Original articleMethotrexate-induced epidermal necrosis: A case series of 24 patients
Section snippets
Study participants
Patients with epidermal necrosis after taking MTX were enrolled from Chang Gung Memorial Hospital (CGMH) system and Wan Fang Hospital between 2007 and 2016. This study was approved by the institutional review board of the study site. Written informed consent was obtained from each participant. All cases were evaluated by at least 2 dermatologists. The diagnosis of epidermal necrosis was made by the clinical presentation or histopathologic findings. Drug causality was determined by the Naranjo
Demographic characteristics of patients with MEN and controls
We enrolled 24 MEN cases and 150 MTX-tolerant controls (Table I). The detailed demographic data of 24 cases are listed in Supplemental Table I (available at http://www.jaad.org), and representative clinical photographs of patients are shown in Fig 1. Four of the 24 patients with MEN died from this episode, and the overall mortality was 16.7% (Table I). Twenty-two (91.7%) patients with MEN received MTX for treating psoriasis or psoriatic arthritis, 1 for bullous pemphigoid, and 1 for rheumatoid
Discussion
To our knowledge, this is the largest study comparing patients with MEN and controls to investigate the clinicopathologic features, risks, and prognostic factors of MEN. The early signs of MEN include painful skin erosions, oral ulcers, leukopenia, and thrombocytopenia. The risks of MEN included older age (>60 years), CKD, and high initial dosage without folic acid supplement. Poor renal function delayed the clearance of plasma MTX. We found that severe renal disease and leukopenia were linked
References (42)
- et al.
Methotrexate-induced necrolysis
J Am Acad Dermatol
(1983) - et al.
Methotrexate-induced toxic epidermal necrolysis in a patient with psoriasis
J Am Acad Dermatol
(1997) - et al.
Low-dose methotrexate-induced skin toxicity: keratinocyte dystrophy as a histologic marker
J Am Acad Dermatol
(2015) - et al.
Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 28 patients
Autoimmun Rev
(2014) - et al.
Methotrexate-induced bullous acral erythema in a child
J Am Acad Dermatol
(2005) - et al.
Oxypurinol-specific T cells possess preferential TCR clonotypes and express granulysin in allopurinol-induced severe cutaneous adverse reactions
J Invest Dermatol
(2015) - et al.
Interleukin-15 is associated with severity and mortality in Stevens–Johnson syndrome/toxic epidermal necrolysis
J Invest Dermatol
(2017) - et al.
Prognostic value of histologic features of toxic epidermal necrolysis
J Am Acad Dermatol
(2013) - et al.
Erosion of psoriatic plaques: an early sign of methotrexate toxicity
J Am Acad Dermatol
(1996) Toward a better understanding of methotrexate
Arthritis Rheum
(2004)
Update on antifolate drugs targets
Curr Drug Targets
Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis
Reumatismo
Methotrexate side effects
Br J Dermatol
Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity?
Immunol Res
Methotrexate-induced epidermal necrosis
Br J Dermatol
The efficacy of methotrexate in psoriasis—a review of 40 cases
Clin Exp Dermatol
Toxic epidermal necrolysis in two patients with pustular psoriasis
Br J Dermatol
Acute methotrexate toxicity seen as plaque psoriasis ulceration and necrosis: a diagnostic clue
Dermatol Online J
Methotrexate-induced toxic epidermal necrolysis-like skin toxicity
Eur J Dermatol
Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme
Arch Dermatol
Epidermal necrolysis: 60 years of errors and advances
Br J Dermatol
Cited by (28)
Undiagnosed and Rare Diseases in Critical Care: Severe Mucocutaneous Medication Reactions
2022, Critical Care ClinicsCitation Excerpt :Methotrexate (4-amino-10-methylfolic acid) (MTX) is a folic acid analog and antagonist used in the treatment of numerous inflammatory and malignant processes.67,68 MTX is first-line treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, and psoriasis.67,69 MTX-induced epidermal necrosis (MEN) is a rare cutaneous reaction that mimics SJS or TEN.69
Methotrexate-induced cutaneous ulceration without pancytopenia in a patient treated for inflammatory arthritis
2021, JAAD Case ReportsCitation Excerpt :Similar to psoriasis, these cases have also been associated with pancytopenia.1 Our patient had a unique presentation in that ulcers presented after 2 years of MTX therapy at a stable dose and at one of the lowest doses that has been reported in the literature in a patient with normal renal function.10 He had no associated pancytopenia with normal leukocytes, platelets, and normocytic anemia consistent with anemia of chronic disease.
Methotrexate-induced cutaneous ulceration and necrosis in chronic atopic dermatitis
2020, JAAD Case ReportsCitation Excerpt :A potential explanation may be increased cell turnover, making these tissues particularly susceptible to cytocidal effects.2 There are only 8 reported cases in nonpsoriatic patients with an underlying primary dermatologic disease, either bullous pemphigoid or mycosis fungoides (Table I).2,5-8 To our knowledge, this is the first reported case of methotrexate-induced cutaneous ulceration and necrosis in atopic dermatitis.
Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies
2020, Journal of the American Academy of DermatologyJAAD Game Changers∗: Methotrexate-induced epidermal necrosis: A case series of 24 patients
2020, Journal of the American Academy of Dermatology
Drs T-J. Chen and Chung contributed equally to this work.
Supported by the grants from the Ministry of Science and Technology, Taiwan (NSC101-2320-B-010-072-MY3, NSC101-2321-B-010-027, NSC101-2628-B-182-001-MY3, NSC101-2321-B-182-008, NSC102-2314-B-010-014-MY3, and NSC104-2320-B-010-036-MY3) and grants from Chang Gung Memorial Hospital (BMRPG290011, CMRPG-290051∼3, OMRPG2C0011, OMRPG2C0021, and CLRPG340599).
Conflicts of interest: None declared.