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Cause And Symptoms

Complications

Diagnosis And Treatment

Overview

Prevention

References

bullous-pemphigoid

Bullous Pemphigoid

<h2>Bullous pemphigoid management: The complexities of treating a chronic skin disease in a fragile patient population</h2>

<h3>Bullous pemphigoid can have relapse rates of up to 53%, regardless of treatments1,2</h3>

The relapse rate of bullous pemphigoid is high – up to 53%, and the majority of relapses occur within 6 months of remission1

<h3>Estimated relapse rates of patients with bullous pemphigoid at different timepoints after disease remission or treatment withdrawal, based on a meta-analysis study1</h3>

Figure adapted from Wang Y, et al. Ann Med. 2018.

<h3>The ultimate goal of bullous pemphigoid management is long-term disease control3</h3>
Treatment for bullous pemphigoid should aim to:3–7

<h3>Treatment strategies should account for the distinct challenges of bullous pemphigoid8–12</h3>
As bullous pemphigoid is most prevalent in the elderly, treatment strategies should consider the following key challenges of older patients with bullous pemphigoid8–12

High burden of bullous pemphigoid itself, and comorbidities9,11

Increased risk of adverse events with corticosteroids and other immunosuppressants8,9,13

Risks associated with polypharmacy12

Age-related changes in drug metabolism and decreased drug tolerance10

<h3>Due to the chronicity of bullous pemphigoid, a safe and effective long-tern management approach is needed to reduce the risk of relapse and achieve disease remission11</h3>

Learn about bullous pemphigoid and its clinical characteristics

What is bullous pemphigoid?

Learn about the significant burden experienced by patients with bullous pemphigoid

Morbidity and mortality in bullous pemphigoid

Learn about autoimmunity and the role of type 2 inflammation in the pathophysiology of bullous pemphigoid

What are the contributing factors in bullous pemphigoid?

Learn more about bullous pemphigoid treatment approaches and the current challenges

Current treatment approaches and challenges in bullous pemphigoid

The management of bullous pemphigoid is challenging and new treatment approaches are needed. Read this article to find out more.

Considerations for bullous pemphigoid management

BULLOUS-PEMPHIGOID

DERMATOLOGY

<h2>Bullous pemphigoid: A chronic disease with high clinical burden, mortality rates, and unmet needs1–6</h2>
<h3>Defining bullous pemphigoid</h3>
<h4>Bullous pemphigoid is a chronic relapsing autoimmune skin disease, predominantly in those ≥60 years of age, characterized by intense itch, inflammatory lesions, and blister formation1, 6–11</h4>
Bullous pemphigoid at a glance…

Diagnosis of bullous pemphigoid can be delayed:&nbsp;The heterogeneous clinical presentation of bullous pemphigoid, in addition to the complexity of diagnostic tests, can lead to underdiagnosis7,12–15

Bullous pemphigoid can persist for months to years:&nbsp;Bullous pemphigoid has a mean duration of 105 months and a high relapse rate,1,6,16&nbsp;with up to&nbsp;53% of patients relapsing within 6 months of disease remission1

Intense itch is almost invariably present in patients with bullous pemphigoid:&nbsp;85% of patients with bullous pemphigoid suffer daily from itch11

Bullous pemphigoid erosions or blisters are often associated with pain:&nbsp;53% of patients with bullous pemphigoid report pain and of these, 26% report moderate-to-severe pain17

Type 2 inflammation is a critical driver of bullous pemphigoid pathogenesis:&nbsp;The pathophysiology of bullous pemphigoid involves autoimmunity to proteins BP180 and BP230 (components of adhesion complexes in the epidermis) and type 2 inflammation18–21

<h3>A typical patient with bullous pemphigoid:</h3>

<h3>The incidence of bullous pemphigoid varies globally,15, 31–37&nbsp;with the reported worldwide incidence being 0.21–7.63 patients per 100,00038</h3>
The incidence of bullous pemphigoid has been rising over the past two decades, in part due to better recognition of clinical presentations of the disease, increased life expectancy of the general population and the increased use of certain drug triggers, such as:15,31,32,39–41
<ul>
 <li>Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins)&nbsp;</li>
 <li>Programmed death (PD)-1/programmed death-ligand (PDL)-1 inhibitors (and other immune checkpoint inhibitors)</li>
 <li>Loop diuretics</li>
 <li>Penicillin</li>
</ul>

<h3>What are the clinical presentations of bullous pemphigoid?</h3>
Bullous pemphigoid is characterized by intense itch and painful polymorphous lesions7,8,11,17,42–44
Bullous pemphigoid can present with or without bullous lesions7,15, 42–45
<ul>
 <li>Bullous presentation (~80%): Can consist of localized or generalized skin blisters arising from erythematous inflamed or normal-appearing skin7,8,42–44</li>
 <li>Non-bullous presentation (~20%): Can consist of urticarial, papular, eczematous lesions, and excoriations may be observed in the early phase of the disease or as the only manifestation of disease in certain patients7,8,15, 42–44</li>
</ul>

<h3>The non-bullous presentation of bullous pemphigoid can be confused with other dermatological conditions, such as atopic dermatitis or urticaria, adding to the burden of underdiagnosis; therefore, accurate identification is important7,13,46</h3>
<h3>How is bullous pemphigoid diagnosed?&nbsp;</h3>
Clinical assessment and obtaining patient history, in addition to techniques such as histopathology, immunofluorescence and/or ELISA are essential for bullous pemphigoid diagnosis; however, access to these resources vary widely by country and region12–14,47
Diagnosis of bullous pemphigoid12,13,42,47,48

<h3>In addition to the heterogenous clinical presentation of bullous pemphigoid, the complexity of diagnostic tests can contribute to underdiagnosis and diagnostic delays of up to 22 months7,12–16</h3>

Bullous pemphigoid in skin of color

Learn about the key challenges to consider when treating bullous pemphigoid

The challenges of managing bullous pemphigoid

Morbidity and mortality in bullous pemphigoid

What are the contributing factors in bullous pemphigoid?

Learn more about bullous pemphigoid treatment approaches and the current unmet needs

Current treatment approaches and unmet needs in bullous pemphigoid

The heterogeneous presentation of bullous pemphigoid may shed light on why patients are underdiagnosed. Read the article to learn more

What is Bullous Pemphigoid

<h2>A closer look at treating bullous pemphigoid: Unmet needs from a therapeutic management perspective</h2>
<h3>Traditional management of bullous pemphigoid includes topical and oral corticosteroids1</h3>
<h4>The European Academy of Dermatology and Venereology (EADV)’s 2022 guidelines for the management of bullous pemphigoid state:*1</h4>
<ul>
 <li>
 Topical steroids and oral antibiotics can be used to treat mild-to-moderate bullous pemphigoid</li>
 <li>Systemic corticosteroids can be introduced for cases of severe bullous pemphigoid</li>
 <li>For steroid-dependent or recalcitrant bullous pemphigoid, treatment options may include other immunosuppressants (e.g., methotrexate, azathioprine), intravenous immunoglobulins, and B-cell depleting therapy (e.g., rituximab)</li>
</ul>
These treatment approaches are the current mainstay of therapy and present challenges, particularly in an elderly population with multiple comorbidities and polypharmacy.2–10
*Please refer to local guidelines regarding the regulatory status and approved indications of any medical intervention discussed.

<h3>Safety considerations with current treatment options for bullous pemphigoid</h3>
<h4>Short-term use of topical and medium-dose systemic corticosteroids is considered a safe and e ective first-line approach to managing bullous pemphigoid.1,11&nbsp;However, the long-term use of systemic corticosteroids (often considered to be greater than 12 months of treatment12) can be associated with severe side e ects, partially due to the advanced age of the patient population1–5</h4>
<h4>Side effects associated with the long-term use of systemic corticosteroids in bullous pemphigoid</h4>

Steroid- induced myopathy2

Sepsis2,3

Thromboembolic events2

Hypertension4,5

Hyperglycemia/ worsening of diabetes mellitus4,5

Worsening of osteoporosis2,4,5

Weight gain4

Additionally, the long-term use of other immunosuppressants is associated with an increased risk of adverse events7–9
The long-term safety risks of other immunosuppressive treatments include:
<ul>
 <li>Hepatotoxicity (methotrexate, azathioprine)7,9</li>
 <li>Nephrotoxicity and hypertension (cyclosporine, methotrexate)8,9</li>
 <li>Thrombophlebitis and thrombosis (mycophenolate mofetil)9</li>
 <li>Gastrointestinal toxicity and distress (azathioprine, mycophenolate mofetil)7</li>
 <li>Increased risk of infection (azathioprine, mycophenolate mofetil)7</li>
 <li>Myelosuppression (azathioprine, methotrexate, cyclosporine)7,9</li>
</ul>
Due to this potential for adverse events, most of the current immunosuppressive drugs used to treat bullous pemphigoid require frequent lab monitoring1,7
Systemic corticosteroid use is likely a strong predictor of serious infections in patients with bullous pemphigoid3
The use of systemic corticosteroids has been shown to be&nbsp;statistically associated with an increased risk of serious infections in patients with bullous pemphigoid&nbsp;(adjusted hazard ratios: 1.53–2.33, p&lt;0.001). This increased risk of serious infections among systemic corticosteroid users was found to be&nbsp;dose dependent3
The dose-dependent relationship between corticosteroids and serious infection risk highlights the importance of safe and effective therapies in bullous pemphigoid management3
Cumulative incidences of serious infections in bullous pemphigoid (N=5006)3

Figure adapted from Chang et al, Acta Derm Venereol. 2023.

<h3>There is an unmet need in the treatment of bullous pemphigoid</h3>
<h3>The goals of maintenance therapy for bullous pemphigoid include:13</h3>
<ul>
 <li>Controlling disease activity</li>
 <li>Prompt tapering of systemic corticosteroids (and of adjuvant immunosuppressive agents if applicable) where possible</li>
 <li>Avoiding relapses</li>
 <li>Monitoring of treatment-related adverse effects</li>
</ul>
With the evolving understanding of the pathophysiology of bullous pemphigoid, there is a need for new advanced therapies that are well-tolerated, provide remission/long-term disease control, and improve patients’ quality of life

What is bullous pemphigoid?

The challenges of managing bullous pemphigoid

Morbidity and mortality in bullous pemphigoid

What are the contributing factors in bullous pemphigoid?

Systemic corticosteroids and other immunosuppressants are the current mainstay of therapy but carry risks for patients with bullous pemphigoid. Read this article to find out more

Bullous Pemphigoid

Latest Articles

Considerations for bullous pemphigoid management

What is Bullous Pemphigoid

Treatments and challenges for bullous pemphigoid