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Immunologically Mediated Blistering Skin Diseases

A number of immunologically mediated diseases with cutaneous manifestations are now recognized as distinct entities with consistent clinical, histologic, and immunopathologic findings. This is a short discussion about immunologically mediated blistering skin diseases…

First try to identify yourself & then check the answer below…

1. Pemphigus foliaceus 2. Pemphigus vulgaris            3. Paraneoplastic pemphigus 4. Bullous pemphigoid               5. Pemphigoid gestationis 6. Linear IgA disease       7. Cicatricial pemphigoid 8. Epidermolysis bullosa acquisita                                  9. Dermatitis herpetiformis

1. Pemphigus foliaceus 2. Pemphigus vulgaris 3. Paraneoplastic pemphigus 4. Bullous pemphigoid 5. Pemphigoid gestationis 6. Linear IgA disease 7. Cicatricial pemphigoid 8. Epidermolysis bullosa acquisita 9. Dermatitis herpetiformis

Immunologically Mediated Blistering Skin Diseases

Disease Clinical Histology Immunopathology Autoantigensa
Pemphigus foliaceus Crusts and shallow erosions on scalp, central face, upper chest, and back Acantholytic blister formed in superficial layer of epidermis Cell surface deposits of IgG on keratinocytes Dsg1
Pemphigus vulgaris Flaccid blisters, denuded skin, oromucosal lesions Acantholytic blister formed in suprabasal layer of epidermis Cell surface deposits of IgG on keratinocytes Dsg3 (plus Dsg1 in patients with skin involvement)
Paraneoplastic pemphigus Painful stomatitis with papulosquamous or lichenoid eruptions that progress to blisters Acantholysis, keratinocyte necrosis and vacuolar interface dermatitis Cell surface deposits of IgG and C3 on keratinocytes and (variably) similar immunoreactants in epidermal BMZ Plakin protein family members and desmosomal cadherins (see text for details)
Bullous pemphigoid Large tense blisters on flexor surfaces and trunk Subepidermal blister with eosinophil-rich infiltrate Linear band of IgG and/or C3 in epidermal BMZ BPAG1, BPAG2
Pemphigoid gestationis Pruritic, urticarial plaques, rimmed by vesicles and bullae on the trunk and extremities Teardrop-shaped, subepidermal blisters in dermal papillae; eosinophil-rich infiltrate Linear band of C3 in epidermal BMZ BPAG2 (plus BPAG1 in some patients)
Linear IgA disease Pruritic small papules on extensor surfaces; occasionally larger, arciform blisters Subepidermal blister with neutrophil-rich infiltrate Linear band of IgA in epidermal BMZ BPAG2
Cicatricial pemphigoid Erosive and/or blistering lesions of mucous membranes and possibly the skin; scarring of some sites Subepidermal blister that may or may not include a leukocytic infiltrate Linear band of IgG, IgA, and/or C3 in epidermal BMZ BPAG2, laminin-332, or others
Epidermolysis bullosa acquisita Blisters, erosions, scars, and milia on sites exposed to trauma; widespread, inflammatory, tense blisters may be seen initially Subepidermal blister that may or may not include a leukocytic infiltrate Linear band of IgG and/or C3 in epidermal BMZ Type VII collagen
Dermatitis herpetiformis Extremely pruritic small papules and vesicles on elbows, knees, buttocks, and posterior neck Subepidermal blister with neutrophils in dermal papillae Granular deposits of IgA in dermal papillae Epidermal transglutaminase

a Autoantigens bound by these patients’ autoantibodies are defined as follows: Dsg1, desmoglein 1; Dsg3, desmoglein 3; BPAG1, bullous pemphigoid antigen 1; BPAG2, bullous pemphigoid antigen 2.

Abbreviation: BMZ, basement membrane zone.

Reference: Harrison’s Principles of Internal Medicine 18th edition.

Difference between Pemphigus vulgaris & Pemphigus foliaceus

                    Features                  Pemphigus vulgaris                 Pemphigus foliaceus
Level of split/cleft Suprabasal Subcorneal
Mucous membrane involvement 100% Not seen
Antibody directed against Desmoglein 3 Desmoglein 1

Note:

  1. Desmoglein 1 is present in skin but absent in mucous membrane. So, P. foliaceus  don’t involve skin.
  2. Desmoglein 3 is present both in skin & mucous membrane. So, P. vulgaris can involve both.

Difference between Pemphigus vulgaris & Bullous Pemphigoid

                              Pemphigus vulgaris                              Bullous Pemphigoid
Seen in middle age group. Seen in older age group.
Flaccid bullae with clear fluid; rupture readily to leave painful erosions which continue to spread. Tense bullae with hemorrhagic contents; rupture less readily to form crusts, but usually the roof just settle down.
Occur on normal skin. On erythematous, edematous skin or normal skin.
Oral lesions universal; usually erosions. Less frequent; can be bullae or erosions.
Histopathology shows intra-epidermal bulla with acantholytic cells. Dermo-epidermal bulla.
DIF shows IgG deposit in intracellular space. IgG and C3 deposit at dermo-epidermal junction.
Circulating IgG against intercellular substance; titres correlate with disease activity. Circulating IgG against basement membrane in 70% of patients; titres don’t correlate with activity.

Extra points:

  1. Among three types of pemphigus: Pemphigus Vulgaris is most common form, Pemphigus Foliaceus is the least severe form and  Paraneoplastic Pemphigus is the least common & most severe type.
  2. If not treated, pemphigus can be fatal due to overwhelming infection of the sores.
  3. Recently, Rituximab, an anti-CD20 antibody, was found to improve otherwise untreatable severe cases of Pemphigus Vulgaris.
  4. Haley-Haley disease ( Familial Benign Pemphigus ) is an inherited skin disease. It is not an autoimmune disease & no sub epidermal blistering; therefore not considered part of the Pemphigus group of diseases.
  5. Pemphigus Erythematosus ( Senear-Usher syndrome ) is an overlap syndrome. It has erythematous, scaly plaques in a lupus like butterfly distribution on the face as well as involving the scalp, back, chest & intertriginous areas. Sunlight may exacerbate the disease.

Last revised: 08/12/2012

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2 Comments

  1. dahliasagucio says:

    Excellent Post. My Mom, 82 years old now has recovered totally of Bhullous phempigoid.I can share to you the ordeal she has gone and the recent medicine given as management. A Derma specialist from Makati Medical Center Philippines has done a good Job. Dr, Peachy Lao. The Bhullous P. was controlled together with the Sugar level of my Mom.

  2. Rinum Gul says:

    Nic

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