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Table of Contents   
CASE REPORT  
Year : 2011  |  Volume : 22  |  Issue : 6  |  Page : 843-846
Darier disease with oral and esophageal involvement: A case report


1 Department of Oral Pathology, SRM Dental College, Ramapuram, Chennai, India
2 Department of Oral Pathology, Sri Ramachandra Dental College, Chennai, India
3 Department of Dermatology, Sri Ramachandra Medical College, Chennai, India

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Date of Submission10-Dec-2009
Date of Decision08-Feb-2010
Date of Acceptance06-Sep-2011
Date of Web Publication5-Apr-2012
 

   Abstract 

A 58-year-old man presented with itchy papular eruptions all over the body since 15 years. Intraoral examination revealed raised papular lesions on the labial mucosa, hard palate, and tongue. The histopathology of the oral and skin lesions was confirmative of Darier disease (DD). This patient also showed esophageal involvement, which was confirmed histopathologically. Such a presentation of DD, with oral and esophageal involvement, is rare.

Keywords: Corp ronds cells, Darier disease, esophagus, leukoplakia, smoker′s palate

How to cite this article:
Thiagarajan MK, Narasimhan M, Sankarasubramanian A. Darier disease with oral and esophageal involvement: A case report. Indian J Dent Res 2011;22:843-6

How to cite this URL:
Thiagarajan MK, Narasimhan M, Sankarasubramanian A. Darier disease with oral and esophageal involvement: A case report. Indian J Dent Res [serial online] 2011 [cited 2014 Jul 22];22:843-6. Available from: http://www.ijdr.in/text.asp?2011/22/6/843/94682

   Introduction Top


Darier disease (DD) is an uncommon genodermatosis also known as keratosis follicularis, dyskeratosis follicularis, and  Darier-White disease More Details. This rare autosomal dominant genodermatosis was independently reported by both Darier and White in 1889. [1],[2] The prevalence of DD has been reported to range from 1 in 50000 in central England to 1 in 100000 in World. DD most commonly presents in the first and second decades of life. Males and females are equally affected, but the clinical expression is usually mild in females. Although it is inherited as an autosomal dominant trait, 47% of the patients do not have a family history. [1] The mutated gene, which was found by Sakuntabhai et al., is located in the ATP2A2 gene on chromosome 12q23-24.1. This gene encodes for a sarco/endoplasmic reticulum calcium ATPase pump (SERCA2) that has a role in the intracellular signaling of calcium. The calcium has a role in regulating cell differentiation and in initiating assembly at desmosomes. The acantholysis in DD is due to the loss of intracellular signaling of calcium, resulting in breakdown of desmosome. [2],[3]

Patients with DD usually present with keratotic papules distributed in the seborrheic areas of the chest, scalp, forehead, shoulders, ears, nasolabial folds, and groin. The oral lesions are asymptomatic and comprise multiple white papules in the buccal mucosa and the soft and hard palate, giving a cobblestone appearance. [4],[5] Involvement of the esophagus is very rare and so far only a few cases have been reported in the literature. [6],[7]

The objective of this study is to report a case of DD with varied manifestations intraorally and wide involvement of the esophagus. Diagnosis was established on the basis of endoscopy and histopathological findings.


   Case Report Top


A 58-year-old male patient presenting with itchy papular eruptions all over the body for 15 years reported to the Department of Dermatology, Sri Ramachandra Medical College. The first skin changes appeared when he was 43 and comprised dark pigmented macules on the genital area. Similar lesions then gradually appeared on the face, scalp, chest, and back. There were multiple warty plaques distributed over the scalp, back, chest, forehead, face, and shoulder. Along with the multiple palmar hyperkeratotic lesions there was characteristic V-shaped nicking and longitudinal ridges in the nails.

The patient was married, with one son and one daughter. Clinical history of the parents and offspring as provided by the patient was not conclusive, for any skin lesions. The patient had no history of tobacco or alcohol consumption. His oral hygiene was very poor and he was therefore referred to the dental department.

Intraoral examination revealed multiple firm papules on the labial mucosa and tongue, with widespread white papules with central depression over the entire palate [Figure 1]. A non-scrapable grayish-white patch resembling leukoplakia was seen in the buccal mucosa on the right side [Figure 2]. The patient had generalized periodontitis, with grade III mobility in most of the teeth. Complete hemogram, renal profile, and liver function tests were within normal limits. He underwent total extraction of teeth, with uneventful healing of the extracted sockets.
Figure 1: Raised papular lesions on the palate.

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Figure 2: Non-scrapable grayish-white patch on the buccal mucosa on the right side.

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Incisional biopsy was taken from the leukoplakia-like lesion in the buccal mucosa and from the warty eruptions on the skin. The eosin and hematoxylin-stained sections of the buccal mucosa revealed hyperorthokeratosis, with keratin plugging, acanthosis, and suprabasilar cleft, leading to suprabasilar acantholysis with acantholytic cells which is characteristic of DD [Figure 3].
Figure 3: Buccal mucosa showing hyperkeratosis, acanthosis, and acantholysis (H and E, ×10). Inset: Acantholytic cells (×40).

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The skin biopsy was confirmative of DD, showing features of keratin plugging and the characteristic corps ronds cells at the superficial keratinized layer [Figure 4].
Figure 4: Skin showing keratin plugging (H and E, ×10). Inset: Characteristic corps ronds cells at the superficial keratinized layer (×40).

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The patient subsequently with in few days developed difficulty in swallowing food. Owing to the extensive involvement of the oral cavity, concurrent esophageal involvement was suspected and upper gastrointestinal endoscopy was performed. This revealed diffuse involvement of the upper one-third of the esophageal mucosa by hyperkeratotic white discrete papules [Figure 5]. Biopsy taken from the hyperkeratotic papules showed typical suprabasillar cleft and acantholytic cells, suggestive of esophageal involvement of DD [Figure 6]. The patient refused any treatment for his condition and declined to come for follow-up visits.
Figure 5: Hyperkeratotic papules in the upper one-third of the esophagus.

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Figure 6: Esophagus showing intraepithelial cleft (H and E, ×10). Inset: Acantholytic cells and intraepithelial cleft (×40).

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   Discussion Top


Mucosal lesions are uncommon in DD, the incidence varying from 15% to 50% in different studies. Palatal lesions may mimic papillary hyperplasia associated with dentures or resemble nicotinic stomatitis. DD can also present as a white patch resembling leukoplakia. [2],[5] Previous studies have suggested that oral involvement may parallel the severity of the skin condition. [4] Our findings support this observation, since the patient had extensive oral mucosal involvement along with severe skin involvement.

Histologically, DD is characterized by the presence of cleavage, loss of epidermal cell adhesions, formation of corps ronds and grains, and hyperkeratosis. 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 and have an elongated densely-stained nucleus surrounded by keratin-like material. Electron microscopy studies reveal basal cell vacuolization, decreased number of desmosomes on the lateral border of the basal cells, separation of tonofilaments from their insertion on the cell membrane and large circular aggregates around the nucleus. [2],[4]

Extension into the oropharynx and esophagus is pathognomonic for darier disease. Involvement of the esopharyngeal mucous membrane is rare; however, the real incidence of esophageal involvement is unknown since it is usually discovered only incidentally on endoscopic examination. Involvement of the esophageal mucous membrane is asymptomatic and rare but there is the possibility of superadded viral infection and severe dysplasia or malignancy arising from these lesions. [6],[7] In our case the esophageal involvement was confirmed histopathologically but there were no features of dysplasia or infection.

The complications in DD include Kaposi-Juliusberg syndrome (a severe herpes simplex virus infection) and squamous cell or other carcinomas. So far only one case of oral squamous cell carcinoma has been reported which developed from oral lesions of DD [3]

Despite much progress in understanding the molecular basis of the disease, disappointingly little has changed in the treatment armory. Conventional treatment for severe disease still relies greatly on oral retinoids. However, retinoids are teratogenic and pregnancy should be avoided during and for a while after treatment. DD is a dominantly inherited condition and non-penetrance is unusual. Genetic counseling should be offered to the patients. Since the patient's parents and offspring could not be examined the possibility of DD cannot be ruled out. Moreover, the possibility of family members having a milder form of the disease which has not been recognized should also be considered. The varied clinical heterogeneity and genetic heterogeneity in DD makes it hard to predict how severely a child will be affected even if the mutation is detected using prenatal diagnostic methods. Repair of the disease gene in DD is still a distant hope. [8]


   Conclusion Top


Darier disease is an uncommon dermatological condition with varied clinical presentation in the oral cavity. Intraoral lesions in DD can mimic leukoplakia and smoker's palate. We strongly recommend an endoscopic examination in patients with intraoral DD lesions, firstly to rule out the possibility of malignancy which can arise from these lesions and, secondly, to find out the real incidence of esophageal involvement in DD. The dentist should be aware of the mucosal manifestations of DD and must view with suspicion any unusual oral lesions with concurrent cutaneous lesions.

 
   References Top

1.Jalil AA, Zain RB, van der Waal I. Darier's disease: A case report.Br J Oral Maxillofac Surg 2005;43:3336-8.  Back to cited text no. 1
    
2.Macleod RI, Munro CS.The incidence and distribution of oral lesionsinpatients with Darier's disease. Br Dent J1991;171:133-6.  Back to cited text no. 2
    
3.Dolci M, Favia G, Scully C, Di Alberti L.Keratosis follicularis of the oral mucosa with oral squamous cell carcinoma. Oral Oncol 2004;40:856-8.  Back to cited text no. 3
    
4.Freedberg IM, Eisen AZ, Wolff K, Frank AK, Goldsmith LA, Katz SI, Editors. Fitzpatrick's Dermatoloy in General Medicine,6 th ed, Vol.I, Chapter 54.USA:McGraw-Hill 2003;523-7.  Back to cited text no. 4
    
5.Bernabé DG, Kawata LT, Beneti IM, Crivelini MM, Biasoli ER. Multiple white papules in the palate: Oral manifestation of Darier's disease. Clin Exp Dermatol 2009;34:270-1.  Back to cited text no. 5
    
6.Al Robaee A, Hamadah IR, Khuroo S, Alfadley A. Extensive Darier's disease with esophageal involvement. Int J Dermatol 2004;43:835-9.  Back to cited text no. 6
    
7.Vieites B, Seijo-Ríos S, Suárez-Peñaranda JM, Lariño-Noia J, Macías-García F, Domínguez-Muñoz E,et al. Darier's disease with esophageal involvement. Scand J Gastroenterol 2008;43:1020-21.  Back to cited text no. 7
    
8.Hulatt L, Burge S. Darier's disease: Hopes and challenges. J R Soc Med 2003;96:439-41.  Back to cited text no. 8
    

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Correspondence Address:
Magesh Karuppur Thiagarajan
Department of Oral Pathology, SRM Dental College, Ramapuram, Chennai
India
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DOI: 10.4103/0970-9290.94682

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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