Core Dermatology Diagnoses / CategoriesInflammatory

Pemphigus vulgaris

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Publish date: Posted on
Last updated: October 21, 2023

Keywords #

bullous disorders
pemphigus vulgaris
PV

Diagnosis #

Pemphigus Vulgaris (PV) is a bullous, blistering disorder that is characterized by disruption of the adhesive connections between keratinocytes of the epidermis and mucosal epithelium. This disruption is caused by antibodies directed towards desmoglein, an adhesive protein of desmosomes. These antibodies lead to the activation of complement and other cellular proteases, resulting in destruction of these important adhesive proteins. The hallmark of PV is the presence of IgG autoantibodies on the cell surface of keratinocytes on direct immunofluorescence testing (DIF). [1,4]

Key Concepts #
  • Pemphigus vulgaris typically presents between the ages of 50-60 years old.
  • Typically presents with flaccid bullae and erosions on skin and mucous membranes.
  • Erosions in the oral cavity are usually the site of initial disease.
  • PV is caused by auto-IgG against desmoglein 1 and 3 resulting in suprabasilar acantholysis.
  • Typically treated with systemic glucocorticoids and rituximab.
Epidemiology #

Equally affects men and women with a median age onset between 50-60 years of age. PV is more common in those of Jewish or Mediterranean descent. [1]

Clinical Features #
  • Typically presents with flaccid bullae and erosions in any area of the body, although mucous membranes are almost always the site of initial disease.
  • Majority of patients will present with mucous membrane erosions in the mouth.
  • Flaccid bullae will rupture easily with lateral pressure (Nikolsky sign).
  • Severe disease often results in high rates of infection which remains the most common cause of death in patients with PV.
Differential Diagnoses #
Diagnostic Workup #

Diagnosis is made through a combination of clinical and laboratory findings that include: histologic, immunopathologic, and serologic findings. The presence of painful mucosal erosions and scattered, flaccid, easily-ruptured bullae are common clinical findings that increase suspicion of PV. Further questioning about medications, infections, and autoimmune disorders should also be done to differentiate the etiology of the lesions.

Work-up includes a lesional skin/mucosal biopsy for H&E staining, perilesional skin/mucosal biopsy for DIF, and serum collection for ELISA or IIF.  Diagnostic findings of these biopsies include suprabasilar acantholysis with “rows of tombstones” of the basal keratinocytes (H&E), reticular IgG DIF pattern surrounding keratinocytes, and circulating autoantibodies against epithelial cell surface antigens. [2,3]

Treatment #

Historically, PV was almost always fatal. However, due to the advent of glucocorticoid therapy and immunosuppressive therapy, this disease has become less deadly – the mortality rate between 4-10 years after onset of disease is about 10% [1].  Despite these new therapies, mortality and morbidity remains high. Systemic glucocorticoids are often used initially, however, rituximab is increasingly being used early in disease to try to limit corticosteroid exposure.  Long-term remission has been obtained in some but not all cases with use of rituximab.  Other immunosuppressive agents such as azathioprine and mycophenolate mofetil have also been used as disease modifying agents. [3] In addition to clinical improvement, IIF may be used to monitor treatment response over time.

Slide Viewer #
https://utahderm.med.utah.edu/image-viewer/
References #
  1. Freedberg, Irwin M, and Thomas B. Fitzpatrick. Fitzpatrick’s Dermatology in General Medicine. New York: McGraw-Hill, Health Professions Division, 1999. Print. p. 655-663
  2. Weedon D. The vesicobullous reaction pattern. In: Weedon’s Skin Pathology, 3rd Elseveier, Edinburgh 2020. p. 123
  3. Diagnosis and management of pemphigus: Recommendations of an international panel of experts. Murrel DF, Pena S, Joly P, Marinovic B, et al. J Am Academy Dermatology 2020, Epub 2018 Feb 10; 82(3):575.
  4. Kumar, Vinay, and Stanley L. 1915- Robbins. Robbins Basic Pathology. 8th ed. Philadelphia, PA: Saunders/Elsevier, 2007. p. 844-846
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