Pemphigus

Basics

Description

Autoantibody (IgG)-mediated blistering disease of the epidermis and mucous membranes:
- Characterized by loss of cell-to-cell adhesion called acantholysis
Age of onset 45–65 yr in most populations:
- 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:
- Pemphigus vulgaris; typically more serious with deeper mucocutaneous involvement:
  - Accounts for 70–80% of all pemphigus
  - Up to 70% 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
- Pemphigus 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
  - Contrasted with 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 the subepidermal layer and are not as fragile as pemphigus:
    - Negative Nikolsky sign
    - Age of onset 60–80 yr
    - Often has pruritus prior to blistering (prodrome may be present for months)
    - Oral lesions are rare
    - Predominantly affects flexor aspects
    - IgG autoantibodies to hemidesmosomes
    - Direct immunofluorescence shows linear deposition of IgG and C3 at the basement membrane

Pediatric Considerations

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

Pregnancy Considerations

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 a 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
Individuals of Jewish (especially Ashkenazi), Indian, Southeast European Middle Eastern descent are more susceptible to pemphigus vulgaris
Drugs such as penicillamine, captopril, rifampin, piroxicam, and phenobarbital can trigger pemphigoid reactions
Endemic pemphigus foliaceus most common in South America, may be triggered or transmitted by bites from flying insects:
- Known in Brazil as fogo selvagem (wild fire)
Pemphigoid reactions may occur in association with a neoplasm, usually lymphoma (paraneoplastic pemphigus):
- Polymorphous clinical presentation with features similar to pemphigus vulgaris as well as bullous pemphigoid

There's more to see -- the rest of this topic is available only to subscribers.

All content is protected by copyright and may not be used for AI model training or other unauthorized purposes.