An 8 year-old girl presented with a two-day history of blisters on her face, trunk, and extremities (Figure 155-1). She complained of moderate discomfort from the blisters, but denied itching, burning, fever, and recent illness. She was not taking any medications. Biopsy demonstrated subepidermal vesicles and a rich neutrophilic infiltrate in the dermal papillary tips. Direct immunofluorescence revealed a linear deposition of IgA along the basement membrane confirming the diagnosis of chronic bullous disease of childhood.The patient was started on systemic therapy with dapsone and her lesions quickly resolved.

Chronic bullous disease of childhood (CBDC) is the most common autoimmune bullous disorder in children.¹ This subepidermal vesiculo-bullous disorder is characterized by linear IgA deposits at the dermal-epidermal junction. It shares the same immunopathologic mechanism with its adult counterpart, adult linear IgA dermatosis. Although there is a great deal of overlap between the adult and childhood forms of linear IgA dermatosis, CBDC classically appears before the age of 5 years old, whereas adult linear IgA disease appears after age 60 years old. CBDC is considered a benign condition because it does not increase mortality; however, it may carry significant morbidity and, therefore, warrants treatment aimed at controlling the disease. Treatment with dapsone or sulfapyridine usually results in rapid resolution of the lesions. No correlation between the severity of blistering and the chronicity of disease exists. Most patients undergo spontaneous remission within months to years of initial presentation.

IgA bullous dermatosis of childhood, Linear IgA dermatosis, bullous disease of childhood, or chronic bullous dermatosis of childhood.

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  CBDC is a rare disorder with an incidence of 1:500,000.²

  
  
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  It is the most common autoimmune bullous disorder in children.¹

  
  
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  Age of onset generally ranges from 1 to 11 years old with a mean of 3.5 to 4.5 years;² however, some case reports have documented neonatal onset of disease.^3,4

  
  
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  All races may be affected, although the disease appears to be more common in developing countries.²

  
  
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  Data on the sex predilection of CBDC is heterogeneous and appears to vary with location.⁵ Both sexes are affected, and some of the literature notes a slight female predominance.^2,6

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  The etiology and exact pathophysiology of CBDC has not yet been defined, although both humoral and cellular immune responses are implicated in the disease process. The characteristic blister formation occurs as a result of IgA antibody formation against a heterogenous group of antigens located in the basement membrane zone of the epidermis. Over the last few decades, studies have identified a significant number of these targeted antigens, most commonly the 120-kDa and 97-kDa protein fragments of collagen XVII. Collagen XVII, also known as the 180-kDa bullous pemphigoid antigen (BP180), is a hemidesmosomal transmembrane protein that helps maintain the structural integrity of the dermal-epidermal junction.⁴

  
  
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  Most cases of CBDC are idiopathic, and the inciting event that induces the production of autoantibodies remains unknown; however, a thorough history is imperative as numerous precipitating factors have been identified. These include:

  
  
  
  
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    Infection—Recent upper respiratory tract infection, gastroenteritis, varicella, and other viral or bacterial infections.^2,7

    
    
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    Drugs—Vancomycin is most commonly associated; others include nonsteroidal antiinflammatory drugs such as diclofenac and naproxen, antibiotics such as amoxicillin, amoxicillin-clavulanate, ampicillin, ceftriaxone-metronidazole, and penicillin, as well as amiodarone, captopril, and phenytoin.^5,6,8

    
    
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    Skin trauma—Local skin injury, burns, UV light exposure^5–7

  
  
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  The literature highlights a notable association between the development of CBDC and the presence of certain human leukocyte antigen (HLA) genotypes, including HLA-B8, CW7, DR3, and DQW2.^2,4,9,10 The presence of these haplotypes has been associated with an early onset of disease,⁶ particularly in homozygous individuals.²

Clinical Features

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  A non-specific prodromal illness may precede development of the skin lesions.

  
  
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  Onset of blisters is abrupt; systemic symptoms such as fever may or may not be present.

  
  
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  Disease presentation is variable with respect to both the distribution and morphology of the skin lesions.

  
  
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  Classically, the primary lesions of CBDC are tense, clear or hemorrhagic vesicles or bullae. The vesicobullous lesions may develop on normal-appearing skin or the skin may appear erythematous or urticated. The blister size is variable, and lesions frequently assume annular or arcuate patterns (Figures 155-2 to 155-4).

  
  
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  The development of new lesions around resolving lesions creates the pathognomonic “string of pearls” or “rosette” appearance of CBDC (Figures 155-2 to 155-4).

  
  
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  Mucous membrane involvement is present in the majority of patients with variable presentation. Possible manifestations include oral ulceration, desquamative gingivitis, erosive cheilitis, nasal congestion, and bleeding. Ocular involvement may present as a conjunctivitis associated with photosensitivity, dryness, and irritation. Importantly, eye involvement can progress to serious sequelae including scarring and blindness.

  
  
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  Patients may be asymptomatic or may experience a variety of symptoms ranging from mild pruritus to severe pruritus or burning.

  
  
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  Skin lesions are usually most severe at initial presentation. Subsequent attacks, if they occur, are less severe.

  
  
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  Healed lesions may cause transient skin hypopigmentation or hyperpigmentation known as “postinflammatory dyspigmentation.” Permanent scarring is not typical.