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

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