Diagnosing And Treating Chemotherapy-Induced Nail Changes
A case study by Wasner and colleagues suggests that peripheral nerve fibers play a role in the development of chemotherapy-induced nail abnormalities.14,15 In this case study, a patient undergoing docetaxel (Taxotere, Sanofi Aventis) treatment for advanced breast cancer had complete peripheral nerve palsy of the right arm due to tumor infiltration of the brachial plexus. During treatment, the patient developed docetaxel-induced onycholysis of all extremities with the exception of the paralytic hand. The authors postulated two mechanisms to account for the absence of nail changes in the paralytic extremity: release of neuropeptides by activation of nociceptive C-fibers as is present in cases of neurogenic inflammation, or release of prostaglandins by sympathetic postganglionic fibers.
In accordance with the hypothesis that chemotherapy-induced onycholysis is an inflammatory process that is maintained by postganglionic sympathetic terminals and nociceptive c-fiber afferents, the authors of the case study treated the patient with a cyclooxygenase-2 inhibitor.14,15 The patient experienced improvement in nail alterations in the neurologically intact limbs.
Dose and frequency of chemotherapy drug administration. For many drugs, there is a dose-specific effect related to chemotherapy-induced nail changes. Hussain and coworkers studied 91 patients receiving treatment with paclitaxel (Abraxane, Celgene).16 Patients receiving more than six weekly doses of paclitaxel developed onycholysis while patients who received fewer weekly treatments did not develop onycholysis.
Further, Spazzan, Mourad and their respective colleagues report a higher incidence of adverse effects on the skin and nail apparatus with weekly versus every three weeks treatment with paclitaxel.17,18 Segaert and Van Cutsem additionally report a dose-dependent effect on the development of skin and nail changes following treatment with epidermal growth factor receptor inhibitors.4
Environmental factors affecting chemotherapy-induced nail changes. In addition to the direct toxic effects that chemotherapy drugs may have on the nail plate and surrounding soft tissues structures, researchers have shown that environmental factors have an effect on chemotherapy-induced nail changes.16
Authors have suggested that chemotherapeutic agents increase sensitivity of the nail apparatus to ultraviolet light. Hussain and colleagues found that onycholysis secondary to paclitaxel treatment for breast carcinoma increases by exposure of the hyponychium to sunlight.16 The researchers additionally found that protecting the nails from sunlight prevented nail loss in a large percentage of patients despite continued chemotherapy treatment.
The hypothesis is that the hyponychium may be more sensitive to UV light following chemotherapy treatment and that UV light may induce nail changes by rupturing the bond between the nail plate and the hyponychium directly or by inhibiting cellular maturation in this area.16 In addition to increased sensitivity to UV light, the toxic effects of chemotherapeutic drugs can make nail plates thin, brittle and more prone to mechanical trauma.
Secondary fungal and bacterial infections. Both bacterial and fungal infections may contribute to chemotherapy-induced nail changes. Researchers believe that nail plate abnormalities combined with immunosuppression may allow colonization of the nail apparatus and surrounding soft tissue structures.13 Several case reports have shown bacterial and fungal infections of the nail apparatus associated with chemotherapeutic treatment.5,16,19 Numerous additional case studies have shown chemotherapy-induced nail changes leading to secondary bacterial and fungal infections of the nail plate and surrounding soft tissue structures.4,16,18-21