Erosive pustular dermatosis of scalp secondary to epidermal growth factor receptor (EGFR) inhibitors

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A 53-year-old man was referred to the dermatology outpatient department for extensive purulent discharge and crusted erosions over the scalp for 2 months. The patient was receiving crizotinib and dacomitinib for non-small-cell lung carcinoma for 2 years. His complaints included generalised itching and pus discharge from nail folds for the past 1.5 years, without hampering daily activities. The patient was on prophylactic long-term doxycycline therapy for 2 years. Examination revealed multiple linear and reticulate, yellow-crusted erythematous macules symmetrically on the chest and neck, sparing flexures [Figure 1a] with generalised xerosis. The scalp showed thick yellow crusted plaque with pus discharge, with brittle hair [Figure 1b]. Nail examination showed nailfold swelling and periungal hypertrophic granulation tissue. Remaining mucocutaneous and systemic examinations were normal.

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Figure 1a:

Multiple linear and reticulate, yellow-crusted erythematous macules symmetrically on the chest, sparing flexures.

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Figure 1b:

Scalp shows thick, yellow-crusted plaque with pus discharge, with brittle hair.

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Biopsy from the crusted linear papule and scalp demonstrated moderately dense perifollicular infiltrate of lymphocytes, histiocytes, plasma cells, and neutrophils in the upper and mid dermis [Figures 2a and 2b]. Routine blood investigations such as complete blood counts, liver function, and renal function tests were normal. Pus culture sensitivity revealed Pseudomonas aeruginosa, and initiated treatment with ciprofloxacin (500 mg) twice daily along with prophylactic doxycycline. Two weeks of therapy remained ineffective. Subsequently, injectable piperacillin and tazobactam, along with oral prednisolone and isotretinoin (20 mg), were administered for 2 weeks. Follow-up showed partial resolution of the lesions, and isotretinoin was continued for the next 3 months. Thereafter, EGFR inhibitors (dacomitinib) was discontinued and shifted to pemetrexed and carboplatin therapy. Complete resolution of lesions was noted at 2 months of follow-up with a tapering dose of isotretinoin.

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Figure 2a:

Histopathology depicts upper and mid dermal, perifollicular dense inflammatory infiltrates (Haematoxylin and eosin, 40x).

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Figure 2b:

Inflammatory infiltrates composed of lymphocytes, histiocytes, plasma cells, and neutrophils (Haematoxylin and eosin, 100x).

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Two major cutaneous adverse events of epidermal growth factor receptor (EGFR) inhibitors have been reported. One is the PRIDE complex (papulopustules and/or paronychia, regulatory abnormalities of hair growth, itching, and dryness due to EGFR inhibitors), and the other is erosive pustular dermatosis of the scalp (EPDS). EPDS is a rare dermatosis affecting elderly females following local trauma such as cryotherapy, radiotherapy, and surgery. It is characterised by pustules, erosions, and crusting with subsequent scarring alopecia of the scalp. Perinatal damage with prolonged labour and caput succedaneum has been linked with EPDS in neonates, while sunburn, flame, scald, and chemical burn from bleaching hair, neurosurgeries, and skin grafts have been associated with EPDS in the elderly.¹ EGFR inhibitors, such as gefitinib, erlotinib, and dacomitinib, have been used for non-small-cell lung carcinoma and head and neck tumours. The use of this class of drugs has been linked to dermatological side effects such as PRIDE complex and EPDS-like eruption.^2,3 There are fewer than 20 reports of EPDS-like eruptions linked to EGFR inhibitors. Dysregulation of follicular keratinocytic proliferation and differentiation is thought to be the pathomechanism for papular and pustular eruptions, whereas elevated production of epidermal chemokines, including CXCL1 and 9 and CCL18, intensifies skin inflammation and pustulation. Premature expression of keratin 1 and signal transducer and activator of transcription 3 (STAT3), as well as accumulation of the drug in the eccrine ducts, impair barrier function and cause xerosis and pruritus.^2,3 The clinical presentation of EPDS-like eruption due to EGFR inhibitors includes pustular eruption, later developing thick purulent and haemorrhagic crusting with or without scarring alopecia, predominantly affecting the frontal and parietal regions of the scalp.^3,4

The stage of the lesion determines the histopathology of EPDS, and it is frequently nonspecific. Psoriasiform hyperplasia and a mixed inflammatory infiltrate characterize early lesions. Mid-stage lesions demonstrate inflammatory infiltrates, occasional fibrosis with reduced follicles and sebaceous glands. More extensive fibrosis with minimal inflammatory infiltrates occur in late stages.⁴ The treatments for EGFR-induced EPDS-like eruptions include topical corticosteroid and photodynamic therapy with minimal side effects or recurrences. Oral dapsone, doxycycline, and isotretinoin were additional effective therapeutic choices in unresponsive cases.⁵ The patient responded inadequately despite the combination therapy of topical and oral corticosteroids, oral isotretinoin, and parenteral antibiotics. The chemotherapeutic agent was replaced by carboplatin and paclitaxel

In conclusion, we report a rare and therapeutically challenging case of dacomitinib-induced EGFR-like eruption.