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Scarring Alopecia Associated With Use of the Epidermal Growth Factor Receptor Inhibitor Gefitinib

Scarring Alopecia Associated With Use of the Epidermal Growth Factor Receptor Inhibitor Gefitinib Follicular eruptions are well-recognized adverse effects of epidermal growth factor receptor (EGFR) inhibitor therapy.1 Although alopecia is uncommon, mice with targeted disruption of the EGFR develop alopecia.2,3 We report the development of scarring alopecia associated with use of the EGFR inhibitor gefitinib (Iressa; AstraZeneca, Mississisauga, Ontario, Canada). Report of a Case A 70-year-old woman with stage IV non–small cell lung cancer was evaluated regarding a 2-year history of scalp erythema and crusting that progressed to scarring alopecia (Figure 1). The eruption began 8 months after the start of gefitinib therapy, 250 mg/d. However, textural changes and slower hair growth were noted after only 2 months of gefitinib treatment. Figure 1. View LargeDownload A 70-year-old woman with marked frontal and vertex alopecia that appeared after the use of the epidermal growth factor receptor inhibitor gefitinib. Note the sharp demarcation of erythema at the frontal hair line and the presence of crusting (arrows). A 4-mm punch biopsy specimen from an erythematous scaly area on the scalp vertex showed parakeratosis with focal follicular plugging containing neutrophils. Periodic acid–Schiff staining did not reveal fungi or basement membrane thickening. Superficial dermal edema was present (Figure 2A, main image); results of a Hale stain for mucin were negative. A chronic inflammatory infiltrate, consisting mostly of plasma cells with some lymphocytes, was seen focally distributed within the dermis. Fibrosis consistent with scarring obscured the upper portion of hair follicles. Abundant collagen was seen under trichrome-Masson stain (Figure 2A, inset). Mature anagen hairs were present in the subcutaneous fat; they were surrounded by numerous plasma cells, a few lymphocytes and eosinophils, and rare neutrophils (Figure 2B). Repeated bacterial cultures from swabs proved negative. Figure 2. View LargeDownload Histologic images of punch biopsy specimens from the scalp vertex of the patient pictured in Figure 1. A, Mature anagen hairs are present in the subcutaneous fat, and loss of the superficial parts of the hair follicles is visible within the inflamed and scarred area. Note the superficial dermal edema (hematoxylin-eosin, original magnification ×50). Trichrome-Masson stain shows abundant collagen throughout the middle and deep dermis (inset) (original magnification ×20). B, High-power magnification of perifollicular infiltrate shows abundant plasma cells and fewer eosinophils and lymphocytes (hematoxylin-eosin, original magnification ×630). The patient's rapidly progressive disease led to gefitinib treatment being discontinued soon after the scalp biopsy procedure. The effect on hair regrowth of discontinuing gefitinib treatment was not possible to evaluate because the patient died of widespread metastatic disease 2 weeks later. Comment The rapid acquisition of hair textural changes along with the histopathologic characteristics of the present case favored a diagnosis of scarring alopecia secondary to gefitinib. The main differential diagnosis was folliculitis decalvans, although the notable plasma cell and eosinophilic cell infiltrate along with absence of Staphylococcus in repeated swabs and cultures suggested a distinct drug-related process. Because the patient died so soon after therapy was discontinued, we could not evaluate the effect of stopping treatment and thus make a more definitive assessment about the role of gefitinib. Graves et al4 first described a patient who developed nonscarring alopecia after 2 years of undergoing gefitinib therapy. Their patient differed from ours in that she was evaluated within a few months of first noticing hair loss rather than many years later. Furthermore, scarring was not present, and hair regrowth was observed after gefitinib treatment was stopped. It is possible that the changes reported by Graves et al4 represent the earliest changes of gefitinib-induced alopecia and that with time, a scarring alopecia may result. Wu et al5 described a 69-year-old woman who developed scarring alopecia following initiation of gefitinib treatment and scalp radiotherapy. A scalp biopsy specimen also revealed an inflammatory infiltrate of mainly plasma cells. The patient was diagnosed as having erosive pustular dermatosis of the scalp. A rapid improvement was noted with the use of topical steroids despite continuation of gefitinib treatment. Whether this was a different condition than we observed in our patient is unknown. The notable plasma cell infiltrate findings would suggest a similar process, although the depth of the infiltrate, the presence of eosinophils, and the more marked fibrosis observed in our patient raise the possibility of a different process. We highlight the present case to alert physicians to the possibility of scarring alopecia developing from the use of EGFR inhibitors such as gefitinib. Correspondence: Dr Donovan, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, M1-700, Toronto, ON M4N 3M5, Canada (jeffrey.donovan@utoronto.ca). Financial Disclosure: None reported. References 1. Agero ALDusza SBenvenuto-Andrade CBusam KJMyskowski PHalpern AC Dermatologic side effects associated with the epidermal growth factor inhibitors. J Am Acad Dermatol 2006;55 (4) 657- 670PubMedGoogle ScholarCrossref 2. Murillas RLarcher FConti CJ et al. Expression of a 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 (21) 5216- 5223PubMedGoogle Scholar 3. Hansen LAAlexander NHogan ME 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 (6) 1959- 1975PubMedGoogle Scholar 4. Graves JEJones BFLind ACHeffernan MP Nonscarring alopecia associated with the epidermal growth factor inhibitor gefitinib. J Am Acad Dermatol 2006;55 (2) 349- 353PubMedGoogle ScholarCrossref 5. Wu CYChen GSLan CC Erosive pustular dermatosis of the scalp after gefitinib and radiotherapy for brain metastases secondary to lung cancer. Clin Exp Dermatol 2008;33 (1) 106- 107PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Scarring Alopecia Associated With Use of the Epidermal Growth Factor Receptor Inhibitor Gefitinib

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Publisher
American Medical Association
Copyright
Copyright © 2008 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.144.11.1524
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Abstract

Follicular eruptions are well-recognized adverse effects of epidermal growth factor receptor (EGFR) inhibitor therapy.1 Although alopecia is uncommon, mice with targeted disruption of the EGFR develop alopecia.2,3 We report the development of scarring alopecia associated with use of the EGFR inhibitor gefitinib (Iressa; AstraZeneca, Mississisauga, Ontario, Canada). Report of a Case A 70-year-old woman with stage IV non–small cell lung cancer was evaluated regarding a 2-year history of scalp erythema and crusting that progressed to scarring alopecia (Figure 1). The eruption began 8 months after the start of gefitinib therapy, 250 mg/d. However, textural changes and slower hair growth were noted after only 2 months of gefitinib treatment. Figure 1. View LargeDownload A 70-year-old woman with marked frontal and vertex alopecia that appeared after the use of the epidermal growth factor receptor inhibitor gefitinib. Note the sharp demarcation of erythema at the frontal hair line and the presence of crusting (arrows). A 4-mm punch biopsy specimen from an erythematous scaly area on the scalp vertex showed parakeratosis with focal follicular plugging containing neutrophils. Periodic acid–Schiff staining did not reveal fungi or basement membrane thickening. Superficial dermal edema was present (Figure 2A, main image); results of a Hale stain for mucin were negative. A chronic inflammatory infiltrate, consisting mostly of plasma cells with some lymphocytes, was seen focally distributed within the dermis. Fibrosis consistent with scarring obscured the upper portion of hair follicles. Abundant collagen was seen under trichrome-Masson stain (Figure 2A, inset). Mature anagen hairs were present in the subcutaneous fat; they were surrounded by numerous plasma cells, a few lymphocytes and eosinophils, and rare neutrophils (Figure 2B). Repeated bacterial cultures from swabs proved negative. Figure 2. View LargeDownload Histologic images of punch biopsy specimens from the scalp vertex of the patient pictured in Figure 1. A, Mature anagen hairs are present in the subcutaneous fat, and loss of the superficial parts of the hair follicles is visible within the inflamed and scarred area. Note the superficial dermal edema (hematoxylin-eosin, original magnification ×50). Trichrome-Masson stain shows abundant collagen throughout the middle and deep dermis (inset) (original magnification ×20). B, High-power magnification of perifollicular infiltrate shows abundant plasma cells and fewer eosinophils and lymphocytes (hematoxylin-eosin, original magnification ×630). The patient's rapidly progressive disease led to gefitinib treatment being discontinued soon after the scalp biopsy procedure. The effect on hair regrowth of discontinuing gefitinib treatment was not possible to evaluate because the patient died of widespread metastatic disease 2 weeks later. Comment The rapid acquisition of hair textural changes along with the histopathologic characteristics of the present case favored a diagnosis of scarring alopecia secondary to gefitinib. The main differential diagnosis was folliculitis decalvans, although the notable plasma cell and eosinophilic cell infiltrate along with absence of Staphylococcus in repeated swabs and cultures suggested a distinct drug-related process. Because the patient died so soon after therapy was discontinued, we could not evaluate the effect of stopping treatment and thus make a more definitive assessment about the role of gefitinib. Graves et al4 first described a patient who developed nonscarring alopecia after 2 years of undergoing gefitinib therapy. Their patient differed from ours in that she was evaluated within a few months of first noticing hair loss rather than many years later. Furthermore, scarring was not present, and hair regrowth was observed after gefitinib treatment was stopped. It is possible that the changes reported by Graves et al4 represent the earliest changes of gefitinib-induced alopecia and that with time, a scarring alopecia may result. Wu et al5 described a 69-year-old woman who developed scarring alopecia following initiation of gefitinib treatment and scalp radiotherapy. A scalp biopsy specimen also revealed an inflammatory infiltrate of mainly plasma cells. The patient was diagnosed as having erosive pustular dermatosis of the scalp. A rapid improvement was noted with the use of topical steroids despite continuation of gefitinib treatment. Whether this was a different condition than we observed in our patient is unknown. The notable plasma cell infiltrate findings would suggest a similar process, although the depth of the infiltrate, the presence of eosinophils, and the more marked fibrosis observed in our patient raise the possibility of a different process. We highlight the present case to alert physicians to the possibility of scarring alopecia developing from the use of EGFR inhibitors such as gefitinib. Correspondence: Dr Donovan, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, M1-700, Toronto, ON M4N 3M5, Canada (jeffrey.donovan@utoronto.ca). Financial Disclosure: None reported. References 1. Agero ALDusza SBenvenuto-Andrade CBusam KJMyskowski PHalpern AC Dermatologic side effects associated with the epidermal growth factor inhibitors. J Am Acad Dermatol 2006;55 (4) 657- 670PubMedGoogle ScholarCrossref 2. Murillas RLarcher FConti CJ et al. Expression of a 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 (21) 5216- 5223PubMedGoogle Scholar 3. Hansen LAAlexander NHogan ME 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 (6) 1959- 1975PubMedGoogle Scholar 4. Graves JEJones BFLind ACHeffernan MP Nonscarring alopecia associated with the epidermal growth factor inhibitor gefitinib. J Am Acad Dermatol 2006;55 (2) 349- 353PubMedGoogle ScholarCrossref 5. Wu CYChen GSLan CC Erosive pustular dermatosis of the scalp after gefitinib and radiotherapy for brain metastases secondary to lung cancer. Clin Exp Dermatol 2008;33 (1) 106- 107PubMedGoogle ScholarCrossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Nov 17, 2008

Keywords: pseudopelade,gefitinib,epidermal growth factor receptor inhibitors

References