Longitudinal Erythro-Leukoxanthonychia Developing after PUVA Therapy

Question

A 53-year-old female presented with a 6-month history of discoloration of the left thumb nail. The patient was receiving topical PUVA sessions (46 sessions at time of presentation) for idiopathic guttate hypomelanosis of her forearms and legs. She reported that her nail change started insidiously after beginning the PUVA therapy.

On examination, longitudinal grooved erythro-leukoxanthonychia with an overlying localized thickening of the nail plate was seen on her left thumb nail (Fig. 1a). Dirt like keratotic debris filled the grooved nail. The lesion was asymptomatic, and the dorsum of her hands showed several classic seborrheic keratoses. Dermoscopic examination revealed that the erythro-leukoxanthonychia was surrounding a longitudinal nail groove, a localized subungual black hyperkeratosis and a triangular erosion of distal nail plate were observed (Fig. 1b).

Fig. 1.

a Erythro-leukoxanthonychia with grooving of the left thumb. b Dermoscopic features showing the leukoxanthonychia and erythronychia surrounding the longitudinal nail groove.

The proximal nail fold was reflected and the lesion in the nail matrix and nail bed was excised. Histopathological examination revealed thickened nail plate and acanthotic distal nail matrix and nail bed epithelium with proliferation of basaloid and squamoid cells with the formation of pseudo-horn cysts and cell whorls (squamous eddies) (Fig. 2).

Fig. 2.

Photomicrographs depicting histopathological features of the nail biopsy. a Thickening of the nail plate, acanthosis of the distal nail matrix and nail bed epithelium with the formation of pseudo-horn cysts and cell whorls (squamous eddies) (H&E. ×40). b Higher magnification highlighting proliferated basaloid and squamoid cells within the acanthotic epithelium. A squamous eddy is seen (black arrow) (H&E. ×100).

What Is Your Diagnosis?

Answer

Subungual seborrheic keratosis (SK) (longitudinal subungual acanthoma).

Discussion

Sks are common benign epithelial skin tumors usually seen among the adult population and their incidence increase with age. They can occur anywhere on the body, except for the palms, soles, and mucous membranes and may show a great clinical and histological variability [1].

The occurrence of SK in relation to the ungual epithelium is uncommon with only few cases previously reported in literature. Terms used to describe these lesions included ungual/subungual SK, subungual keratosis, and longitudinal keratosis. Several clinical presentations were described, the most frequent of which was leukoxanthonychia, as in our case. Other presentations included brown-red bands and longitudinal melanonychia which may be associated with nail plate thickening [2, 3, 4, 5, 6, 7]. In all cases, histopathological features were reminiscent of SK with well-defined tumorous proliferation of the distal matrix and proximal nail bed made up of basaloid cells with cell whorls (eddies) and pseudo-horn cysts. Onychocytic matricoma is another term used to describe similar cases that presented with longitudinal melanonychia and thickened nail plate which according to the authors differed from SK in that the whorls were formed of larger pink cells corresponding to the prekeratogenous zone arranged in an onion-peel pattern with central eosinophilic masses [8, 9, 10].

However, in order to avoid confusion, Baran and colleagues in 2018 proposed the term “nail unit longitudinal acanthoma” or “longitudinal subungual acanthoma” to encompass all entities described as ungual/subungual SK, subungual keratosis, longitudinal keratosis, or onychocytic matricoma as they all belong to a single spectrum of seemingly related benign epithelial tumors of the nail unit [2]. While the proposed unifying term describes the same underlying histopathological process, the distinct clinical characterization as leukoxanthonychia or melanonychia reflects their anatomic localization in the variable zones of the nail unit.

The exact etiology of SK remains to be unclear. Aging, human papilloma virus and mutations of the tyrosine kinase fibroblast growth factor receptor 3 has all been incriminated in the pathogenesis of SK [11, 12]. Exposure to sunlight is considered to be a risk factor for SK as their number significantly increased with age only on exposed skin [13, 14]. Ultraviolet exposure was found to down-regulate the tumor suppressor phosphatase and tensin homolog gene in mice and cause the development of tumors resembling human SK [15]. Although our patient had several seborrheic keratoses on the exposed skin of the back of her hands, her subungual lesion developed only after intense hand and feet ultraviolet exposure in the form of PUVA therapy which further supports the role of sunlight and ultraviolet exposure in the development of SK.

To the best of our knowledge, this is the first case of subungual SK (longitudinal subungual acanthoma) to be reported after PUVA therapy. Subungual SK should be considered in the differential diagnosis of longitudinal grooved erythro-leukoxanthonychia with nail plate thickening. Surgical excision is the treatment of choice in such cases but recurrences can still occur.

Statement of Ethics

The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. A written informed consent was obtained from the patient for publication of this case report and any accompanying images. The Dermatology Department Research Ethical Committee (Derma REC), Cairo University has exempted this case report from the need of ethical approval.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding was received.

Author Contributions

Mohamed El-Komy contributed to collection of references, revision, and editing of the manuscript. Basma Gaballa contributed to writing the manuscript. Mona Abdel-Halim performed the pathological diagnosis, prepared the photomicrographs, and contributed to revision, editing, and submission of the manuscript.