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A case of bullous Darier's disease histologically mimicking Hailey-Hailey disease

  • Author(s): Kakar, Bhawna
  • Kabir, Sardana
  • Garg, Vijay K
  • Bhushan, Premanshu
  • et al.
Main Content

A case of bullous Darier's disease histologically mimicking Hailey-Hailey disease
Bhawna Kakar1, Sardana Kabir1, Vijay K Garg1, Premanshu Bhushan2
Dermatology Online Journal 13 (3): 28

1. Department of Dermatology, Maulana Azad Medical College, New Delhi, India 2. Department of Dermatology, Lady Hardinge Medical College Shika Bansal; Department of Dermatology, Maulana Azad Medical College

Abstract

The bullous variant of Darier's disease is a rare type and the exact nosological position relative to Hailey Hailey disease has been doubtful. We report a case of bullous Darier's disease with histological picture suggestive of Hailey-Hailey disease. We have also reviewed and summarized the differences between Darier's disease and Hailey-Hailey disease.



Clinical synopsis

A 45-year-old woman presented with multiple dark, raised, keratotic, foul smelling lesions for 2 years. The lesions started from abdomen and gradually progressed to involve the neck, axillae, front of elbows, lower back, groins and back of knees. The patient also developed lentil sized fluid-filled lesions, rupturing within 3-4 days to leave behind red raw areas healing without sequelae. Mucocutaneous examination revealed multiple hyperpigmented, warty, greasy papules present over the flexural areas (Figs. 1A, 1B). Superimposed on these were multiple clear fluid filled vesicles and bullae of size 2x2-7x7mm present on normal to slightly erythematous base (Fig. 1C). Palms and soles, oral mucosa, genital mucosa, and nails were within normal limits.


Figure 1Figure 2
Figures 1A, B: Hyperpigmented warty greasy grouped papules seen over the neck and antecubital fossae. Figure 1C. Vesicles seen on a erythematous base superimposed on the warty papules over the popliteal fossa.
Figure 2A: Hematoxylin-Eosin 40X . Biopsy of the papule showing hyperkeratosis, suprabasal cleft with multiple acantholytic cells showing dilapidated brick wall appearance (shown by arrow a) and a few dyskeratotic cells (Corps ronds) in the stratum malphigii (shown by arrow b). Figure 2B: Hematoxylin-Eosin 40X. Biopsy of the vesicle revealing hyperkeratosis, suprabasal cleft with a few corps ronds and clustered cells mimicking a "dilapidated brick wall" (shown by arrow).

All routine hematological investigations were normal. Tzanck smear from the vesicle revealed multiple acantholytic cells. Histopathology from the papule and vesicle showed hyperkeratosis, papillomatosis, follicular plugging, suprabasal clefting with acantholysis, dyskeratosis and villi formation (Figs. 2A, 2B). A few foci resembling dilapidated brick wall could also be visualized (Fig. 2B). Direct immunofluorescence was negative.

In view of the clinico-pathological findings we arrived at a diagnosis of bullous Darier's disease, though the histology was suggestive of Hailey-Hailey disease. She was treated with oral predinisolone with improvement in the warty lesions and total subsidence of vesicles.


Discussion

Darier's disease is an autosomal dominant disorder with altered keratinisation of the epidermis, nails and mucous membranes. Mutations in a sarcoendoplasmic reticulum Ca+2 ATPase isoform 2b (SERCA 2b) is the main association of Darier's disease[1]. The rare vesiculobullous variant of Darier's disease was first described by Pels and Goodman in 1939[2] with only few published case reports of the same [3, 4, 5].

The exact nosology of Hailey-Hailey disease has been debated, although the confusion may be on account of the occasional histological overlap [3]. Two points in favor of the basic unity of the two diseases were the alleged simultaneous occurence in the same patient, and the occurrence of corp ronds in both diseases [6, 7, 8]. However, the patients described as having both diseases were apparently either cases of Darier's with vesicular lesions[6] or cases of familial benign pemphigus (Hailey-Hailey disease) with the presence of corps ronds [7].

Occasionally, some edema in Darier's disease and dyskeratosis in Hailey-Hailey disease may be observed; but fundamentally Darier's disease is a keratinising disorder and Hailey-Hailey is an edematous disease [9]. Clinically, genetically and histopathologically they are now known to be distinct entities [10].

We tabulated the differences between the two entities to arrive at our final diagnosis, (see Table 1). The warty malodorous greasy papules and vesicles with lack of maceration, the histological finding of marked hyperkeratosis, villi formation, and presence of dyskeratotic cells pointed towards the diagnosis of bullous Darier's disease. But the age of onset, typical flexural involvement, relapsing and remitting course of the vesicles and the lack of profound dyskeratosis and presence of foci of dilapidated brick wall appearance suggested Hailey-Hailey disease. The almost complete resolution of the vesicles on treatment with steroids[11] with persistence of papules, their generalized distribution, and the histological evidence pointed in favor of Darier's disease. The occasional histopathological findings suggestive of Hailey-Hailey disease have been reported previously and do not contradict our final diagnosis [6, 7, 8, 9].

In conclusion the historical debate about the link between the two entities has been put to rest at the altar of genetic research [10], which inconvertibly has differentiated between the two conditions. Obviously the histological overlap seen occasionally is of interest to pathologist, though the nuances of this overlap may have little bearing on the clinical diagnosis or management.

References

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