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• W1979761444 abstract "To the Editor: Erlotinib (Tarceva; Genentech, South San Francisco, CA) is an oral anticancer agent that blocks the function of the epidermal growth factor receptor (EGFR) and has been approved by the US Food and Drug Administration for the treatment of non–small cell lung and pancreatic cancers. Therapy is frequently complicated by multiple cutaneous adverse effects ranging from follicular papulopustular (“acneiform”) eruptions, xerosis, nail changes (including paronychia and pyogenic granulomas in the lateral nail folds), and hair texture changes.1Jacot W. Bessis D. Jorda E. Ychou M. Fabbro M. Pujo J.L. et al.Acneiform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumors.Br J Dermatol. 2004; 151: 238-241Crossref PubMed Scopus (172) Google Scholar Previous reports exist of both nonscarring and scarring alopecia with gefitinib (Iressa; AstraZeneca, Wilmington, DE), another EGFR inhibitor; however, to date there are no reports of scarring alopecia with erlotinib. A 77-year-old white female with metastatic non-small cell lung cancer was referred to our department by her oncologist for the evaluation of scalp erythema, pustules, and alopecia (Fig 1). The scalp eruption started 18 months before the referral and within 2 weeks of initiating therapy with erlotinib 100 mg daily for progressive metastatic disease. She was initially treated by her oncologist with minocycline 50 mg twice daily. This was discontinued because of intolerable dizziness. She presented to the dermatology clinic with diffuse scalp erythema, many pustules, altered hair texture, alopecia, and a loss of follicular orifices at the vertex of the scalp. The patient described moderate pruritus. No other significant cutaneous findings or symptoms were present. The patient denied scalp pruritus or hair loss before beginning erlotinib therapy. Cultures for superinfection taken when the patient had been off oral antibiotics for longer than 8 months were negative. Two 4-mm punch biopsy specimens were obtained from an erythematous scaly alopecic patch on the scalp at the initial visit (Fig 2). Sections of the vertically oriented punch biopsy show chronic folliculitis and perifolliculitis with abundant plasma cells and lymphocytes and rare neutrophils and eosinophils. There was associated perifollicular fibrosis of the lower infundibular and upper isthmus portions of the hair follicles. Histiocytic and foreign body giant cell reactions around residual follicular structures were seen. Horizontally sectioned tissue showed an increased number of telogen and catagen hairs with perifollicular chronic inflammation and fibrosis consistent with a scarring alopecia. Topical clobetasol solution and oral acitretin 25 mg daily were started, given the reports of successful treatment of erlotinib-induced cutaneous side effects with low dose acitretin.2Pomerantz R.G. Chirinos R.E. Falo L.D. Geskin L.J. Acitretin for treatment of EGFR inhibitor-induced cutaneous toxic effects.Arch Dermatol. 2008; 144: 949-950Crossref PubMed Scopus (17) Google Scholar, 3Gutzmer R. Werfel T. Mao R. Kapp A. Elsner J. Successful treatment with oral isotretinoin of acneiform skin lesions associated with cetuximab therapy.Br J Dermatol. 2005; 153: 849-851Crossref PubMed Scopus (66) Google Scholar Acitretin (and subsequent low dose isotretinoin at 30 mg/day) therapy led to intolerable dryness of the skin and lips and was discontinued. Because of the patient's scalp discomfort and progressive erythema and alopecia, erlotinib therapy was held for 3 weeks. This led to marked improvement of the scalp eruption and symptoms. When erlotinib was reinitiated at a reduced dose of 50 mg daily, the patient experienced another scalp flare. Alopecia is a rare side effect of EGFR inhibitors when compared to the far more prevalent papulopustular eruption on the face and trunk. EGFR null mice have been shown to develop alopecia.4Murillas R. Larcher F. Conti C.J. Santos M. Ullrich A. Jorcano J.L. Expression of dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure.EMBO J. 1995; 14: 5216-5223Crossref PubMed Scopus (240) Google Scholar, 5Hansen L.A. Alexander N. Hogan M.E. Sundberg J.P. Dlugosz A. Threadgill D.W. et al.Genetically null mice reveal a central role for the epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development.Am J Pathol. 1997; 150: 1959-1975PubMed Google Scholar Graves et al6Graves J.E. Jones B.F. Lind A.C. Heffernan M.P. Nonscarring alopecia associated with the epidermal growth factor inhibitor gefitinib.J Am Acad Dermatol. 2006; 55: 349-353Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar first described a nonscarring inflammatory alopecia in a patient soon after starting gefitinib therapy. Scarring was not present, and hair regrowth occurred after treatment was discontinued.6Graves J.E. Jones B.F. Lind A.C. Heffernan M.P. Nonscarring alopecia associated with the epidermal growth factor inhibitor gefitinib.J Am Acad Dermatol. 2006; 55: 349-353Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Donovan et al7Donovan J.C. Ghazarian D.M. Shaw J.C. Scarring alopecia associated with the use of the epidermal growth factor receptor inhibitor gefitinib.Arch Dermatol. 2008; 144: 1524-1525Crossref PubMed Scopus (32) Google Scholar described a patient who developed scarring alopecia after 8 months of gefitinib therapy. Similar histopathologic changes were reported, including chronic follicular inflammatory infiltrate, consisting mainly of plasma cells and lymphocytes, and fibrosis consistent with scarring in the upper portion of hair follicles. In the case published by Donovan et al,7Donovan J.C. Ghazarian D.M. Shaw J.C. Scarring alopecia associated with the use of the epidermal growth factor receptor inhibitor gefitinib.Arch Dermatol. 2008; 144: 1524-1525Crossref PubMed Scopus (32) Google Scholar the authors were unable to evaluate the effect of discontinuing gefitinib treatment because their patient died shortly thereafter of widespread metastatic disease. In our case, erlotinib was discontinued for 3 weeks with significant improvement of the scalp erythema, scaling, and pustules, but without significant hair regrowth. Retrial with erlotinib, despite a dose reduction, caused a recurrence of the scalp eruption. To our knowledge, this is the first case of scarring alopecia from erlotinib that was confirmed by histopathology with a recurrence or eruption upon the reinitiation of erlotinib. We report the present case to show the possible association of scarring alopecia with not only the EGFR inhibitor gefitinib, but also another member of this class, erlotinib. We believe that this is likely a class effect—although rare—with all systemic EGFR antagonists. We thank Dr Anne Lind and Dr Omar Jassim for histopathological evaluation and photos." @default.
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• W1979761444 title "Scarring alopecia associated with the epidermal growth factor receptor inhibitor erlotinib" @default.
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