Although vesicles and bullae (blisters) occur as secondary phenomena in several unrelated conditions (e.g., herpes-virus infection, spongiotic dermatitis), there is a group of disorders in which blisters are the primary and most distinctive feature. Blistering in these diseases tends to occur at specific levels within the skin, a morphologic distinction that is critical for diagnosis (
Fig. 24.8
Pemphigus is an uncommon autoimmune blistering disorder resulting from loss of normal intercellular attachments within the epidermis and the squamous mucosal epithelium. There are three major variants:
Pemphigus vulgaris (the most common type)
The last entity is associated with internal malignancy and is not discussed here.
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Fig. 24.7 Verrucavulgaris.(A)Multiplewarts,withcharacteristicrough,pebblelikesurfaces.(B)Microscopically,commonwartscontainzonesofpapillaryepidermalproliferationthatoftenradiatesymmetricallylikethepointsofacrown(top). Pallororhalosaroundnuclei,prominentkeratohyalingranules,andrelatedcytopathicchangesareseenathighermagnification (bottom).
Pemphigus vulgaris and pemphigus foliaceus are autoimmune diseases caused by antibody-mediated (type II) hypersensitivity reactions (Chapter 5). The pathogenic antibodies are IgG autoantibodies that bind to intercellular desmosomal proteins (desmoglein types 1 and 3) found in the skin and mucous membranes. The antibodies disrupt the intercellular adhesive function of desmosomes and may activate intercellular proteases as well. The distribution of desmoglein proteins within the epidermis determines the location of the lesions. By direct immunofluorescence study, lesional sites show a characteristic fishnet-like pattern of intercellular IgG deposits (
Fig. 24.9 ). As with many other autoimmune diseases, pemphigus is associated with particular HLA alleles.
MORPHOLOGYPemphigus vulgaris involvesbothmucosaandskin,especiallyonthescalp,face,axillae,groin,trunk,andpointsofpressure.Thelesionsaresuperficialflaccidvesiclesandbullaethatruptureeasily,leavingdeepandoftenextensiveerosionscoveredwithaserumcrust(
Fig.24.10A ).Pemphigus foliaceus, arare,milderformofpemphigus,resultsinbullaethataremainlyconfinedtotheskin,withonlyinfrequentinvolvementofmucousmembranes.Theblistersinthisdisorderaresuperficial,suchthatmorelimitedzonesoferythemaandcrustingofrupturedblistersareseen(
Fig.24.11A
Thecommonhistologicdenominatorinallformsofpemphigusisacantholysis, lysisoftheintercellularadhesivejunctionsbetweenneighboringsquamousepithelialcellsthatresultsintheroundingupofdetachedcells.Inpemphigusvulgaris,acantholysisselectivelyinvolvesthelayerofcellsimmediatelyabovethebasalcelllayer,givingrisetoasuprabasal acantholytic blister (
Fig.
24.10B ).Inpemphigusfoliaceus,acantholysisselectivelyinvolvesthesuperficialepidermisatthelevelofthestratumgranulosum(
Fig.24.11B ).Variablesuperficialdermalinfiltratescomposedoflymphocytes,macrophages,andeosinophilsaccompanyallformsofpemphigus.