Correct answer: 5 (D & E) - peri-lesional/bullae skin

BP: DON'T MISS THE DIAGNOSIS CLICK HERE

Bullous pemphigoid is an autoimmune blister disease that typically presents in elderly patients with tense bullae (indicating a subepidermal split) on erythematous or normal skin, often accompanied by severe pruritus. Early or nonbullous variants may manifest as urticar-like, eczematous, or excoriated lesions, and up to 20% of patients may lack blisters at presentation, complicating diagnosis; bullous pemphigoid should be in the differential diagnosis of pruritus without rash in the elderly.[1-6] Mucosal involvement is uncommon but can occur in a minority of cases.[6]

Diagnosis relies on a combination of clinical, histopathologic, and immunopathologic findings. The diagnosis is confirmed with a lesional biopsy for routine histology (H&E) and perilesional skin biopsy for direct immunofluorescence (DIF).  A lesional biopsy demonstrates a subepidermal blister with an inflammatory infiltrate composed predominantly of eosinophils.  A perilesional biopsy demonstrates linear IgG and/or C3 deposition along the basement membrane zone. Site selection for DIF is critical: the biopsy should be taken from perilesional, nonbullous, non-excoriated skin (within 1–2 cm of a fresh lesion) to maximize diagnostic yield and avoid false negatives due to loss of immunoreactants in older or ulcerated lesions.[2-4][6] Indirect immunofluorescence on salt-split skin (IIF SSS) is highly specific and complements DIF, especially in cases with negative or equivocal DIF results, with autoantibodies binding to the roof of the split.[2] Serologic assays for BP180 and BP230 antibodies are useful adjuncts, and can be helpful in confirmation of the diagnosis and disease activity monitoring, but are less sensitive for initial diagnosis.[2][4]\

First-line treatment for localized or mild disease is high-potency topical corticosteroids. For moderate-to-severe or generalized disease, systemic corticosteroids are standard, often combined with steroid-sparing immunosuppressants (e.g., azathioprine, mycophenolate mofetil, methotrexate) to minimize long-term steroid exposure.[1][3-5][7] In refractory or high-risk cases, biologics have shown efficacy and are increasingly used.[1][3][7] Treatment selection should be individualized, considering patient comorbidities and risk profiles.

  1. Akbarialiabad H, Schmidt E, Patsatsi A, et al. Bullous Pemphigoid. Nature Reviews. Disease Primers. 2025;11(1):12. doi:10.1038/s41572-025-00595-5.
  2. Meijer JM, Diercks GFH, de Lang EWG, Pas HH, Jonkman MF. Assessment of Diagnostic Strategy for Early Recognition of Bullous and Nonbullous Variants of Pemphigoid. JAMA Dermatology. 2019;155(2):158-165. doi:10.1001/jamadermatol.2018.4390.
  3. Powers CM, Thakker S, Gulati N, et al. Bullous Pemphigoid: A Practical Approach to Diagnosis and Management in the Modern Era. Journal of the American Academy of Dermatology. 2025;92(6):1337-1350. doi:10.1016/j.jaad.2025.01.086.
  4. Bernard P, Antonicelli F. Bullous Pemphigoid: A Review of Its Diagnosis, Associations and Treatment. American Journal of Clinical Dermatology. 2017;18(4):513-528. doi:10.1007/s40257-017-0264-2.
  5. Bağcı IS, Horváth ON, Ruzicka T, Sárdy M. Bullous Pemphigoid. Autoimmunity Reviews. 2017;16(5):445-455. doi:10.1016/j.autrev.2017.03.010.
  6. Yancey KB, Egan CA. Pemphigoid: Clinical, Histologic, Immunopathologic, and Therapeutic Considerations. 2000;284(3):350-6. doi:10.1001/jama.284.3.350.
  7. Karakioulaki M, Eyerich K, Patsatsi A. Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update. American Journal of Clinical Dermatology. 2024;25(2):195-212. doi:10.1007/s40257-023-00832-1.