Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Try free for 5 days
Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

Autoimmune blistering diseases

Last updated: June 4, 2021

Summarytoggle arrow icon

Autoimmune blistering diseases are skin conditions characterized by the formation of blisters, which are the result of the destruction of cellular or extracellular adhesion molecules by antibodies. The three most significant autoimmune blistering diseases are bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis. The most common among these is bullous pemphigoid, which leads to the formation of large, tense bullae. It is a chronic disease that mainly affects elderly individuals and responds well to treatment with steroids. Pemphigus vulgaris, which is characterized by fragile, superficial flaccid bullae that leave crusted erosions, is a rare condition that occurs mainly in middle-aged adults. In contrast to bullous pemphigoid, it is a severe condition that is more difficult to treat and can be fatal. Dermatitis herpetiformis mainly affects the extensor surfaces of the extremities and is associated with celiac disease. It has a chronic course that leads to the formation of intensely pruritic papules and vesicles. In addition to evaluating clinical appearance, the Nikolsky sign, Tzanck test, skin biopsy, and direct immunofluorescence are indicated to confirm the diagnosis. Serologic testing of autoantibodies may also be useful. Management usually consists of oral and topical steroids, as well as immunosuppressive therapy.

Bullous pemphigoid Pemphigus vulgaris Dermatitis herpetiformis
Epidemiology
Etiology
Clinical findings
  • Progression in stages
  • Pruritus is typically absent.
  • Lesions typically first present on the oral mucosa (> 50% of cases), then on body parts exposed to pressure (e.g., intertriginous areas)
  • Tense, grouped subepidermal vesicles, papules, and/or bullae (herpetiform appearance)
  • Intense pruritus
  • Bilateral, symmetrical distribution, commonly over elbows, knees, buttocks, shoulders, scalp
  • No mucosal involvement
Diagnostics Autoantibodies against
  • BPAg1 (BP230)
  • BPAg2 (BP180)
Tzanck test
  • Negative
  • Positive
  • Negative
Nikolsky's sign
  • Negative
  • Positive
  • Negative
Histology and immunohistochemistry
Treatment
Prognosis
  • Benign disease, usually responds well to treatment
  • Often fatal without treatment!
  • Usually a lifelong condition requiring continuous treatment and dietary adjustments

In bullows (bullous) pemphigoid, antibodies attack the hemidesmosomes located below the epidermis.

References:[1][2][3][4][5][6][7][8][9][10]

Variant forms of bullous pemphigoid

Gestational pemphigoid [11]

Variant forms of pemphigus vulgaris

Pemphigus foliaceus [12][13][14]

Other variants and subtypes

Epidermolysis bullosa acquisita (EBA) [15][16]

Mucous membrane pemphigoid (MMP) [17]

References:[18][19]

In addition to evaluating clinical appearance, specific tests are performed to confirm the diagnosis of a blistering disease. For specific diagnostic findings, see differential diagnosis of autoimmune blistering diseases.

References:[5][7][20]

  1. Hertl M, Sitaru C. Pathogenesis, Clinical Manifestations, and Diagnosis of Pemphigus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pathogenesis-clinical-manifestations-and-diagnosis-of-pemphigus.Last updated: May 23, 2017. Accessed: November 4, 2017.
  2. Murrell DF, Ramirez-Quizon M. Management and Prognosis of Bullous Pemphigoid. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-and-prognosis-of-bullous-pemphigoid.Last updated: June 30, 2017. Accessed: November 4, 2017.
  3. Joly P, Roujeau J-C, Benichou J, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. New England Journal of Medicine. 2002; 346 (5): p.321-327. doi: 10.1056/nejmoa011592 . | Open in Read by QxMD
  4. Guidelines for the management of bullous pemphigoid. http://www.pemphigus.org/guidelines-for-the-management-of-bullous-pemphigoid-ii/. Updated: January 12, 2010. Accessed: November 4, 2017.
  5. Leiferman KM. Clinical Features and Diagnosis of Bullous Pemphigoid and Mucous Membrane Pemphigoid. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bullous-pemphigoid-and-mucous-membrane-pemphigoid.Last updated: November 17, 2017. Accessed: March 12, 2018.
  6. Mustafa MB, Porter SR, Smoller BR, Sitaru C. Oral mucosal manifestations of autoimmune skin diseases. Autoimmun Rev. 2015; 14 (10): p.930-951. doi: 10.1016/j.autrev.2015.06.005 . | Open in Read by QxMD
  7. Hassan I, Yaeen A, Ahmad Q, Farhana A, Shah P. Diagnostic value of Tzanck smear in various erosive, vesicular, and bullous skin lesions. Indian Dermatol Online J. 2015; 6 (6): p.381. doi: 10.4103/2229-5178.169729 . | Open in Read by QxMD
  8. Hertl M, Geller S. Initial Management of Pemphigus Vulgaris and Pemphigus Foliaceus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/initial-management-of-pemphigus-vulgaris-and-pemphigus-foliaceus.Last updated: December 5, 2017. Accessed: March 12, 2018.
  9. Hull C. Dermatitis Herpetiformis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/dermatitis-herpetiformis.Last updated: October 14, 2016. Accessed: March 12, 2018.
  10. Clarindo MV, Possebon AT, Soligo EM, Uyeda H, Ruaro RT, Empinotti JC. Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment. An Bras Dermatol. 2014; 89 (6): p.865-877. doi: 10.1590/abd1806-4841.20142966 . | Open in Read by QxMD
  11. Ganapati S. Eponymous dermatological signs in bullous dermatoses. Indian J Dermatol. 2014; 59 (1): p.21. doi: 10.4103/0019-5154.123483 . | Open in Read by QxMD
  12. Huilaja L, Mäkikallio K, Tasanen K. Gestational pemphigoid. Orphanet J Rare Dis. 2014; 9 (1). doi: 10.1186/s13023-014-0136-2 . | Open in Read by QxMD
  13. James KA, Culton DA, Diaz LA. Diagnosis and Clinical Features of Pemphigus Foliaceus. Dermatol Clin. 2011; 29 (3): p.405-412. doi: 10.1016/j.det.2011.03.012 . | Open in Read by QxMD
  14. Gürcan HM, Ahmed AR. Efficacy of Dapsone in the Treatment of Pemphigus and Pemphigoid. Am J Clin Dermatol. 2009; 10 (6): p.383-396. doi: 10.2165/11310740-000000000-00000 . | Open in Read by QxMD
  15. Pemphigus Foliaceus. https://www.merckmanuals.com/professional/dermatologic-disorders/bullous-diseases/pemphigus-foliaceus. . Accessed: September 9, 2020.
  16. Ludwig RJ. Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita. ISRN Dermatology. 2013; 2013 : p.1-25. doi: 10.1155/2013/812029 . | Open in Read by QxMD
  17. Koga H, Prost-Squarcioni C, Iwata H, Jonkman MF, Ludwig RJ, Bieber K. Epidermolysis Bullosa Acquisita: The 2019 Update. Frontiers in Medicine. 2019; 5 . doi: 10.3389/fmed.2018.00362 . | Open in Read by QxMD
  18. Xu H-H, Werth VP, Parisi E, Sollecito TP. Mucous Membrane Pemphigoid. Dent Clin North Am. 2013; 57 (4): p.611-630. doi: 10.1016/j.cden.2013.07.003 . | Open in Read by QxMD
  19. Marks JG Jr, Miller JJ . Lookingbill and Marks' Principles of Dermatology. Saunders Elsevier ; 2013
  20. James WD, Elston D, Treat JR, Rosenbach MA, Neuhaus I. Andrews' Diseases of the Skin. Elsevier ; 2019