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Keratosis follicularis (Darier-White Disease), with an unusual palmoplantar keratoderma

  • Author(s): Kim, Carolyn
  • Fangman, William
  • et al.
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Keratosis follicularis (Darier-White Disease), with an unusual palmoplantar keratoderma
Carolyn Kim MD, William Fangman MD
Dermatology Online Journal 13 (1): 7

New York University Department of Dermatology

Abstract

A 38-year-old woman presented with widespread, hyperkeratotic papules and plaques that had been present since childhood. Her mother, brother, and son have similar lesions. A diagnosis of keratosis follicularis was made, which has been treated with isotretinoin. Palmoplantar lesions of keratosis follicularis have been described as discrete, punctate keratoses, hyperkeratotic papules, small pits, or keratin-filled depressions. This patient has an unusual palmoplantar keratoderma in association with keratosis follicularis. The lesions are elevated, discrete, filiform, hyperkeratotic spires, which coalesce into large, hyperkeratotic plaques on the palms and soles.



Clinical synopsis

A 38-year-old woman presented to the Bellevue Hospital Center Dermatology Clinic in August 2005 with a life-long history of dark papules and plaques with scales in a widespread distribution. She reported that her condition was a familial trait, inasmuch as her mother, brother, and 6-year-old son have similar lesions. Previous treatments include intermittent courses of isotretinoin since she was 19-years old. Although the lesions improved with oral isotretinoin, they never completely resolved. Her last course of isotretinoin was over 3 months ago, and her skin condition had deteriorated. The thick, hard lesions on her palms and soles became so extensive that her manual dexterity was impaired, and she was unable to walk or place any pressure on her soles owing to pain. Isotretinoin 40 mg daily was started. Salicylic acid 5 percent in petrolatum was applied to the lesions. At 1-month followup, her lesions had improved; she was able to walk a few steps. The dose of isotretinoin was increased to 40 mg twice a day, with continued improvement.

Hyperpigmented, hyperkeratotic papules were located on the nasolabial folds, chin, and post-auricular regions. Thick, hyperpigmented, hyperkeratotic plaques covered much of the inframammary region as well as the intragluteal cleft. The axillae were spared. There were discrete, hyperkeratotic papules located on the abdomen. In the lumbar region was a large plaque that was comprised of confluent, hyperpigmented, hyperkeratotic papules. There were white papules that coalesced on the hard palate and resulted in a cobblestone appearance. On the upper arms were numerous, 1-2-mm, scattered, hypopigmented macules. The fingernails have V-shaped nicks, longitudinal ridges, subungual keratoses as well as alternating, longitudinal red and white lines. On the central palms and soles were white-yellow, discrete, filiform hyperkeratoses that coalesced into hyperkeratotic plaques with a maximal elevation of 1 cm.


Figure 1Figure 2

A complete blood count, basic metabolic panel, hepatic function panel, and lipid panel were normal. Serum and urine pregnancy tests were negative.


Figure 3

Histopathology reveals a suprabasal acantholysis with cleft formation. Dyskeratotic cells with pyknotic nuclei, clear perinuclear halos, and brightly eosinophilic cytoplasms (corp ronds) are noted in the upper malpighian layer and stratum corneum.


Comment

First described independently in 1889 by the French dermatologist Jean Darier and the American dermatologist James White, keratosis follicularis is an autosomal dominant genodermatosis. Altered function of a sarco-endoplasmic reticulum Ca2+ ATPase (SERCA2) and resultant abnormal intracellular Ca2+ signaling leads to loss of suprabasilar cell adhesion and apoptosis induction, which correlates histologically with acantholysis and dyskeratosis, respectively [1, 2].

Palmoplantar involvement in keratosis follicularis is usually described as discrete, punctate keratoses that appear as small, hyperkeratotic papules or small, centrally depressed pits. If numerous, closely set, small papules coalesce; they may appear as a general thickening of the palms and soles [3]. Several case reports have described variants of palmoplantar involvement that include scattered palmoplantar orthokeratotic filiform hyperkeratosis (PPOFH) and well-circumscribed, localized palmoplantar keratodermas. The PPOFH variant occurs as multiple, spiny, hyperkeratotic projections on the palms and soles [4, 5]. Histopathologic examination of these digitate keratotic plugs showed columns of orthokeratotic hyperkeratosis without acantholysis, dyskeratosis, cytologic atypia, or vacuolation of keratinocytes. However, biopsy specimens of chest lesions in the same patients showed the classical histologic findings of keratosis follicularis. A case of localized keratosis follicularis was reported in which the only finding was an asymptomatic palmoplantar keratoderma [6]. Lesions were described as well-defined, hyperkeratotic plaques on the plantar arches and localized hyperkeratosis with fissures on the heels. The histopathologic examination showed hyperkeratosis, intraepidermal acantholytic lacunae, and dyskeratotic cells. A case of classic keratosis follicularis with a circumscribed, plantar keratoderma but with no palmar involvement was described [7]. Histopathologic examination of a plantar lesion showed hyperkeratosis without dyskeratosis or acantholysis, whereas a skin biopsy specimen showed a suprabasilar split with dyskeratotic and acantholytic cells.

These case reports illustrate the unusual variations of palmoplantar lesions that can be associated with keratosis follicularis. These filiform hyperkeratotic spines or well-circumscribed keratodermas are typically observed in conjunction with classic lesions on the trunk, face, and intertriginous areas. Although the acral biopsy specimens may not show evidence of keratosis follicularis, biopsy specimens of the characteristic truncal lesions show classical acantholysis and dyskeratosis.

References

1. Goldsmith LA, Baden HP. Darier-White disease (keratosis follicularis) and acrokeratosis verruciformis. In: Freedburg IM, et al., eds. Fitzpatrick's Dermatology in General Medicine. 6th edition. New York: McGraw-Hill, 2003: 523

2. Hohl D, et al. Darier's disease and Hailey-Hailey disease. In: Bolognia JL, et al., eds. Dermatology. Edinburgh: Mosby, 2003: 823

3. Grekin RC, et al. Darier's disease (keratosis follicularis). In: Odom R, et al., eds. Andrews' Diseases of the Skin. 9th edition. Philadelphia: W.B. Saunders Company, 2000:716

4. Zarour H, et al. Palmoplantar orthokeratotic filiform hyperkeratosis in a patient with associated Darier's disease: classification of filiform hyperkeratosis. Dermatology 1992; 185: 205

5. Salmon-Her V, et al. Palmoplantar filiform hyperkeratosis with Darier's disease: association or coincidence? Eur J Dermatol 1998; 8:519

6. Yoshikawa Y, et al. A unique case of palmoplantar keratoderma. J Dermatol 2003; 30:755

7. Thappa DM, Garg BR. Darier's disease with circumscribed plantar keratoderma. J Dermatol 1996; 23:139

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