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Corticosteroids (CS) describe a group of versatile pharmacological agents, as 1.2 percent of the adult US population received an oral CS during the period from 1999-2008.1 The short- and long-term effects of systemic CS (SCS) have been established in almost every organ system. Dr. Anthony Fauci, now NIAID director and lead member of the White House Coronavirus Task Force, detailed CS’s immunologic mechanisms and implications in 1976. CSs provide therapeutic benefit in many inflammatory and immune-mediated conditions, but also result in increased risk of infection. A 1989 meta-analysis of 71 controlled clinical trials found a significantly increased infectious complication rate in patients receiving SCS across multiple medical specialties. The authors provided two additional takeaways. First, a qualitative deficiency exists in the reporting of infectious complications; in the meta-analysis less than eight percent of trials reported infectious etiology. Second, underlying disease influences infection risk. When stratified by underlying disease, the relative risk of infectious complications was highest in those receiving SCS for neurologic diseases.

The Bottom Line

Amid the ongoing COVID-19 pandemic, there is concern for increased risk of viral infection among individuals on immunosuppressive or immunomodulatory therapy. The theoretical risk of a patient on long-term systemic corticosteroid therapy for chronic inflammatory cutaneous disease has not been established. In the absence of high-risk comorbidities identified by the CDC, there is no adequate evidence suggesting that dermatologic patients on long-term systemic corticosteroids are at an increased risk of COVID-19 respiratory viral infection.

To date, the FDA has approved remdesivir and issued early-use authorization for bamlanivimab for COVID-19 treatment. SCS’s role in treatment is under active investigation. Although found to delay viral clearance during previous novel coronavirus outbreaks, low-dose CS therapy may not delay SARS-CoV-2 clearance, initial data suggests.2 Further, there is preliminary evidence of dexamethasone’s benefit in a subset of infected patients.3 While SCS as a therapeutic option is being studied, little is known regarding risk of COVID-19 infection in dermatologic patients on long-term SCS. In light of this, we consulted the literature for published safety data to assess infection risk in patients receiving SCS for chronic inflammatory skin diseases.

One randomized clinical trial (RCT) investigating efficacy of prednisolone versus cyclosporine for atopic dermatitis (AD) reported no infections among the prednisolone group (n=21) and four common colds in the cyclosporine group (n=17).4 (Table 1) Despite this, authors ultimately argued against prednisolone use in AD due to high rebound rates following discontinuation after short-term therapy. Another RCT investigating oral CS vs. methotrexate for generalized lichen planus (LP) reported no remarkable adverse events with either agent.5 (Table 1) Methotrexate was not found to be significantly more efficacious over oral CS, however authors concluded methotrexate is a “good steroid-sparing alternative” for LP. Two limitations of these RCTs include small sample size and short duration of SCS therapy. Therefore, we are cautious to suggest generalizability to dermatologic patients receiving long-term SCS.

Overall, there is a paucity of primary safety data for long-term SCS use in inflammatory cutaneous disease. There are multiple explanations for this, such as RCTs being designed to primarily evaluate efficacy rather than safety, a shift in focus to steroid-sparing agents for chronic inflammatory conditions, due to the multiple adverse effects seen with CSs, and the advent of immunomodulators/biologics. In the absence of high-risk comorbidities identified by the CDC, there is no adequate evidence suggesting that dermatologic patients on long-term SCS are at an increased risk of COVID-19 respiratory viral infection. Per AAD recommendations, discontinuation of systemic immunosuppressants may be warranted in COVID-19-infected patients upon an individual case basis.

To learn more about this topic, consider attending the 3rd Annual San Diego Dermatology Symposium® on March 11-13, 2022 at the Hilton San Diego Bayfront or the 2nd Annual Dermatology Refresher Symposium™ on April 8-10, 2022 at the Grand Hyatt San Antonio River Walk.

1. Overman RA, Yeh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res (Hoboken). 2013 Feb;65(2):294-8. doi: 10.1002/acr.21796. PMID: 22807233.

2. Fang X, Mei Q, Yang T, Li L, Wang Y, Tong F, Geng S, Pan A. Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19. J Infect. 2020 Jul;81(1):147-178. doi: 10.1016/j.jinf.2020.03.039. Epub 2020 Apr 11. PMID: 32283153; PMCID: PMC7151466.

3. RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med. 2020 Jul 17:NEJMoa2021436. doi: 10.1056/NEJMoa2021436. Epub ahead of print. PMID: 32678530; PMCID: PMC7383595.

4. Schmitt J, Schäkel K, Fölster-Holst R, Bauer A, Oertel R, Augustin M, Aberer W, Luger T, Meurer M. Prednisolone vs. ciclosporin for severe adult eczema. An investigator-initiated double-blind placebo-controlled multicentre trial. Br J Dermatol. 2010 Mar;162(3):661-8. doi: 10.1111/j.1365-2133.2009.09561.x. Epub 2009 Oct 26. PMID: 19863501.

5. Bakhtiar R, Noor SM, Paracha MM. Effectiveness of Oral Methotrexate Therapy versus Systemic Corticosteroid Therapy in Treatment of Generalised Lichen Planus. J Coll Physicians Surg Pak. 2018 Jul;28(7):505-508. doi: 10.29271/jcpsp.2018.07.505. PMID: 29950252.

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