PracticalDermatology

Darier disease (DD) is a rare, autosomal dominant disorder with an approximated prevalence of one to two cases per 100,000 people.^1,2 It is caused by mutations in the ATP2A2 gene coding for the SarcoEndoplasmic Reticulum Calcium-ATPase 2 (SERCA2) pump, which leads to desmosome protein dysfunction and abnormal keratinization.^1-3 Approximately 10% of cases represent the localized form of DD, causing a mosaic pattern of skin involvement. Several variants of localized DD have been reported, including unilateral, zosteriform, segmental, and linear.² Here we present a rare case of linear DD.

Case Report

A 25-year-old Caucasian female presented with a 10-year history of an intermittent itchy rash on her right upper arm and right upper back that recurred 1 to 3 times per year, typically in the summer. Each episode lasted 3 weeks and began as small, itchy vesicles that drained clear fluid and blood, followed by crusting and eventual resolution. The rash always recurred in the same locations and worsened with heat and exercise. The patient had no known medical problems, no known allergies, and did not take any medications.

On physical examination, pink-to-tan scaly keratotic papules with a rough, verrucous-like texture were present on the right upper extremity and right scapular area in a linear pattern following Blaschko lines (Figure 1).² No mucosal lesions or nail changes were present.

Figure 1. Physical Exam Findings. Patient with pink-to-tan scaly keratotic papules extending from the right scapular area to the right upper extremity in a linear pattern.

A punch biopsy was performed, and histopathological results revealed intraepidermal acantholytic dyskeratosis, consistent with DD (Figure 2).¹ Given the pattern and localization of the lesions, a diagnosis of linear DD was made.

Figure 2. Photomicrograph of Lesional Skin Biopsy Specimen. This specimen reveals dyskeratosis and acantholysis with loss of intraepidermal cohesiveness and formation of clefts and lacunae (hematoxylin-eosin, original magnification (A) 25X (B) 35X).

Discussion

Darier disease is an autosomal dominant disorder that occurs due to dysfunctional keratinization and lack of adhesion between epidermal cells.³ Two types of mosaic DD exist. In type I, a post-zygotic mutation results in affected skin along Blaschko lines surrounded by normal skin, as seen in this case. Type II is secondary to two events: a germline heterozygotic mutation and segmental, somatic loss of heterozygosity of the other, wild-type allele. This manifests as areas of localized, severe disease overlying general DD.²

Linear DD classically presents as reddish-brown, wart-like or hyperkeratotic papules that follow lines of Blaschko and may be painful, pruritic, or malodorous. Histologically, it is not possible to differentiate between the variants of DD. Typical findings include papillomatous epidermal hyperplasia, intraepidermal acantholytic dyskeratosis, and classic dyskeratotic cells including corp ronds and grains.^1,2

Systemic retinoids, including isotretinoin (starting dose of 0.5 mg/kg/day) and acitretin (starting dose of 10-25 mg daily), are first-line therapies for DD, but given the localized distribution of linear DD, topical therapy is generally preferred.^1,4 Our patient was initiated on tretinoin 0.05% cream nightly to reduce hyperkeratosis and was advised to avoid known triggers such as heat and sun exposure. Other reported treatments include keratolytic agents such as salicylic or lactic acid, topical corticosteroids, and immunosuppressant agents.^4-6 Secondary infection is common and must be treated appropriately.²

Darier disease is uncommon, and cases with a linear distribution are especially rare. While linear DD is typically a relatively benign condition, if the gonads are involved in the genetic mosaicism, it is possible for the mutation to be inherited by offspring and cause widespread DD.² We present this case to highlight the unique clinical presentation of a linear variant of DD and to encourage prompt recognition and appropriate patient counseling.

1. Cooper SM, Burge SM. Darier’s disease: epidemiology, pathophysiology, and management. Am J Clin Dermatol. 2003;4(2):97-105. doi:10.2165/00128071-200304020-00003

2. Medeiros PM, Alves NR, Trujillo JM, Silva CC, Faria PC, Silva RS. Segmental Darier’s disease: a presentation of a difficult diagnosis. An Bras Dermatol. 2015;90(3 Suppl 1):62-65. doi:10.1590/abd1806-4841.20153581

3. Dhitavat J, Cobbold C, Leslie N, Burge S, Hovnanian A. Impaired trafficking of the desmoplakins in cultured Darier’s disease keratinocytes. J Invest Dermatol. 2003;121(6):1349-1355. doi:10.1046/j.1523-1747.2003.12557.x

4. Casals M, Campoy A, Aspiolea F, Carrasco MA, Camps A. Successful treatment of linear Darier’s disease with topical adapalene. J Eur Acad Dermatol Venereol. 2009;23(2):237-238. doi:10.1111/j.1468-3083.2008.02815.x

5. Burkhart CG, Burkhart CN. Tazarotene gel for Darier’s disease. J Am Acad Dermatol. 1998;38(6 Pt 1):1001-1002. doi:10.1016/s0190-9622(98)70168-9

6. Rubegni P, Poggiali S, Sbano P, Risulo M, Fimiani M. A case of Darier’s disease successfully treated with topical tacrolimus. J Eur Acad Dermatol Venereol. 2006;20(1):84-87. doi:10.1111/j.1468-3083.2005.01352.x