Viewpoints in dermatology • Correspondence
Correspondence
Erlotinib-induced folliculitis decalvans doi: 10.1111/ced.12083
We report a case of erlotinib-induced folliculitis decalvans in an elderly man. Folliculitis is a commonly reported sideeffect of erlotinib and other tyrosine kinase receptor inhibitors. Folliculitis decalvans (FD) is an under-recognized adverse effect that may become more widespread with the greater use of tyrosine kinase inhibitors (TKIs). A 76-year-old man presented to dermatology with ‘scalp symptoms’. He had been diagnosed some time previously with metastatic pulmonary adenocarcinoma and started on erlotinib, to which his cancer had responded well. He reported an itchy, crusting scalp eruption that had developed since starting erlotinib, and which had briefly resolved during an intermission in treatment. The symptoms had gradually worsened since he had been put on a maintenance dose of 75 mg once daily. Ketoconazole shampoo and topical potent corticosteroids had made no improvement. On physical examination, a scaly erythematous eruption was seen on the patient’s scalp, with scarring alopecia at the vertex, and some areas of pustules and crusting (Fig. 1). Two punch biopsies were taken for evaluation. On histological examination, features of alopecia and nonspecific perifolliculitis were seen, including predominantly neutrophilic perifolliculitis with occasional foreign-body giant cells that were negative for periodicacid–Schiff staining, and a marked decrease in the number of hair follicles (Fig. 2). These findings were consistent with a diagnosis of FD. The patient was treated with oxytetracycline 500 mg twice daily, betamethasone 0.1% with clioquinol 3% cream (Betnovate-C®; Chemidex Pharma, Egham, Surrey, UK) and cetrimide 10% with undecanoic acid 1% shampoo (Ceanel Concentrate®; Ferndale Pharmaceuticals Ltd, Wetherby, Yorkshire, UK) and is showing improvement. Erlotinib is an inhibitor targeting the epidermal growth factor receptor (EGFR) tyrosine kinase and is
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Clinical and Experimental Dermatology (2013) 38, pp924–935
particularly promising as a new drug for non-small-cell lung cancer (NSCLC) with proven benefits on survival. TKIs are known to be responsible for cutaneous sideeffects in up to 50% of patients, with the conditions including simple folliculitis, acneiform eruptions, alopecia and other hair-growth abnormalities. EGFR receptor inhibitors cause the largest number of skin problems. The cutaneous side-effects correlate with enhanced survival of patients with lung cancer.1 One other case of FD associated with erlotinib has been reported.2 However, FD may be under-recognized in patients prescribed EGFR inhibitors. Hepper et al.3 in 2011 described scarring alopecia in a patient treated with erlotinib. This also resolved when the treatment was stopped, and recurred on restarting. The histology was reported as perfolliculitis with scarring alopecia. Their diagnosis was that of scarring alopecia, but the similarities in the clinical and histopathological findings with our case suggest
Figure 1 Folliculitis decalvans. Scalp of patient showing perifol-
liculitis, crusting and scarring alopecia.
ª 2013 British Association of Dermatologists
Correspondence
(a)
(b)
Figure 2 Perifolliculitis and alopecia. (a) Vertical section showing predominantly neutrophilic perifolliculitis with occasional foreign-
body giant cells that were negative for periodic-acid–Schiff (PAS); (b) horizontal section showing a marked decrease in the number of hair follicles, with several remnants present. (a,b) Haematoxylin and eosin, counterstained with (a) PAS and (b) Alcian blue, original magnification (a,b) 9 40.
that this may be the same condition as in our patient. Other EGFR inhibitors are also associated with similar cutaneous effects. Graves et al.4 described a case of nonscarring alopecia associated with gefitinib, a TKI used in breast and lung cancer treatment. EGFR knockout mice have disordered hair growth, as well as some fatal systemic implications. In studies in which skin was grafted onto nude mice, the histology description was of follicle buds ‘consumed’ by inflammatory reaction. The authors suggested that EGFR may have a role not only in development of hair follicles, but also in protection from immunological reactions.5 The mechanism in our case may involve inhibition of just such a protection. Greater use of TKIs means we are likely to see more cutaneous adverse effects in dermatological clinics. D. J. Keith, and D. G. Stewart Department of Dermatology, Dudley Group Hospitals NHS Foundation Trust, Dudley, West Midlands, UK E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 15 October 2012 This case was presented as a poster at the SCAR-UK Symposium at the RCP, London, UK, October 2011
References 1 Becker A, van Wijk A, Smit EF, Postmus PE. Side-effects of long-term administration of erlotinib in patients with non-small cell lung cancer. J Thorac Oncol 2010; 5: 1477– 80.
ª 2013 British Association of Dermatologists
2 Hoekzema R, Drillenburg P. Folliculitis decalvans associated with erlotinib. Clin Exp Dermatol 2010; 35: 916–18. 3 Hepper DM, Wu P, Anadkat MJ. Scarring alopecia associated with the epidermal growth factor receptor inhibitor erlotinib. J Am Acad Dermatol 2011; 64: 996–8. 4 Graves JE, Jones BF, Lind AC, Heffernan MP. Nonscarring alopecia associated with the epidermal growth factor inhibitor gefitinib. J Am Acad Dermatol 2006; 55: 349–53. 5 Hansen LA, Alexander N, Hogan ME et al. Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. Am J Pathol 1997; 150: 1959–75.
Progressive symmetrical erythrokeratoderma: report of two Chinese families and evaluation for mutations in the loricrin, connexin 30.3 and connexin 31 genes doi: 10.1111/ced.12135
The erythrokeratodermas (EKs) are a group of monogenic skin disorders with both clinical and genetic heterogeneity. They are characterized by well-demarcated erythematous and hyperkeratotic lesions, and include two major subtypes: erythrokeratoderma variabilis (EKV) and progressive symmetrical erythrokeratoderma (PSEK). EKV is characterized by the coexistence of transient, figurate, erythematous patches and localized keratotic
Clinical and Experimental Dermatology (2013) 38, pp924–935
925
Correspondence
Erlotinib-induced folliculitis decalvans doi: 10.1111/ced.12083
We report a case of erlotinib-induced folliculitis decalvans in an elderly man. Folliculitis is a commonly reported sideeffect of erlotinib and other tyrosine kinase receptor inhibitors. Folliculitis decalvans (FD) is an under-recognized adverse effect that may become more widespread with the greater use of tyrosine kinase inhibitors (TKIs). A 76-year-old man presented to dermatology with ‘scalp symptoms’. He had been diagnosed some time previously with metastatic pulmonary adenocarcinoma and started on erlotinib, to which his cancer had responded well. He reported an itchy, crusting scalp eruption that had developed since starting erlotinib, and which had briefly resolved during an intermission in treatment. The symptoms had gradually worsened since he had been put on a maintenance dose of 75 mg once daily. Ketoconazole shampoo and topical potent corticosteroids had made no improvement. On physical examination, a scaly erythematous eruption was seen on the patient’s scalp, with scarring alopecia at the vertex, and some areas of pustules and crusting (Fig. 1). Two punch biopsies were taken for evaluation. On histological examination, features of alopecia and nonspecific perifolliculitis were seen, including predominantly neutrophilic perifolliculitis with occasional foreign-body giant cells that were negative for periodicacid–Schiff staining, and a marked decrease in the number of hair follicles (Fig. 2). These findings were consistent with a diagnosis of FD. The patient was treated with oxytetracycline 500 mg twice daily, betamethasone 0.1% with clioquinol 3% cream (Betnovate-C®; Chemidex Pharma, Egham, Surrey, UK) and cetrimide 10% with undecanoic acid 1% shampoo (Ceanel Concentrate®; Ferndale Pharmaceuticals Ltd, Wetherby, Yorkshire, UK) and is showing improvement. Erlotinib is an inhibitor targeting the epidermal growth factor receptor (EGFR) tyrosine kinase and is
924
Clinical and Experimental Dermatology (2013) 38, pp924–935
particularly promising as a new drug for non-small-cell lung cancer (NSCLC) with proven benefits on survival. TKIs are known to be responsible for cutaneous sideeffects in up to 50% of patients, with the conditions including simple folliculitis, acneiform eruptions, alopecia and other hair-growth abnormalities. EGFR receptor inhibitors cause the largest number of skin problems. The cutaneous side-effects correlate with enhanced survival of patients with lung cancer.1 One other case of FD associated with erlotinib has been reported.2 However, FD may be under-recognized in patients prescribed EGFR inhibitors. Hepper et al.3 in 2011 described scarring alopecia in a patient treated with erlotinib. This also resolved when the treatment was stopped, and recurred on restarting. The histology was reported as perfolliculitis with scarring alopecia. Their diagnosis was that of scarring alopecia, but the similarities in the clinical and histopathological findings with our case suggest
Figure 1 Folliculitis decalvans. Scalp of patient showing perifol-
liculitis, crusting and scarring alopecia.
ª 2013 British Association of Dermatologists
Correspondence
(a)
(b)
Figure 2 Perifolliculitis and alopecia. (a) Vertical section showing predominantly neutrophilic perifolliculitis with occasional foreign-
body giant cells that were negative for periodic-acid–Schiff (PAS); (b) horizontal section showing a marked decrease in the number of hair follicles, with several remnants present. (a,b) Haematoxylin and eosin, counterstained with (a) PAS and (b) Alcian blue, original magnification (a,b) 9 40.
that this may be the same condition as in our patient. Other EGFR inhibitors are also associated with similar cutaneous effects. Graves et al.4 described a case of nonscarring alopecia associated with gefitinib, a TKI used in breast and lung cancer treatment. EGFR knockout mice have disordered hair growth, as well as some fatal systemic implications. In studies in which skin was grafted onto nude mice, the histology description was of follicle buds ‘consumed’ by inflammatory reaction. The authors suggested that EGFR may have a role not only in development of hair follicles, but also in protection from immunological reactions.5 The mechanism in our case may involve inhibition of just such a protection. Greater use of TKIs means we are likely to see more cutaneous adverse effects in dermatological clinics. D. J. Keith, and D. G. Stewart Department of Dermatology, Dudley Group Hospitals NHS Foundation Trust, Dudley, West Midlands, UK E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 15 October 2012 This case was presented as a poster at the SCAR-UK Symposium at the RCP, London, UK, October 2011
References 1 Becker A, van Wijk A, Smit EF, Postmus PE. Side-effects of long-term administration of erlotinib in patients with non-small cell lung cancer. J Thorac Oncol 2010; 5: 1477– 80.
ª 2013 British Association of Dermatologists
2 Hoekzema R, Drillenburg P. Folliculitis decalvans associated with erlotinib. Clin Exp Dermatol 2010; 35: 916–18. 3 Hepper DM, Wu P, Anadkat MJ. Scarring alopecia associated with the epidermal growth factor receptor inhibitor erlotinib. J Am Acad Dermatol 2011; 64: 996–8. 4 Graves JE, Jones BF, Lind AC, Heffernan MP. Nonscarring alopecia associated with the epidermal growth factor inhibitor gefitinib. J Am Acad Dermatol 2006; 55: 349–53. 5 Hansen LA, Alexander N, Hogan ME et al. Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. Am J Pathol 1997; 150: 1959–75.
Progressive symmetrical erythrokeratoderma: report of two Chinese families and evaluation for mutations in the loricrin, connexin 30.3 and connexin 31 genes doi: 10.1111/ced.12135
The erythrokeratodermas (EKs) are a group of monogenic skin disorders with both clinical and genetic heterogeneity. They are characterized by well-demarcated erythematous and hyperkeratotic lesions, and include two major subtypes: erythrokeratoderma variabilis (EKV) and progressive symmetrical erythrokeratoderma (PSEK). EKV is characterized by the coexistence of transient, figurate, erythematous patches and localized keratotic
Clinical and Experimental Dermatology (2013) 38, pp924–935
925
