A Possible Type IV Hypersensitivity Reaction to Older Antiepileptic Drugs During and After Recovery from COVID-19 Infection

To the Editor

Nearly two years after the onset of the coronavirus disease 2019 (COVID-19) pandemic, healthcare workers face new and unexpected complications. Although accelerating the vaccination process in recent months has reduced the incidence and mortality of the COVID-19 infection, the general population (particularly vulnerable groups) remains at risk of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Over the last two months, Iran has encountered the fifth wave of the COVID-19 pandemic, i. e., the B.1.617.2 (Delta) variant of the SARS-CoV-2, with faster infectiousness and higher severity and mortality among hospitalized patients [1]. Although fever, cough, and expectoration are the most common clinical features of COVID-19, recent studies have indicated an increasing number of skin manifestation reports in the disease. Besides, there is growing evidence that underlying SARS-CoV-2 infection may increase the risk of adverse drug reactions [2]. However, the enduring concern in our medical centers in recent days is a raised incidence of Stevens-Johnson syndrome (SJS) in recovered COVID-19 patients following monotherapy with older antiepileptic drugs (0.004 vs. 0.0008% – i. e., 5 times higher than the pre-COVID-19 period) [3]. It is worth noting that these patients did not have any history of SJS/toxic epidermal necrolysis (TEN) or additional etiopathogenic factors, including infections, genetic factors (particularly HLA-B*1502 allele), and malignancy. Furthermore, for many years before developing the COVID-19 and recovering from it, they had been treated with the above drugs without showing any cutaneous hypersensitivity reactions. These observational findings raise two important questions: (i) Could a history of the COVID-19 infection be a potential risk factor for type IV hypersensitivity reactions to older antiepileptic drugs? (ii) If so, what are its mechanisms of action?

Publication History

Received: 29 September 2021
Received: 16 October 2021

Accepted: 25 October 2021

Article published online:
10 November 2021

• References

• 1 Lee JK. How to deal with the Delta variant this fall. Osong Public Health Res Perspect 2021; 12: 201-202
• 2 Conforti C, Dianzani C, Agozzino M. et al. Cutaneous manifestations in confirmed COVID-19 patients: A systematic review. Biology 2020; 9: 449
• 3 Lin CC, Chen CB, Wang CW. et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: Risk factors, causality assessment and potential prevention strategies. Expert Rev Clin Immunol 2020; 16: 373-387
• 4 Imatoh T, Saito Y. Associations between Stevens–Johnson syndrome and infection: Overview of pharmacoepidemiological studies. Front Med 2021; 8: 644871
• 5 Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect 2020; 53: 368-370
• 6 Charlton OA, Harris V, Phan K. et al. Toxic epidermal necrolysis and Steven–Johnson syndrome: A comprehensive review. Adv Wound Care 2020; 9: 426-439
• 7 Davoodi L, Jafarpour H, Kazeminejad A. et al. Hydroxychloroquine-induced Stevens–Johnson syndrome in COVID-19: a rare case report. Oxf Med Case Reports 2020; 2020: omaa042