Bullous Pemphigoid

What is Bullous Pemphigoid?

Bullous Pemphigoid is a chronic autoimmune, subepidermal blistering skin disease. It is more common in people above age 60 years. As it is a chronic disease, if left untreated it can persist for months to years with periods of exacerbations and remissions. 

Bullous Pemphigoid may cause mortality/morbidity especially for those who are debilitated. Cause of death may be due to infection or adverse events due to treatment. Treatment with steroids may also increase risk of diabetes, immune suppression with agranulocytosis, peptic ulcer disease and gastrointestinal bleeds.

What causes Bullous Pemphigoid?

Bullous Pemphigoid is an autoimmune disorder whereby IgG antibodies and activated T cells attack the protein BP antigen BP180, or less frequently BP230 of the skin basement membrane (a thin layer of fibers that connect the epidermis to the dermis). The binding of the antibodies to the skin basement membrane triggers off a cascade of inflammatory and complement mediators that cause the inflammatory cascade and formation of skin blisters.

There are certain drugs that are associated with bullous Pemphigoid such as NSAIDs, frusemide, ibuprofen, captopril, penicillamine and certain antibiotics.

Clinical symptoms of Bullous Pemphigoid

Before the onset of blisters, some patients may have a preceding non-specific itchy red rash which resembles dermatitis or Urticaria which later erupts into blisters.

Most patients will present with tense fluid filled blisters localized to one site or widespread to torso and limbs. The fluid in the blisters can be clear, blood stained or cloudy. In severe cases, blisters may also appear in the oral cavity.

As the blisters heal they may form post inflammatory hyper-pigmented brown marks.

Diagnostic Tests for Bullous Pemphigoid

To confirm diagnosis of bullous Pemphigoid, a skin biopsy sample of the skin is sent for histopathologic analysis. Direct Immunofluorescence Study (DIF) will highlight deposits of IgG auto-antibodies and complement C3 along the basement membrane that lies between the dermis and epidermis.

If DIF is positive, the indirect immunofluorescence (IDIF) is performed using the patient’s serum. IDIF will identify the presence of circulating IgG auto-antibodies that target the skin basement membrane.

Treatment of Bullous Pemphigoid

The goal of treatment is to minimize formation of blister, promote blister healing and prevent secondary infection of the skin. Medications are used to reduce the inflammatory process and autoantibody production.

Oral corticosteroids

It is the first line therapy treatment for bullous Pemphigoid. Depending on the severity of the condition, the starting dose range from 0.3mg/kg for mild disease, 0.6mg/kg for moderate disease to 0.75-1.0mg/kg for severe diseases. The dose is titrated until the blisters have stopped forming and then the dose is tapered down slowly over several months to years.

Prolonged usage of steroids may reduce the immune system, cause skin striae, raise blood pressure and glucose levels, cataracts, gastritis and osteoporosis.

For those who can’t tolerate steroids or those who have medical contra-indications for steroid usage, other alternative first line treatments are: Oral tetracycline, oral erythromycin and topical steroids that also have anti-inflammatory effects.

Immunosuppressive medications

For patients who have frequent relapse during tapering of steroids or those who require high doses of steroid or those who can’t tolerate the side effects of steroids, immunosuppressive medications may be added as adjuvants to systemic steroids. The first choice is dapsone, followed by second choice methotrexate followed by third choice azathioprine and mycophenolate mofetil followed by 4th choice chloramucil. 

Immunosuppressive treatment requires frequent follow up with the doctor and blood tests to monitor its effects on the hematologic cells, kidneys, liver function and so on. This is because immunosuppressive medications can cause immunosuppression, hypersensitivity reaction, hepatic and renal impairment, bone marrow suppression, malignancies and opportunistic infections.

Others

For severe bullous Pemphigoid that do not respond to oral steroids and immunosuppressive, then other treatments available include intravenous immunoglobulin, plasmapheresis, pulsed cyclophosphamide and biologics like rituximab (a form of mononuclear therapy).

Almost all the systemic medications have adverse side effects and hence patients should be monitored closely under the supervision of specialized dermatologists. Most patients require 6-60 months of treatment after which remission of disease may occur. However a minority may need medications for years.

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