Trichomegaly Induced by Cetuximab: Case Series and Review the Literature Ulkuhan I. Koksal, MD,* Kezban N. Pilanci, MD, Cetin Ordu, MD, Kerem Okutur, MD, Sezer Saglam, MD, and Gokhan Demir, MD Trichomegaly is a rare side effect of epidermal growth factor receptor inhibitors. We present here 4 patients who treated with cetuximab (an epidermal growth factor receptor inhibitor) for metastatic colorectal cancer. All of the cases were treated with cetuximab 500 mg/m 2 biweekly in combination protocol. The mean period from the start of the treatment until the development the trichomegaly was 4.75 (3–6) months. In all of the patients after the end of the cetuximab therapy, trichomegaly was regressed. Only 1 case resolved with topical treatment that conjunctivitis with trichomegaly. Tricho- megaly is an important ocular toxicity of cetuximab that can cause visual discomfort and corneal damages. However, these side effects usually do not require discontinuation of treatment. Keywords: cetuximab, trichomegaly, colorectal carcinoma INTRODUCTION Epidermal growth factor receptor (EGFR), a transmem- brane glycoprotein, is a member of the ErbB family of receptors. It has an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyrosine kinase domain. It is activated by epidermal growth factor and transforming growth factor-a, and it turns from an inactivate monomeric form to an active homodimer. EGFR dimerization stimulates its intrinsic intracellular protein kinase activity and initiates several signal trans- duction cascades. 1 The EGFR signaling pathway regulates cell differentiation, migration, proliferation, apoptosis, and angiogenesis that are deregulated in cancer cells. 2,3 The effects of EGF on turnover of the hair follicle has been known for a long time. Epithelial growth factor (EGF) was shown to retard hair growth. Because EGFR promotes the discontinuation of the anagen stage, its downregulation is associated with hair follicle formation. 4 Cetuximab is a chimeric IgG1 monoclonal antibody that blocks the EGFR. Dermatologic side effects of ce- tuximab are acneiform rash, paronychia, xerosis, dermatitis-like eruption, pruritus, skin fissures, and hair changes. 5,6 Skin toxicity is the most common side effect and a predictive indicator of treatment response. 6 The most common ocular side effects are dysfunctional tear syndrome, blepharitis, eyelid skin rash/hyperemia, and eyelash changes (trichomegaly and trichiasis). 7 Trichomegaly is the lengthening of the eyelashes. Familial diseases (Oliver-McFarlane syndrome, Corne- lia de Lange syndrome, Aghaei-Dastgheib syndrome, Goldstein-Hutt syndrome, cone-rod dystrophy, type I oculocutaneous albinism, familial trichomegaly), para- neoplastic syndromes, malignancies (kidney adenocar- cinoma), AIDS, dermatomyositis, systemic lupus erythematosus, and drugs (interferon alfa-2b, cyclo- sporine, bimatoprost, latanoprost, phenytoin, zidovu- dine, penicillamine, tacrolimus, topiramate, erlotinib, gefitinib, panitumumab) can cause trichomegaly. 3,8,9 The EGFR is expressed in the epidermis, the sweat gland apparatus, and hair follicle epithelium by basal keratinocytes and outer root sheath cells. 3 Disregu- lated keratin expression due to inhibition of EGFR Department of Medical Oncology, Faculty of Medicine, Bilim University, Istanbul, Turkey. The authors have no conflicts of interest to declare. *Address for correspondence: Department of Medical Oncology, Faculty of Medicine, Bilim University, Bedrettin Mah. Bedii Gor- bon Sk. No: 1 S ¸is ¸hane, Beyo glu/ _ Istanbul, Istanbul 34440, Turkey. E-mail: drulkuhankoksal@yahoo.com American Journal of Therapeutics 0, 1–4 (2015) 1075–2765 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. www.americantherapeutics.com Copyright Ó 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.