Severe nail changes due to Docetaxel treatment

ARTICLE

Auteur(s) : Leyla RAFI¹, Michael FRIEDRICH², Wolfgang TILGEN¹ Jörg REICHRATH¹

¹ Department of Dermatology, The Saarland University Hospital, 66421 Homburg/Saar, Germany
² Department of Gynecology, The Saarland University Hospital, 66421 Homburg/Saar, Germany

Article accepted on 22/09/2003

The semi-synthetic taxoid docetaxel (RP 56976, Taxotere^®), that belongs to the taxane group of chemotherapeutic agents, is successfully used in the treatment of various malignancies including ovarian, breast, lung and head and neck cancer [1-3]. Neutropenia, myalgia, fluid retention, neuropathy, hypersensitivity reaction and mucositis represent well-documented side-effects due to docetaxel treatment. Additionally, it has been shown that skin toxicity may occur in as many as 50-70% of patients. Cutaneous side effects may present clinically as an erythematous pruritic maculopapular rash, desquamation of the hands and feet, dry skin, erythematous plaques, alopecia, hyperpigmentation, palmoplantar erythrodysaesthesia or nail changes [4-12]. The incidence of nail changes [4-12] that may include nail bed dyschromia, onychodystrophia, onycholysis, red or orange Beau's lines with or without paronychia, subungual haemorrhage or subungual abscess has been reported to occur in as many as up to 35% of patients treated with docetaxel [9]. Most of these patients develop only minor signs of skin or nail toxicity.
We report a patient with unusual nail changes following docetaxel therapy. This 46-year-old woman was diagnosed as having metastatic breast cancer (bone, lung, hepar; pT2pN1biii), received chemotherapy with docetaxel (Taxotere^®, Rhône-Poulenc Rorer) every three weeks starting November 2001. At the end of six cycles (cumulative dose 1110 mg), she developed changes in the nails of all the digits of both hands in the form of dyschromasia, dystrophia, onycholysis, subungual haemorrhages and abscesses (Fig. 1). Dyschromia of the nail bed and Beau's lines were found as well. Nail changes were not painful. The toenails were not involved. Microbiological analysis of nails revealed no evidence for bacterial infection or onychomycosis. The nail changes diminished slowly under topical antiseptic treatment (Octenisept^®-solution) after discontinuation of docetaxel-treatment.
It is well known that skin and nail toxicities belong to more frequent non-haematological adverse reactions following docetaxel therapy [4-12]. However, these symptoms are mild in most cases. The combination of nail dyschromia, onycholysis, subungual hyperkeratosis and Beau's lines, that we report here in our patient is published only rarely [4, 8, 9]. Nothing can be said about the true occurrence of nail changes due to taxane because only an unknown fraction is published. Especially subungual haemorrhages, that may be observed in various systemic diseases, are very rare following docetaxel therapy: only a few cases have been reported previously [9, 10, 12]. It has been speculated that the type of nail alteration may be related to the cumulative docetaxel-dose or the number of cycles administered [9]. Subungual haemorrhages have been reported after relatively high cumulative doses and after several cycles of docetaxel-treatment [9, 10, 12]. Recently, it has been suggested that the integrity of peripheral nerves is necessary for developing nail alterations secondary to docetaxel [12]. Two neurotropic mechanisms have been envisioned: taxoids may activate nociceptive C-fibres that cause neurogenic inflammation by release of neuropeptides or they may enhance inflammatory processes by releasing prostaglandins from sympathetic postganglionic terminals [12]. In accordance with the latter, it has been reported that a cyclooxygenase-2 inhibitor improved docetaxel-induced nail changes in a patient [12]. So far, there are no effective preventive measures known. As these nail changes are prone to develop bacterial infection secondary to the chemotherapy-induced immunosuppression, we recommend topical antiseptic treatment. Severe bacterial paronychia or subungual abscesses should be treated systemically with antibiotics. In general, the nail changes reverse fully on discontinuation of docetaxel-treatment. As taxoids are being used for an increasing number of indications, it is of high importance that clinicians are aware of these side-effects and that patients are informed about the possibility of skin and nail toxicity due to docetaxel treatment. n

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