• Clinical science

Autoimmune blistering diseases


Autoimmune blistering diseases are skin conditions characterized by the formation of blisters, which are the result of the destruction of cellular or extracellular adhesion molecules by antibodies. The three most significant autoimmune blistering diseases are bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis. The most common among these is bullous pemphigoid, which leads to the formation of large, tense bullae. It is a chronic disease that mainly affects elderly individuals and responds well to treatment with steroids. Pemphigus vulgaris, which is characterized by fragile, superficial flaccid bullae that leave crusted erosions, is a rare condition that occurs mainly in middle-aged adults. In contrast to bullous pemphigoid, it is a severe condition that is more difficult to treat and can be fatal. Dermatitis herpetiformis mainly affects the extensor surfaces of the extremities and is associated with celiac disease. It has a chronic course that leads to the formation of intensely pruritic papules and vesicles. In addition to evaluating clinical appearance, the Nikolsky sign, Tzanck test, skin biopsy, and direct immunofluorescence are indicated to confirm the diagnosis. Serologic testing of autoantibodies may also be useful. Management usually consists of oral and topical steroids, as well as immunosuppressive therapy.

Differential diagnosis of autoimmune blistering diseases

Bullous pemphigoid Pemphigus vulgaris Dermatitis herpetiformis
  • Peak incidence: > 60 years of age
  • Most common bullous autoimmune disease
  • Peak incidence: 40–60 years of age
  • Peak incidence: 15–40 years
  • >
  • Most likely genetic predisposition to autoimmune reaction (associated with HLA-DR3 and HLA-DQ2)
  • Associated with celiac disease; sensitivity to potassium iodide (e.g., contrast medium)
Clinical findings
  • A prodromal stage with formation of urticarial lesions may occur weeks to months before onset of blistering.
  • Large, tense, subepidermal blisters on normal, erythematous, or erosive skin
  • Intensely pruritic lesions, possibly hemorrhagic, heal without scar formation
  • Distributed on palms, soles, lower legs, groin and axillae
  • Oral involvement rare
  • Progression in stages
    • Spontaneous onset of painful flaccid, intraepidermal blisters → lesions rupture and become confluent → erosions and crustsre-epithelialization with hyperpigmentation but without scarring
  • Pruritus is typically absent.
  • Lesions typically first present on the oral mucosa (> 50% of cases), then on body parts exposed to pressure (e.g., intertriginous areas)
  • Tense, grouped subepidermal vesicles (herpetiform appearance)
  • Intense pruritus
  • Bilateral, symmetrical distribution, commonly over elbows, knees, buttocks, shoulders, scalp
  • No mucosal involvement
Diagnostics Autoantibodies against
  • BPAg1 (BP230)
  • BPAg2 (BP180)
  • Tissue transglutaminase
  • Epidermal transglutaminase
  • Endomysium
Tzanck test
  • Negative
  • Positive
  • Negative
Nikolsky's sign
  • Negative
  • Positive
  • Negative
Histology and immunohistochemistry
  • Subepidermal vesicle formation
  • Neutrophilic papillary microabscesses
  • Deposition of granular IgA in dermal papillae
  • First-line: Dapsone
  • Gluten-free diet
  • Topical steroids may be adjunctively used to control severe pruritus
  • Low dietary intake of iodine
  • Benign disease, usually responds well to treatment
  • Often fatal without treatment!
  • Usually a lifelong condition requiring continuous treatment and dietary adjustments


Subtypes and variants

Variant forms of bullous pemphigoid

  • Gestational pemphigoid
    • Definition: bullous, pemphigoid-like dermatosis during pregnancy of unknown cause (most likely immunological)
    • Epidemiology: 1:50,000 pregnancies (in the US)
    • Clinical presentation
      • Commonly starts in the periumbilical region during the 2nd and 3rd trimester
      • Intensely pruritic, mostly non-blistering lesions (eczema, urticarial or papular lesions) on extremities and mucous membranes
      • Grouped vesicles with herpetiform appearance (“gestational herpes”) usually occur as the disease advances.
    • Diagnostics: The diagnosis is confirmed via biopsy and immunofluorescence.
    • Prognosis
      • Usually self-limiting; heals spontaneously after delivery; , but associated with complications (e.g., premature labor; , increased lifetime risk of autoimmune disease)

Variant forms of pemphigus vulgaris

  • Pemphigus foliaceus
    • Etiology: : autoimmune disease (only antibodies against desmoglein 1 detectable)
    • Clinical presentation
      • Formation of bullae in the epidermis; , which burst spontaneously because of their (superficial) location
      • Localized mainly on the face, head, stomach, and back
      • Almost never with mucosal involvement (unlike pemphigus vulgaris)
    • Treatment
      • First-line: systemic steroids
      • Dapsone
      • Topical steroids



In addition to evaluating clinical appearance, specific tests are performed to confirm the diagnosis of a blistering disease. For specific diagnostic findings, see differential diagnosis of autoimmune blistering diseases.