II. Epidemiology

  1. Incidence: 0.5 to 3.2 cases per 100,000 (U.S.)
  2. Higher Incidence in Ashkenazi jews
  3. Mean age of onset: 40 to 60 years old
  4. Men and women are affected equally

III. Definition

  1. Most common, severe and deeper form of Pemphigus

IV. Risk Factors

  1. Ashkenazi jewish descent
  2. Autoimmune Condition (e.g. SLE, Rheumatoid Arthritis, Myasthenia Gravis)
  3. Triggers
    1. See medications below
    2. Burn Injury
    3. Infections

V. Pathophysiology

  1. IgG against Keratinocyte cell surface molecules (desmoglein 1 and 3) in skin and mucosa
    1. Antibody binding results in Acantholysis (loss of cell to cell adhesion)
  2. May be unmasked by certain medications (e.g. Penicillin, NSAIDs, ACE Inhibitors, Pyrazolones)
    1. See Drug-Triggered Pemphigus

VI. Symptoms

  1. Painful, often burning lesions (may be pruritic)
  2. Oral symptoms with mucosal involvement
    1. Dysphagia
    2. Hoarseness
    3. Epistaxis
  3. Constitutional symptoms
    1. Weakness
    2. Malaise

VII. Signs

  1. Mucosal sites of involvement
    1. Painful Gingival erosions (50-70% of patients)
    2. May precede skin bullae by months
    3. Conjunctiva and Esophagus may also be involved
  2. Flaccid bullae (difficult to see due to flaccidity)
    1. Clear fluid filled Blisters with thin walls that easily rupture, developing into painful erosions
    2. Blisters overly an erythematous base
    3. Nikolsky Sign positive
  3. Painful erosions (most common skin finding)
    1. May bleed easily
    2. Crusting is often present
    3. Lesions are painful rather than pruritic (contrast with Bullous Pemphigoid)
  4. Skin Sites of involvement
    1. Face
    2. Scalp
    3. Upper body
    4. Intertriginous areas (axillae, groin)
    5. Umbilicus
    6. Nails (Subungual Hematoma, Chronic Paronychia)

VIII. Labs

  1. Biopsy of bulla margin
    1. Suprabasilar Blister (above Basal Cell Layer)
    2. Acantholysis
    3. Rounded basal cells appear as row of tombstones
    4. Eosinophilic infiltrates
  2. Direct Immunofluorescence
    1. Intercellular deposits of IgG and C3 on Keratinocytes

IX. Course

  1. Onset on Oral Mucosa
  2. Skin lesions follow Oral Lesions by months
  3. Localized skin involvement for 6-12 months
  4. Generalized involvement then ensues

X. Associated Conditions

  1. Thymoma (and Myasthenia Gravis)
  2. Possible complications of immunosuppressive therapy
    1. Kaposi's Sarcoma
    2. Lymphoreticular malignancy

XII. Management: Immunosuppressive Therapy

  1. Disposition
    1. Most patients are treated out of the hospital
    2. Admit patients with extensive bullae and erosions for IV fluids and Electrolyte management
  2. Prednisone 1 mg/kg/day
    1. Reduce dose by 50% when no new Blister formation
    2. Gradually taper to minimum effective dose
    3. Topical Corticosteroids may also be used as an adjunct
  3. Adjunctive Immunosuppressive Drugs
    1. Methotrexate
    2. Azathioprine (Imuran)
    3. Cyclophosphamide (Cytoxan)
    4. Mycophenolate mofetil (Cellcept)
  4. Other measures in severe cases
    1. Plasmapheresis

XIII. Complications

  1. Secondary infection (due to immunosuppressive therapy)

XIV. Prognosis

  1. Mortality highest in first few years (up to 10%)
    1. Complications of Corticosteroids

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