Complete sustained regression of extensive psoriasis with cetuximab combination chemotherapy

To the Editor Cetuximab is a monoclonal antibody with high affinity for epidermal growth factor receptor (EGFR). Its capacity to specifically inhibit EGF-R is useful for the treatment of epithelial tumours over-expressing EGFR (1). The main adverse effects are dermatological disorders: acute acne, maculopapular eruptions, seborrheic dermatitis, perionyxis, and trichomegaly. The presence and intensity of these adverse effects are considered to have positive predictive value for tumour response (2 /4). We report the case of a patient with longstanding psoriasis who developed metastatic colon cancer. A combination chemotherapy regimen containing cetuximab led to rapid complete and sustained regression of the psoriasis. A 65-year-old man was included in a phase II trial of a combination chemotherapy protocol delivered every two weeks for the treatment of colon cancer. The regimen included irinotecan 180 mg/m on day 1, l-folinic acid 200 mg/m on day 1, 5-fluorouracil 400 mg/m bolus on day 1, 5-fluorouracil 2400 mg/m continuous infusion for 46 hours, and 1-hour infusion of cetuximab (Erbitux†, MerckLipha Santé, 116 rue Carnot 92152, Suresnes Cedex, France) delivered weekly (400 mg/m for the first delivery and 250 mg/m thereafter). Since the age of 15 years, the patient had typical uncomplicated psoriasis affecting the lumbar area, the lower limbs, the elbows, and the forearms. Diverse local treatments (UVB phototherapy, local corticosteroids, keratolytic ointment) had provided partial and temporary relief. At onset of chemotherapy on 26 May 2003, the patient had non-inflammatory and non-pruriginous squamating psoriasis lesions affected the lumbar area and the lower limbs. He had not taken any treatment for several months. One week after starting the chemotherapy protocol, the patient received his second cetuximab infusion and noted a clear improvement in his psoriasis lesions. By 11 June 2003, all cutaneous lesions had totally regressed, simply leaving a few areas of dyschromism on otherwise healthy skin. Adverse effects were moderate and limited to dermatological disorders: acne affecting the face and neck, perionyxis affecting the fingers, and trichomegaly. These undesirable effects of cetuximab disappeared at withdrawal. The only persistent effect was the presence of very long eyelashes. The patient completed 12 chemotherapy sessions, receiving 24 cetuximab infusions. Objective tumour response was achieved and secondary liver surgery was scheduled. The psoriasis lesions did not reappear during treatment or after treatment end (current follow-up six months). This patient, who had lived with psoriasis for 50 years, stated he had never experienced such a complete regression for such a long period. EGFR is important for normal skin development and function; EGF receptors are located in keratinocytes and hair follicles in the outer root sheath (5). Psoriasis is a proliferative disease of the epidermis that leads to major disorders in keratinocyte differentiation. It has been hypothesized that intrinsic alterations of the keratinocyte or local or general immune disorders could be involved (6). The causal abnormality could be the result of an increased recruitment of cycling cells from the resting fractions. Inappropriate survival of keratinocytes due to EGFRmediated hyperstimulation could contribute to the pathogenesis of psoriasis (6, 7). The complete resolution of psoriasis in our patient given cetuximab may have resulted from its regularizing effect on the cell cycle of keratinocytes abnormally stimulated by psoriasis (8). It is unlikely that the improvement resulted from the other chemotherapy agents or the corticosteroids. This possible ‘collateral’ effect of cetuximab is noteworthy and might offer a promising new opportunity for the treatment of extensive or complicated psoriasis unresponsive to usual treatments. LETTER TO THE EDITOR