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PubMed This is a summary of 13 peer-reviewed journal articles Updated
Dermatology

The Science of Skin Separation

At a Glance

Bullous Pemphigoid (BP) occurs when the immune system mistakenly attacks BP180 and BP230, the proteins that glue skin layers together. This immune attack causes white blood cells to release enzymes, separating the skin layers and forming deep, tense blisters that are hard to pop.

To understand Bullous Pemphigoid (BP), it helps to look at the microscopic world of your skin. While the blisters appear on the surface, the “engine” of the disease is located deep within the structure of your skin cells and your immune response.

The Microscopic Anchors

Your skin is composed of layers that must remain tightly glued together to function. This “glue” consists of specialized structures called hemidesmosomes [1]. Within these structures are two vital proteins:

  • BP180 (Type XVII Collagen): This protein acts like a physical bridge or “anchor” that connects the outer layer of skin (epidermis) to the deeper support layer (dermis) [1][2].
  • BP230 (Dystonin): This protein works from the inside of the cell to help organize and strengthen the anchor points [1][3].

In BP, your immune system mistakenly creates autoantibodies that target these specific proteins [4]. When these antibodies attach to the BP180 and BP230 anchors, they signal the body to begin an inflammatory attack, causing the “glue” to dissolve and the skin layers to separate [1][2].

The Role of Eosinophils

While antibodies start the process, a type of white blood cell called an eosinophil does much of the physical work of creating a blister [5]. In BP, large numbers of eosinophils are recruited to the skin [6]. These cells release powerful enzymes and proteins intended to kill parasites; however, in BP, they mistakenly release these chemicals into the skin layers, causing the tissue damage and fluid buildup that we see as blisters [5][7].

How Doctors Distinguish BP from Other Conditions

Because many skin diseases cause rashes or blisters, doctors use a process called differential diagnosis to ensure you have Bullous Pemphigoid and not something else.

Condition Blister Type Location of Split Key Difference
Bullous Pemphigoid (BP) Tense (firm, hard to pop) Subepidermal (between layers) Most common in elderly; targets BP180/BP230 [1][8].
Pemphigus Vulgaris Flaccid (fragile, pops easily) Intraepidermal (within top layer) Often starts with painful mouth sores; skin peels away easily [8][9].
Epidermolysis Bullosa Acquisita (EBA) Tense Subepidermal Targets Collagen VII; often causes scarring and tiny white bumps (milia) [2][10].
Mucous Membrane Pemphigoid (MMP) Tense Subepidermal Primarily affects eyes, mouth, and throat; can cause significant scarring [11][12].
Chronic Spontaneous Urticaria No blisters (just hives) None Can look like the early (prodromal) phase of BP, but does not progress to blisters [13].

To confirm the diagnosis, your doctor likely used a test called Direct Immunofluorescence (DIF). Learn more about this test in Decoding Your Pathology and Lab Reports.

Common questions in this guide

What proteins does Bullous Pemphigoid attack?
In Bullous Pemphigoid, the immune system mistakenly creates autoantibodies that target BP180 and BP230. These proteins are located in structures called hemidesmosomes, which act like glue to hold your skin layers tightly together.
How is Bullous Pemphigoid different from Pemphigus Vulgaris?
Bullous Pemphigoid causes deep, tense blisters that are firm and hard to pop. In contrast, Pemphigus Vulgaris causes fragile, superficial blisters that pop very easily and often begins with painful mouth sores.
What role do eosinophils play in BP blisters?
Eosinophils are a type of white blood cell that do much of the physical work of creating the blister. In BP, they gather in the skin and mistakenly release powerful enzymes that cause tissue damage and fluid buildup.
What does it mean if my biopsy shows a subepidermal blister?
A subepidermal blister forms deep between the outer layer of skin (epidermis) and the deeper support layer (dermis). Because the roof of the blister is made up of the entire top layer of skin, these blisters are typically thick, firm, and hard to break.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Did my biopsy show the split between the skin layers (subepidermal) or within the top layer (intraepidermal)?
  2. 2.Was my Direct Immunofluorescence (DIF) test positive for IgG or C3 along the basement membrane?
  3. 3.Did my blood work show high levels of eosinophils or IgE antibodies?
  4. 4.How do my BP180 and BP230 antibody levels compare to the typical range for this diagnosis?
  5. 5.Could my symptoms be a different condition like EBA or MMP, and how have we ruled those out?

Questions For You

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References

References (13)
  1. 1

    Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

    Dikmen HO, Yilmaz K, Benoit S, et al.

    Journal of the European Academy of Dermatology and Venereology : JEADV 2022; (36(11)):2181-2189 doi:10.1111/jdv.18414.

    PMID: 35796163
  2. 2

    Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

    de Graauw E, Sitaru C, Horn M, et al.

    Allergy 2017; (72(7)):1105-1113 doi:10.1111/all.13131.

    PMID: 28135772
  3. 3

    The molecular architecture of hemidesmosomes, as revealed with super-resolution microscopy.

    Nahidiazar L, Kreft M, van den Broek B, et al.

    Journal of cell science 2015; (128(20)):3714-9 doi:10.1242/jcs.171892.

    PMID: 26330528
  4. 4

    From Molecular Insights to Clinical Perspectives in Drug-Associated Bullous Pemphigoid.

    de Nicolas-Ruanes B, Ballester-Martinez A, Garcia-Mouronte E, et al.

    International journal of molecular sciences 2023; (24(23)) doi:10.3390/ijms242316786.

    PMID: 38069109
  5. 5

    Treatment of refractory bullous pemphigoid with IFN-α-2b: A case report.

    Wang T, Xu Y, Ren Y, Luo G

    Dermatologic therapy 2020; (33(2)):e13080 doi:10.1111/dth.13080.

    PMID: 31465616
  6. 6

    Peripheral eosinophilia in bullous pemphigoid: prevalence and influence on the clinical manifestation.

    Kridin K

    The British journal of dermatology 2018; (179(5)):1141-1147 doi:10.1111/bjd.16679.

    PMID: 29663327
  7. 7

    Eosinophils as putative therapeutic targets in bullous pemphigoid.

    Simon D, Borradori L, Simon HU

    Experimental dermatology 2017; (26(12)):1187-1192 doi:10.1111/exd.13416.

    PMID: 28833620
  8. 8

    The spectrum of histopathologic findings in pemphigoid: Avoiding diagnostic pitfalls.

    Hodge BD, Roach J, Reserva JL, et al.

    Journal of cutaneous pathology 2018; (45(11)):831-838 doi:10.1111/cup.13343.

    PMID: 30141231
  9. 9

    Bullous pemphigoid and pemphigus vulgaris.

    Kayani M, Aslam AM

    BMJ (Clinical research ed.) 2017; (357()):j2169 doi:10.1136/bmj.j2169.

    PMID: 28596152
  10. 10

    The Syk Tyrosine Kinase Is Required for Skin Inflammation in an In Vivo Mouse Model of Epidermolysis Bullosa Acquisita.

    Németh T, Virtic O, Sitaru C, Mócsai A

    The Journal of investigative dermatology 2017; (137(10)):2131-2139 doi:10.1016/j.jid.2017.05.017.

    PMID: 28576735
  11. 11

    A sensitive and specific assay for the serological diagnosis of antilaminin 332 mucous membrane pemphigoid.

    Goletz S, Probst C, Komorowski L, et al.

    The British journal of dermatology 2019; (180(1)):149-156 doi:10.1111/bjd.17202.

    PMID: 30216412
  12. 12

    Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

    Borradori L, Van Beek N, Feliciani C, et al.

    Journal of the European Academy of Dermatology and Venereology : JEADV 2022; (36(10)):1689-1704 doi:10.1111/jdv.18220.

    PMID: 35766904
  13. 13

    Phototherapy with UVB-NB as a new adjuvant therapy for bullous pemphigoid: A pilot study.

    Vassallo C, Pellico MR, Gherzi S, et al.

    Photodermatology, photoimmunology & photomedicine 2022; (38(2)):169-172 doi:10.1111/phpp.12722.

    PMID: 34351011

This page explains the underlying science and pathology of Bullous Pemphigoid for educational purposes only. Always consult your dermatologist or healthcare provider for an accurate medical diagnosis.

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