Herpes Zoster Reactivation in Patients on Methotrexate: An Important Consideration

Abstract,

Rheumatoid arthritis frequently necessitates treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs). Methotrexate (MTX), a commonly prescribed DMARD, has known immunosuppressive properties along with various side effects. We report a case of an adult with rheumatoid arthritis on MTX, who experienced herpes zoster reactivation due to MTX’s immunosuppressive properties. Furthermore, we emphasize the importance of Shingles vaccination in patients on MTX and thorough examination to prevent delayed diagnosis. We describe the case of a 76-year-old male with a history of rheumatoid arthritis who presented to multiple healthcare settings with constant chest pain with radiation to the left shoulder and upper back. Laboratory results and imaging ruled out potential cardiac and pulmonary etiologies of pain. On presentation to his rheumatologist, examination revealed a truncal polyphasic rash, affecting multiple dermatomes. After complete examination, the chest pain was attributed to postherpetic neuralgia secondary to herpes zoster reactivation, and treatment consisted of Gabapentin. Postherpetic neuralgia improved within two weeks, however, the rash persisted. This report presents a rare case of herpes zoster reactivation secondary to MTX immunosuppression. This case report aims to emphasize the importance of increased monitoring and thorough examination in patients treated with immunosuppressive agents and administration of Shingrix vaccine prior to initiating immunosuppressive therapy.

Keywords: Methotrexate; Herpes Zoster; Shingles; Immunosuppression

Introduction,

Rheumatoid arthritis is a common chronic inflammatory joint disease in today’s society, often necessitating treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs) [1]. The most frequently prescribed conventional synthetic DMARD is Methotrexate (MTX) whose mechanism involves inhibition of DNA synthesis via dihydrofolate reductase antagonism [2]. Notably, side effects of MTX include hepatotoxicity, pulmonary toxicity, and immunosuppression, which can place patients at a higher risk for opportunistic infections and reactivation of latent infections [3]. In this report, we describe a patient taking MTX who was misdiagnosed on multiple occasions before ultimately being diagnosed with herpes zoster reactivation due to MTX’s immunosuppressive properties.

Case Report,

Informed consent was obtained and signed from the following patient regarding the use of patient health information for the purposes of writing a case report publication.

The patient is a 76-year-old male with a history of rheumatoid arthritis who presented to a local Emergency Department (ED) with a 1-day history of constant chest pain with radiation to the left shoulder and upper back. Medical history includes coronary artery disease requiring percutaneous intervention, chronic kidney disease (stage 3), chronic obstructive pulmonary disease, hypertension, and rheumatoid arthritis on 20 mg of MTX weekly.

In the ED, his musculoskeletal and cardiopulmonary physical exam were unremarkable. His cardiac workup including cardiac enzymes, stress testing, and imaging returned within normal limits. The patient was discharged home with recommendations to follow-up with cardiology. However, upon presentation to his cardiologist, no abnormalities were found. Nine days following the initial ED presentation, the patient presented to a tertiary care hospital due to persistent pain. There, the pain was attributed to musculoskeletal causes. Given his history of rheumatoid arthritis, the patient was recommended to follow up with outpatient rheumatology.

Upon presentation to his rheumatologist’s clinic, he continued to report persistent, sharp chest pain. A thorough history and review of systems revealed that the patient had developed a new rash at approximately the same time of onset as his chest pain. A complete physical exam was performed, which was remarkable for a polyphasic rash in various stages of healing, affecting multiple dermatomes on the left side of the chest (Figure 1A). Given the patient’s history of MTX use, a diagnosis of postherpetic neuralgia secondary to herpes zoster reactivation was made. The patient was treated with Gabapentin 100 mg daily with instruction to gradually increase to 300 mg daily. Upon follow-up, the patient noted significant improvement in chest pain caused by postherpetic neuralgia, however, endorsed a persistent rash (Figure 1B).

    


    


    Figure 1: (A) Polyphasic rash at initial appointment with rheumatologist (B) Rash 2 weeks later (right).