From the Guidelines
Methotrexate is a risk factor for Cytomegalovirus (CMV) colitis, as evidenced by a recent retrospective case-control study that found immunosuppressive agents such as azathioprine or methotrexate to be significantly associated with CMV disease [OR: 1.95; 95% CI: 1.05–3.62] 1. The use of methotrexate as an immunosuppressive medication can compromise the immune system's ability to control latent CMV infection, thereby increasing the risk of CMV colitis. Key factors that contribute to this risk include:
- Higher doses of methotrexate
- Longer duration of therapy
- Combination with other immunosuppressive agents such as corticosteroids or biologics The mechanism by which methotrexate increases the risk of CMV colitis involves its inhibition of lymphocyte proliferation and function, particularly affecting T-cell immunity which is crucial for controlling viral infections like CMV 1. Patients on methotrexate therapy who develop persistent diarrhea, abdominal pain, or bloody stools should be evaluated for CMV colitis, especially if symptoms don't respond to conventional treatment. This is particularly important in patients with additional immunocompromising conditions or those on combination immunosuppressive therapy. Some key points to consider in the management of patients on methotrexate who are at risk of CMV colitis include:
- Regular monitoring for symptoms of CMV colitis
- Maintaining the lowest effective dose of methotrexate to minimize immunosuppression
- Being aware of the increased risk of CMV colitis in patients with refractory disease, steroid refractoriness, or those on combination immunosuppressive therapy 1.
From the Research
Methotrexate as a Risk Factor for Cytomegalovirus Colitis
- The use of immunosuppressive medications, including methotrexate (MTX), is considered a risk factor for Cytomegalovirus (CMV) infection in patients with ulcerative colitis (UC) 2.
- A study found that CMV infection is rare in new onset UC, suggesting that the use of immunosuppressive medications is an important risk factor for CMV infection in UC 2.
- Another study reported a case of CMV colitis in a patient with severe treatment-refractory UC, highlighting the importance of evaluating CMV colitis in patients with worsening symptoms despite increased immunosuppressive therapy 3.
- Risk factors for CMV colitis include severe colitis, treatment with immunosuppressive medications, particularly corticosteroids and immunomodulators, and the use of multiple lines of immunosuppressive therapy 3, 4.
- A retrospective study found that glucocorticoids, calcineurin inhibitors, and >2 concurrent lines of treatment with immunosuppressive drugs were risk factors for CMV colitis in patients with IBD 4.
- Methotrexate is an immunosuppressant drug that has been used to treat various inflammatory disorders, including Crohn's disease, but its use in ulcerative colitis is not well established 5.
- A systematic review found that there is no evidence supporting the use of methotrexate for maintenance of remission in ulcerative colitis, and more studies are needed to determine its efficacy and safety in this context 5.
Diagnostic Approaches for CMV Colitis
- The diagnosis of CMV colitis can be made using various methods, including histopathological examination, immunohistochemical staining, and tissue polymerase chain reaction (PCR) 6, 4.
- A high index of suspicion is needed to diagnose CMV colitis, particularly in patients with severe active UC or those who are immunocompromised 2, 6.
- The sensitivity and specificity of different diagnostic methods for CMV colitis vary, and the choice of method depends on the clinical context and the availability of resources 6, 4.