Chronic Bullous Disease of Childhood

November 4, 2011

A 4-year-old, previously healthy girl presented to a tertiary care children’s hospital emergency department (ED) with large, tense bullae involving up to 40% of her body surface area. The patient’s parents described a 12-day history of itchy, papulovesicular lesions that had progressed into large blisters.

Presentation
A 4-year-old, previously healthy girl presented to a tertiary care children’s hospital emergency department (ED) with large, tense bullae involving up to 40% of her body surface area. The patient’s parents described a 12-day history of itchy, papulovesicular lesions that had progressed into large blisters.

The rash began as pruritic pink bumps around the child’s umbilicus that spread over several days to her abdomen and extremities. She was evaluated by her pediatrician 4 days after the initial eruption; an empiric diagnosis of varicella was made although the patient’s temperature was normal and she had no constitutional symptoms. Calamine lotion was recommended to treat the pruritis.

Over the next 3 days, the lesions spread and enlarged, progressing from vesicles to bullae. The child was taken to the ED for re-evaluation. There, therapy with amoxicillin, mupirocin, and oral diphenhydramine was initiated for presumed bullous impetigo.

At home, over the next 5 days, the lesions continued to enlarge and spread, causing significant discomfort, and limiting ambulation. The parents brought the child back to the ED. She was evaluated and transferred for admission to the children’s hospital. The patient had no history of illness, medication use, or known allergy to medications and her immunizations were up-to-date. There was no personal or family history of similar skin lesions, abscesses, or cellulitis. The family had not traveled recently; they were not aware of exposure to ticks or other disease-carrying insects.


Figure 1


The patient’s vital signs were stable and temperature normal on admission. Her height and weight were at the 97th and 89th percentiles, respectively. The physical examination found an otherwise healthy child with a uniform bullous eruption covering most of her body. The presentation was worst on her legs (Figure 1), and her arms and trunk were also affected. There were a few smaller lesions on palms, soles, neck, and ears, but her face, scalp, and anogenital mucosa were spared.


Figure 2


The lesions were pink-to-red, discoid, sharply-circumscribed discreet and coalesced, 1- to 3-cm bullae and erosions. Many had central hemorrhagic crusting (Figure 2). Intact bullae were filled with straw-colored fluid. A few lesions had a raised border, suggestive of a “rosette” configuration (Figure 3).

Two 3-millimeter punch biopsy skin specimens were submitted on hospital day 1 for light and immunofluorescent microscopy. Histopathologic findings included a linear band of IgA at the basement membrane zone and a subepidermal split with a dense neutrophilic infiltrate. Additional investigation revealed a normal titer for glucose-6-phosphate dehydrogenase (G6PD).


Figure 3


The skin-care regimen during the patient’s 4-day hospitalization included a daily whirlpool with ½ cup added bleach followed by application of petroleum jelly and this was to be continued at home until her skin cleared. Oral dicloxacillin, 250 mg (12 mg/kg), was administered twice daily along with prednisolone, 30 mg (1.5 mg/kg) daily. After 1 month, there was significant improvement (Figure 4).  Topical dapsone 5% gel was recommended for application to affected areas but was not authorized by the patient’s insurance plan.


Figure 4

Discussion on Next Page…

Discussion
Although rare, chronic bullous disease of childhood (CBDC) is the most common immunobullous disorder seen in children. The acquired condition was initially described in 1970.2 CBDC is immunohistochemically similar to linear IgA bullous disease (LABD) of adults. Both are characterized by a linear pattern of IgA deposition directed against a fragment of collagen XVII known as linear IgA disease antigen (LAD-1), located at the epidermal basement membrane zone.1-2 Disease expression is similar in the childhood and adult types with minor differences: mean age of onset, distribution and configuration of skin lesions, and risk of recurrence. Our patient presented at the recognized mean age of onset for CBDC, around age 4.5 years.1  LABD presents between 60 to 65 years of age with large bullae on the extremities.3  The classic CBDC skin lesion is a central bulla rimmed by smaller curved or ovoid vesicles-a pattern that has earned them several descriptive names: “rosette”, “string of pearls” and “cluster of jewels”.  The most commonly involved sites in children are the lower trunk, vulvar area and upper thighs. Recurrence rates are higher in children than in adults.

Although not seen in our patient, onset of CBDC lesions is usually insidious. Despite this typical course, however, CBDC is frequently mistaken for acute varicella or bullous impetigo on initial diagnosis. More characteristic lesions generally arise after several weeks. At the peak of a CBDC outbreak, the sheer number of vesicles can be disabling, cosmetically disfiguring, and may interfere with activities of daily living and school attendance.

Our patient’s initial lesions suggested CBCD, but were not classic, so histologic confirmation was required. The differential diagnosis includes bullous impetigo, bullous erythema multiforme, and bullous pemphigoid and pemphigus vulgaris, although all of these were less likely in this case given the patient’s history, demographics, and clinical appearance.

The course of CBDC is marked by intermittent flares and improvement that alternate over a period of months to years before the disease resolves. No prodrome or trigger has been recognized. Bland skin care is recommended for optimal outcome. Where possible, blisters should be left intact to allow the blister roof to serve as a biologic dressing. Daily bathing followed by application of petroleum jelly will help maintain skin integrity.  Lesions generally heal with residual transient dyspigmentation, but without scars.2  

There is no well-defined standard of care for CBDC. First-line treatment has been with an oral sulfone, dapsone or sulfapyridine, with an oral corticosteroid added as needed. Sulfapyridine, once widely available, is now manufactured by only one company and requires IRB approval for distribution.  Long-term use of either sulfone drug carries the risk of hemolysis. The risk of sulfone-associated severe hemolytic anemia is high in people with inherited G6PD deficiency, so a normal screening G6PD level is required before initiating treatment.

The FDA has recently approved a 5% topical formulation of dapsone for the treatment of acne that may be a safer long-term alternative to oral dapsone for CBDC. Oral corticosteroids offer short term improvement, but chronic use is associated with several adverse reactions, which limit their long-term benefit.

Oral antibiotics, most often dicloxacillin, have been reported as a steroid-sparing alternative for symptom resolution and prevention of future outbreaks.1

Teaching Points
  • CBDC is the most common autoimmune blistering disease of childhood.
  • The initial pruritic papulovesicular lesions may be misdiagnosed as acute varicella.
  • There is no well-defined treatment for CBDC; referral to a dermatologist is indicated.

References:

References

1. Siegfried EC, Sirawan S. Chronic bullous disease of childhood: successful treatment with dicloxacillin. J Am Acad Dermatol. 1998;39(5 Pt 1):797-800.

2. Mintz EM, Morel KD. Clinical features, diagnosis, and pathogenesis of chronic bullous disease of childhood. Dermatol Clin. 2011;29:459-462.

3. Egan, CA, Zone, JJ. Linear IgA bullous dermatosis. Int J Dermatol. 1999:38:818-827.