Persistent Toenail Onycholysis Associated With Beta-Papillomavirus Infection of the Nail Bed

Abstract

Onycholysis, separation of the nail plate from the nail bed, is etiologically classified as primary (idiopathic) or secondary (eg, caused by psoriasis, squamous cell carcinoma). Repetitive microtrauma plays a role in idiopathic onycholysis and also facilitates human papillomavirus (HPV) infection. Herein, we report a case of persistent primary onycholysis associated with repetitive trauma and infection by a multiplicity of Beta-papillomavirus (Beta-PV) genotypes. An otherwise healthy 27-year-old woman presented with a 6-year history of onycholysis of the halluces and right second toe. Her occupation required wearing steel-toed boots. Fungal cultures were negative and antifungal therapy was ineffective. Punch biopsy of the hallux nail bed revealed epidermal hyperplasia, acanthosis, hypergranulosis, hyperkeratosis, and regions of koilocytosis without significant inflammation. This histopathology implicated chronic irritation and HPV infection. Immunohistochemistry demonstrated productive HPV infection. Nested PCR using degenerate consensus primers revealed infection with 5 known and 1 novel Beta-PV genotypes (HPV 5, HPV 8, HPV 20, HPV 23, HPV 37, and FA25). The histopathology of primary onycholysis is unknown. Based on the aforementioned, we propose that repetitive microtrauma caused by wearing steel-toed boots promoted onycholysis and HPV infection, the latter of which, altered the differentiation of nail bed epithelium, preventing adhesion of nail plate to the nail bed. Lastly, the presence of oncogenic Beta-PV genotypes (ie, HPV 5, 8, and 20) implicates a risk for subungual squamous cell carcinoma, particularly if the nail remains symptomatic and persistently irritated.

Genome Sequence of Human Papillomavirus 23 Strain HPV-23/Lancaster/2015

“…U31781), as well as two shorter fragments (3, 4). HPV-23 is a clinically significant papillomavirus, having been implicated in epidermodysplasia verruciformis (2), skin cancer (5), ocular syringoma (6), nongenital seborrhoeic keratosis (7), breast cancer (8), and toenail onycholysis (9). …”

Genome Sequence of Human Papillomavirus Type 20, Strain HPV-20/Lancaster/2015

“…Within the genus Betapapillomavirus , type 20 of the species Betapapillomavirus 1 (HPV-20) is represented in GenBank by a single complete genome ( 2 ), a circular double-stranded DNA of 7.8 kb (U31778), and three shorter fragments ( 3 – 5 ). HPV-20 is a clinically significant papillomavirus, having been implicated in epidermodysplasia verruciformis ( 2 ), skin cancer ( 6 ), ocular syringoma ( 7 ), nongenital seborrhoeic keratosis ( 8 ), conjunctival papillomas ( 9 ), verrucous carcinoma of the lip ( 10 ), condylomatous lesions of the mammillae ( 11 ), squamous cell carcinoma of the esophagus ( 12 ), and toenail onycholysis ( 13 ).…”