Can Darrier Disease be Localized Bullous??!!

Sir,

Darier disease, also known as keratosis follicularis or dyskeratosis follicularis, is a rare keratinization disorder. It is an autosomal dominant genodermatosis with high penetrance and variable expressivity. Its manifestations appear in childhood and adolescence. The clinical signs are represented by several hyperkeratotic papules primarily affecting seborrheic areas on the head, neck, thorax, palms and soles, and less frequently the oral mucosa.[1-6] The formation of nails is also altered, with presence of longitudinal lines or grooves and painful fissures. Associated anomalies have been described in the literature, including mental retardation and psychosis.[4] Its etiology is poorly explained in the literature. It is believed to be related to structural disorders in cell adhesion complexes (components of desmosomes), triggering self-immune reactions among epithelial cells. More recently, it has been related to mutations in the gene encoding the sarco/endoplasmic reticulum Ca2 + ATPase pump (SERCA2), resulting in abnormal organization or maturation of complexes responsible for cell adhesion, thus leading to the disturbance.[17-9] Histologically, it is characterized with: (a) a peculiar form of dyskeratosis resulting in the formation of corps ronds and grains; (b) suprabasal acantholysis leading to the formation of suprabasal clefts or lacunae; (c) irregular upward proliferation into the lacunae of papillae lined with a single layer of basal cells so called villi.

This paper reports a case of a patient with Darier disease presenting with rare presentation of localised bullous lesions on lower limb.

A 57-year-old female [Figure 1] presented with complain of recurrent painless vesiculobullous lesions on dorsum of hand and foot for last two years. On examination, few skin coloured non purulent vesiculobullous lesions without erythema were present over dorsum of both feet [Figure 2], keratotic lesions over palms and soles [Figure 3] and hyperkeratotic, skin coloured, flat, verrucous papules on dorsum of fingers [Figure 4]. V-shaped nicking on nails was noted on examination [Figure 5]. No lesions were found in flexural sites. Differential diagnosis of the localized bullous lesion was kept as localized bullous pemphigoid, diabetic bulla, localized bullous Darrier's disease and epidermolysis bullosa acquisita. There was family history of similar keratotic lesions on palms of her father and elder sister.

Figure 1

A 57 year old patient

Figure 2

Bullous lesion on dorsum of foot (arrow), ruptured mechanically

Figure 3

Keratotic lesions over palms

Figure 4

Hyperkeratotic, skin coloured, flat, verrucous papules on dorsum of fingers

Figure 5

V-shaped nicking on nails (arrow)

All routine investigations including FBS and PPBS were normal. The punch biopsy of the vesicular lesions on the dorsum of foot on histopathological examination revealed hyperkeratosis, focal parakeratosis, low papillomatosis, suprabasal clefting and occasional vesicle with acantholysis in epidermis [Figure 6]. Few dyskeratotic cells were seen in granular layer resembling corps ronds and in keratin layer resembling grains [Figure 7a and b]. Dermis had mild lymphocytic infilterate. Direct Immunofloroscence of the perilesional skin was negative for IgG, IgA, IgM, C3.

Figure 6

(H and E) ×100, showing hyperkeratosis, suprabasal cleft and villi (arrow)

Figure 7

(a) (H and E) ×100 showing corp ronds and grains (arrow) (b) (H and E) ×100 showing Corp ronds (arrow)

So the diagnosis was confirmed as localized bullous form of Darrier disease which is very rare variant of the disease rarely presenting in late 50's. She was treated with oral Acitretin 25mg OD and topical retinoid. The patient responded very well to the treatment. Histopathology came to great aid in the diagnosis of the patient with rare localized bullous type of presentation.

Other clinical variants of Darier's disease documented so far are hypertrophic type,[10] vesiculobullous type,[1112] linear or zosteriform type, follicular/Comedonal type. Oral vitamin A can be effective in treating Darier's disease in high doses. Etretinate is also effective. Topical tretinoin is effective in localized variant. Keratolytics can be used for hyperkeratotic variants. Hypertrophic lesions can be treated with dermabrasion, laser excision, surgical excision and grafting.