British Journal of Oral and Maxillofacial Surgery (2005) 43, 336—338
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Darier disease: a case report Ajura Abdul Jalil a, Rosnah Binti Zain a, Isa¨ ac van der Waal b, ∗ a
Oral Medicine, Oral Pathology and Periodontology Department, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia b Department of Oral and Maxillofacial Surgery/Pathology, ACTA/Vrije Universiteit Medical Centre, P.O. Box 7057, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands Accepted 4 October 2004 Available online 8 February 2005 KEYWORDS Darier disease; Keratosis follicularis; Dyskeratosis follicularis; Benign dyskeratosis
Summary The diagnosis of Darier disease of the oral mucosa was made only after biopsying a leukoplakia-like lesion of the palate. © 2004 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Introduction Darier disease, also known as keratosis follicularis, dyskeratosis follicularis, and benign dyskeratosis, is a rare disorder of keratinisation that primarily affects the skin and, to a lesser extent, the oral mucosa. It was described independently by both Darier and White in 1889. It has a prevalence of 1:100,000 of the population and is inherited as an autosomal dominant trait.1 The age of onset is childhood or adolescence. Patients usually present with multiple small firm reddish-brown papules on the forehead, scalp, neck, shoulders, chest, and limbs. Other cutaneous signs include punctate keratotic pits of the palms and soles and dystrophy of the nails, which is characterised by a red and white sandwich of streaks * Corresponding author. Tel.: +31 20 444 4039; fax: +31 20 444 4046. E-mail address:
[email protected] (I. van der Waal).
associated with a V-shaped notch. The oral lesions are usually asymptomatic and are seen as multiple, normal-coloured or white flat-topped papules that predominantly affect the palate.
Case report A 42-year-old white man was referred by his dentist with leukoplakia of the palate. He had a diffuse white leukoplakia-like change of the palatal mucosa. Similar white changes were noticed at multiple sites on the mandibular gingiva (Fig. 1). The patient was otherwise healthy. He smoked a few cigarettes a day, and drank less than two units of alcohol a day. Under local anaesthesia a biopsy specimen was taken from the palatal lesion. Histological examination showed the presence of keratosis follicularis, also referred to as Darier disease. The patient was interviewed again and examined. Although he initially denied the presence of
0266-4356/$ — see front matter © 2004 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjoms.2004.10.017
Darier disease
337 follicularis of the skin, particularly on the back and the chest (Figs. 2 and 3). He also had atrophy of the nails of the fingers. He refused follow-up visits for his oral condition. He did not want genetic counselling.
Discussion
Figure 1 Leukoplakia-like appearance of entire palatal mucosa.
Figure 2 Darier disease affecting the skin of the back.
any medical condition or the taking of drugs, he admitted to regular visits to a dermatologist for several years because of skin disease of the trunk. After consultation with his dermatologist, it became clear that he also had biopsy-proven dyskeratosis
Figure 3 Suprabasal clefting and several ‘‘corps ronds’’ in biopsy of the skin. Haematoxylin and eosin, original magnification ×100.
Although it is inherited as an autosomal dominant, 47% of the families with Darier disease do not have a family history,2 but mild forms of the disease may not have been recognised among family members. The mutated gene, which was found by Sakuntabhai et al.,3 encodes for a sarco/endoplasmic reticulum calcium ATPase pump (SERCA2) that has a role in the intracellular signalling of calcium.4 Calcium has a role in regulating cell differentiation and in initiating assembly at desmosomes; the acantholysis is the result from loss of adhesion as a result of breakdown of desmosome.4 Oral lesions are seldom reported. They were found in 50% of patients with Darier disease in a study by Macleod and Munro,5 and in only 15% in another study. The lesions consisted of whitish papules of varying size in which the palate was the most commonly affected site and varied from a fine grainy to a course pebbly appearance.2,5 Palatal lesions in Darier disease may mimic papillary hyperplasia associated with dentures, or resemble nicotinic stomatitis. Other commonly involved sites are the gingiva followed by buccal mucosa, tongue, and floor of the mouth.5 Furthermore, recurrent parotid swelling from obstructive sialadenitis in which the sialogram showed stricturing within the main ducts has been reported.1,5 Histologically, Darier disease is characterised by acantholysis leading to the formation of suprabasal clefts into which there is villous proliferation of basal cells and also formation of corps ronds and grains superficially.6 Corps ronds are usually seen in the granular cell layer and consist of central large round dyskeratotic basophilic masses surrounded by a clear halo-like zone. The grains resemble enlarged parakeratotic cells with an elongated densely stained nucleus surrounded by keratin-like material. Darier disease must be distinguished histologically from other acantholytic dyskeratoses, such as Hailey—Hailey disease (familial benign pemphigus) and Grover disease. The clinical characteristics of those diseases are different from those of Darier disease. It is important to recognise the oral manifestations of Darier disease, and to diagnose the accompanying skin disorder. If there are no accompanying cutaneous manifestations one may be dealing with
338 a localized form of Darier disease, often referred to as oral warty dyskeratoma. Patients with oral lesions in Darier disease do not require any specific treatment. Malignant transformation has not been reported. The disease is not usually associated with other medical problems but an association between this disease and mental impairment has been reported in a few families.2 For the skin problems, itch, and body malodour are the most common complaints.2 Simple measures, such as emollients and wearing cool clothing are used to relieve the symptoms. Topical and systemic retinoids are usually given to patients with generalized or severe skin lesions. However, the oral lesions persist despite the retinoid treatment.5 Genetic counselling may be helpful in helping the patient to understand inheritance and the risk of transmission to offspring.5
A.A. Jalil et al.
References 1. Ferris T, Lamey PJ, Rennie JS. Darier’s disease: oral features and genetic aspects. Br Dent J 1990;168:71—3. 2. Burge SNE, Wilkinson JD. Darier—White disease: a review of the clinical features in 163 patients. J Am Acad Dermatol 1992;27:40—50. 3. Sakuntabhai A, Burge S, Monk S, Hovnanian A. Spectrum of novel ATP2A2 mutations in patients with Darier’s disease. Hum Mol Genet 1999;8:1611—9. 4. Cooper SM, Burge SM. Darier’s disease. Epidemiology, pathophysiology and management. Am J Clin Dermatol 2003;4:97—105. 5. Macleod RI, Munro CS. The incidence and distribution of oral lesions in patients with Darier’s disease. Br Dent J 1991;171:131—6. 6. Cawson RA, Binnie WH, Eveson JW. Color atlas of oral disease. Clinical and pathologic correlations. 2nd ed. Hong Kong: Wolfe; 1994 [paragraph 12.5.].
