Methotrexate exposure and risk of strongyloidiasis

Abstract

Objective Rheumatologic disease patients receiving immunomodulating drugs such as methotrexate (MTX) have increased infection rates. Strongyloides, a global endemic intestinal parasite, can cause significant or fatal disease in immunocompromised patients. The risk of serious Strongyloides infection with MTX dosed for rheumatologic disease is unknown. Methods We performed a systematic literature review searching EMBASE, Medline and Web of Science databases. All studies reporting humans exposed to MTX and tested for Strongyloides were reviewed. Exclusion criteria were bone marrow transplantation, intrathecal route and MTX exposure completed >1 year prior to clinically apparent Strongyloides disease. Results After excluding duplicates, 294 articles were reviewed. Of these, 29 cases were described in 27 papers. Twenty cases (69%) had an underlying rheumatologic or dermatologic disease, the rest had a haematologic disease. Hyperinfection or dissemination was found in 59% of cases (52% low‐dose MTX; 75% high‐dose MTX). Death occurred in 34% of cases (19% low‐dose MTX; 75% high‐dose MTX, P < 0.01). All eight patients on high‐dose MTX received other immunosuppressants. Corticosteroids were taken in 18/21 patients on low‐dose MTX. One of the three patients on MTX monotherapy had hyperinfection syndrome. None had disseminated Strongyloides. Conclusions Serious Strongyloides infection can occur with low‐dose MTX particularly when given with other immunosuppression. Global travel and greater awareness of rheumatologic conditions in low‐ to middle‐income countries will increase the exposure of individuals prescribed MTX (with or without corticosteroids) to Strongyloides. Strongyloides screening and treatment should be considered for individuals receiving low‐dose MTX therapy, particularly if combined with additional immunosuppression.

Tratamento Farmacológico Da Estrongiloidíase Em Humanos: Uma Revisão Integrativa

“…Para pacientes que iniciarão terapia com metotrexato, o tratamento profilático com ivermectina é ponderado, considerando os riscos imunossupressores. Apesar da eficácia comprovada da ivermectina em dose única, ainda não há recomendação preventiva pela Organização Mundial da Saúde (OMS), apesar de evidências de redução consistente da prevalência de Strongyloides (RICHARDS et al, 2019).…”

Strongyloides hyperinfection syndrome precipitated by immunosuppressive therapy for rheumatoid arthritis and COVID-19 pneumonia

“…Courses of corticosteroids as short as six days and with a dose of oral prednisone as low as 20 mg per day have been shown to result in SHS [ 6 ]. Other immunomodulating medications such as methotrexate have also demonstrated association with accelerating Strongyloides’ autoinfection cycle [ 12 ]. In our case, the pre-existing immunosuppression for rheumatoid arthritis with methotrexate, hydroxychloroquine, and sulfasalazine likely contributed to his symptoms leading up to presentation and primed his condition for the rapid progression of larvae dissemination after receiving corticosteroids.…”

Tratamento farmacológico da estrongiloidíase em humanos: uma revisão integrativa

“…Nesse sentido, o mesmo raciocínio pode ser aplicado para pacientes que irão começar terapia com metotrexato, usado em diversas doenças reumatológicas e dermatológicas, por estar associado a maior risco de hiperinfecção por seus efeitos imunossupressores, mesmo em baixas doses. Então, na ausência de contraindicações (gravidez ou lactação), é razoável considerar o tratamento profilático com ivermectina se a triagem não for viável 27 .…”