Dermatologica Sinica

REVIEW ARTICLE
Year
: 2022  |  Volume : 40  |  Issue : 2  |  Page : 67--70

Recommendations on use of systemic treatments for immune-mediated dermatologic disorders in patients with confirmed COVID-19 infection: A rapid review


Chia-Ling Yu1, Yu-Ting Lin1, Ching-Chi Chi2,  
1 Department of Pharmacy, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
2 Department of Dermatology, Chang Gung Memorial Hospital, Linkou; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

Correspondence Address:
Prof. Ching-Chi Chi
Department of Dermatology, Chang Gung Memorial Hospital, Linkou, 5, Fuxing Street, Guishan District, Taoyuan
Taiwan

Abstract

With the rapid outbreak of the coronavirus disease 2019 (COVID-19) pandemic, considerable concerns about the safety of systemic treatments of immune-mediated dermatologic disorders has been raised by dermatologists and their patients. We aimed to perform a rapid review of latest American and European guidelines on the use of systemic treatments in patients with immune-mediated dermatologic disorders and confirmed COVID-19 infection and to provide recommendations to inform practice. Based on the current limited guidelines and evidence, systemic corticosteroids should not be abruptly discontinued and the lowest effective dose should be continued. Systemic immunosuppressants (including methotrexate, cyclosporine, azathioprine, cyclophosphamide, and leflunomide), biologics, and sulfasalazine should be withheld in patients with confirmed COVID-19 infection. Whether to continue Janus kinase inhibitors should be determined following a shared decision-making process between dermatologists and patients after considering patients' medical conditions and risk for severe COVID.



How to cite this article:
Yu CL, Lin YT, Chi CC. Recommendations on use of systemic treatments for immune-mediated dermatologic disorders in patients with confirmed COVID-19 infection: A rapid review.Dermatol Sin 2022;40:67-70


How to cite this URL:
Yu CL, Lin YT, Chi CC. Recommendations on use of systemic treatments for immune-mediated dermatologic disorders in patients with confirmed COVID-19 infection: A rapid review. Dermatol Sin [serial online] 2022 [cited 2022 Dec 3 ];40:67-70
Available from: https://www.dermsinica.org/text.asp?2022/40/2/67/349030


Full Text



 Introduction



Due to the recent outbreak of coronavirus disease 2019 (COVID-19) pandemic in Taiwan, there is growing concern about the safety of systemic treatments in dermatology patients with confirmed COVID-19 infection.[1] Immunomodulators are usually indicated for the treatment of immune-mediated dermatologic disorders, for example, psoriasis, atopic dermatitis, and autoimmune bullous dermatoses. However, immunomodulators may suppress patients' immunity and theoretically lead to worse outcomes in patients with confirmed COVID-19 infection. We aimed to perform a rapid review of latest American and European guidelines on the use of systemic treatments in patients with immune-mediated dermatologic disorders and confirmed COVID-19 infection and to provide relevant evidence to inform practice. We extracted relevant recommendations from guidelines provided by the American Academy of Dermatology (AAD),[2] the American College of Rheumatology (ACR),[3] the UK National Institute for Health and Care Excellence (NICE),[4],[5] the European Alliance of Associations for Rheumatology (EULAR),[6] the European Academy of Dermatology and Venereology (EADV), and Skin Inflammation and Psoriasis International Network (SPIN).[7]

 Recommendations



A summary of guidelines on the use of systemic treatments for immune-mediated dermatologic disorders in patients with confirmed COVID-19 infection is shown in [Table 1]. We use a traffic light system to denote the recommendations, with green light indicating continuation of treatments, red light indicating stopping or withholding of treatments, and yellow light indicating modification of dosage.{Table 1}

Systemic corticosteroids

According to the guidelines of the AAD, ACR, and NICE, abrupt withdrawal of systemic corticosteroids among patients with confirmed COVID-19 infection should be avoided and the lowest effective dose to control the immune-mediated dermatologic disorders should be continued.[2],[3],[4],[5] Abrupt withdrawal of corticosteroids may result in acute flare of the immune-mediated dermatologic disorders, which can in turn lead to adverse outcome of COVID-19.[6] For patients receiving long-term systemic corticosteroids, corticosteroid supplement may also be needed in stressful conditions such as COVID-19 infection.[6]

The RECOVERY trial showed that in patients hospitalized with COVID-19, dexamethasone 6 mg (equivalent to 40 mg of prednisone) once daily for 3–10 days was associated with reduced 28-day mortality.[8] However, there is currently a lack of safety and efficacy data on the use of corticosteroids in outpatients with COVID-19. The US National Institute of Health recommends against the use of dexamethasone or other systemic corticosteroids to treat outpatients with mild-to-moderate COVID-19 who do not require hospitalization or supplemental oxygen.[9] Moreover, physicians should be aware that COVID-19 patients taking prednisolone may not develop fever.[4],[5] The mask of fever may delay the diagnosis of severe COVID-19 infection or inflammation of the preexisting immune-mediated dermatologic disorders.

Systemic immunosuppressants (including methotrexate, cyclosporine, azathioprine, cyclophosphamide, and leflunomide) and biologics

The AAD, ACR, NICE, EULAR, EADV, and SPIN are unanimous in their recommendations that any biologics and oral systemic immunosuppressants (e.g., methotrexate, cyclosporine azathioprine, and leflunomide) treatment should be withheld in patients with active COVID-19 infection.[10] However, the risk of biologics with dupilumab, an anti-IL-4/13 biologic which theoretically, should not impair the immunity against COVID-19. Current limited data suggest that dupilumab does not appear to worsen COVID-19 outcomes.[11]

Sulfasalazine

The AAD and ACR guidelines recommend discontinuation of sulfasalazine,[2],[3] while the NICE and EULAR guidelines recommend continuation of sulfasalazine.[4],[5],[6] Nevertheless, sulfasalazine has recently been associated with three-fold increased odds for mortality in patients with COVID-19.[12],[13] Sulfasalazine inhibits type I interferon which plays an important in immunity against viruses and thus may increase the risk for death due to COVID-19 infection.[14] Due to the recently raised safety concerns, we suggest to discontinue sulfasalazine in patients with confirmed COVID-19 infection.

Small molecule inhibitors

The AAD, ACR, and NICE guidelines recommend that in COVID-19 patients, Janus kinase (JAK) inhibitors should be temporarily stopped, pending 2 weeks of symptom-free observation.[2],[3],[4] However, JAK inhibitors have been shown to reduce mortality in hospitalized COVID-19 patients.[15] Baricitinib has obtained emergency use authorization by the US and Taiwan Food and Drugs Administration for use in hospitalized patients with COVID-19. We encourage dermatologists and patients to actively engage in shared decision-making about the use of JAK inhibitors. Decisions should be made considering the following factors: severity of COVID-19, individual patients' risk for severe COVID-19 (for example, patients' age and comorbidities), and severity of immune-mediated dermatologic disorders.

The NICE guidelines recommend discontinuation of apremilast in patients with confirmed COVID-19 infection,[4] while the other organizations do not provide relevant recommendations.

Dapsone

The NICE guidelines recommend continuation of dapsone in patients with confirmed COVID-19 infection.[5] The other organizations do not provide relevant guidelines.

Hydroxychloroquine

The AAD, ACR, EADV, and SPIN guidelines recommends discontinuation of hydroxychloroquine among patients with confirmed COVID-19 infection, but the NICE guidelines recommend that hydroxychloroquine may be continued.[4],[5] The half-life of hydroxychloroquine is 40–50 days;[16] therefore, short-term withdrawal of hydroxychloroquine may not carry a risk of flares of preexisting immune-mediated dermatologic disorders.

Reinitiating systemic treatments following coronavirus disease 2019infection

The ACR recommends that for patients with uncomplicated COVID-19 infections (characterized by mild or no pneumonia), consideration may be given to restarting systemic treatments within 7–14 days following resolution of symptoms. For patients who have a positive PCR test result for SARS-CoV-2 but are (and remain) asymptomatic, consideration may be given to restarting treatments 10–17 days after the PCR result is reported as positive.[3] The EULAR follows the ACR guidelines, while the NICE does not provide relevant recommendations.

Limitations

Our study illustrates several limitations of the currently available guidelines. First, most of the included guidelines were developed by expert consensus statements without a systematic review of available evidence. Second, though the knowledge about COVID-19 evolves rapidly, the published date of the most available guidelines was >1 year ago. For example, the release date of the AAD guidance was October 15, 2020,[2] and there were no more new data or information updated. Third, the guidelines for the use of systemic treatments during COVID-19 infection from the AAD, ACR, NICE, EULAR, EADV, and SPIN have different targeted diseases.[2],[3],[4],[5],[6],[7] For example, the recommendations from the EADV and SPIN focus on psoriasis. The ACR and EULAR guidelines involve rheumatic and musculoskeletal diseases but do not provide specific suggestions for various diseases.[3],[6] In addition, the other guidelines do not provide specific recommendations for different immune-mediated dermatologic disorders.

 Conclusions



For patients with confirmed COVID-19 infection, systemic corticosteroids should not be abruptly discontinued, but the lowest effective dose should be continued. Systemic immunosuppressants (including methotrexate, cyclosporine, azathioprine, cyclophosphamide, and leflunomide), biologics, and sulfasalazine should be withheld in patients with confirmed COVID-19 infection. The decision of whether to continue JAK inhibitors should be made following a shared decision-making process between dermatologists and patients after considering patients' medical conditions and risk for severe COVID.

Financial support and sponsorship

Nil.

Conflicts of interest

Prof. Ching-Chi Chi, the Editor-in-Chief of Dermatologica Sinica, had no role in the peer review process or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.

References

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