• Clinical science

Autoimmune blistering diseases

Abstract

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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

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Bullous pemphigoid Pemphigus vulgaris Dermatitis herpetiformis
Epidemiology
  • Peak incidence: > 60 years of age
  • Most common bullous autoimmune disease
  • Peak incidence: 40–60 years of age
  • Peak incidence: 15–40 years
  • >
Etiology
  • 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
  • Intradermal suprabasal clefting and blistering just above the basal layer of the epidermis
  • Separated standing acantholytic cells on the floor of the blister, similar in appearance to a row of tombstones
  • Acantholysis seen in biopsy
  • Deposition of IgG in the intercellular spaces of the epidermis (esp. early lesions)
  • Subepidermal clefting and blistering
  • IgA and complement C3 deposits in dermal papillae
Treatment
  • First-line: Dapsone
  • Gluten-free diet
  • Topical steroids may be adjunctively used to control severe pruritus
  • Low dietary intake of iodine
Prognosis
  • Benign disease, usually responds well to treatment
  • Often fatal without treatment!
  • Usually a lifelong condition requiring continuous treatment and dietary adjustments

References:[1][2][3][4][5][6][7][8][9][10][11]

Subtypes and variants

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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)
      • Recurrence is possible, especially appearing:
        • Spontaneously in the postpartum period
        • In subsequent pregnancies
        • When taking contraceptives containing progestin or estrogen
        • During menstruation
      • 5–10% of infants born to women with gestational pemphigoid develop transient blistering that resolves spontaneously.

Variant forms of pemphigus vulgaris

Other variants and subtypes

References:[12][13]

Diagnostics

Content currently under development

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][14]