Letter

Paronychia induced by cetuximab, an antiepidermal growth factor receptor antibody

Targeted anticancer therapies, unlike the traditional cytotoxic chemotherapies which lead to systemic toxicities, frequently cause cutaneous adverse events that are symptomatic and manifest in cosmetically sensitive areas. The most common dermatologic toxicities related to epidermal growth factor receptor (EGFR) inhibitors are papulopustular eruption, xerosis, pruritus and paronychia. Vascular endothelial growth factor receptor (VEGFR) inhibitors usually cause hand-foot skin reaction. Reports of dermatologic side effects such as abnormalities of hair growth and mucosal changes also increased.

These events may contribute to poor adherence, dose interruption and discontinuation of the regimens. In addition, psychosocial discomfort causing reduction in the quality of life does occur. However, the presence and severity of cutaneous adverse events has shown to have positive correlation with treatment response.

The management of these side effects can be categorized into prophylaxis and reactive treatment. Systemic antibiotics and topical corticosteroid could possibly prevent or alleviate symptoms caused by EGFR inhibitors. The prevention of sun exposure is recommended to all patients on targeted therapy, and emollients and lubricants can be used to relieve and improve the hand-foot skin reaction.

Brittle nail, simple chronic paronychia, and onycholysis represent three of the most prevalent nail disorders. Brittle nails are characterized by increased fragility of the nail plate due to damage to the nail matrix or changes to nail plate cohesion, caused by internal and/or external factors. Simple chronic paronychia represents an inflammatory process of the lateral and/or proximal nail folds of the fingernails or toenails often preceded by damage to the cuticle. Onycholysis describes the detachment of the nail plate from its nail bed, often attributable to dermatologic conditions, infections, drug therapy, or trauma.

Chemotherapy and its cutaneous side effects are an increasingly common source of iatrogenic injury to the skin, hair, and nails. Cutaneous changes are among the most common side effects from treatment with particular targeted chemotherapeutic agents, especially those that target the epidermal growth factor receptor and small molecule multikinase inhibitors. Less common, but growing in recognition, are the development of secondary cutaneous neoplasms and subacute cutaneous lupus erythematosus as a result of chemotherapy. There is considerable overlap of the multiple entities described as a side effect from conventional chemotherapeutic agents; therefore, the term “toxic erythema of chemotherapy” can be used as an easily understood name.

Inhibition of the epidermal growth factor receptor (EGFR) represents one of the most important avenues for research and development in the field of cancer therapy. The EGFR is a member of the ErbB receptor tyrosine kinase (TK) family, which also includes ErbB-2 (HER2/neu), ErbB-3 (HER3), and ErbB-4 (HER4). Current EGFR therapies available for use include monoclonal antibodies such as cetuximab and small-molecule EGFR TK inhibition by agents such as erlotinib. Side effects of these agents include dermatologic manifestations, without the bone marrow suppressive properties of chemotherapy. Understanding of rash and how it relates to EGFR inhibitor toxicity and, perhaps more importantly, EGFR inhibitor response, must be more clearly defined with clinical trials. The optimum management of rash in patients receiving anti-EGFR therapy remains somewhat controversial; this is secondary to imprecise classification of rash as well as the lack of clinical trials to determine the most appropriate treatment algorithm for these patients. We propose a treatment strategy to help aggressively treat dermatologic side effects, allowing patients to continue receiving therapy without dose interruption or drug discontinuation.

The human epidermal growth factor receptor (EGFR) signaling is overexpressed in many solid malignancies, making it an appealing target for biologic agents. A number of agents that target this receptor are in use or in development. A specific adverse effect common to this class of agents is an acneiform-like skin rash that has been related to EGFR inhibition in the skin. Little is known about the etiology of this rash, and there are no clear evidence-based management recommendations. Findings suggest that there is a relationship between the development of rash and response and/or survival, making rash a potential surrogate marker of activity. This review summarizes and updates the current knowledge of the clinical presentation, etiology, and predictive and prognostic value of erlotinib-induced skin rash and establishes a treatment strategy to help treat dermatologic adverse events and allow patients to continue therapy without dose interruption or drug discontinuation.