Autoimmune blistering diseases

Last updated: July 25, 2022

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.

Differential diagnosis of autoimmune blistering diseasestoggle arrow icon

Characteristics Bullous pemphigoid Pemphigus vulgaris Dermatitis herpetiformis
Clinical findings
  • 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 sign
Histology and immunohistochemistry
  • 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.


Subtypes and variantstoggle arrow icon

Variant forms of bullous pemphigoid

Gestational pemphigoid [11]

Variant forms of pemphigus vulgaris

Pemphigus foliaceus [12][13][14]

Epidermolysis bullosa (EB)

Epidermolysis bullosa simplex (EBS)

Clinical features of EBS subtypes
Characteristics Localized EBS Intermediate EBS Severe EBS
Age of onset [15]
Blisters Features
  • Trauma- or friction-induced blistering
  • Disseminated, grouped blisters with herpetiform spreading [16]
  • Mainly limited to the palms and soles
  • Blistering of the oral mucosa may occur (e.g., triggered by bottle feeding).
  • Involves the hands, feet, and extremities
  • Generally heal without scarring
Extracutaneous manifestations
  • Rarely, nails are involved.

Epidermolysis bullosa acquisita (EBA) [18][19]

Other variants and subtypes

Mucous membrane pemphigoid (MMP) [20]


Diagnosticstoggle arrow icon

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.


Referencestoggle arrow icon

  1. Hertl M, Sitaru C. Pathogenesis, Clinical Manifestations, and Diagnosis of Pemphigus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. 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. 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
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  9. Hull C. Dermatitis Herpetiformis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. 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
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  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. . Accessed: September 9, 2020.
  16. Epidermolysis Bullosa Simplex. Updated: January 1, 1993. Accessed: June 24, 2022.
  17. Rugg EL, Rachet-Préhu MO, Rochat A, et al. Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex.. Eur J Hum Genet. 1999; 7 (3): p.293-300.doi: 10.1038/sj.ejhg.5200292 . | Open in Read by QxMD
  18. Sprecher E. Epidermolysis Bullosa Simplex. Dermatol Clin. 2010; 28 (1): p.23-32.doi: 10.1016/j.det.2009.10.003 . | Open in Read by QxMD
  19. 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
  20. 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
  21. 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
  22. Marks JG Jr, Miller JJ . Lookingbill and Marks' Principles of Dermatology. Saunders Elsevier ; 2013
  23. James WD, Elston D, Treat JR, Rosenbach MA, Neuhaus I. Andrews' Diseases of the Skin. Elsevier ; 2019

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