What is the cause of a rash on both hands in a patient taking methotrexate (MTX) for 2 days?

Methotrexate-Induced Cutaneous Toxicity Requiring Immediate Evaluation

This rash on both hands after 2 days of methotrexate is most likely methotrexate-induced cutaneous toxicity, which can signal life-threatening pancytopenia and requires immediate discontinuation of the drug and urgent laboratory evaluation.

Immediate Actions Required

Stop methotrexate immediately and obtain urgent complete blood count with differential to assess for pancytopenia, as cutaneous ulceration may indicate bone marrow suppression 1, 2.

Critical Laboratory Assessment

• Check CBC with differential urgently - methotrexate-induced pancytopenia can occur after even a single dose and typically manifests early in treatment (first 4-6 weeks) 3, 1
• Assess renal function (creatinine, BUN) as renal impairment increases methotrexate toxicity risk 1
• Check liver function tests, as hepatotoxicity commonly occurs with methotrexate 1

Understanding the Clinical Presentation

Methotrexate-Induced Cutaneous Reactions

Severe dermatologic reactions can occur within days of methotrexate administration, including toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, and erythema multiforme 1. These reactions have been documented after single or multiple doses at any dosage level in both neoplastic and non-neoplastic diseases 1.

The Critical Association with Pancytopenia

Methotrexate-induced cutaneous ulceration strongly suggests concurrent life-threatening pancytopenia 2. In documented cases, patients presenting with painful ulcerative nodules on hands were found to be pancytopenic, and ulcers resolved within weeks of methotrexate discontinuation 2, 4.

Management Algorithm

Step 1: Discontinue Methotrexate

• Immediately stop methotrexate - do not wait for laboratory results 2, 4
• Consider leucovorin (folinic acid) rescue if severe toxicity is suspected 3

Step 2: Assess for Bone Marrow Suppression

• Obtain urgent CBC with differential 3, 1
• If pancytopenia is present, consider filgrastim for toxic bone marrow suppression 3
• Monitor for signs of infection given immunosuppression risk 1

Step 3: Evaluate for Other Toxicities

• Check for concurrent infections - methotrexate should be used with extreme caution in active infection and is usually contraindicated in immunodeficiency states 1
• Assess for pulmonary symptoms (dry cough, dyspnea) as methotrexate can cause pneumonitis 1
• Monitor renal function closely as decreased function increases methotrexate levels and toxicity 5

Step 4: Skin Biopsy Consideration

• Biopsy ulcerated areas to exclude vasculitis and confirm methotrexate-induced changes 4
• Histopathology typically shows no vasculitis in methotrexate-induced ulceration 4

Risk Factors Present in This Case

The extremely short duration (2 days) is concerning because:

• Severe reactions can occur during initial exposure to methotrexate, contrary to older literature suggesting prior exposure is required 6
• Anaphylactoid reactions have been documented within 10-30 minutes of first methotrexate administration 6
• Cutaneous reactions can appear within days of oral, intramuscular, intravenous, or intrathecal administration 1

Critical Pitfalls to Avoid

Do Not Rechallenge

Never restart methotrexate if severe cutaneous reactions occurred - recovery has been reported with discontinuation, but rechallenge can cause recurrent life-threatening symptoms 1, 6.

Do Not Delay Laboratory Evaluation

Cutaneous ulceration may be the first visible sign of pancytopenia before other symptoms manifest 2, 4. Waiting for symptoms to worsen before checking labs can be fatal.

Do Not Assume Infection Alone

While methotrexate increases infection risk 7, 5, the bilateral hand distribution and acute onset after drug initiation strongly suggests drug toxicity rather than primary infection 2, 4.

Expected Clinical Course

With methotrexate discontinuation:

• Cutaneous ulcers typically heal within 2-4 weeks 2, 4
• Bone marrow suppression is reversible with cessation 3
• Supportive rehabilitative skin care accelerates healing 4

Long-Term Considerations

This patient should never receive methotrexate again given the severe early reaction 1, 6. Alternative immunosuppressive agents should be considered for the underlying condition requiring treatment 8.