Two Consecutive Days of Low-Dose Methotrexate Toxicity: A Diagnostic Challenge

Area of Science:

• Pharmacology
• Immunology
• Toxicology

Background:

• Methotrexate (MTX) is a cornerstone immunosuppressive drug for rheumatological conditions.
• Its efficacy relies on inhibiting the folic acid cycle, but this mechanism carries dose-dependent toxicity risks.
• Patients with rheumatoid arthritis (RA) may require MTX therapy, necessitating careful monitoring.

Observation:

• A 54-year-old female with RA, previously on MTX, restarted it without folic acid after treatment gaps.
• She developed severe oral ulcers, fatigue, and pancytopenia (low WBC, hemoglobin, platelets).
• Symptoms initially suggested Stevens-Johnson Syndrome (SJS), but the absence of rash favored MTX toxicity.

Findings:

• The patient exhibited pancytopenia, a critical indicator of MTX toxicity.
• Despite a low MTX dose, her reaction suggested a rare idiosyncratic response rather than standard dose-dependent effects.
• Leucovorin rescue and filgrastim administration led to significant clinical improvement.

Implications:

• This case underscores the diagnostic challenge distinguishing MTX toxicity from SJS based on mucosal lesions alone.
• It highlights the critical need for folic acid supplementation with MTX to mitigate toxicity.
• Vigilance for rare, severe idiosyncratic reactions to MTX is essential, even at lower doses.