Methotrexate-Induced Neutropenia

Clinical Presentation

The American Academy of Dermatology identifies mucocutaneous effects such as stomatitis and mouth ulcers as very common early toxicities of methotrexate 1
Pancytopenia can occur after even a single dose of methotrexate and can develop at any time during treatment, typically in patients with at least one risk factor 1
Concomitant SLE would not explain the acute presentation of fever with mouth ulcers in a patient on methotrexate, while the temporal relationship with MTX therapy and the fever pattern suggest drug toxicity 2
Viral infection is possible but less likely given the specific constellation of symptoms, while the combination of oral mucositis with fever is more characteristic of bone marrow suppression than simple viral infection 1, 2

Obtain urgent complete blood count with differential to confirm neutropenia, which is the critical first step 1
Discontinue methotrexate immediately if neutropenia is confirmed, as recommended by the British Journal of Dermatology and Praxis Medical Insights 1, 3
Initiate leucovorin (folinic acid) rescue therapy if severe bone marrow suppression is present, with an initial dose of up to 100 mg/m² every 6 hours until hematological abnormalities normalize and mucosal ulceration heals 3
Consider filgrastim (G-CSF) at 5 mcg/kg daily subcutaneously for toxic bone marrow suppression to accelerate myeloid recovery, as recommended by the British Journal of Dermatology 3

Renal insufficiency is a major modifiable risk factor for MTX-induced myelosuppression 1
Drug interactions, particularly NSAIDs, trimethoprim-sulfamethoxazole, and penicillins, increase the risk of MTX-induced myelosuppression 1
Dosing errors, such as daily instead of weekly administration, can lead to MTX-induced myelosuppression 1
Hypoalbuminemia increases free drug levels, which can contribute to MTX-induced myelosuppression 1
Folic acid deficiency or non-supplementation can increase the risk of MTX-induced myelosuppression 1