Episode 140: Bullous pemphigoid basics
Future Dr. Stetkevych explains the diagnosis and treatment of bullous pemphigoid. She explains how to differentiate BP from pemphigus vulgaris. Dr. Arreaza added some comments and summaries.
Written by Katherine Stetkévych, MSIV, Ross University School of Medicine.
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Definition. Bullous pemphigoid is an autoimmune condition in which the body produces antibodies against hemidesmosomes at the basement membrane of the skin. (Hemidesmosomes anchor the epidermis to the dermis.) As a result of this autoimmune reaction, inflammatory cells, and fluid fill under the epidermis, creating a blister.
As a reminder, a vesicle is a collection of free fluid <0.5 cm, and a bulla is the same but larger than 0.5 cm. Bullous pemphigoid is a member of the family of autoimmune subepidermal blistering diseases, which also includes herpes gestationis and cicatricial (sicatríshal) pemphigoid, but bullous pemphigoid is the most common out of that family and the one with the highest mortality. Let’s talk about the presentation.
Presentation.
Typically, bullous pemphigoid affects adults over the age of 60. We can say that it is a disease of elderly patients; the mean age of diagnosis is 80. There is no race or gender preference. The initial presentation is hives and pruritus. Patients may be itchy for ~10 months before the diagnosis. After patients have plaques, erythema, and itching, they have blisters.
What is notable about the blisters in bullous pemphigoid is that the blisters are taut. They bulge out from the skin; however, they do not spread when pressure is applied laterally to the blister, and pressing on an unaffected skin area will not cause a new blister to form. The spread or creation of a blister with pressure is called the Nikolsky sign, and the fact that bullous pemphigoid is negative for the Nikolsky sign helps differentiate this condition from pemphigus vulgaris. Another notable feature is that the blisters of bullous pemphigoid are painless.
If the blisters rupture, patients may experience short-term pain, but the erosion on the skin after the blisters rupture heal fast without scarring.
Bullous pemphigoid typically does not involve the oral mucosa; however, there is a subtype that does. Nonetheless, should a patient present with bullae that involve the oral mucosa, it is important to test for the Nikolsky skin, determine whether the blisters are painful, and work up the blisters to determine the correct diagnosis.
Diagnosis.
The differential diagnosis is extensive and includes dermatitis herpetiformis, bullous systemic lupus erythematous, bullous drug eruptions, bullous impetigo, even insect bites, burns, erythema multiforme, and contact dermatitis.
You can find non-specific findings such as peripheral eosinophilia in 50% of the patients. Serum tests include pemphigoid antibodies ELISA: BP 180 and 230 autoantibodies, desmoglein (desmoglain) 1 and 3. To get to a definitive diagnosis, you need a skin biopsy for histology and immunofluorescence. Histology will show subepidermal cleavage and the presence of inflammatory infiltrate with eosinophils or neutrophils.
The diagnosis will be confirmed by direct immunofluorescence (DIF). The biopsy should be taken from inflamed skin next to a blister with 2/3 of normal skin and 1/3 of inflamed skin. The sample can be transported in normal saline.
Management.
Bullous pemphigoid is treated with first-line topical high-potency corticosteroids, such as clobetasol. In cases of severe bullae, systemic corticosteroids or doxycycline may be prescribed. For patients with refractory bullous pemphigoid, the appropriate next step is to start biologic therapies.
With treatment, the prognosis is generally good for bullous pemphigoid. Some patients have spontaneous remission of the disease within a few years; however, for many, the disease is chronic, with recurrence and remission over months to years. If left untreated, bullous pemphigoid is usually a chronic, progressive disease that may cause functional limitation. Mucous membranous pemphigoid, the subtype of bullous pemphigoid which involves mucous membranes, may potentially be life-threatening if it involves the airway.
Pemphigus vulgaris.
Pemphigus vulgaris is an autoimmune condition similar to bullous pemphigoid. In pemphigus vulgaris, autoantibodies attack desmosomes in the epidermis, specifically desmoglein. Desmoglein is a cadherin protein that holds cells within the spinous layers of the epidermis together. Autoimmune destruction of desmoglein causes blisters to form superior to the basement membrane.
The average age of onset for pemphigus vulgaris is 40-60 years old. There is an increased prevalence of the disease in Ashkenazi Jewish, Indian, Southeast European, and Middle Eastern descent.
Presentation.
Because the basement membrane of the epidermis remains intact, and the protein responsible for cell-to-cell adhesion is destroyed by the immune system, bullae are easily formed. Thus, Nikolsky sign will be positive with pemphigus vulgaris—lateral friction on a blister will cause it to expand, and it may be possible to create new blisters by applying pressure to a normal-appearing area of skin. These blisters may rupture easily, leaving painful sores which may become infected. Additionally, the oral mucosa is frequently involved in pemphigus vulgaris, which helps distinguish it from bullous pemphigoid.
So, if you have a patient with skin blisters, and Nikolsyky sig is positive, and the oral mucosa is affected, then you can tell that this patient probably has pemphigus vulgaris. Tell us about the diagnosis.
Diagnosis involves taking a skin biopsy and examining it under immunofluorescence. Antibodies will be seen surrounding keratinocytes in a net-like pattern, which makes sense because desmoglein surrounds keratinocytes so that it can be attached to its neighboring keratinocytes. Histology of a skin biopsy may also be obtained, which will show a “row-of-tombstones” appearance along the inferior margin of the blister. This is because the so-called tombstones are the keratinocytes of the basement membrane, which remain anchored due to untouched hemidesmosomes.
Treatment.
Treatment is similar to that for bullous pemphigoid but more aggressive. Initial treatment includes a systemic glucocorticoid and rituximab; if rituximab treatment is not possible, mycophenolate or azathioprine may be substituted instead. For refractory cases, glucocorticoid, rituximab, and mycophenolate/azathioprine may be given at the same time. Once the disease has improved, the tapering of the glucocorticoid may be initiated.
Due to the risk of infection, loss of fluid from disseminated blisters, and potentially life-threatening involvement of the airway, the prognosis is poor with pemphigus vulgaris if left untreated.
In summary, bullous pemphigoid is a blistering, autoimmune disease that normally presents in elderly patients and does not involve the oral mucosa. The diagnosis may require a skin biopsy, and the treatment starts with topical steroids; for severe cases, you may need systemic steroids and antibiotics. Pemphigus vulgaris affects the oral mucosa, it presents in younger patients (40-60), and the treatment is more aggressive with systemic glucocorticoids and immunosuppressants.
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Conclusion: Now we conclude episode number 140, “Bullous Pemphigoid.” Katherine explained that bullous pemphigoid is an autoimmune disease that causes skin blisters more frequently in elderly patients. She then explained that pemphigus vulgaris is a similar disease but more serious, and it requires more aggressive treatment.
This week we thank Hector Arreaza and Katherine Stetkevych (pronounced as Stet-KE-vish). Audio editing by Adrianne Silva.
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Links:
- Leiferman, Kristin M. “Clinical Features and Diagnosis of Bullous Pemphigoid and Mucous Membrane Pemphigoid.” UpToDate, www.uptodate.com/contents/clinical-features-and-diagnosis-of-bullous-pemphigoid-and-mucous-membrane-pemphigoid. Accessed 23 May 2023.
- Hertl, Michael, and Shamir Geller. “Initial Management of Pemphigus Vulgaris and Pemphigus Foliaceus.” UpToDate, www.uptodate.com/contents/initial-management-of-pemphigus-vulgaris-and-pemphigus-foliaceus. Accessed 23 May 2023.
- Habif, Thomas P. Clinical Dermatology, 6th edition, 2016, Elsevier, Inc. Page 655.
