Mucous Membrane (CICATRICAL) Pemphigoid (MMP)

  • Annual incidence: 1-5 cases per million
  • Elderly
  • Females ˃ males (1.5-2:1)
  • HLA associations: oral and ocular forms HLA-DQw7 (subtype of HLA-DQB1*0301)

Autoantibodies to self-antigens 

  • BP180, BP230
  • laminin 332, laminin 311
  • integrin β4 subunit (hemidesmosome adhesion complex & anchoring filaments of mucosa and skin)

4 types: 

Anti-laminin 332 mucous membrane pemphigoid (anti-epiligrin cicatricial pemphigoid)

  • 18-30% of MMP cases 
  • paraneoplastic

Ocular mucous membrane pemphigoid

  • Ocular disease
  • IgG against β4 subunit of α6β4 integrin 

BP-like 

  • Largest subgroup 
  • Mucosa and skin 
  • BP180 or 230

Heterogeneous group: Variable involvement of mucosa without skin involvement

Heterogeneous, chronic and progressive blistering diseases with predominant involvement of external mucosa, with tendency for scarring and potential for serious complications.

Oral mucosa (90%) – gingiva, buccal mucosa, palate 

  • Desquamative gingivitis (#1 presentation): mucosal sloughing, bleeding erosions, parasthesias
  • Periodontal ligament damage and loss of teeth 
  • Short-lived vesicles, chronic erosions (mainly on palate), and pain
  • Adhesions and white reticular striations post healing

Conjunctiva (40%)

  • Usually bilateral
  • Severity range from nonspecific chronic conjunctivitis, burning, soreness, mucus production, foreign body sensation, rare conjunctival vesicles/blisters on tarsal conjunctiva to scarring disease w/ shortened inferior fornices, symblepharon, ankyloblepharon, trichiasis, entropion, superficial corneal trauma, corneal neovascularization, corneal ulceration, blindness 

Aerodigestive tract (1/3 of patients) 

  • Asymptomatic
  • Nose: crusted intranasal ulcerations, epistaxis, adhesions, airway obstruction 
  • Pharynx: ulceration, dysphagia 
  • Larynx: hoarseness, loss of speech, life-threatening stenosis requiring tracheostomy 
  • Esophageal: strictures, stenosis, dysphagia

External genitalia and anus – rare and scarring
Skin lesions (25-40%) scalp, face and upper trunk 

  • Erythematous plaques or BP-like lesions
  • Brunsting-Perry variant: lesions limited to head and neck with minimal or absent mucosal involvement

Histopathology: 

  • Subepithelial or subepidermal blister 
  • Variable mixed inflammatory infiltrate – predominant neutrophils but  ↑ eosinophils in older lesions (less than in BP)
  • scarring in older lesions

DIF: Linear IgG (IgG4, IgG1) > IgA, IgM and/or C3 along the basement membrane zone of mucosa (50-90%) more than along the skin (20-50%) 

IIF: low titer linear IgG > IgA, IgE > IgM or complement along dermal side of blister (20-30% of patients)

  • Higher titers correlated with disease severity 
  • ↑ sensitivity if used on normal human mucosa or with salt-split skin (most cases IgG binds to epidermal roof whereas, in anti-laminin 332, IgG binds to dermal side)

Other tests: ELISA, immunoblotting, immunoprecipitation, Immunoelectron microscopy, serration analysis 

Other autoimmune blistering diseases (pemphigus, pemphigoid family, LABD, EBA) 

  • If only oral disease: pemphigus vulgaris, erosive lichen planus
  • End-stage cicatricial conjunctival lesions: severe chronic infectious conjunctivitis, ocular pseudopemphigoid secondary to opthalmic medications, late stage Stevens-Johnson syndrome/toxic epidermal necrolysis

Mild oral (or skin) disease:

  • Potent topical corticosteroid ointment or gels (± intralesional) or mouthwashes
  • Topical tacrolimus, topical cyclosporine, topical dapsone

Moderate to severe oral (or skin) disease: 

  • Systemic corticosteroids
  • Dapsone
  • immunosuppressants (Azathioprine, MMF, Cyclophosphamide)
  • IVIG
  • rituximab

Mild ocular:

  • dapsone

Moderate-severe ocular

  • cyclophosphomide + prednisone
  • rituximab 
  • IVIG

Adjuctive therapies

  • mucosal hygiene/care
  • local anesthetics

Surgical interventions to improve scarring/reverse sequela