Linear IGA Bullous Dermatosis (LABD)

  • Incidence of 1 per 250,000 per year in southern England
  • Occurs in children (mean 4.5 yo) and adults (mean > 60 yo)
  • Slight female predominance

  • Deposition of IgA immunoglobulin in the lamina lucida (majority) > sublamina densa 🡪 BMZ vesiculation 
  • Antigens: 
    • IgA autoantibody against the LABD97 region (cleaved ectodomain) of the extracellular non-collagenous NC16A domain of BP180 protein (see bullous pemphigoid)
    • Others: BP180, BP230, type VII collagen 
  • Unknown autoantibodies for the sublamina densa type of LABD – possibly autoantibodies against type VII collagen within the anchoring fibrils 
  • Associations of LABD (see below) thought to stimulate the production of the IgA autoantibodies by the immune system in predisposed individuals

Associations

  • GI: gluten-sensitive enteropathy (0-24%), ulcerative colitis (LABD resolves post colectomy), Crohn’s disease and gastric hypochlorhydria
  • Autoimmune (not statistically significant): SLE, DM, thyrotoxicosis, autoimmune hemolytic anemia, RA 
  • Malignancies: B-cell lymphoma, CLL, thyroid carcinoma, bladder carcinoma, colon carcinoma and esophageal carcinoma 
  • Infections: varicella zoster, antibiotic-treated tetanus, URTI
  • Drugs: 
    • Most common: vancomycin
    • Less common: penicillins, cephalosporins, captopril > other ACEi, NSAIDs  
    • Uncommon: phenytoin, sulfonamides

  • Polymorphic clinical features in adults that can be similar to those of DH or bullous pemphigoid:
    • Vesiculobullae in herpetiform arrangement on normal or erythematous skin 
    • Tense bullae 
    • Expanding annular plaques
    • “Crown of jewels” 
    • Scattered asymmetric vesiculobullous lesions 
    • Variant of mucous membrane pemphigoid: oral, nasal, pharyngeal, esophageal, ocular involvement 
    • Drug-induced LABD can have a TEN-like or morbilliform appearance
  • Chronic bullous disease of childhood” (CBDC)
    • Unique clinical appearance in children
    • Annular erythematous bullae (crown of jewels) with central crusting in flexural areas (lower trunk, thigh, groin)
Idiopathic LABD Drug-Induced LABD
  • Common in children
  • Insidious onset
  • Mucosal lesions in up to 50%
  • Tense bullae in annular configuration (“crown of jewels”)
  • Resolves after many years
  • Uncommon in children
  • Acute onset
  • Mucosal/conjunctival lesions less common
  • DH-like, BP-like, morbilliform, TEN-like
  • Resolved 2-6 weeks after drug discontinuation

Histology: 

  • Early stage: neutrophilic infiltrate along the BMZ with vacuolar change and dermal papillary neutrophilic microabscesses
  • Fully developed lesions: subepidermal vesicles/bullae with predominant neutrophilic infiltrate ± eosinophils
  • Usually cannot distinguish LABD from DH on light microscopy but linear neutrophils along BMZ and at dermal papillary tips favor LABD (not specific)

Immunoelectron microscopy: IgA deposits within lamina lucida > sublamina densa

Perilesional DIF: linear IgA deposition along the BMZ

IIF on salt-split skin: IgA deposits on the epidermal side of the blister

Laboratory Investigations: circulating anti-BMZ IgA antibodies found in 60-70% of LABD sera (vs DH = 0%,)

  • Dermatitis Herpetiformis
  • Bullous Pemphigoid

  • Dapsone or sulfapyridine (response within 48-72h) ± prednisone 40mg daily 
    • Average dapsone dose disease required is 100 mg po die but may go as high as 300 mg po die
    • Pediatric dapsone dose 1-2mg/kg/d po die
    • Patients with both IgG and IgA 🡪 likely to require additional therapies (better response to dapsone if only IgA)
  • Other reported successful treatments: dicloxacillin, erythromycin, tetracycline (>9 yo) and trimethoprim-sulfamethoxazole
  • Mycophenolate mofetil, azathioprine and IVIg – for patients who do not improve with combination of prednisone/dapsone or with severe disease
  • Repeated attempts to taper treatment allow to identify spontaneous remission 
  • Prognosis:
    • Persistence for many years with spontaneous remission in 30-60%
    • Childhood – remits within 2-4 years
    • Drug-induced LABD resolves 2-6 weeks after drug discontinuation