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…
Immunologically Mediated Blistering Skin Diseases
|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|
- Desmoglein 1 is present in skin but absent in mucous membrane. So, P. foliaceus don’t involve skin.
- 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.|
- 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.
- If not treated, pemphigus can be fatal due to overwhelming infection of the sores.
- Recently, Rituximab, an anti-CD20 antibody, was found to improve otherwise untreatable severe cases of Pemphigus Vulgaris.
- 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.
- 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