A 25-year-old female presented with unilateral, greasy, follicular and nonfollicular papules over the forehead, retroauricular region and abdomen on the left side of body. They were mildly pruritic. Numerous discrete hypopigmented macules scattered over medial side of forearm and upper back on the left side. Skin biopsy from one of the papules over the forearm showed features of Darier’s disease. The present case is reported for the rare unilateral presentation and distribution of lesions of Darier’s disease along with hypopigmented macules.

Case Report

A 25-year-old female presented with complaints of mildly pruritic papules over the left side of the body of 10-year duration. Initially, she developed the skin lesions over the left retroauricular region, which gradually extended over the chest and abdomen limited to the left side of the body. There was history of exacerbation of skin lesions during summer. There was no family history of the disease. There were no systemic complaints.

Dermatological examination revealed few grouped and few discrete, crusted, greasy follicular and nonfollicular papules of 1-3 mm size over the scalp, forehead, retroauricular region, trunk, abdomen and cubital and popliteal fossa on the left side of the body. Numerous discrete hypopigmented macules of 1 mm diameter were observed scattered over the medial side of forearm arm and upper back on the left side. She also had small flat topped papular lesions of 2 mm size over the dorsum of left hand. Multiple punctuate keratoses and pits were seen over the left palm. Right hemithorax, limbs and face were completely spared. Oral mucosa and nails were normal. Systemic examination was normal.

Routine hematological and biochemical parameters were normal. Skiagram of the chest and long bones were normal. Histopathological examination of one of the crusted papules showed classical features of Darier’s disease (DD). The patient was treated with topical retinoic acid 0.05%, topical clindamycin and oral isotretinoin 20 mg/day.

This resulted in partial flattening of the lesions in 1 month.

Discussion

Darier’s disease (DD) also known as keratosis follicularis, is an inherited genodermatosis of autosomal dominant inheritance with variable penetrance. The disease is mostly sporadic and occasionally develops from spontaneous mutations in the gene coding for the disease.1 In 1889, James White and Jean Darier’s described this condition.

The prevalence of the disease has been estimated at 1,100,000.2 Pathogenesis of the disease is unknown, but abnormalities of structural proteins may underline the deficiency.2 DD has been shown in some cases to result from genetic mosaicism with the discovery that mutations in ATP2A2 cause.3 Gene sequencing can be used to confirm the diagnosis. DD most commonly manifests from age 6 to 20 years in both sexes. It is characterized by diffuse greasy hyperkeratotic follicular and extrafollicular papules predominantly in the seborrheic regions of the body along with nail abnormalities and mucous membrane changes. Its clinical variants include the hypertrophic, vesicular, vesiculobullous, localized comedonal, unilateral and zosteriform types. Approximately 80% of patients have mild flexural involvement and in only <10% of patients, flexural disease predominates, which is frequently associated with pruritus. Multiple guttate tiny hypopigmented macules are also seen in patients with DD on trunk and limbs. Such lesions were observed in this patient but were limited to left side of the body. Nail changes include white and red longitudinal bands, longitudinal nail ridges, splitting and subungual hyperkeratosis, often with a characteristic V-shaped nick at the free margin of the nail. Mucosal lesions are seen in 15% of patients as white papules with a central depression. They are commonly observed in buccal mucosa. Nail and mucosal changes were not observed in this present patient.

Classical histological features of DD include: a) Acantholysis resulting in the formation of characteristic suprabasal clefts and b) dyskeratosis presenting as corps ronds and grains. The underlying dermal papillae, which are covered by a single layer of epithelium, project into these clefts and form villus-like structure. All these features were observed in the skin biopsy of this patient.

When the patient first presented to us, we considered acne form eruption as one of the differential diagnosis due to the presence of eruption unilaterally. However, the onset of the disease in the second decade, presence of follicular and nonfollicular crusted papules, characteristic keratoses of the palms with pathognomonic minute pits gave a strong clinical suggestion of ‘unilateral Darier’s disease’, which was confirmed by the histopathological findings in our case. This conglomeration of features is enough to differentiate unilateral DD from ‘acantholytic dyskeratotic epidermal nevi’ with which it could also be confused due to its unilateral presentation.

Unilateral involvement in DD was first reported in 1948 by Anderson.4 It occurs in 10% of cases but this high percentage may be due to close resemblance between this type of keratosis follicularis and linear dyskeratotic epidermal nevi.5,6 Unlike the classical type of DD, the unilateral variety is thought to be of nongenetic origin with a delayed onset.1 A review of literature revealed that majority of cases had the onset in adult life.6 The unilateral form of disease differs from classic form in having linear or zosteriform distribution. A case of unilateral DD that followed the lines of Blascho was also reported in 1992.2

In our case, the distribution of lesions was neither linear nor zosteriform but was strictly unilateral over entire body surface, almost never crossing the midline. The presence of hypopigmented macules which is a rare manifestation in DD was first described by Goddal and Richmond in 1965.7 In the present patient, hypopigmented macules were seen unilaterally on the medial side of left arm, forearm and upper trunk.

This case is reported for the unilateral presentation of keratosis follicularis skin lesions as well as guttate hypopigmented macules in a nonzosteriform pattern on left upper and lower limbs, face and trunk and punctuate keratoderma of left palm, with classical histological features of DD.

References

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2. Burg SM, Cederholm-Williams SA, Garrod DR, et al. Cell adhesion in Hailey-Hailey disease and Dariers disease immunocytological and ex-plant tissueculture studies. Br J Dermatol 1991;125:426-35.
3. Onozuka T, Sawamura K, Yokota, et al. Mutational analysis of the ATP2A2 gene in two Darier’s disease families with intrafamilial variability. British J Derm 2004;150:652-7.
4. Anderson AP. Darier’s disease unilateral. Arch Dermatol Syphilol 1948;58:581-3.
5. Kumar P, Thomas J. Unilateral Dariers disease (DD) masquerading as acne vulgaris. Indian Soc Teledermatol 2008;Vol. 2, No. 3.
6. Gupta S, Shaw JC. Unilateral Darier’s disease with unilateral guttate leukoderma. J Am Acad Dermatol 2003;48:955-7.
7. Manimegalai M, Kumar P, Premalatha S. Unilateral Darier’s disease. Ind J Derm Venerol Lep 1997;63: 323-5.