Bullous pemphigoid

Last Updated: 2023-07-07

Author(s): Anzengruber F., Navarini A.

ICD11: EB41.0

1/21

Lever 1953

Dermatitis herpetiformis senilis, parapemphigus, senile pemphigus

  • Autoimmune disease in which autoantibodies attack hemidesmosomal structural proteins of the basement membrane zone, eventually leading to blister formation.
  • Special forms:
    • Bullous localised pemphigoid
    • Bullous vegetating pemphigoid
    • Scarring pemphigoid
    • Pemphigoid gestationis
    • IgA-linear dermatosis

  • Incidence: approx. 13 cases/1'000'000/year
  • Incidence (>80 y.): 190/1,000,000/ year
  • Men : women = 2 : 1
  • Associations
    • Dementia
    • Morbus Parkinson
    • Epilepsy
    • Multiple sclerosis

  • Molecular pathogenesis:
    • In bullous pemphigoid, 2 IgG autoantibodies, anti-BP-180 and anti-BP-230, attack hemidesmosomal proteins. Antibodies also attack the NC16A epitope of the BP 180 protein. This leads to the formation of antigen-antibody complexes and eventually to complement activation. This molecular damage leads to subepidermal blistering.
  • Associations / triggers:
    • 1/3 of all patients suffer from neurological and/or psychiatric diseases
      • Dementia
      • M. Parkinson's
      • Stroke
      • Epilepsy
      • Multiple sclerosis
    • Hematological diseases
    • Oncological diseases
    • Genetics
      • Haplotype HLA-DQB1*0301
  • Drug as possible trigger:
    • Antibiotics
      • Amoxicillin
      • Ampicillin
      • Cephalexin
      • penicillamine
      • Penicillin V
      • Sulfonamides and derivatives
    • Antihypertensives
      • ACE inhibitors
        • Captopril
      • Enalapril
      • Furosemide
      • Hydroxychloroquine
    • TNF antagonists
    • Cytostatic agents
      • Locally applied 5-fluorouracil
    • Antiparkinsonian drugs
      • Levodopa
    • Analgesics
      • NSAIDs
    • Aminosalicylates
      • Sulphonamides
        • Sulfasalazine
        • Salazosulfapyridine
    • Antifungals
      • Terbinafine
  • Light
    • UVA rays
    • UVB rays
    • Photodynamic therapy
  • Neoplasia

  • Blisters (and erosions), sometimes urticaria
  • In some cases, a premonitory stage may precede, in which the patient complains of severe itching but no blisters are visible
  • Mucosal involvement is seen in up to 30% (always inspect mucosa!)
  • Nikolski phenomenon I: lateral spatula pressure causes bullae to develop: negative
  • Nikolski phenomenon II: Bullae can be displaced by lateral spatula pressure: positive

  • Anamnesis
    • Itching?
    • Intake of spironolactone, phenothiazines (e.g. furosemide)?
    • Associated underlying diseases?
  • Clinic
    • Always inspect mucosa!
    • Nikolski sign
  • Biopsy
    • Dermatopathology (it is recommended that a small intact blister be completely removed by biopsy.)
    • Direct immunofluorescence

  • Dermopathological examination alone is not diagnostic
  • Subepidermal cleft formation, lymphocytic inflammatory infiltrate, eosinophilic granulocytes
  • Direct immunofluroescence has very high sensitivity (90%)

None possible.

  • Chronic-recurrent course, disease typically in remission after 2-5 years
  • 1-year mortality: 30%

  1. De Jong MCJM. Bullous Pemphigoid and Epidermolysis Bullosa Acquisita. Arch Dermatol 1996;132:151.
  2. Darling TN, McGrath JA, Yee C, et al. Premature Termination Codons Are Present on Both Alleles of the Bullous Pemphigoid Antigen 2/Type XVII Collagen Gene in Five Austrian Families with Generalized Atrophic Benign Epidermolysis Bullosa. Journal of Investigative Dermatology 1997;108:463-8.
  3. Majamaa H, Vaalasti A, Reunala T. [A difficult impetigo or an autoimmune bullous dermatosis in a child?]. Duodecim 2000;116:2777-9.
  4. Favre B, Fontao L, Koster J, et al. The Hemidesmosomal Protein Bullous Pemphigoid Antigen 1 and the Integrin  4 Subunit Bind to ERBIN: MOLECULAR CLONING OF MULTIPLE ALTERNATIVE SPLICE VARIANTS OF ERBIN AND ANALYSIS OF THEIR TISSUE EXPRESSION. Journal of Biological Chemistry 2001;276:32427-36.
  5. 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;346:321-7.
  6. Khumalo NP, Murrell DF, Wojnarowska F, Kirtschig G. A Systematic Review of Treatments for Bullous Pemphigoid. Arch Dermatol 2002;138.
  7. Amato L, Mei S, Gallerani I, Moretti S, Fabbri P. A case of chronic herpes gestationis: Persistent disease or conversion to bullous pemphigoid? Journal of the American Academy of Dermatology 2003;49:302-7.
  8. Fisler RE, Saeb M, Liang MG, Howard RM, McKee PH. Childhood Bullous Pemphigoid. The American Journal of Dermatopathology 2003;25:183-9.
  9. Hoque S, Hextall J, Hay R. Clinicopathological case 3: pemphigus foliaceus; bullous impetigo; subcorneal pustular dermatoses. Clin Exp Dermatol 2003;28:465-6.
  10. Shimanovich I, Mihai S, Oostingh GJ, et al. Granulocyte-derived elastase and gelatinase B are required for dermal–epidermal separation induced by autoantibodies from patients with epidermolysis bullosa acquisita and bullous pemphigoid. J Pathol 2004;204:519-27.
  11. Shimanovich I, Rose C, Hirako Y, Butt-Dorje E, Zillikens D. Anti-p200-Pemphigoid - Eine neue blasenbildende Autoimmundermatose. Anti-p200 pemphigoid - a new bullous autoimmune dermatosis. Journal der Deutschen Dermatologischen Gesellschaft 2004;2:7-14.
  12. Joly P, Benichou J, Lok C, et al. Prediction of Survival for Patients With Bullous Pemphigoid. Arch Dermatol 2005;141.
  13. Patton T, Korman NJ. Bullous pemphigoid treatment review. Expert Opinion on Pharmacotherapy 2006;7:2403-11.
  14. Beissert S, Werfel T, Frieling U, et al. A Comparison of Oral Methylprednisolone Plus Azathioprine or Mycophenolate Mofetil for the Treatment of Bullous Pemphigoid. Arch Dermatol 2007;143.
  15. Di Zenzo G, Marazza G, Borradori L. Bullous Pemphigoid: Physiopathology, Clinical Features and Management. Advances in Dermatology 2007;23:257-88.
  16. Lazarova Z, Salato VK, Lanschuetzer CM, Janson M, Fairley JA, Yancey KB. IgG anti-laminin-332 autoantibodies are present in a subset of patients with mucous membrane, but not bullous, pemphigoid. Journal of the American Academy of Dermatology 2008;58:951-8.
  17. Olasz EB, Yancey KB. Bullous Pemphigoid and Related Subepidermal Autoimmune Blistering Diseases.  Current Directions in Autoimmunity: S. Karger AG; 2008:141-66.
  18. Iwata H, Kamio N, Aoyama Y, et al. IgG from Patients with Bullous Pemphigoid Depletes Cultured Keratinocytes of the 180-kDa Bullous Pemphigoid Antigen (Type XVII Collagen) and Weakens Cell Attachment. Journal of Investigative Dermatology 2009;129:919-26.
  19. Bastuji-Garin S, Joly P, Lemordant P, et al. Risk Factors for Bullous Pemphigoid in the Elderly: A Prospective Case–Control Study. Journal of Investigative Dermatology 2011;131:637-43.
  20. Nast, A. (2016). S2k-Leitlinie: Diagnostik und Therapie des Pemphigus vulgaris / foliaceus und des bullösen Pemphigoids. Awmf.org. Retrieved 31 May 2016, from http://www.awmf.org/leitlinien/detail/ll/013-071.html
  21. Lebwohl, Mark. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. Elsevier, 2014. Print