pemphigus vulgaris

Etiology

• specific IgG against intercellular adhesion molecule, resulting in skin separation within the epidermal layer
• drug-induced pemphigus secondary to captopril & penicillamine
• pemphigus has occurred in association with thymoma & myasthenia gravis
• paraneoplastic pemphigus associated with lymphoreticular neoplasia
• may be drug-induced

Epidemiology

• middle-aged or older (4th-6th decade most common)
• all ethnicities affected
• certain HLA types at higher risk
• high incidence of Ashkenazi Jews
• no sex preference
• 0.5-3.2 cases/100,000/year

Pathology

• loss of intercellular cohesion in lower part of epidermis
• acantholysis & bullae split just above the basal cell layer
  • suprabasilar clefting
• bullae contain acantholytic keratinocytes (Tzank cells)
• infiltration with predominantly neutrophils & eosinophils
• IgG & C3 deposited on plasma membranes of epithelial cells & in intercellular region of epidermis within lesions & in perilesional areas (contrast with pemphigoid where IgG & C3 found in epidermal basement membrane)
• IgA & IgM antibodies may also be found
• anti-desmoglein-3 (DSG3) is the major autoantibody
• other autoantibodies against DSG4, ANXA9 & other proteins

* histopathology image

Clinical manifestations

• skin manifestations
  • insidious onset of flaccid bullae, often beginning in the mouth or on the scalp
  • months may elapse from the onset of oral lesions to the appearance of skin lesions
  • skin lesions may be localized for 6-12 months before generalizing
  • vesicles & seropurulent bullae, flaccid, easily ruptured, arising on normal skin
  • bullae rupture resulting in large areas of denuded skin that ooze serous fluid, bleed &/or cover with crusts
  • vesicles & bullae so fragile the are rarely seen
  • positive Nikolsky's sign & Asboe-Hansen sign (in contrast to the less severe bullous pemphigoid)
  • skin lesions may be burning & painful
  • pruritus may or may not be present
  • lesions have predilection for scalp, face, chest, axillae, groin, umbilicus
    • esophagus & vulva may also be involved
• mucous membrane manifestations
  • mouth lesions may be painful & tender
    • oral involvement in ~60%; always involves oral mucosa
    • lesions may be on hard palate & soft palate including buccal mucosa
    • less common in drug-induced pemphigus
  • mucosal bullae easily rupture leaving erosions
  • mucous membrane lesions generally appear as erosions
  • mouth, nose, pharynx, larynx, vagina affected
  • epistaxis, hoarseness, dysphagia may occur
• general manifestations
  • systemic toxicity
  • 'mousy' odor

* images

Laboratory

• desmoglein 1 & desmoglein 3 Ab panel
  • serum IgG autoantibodies against desmoglein-1 & desmoglein-3
  • follow antibody titers
  • antibody titer correlates with disease activity
• biopsy early small bulla or margin of larger bulla (diagnostic, see pathology)
• monitor laboratory indicators of immunosuppressive agents
• see ARUP consult

Complications

• Staphylococcus aureus sepsis
• may be life-threatening if left untreated

Differential diagnosis

• bullous pemphigoid
  • tense bullae & prurtitus often presenting symptoms
  • mucosal lesions less common
  • subepidermal clefting
  • negative Nikolsky's sign
  • IgG & C3 deposition in epidermal basement membrane
• lichen planus
  • no cutaneous blistering or erosions
  • Wickham's striae
• cicatricial pemphigoid usually involves only oral mucosal tissues
• Stevens-Johnson syndome
  • lesions most prominent on extremities, palms & soles

Management

• localized lesions may be treated with intralesional or topical steroids
• hospitalization for severe cases or evidence of infection
• treat skin lesions as burns
• high dose systemic steroids in conjunction with other immune suppressants
  • prednisone
    • 2-3 mg/kg PO QD until cessation of new blister formation
    • then, rapid taper to 1/2 the initial dose until patient is almost clear
    • slow taper to minimal effective maintenance dose
    • glucocorticoids are 1st line therapy
  • azathioprine
    • 2-3 mg/kg PO QD until completely clear
    • then taper to 1 mg/kg PO QD
    • continue azathioprine even after discontinuation of glucocorticoids
    • discontinue when clinically free of disease & negative pemphigus titer for 3 months
  • methotrexate
    • 25-35 mg PO/IM weekly until completely clear
    • then taper to 1/2 original dose
    • continue methotrexate even after discontinuation of glucocorticoids
    • discontinue when clinically free of disease & negative pemphigus titer for 3 months
  • cyclophosphamide
    • 100-200 mg PO QD until clear
    • maintenance dose: 50-100 mg PO QD
    • alternative bolus therapy
      • 1000 mg IV once a week or once every other week until clear
      • daily maintenance therapy as above
  • plasmapheresis in conjunction with corticosteroids & immunosuppressive agents in poorly controlled patients
  • intravenous immune globulin (approved by Medicare but not FDA)
  • gold therapy
    • test dose 10 mg IM
    • 25-50 mg gold sodium thiomalate IM weekly to a cumulative maximum dose of 1 g
  • rituximab
• parenteral nutrition if oral lesions prevent oral feeding
• aggressive treatment of infection

Prognosis:

• nearly 100% fatal if not treated
• mortality of 10% with treatment
• chronic course in ultimate remission in most cases
• death most often from sepsis (Staphylococcus aureus)

More general terms

• pemphigus

Additional terms

• Asboe-Hansen sign
• bullous pemphigoid; parapemphigus
• Nikolsky's sign
• paraneoplastic pemphigus

Patient information

pemphigus vulgaris patient information

Database

• OMIM: https://mirror.omim.org/entry/169615
• OMIM: https://mirror.omim.org/entry/169610