Erosive pustular dermatosis of the scalp due to EGFR inhibitors: A multicentric study by EADV task force of ‘Dermatology for Cancer Patients’

We conducted a multicentre retrospective study through the European Academy of Dermatology and Venereology's task force of 'Dermatology for Cancer Patients' to collect cases of erosive pustular dermatosis of the scalp (EPDS) induced by epidermal growth factor receptor (EGFR) inhibitors. EPDS is a rare inflammatory condition marked by erosions, thick brown-yellowish crusts and pustules with serum-hematic exudate, often resulting in skin atrophy and scarring alopecia.1 EPDS usually affects elderly patients with severe androgenetic alopecia and sun-damaged scalps, often following local trauma.1, 2 Common triggers include mechanical injuries, followed by physical therapies, herpes zoster infections, surgical procedures and topical medications.1, 2 Stopping the trauma does not always resolve EPDS, which typically appears around 6 months after the initial trigger.2 Recent reports indicate that EGFR inhibitors, used in cancer treatment, can also trigger EPDS, although only a few cases have been documented.3-6 Fourteen Oncodermatology Units from Greece, Spain, Italy, France, the Netherlands, Switzerland and Argentina, participated in the study. We gathered data on patient demographics, primary cancer types, oncologic treatment protocols, prescribed medications, clinical, trichoscopic and histological characteristics of EPDS, as well as other related skin toxicities. The study included 46 patients (24 females, 22 males; median age 64). Primary cancers were non-small-cell lung cancer (47.8%), colorectal cancer (39.2%), head and neck squamous cell carcinoma (6.5%) and breast cancer (6.5%). The patients' clinical characteristics, trichoscopic and histological findings and established management are fully summarized in Table 1. EPDS typically appeared around 17 weeks after starting EGFR inhibitors, which is a shorter interval compared to the conventional onset time of about 6 months after other triggering factors.1, 2 This shorter latency period is important for patient counselling and anticipating potential adverse events. Clinical findings, trichoscopy and histological features resembled those of primary EPDS2, 5-7 (Figure 1), making it indistinguishable from EGFR inhibitor-induced EPDS without a clinical history. The most common clinical features included diffuse erythema, hyperkeratotic crusts, erosions and erythematous crusted pustular patches. Atrophy and localized hyperkeratotic nodules were also noted. The severity varied, with 47.8% of cases classified as Grade 3 according to the CTCAE v5.0 system. The distribution of scalp lesions was notable: our data showed widespread involvement in most cases (43.5%), in contrast to primary EPDS, which typically affects the vertex region.1 This finding suggests that EPDS induced by EGFR inhibitors could affect the scalp more extensively due to systemic intake. Bacterial cultures were negative in 34.8% of cases and positive in 21.7%, with the remaining cases either inconclusive or not tested, suggesting a limited role for bacterial pathogens. Concomitant skin toxicities included acneiform rash, trichomegaly, hypertrichosis, periungual pyogenic granulomas, pruritus, xerosis, paronychia and papulo-pustular rash, commonly found in patients undergoing therapy with EGFR inhibitors.8 High-potency topical corticosteroids were a key treatment option. Combining topical corticosteroids with oral tetracyclines (doxycycline 200 mg daily or minocycline 50–100 mg daily) was also common, leveraging the anti-inflammatory properties of tetracyclines.6, 9 Therapeutic outcomes showed EPDS regression in 50% of patients, stability in 34.8%, and progression in 15.2%. Most patients (82.6%) did not require changes to their oncology treatment regimens. Our study is the largest multicentre international series on EPDS induced by EGFR inhibitor therapy. The lack of a control group, potential variability in reporting standards across different centres and the presence of confounding factors (e.g. other skin toxicities) are notable limitations. This study highlights the importance of identifying EPDS cases caused by EGFR inhibitors. Given the high frequency of this side effect, early prophylactic minocycline administration is recommended to reduce the risk in patients undergoing anti-EGFR therapy. All authors declare that no funds, grants or other support were received during the preparation of this manuscript. All authors have no relevant financial or non-financial interests to disclose regarding this manuscript. The patients were informed about the use of their clinical information according to the Declaration of Helsinki principles and photos for publication intent. The informed consent was appropriately obtained during the medical examination. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.