Cutaneous erosions: a herald for impending pancytopenia in methotrexate toxicity

Abstract

Psoriatic plaque erosion is a rare toxic side effect of low-dose methotrexate (LDMTX) that has been reported during the treatment of psoriasis and described as a herald for impending pancytopenia. Fatalities from this have rarely been reported. Even rarer is methotrexate (MTX)-induced erosions of clinically normal skin in patients without a history of psoriasis. We report 3 rare presentations of MTX-induced cutaneous erosions, 2 fatalities occurring with MTX-induced psoriatic plaque erosions, and the sixth reported case of MTX-induced erosions with no prior history of psoriasis. Each were elderly patients on proton pump inhibitors with a history of chronic non-steroidal anti-inflammatory drug (NSAID) use. They all presented with acute onset of erosions after a recent change in their MTX dose. Pancytopenia followed in each case. Physicians' awareness of the sequelae in MTX-induced cutaneous erosions is imperative so MTX can be discontinued and treatment instituted to prevent fatal bone marrow suppression.

Surfactant-Free, Self-Assembled Nanomicelles-Based Transdermal Hydrogel for Safe and Targeted Delivery of Methotrexate against Rheumatoid Arthritis

“…The skin irritation study was performed to check the safety of the prepared hydrogel for skin application. Free MTX has the potential to cause serious skin reactions, , and it was hypothesized that loading of MTX into a biocompatible nanocarrier would limit this skin irritation. The erythema and edema scores were found to be highest for the negative control group treated with 0.8% formalin (Figure C­(b2)).…”

Severe Adverse Toxic Effects of Low-Dose Methotrexate Treatment on an Ectopic Pregnancy Patient With Methylenetetrahydrofolate Reductase Mutations: A Case Report

“…Once the toxicity of LD-MTX is recognized, e.g., high-dose MTX, it is essential to take a series of measures, including CF rescue, adequate hydration, urine alkalinization, monitoring of MTX concentration, and timely treatment of adverse reactions ( 28 ). Leucovorin supplies the active form of folic acid, bypassing DHFR inhibition ( 6 ). In general, the recommended dose of CF rescue is 12–15 mg/m 2 , with an intravenous drip every 6 h, until the MTX concentration falls below 0.01 uM/L ( 28 , 29 ).…”

“…In this case, the serum MTX concentration was still higher than the aforementioned threshold after 4 days of CF rescue with 20 mg, IV q6h, thus, the dose of CF was elevated to 100 mg, IV q6h. However, Shiver et al pointed that serum MTX concentration is a poor indicator of intracellular toxicity, because MTX is retained in toxic amounts in the polyglutamated form within the cells ( 6 , 19 ). The status of the patient investigated in this report also confirmed the mentioned finding, in which rescue measures should be taken independent of serum MTX concentration.…”

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“…Once the toxicity of LD-MTX is recognized, e.g., high-dose MTX, it is essential to take a series of measures, including CF rescue, adequate hydration, urine alkalinization, monitoring of MTX concentration, and timely treatment of adverse reactions (28). Leucovorin supplies the active form of folic acid, bypassing DHFR inhibition (6). In general, the recommended dose of CF rescue is 12-15 mg/m 2 ,…”

“…Furthermore, MTX is highly toxic to rapidly replicating tissues, and it may cause hematologic, gastrointestinal (hepatic, nausea, etc. ), and mucocutaneous adverse effects (5)(6)(7). However, in the case of administration of LD-MTX, its toxic effects are generally mild and self-limiting (8).…”