We searched PubMed to identify the references for this Review using the terms “nails”, “paronychia”, and “chemotherapy”, or “targeted therapy”, “melanonychia”, “leukonychia”, “onycholysis”, “pyogenic granuloma-like lesions”, “onychomadesis”, and “brittle nail” between Jan 1, 1990, and Dec 31, 2013. Articles were also identified through hand searches through the authors' own files. The final reference list was generated based on their originality and relevance to the broad scope of this Review.
ReviewNail toxicities induced by systemic anticancer treatments
Introduction
Changes in the nail unit are common during the course of systemic cancer treatment and sometimes can be associated with pain and functional impairment. In a prospective study1 of 91 women with advanced cancers, 21 (23%) women developed nail changes and of these, five (24%) women reported this adverse effect was the most unpleasant side-effect.
There is a dearth of information about nail changes in the specialty of oncology, but these data are probably not representative of patient curiosity about their nail changes and how these can affect their daily activities. This discrepancy could stem, partly, from the grading system used by clinicians that is based on the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE; appendix), which does not incorporate the range of nail changes or their effect on patients. These changes are usually noted on several nails and mostly in fingernails rather than in toenails, except for changes aggravated by pressure, rubbing, and traumas—eg, EGFR-induced paronychia, which is mostly noted in the big toenail. A single centre study2, 3 was done in Gustave Roussy (Paris, France) between Aug 1, 2008, and Dec 31, 2011, and included 607 patients who were referred to the dermatology unit for any skin, hair, or nail adverse event due to anticancer agents. Findings of this study2, 3 showed 235 (39%) patients presented with nail changes. The distribution of patients presenting with changes was well balanced between those receiving targeted therapies and those receiving cytotoxic chemotherapies. Of the targeted treatments given to participants, cetuximab was the most frequently reported cause of painful paronychia, noted in 18 (20% from 88 patients receiving cetuximab) patients.
The occurrence and disappearance of nail changes are delayed relative to the initiation and interruption of systemic treatments because of the kinetics of nail formation and growth. Knowledge of the nail growth rate is useful to help to understand why nail plate changes show past events and to establish onset and duration of these events. Nails grow continuously at an average rate of 0·1 mm per day (3 mm per month) for fingernails and at 0·03 mm per day (1 mm per month) for toenails. Thus, complete regrowth takes 4–6 months for a fingernail and 12–18 months for a toenail. Knowledge of the anatomy and physiology of nails is crucial to analyse changes induced in the nail and surrounding tissue by anticancer treatments (Figure 1, Figure 2, Figure 3).
The effect of nail changes induced by anticancer drugs on a patient's quality of life varies and has rarely been assessed prospectively, but some symptoms (eg, anti-EGFR-induced paronychia or subungual haematomas) can be painful and functionally debilitating. Although some preventive measures that aim to decrease the incidence or severity of nail-induced adverse events can be proposed to patients before initiating anticancer therapies, most nail toxic effects cannot be avoided completely. When such adverse events do occur, some nail symptoms need a therapeutic intervention, but, in many cases, patients only need reassurance from their physicians that these nail changes are expected adverse effects of anticancer therapies, and are reversible after treatment discontinuation. For targeted therapies, which are often administered in long durations, preventive and therapeutic measures are more frequently needed and are more useful than for conventional chemotherapies.
Changes in the nail apparatus induced by anticancer therapies are usually classified using the NCI-CTCAE v4·3. Five changes are considered in this grading scale: paronychia, nail loss, nail ridging, nail discoloration, and nail infection (appendix). However, this classification is inadequate to capture the entire range of nail changes with anticancer therapies or drugs and the effects that such symptoms can have on a patient's quality of life. For example, painful nail bed haemorrhages due to treatment with taxanes can impair patients' daily living, but cannot be correctly reported with this grading system. A different scale4 has been proposed that divides nail changes into those of the nail plate, folds, or digit tips and is more adapted to note toxic effects to the nail apparatus specifically induced by EGFR inhibitors (which could be extended to also assess MEK inhibitors) than the CTCAE scale is.
Nail changes can involve the nail plate, nail bed, periungual area, or all of these. Toxic effects on the nail plate and changes to the nail bed occur more frequently with cytotoxic chemotherapies than with targeted anticancer therapies. By contrast, periungual lesions are the most common and debilitating manifestations in patients treated with targeted anticancer therapies.
Section snippets
Nail changes induced by cytotoxic chemotherapies
Nail plate colour abnormalities (chromonychia), transverse grooves on the nail plate (Beau's lines), and decreased linear nail growth are the most common changes to nails due to cytotoxic chemotherapies.
Toxic effects to the nail plate and nail bed
Changes in nail pigmentation can occur but are less frequent in patients treated with targeted therapies than in patients treated with cytotoxic chemotherapies.29
Imatinib can induce longitudinal, transverse, or diffuse melanonychia on both fingernails and toenails.30, 31 The mechanism of action is uncertain, but it is probably associated with the effect of c-KIT blockade on microphthalmia-associated transcription factor, which controls melanogenesis.32 If true, this association could also
Management of nail adverse events induced by anticancer drugs
Many of the nail changes induced by anticancer drugs do not need specific treatment, because they show only past damage to the matrix and are often asymptomatic and reversible. Such is the case for Beau's lines, onychomadesis, melanonychia, and true or apparent leukonychia. All these lesions will grow distally with nail growth and eventually disappear with treatment discontinuation. However, patients are often curious and sometimes worried by the appearance of these nail changes, emphasising
Conclusion
Nail adverse events are very frequent in patients who are treated with anticancer drugs. These events mostly affect the nail plate or bed with cytotoxic chemotherapies and result from their antimetabolite effects compared with targeted therapies that more frequently involve the perionchium and result from off-target effects.
Classification of these toxic effects should allow patients to receive adequate treatment, but this grading system cannot replace the common sense and the skills of a
Search strategy and selection criteria
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