|Year : 2016 | Volume
| Issue : 2 | Page : 177-179
Darier's disease - Oral, general and histopathological features in a 7 year old child
Sreedevi Dharman, Muthukrishnan Arvind
Department of Oral Medicine and Radiology, Saveetha Dental College and Hospital, Chennai, Tamil Nadu, India
|Date of Web Publication||14-Apr-2016|
Dr. Sreedevi Dharman
Department of Oral Medicine and Radiology, Saveetha Dental College and Hospital, 162, Poonamallee High Road, Thiruverkadu, Chennai - 600 077, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Darier's disease, also known as keratosis follicularis, is a rare autosomal dominant genodermatosis, manifesting clinically as hyperkeratotic, firm papule that predominates in the seborrheic areas and flexures with accompanying nail abnormalities. Heat, sweating, sunlight, and stress are exacerbating factors of the lesion. The oral lesions are asymptomatic and comprise multiple white papules in the buccal mucosa and hard palate, giving a cobblestone appearance, and it is characterized histologically by loss of desmosomal adhesion and abnormal keratinization resulting in mucocutaneous abnormalities. Pruritus, recurrent infections, and malodor can decrease the quality of life. We report a case of a 7-year-old boy with clinical and histological features of Darier's disease.
Keywords: Hyperkeratotic, keratosis follicularis, pruritus, seborrheic
|How to cite this article:|
Dharman S, Arvind M. Darier's disease - Oral, general and histopathological features in a 7 year old child. J Indian Soc Pedod Prev Dent 2016;34:177-9
|How to cite this URL:|
Dharman S, Arvind M. Darier's disease - Oral, general and histopathological features in a 7 year old child. J Indian Soc Pedod Prev Dent [serial online] 2016 [cited 2021 Sep 19];34:177-9. Available from: https://www.jisppd.com/text.asp?2016/34/2/177/180449
| Introduction|| |
Oral genodermatosis is a genetically determined disease of the oral mucosa and skin. The common oral genodermatosis are white sponge nevus, pachyonychia congenita, dyskeratosis congenita, and Darier's disease.
Darier's disease was initially described by Prince Marrow in 1886 and simultaneously by Darier and White in 1889, independently. In 1917, the first case with oral manifestation was reported by Reenstierna.  It is a rare, autosomal, dominantly inherited condition with complete penetrance and variable expressivity.  It is caused by mutations in a gene, mapped to a single locus on chromosome 12q23-q24.1, which encodes a sarco/endoplasmic reticulum calcium ATPase pump.  SERCA2 dysfunction causes endoplasmic reticulum stress and impaired cell-to-cell adhesion strength. 
Although there is variable expressivity, affected individuals classically develop red-brown hyperkeratotic papules characteristically located on the trunk, scalp, face, and neck.  Confluent papules enlarge and develop into verrucous or vegetating plaques.  Characteristic nail abnormalities, hand and foot lesions, and oral white papules are often found in affected individuals. Lesions typically first appear between the ages of 6 and 20 years, and are characterized by wart-like blemishes on body areas with more exposure to heat, humidity, and sunlight. Patients often experience itchiness and are troubled by malodors due to frequent infections of the cutaneous lesions with bacteria, yeast, and dermatophytic fungi.  Similar changes occur in the mucous part of the hypopharynx, larynx, or rectum. Neuropsychiatric features, including mental retardation (in 10% of patients), schizophrenia, bipolar disorder, and epilepsy, have also been reported.  The degree and severity of clinical manifestations depend on the severity of genetic penetration or domination.
In this paper, we present a rare case of Darier's disease with only mucocutaneous manifestations at the time of presentation.
| Case Report|| |
A 7-year-old boy presented to the Department of Oral Medicine and Radiology, Saveetha Dental College and Hospital, with a chief complaint of persistent white patch bilaterally on the buccal mucosa for 4 years. It was insidious in onset and was neither painful nor associated with burning sensation. No clear family history of any hereditary diseases was elicited. History and clinical examination did not reveal any systemic abnormality.
On general examination, hyperkeratotic papules were present on the extensor aspect of elbow and knee joints [Figure 1]. The patient gave a history of intense pruritus in these patches in elbows and knees, which was aggravated on exposure to sunlight.
On intraoral examination, a diffuse grayish white patch of 2 cm × 1 cm, irregular in shape was present in buccal mucosa on either side with ill-defined margin, smooth surface, extends anteriorly from commissure of lip, posteriorly to distal cusp of deciduous second molar in occlusal plane. The surrounding mucosa was pigmented [Figure 2]. On palpation, this nonscrapable smooth-surfaced white patch was nontender. There were no secondary changes associated with the bilateral white patch.
As the white patch is present for a 4-year duration, asymptomatic, with associated pigmentation and keratotic papules in elbows and knees, it was provisionally diagnosed as hyperkeratotic patch with pigmentation. As the lesion was involving the oral and cutaneous region for 4 years, it could be an oral genodermatosis such as White sponge nevus, Darier's disease, or an immune-mediated inflammatory lesion such as lichen planus.
The patient was subjected to thorough systemic examination by a pediatric physician and subjected to complete blood examination, both of which did not reveal any abnormality.
Based on the pediatric dermatologist suggestion that both oral and cutaneous lesion could be part of the same disease process, an incisional biopsy of right buccal mucosa was done.
Histological picture revealed the presence of suprabasal clefts with focal hyperkeratosis. Acantholytic dyskeratosis, conspicuous corps ronds, and grains with mild degree of perivascular lymphocyte infiltrate, which is suggestive of keratosis follicularis [Figure 3].
|Figure 3: Histological picture showing suprabasal clefts with acantholytic dyskeratosis, conspicuous corps ronds, and grains|
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Conclusion with history, clinical examination, histopathological examination, a final diagnosis of keratosis follicularis/Darier's disease was made.
As the oral lesions were asymptomatic, no active treatment was initiated at this stage. For the hyperkeratotic papules, the patient was treated with topical Dermadew (keratolytic) lotion twice daily for 7 days. He is on constant review and follow-up.
| Discussion|| |
Darier's disease, also known as keratosis follicularis, is a rare keratinization disorder.  Keratinocytes display abnormal trafficking of the desmosomal protein desmoplakin and abnormal expression of cytokeratins 10 and 14. 
Although this is a genetically transmitted disease according to a larger series, about 47% of patients had no clear family history, presumably because of incomplete penetrance. Our case also did not have clear family history. Absence of family history could also be attributed to the fact that mild forms of the disease have not been recognized among the family members, lesions are clinically asymptomatic,  and are discovered only during routine dental examination. 
The sex incidence is equal, although the males appear to be more severely affected than females. The oral mucosa is affected in 50% of the cases, less often lingual or buccal involvement occurs.  Intraoral lesions are usually whitish and show variable consistency. The papules usually become apparent in the second or third decade, but can be visible from around the fourth year of life, as in our case. Pruritus is the most frequent symptom, occurring in 88% of patients.  Heat, sweating, sunlight, and stress may exacerbate the lesions. Involvement of the hands occurs in 96-98% of patients, with palmar pits and punctate hyperkeratotic papules on the dorsal and palmar aspects. Similarly, our case was a male patient presenting with asymptomatic nonscrapable bilateral white patch in buccal mucosa for past 4 years. Keratotic papules in elbows and knees in our patient which were pruritic got aggravated on exposure to sunlight.
Histologically, characteristic feature of suprabasal clefts, corps ronds, and grains present in our case were pathognomonic of Darier's disease. At the time of presentation, our case did not have other accompanying feature such as nail abnormality or hematological changes. The patient is likely to develop these changes over a period of time. He needs to be monitored under regular intervals.
Most patients with severe form of Darier's disease should receive genetic counseling, including information of inherited condition and risk of transmission to offspring. 
The complications in Darier's disease include Kaposi-Juliusberg syndrome (a severe herpes simplex virus infection) and squamous cell or other carcinomas.  Simple measures such as cool clothing and emollients may help considerably to manage symptoms such as itching, but advanced lesions require topical and systemic retinoids.
| Conclusion|| |
Diagnosis of mucocutaneous white lesions is always challenging because of similarity in their clinical presentations. Further, if it occurs in children, oral lesions are asymptomatic, constant follow-up and monitoring are mandatory. Darier's disease could be considered as a likely diagnosis of intraoral keratotic white lesion in children with accompanying skin lesions.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Prindiville DE, Stern D. Oral manifestations of Darier′s disease. J Oral Surg 1976;34:1001-6.
Godic A. Darier disease: A guide to the physician. J Med 2004; 35:5-17.
Sakuntabhai A, Ruiz-Perez V, Carter S, Jacobsen N, Burge S, Monk S, et al.
Mutations in ATP2A2, encoding a Ca2 pump, cause Darier disease. Nat Genet 1999;21:271-7.
Savignac M, Simon M, Edir A, Guibbal L, Hovnanian A. SERCA2 dysfunction in Darier disease causes endoplasmic reticulum stress and impaired cell-to-cell adhesion strength: Rescue by Miglustat. J Invest Dermatol 2014;134:1961-70.
Ringpfeil F, Raus A, DiGiovanna JJ, Korge B, Harth W, Mazzanti C, et al.
Darier disease - novel mutations in ATP2A2 and genotype-phenotype correlation. Exp Dermatol 2001; 10:19-27.
Zaias N, Ackerman AB. The nail in Darier-White disease. Arch Dermatol 1973;107:193-9.
Jacobsen NJ, Lyons I, Hoogendoorn B, Burge S, Kwok PY, O′Donovan MC, et al.
ATP2A2 mutations in Darier′s disease and their relationship to neuropsychiatric phenotypes. Hum Mol Genet 1999;8:1631-6.
Ferris T, Lamey PJ, Rennie JS. Darier′s disease: Oral features and genetic aspects. Br Dent J 1990;168:71-3.
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;121:1349-55.
Cooper SM, Burge SM. Darier′s disease: Epidemiology, pathophysiology, and management. Am J Clin Dermatol 2003; 4:97-105.
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:e270-1.
Burge SM, Wilkinson JD. Darier-White disease: A review of the clinical features in 163 patients. J Am Acad Dermatol 1992;27:40-50.
Ferizi M, Begolli-Gerqari A, Luzar B, Kurshumliu F, Ferizi M. A rare clinical presentation of Darier′s disease. Case Rep Dermatol Med 2013;2013:419797.
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.
[Figure 1], [Figure 2], [Figure 3]