Fig. 24.10 Pemphigusvulgaris.(A)Anerosiononthelegarisingfromcoalescenceofagroupof“unroofed”blisters.(B)Suprabasalintraepidermalblisterinwhichrounded,dissociated(acantholytic)keratinocytesareplenti-ful(inset).
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Fig. 24.11 Pemphigusfoliaceus.(A)Atypicalblister,whichismoresuperfi-cialthanthoseseeninpemphigusvulgaris.(B)Microscopicappearanceofacharacteristicsubcornealblister.
Dermatitis herpetiformis is an autoimmune blistering disorder associated with gluten sensitivity that is characterized by extremely pruritic grouped vesicles and papules. The disease affects predominantly males, often in the third and fourth decades of life. Up to 80% of cases are associated with celiac disease; conversely, only a small fraction of patients with celiac disease develop dermatitis herpetiformis. Like celiac disease, dermatitis herpetiformis responds to a gluten-free diet.
The strong association of dermatitis herpetiformis with celiac disease provides a clue to its pathogenesis. Geneti-cally predisposed individuals develop IgA antibodies to dietary gluten (derived from the wheat protein gliadin) as well as IgA autoantibodies that cross-react with endomysium and tissue transglutaminases, including epidermal transglutaminase expressed by keratinocytes. By direct immunofluorescence, the skin shows discontinuous, granular deposits of IgA selectively localized in the tips of dermal papillae (
Fig. 24.13A ). The resultant injury and inflammation produce a subepidermal blister.
Fig. 24.12 Bullouspemphigoid.(A)DepositionofIgGantibody(detectedbydirectimmunofluorescence)inthesubepidermalbasementmembrane(epidermisisontheleftsideofthefluorescentband).(B)Grossappearanceofcharacteristictense,fluid-filledblisters.(C)Subepidermalvesiclewithaneosinophil-richinflammatoryinfiltrate.(C, Courtesy of Dr. Victor G. Prieto, Houston,Texas.) http://ebooksmedicine.net
MORPHOLOGYThelesionsofdermatitisherpetiformisarebilateral,symmetric,andgroupedandpreferentiallyinvolvetheextensorsurfaces,elbows,knees,upperback,andbuttocks(
Fig.24.13B ).Initially,neutrophilsaccumulateselectivelyatthetips of dermal papillae, formingsmallmicroabscesses(
Fig.24.13C ).Thebasalcellsoverlyingthesemicroabscessesshowvacuolizationandfocaldermoepidermalseparationthatultimatelycoalescetoformatruesubepidermal blister.
Blisteringdisordersareclassifiedbasedontheleveloftheepidermisthatisaffected.
Thesedisordersoftenarecausedbyautoantibodiesspecificforepithelialorbasementmembraneproteinsthatleadtounmooringofkeratinocytes(acantholysis).
PemphigusisassociatedwithIgGautoantibodiestovariousintercellulardesmogleins(partofthedesmosome),resultinginbullaethatareeithersubcorneal(pemphigusfoliaceus)orsuprabasilar(pemphigusvulgaris).
BullouspemphigoidisassociatedwithIgGautoantibodiestobasementmembraneproteins(partofthehemidesmosome)andproducesasubepidermalblister.
DermatitisherpetiformisisassociatedwithIgAautoantibodiestotransglutaminase,andalsoischaracterizedbysubepidermalblisters.