Chapter 7: Autoimmune Bullous Diseases

TERMINOLOGY AND CONCEPTS

Indirect Immunofluorescence

• Goal: to detect circulating autoantibodies in serum by purposefully incubating it with a test substrate

• Method: serum from a patient is collected and directed against a substrate (such as monkey esophagus, rat bladder, or salt-split skin), followed “indirectly” by the addition of fluorescein-conjugated antibodies directed against specific complement fractions and immunoglobulins to label any resultant complexes

Direct Immunofluorescence

• Goal: to detect antibody and immunoreactants already deposited in tissue of the patient

• Method: tissue from a patient is incubated “directly” with fluorescein-conjugated antibodies directed against specific complement fractions and immunoglobulins (IgG, IgM, and IgA) to label any resultant complexes

Use of Salt-Split Skin

• Goal: to differentiate among autoimmune bullous conditions via the level of any deposition of immunoreactants within salt-split skin (i.e., deposition either “above” or “below” the lamina lucida, where the split occurs)

• Methods:

  • Direct: incubate the patient's skin in 1 molar saline to induce a split through the lamina lucida; add fluorescein-conjugated antibodies to label any resultant complexes; identify the level of deposition (“roof” or “floor”)

  • Indirect: incubate the patient's serum with normal skin already presplit with 1 molar saline; add fluorescein-conjugated human anti-immunoglobulin to label any resultant complexes; identify the level of deposition (“roof” or “floor”)

• Immunoreactants deposit in the “roof” (“above” the split) in:

  • bullous pemphigoid

• Immunoreactants deposit in the “floor” (“below” the split) in:

  • Bullous systemic lupus erythematosus (SLE)

  • Antiepiligrin cicatricial pemphigoid (autoantibodies to laminin-5)

  • Anti-p105 pemphigoid (autoantibodies to 105-kDa lower lamina lucida protein)

  • Anti-p200 pemphigoid (autoantibodies to a 200-kDA protein of the C-terminus of laminin γ1 although the pathogenicity of the antibody is disputed)

  • Ghohestani disease (autoantibodies to α-5 chain of type IV collagen)

  • Epidermolysis bullosa acquisita (EBA)

Nikolsky Sign (“direct” Nikolsky sign)

• Positive: pressure applied laterally at the edge of lesion results in blister extension

• Indicative of epidermal fragility

• Diseases with a “positive” direct Nikolsky sign include the following:

  • Pemphigus foliaceus

  • Pemphigus vulgaris

  • Staphylococcal scalded skin syndrome (Ritter disease)

• Recent evidence shows that a “direct” Nikolsky sign is moderately sensitive but highly specific for pemphigus

• The “marginal” variant of the Nikolsky sign involves lateral extension of the blister via either pulling of the lateral remnants or rubbing at the edge of a lesion

Pseudo-Nikolsky Sign

• Positive: separation of the epidermis from the dermis by lateral pressure (rubbing) on erythematous skin (but not a blister itself—see “marginal” Nikolsky sign)

• Diseases with a “positive” pseudo-Nikolsky sign include the following:

  • Stevens-Johnson syndrome (SJS)

  • Toxic epidermal necrolysis (TEN)

Asboe-Hansen Sign (“indirect” Nikolsky sign)

• Positive: pressure applied to the top of a lesion results in lateral extension of the blister

• Diseases with a “positive” Asboe-Hansen sign include:

  • bullous pemphigoid

AUTOIMMUNE BULLOUS ...