Narrative Review of Drug-Associated Nail Toxicities in Oncologic Patients

Abstract

Introduction: Nail toxicity represents one of the most common cutaneous adverse effects of both classic chemotherapeutic agents and new oncologic drugs, including targeted treatments and immunotherapy.

Objectives: We aimed to provide a comprehensive literature review of nail toxicities derived from conventional chemotherapeutic agents, targeted therapies (EGFR inhibitors, multikinase inhibitors, BRAF and MEK inhibitors) and immune checkpoint inhibitors (ICIs), including clinical presentation, implicated drugs and approaches for prevention and management.

Methods: Retrieved literature from PubMed registry database was reviewed to include all articles published up to May 2021 relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of oncologic treatment-induced nail toxicity. The internet was searched for relevant studies.

Results: A wide spectrum of nail toxicities is associated with both, conventional and newer anticancer agents. The frequency of nail involvement, especially with immunotherapy and new targeted agents remains unknown and patients with different cancer types receiving different regimens may develop the same nail disorder, whereas patients with the same type of cancer under the same chemotherapeutic treatment may develop different types of nail alterations. The underlying mechanisms of the varying individual susceptibility and the diverse nail responses to various anticancer treatments need further investigation.

Conclusion: Early recognition and treatment of nail toxicities can minimize their impact, allowing better adherence to conventional and newer oncologic treatments. Dermatologists, oncologists and other implicated physicians should be aware of these burdensome adverse effects in order to guide management and prevent impairment of patients' quality of life.

Figure 1

Nail toxicities due to conventional chemotherapeutic drugs. A. Muehrcke’s lines due to treatment with cisplatin: Transversal white lines with healthy nail bed between them. B. Dermosopic examination of the same patient with clear visualization of the leukonychia in the form of Muehrcke’s lines. C. Red-brown discoloration of the nails associated with painful subungual hematomas and onycholysis following treatment with taxol. D. Dermoscopic image of the chemotherapy-induced central subungual hematoma that differs from traumatic subungal hematoma: note the bright red color with an orange/brown halo (in trauma: dark violet with globular pattern accompanied by transversal whitish line). E. Longitudinal melanonychia following cyclophosphamide treatment. F. Dermoscopy image of the cyclophosphamide-induced melanonychia with a homogenous brown band with absence of Hutchinson or micro-Hutcinson’s sign. Borders appear blurry but this may happen in the great toenail due to thickness of the nail plate. This is a false positive sign that should be interpreted together with the clinical history of the patient.

Figure 2

Nail toxicities due to targeted biologic drugs. A. Paronychia due to treatment with EGFR tyrosine kinase inhibitor (panitumumab) for colorectal cancer: proximal nail fold is painful, erythematous and swollen with presence of oozing and crusting, B. Same patient as a.: close-up to a pyogenic granuloma that frequently accompanies paronychia due to EGFR inhibitors. C and D. Clinical and dermoscopy image of brittle nails during EGFR inhibitor therapy for lung cancer. The nail plate is fragile and the surface of the nail presents longitudinal fine fissures while the distal edge of the plate appears to crumble and is not sharply delineated. In dermoscopy presence of splinter hemorrhages can also be detected. E and F. Acute photo-onycholysis in a melanoma patient treated with BRAF inhibitors: clinical and dermoscopic image. The nails were extremely painful with almost total detachment of the nail plate and presence of oozing and subungual hematoma.

Figure 3

Nail toxicities due to immunotherapy. A. Psoriatic changes in nails following treatment with immune checkpoint inhibitor (pembrolizumab): presence of subtle pitting, onycholysis and paronychia with scaling of the skin. B. Same patient as a, dermoscopic image: Remark the presence of splinter hemorrhages as well as the yellow discoloration of the onycholysis suggestive of psoriatic disease. C, D. Lichenoid-like reactions in a melanoma patient treated with nivolumab: Onychorhexis visualized both clinically and with dermoscopy. In the dermoscopic image the presence of dust in the nail fissures gives the characteristic image of “dirty nail” that is a common finding in lichen-like reactions of the nail plate. E, F: Same patient as c, d different nails, dermoscopic images. Characteristic presence of erythema in the lunula seen in patients treated with nivolumab.

Figure 4

A. Onycholysis due to taxane treatment. Observe important detachment of plate from bed and presence of purulent discharge, B. Clipping of the onycholytic part of the nails relieves pain and allows for better hygiene.