Darier-White disease is a relatively common autosomal dominant
genodermatosis caused by mutation in the ATP2A2 gene. It is characterized by
multiple warty papules coalescing into plaques in the seborrheic areas and by
specific histological skin changes. Palm and sole involvement in Darier-White
disease is usually mild, mainly featuring discrete and small keratotic papules. We
present a unique case of Darier-White disease presenting with a diffuse, mutilating
hystrix-like palmoplantar keratoderma

Ellenbogen, Eran

Gat, Andrea

Goldberg, Ilan

Jammal, Anwar

Martinez, Helena

Pessach, Yakov

Sprecher, Eli

English

Darier-White disease is a relatively common autosomal dominant

genodermatosis caused by mutation in the ATP2A2 gene. It is characterized by

multiple warty papules coalescing into plaques in the seborrheic areas and by

specific histological skin changes. Palm and sole involvement in Darier-White

disease is usually mild, mainly featuring discrete and small keratotic papules. We

present a unique case of Darier-White disease presenting with a diffuse, mutilating

hystrix-like palmoplantar keratoderma

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ACTA DERMATOVENEROLOGICA CROATICA 39An Uncommon Presentation of Darier-White Disease with Hystrix-like Palmoplantar KeratodermaYakov Pessach1, Anwar Jammal2, Andrea Gat3, Helena Martinez2,  Eran Ellenbogen1, Eli Sprecher1, Ilan Goldberg11Departments of Dermatology and Pathology, Tel-Aviv Sourasky Medical Center,  Tel-Aviv, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 2Department of Dermatology, Rabin Medical Center, Petach Tikva, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Clalit Health Care Services, Tel Aviv, IsraelCorresponding author:Ilan Goldberg, MDDepartment of DermatologyTel-Aviv Sourasky Medical Center6 Weizmann StreetTel-AvivIsraelilangoldberg1@gmail.comReceived: January 28, 2019Accepted: January 15, 2021Acta Dermatovenerol Croat                              2021;29(1):39-41                                                    CASE REPORTABSTRACT Darier-White disease is a relatively common autosomal dominant genodermatosis caused by mutation in the ATP2A2 gene. It is characterized by multiple warty papules coalescing into plaques in the seborrheic areas and by specific histological skin changes. Palm and sole involvement in Darier-White disease is usually mild, mainly featuring discrete and small keratotic papules. We present a unique case of Darier-White disease presenting with a diffuse, mutilat-ing hystrix-like palmoplantar keratoderma.KEY WORDS: Darier-White disease, palmoplantar keratoderma, genodermatosisINTRODUCTION Darier-White disease is a relatively common au-tosomal dominant genodermatosis caused by muta-tion in the ATP2A2 gene (1,2). It is characterized by multiple warty papules coalescing into plaques in the seborrheic areas and by specific histological skin changes. Palm and sole involvement in Darier-White disease is not uncommon but is usually mild, featur-ing mainly discrete and small keratotic papules (3). We herein present a unique case of Darier-White dis-ease presenting with a diffuse, mutilating hystrix-like palmoplantar keratoderma.CASE REPORT A 31-year-old woman presented to our outpatient clinic with exceedingly painful palmoplantar kerato-derma. She first noticed thickening of her palmar skin at age 21. Five years later, similar lesions were seen on her soles as well. The disease gradually worsened, af-fecting her ability to stand on her feet. One year prior to admission, she reported that she could not walk on her feet and instead moved by crawling on her knees.Upon examination, the palms and soles showed a severe diffuse keratoderma with massive and spiny hyperkeratosis and deep and painful fissures (Figure 1, a-b). In addition, reddish-brown papules covered with scales or crusts were symmetrically distributed over the entire surface of the skin, more prominently over seborrheic areas (Figure 2, a). Discrete, flat-topped, skin-colored papules were observed on the dorsal aspects of hands and feet (Figure 2, b). The fingernails demonstrated longitudinal ridg-ing, subungual hyperkeratosis, and V-shaped distal notches (Figure 2, c). The rest of the physical examina-tion as well as routine laboratory results were normal.ACTA DERMATOVENEROLOGICA CROATICA40Figure 1. Palmoplantar involvement. (a) Plantar keratoderma extends onto the sides of the feet and consists of thick yellow-ish plaques covered with horny spiky excrescences. (b) The palmar skin surface is covered with thick yellowish plaques. (c) The Soles and (d) palms after 6 months of treatment with acitretin 25 mg/day.Figure 2. Clinical features suggestive of Darier-White disease. (a) Brownish papules located on the forehead and sides of the face, covered with fine adherent grayish scales. (b) Skin-colored papules on the dorsal aspects of the hands and feet sugges-tive of acrokeratosis verruciformis of Hopf. (c) Longitudinal ridging and distal V-notching of the finger nails. Figure 3. Histopathologic features. (a, b) A skin biopsy obtained from the right plantar foot demonstrates marked hyperkera-tosis and villi protruding into the suprabasal lacunae (original magnifications, ×40 and ×100, respectively). (c) A skin biopsy specimen obtained from the dorsal aspect of the right foot shows hyperkeratosis and suprabasal lacunae (original magnifica-tion ×100). (d) A skin biopsy derived from the forehead shows villi protruding into the suprabasal lacunae and corps ronds in the upper Malpighian layers (original magnification ×100).Pessach et al. Acta Dermatovenerol CroatDarier-White disease  2021;29(1):39-4141ACTA DERMATOVENEROLOGICA CROATICAThe characteristic skin findings, including the ones suggestive of acrokeratosis verruciformis of Hopf on the dorsal aspects of the hands as well as feet and the nail findings, were highly indicative of Darier-White disease. The severity of the palmoplantar involve-ment was, however, rather unusual (3). We performed additional ancillary tests to rule out possible non-ge-netic etiologies for the severe palmoplantar involve-ment observed in our patient, including mycological cultures, thyroid function tests, total body computed tomography, panendoscopy, and auditory and oph-thalmologic examinations, which were unrevealing. In order to assess the possibility that the palmo-plantar keratoderma was indeed one of the mani-festations of Darier-White disease in our patient, we obtained skin biopsies from the right palm, right sole, dorsal right hand, and forehead. All biopsies showed similar findings, including suprabasal acantholysis, la-cunae formations with villi protruding into them, and typical dyskeratotic cells seen in the granular layer and keratin layer, i.e. corps ronds and grains, respec-tively (Figure 3). These findings confirmed the diag-nosis of Darier-White disease. Treatment with acitre-tin brought about rapid improvement of both palm and sole hyperkeratosis (Figure 1, c, d).DISCUSSIONWe have presented a case of Darier-White disease manifesting with a severe mutilating form of hystrix-like palmoplantar keratoderma. Palmar lesions are found in 84% of patients with Darier-White disease, and consist mainly of discrete small keratotic papules with or without pit formations. Similar lesions can also be detected over the soles in some patients(3). Several case reports have described atypical variants of palmoplantar involvement in Darier-White disease including palmoplantar orthokeratotic filiform hy-perkeratosis(4, 5) and well-circumscribed, localized palmoplantar keratoderma(6, 7). The concomitant occurrence of palmoplantar keratoderma and Darier-White disease in one individual should be considered as evidence for a common etiology, although biopsy specimens taken from the palmoplantar skin in these cases have failed to reveal changes specific for Darier-White disease(4-7).  The present case displayed unique features in-cluding severe spiny and mutilating palmoplantar hyperkeratosis reminiscent of ichthyosis hystrix (8), previously reported in association with Darier-White disease (6, 9). Here, in contrast with this previous case, histopathological evidence for Darier-White disease was obtained from biopsies taken from the palmo-plantar skin, definitely proving that mutilating diffuse palmoplantar keratoderma can be part of the spectrum of clinical manifestations in Darier-White disease. References:1. Szigeti R, Kellermayer R. Autosomal-dominant calcium ATPase disorders. J Invest Dermatol. 2006;126:2370-6.2. Dhitavat J, Fairclough RJ, Hovnanian A, Burge SM. Calcium pumps and keratinocytes: lessons from Darier’s disease and Hailey-Hailey disease. Br J Dermatol. 2004;150:821-8.3. Burge SM, Wilkinson JD. Darier-White disease: a review of the clinical features in 163 patients. J Am Acad Dermatol. 1992;27:40-50.4. Zarour H, Grob JJ, Andrac L, Bonerandi JJ. Palmo-plantar orthokeratotic filiform hyperkeratosis in a patient with associated Darier’s disease. Classi-fication of filiform hyperkeratosis. Dermatology. 1992;185:205-9.5. Salmon-Ehr V, Grosieux C, Derancourt C, Durlach A, Kalis B, Bernard P. Palmoplantar filiform hy-perkeratosis with Darier’s disease. Association or coincidence? Eur J Dermatol. 1998;8:519-20.6. Yoshikawa Y, Tanaka T, Toda K, Miyachi Y. A unique case of palmoplantar keratoderma. J Dermatol. 2003;30:755-7.7. Thappa DM, Garg BR. Darier’s disease with circumscribed plantar keratoderma. J Dermatol. 1996;23:139-40.8. Anton-Lamprecht I. Genetically induced ab-normalities of epidermal differentiation and ul-trastructure in ichthyoses and epidermolyses: pathogenesis, heterogeneity, fetal manifesta-tion, and prenatal diagnosis. J Invest Dermatol. 1983;81(1 Suppl):149s-56s.9. Kim C, Fangman W. Keratosis follicularis (Darier-White disease), with an unusual palmoplan-tar keratoderma. Dermatology online journal. 2007;13:7.Pessach et al. Acta Dermatovenerol CroatDarier-White disease  2021;29(1):39-41

An Uncommon Presentation of Darier-White Disease with Hystrix-like Palmoplantar Keratoderma

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