• Clinical science

Autoimmune blistering diseases

Summary

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
Epidemiology
Etiology
Clinical findings
  • Progression in stages
  • 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, papules, and/or bullae (herpetiform appearance)
  • Intense pruritus
  • Bilateral, symmetrical distribution, commonly over elbows, knees, buttocks, shoulders, scalp
  • No mucosal involvement
Diagnostics Autoantibodies against
  • BPAg1 (BP230)
  • BPAg2 (BP180)
Tzanck test
  • Negative
  • Positive
  • Negative
Nikolsky's sign
  • Negative
  • Positive
  • Negative
Histology and immunohistochemistry
  • Subepidermal vesicle formation
  • Eosinophil-rich infiltrate in underlying dermis
  • Immunofluorescence: deposition of linear IgG and C3 along the dermo-epidermal junction
  • Intradermal vesicle formation just above the basal layer of the epidermis
  • Acantholysis on biopsy: loss of intercellular connections between keratinocytes (“row of tombstones” appearance)
  • Deposition of IgG in the intercellular spaces of the epidermis (esp. early lesions)
  • Immunofluorescence: deposition of IgG in a reticular pattern around epidermal cells
  • Subepidermal vesicle formation
  • Neutrophilic papillary microabscesses
  • Deposition of granular IgA in dermal papillae
Treatment
Prognosis
  • Benign disease, usually responds well to treatment
  • Often fatal without treatment!
  • Usually a lifelong condition requiring continuous treatment and dietary adjustments

In bullows (bullous) pemphigoid, antibodies attack the hemidesmosomes located below the epidermis.

References:[1][2][3][4][5][6][7][8][9][10]

Subtypes and variants

Variant forms of bullous pemphigoid

Gestational pemphigoid [11]

  • Definition: bullous, pemphigoid-like dermatosis during pregnancy of unknown cause (most likely immunological)
  • Epidemiology: 1:50,000 pregnancies (in the US)
  • Clinical features
    • 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

Variant forms of pemphigus vulgaris

Pemphigus foliaceus [12][13][14]

Other variants and subtypes

Epidermolysis bullosa acquisita (EBA) [15][16]

Mucous membrane pemphigoid (MMP) [17]

References:[18][19]

Diagnostics

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.

References:[5][7][20]