Description

• Autoantibody (IgG)-mediated blistering disease of the skin and mucous membrane:
  • Characterized by loss of cell-to-cell adhesion called acantholysis
• Median age 71 yr:
  • Reports of disease occurring in neonates through elderly
• Rare; worldwide incidence 0.7/100,000
• Women more often than men (66%)
• Pemphix is Greek for bubble or blister
• Pemphigus – specific term for autoantibody disease–targeting desmogleins (Dsgs) which are cell-to-cell adhesion molecules
• Mortality is highest in those with mucocutaneous involvement:
  • If untreated, mortality rates average 60–90%
  • With treatment this nears 5%
• 3 major subtypes exist:
  • Vulgaris; typically more serious with deeper mucocutaneous involvement:
    • Accounts for 70–80% of all pemphigus
    • Up to 70% with vulgaris present with oral lesions
    • May or may not have skin involvement
    • Flaccid bullae
    • Autoantibodies to Dsg 1 and 3
    • Affects most races in middle age and elderly Ashkenazi Jews
  • Foliaceus; milder and more superficial cutaneous lesions:
    • Involves skin only
    • Autoantibodies to Dsg 1 only
  • Paraneoplastic pemphigus; often with severe mucocutaneous involvement
    • Most commonly seen in lymphoreticular malignancies
    • Pemphigoid: A term describing the group of syndromes that cause a separation of the epidermis from the dermis, typically more benign course
    • Bullous pemphigoid has tense bullae that arise from skin and are not as fragile as pemphigus
      • Negative Nikolsky sign
      • Often has pruritus prior to blistering (may be present for months)
      • Oral lesions are rare

• Pemphigus is rare in neonates and children but may occur in adolescents
• Early diagnosis and treatment significantly impact growth, psychological, social, and cultural development
• Histopathology is identical to adult disease
• Neonates may develop the disease secondary to transplacental transfer of IgG
• Neonatal pemphigus spontaneously resolves in several weeks as the maternal antibodies are catabolized

• Effective treatment of maternal disease prior to conception lowers the risk of neonatal transmission and gestational complications
• Pregnancy may precipitate or aggravate pemphigus

Etiology

• IgG autoantibodies are directed against desmosomal cadherins Dsg 1 and Dsg 3 found in all keratinocytes
• Autoantibodies cause histopathologic acantholysis, cytoskeletal derangements, and apoptosis
• Bullae formation is caused by the loss of cell–cell adhesion and separation of the keratinocytes
• Immunogenetic predisposition secondary to higher frequencies of specific human leukocyte antigen HLA haplotypes including DR4 and DRw6
• Drugs such as penicillamine, captopril, rifampin, piroxicam, and phenobarbital can trigger pemphigoid reactions
• Endemic pemphigus foliaceus (fogo selvagem), most common in South America, may be triggered or transmitted by bites from flying insects
• Pemphigoid reactions may occur in association with a neoplasm, usually lymphoma (paraneoplastic pemphigus)