Erosive Pustular Dermatosis and Amivantamab for Lung Cancer: A Case Report Open Access

The monoclonal antibody amivantamab is indicated as a second-line treatment for certain types of non-small cell lung cancer (NSCLC) [1]. Linked to its anti-epidermal growth factor receptor (EGFR) and anti-mesenchymal-epithelial transition (MET) mechanisms, there is an entire array of cutaneous adverse effects that should be rapidly and adequately dealt with to avoid a negative impact on the quality of life of the patient. Despite prophylactic measures in association with amivantamab treatment [2], severely disfiguring cutaneous adverse events may occur, such as erosive pustular dermatosis (EPD) with alopecia, an exceptional event, presented in this case report.

The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000546616). Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

A 67-year-old woman presented with a lower right lobar adenosquamous carcinoma, stage T3N2M1c, with pulmonary, hepatic, and nodal carcinomatosis as well as a single brain metastasis. The cancer presented an insertion in exon 20 of the EGFR gene. Despite 4 courses of first-line chemotherapy with cisplatin 80 mg/m² and pemetrexed 500 mg/m², tumor progression was observed. Subsequently, an intravenous therapy with amivantamab, 1,050 mg every week for 4 weeks, followed by injections every 2 weeks, was initiated. After 5 months of therapy, the patient developed disseminated crusted lesions on her scalp. According to recommendations, oral minocycline 50 mg/day and a medium potency topical corticosteroid once a day were initiated. However, after 1 month, the severity of the lesions worsened. The patient presented large, eroded, pustular and oozing plaques affecting almost 50% of her scalp (Fig. 1a). Histology revealed a dense neutrophilic inflammatory infiltrate underlying an eroded epidermis (Fig. 1b). No fever or septic signs were evidenced. The wound culture demonstrated Staphylococcus aureus resistant to clindamycin and erythromycin. The patient was treated with amoxicillin/clavulanic acid 875/125 mg 3 times a day for 10 days, and a local treatment with povidone iodine soap and fusidic acid cream. The patient’s hair extensions had to be removed, and her hair cut was cut short to allow adequate local care, severely affecting her self-esteem and personal image. Amivantamab was put on hold. A complementary treatment with oral methylprednisolone 0.5 mg/kg/day and a topical alginate dressing were initiated according to the recommendations [2]. The infection was rapidly cleared. A skin biopsy evidenced a post-infectious non-specific ulceration. Three weeks later the patient was completely healed. Hair regrowth was observed after 8 weeks with partial cicatricial alopecia of the prior sites of EPD. Six months later, the patient is still in oncologic remission and the metastatic pulmonary tumor showed no further sign of progression. Unfortunately, identical EPD lesions spontaneously reappeared recently with alopecia of the eroded areas (Fig. 2).

Amivantamab is a bispecific monoclonal antibody directed against EGFR and MET receptors. Amivantamab is primarily used in the treatment of certain types of NSCLC, particularly those with specific alterations in the EGFR or MET genes. These alterations include an EGFR mutation with exon 20 insertions or an activating MET mutation, both of which drive tumor growth. Due to its multiple modes of action, it is a promising new option in the management of patients with metastatic NSCLC [3].

However, linked to its mode of action, amivantamab is responsible for multiple cutaneous adverse events [1‒3]. The expected cutaneous toxicities are linked to EGFR and MET inhibition. The EGFR gene is abundantly expressed in keratinocytes, dendritic cells, connective tissue cells as well as in skin adnexa. The activation of the EGFR gene promotes wound healing, counters inflammation and stimulates the constriction of capillaries [2]. EGFR inhibition, hence, conducts to cutaneous adverse effects by the destruction of the physical barrier, damages hair follicles, and activates host immune reactions. The destruction of the hair follicles leads to the acneiform eruption and the papulopustular exanthema. Furthermore, EGFR plays an important role during the hair growth cycle [2]. Hair can become brittle, thin, and curly [2]. MET tyrosine kinase inhibitors may also lead to cutaneous toxic effects with hand-foot skin reaction, hair depigmentation, and skin xerosis [2].

The most frequent dermatologic adverse events are acneiform rashes [4] and paronychia (100% of cases). Other reported effects include hair growth changes (hypertrichosis in 50% of men and hirsutism in 80% of women), scalp abrasions (71%), and skin fissures (57%) [2]. To mitigate these cutaneous toxicities, specific recommendations have been developed [2], including the following prophylactic measures: 2 weeks before treatment initiation, tetracyclines 300 mg/day, skin hydration, and appropriate local hygiene measures are initiated.

This patient showed an exceptional and severe adverse cutaneous reaction in the form of extensive crusting and oozing plaques, erosions and ulcerations. Three prior cases have been reported [5] and were classified as EPD of the scalp. Two were managed with low-dose oral prednisolone, oral and topical antibiotics, and the cessation of amivantamab, as in our patient. The third patient required oral dapsone to control the scalp lesions and amivantamab was continued every 3 weeks. Our patient reflects this EPD-like eruption as it occurred between 4 and 13 months after initiation of amivantamab. Hence, our patient presented an additional case of EPD under amivantamab.

This report also underlines the importance of rapid and appropriate care to avoid disfiguring and recurring consequences that, if not treated as soon as possible, may lead to the need of cutting the hair short, which is a very traumatizing experience for the patient, already coping with metastatic cancer [6]. Long-term follow-up is recommended as spontaneous recurrences can occur, as in this case.

To date, the exact pathophysiology of this adverse effect is still unknown. It is assumed to be related to the integral role of EGFR in cellular signaling pathways in the skin.

In conclusion, patients receiving amivantamab should be closely monitored for cutaneous adverse reactions and prophylactic treatment should be provided. EPD should be managed with adequate topical care, oral tetracyclines and oral methylprednisolone and the discontinuation of amivantamab. A long-term follow-up is recommended as recurrences can spontaneously occur, despite the discontinuation of amivantamab.

Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. In addition, this study was reviewed and the need for approval was waived by EC CHU Liège, Accreditation No.: 707, Liège, Belgium.

The authors have no conflicts of interest to declare.

The authors declare that no funding was obtained or used for this study.

Conception and design of study: Yseult Senterre, Amandine Bouillenne, Murielle Sabatiello, and Arjen F. Nikkels, Acquisition of data: Yseult Senterre and Murielle Sabatiello. Analysis and/or interpretation of data: Murielle Sabatiello, Anne-Sophie Demoulin, and Arjen F. Nikkels. Drafting the manuscript: Yseult Senterre and Arjen F. Nikkels. Approval of the version of the manuscript to be published: Yseult Senterre, Amandine Bouillenne, Murielle Sabatiello, Anne-Sophie Demoulin, and Arjen F. Nikkels.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.