Definition:

Bullous pemphigoid is the predominant type of autoimmune blistering disease that affects the subepidermal layer

Bullous pemphigoid often manifests in those aged 80 and above, mainly affecting those aged 50 and above. Although bullous pemphigoid in newborns and children is rare, it can happen in younger individuals.

Etiology:

Bullous pemphigoid occurs when IgG and IgE immunoglobulins (antibodies) and activated T lymphocytes (white blood cells) attack the basement membrane of the epidermis. The target protein is BP180, also known as Type XVII collagen, or occasionally BP230, which is a plakin. The proteins are located inside the NC16A domain of collagen XVII. They are linked to the hemidesmosomes, which are structures responsible for the adhesion of epidermal keratinocyte cells to the dermis, creating a water-resistant barrier.

The autoantibodies attaching to the proteins and subsequent release of cytokines from the T cells result in complement activation, recruitment of neutrophils (acute inflammatory cells), and the release of proteolytic enzymes. These disrupt the hemidesmosomes and induce the development of blisters under the epidermis.

Clinical features:

Bullous pemphigoid causes intense pruritus and typically results in the development of large, tense fluid-filled vesicles/bullae (blisters) arising on urticarial background that eventually rupture leading to the formation of crusted erosions.

Bullous pemphigoid commonly affects the flexor surfaces of the limbs. It might be confined to a specific location or extend over the trunk.

It frequently affects the skin in areas where there are folds or creases.
Occurrence of blisters within the oral cavity and the genital area areas is infrequent.

Some individuals are diagnosed with bullous pemphigoid even if they do not have any bullae, which is known as non-bullous pemphigoid. This may affect any part of the body.

Diagnosis:

The diagnosis is suspected clinically when typical bullae are present. A skin biopsy of an early lesion will typically confirm the diagnosis. The diagnosis can also be made from inflamed, non-blistered epidermis.

The pathological examination of bullous pemphigoid reveals a separation beneath the epidermis. A dermal neutrophilic infiltrate is commonly observed, although it may not be present in all cases. Eosinophils may be prominent.

Direct immunofluorescence staining of a skin sample collected next to a blister reveals antibodies specifically located along the basement membrane, which is situated between the epidermis and dermis.

Management:

Pharmacologic therapy for bullous pemphigoid primarily relies on immunosuppressants and other anti-inflammatory medications. Patients may need treatment for up to several years

Most of the morbidity and mortality associated with bullous pemphigoid results from the association between patient comorbidities and treatment side effects rather than from the disease itself. Thus, it is advisable to adopt a cautious approach to treatment, using only the necessary amount of medication to achieve remission.

The primary mode of therapy for bullous pemphigoid typically includes one of the following as the initial treatment:

High potent topical corticosteroid (such as clobetasol propionate)
Oral Corticosteroid (such as prednisone or prednisolone)
Doxycycline

Corticosteroid-sparing agents (e.g., doxycycline, dapsone, methotrexate, mycophenolate, azathioprine) are frequently added to an oral corticosteroid regimen after achievement of disease control in an attempt to facilitate corticosteroid tapering. This is because bullous pemphigoid is a chronic condition and because systemic corticosteroids have multiple toxic side effects.

Written by:

Mashael Alanazi, Medical Intern.

Revised by:

Naif Alshehri, Medical Intern.

Resources:

DermNet

Review of Dermatology textbook