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Pemphigus Vulgaris (PV)

Introduction

Pemphigus vulgaris (PV) is a rare, chronic, autoimmune blistering disorder affecting the skin and mucous membranes. It is characterized by the formation of painful blisters and erosions due to the loss of adhesion between keratinocytes in the epidermis. PV is potentially life-threatening if untreated, but advances in immunosuppressive therapy have significantly improved patient outcomes. 

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Epidemiology

  • Incidence: Approximately 0.1–0.5 cases per 100,000 individuals per year.
  • Age: Most commonly affects adults between 40 and 60 years.
  • Sex: Slightly more prevalent in females.
  • Geographic variation: Higher prevalence in populations of Ashkenazi Jewish, Mediterranean, and Middle Eastern descent.

Pathophysiology

Pemphigus vulgaris is an autoimmune disease in which the body produces IgG autoantibodies against desmogleins, which are cadherin-type proteins essential for keratinocyte adhesion:

  • Desmoglein 3 (Dsg3): Predominantly expressed in mucous membranes → explains early oral involvement.
  • Desmoglein 1 (Dsg1): Found more in the superficial epidermis → explains skin involvement in some cases.

The binding of autoantibodies to desmogleins leads to acantholysis, the loss of cell-to-cell adhesion, resulting in intraepidermal blister formation.

Clinical Features

  1. Mucosal involvement (often the first sign):
    • Painful oral ulcers.
    • Erosions in the pharynx, larynx, or genital mucosa in severe cases.
  2. Cutaneous involvement:
    • Flaccid blisters that rupture easily, leaving painful erosions.
    • Nikolsky sign: Gentle lateral pressure on intact skin causes epidermal sloughing.
  3. Symptoms:
    • Pain, discomfort, difficulty eating.
    • Possible secondary infection in eroded areas.

Diagnosis

Diagnosis of PV is based on clinical presentation, histopathology, and immunopathology:

  1. Skin or mucosal biopsy:
    • Histology shows suprabasal acantholysis and “row of tombstones” appearance of basal keratinocytes.
  2. Direct immunofluorescence (DIF):
    • Intercellular deposition of IgG and C3 in the epidermis.
  3. Serology:
    • ELISA tests detect circulating anti-Dsg1 and anti-Dsg3 antibodies.

Treatment

Treatment aims to suppress autoimmunity, promote healing, and prevent complications:

  1. First-line therapy:
    • Systemic corticosteroids (e.g., prednisone) to control acute disease.
  2. Adjunct immunosuppressants:
    • Azathioprine, mycophenolate mofetil, cyclophosphamide.
  3. Biologic therapy:
    • Rituximab (anti-CD20 monoclonal antibody) is now considered a first-line option in moderate-to-severe cases.
  4. Supportive care:
    • Pain management, topical steroids, prevention of secondary infections, proper nutrition.

Prognosis

  • Before modern therapies, PV had a high mortality rate (~75% within 1 year).
  • With corticosteroids and immunosuppressants, mortality has decreased to <10%.
  • Disease course is often chronic and relapsing, requiring long-term follow-up.

Conclusion

Pemphigus vulgaris is a rare autoimmune blistering disorder with significant morbidity if untreated. Early recognition, accurate diagnosis, and timely immunosuppressive therapy are essential to prevent complications. Advances in targeted biologic therapies have dramatically improved patient outcomes and quality of life.