Methotrexate-induced mucocutaneous toxicity
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Synopsis

Mucocutaneous toxicity in the form of necrosis, erosions, and ulcers can occur in patients taking low-dose or high-dose methotrexate (MTX). A rarer form of skin toxicity is that of methotrexate-induced skin necrosis (MEN). This simulates Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) and may also be accompanied by mucosal ulceration. MTX is commonly prescribed for inflammatory or autoimmune disorders like psoriasis or rheumatoid arthritis, and it is also used as a chemotherapeutic agent.
Some risk factors for developing mucocutaneous toxicity include age older than 55 years; renal impairment; folate deficiency; low serum albumin; an alteration in MTX dose, such as taking a higher dose of the medication; restarting MTX after a hiatus; or initiation of a high dose of MTX without concomitant folic acid. In a case series of patients with MEN, many patients had more than one risk factor, including older age, renal impairment, and initiation of high-dose MTX without folic acid. Additionally, the likelihood of developing skin erosions due to MTX therapy has been shown to increase with concomitant NSAID, aspirin, trimethoprim / sulfamethoxazole, allopurinol, and proton pump inhibitor use.
The appearance of skin toxicity may indicate the impending onset of life-threatening pancytopenia and organ failure. Drug cessation typically results in rapid healing and recovery; however, a few instances of MTX toxic skin eruptions have ended fatally.
Some risk factors for developing mucocutaneous toxicity include age older than 55 years; renal impairment; folate deficiency; low serum albumin; an alteration in MTX dose, such as taking a higher dose of the medication; restarting MTX after a hiatus; or initiation of a high dose of MTX without concomitant folic acid. In a case series of patients with MEN, many patients had more than one risk factor, including older age, renal impairment, and initiation of high-dose MTX without folic acid. Additionally, the likelihood of developing skin erosions due to MTX therapy has been shown to increase with concomitant NSAID, aspirin, trimethoprim / sulfamethoxazole, allopurinol, and proton pump inhibitor use.
The appearance of skin toxicity may indicate the impending onset of life-threatening pancytopenia and organ failure. Drug cessation typically results in rapid healing and recovery; however, a few instances of MTX toxic skin eruptions have ended fatally.
Codes
ICD10CM:
L27.0 – Generalized skin eruption due to drugs and medicaments taken internally
SNOMEDCT:
290680001 – Methotrexate poisoning
95346009 – Mucocutaneous ulcer
L27.0 – Generalized skin eruption due to drugs and medicaments taken internally
SNOMEDCT:
290680001 – Methotrexate poisoning
95346009 – Mucocutaneous ulcer
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Differential Diagnosis & Pitfalls
- Pemphigus vulgaris
- Paraneoplastic pemphigus
- Bullous pemphigoid
- SJS / TEN
- Venous (stasis) ulcers – Usually confined to the lower extremities with deep ulcerations.
- Aphthous ulcers
- Erosive lichen planus
- Oral manifestations of an autoimmune blistering disease
- SJS / TEN
- Severe systemic lupus erythematosus may present with full thickness skin necrosis
- Acute graft-versus-host disease
- Staphylococcal scalded skin syndrome
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
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Last Reviewed:10/10/2019
Last Updated:11/19/2019
Last Updated:11/19/2019