This article is more than 5 years old. Information may no longer be current.

Factors of methotrexate-induced epidermal necrosis identified

Researchers identified early signs and risk factors of methotrexate-induced epidermal necrosis, and physicians should use caution when deciding when to prescribe methotrexate to high-risk patients, according to recently published study results in the Journal of the American Academy of Dermatology.

The researchers in Taiwan enrolled 24 patients with methotrexate-induced epidermal necrosis (MEN; mean age, 65.8 years; 13 men) and 150 methotrexate-tolerant controls (mean age, 40.7 years; 86 men) between 2007 and 2016. Demographics, pathology and plasma concentration of methotrexate were analyzed.

Patients with MEN included 22 who received methotrexate for psoriasis or psoriatic arthritis, one for bullous pemphigoid and one for rheumatoid arthritis. The controls were being treated for psoriasis or psoriatic arthritis for at least 3 months without cutaneous reactions.

Extensive skin necrosis (mean, 33.2% of total body surface area) was seen in the patients with MEN; however, there were no target lesions. Keratinocyte dystrophy was shown in histopathology.

Painful skin erosions, oral ulcers, leukopenia (58.3%) thrombocytopenia (37.5%) were early signs of MEN. Nineteen patients received leucovorin, with a morality rate of 15.8% for those patients. The death rate was 20% for the five patients who were treated with systemic steroid, granulocyte colony-simulating factor, or supportive care.

Older age (> 60 years; P < .001), chronic kidney disease (P < .001) and a high initial dosage of methotrexate without folic acid supplementation (P = .001) were significant risk factors for MEN.

Methotrexate clearance was delayed by renal deficiency.

“Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN,” the researchers wrote.

“Although there are some clinical similarities between [Steven-Johnson syndrome and toxic epidermal necrolysis] and MEN, the latter is a distinct condition,” the researchers concluded. “Our results suggest that renal insufficiency and high initial dosage of [methotrexate] may result in elevated plasma drug levels, leading to skin toxicity and leukopenia, resulting in increased risk of and mortality from MEN. [Methotrexate] should be prescribed with great caution to older patients with chronic renal disease, and low initial dosage with folic acid supplement should be strictly followed by avoid MEN.” – by Bruce Thiel

Disclosure: The researchers report no relevant financial disclosures.