Dermoscopy in Darier Disease: A Missing Link in an Unusual Hyperkeratotic Disorder

Introduction

Darier disease is a rare autosomal dominant disorder characterized by greasy hyperkeratotic papules predominantly in the seborrheic areas along with nail and mucous membrane changes [1]. It is caused by a mutation in the gene ATP2A2, which results in a dysfunctional sarcoplasmic/endoplasmic Ca2+ ATPase isoform 2 (SERCA2) proteins [2]. It was first reported by Darier J [3] and White J [4] in 1989 and is also known as Darier–White disease, keratosis follicularis, and dyskeratosis follicularis. Epidemiologically, its reported prevalence is 1:100,000 with a slight male preponderance [1] Due to its rarity, it may be difficult to distinguish it from acne vulgaris, seborrheic dermatitis, acanthosis nigricans, confluent reticulate papillomatosis, prurigo pigmentosa, and reticulate erythematomucinous syndrome [1].

Darier disease has no known cure till date and is characterized by a relapsing and remitting course. It requires early diagnosis and treatment to avoid complications, such as foul-smelling lesions, secondary infections, and poor quality of life [5]. Non-pharmacological interventions include photoprotection, avoidance of synthetic clothing, and frequent use of emollients. Systemic and topical retinoids remain the pharmacological cornerstone of management [6].

Dermoscopy has been found to provide a few clues in diagnosing Darier disease [7, 8, 9, 10]. Herein, we present a case report to highlight the diagnostic utility of dermoscopy in recognizing this rare disorder.

Case Report

A 60-year-old female presented with multiple non- itchy papules over the face, neck, trunk and extremities since childhood and photosensitivity. Similar lesions were noted in her mother and two elder sisters. Skin-coloured and hyperpigmented, firm, slightly greasy papules with cobblestone appearance were noted over the face, neck, dorsum of hands and feet, and posterior trunk (Figure 1). A dirty-yellow membrane was observed over the posterior aspect of the hard palate with dirty yellowish-white wart- like lesions over the toes.

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Histopathological examination of the lesions revealed parakeratosis, papillomatosis, and suprabasal acantholysis and cleft with corps ronds in the granular layer (Figure 2). Dermoscopy revealed cobblestone appearance over the toes with tire-tread and cracked riverbed-like appearances along with palmar hemorrhages and V-shaped nicking over the nails (Figure 3). On clinico-pathologico-dermoscopic correlation, the patient was diagnosed with Darier disease and treated with daily oral isotretinoin 10 mg, topical salicylic acid (3%), emollients, and photoprotection.

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Discussion

Darier disease generally presents with characteristic cobblestone lesions over seborrheic and intertriginous lesions; similar mucosal lesions are noted in half of patients [1]. Interestingly, in this patient, the lesions began on the extremities; therefore, the patient was misdiagnosed elsewhere with photodermatitis and actinic lichen planus. Dermoscopy provided clues to the disease while awaiting histopathological results. In 2004, Vazquez LF, et al. [11] described the dermoscopic findings of pseudocomedones in five patients with biopsy-proven Darier disease [11]. In contrast, Errichetti E, et al. [12] evaluated 11 patients with biopsy‐proven Darier disease and reported a central yellow‐ brown area (polygonal or star‐like) with a surrounding white halo and pinkish homogeneous structure-less background in all patients. Other dermoscopic features included linear and/ or dotted vessels (63.8%) and whitish scales surrounding polygonal brown‐yellow areas (27.3%) [12]. According to Adya KA, et al. [8] three zones can be distinguished on dermoscopy in Darier disease a central light br own follicular opening, surrounding dark brown structure, and peripheral whitish halo [8].

We, however, noted tire-tread and cracked riverbed-like appearances along with palmar hemorrhages and V-shaped nicking over the nails. The varied findings may be due to the differences in the patient population and the duration of the disease. While Vazquez-Lopez et al. reported from New York, Errichetti E, et al. [12] reported from Italy. Adya KA, et al. [8] reported from India, which is where we are reporting from; however, their patient was a 25-year-old female with a 6-month history of lesions, while our patient was a

60-year-old female with lesions since childhood. Therefore, we believe that the Fitzpatrick skin type and the duration of lesions affect the dermoscopic features in Darier disease.

Clinicopathological correlation is time-consuming and requires dermatopathologists for precise interpretations. In resource-limited and time-limited settings, a more rapid and non-invasive tool of diagnosis will be hugely helpful. Dermoscopy in Darier disease can help distinguishing it from other disorders, especially in atypical or early presentations. The commonest differentials include acne vulgaris, seborrheic dermatitis, acanthosis nigricans, confluent reticulate papillomatosis, prurigo pigmentosa, and reticulate erythematomucinous syndrome. On dermoscopy, acne vulgaris is characterized by papules, pustules, and comedones with varying degrees of erythema [13] while Darier disease demonstrates pseudocomedones and seborrheic dermatitis demonstrates twisted red loops and comma vessels [14]. Pigmentation helps in identifying acanthosis nigricans, while confluent reticulate papillomatosis includes flat lesions predominantly confined to the upper trunk only [1]. Lastly, palpation of rough lesions in Darier disease helps in differentiating it from prurigo pigmentosa and reticulate erythematomucinous syndrome [1].

The limitation our report is the evaluation of a single patient, which limits the generalizability of our findings. Genetic analysis was not performed in this patient due to financial constraints. Evaluation of the dermoscopic features of Darier disease in more patients may enable its utility in diagnosing this disease.

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Informed Consent

Written informed consent was obtained from the patient for publication of anonymized data in the form of a case report. Ethical committee clearance was waived in view of the case report design.

Author Statement

The manuscript has been read and approved by all the authors, that the requirements for authorship as stated earlier in this document have been met and that each author believes that the manuscript represents honest work.