title: Targeting the adnexal epithelium: an unusual case of syringometaplasia in a patient on vemurafenib.
abstract: Cutaneous adverse events (cAEs) are reported in 90% of all patients on selective BRAF inhibitors and contribute significantly to patient morbidity. Two weeks after initiating vemurafenib for metastatic melanoma, our patient developed a pruritic eruption with numerous, 1-2 mm pink hyperkeratotic follicular papules over his trunk and upper extremities. A biopsy demonstrated squamous metaplasia of the eccrine ducts with irregular hyperplasia of hair follicles sparing the interfollicular epidermis. Diffuse adnexal metaplasia is a novel and unusual cutaneous response to vemurafenib. The patient was started on acitretin 10 mg daily with improvement of the eruption after 4 weeks. We report an unusual cAE of vemurafenib selectively targeting the adnexal epithelium with relative sparing of the interfollicular epidermis. Interval improvement was noted after 4 weeks of acitretin, which is an effective therapeutic option for patients with cAEs involving squamous hyperplasia secondary to vemurafenib. Our case illustrates the particular sensitivity of the adnexal epithelium for vemurafenib-induced dysfunction in proliferation and differentiation, providing the basis for common cAEs observed on this medication.
authors.affiliation: Departments of *Dermatology, and †Pathology, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: JiaDe
authors.initials: J
authors.lastname: Yu
authors.forename: Sitara
authors.initials: S
authors.lastname: Ravikumar
authors.forename: Jose A
authors.initials: JA
authors.lastname: Plaza
authors.forename: James L
authors.initials: JL
authors.lastname: Troy
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Schieke
mesh_terms: D017255:Acitretin / Q000627:therapeutic use; D000368:Aged; D001706:Biopsy; D049109:Cell Proliferation / Q000187:drug effects; D003875:Drug Eruptions / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D004439:Eccrine Glands / Q000187:drug effects* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007641:Keratolytic Agents / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008679:Metaplasia; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects*; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D007641:Keratolytic Agents; D013449:Sulfonamides; D000077484:Vemurafenib; D017255:Acitretin