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Darier disease complicated by disseminated zoster

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Darier disease complicated by disseminated zoster
Rajesh Kandasamy1, Michelle Hecker MD2, Michael Choi MD3, James Pile MD2,4
Dermatology Online Journal 15 (2): 6

1. Department of Medicine.
2. Division of Infectious Diseases.
3. Department of Pathology.
4. Division of Hospital Medicine.
Case Western Reserve University/MetroHealth Medical Center Cleveland, Ohio


A 58-year-old man with Darier disease and end-stage renal failure on hemodialysis who developed disseminated Herpes Zoster is presented. He was cleared with intravenous acyclovir given at the time of dialysis.

Report of a case

A 58-year-old man with extensive biopsy-proven Darier disease (DD) involving the scalp, ears, neck, trunk, back, and extremities was admitted with fever and progressive rash. The patient was in his usual state of health until one week prior to admission when he developed vesicular lesions on his back and legs, subsequently spreading to include essentially all areas involved by his DD. He reported general malaise, as well as temperature up to 103° Fahrenheit.

Figure 1Figure 2
Figures 1 & 2. Disseminated zoster superimposed on lesions of Darier disease

The patient was diagnosed with DD at age six. Both his father and two of his children have also been diagnosed with the disease. Prior treatment of his DD included oral retinoids, dermabrasion and CO2 laser therapy. His medical history was also notable for well-controlled type two diabetes mellitus, hypertension and hemodialysis-dependent end stage renal disease. He reported having varicella as a child. At the time of presentation his temperature was 38.1° Celsius, and widespread vesicular to vesiculo-pustular lesions with an erythematous base were superimposed on his baseline exam (verrucous papules and coalesced plaques over much of his body) (Figs. 1 & 2). Bacterial cultures of unroofed lesions were negative, as were both culture and direct fluorescent antibody testing for herpes simplex virus. Direct fluorescent antibody testing for varicella-zoster virus was positive. Intravenous acyclovir was initiated at a dose of 10 mg/kg with dialysis and the patient defervesced over the next several days, with crusting and progressive improvement in his skin lesions. He was discharged on oral acyclovir and has not experienced further vesicular lesions.


Figure 3
Figure 3. Prior skin biopsy of our patient demonstrating characteristics acantholytic dyskeratosis, with loss of cohesion between keratinocytes (thin arrows) and abnormal premature keratinization of epidermal cells (thick arrow) (40X)

Darier disease, also known as Darier-White disease and keratosis follicularis, was initially described in 1889. The disease is transmitted via an autosomal dominant mechanism, with high penetrance but widely variable expression [1]. The genetic basis of Darier disease was recently demonstrated to result from multiple mutations in the ATP2A2 gene located on chromosome 12q23-24, which encodes for a sarco/endoplasmic reticulum calcium-ATPase pump isoform, SERCA 2 [2]. ATP2A2 is highly expressed in keratinocytes and the mutation appears to underly the characteristic defects of acantholysis and dyskeratosis (Fig. 3).

Darier disease is characterized by "greasy" hyperkeratotic papules which frequently coalesce to form plaques, particularly in seborrheic areas. Areas of flexure are often involved; a minority of patients have disease predominantly or exclusively in a flexural distribution. Palmar and nail involvement is very common [1]. Significant disfigurement occurs in individuals with high disease expression, and marked pruritus is seen in a majority of patients, as well as an unpleasant odor in many [3]. Darier disease is rare, with a prevalence estimated between 1 in 55,000 and 1 in 100,000, and typically presents during the first 2 decades of life, although rare cases presenting in late adult life have been reported [3]. Treatment consists of emollients for those with mild disease, with oral retinoids reserved for more severe cases. As with our patient, a variety of surgical techniques have been employed for those with extensive disease, although the role of surgery remains poorly defined.

Kaposi varicelliform eruption, or widespread vesicular superinfection, is a rare but well-reported complication of DD, and is typically caused by herpes simplex virus [4, 5, 6]. One prior case of multi-dermatomal zoster has been reported in the setting of DD, an HIV-positive man with a CD4+ count of approximately 300 with linear DD involving the right chest and arm, who developed zoster in the same distribution [7]. Disseminated zoster occurs in the setting of impaired cell-mediated immunity, particularly hematopoietic stem cell and solid organ transplantation, as well as advanced HIV infection [8, 9, 10, 11]. We report what to our knowledge is the first case of widely disseminated zoster in a patient with DD, and the first case of Darier-related disseminated zoster in an individual without overt immunocompromise. End-stage renal disease is a known predisposing factor for various bacterial infections, particularly with Staphylococcus aureus. Deficiencies in cell-mediated immunity are typically not characteristic of this condition, however; and chronic kidney disease has not been linked to disseminated zoster apart from the setting of renal transplantation. Although others have speculated that Kaposi varicelliform eruption may relate to an as-yet-poorly understood cell-mediated immunity defect in DD [5], this remains unproven, and we are unable to comment on whether this predisposed our patient to disseminated zoster. The possibility of disseminated zoster should be entertained, and testing for varicella-zoster virus considered, in patients with DD presenting with apparent Kaposi varicelliform eruption.


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