Methotrexate-Induced Cutaneous Ulcers in a Nonpsoriatic Patient: Case Report and Review of the Literature

Kurian, Anil; Haber, Richard M.

doi:10.2310/7750.2011.10078

Cited by 36 publications

(19 citation statements)

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“…These ulcerations are painful, and it has recently been suggested that they are more frequent on acral areas [15]. Skin ulceration has also been described in patients with mycosis fungoides receiving MTX [16,17] as well as in patients without skin lesions receiving MTX [18,19,20]. In the latter the exact mechanism of ulceration has not been elucidated, but direct toxicity associated with local factors has been suggested [19].…”

Section: Discussionmentioning

confidence: 99%

Acute Severe Methotrexate Toxicity in Patients with Psoriasis: A Case Series and Discussion

et al. 2014

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Background: Methotrexate (MTX) is considered a relatively safe drug when prescribed at low-dose regimens not exceeding 25 mg/week. Severe acute toxicity is rare and presents with mucositis, cutaneous ulceration and pancytopenia. Most cases occur as the result of inadvertent overdosing due to erroneously taking the drug daily. However, concomitant factors such as older age, co-medication and renal failure may increase the drug's toxicity. Case Reports: We report four consecutive cases of acute MTX toxicity in patients with psoriasis vulgaris. In three patients, MTX was erroneously taken daily for 2-4 weeks. All three patients recovered following MTX withdrawal and intensive treatment. The fourth patient was taking 7.5 mg weekly MTX as prescribed, but had concomitant factors and died. Conclusion: Although low-dose MTX appears to be a safe medication, acute MTX toxicity can be a life-threatening emergency. Greater awareness of possible MTX toxicity is still needed for its prevention, early diagnosis and management.

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Section: Discussionmentioning

confidence: 99%

Acute Severe Methotrexate Toxicity in Patients with Psoriasis: A Case Series and Discussion

et al. 2014

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“…One week after MTX discontinuation the skin lesions had resolved ( D−F ). MTX‐induced erosions in patients without a history of psoriasis are rare . Reported predisposing factors include initiation/increase or restarting MTX treatment, renal impairment, NSAID intake, age >55 years, folate deficiency, low serum albumin level, and drug interactions (e.g.…”

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confidence: 99%

Methotrexate‐Induced Cutaneous Erosions

Mönch

Zimmo

Helou

et al. 2015

Arthritis & Rheumatology

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The patient, a 70-year-old woman with type 2 diabetes mellitus and rheumatoid factor2positive (130 KIU/liter) erosive nodular rheumatoid arthritis, presented with a 4-week history of painful superficial erosions and ulcers involving the lower lip (A), left submammary crease (B), and left inguinal area extending to the proximal thigh (C). Her medications included methotrexate (MTX) 20 mg/week (total duration of treatment 6 months; dosage increased from 15 mg/week 3 months prior), hydroxychloroquine 400 mg/day, folic acid 10 mg/week, and aspirin 80 mg/day. There was no history of exposure to antibiotics, diuretics, or other nonsteroidal antiinflammatory drugs (NSAIDs). Laboratory studies revealed the following: creatinine 91 mmoles/liter (pre-MTX 55 mmoles/liter), albumin 34 gm/liter, white blood cell count 4.70 3 10 9 /liter, hemoglobin 82 gm/liter (pre-MTX 130 gm/liter), mean corpuscular volume 98.5 fL, platelet count 427 3 10 9 /liter, alanine aminotransferase 17 units/liter, aspartate aminotransferase 19 units/liter, serum MTX ,0.06 mmoles/liter, and vitamin B 12 74 pmoles/liter. MTX-induced cutaneous erosion/ulceration was suspected, and this drug was stopped. Leucovorin and B 12 treatment were prescribed. Pathologic examination of the skin showed hyperplastic epidermal changes with mild dermal chronic inflammation, fibrosis, and vascular telangiectasia. One week after MTX discontinuation the skin lesions had resolved (D2F). MTX-induced erosions in patients without a history of psoriasis are rare (1). Reported predisposing factors include initiation/increase or restarting MTX treatment, renal impairment, NSAID intake, age .55 years, folate deficiency, low serum albumin level, and drug interactions (e.g. with trimethoprim/sulfamethoxazole) (2). Psoriatic plaque erosions as a side effect of low-dose MTX are an indicator of impending life-threatening pancytopenia; thus, rapid discontinuation of this drug is critical (3).1. Kurian A, Haber R. Methotrexate-induced cutaneous ulcers in a nonpsoriatic patient: case report and review of the literature. J Cutan Med Surg 2011;15: 275-9. 2. Shiver MB, Hall LA, Conner KB, Brown GE, Cheung WL, Wirges ML. Cutaneous erosions: a herald for impending pancytopenia in methotrexate toxicity. Dermatol Online J 2014;20(7). 3. Jariwala P, Kumar V, Kothari K, Thakkar S, Umrigar DD. Acute methotrexate toxicity: a fatal condition in two cases of psoriasis.

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“…He had not undergone any changes in dosage, nor was he resuming treatment after a drug hiatus, both of which may precipitate MTX toxicity . Compared with previous reports of toxicity, which occurred at 15 mg/week to 5 mg/day, we suggest that his remarkable susceptibility was due to decreased renal clearance …”

Section: Discussionmentioning

confidence: 99%

“…Previous cases of MTX‐induced skin necrosis in patients without psoriasis have described ulcerations affecting the oral, acral and extensor surfaces . Rapid proliferation of the oral mucosa or increased epithelial thickness with high mitotic indices at the acral or extensor surfaces may explain the increased susceptibility to MTX at these sites .…”

Section: Discussionmentioning

confidence: 99%

Painful, violaceous plaques in a patient with pruritus

2017

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A 51-year-old man presented with a 2-week history of acute-onset, painful, violaceous plaques involving the bilateral medial thighs. The patient's medical history included end-stage renal disease requiring haemodialysis, along with lichen simplex chronicus and prurigo nodularis, which had failed to respond to topical steroids and narrowband ultraviolet B phototherapy. After discussion with his nephrologist, the patient had been started on weekly low-dose methotrexate for persistent pruritus. At his presentation to us 2 weeks later, physical examination revealed ill-defined, violaceous indurated plaques with central erosion and surrounding scale on the bilateral medial thighs and inguinal folds ( Fig. 1). Laboratory investigation revealed pancytopenia, elevated creatinine (8.5 mg/dL; normal range 0.7-1.3 mg/dL), and normal hepatic transaminases. Histopathological findingsA punch biopsy was taken, and histopathological examination revealed basal vacuolar change with epidermal apoptosis and oedema, and a superficial dermal infiltrate consisting of lymphocytes, neutrophils and eosinophils with mild haemorrhage (Fig. 2).What is your diagnosis? DiagnosisMethotrexate (MTX)-induced skin necrosis. DiscussionCutaneous ulceration is a rare adverse effect of MTX therapy. It is most commonly reported in patients with psoriasis, in whom the rapidly proliferating cells of psoriatic plaques are thought to demonstrate increased uptake of MTX, leading to antimitotic activity and cell death.1 Ours is the seventh reported case of MTX-induced cutaneous erosions in a patient without psoriasis.Our patient had been started on methotrexate 7.5 mg/week and had completed 2 weeks of therapy when he noted tenderness in the inguinal region. He had not undergone any changes in dosage, nor was he resuming treatment after a drug hiatus, both of which may precipitate MTX toxicity.1 Compared with previous reports of toxicity, which occurred at 15 mg/week to 5 mg/day, we suggest that his remarkable susceptibility was due to decreased renal clearance. 2Previous cases of MTX-induced skin necrosis in patients without psoriasis have described ulcerations affecting the oral, acral and extensor surfaces.2 Rapid proliferation of the oral mucosa or increased epithelial

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Methotrexate-Induced Cutaneous Ulcers in a Nonpsoriatic Patient: Case Report and Review of the Literature

Cited by 36 publications

References 8 publications

Acute Severe Methotrexate Toxicity in Patients with Psoriasis: A Case Series and Discussion

Acute Severe Methotrexate Toxicity in Patients with Psoriasis: A Case Series and Discussion

Methotrexate‐Induced Cutaneous Erosions

Painful, violaceous plaques in a patient with pruritus

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