Pseudopemphigoid as caused by topical drugs and pemphigus disease

Table 1 Staging for severity of cicatricial conjunctivitis

Staging for severity of cicatricial conjunctivitis
Foster Staging[7]
I	Subepithelial fibrosis, positive rose-bengal staining in conjunctiva, conjunctival “shrinkage” from abnormal connective tissue due to small white striae that form around the superficial vessels in substantia propria
II	Marked foreshortening of inferior conjunctiva described by (1) 0%-25%; (2) 25%-50%; (3) 50%-75%; and (4) 75%-100%
III	Corneal neovascularization, trichiasis, dystichiasis, keratopathy, subepithelial bands of connective tissue resulting in symblepharon (conjunctival adhesions) formation that is described by (1) 0%-25%; (2) 25%-50%; (3) 50%-75%; and (4) 75%-100%
IV	Severe sicca syndrome, keratinization, ankyloblepharon
Mondino Staging[134]
I	0%-25% loss of inferior conjunctival fornix depth
II	25%-50% loss of inferior conjunctival fornix depth
III	50%-75% loss of inferior conjunctival fornix depth
IV	75%-100% loss of inferior conjunctival fornix depth

Table 2 Conditions associated with cicatricial conjunctivitis

Trauma

Physical trauma

Chemical burn

Thermal burn

Radiation burn

Infection

Trachoma

Membranous conjunctivitis

Allergic

Chronic atopic keratoconjunctivitis

Mucocutaneous disease

Erythema multiforme

Stevens-Johnson Syndrome

Toxic epidermal necrolysis

Immunobullous disorders

Mucous membrane pemphigoid

Bullous pemphigoid

Pemphigus vulgaris

Paraneoplastic pemphigus

Lichen planus

Dermatitis herpetiformis

Systemic lupus erythematosus

Systemic disorders

Rosacea

Sjogren's syndrome

Graft-vs-host disease

Sarcoidosis

Ectodermal dysplasia

Erythroderma ichthyosiform congenital

Drug-induced

Systemic

Topical

Table 3 Diagnostic criteria for paraneoplastic pemphigus

Diagnostic criteria for paraneoplastic pemphigus
Anhalt et al[94]	Camisa et al[95]
Painful mucosal and polymorphous skin erosions that involves the trunk, extremities, palms, and soles of a patient with a neoplasm Histological changes including intraepidermal acantholysis, keratinocyte necrosis, and vacuolar interface dermatitis) Direct immunofluorescence findings of IgG and complement localized to the intercellular regions of the epithelium in a linear or granular fashion at the basement membrane zone Circulating autoantibodies that bind to stratified squamous epithelium as well as simple, columnar, and transitional epithelium Immunoprecipitation studies that demonstrate the presence of autoantibodies directed against a complex of five proteins of 250, 230, 210, 190, and 170 kDa	Major criteria Polymorphous mucocutaneous eruption Concurrent internal neoplasia Specific serum immunoprecipitation pattern Minor criteria Histology demonstrating acantholysis Direct immunofluorescence demonstrating intercellular and basement membrane staining Indirect immunofluorescence staining with rat murine epithelium Diagnosis: All three major or two major and two minor required to diagnosis paraneoplastic pemphigus

Table 4 Overview of mucous membrane pemphigoid and pseudopemphigoid as caused by the pemphigus disease

	MMP	Pseudopemphigoid
		PNP	OPV
Location	Subepidermal	Intraepidermal	Intraepidermal
DIF	IgG/IgA/IgM/C3	IgG/C3	IgG/C3
IIF on salt-split skin	Dermal, epidermal, or combined depending on antigen	Not applicable	Not applicable
IEM: ultrastructural location of antigen	Lamina lucida	Hemidesmosomes	Desmosomes
	Lamina densa	Desmosomal plaques
	Sublamina densa (anchoring fibrils)	Lamina lucida
Immunoblot: determination of antigen	Bullous pemphigoid antigen 1 (Bullous Pemphigoid 230) Bullous pemphigoid antigen 2 (Bullous Pemphigoid 180, type XVII collagen) Type VII collagen (290 kDa) Laminin332, epiligrin, or laminin 5 α3β3γ2 (165, 145, 140, 105 kDa) Laminin 6 (α3) Integrin beta 4 45 kDa epithelial protein 130 kDa epithelial protein 140 kDa epithelial protein 205 kDa epithelial protein 168 kDa epithelial protein Uncein LAD-1 (97/120 kDa)	Plakin protein family: Desmoplakin I (250 kDa) Bullous pemphigoid antigen 1 (230 kDa) Desmoplakin II and envoplakin (210 kDa) Periplakin (190 kDa) Plectin (500 kDa) Desmocollin 2 (105 kDa) Desmocollin 3 α2-macroglobulin-like-1 (A2LM1, 170 kDa) Desmoglein 1 (160 kDa) Desmoglein 3 (130 kDa)	Desmoglein 1 (160 kDa) Desmoglein 3 (130 kDa)
Increased malignancy	Yes - solid malignancies (laminin 332 subtype)	Yes - lymphoproliferative malignancies	--

MMP: Mucous membrane pemphigoid; PNP: Paraneoplastic pemphigus; OPV: Ocular pemphigus vulgaris; DIF: Direct immunofluorescence; IIF: Indirect immunofluorescence; IEM: Immunoelectron microscopy; LAD-1: Linear IgA bullous dermatosis autoantigen 1.