title: Low-dose methotrexate-induced skin toxicity: Keratinocyte dystrophy as a histologic marker.
abstract: BACKGROUND
  Skin toxicity during low-dose methotrexate therapy is rare, ill described, and reported to have nonspecific histologic characteristics. Thus, misdiagnosis is common in patients with mucosal ulcers and/or skin erosions related to low-dose methotrexate.
  
  
  OBJECTIVE
  We sought to describe the features of skin toxicity induced by low-dose methotrexate.
  
  
  METHODS
  We evaluated the clinical and histologic features in 5 patients who experienced skin toxicity induced by low-dose methotrexate between 2011 and 2013.
  
  
  RESULTS
  All 5 patients had acute mucosal ulcers, 4 had moderately abnormal blood cell counts, and 3 had skin erosions. In 3 patients, methotrexate dosage or dosing-schedule errors were identified. No other contributing factors (eg, renal dysfunction or interacting drugs) were identified. Mucocutaneous biopsy specimens consistently showed multiple dystrophic keratinocytes.
  
  
  CONCLUSIONS
  We studied only 5 patients and obtained no sensitivity or specificity data on the diagnostic value of keratinocyte dystrophy.
  
  
  CONCLUSIONS
  Keratinocyte dystrophy may help to diagnose skin toxicity of low-dose methotrexate, even in the absence of known risk factors or methotrexate administration errors. Studies of the diagnostic performance of this histologic sign are needed.
authors.affiliation: Département de Dermatologie, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Delyon
authors.affiliation: Département de Pathologie, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.affiliation: Département de Hématologie Biologique, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Benayoun
authors.affiliation: Département de Pathologie, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Moroch
authors.affiliation: Département de Dermatologie, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France; Inserm, Centre d'Investigation Clinique 1430, Créteil, France; Equipe d'Accueil (EA) EpiDermE, Université Paris-Est Créteil, Créteil, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wolkenstein
authors.affiliation: Département de Dermatologie, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France; Pôle Recherche Clinique Santé Publique, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France; Inserm, Centre d'Investigation Clinique 1430, Créteil, France; Equipe d'Accueil (EA) EpiDermE, Université Paris-Est Créteil, Créteil, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Sbidian
authors.affiliation: Département de Dermatologie, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France; Inserm, Centre d'Investigation Clinique 1430, Créteil, France; Equipe d'Accueil (EA) EpiDermE, Université Paris-Est Créteil, Créteil, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chosidow
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy; D015415:Biomarkers; D001707:Biopsy, Needle; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000209:etiology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D010391:Pemphigoid, Bullous / Q000175:diagnosis / Q000188:drug therapy; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy; D035583:Rare Diseases; D012189:Retrospective Studies; D018570:Risk Assessment; D012883:Skin Ulcer / Q000139:chemically induced* / Q000473:pathology
chemical_list: D015415:Biomarkers; D008727:Methotrexate
keywords: keratinocyte dystrophy; methotrexate; pancytopenia; psoriasis; skin toxicity; ulcers