After 3 months of treatment, the patient developed mild typical acneiform lesions commonly described in patients receiving EGFR inhibitors. She also observed a marked increase in the length of her eyelashes after 5 months of treatment (Figure 1) without associated hypertrichosis. This trichomegaly induced visual discomfort and obligated the patient to cut her eyelashes. She received 36 courses of cetuximab during 9 months with stabilization of metastatic lesions, but the last assessment, performed in December 2004, showed progressive disease. Our patient did not receive other trichomegaly-inducing drugs. One month after the stopping of cetuximab the eyelashes were normal.
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Cetuximab is the first monoclonal antibody (IgG1) that has demonstrated activity in metastatic colorectal cancer patients with EGFR expression [5]. Cetuximab binds specifically to the EGFR preventing dimerization, and blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and improve apoptosis [5
]. EGFR is expressed in the epidermis, the sweat gland apparatus and hair follicle epithelium, especially the outer root sheath of the hair follicles. Experimental studies have demonstrated a central role of the EGFR in the normal differentiation and development of the hair follicle [6
]. Acneiform eruptions, paronychial swellings, are more specific skin toxicity observed with cetuximab. Busam et al. [6
] suggested that alteration of p27kip1 (negative growth regulator) may be the mechanism by which cetuximab can affect follicular and epidermal homeostasis.
This upregulation of p27kip1 has also been reported with gefitinib (Iressa®; AstraZeneca, Wilmington, DE, USA), which increase apoptosis and maturation. This maturation can explain trichomegaly induced by gefitinib [4]. Two cases of trichomegaly associated with cetuximab were reported by Dueland et al. [7
], who suggested that the mechanism regulating the growth of hair may differ in different parts of the body, with stimulation of the growth of the eyelashes at the same time as hair loss induced by irinotecan.
In our case, trichomegaly of the eyelashes was reported after the beginning of cetuximab with completely regression of this symptom 1 month after stopping administration of cetuximab, and the patient did not receive other trichomegaly-inducing drugs. These arguments can confirm the relationship between cetuximab and trichomegaly. Cetuximab can be added to the list of drugs responsible for trichomegaly of the eyelashes.
Departments of 1 Gastroenterology and 2 Dermatology, University Hospital of Reims, Reims, France
* E-mail: obouche{at}chu-reims.fr
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