication of our initial recommendations for the management of autoimmune bullous diseases (AIBDs) during the COVID‐19 outbreak in April 2020. ¹ Based on the rapidly emerging increase in knowledge, this consensus of an expanded panel of international AIBD experts proposes updated recommendations to promote the optimal care of AIBD patients during the pandemic. The updated scientifically based guidance specifically pertains to the following questions:

What do we recommend for AIBD patients considering the effects of immunomodulating therapy on SARS‐CoV‐2 infection?

Patients with AIBDs treated with immunosuppressive therapies are generally prone to develop opportunistic infections, ² , ³ which raised concerns that they could be more susceptible to SARS‐CoV‐2 infection and/or have worse COVID‐19 outcomes. Nevertheless, patients with AIBDs receiving immunomodulating therapies do not appear to have higher rates of manifest SARS‐CoV‐2 infection or more severe COVID‐19 than the general population according to a systematic review of 732 AIBD patients on various immunomodulating treatments including rituximab. ⁴ While overall 9.5% of them had COVID‐19 symptoms, 0.8% showed severe symptoms requiring hospitalization and 0.4% died of COVID‐19, with the latter being elderly people and/or having comorbidities. ⁴ However, since it has been also reported that patients with AIBDs or rheumatic diseases diagnosed with and dying of COVID‐19 were more likely to be receiving rituximab treatment and that each passing month from the last rituximab dose decreased the risk of getting COVID‐19 and related hospitalization, ⁵ , ⁶ , ⁷ we currently do not recommend the use of rituximab as maintenance therapy to prevent relapses. This particularly applies to individuals who have not received a SARS‐CoV‐2 vaccine (see below). Therefore, while the decision to initiate B‐cell depletion therapy remains to be made on a case‐by‐case basis, delays or obstructions in other important immunomodulatory treatments should be avoided during the pandemic, supporting our initial advice. Temporary changes in some immunosuppressive medications are still recommended in patients who have active COVID‐19, as detailed in our previously suggested guidelines. ¹

What should patients with AIBDs do to protect themselves from SARS‐CoV‐2 infection?

Patients should continuously follow generally recommended measures to prevent SARS‐CoV‐2 infection (www.who.int, www.cdc.gov) and preferentially be managed with telemedicine instead of in‐person visits where appropriate. The major advance in protection from COVID‐19 is the recent advent of mRNA vaccines [from Pfizer‐BioNTech and Moderna, authorized by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA)] and adenoviral vector vaccines (from AstraZeneca and Johnson & Johnson, authorized by EMA and/or FDA), which induce an immune response to the SARS‐CoV‐2 spike protein, while additional vaccines are pending authorization or undergoing testing (www.who.int, www.cdc.gov). Therefore, it is recommended that every AIBD patient without contraindications to vaccination is immunized with one of the authorized vaccines to prevent COVID‐19. Since the effect of AIBD treatment on the efficacy of COVID‐19 vaccines is widely unknown, it is preferred to vaccinate patients while in remission or before planned immunosuppression, if feasible. In the case of rituximab, it is suggested to complete the entire vaccination series ≥4 weeks prior to the initiation of infusions or 12–20 weeks after completion of a rituximab cycle, ⁸ but the optimal time points are not clearly defined. Although vaccination is expected to be most effective when immunosuppression is low, we do not advise deliberately decreasing the patients’ immunomodulatory medications before or during the vaccination period because of the risk of disease exacerbation.

Finally, it is worth mentioning that the European Academy of Dermatology and Venereology task force has initiated a registry for AIBD patients with confirmed COVID‐19 (https://recovab.umcg.nl). This online registry, which is open to physicians worldwide, will help determine how the SARS‐CoV‐2 infection impacts patients with AIBDs and provide future recommendations.

Conflicts of interest

Dr. Schmidt reports grants and personal fees from UCB, grants and personal fees from Biotest, grants from Incyte, grants from Euroimmun, personal fees from Novartis, grants and personal fees from ArgenX, personal fees from Astra Zeneca, grants and personal fees from Fresenius Medical Care, grants from Dompe, grants from Synthon, grants from Admirx and personal fees from Thermo Fisher, outside the submitted work; Dr. Amagai reports grants from Ono Pharmaceutical Company, grants from MBL and grants from RegCell, outside the submitted work; Dr. Fairley reports grants from National Institutes of Health and other from AstraZeneca, outside the submitted work; Dr. Murrell has served as a Principal Investigator and Advisor for trials with Principia Biopharma, Roche and Sanofi; Dr. Payne reports grants, personal fees and non‐financial support from Cabaletta Bio and personal fees from Villaris Therapeutics, outside the submitted work; in addition, Dr. Payne has a patent Compositions and methods of chimeric autoantibody receptor T cells with royalties paid from Cabaletta Bio, a patent Compositions and methods for selective protein expression with royalties paid from Novartis, and a patent Method of redirecting T cells to treat HIV infection with royalties paid from Tmunity; Dr. Zillikens reports personal fees from UCB, Almirall, ArGEN‐x, grants from Biotest, Euroimmun, Fresenius, personal fees from Biotest, Fresenius, Miltenyi, Roche, Biogen, Abbvie, UCB, Janssen, Novartis, outside the submitted work; Mr. Yale and Drs. Kasperkiewicz, Joly and Woodley have nothing to disclose.