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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Dermatology

Phases and Warning Signs

At a Glance

Bullous Pemphigoid (BP) develops in two phases: an early stage of severe itching and hive-like rashes, followed by a blister phase characterized by firm, fluid-filled blisters. Certain diabetes or blood pressure medications, as well as neurological conditions, can trigger or increase the risk of BP.

Understanding the timeline and physical signs of Bullous Pemphigoid (BP) can help you and your care team manage the condition more effectively. BP does not always start with blisters; it often follows a predictable progression of phases that can look like other skin issues at first.

The Two Clinical Phases

Bullous Pemphigoid typically moves through two distinct stages. Recognizing the first phase can sometimes lead to an earlier diagnosis before significant skin damage occurs.

1. The Prodromal (Non-Bullous) Phase

The word prodromal refers to the period between the initial symptoms and the full development of the disease. In BP, this phase can be very deceptive because it doesn’t involve blisters [1][2].

  • Intense Itching: This is often the very first sign. The itch (pruritus) is frequently severe and can significantly disrupt sleep and daily life [3][4].
  • Hives and Rashes: You may see red, raised patches that look like urticaria (hives) or scaly areas that resemble eczema [1][4].
  • Duration: This phase is highly variable. It can last for weeks or even several months before the first blister appears [5]. Because it looks like a common allergy or eczema, it is often misdiagnosed during this stage.

2. The Bullous Phase

This is the stage where the characteristic skin changes occur.

  • Tense Blisters: Unlike other skin conditions where blisters are fragile and pop easily, BP blisters are typically “tense” [6][7]. This means they are firm to the touch and filled with clear or slightly bloody fluid [1].
  • Location: Blisters commonly appear on the lower abdomen, inner thighs, groin, and the “flexor” surfaces of the arms (the inside of the elbows and wrists) [8][9].
  • Healing: When these blisters do break, they usually leave behind raw, sore areas of skin that eventually heal without leaving deep scars [1].

To learn how to care for these blisters, see Managing Your Care and Blisters.

Potential Triggers: Medications

In some cases, medications can act as a “trigger” that causes the immune system to begin attacking the skin. This is sometimes called Drug-Induced Bullous Pemphigoid (DABP). Notable triggers include:

  • DPP-4 Inhibitors: Also known as “gliptins,” these are common medications for Type 2 diabetes (such as sitagliptin or linagliptin) [10][11].
  • Immune Checkpoint Inhibitors: These are advanced therapies used to treat certain types of cancer [12][13].
  • Diuretics: Specifically “loop diuretics” used for blood pressure or fluid retention, such as furosemide [10][14].

Associated Health Conditions (Comorbidities)

Researchers have noted that BP occurs more frequently in individuals with certain neurological disorders [15][16]. These include:

The connection exists because the proteins being attacked in the skin (BP180 and BP230) are also found in the brain and nervous system [21][22]. Scientists believe the immune system may start attacking these proteins in the brain first, and then later “cross-reacts” with the same proteins in the skin [21]. Finding this link is helpful because it allows doctors to provide more comprehensive care for both the skin and the underlying neurological health [8].

Common questions in this guide

What are the first warning signs of Bullous Pemphigoid?
The earliest sign is often intense, severe itching that can disrupt your sleep. During this early stage, you might also develop red, raised patches that look like hives or scaly rashes weeks or months before any actual blisters appear.
Where do Bullous Pemphigoid blisters usually appear?
Blisters most commonly form on the lower abdomen, inner thighs, groin, and the inside of the elbows and wrists. Unlike other types of blisters, they are usually very firm to the touch and filled with clear or slightly bloody fluid.
Can medications cause Bullous Pemphigoid?
Yes, certain medications can trigger the immune system to attack the skin, causing drug-induced Bullous Pemphigoid. Common triggers include certain diabetes drugs (DPP-4 inhibitors), blood pressure diuretics, and specific cancer therapies.
Why is Bullous Pemphigoid linked to neurological conditions?
BP is linked to neurological conditions like Parkinson's, Alzheimer's, and stroke because the specific proteins targeted by the immune system in the skin are also naturally found in the brain and nervous system.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Given my history of itching, is this likely the prodromal phase of Bullous Pemphigoid?
  2. 2.Should I stop or switch any of my current medications, specifically my diabetes or blood pressure medicine, to see if it improves my skin?
  3. 3.Does my history of a stroke or neurological issues change how we should manage this condition?
  4. 4.What should I do if a blister breaks, and how can I prevent infection in those areas?
  5. 5.Are there specific blood tests or biopsies that can determine if my medications are triggering these blisters?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (22)
  1. 1

    Unilateral, localized bullous pemphigoid in a patient with chronic venous stasis.

    Shi CR, Charrow A, Granter SR, et al.

    JAAD case reports 2018; (4(2)):162-164 doi:10.1016/j.jdcr.2017.09.032.

    PMID: 29387773
  2. 2

    Occurrence of Bullous Pemphigoid in a Longstanding Case of Rheumatoid Arthritis in an Indian Patient: A Rare Association.

    Deo KS, Chaurasia P, Sharma Y, et al.

    Cureus 2024; (16(4)):e59226 doi:10.7759/cureus.59226.

    PMID: 38807846
  3. 3

    Actigraphy-measured nocturnal wrist movements and assessment of sleep quality in patients with bullous pemphigoid: a pilot case-control study.

    Kalinska-Bienias A, Piotrowski T, Kowalczyk E, et al.

    Clinical and experimental dermatology 2019; (44(7)):759-765 doi:10.1111/ced.13902.

    PMID: 30652344
  4. 4

    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
  5. 5

    Case Report: A Rare Case of Pembrolizumab-Induced Bullous Pemphigoid.

    Zhang X, Sui D, Wang D, et al.

    Frontiers in immunology 2021; (12()):731774 doi:10.3389/fimmu.2021.731774.

    PMID: 34594337
  6. 6

    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
  7. 7

    Erythematous Plaques and Tense Bullae in an Infant.

    Ederle A, Whisonant CT, Nymeyer H

    Cureus 2021; (13(7)):e16623 doi:10.7759/cureus.16623.

    PMID: 34336533
  8. 8

    Multimorbidity in bullous pemphigoid: a case-control analysis of bullous pemphigoid patients with age- and gender-matched controls.

    Sim B, Fook-Chong S, Phoon YW, et al.

    Journal of the European Academy of Dermatology and Venereology : JEADV 2017; (31(10)):1709-1714 doi:10.1111/jdv.14312.

    PMID: 28485892
  9. 9

    Bilateral localized bullous pemphigoid in a young adult patient: A case report.

    Nourmohammadpour P, Akhdar M, Ghanadan A, et al.

    SAGE open medical case reports 2023; (11()):2050313X231190730 doi:10.1177/2050313X231190730.

    PMID: 37533489
  10. 10

    A Systematic Review of Drug-Induced Pemphigoid.

    Verheyden MJ, Bilgic A, Murrell DF

    Acta dermato-venereologica 2020; (100(15)):adv00224 doi:10.2340/00015555-3457.

    PMID: 32176310
  11. 11

    The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: a ten-year prospective observational study.

    Lambadiari V, Kountouri A, Kousathana F, et al.

    BMC endocrine disorders 2021; (21(1)):23 doi:10.1186/s12902-021-00689-7.

    PMID: 33573656
  12. 12

    Neutrophil-predominant bullous pemphigoid induced by checkpoint inhibitors: A case series.

    Morris LM, Lewis HA, Cornelius LA, et al.

    Journal of cutaneous pathology 2020; (47(8)):742-746 doi:10.1111/cup.13687.

    PMID: 32196722
  13. 13

    Remote presentation of nivolumab-induced bullous pemphigoid in hepatocellular carcinoma.

    Yoo A, Chen J, Sarma V, Arundel C

    BMJ case reports 2025; (18(4)) doi:10.1136/bcr-2024-263285.

    PMID: 40199591
  14. 14

    Bullous Pemphigoid Induced by Cefixime: A Rare Side Effect.

    Sandakly N, El Koubayati G, Nassereddine H, Haddad F

    Cureus 2024; (16(11)):e74246 doi:10.7759/cureus.74246.

    PMID: 39712738
  15. 15

    Evaluation of Comorbidities in Patients with Autoimmune Bullous Diseases: A Retrospective Study.

    Karabay EA, Çerman AA, Altunay İK

    Sisli Etfal Hastanesi tip bulteni 2018; (52(4)):302-306 doi:10.14744/SEMB.2018.55376.

    PMID: 32774095
  16. 16

    Neurological disorders are associated with bullous pemphigoid.

    Papakonstantinou E, Limberg MM, Gehring M, et al.

    Journal of the European Academy of Dermatology and Venereology : JEADV 2019; (33(5)):925-929 doi:10.1111/jdv.15444.

    PMID: 30663128
  17. 17

    Comorbid diseases among bullous pemphigoid patients in Germany: new insights from a case-control study.

    Martin E, Mauer I, Malzahn U, et al.

    Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 2022; (20(6)):798-805 doi:10.1111/ddg.14738.

    PMID: 35657083
  18. 18

    The association between bullous pemphigoid and neurological disorders: a systematic review.

    Milani-Nejad N, Zhang M, Kaffenberger J

    European journal of dermatology : EJD 2017; (27(5)):472-481 doi:10.1684/ejd.2017.3066.

    PMID: 28681724
  19. 19

    Prognostic factors for mortality in bullous pemphigoid: A systematic review and meta-analysis.

    Chen X, Zhang Y, Luo Z, et al.

    PloS one 2022; (17(4)):e0264705 doi:10.1371/journal.pone.0264705.

    PMID: 35427358
  20. 20

    Survival and prognostic factors in bullous pemphigoid: A retrospective cohort study.

    Papara C, Chiorean R, Leucuta DC, et al.

    Indian journal of dermatology, venereology and leprology 2023; (89(3)):363-371.

    PMID: 36331841
  21. 21

    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
  22. 22

    Three Cases of Bullous Pemphigoid Associated with Dipeptidyl Peptidase-4 Inhibitors - One due to Linagliptin.

    Mendonça FM, Martín-Gutierrez FJ, Ríos-Martín JJ, Camacho-Martinez F

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This page explains the phases and warning signs of Bullous Pemphigoid for educational purposes only. Always consult a dermatologist or healthcare provider for an accurate diagnosis and before stopping or changing any medications.

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