Table 1.

Summary of clinical, histologic, and immunologic findings in pemphigus

	Epidemiology	Clinical Features	Histopathology	Direct immune-fluorescence	Indirect immune-fluorescence	ELISA	Variants
PV	•Most common (in most populations) •Mostly middle-aged:, 50-60 years old, men and women affected equally	•At presentation: mucosal erosions (oropharyngeal and/or genital) •Mucosal lesions ➔ Pain when chewing and swallowing ➔ poor alimentation, weight loss, and malnutrition •Flaccid blisters on normal-looking or erythematous skin; palms and soles usually spared •Pruritus often absent •Nikolsky sign can be provoked	Suprabasilar split with acantholysis	Intercellular IgG deposition	Intercellular IgG deposition. Preferred substrate is monkey esophagus	•Dsg 3 auto-antibodies •Dsg 1 and Dsg 3 auto-antibodies	•Pemphigus vegetans •Pemphigus herpetiformis
PF	•Second most common form •PV incidence > PF incidence except in vicinities with endemic form •Mostly middle-aged: 50-60 years old, men and women affected equally •Endemic form mainly in children and young adults	•At presentation: superficial blisters + erosions on trunk and extremities •Common for blisters to rupture before presentation, thus examination reveals superficial crusting and erosions or erythematous patches •Usually seborrheic distribution •Nikolsky sign can be provoked •No mucosal involvement thus systemic symptoms absent	Subcorneal split with acantholysis	Intercellular IgG deposition	Intercellular IgG deposition Preferred substrate: normal human skin or Monkey esophagus	Dsg 1 autoantibodies	•FS (believed to have environmental trigger) •Pemphigus erythematosus •Pemphigus herpetiformis •Pemphigus vegetans
PNP	•Any age though mostly adults	•In setting of malignancy •Extensive mucositis •Polymorphic cutaneous lesions e.g. blisters, erosions, lichenoid lesions which may resemble other autoimmune blistering diseases •Bronchiolitis obliterans	Intraepidermal clefting with acantholysis Dense lichenoid infiltrate + interface dermatitis + necrotic keratinocytes	Intercellular and/or basement membrane zone deposition of C3 and/or IgG	IgG intercellular deposition Preferred substrate: rat bladder	•Dsg 1 and Dsg 3 auto-antibodies •Auto-antibodies to plakin proteins (e.g., envoplakin and periplakin)
IgA pemphigus- subcorneal pustular dermatosis	Any age	•Grouped vesicles or pustules •Erythematous plaques with crusts •Annular, circinate, or herpetiform morphology •Trunk and proximal extremities most commonly involved •Mucosa usually spared	Subcorneal clefting and pustules + nominal acantholysis Mixed dermal infiltrate	Intercellular IgA deposition	Negative in 50% Intercellular IgA deposition Preferred substrate: monkey esophagus	•Desmocollin 1 auto-antibodies •Target antigens likely non-desmosomal	•IgA/IgG subtype (demonstrates intercellular deposition of both IgG and IgA); atypical clinical and histologic manifestations due to heterogeneity of auto antigens (desmocollins, Dsg 1 and Dsg 3), associated with internal malignancies (lung cancer)
IgA pemphigus – intraepiderm-al neutrophilic dermatosis	Any age	•Grouped vesicles or pustules •Erythematous plaques with crusts •Annular, circinate, or herpetiform morphology •Trunk and proximal extremities most commonly involved Mucosa usually spared	Intraepidermal pustules + nominal acantholysis Mixed dermal infiltrate	Intercellular IgA deposition	Intercellular IgA deposition Preferred substrate: Monkey esophagus	•Desmocollin 1 auto-antibodies •Desmoglein 1 and Desmoglein 3 auto-antibodies	•IgA/IgG subtype
Dsg = desmoglein; ELISA = enzyme-linked immunosorbent assay; FS = fogo selvage; IgA = immunoglobulin A; IgG = immunoglobulin G; PV = pemphigus vulgaris; PF = pemphigus foliaceus; PNP = paraneoplastic pemphigus. Sources: Evangelista et al., 2015, Hertl et al., 2006, Hertl and Sitaru, 2015, Mihai and Sitaru, 2007, Oiso et al., 2002, Santoro et al., 2013, Tsuruta et al., 2011, Yeh et al., 2003.