Bullous Pemphigoid

What is bullous pemphigoid?

Bullous pemphigoid is a chronic blistering autoimmune disease of the skin. The occurrence of this disease rise considerably with age, and it mainly affects patients over 70 years old. With about 1-4 newly diagnosed patients per 100000 individuals per year, bullous pemphigoid is a rare condition.

Patients almost always suffer from severe itching accompanied by tense blisters on red or otherwise normal skin. Itching may start weeks or even months before the fist skin manifestations arise. The blisters contain a clear or bloody fluid and develop further into erosions and crusts when damaged, but they normally heal without scarring. In about one-fifth of patients erosions may develop in the mouth or on the genitalia. Initially, blisters may not be pres3ent, and skin lesions may look more like eczema erythema or urticaria. While blisters only appear on some parts of the body in some patients, in others the whole body is affected. Apart from intensive itching, general health is not affected in most patients. However loss of appetite body weight fever infections and general weakness can develop during the course of the disease.

What causes the blistering?

Our immune system produces specialised proteins call antibodies, which bin to bacteria, viruses, fungi and tumor cells and protect us from these infections as well as cancer. In patients with bullous pemphigoid their immune system mistakenly produces antibodies that bind to certain structures in the skin and mucous membranes termed BP180 and BP230. These disease causing antibodies that bind to the skin are call auto-antibodies. This binding triggers a complex inflammatory reaction that finally leads to the separation of the upper lay of the skin from the deeper layers. So far, it is unclear what factors trigger the immune system to produce the disease causing auto antibodies against BP180 and BP230. In some patients certain medications have been associated with the onset of the disease.

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Pemphigus Vulgaris

Key features: Mucosal and/or skin involvement with blisters on the upper skin layers. This happens when autoantibodies attack desmoglein 3 or both desmoglein 1 and desmoglein 3 (the “glue” holding the cells together).

Clinical variants: Pemphigus vegetans, pemphigus herpetiformis

• The pain associated with mucosal involvement of pemphigus vulgaris can be severe.

• Oral pain is often augmented by chewing and swallowing, which may result in poor alimentation, weight loss, and malnutrition.

Almost all pemphigus vulgaris patients will have some mucosal involvement. The mouth is the most common location of mucosal lesions, and often is the first area the disease manifests. Other mucous membranes areas are also often affected (e.g., eyes, nose, esophagus, vulva, vagina, cervix, and anus). In women with cervical involvement, pemphigus vulgaris may be mistaken for cervical dysplasia during Papanicolaou (Pap) smears.

Because mucosal blisters erode quickly, erosions are often the only clinical findings. The inner mouth (cheeks, lips, and floor of the mouth) are the most common areas for oral lesions.

Many patients also have skin involvement. These soft blisters occur on normal or reddened, irritated skin. The blisters pop easily, resulting in painful sores that bleed. While any area of the skin may be affected, the palms and soles are usually not.

Blistering may be accompanied by severe pain, itching, burning, and stinging. If extensive, blistering can lead to life-threatening fluid loss, infection, and disfigurement. PV can also cause significant damage to the skin, including nail loss and pigmentary alteration, making timeliness of intervention and treatment essential to prevention of disability.

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Pemphigus Foliaceus

 Key features: Skin involvement only with blisters caused when autoantibodies attack desmoglein 1

Clinical variants: Endemic pemphigus foliaceus (fogo selvagem), pemphigus erythematosus (Senear-Usher syndrome), pemphigus herpetiformis

• Pain or burning sensations frequently accompany the cutaneous lesions.

• Systemic symptoms are usually absent.

• The clinical manifestations of drug-induced pemphigus foliaceus are similar to idiopathic disease.

Pemphigus foliaceous is superficial with skin lesions. The mucous membranes are typically not affected.

Pemphigus foliaceous usually affects the scalp, face, toros, and/or armpits. The skin lesions usually are small, scattered blisters that rapidly evolve into scaly, crusted erosions. The Nikolsky sign often is present. The skin lesions may remain localized or may join to cover large areas of skin. Occasionally, pemphigus foliaceous may encompass the entire skin surface as an abnormal redness.

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Mucous Membrane Pemphigoid

 Mucous membrane pemphigoid (MMP) is a chronic autoimmune disorder characterized by blistering lesions that primarily affect the various mucous membranes of the body, but also affects the skin (MMP is now the preferred term for lesions only involving the mucosa). It is also known as Cicatricial Pemphigoid (CP), as it is often scarring.

The mucous membranes of the mouth and eyes are most often affected, but those of the nose, throat, genitalia, and anus may also be affected. The symptoms of MMP vary among affected individuals depending upon the specific site(s) involved and the progression of the disease. Disease onset is usually between 40 and 70 years and oral lesions are seen as the initial manifestation of the disease in about two thirds of the cases. Blistering lesions eventually heal, sometimes with scarring. Progressive scarring may potentially lead to serious complications affecting the eyes and throat.

There is no racial or ethnic predilection, although most studies have demonstrated a female to male ratio of approximately 2:1. The diagnosis of MMP is mainly based on history, clinical examination and biopsy of the lesions.

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 Pemphigoid Gestationis

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis of pregnancy. The disease was originally named herpes gestationis on the basis of the morphological herpetiform feature of the blisters, but this term is a misnomer because PG is not related to or associated with any active or prior herpes virus infection. PG typically manifests during late pregnancy, with an abrupt onset of extremely pruritic urticarial papules and blisters on the abdomen and trunk, but lesions may appear any time during pregnancy, and dramatic flares can occur at or immediately after delivery. PG usually resolves spontaneously within weeks to months after delivery.

Pemphigoid Gestationis:

• Is a condition of pregnancy (childbearing age women).

• In the United States, PG has an estimated prevalence of 1 case in 50,000-60,000 pregnancies.

• No increase in fetal or maternal mortality has been demonstrated, although a greater prevalence of premature and small-for-gestational-age (SGA) babies is associated with PG.

• Patients with PG have a higher relative prevalence of other autoimmune diseases, including Hashimoto thyroiditis, Graves disease, and pernicious anemia.

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Epidermolysis Bullosa

Epidermolysis Bullosa (EB) is a rare disease whereby the skin blisters and peels at the slightest touch. Living with EB has been likened to living with third degree burns. It is very painful, and sufferers must be bandaged every day with dressings to protect and medicate their wounds.

EB is characterised by skin fragility with blister formation occurring spontaneously or following minor trauma. EB can be broadly divided into four major categories: Simplex, Junctional, Dystrophic and Kindler Syndrome. These categories can be further subtyped based on inheritance and clinical features.

It is estimated that there are around 1,000 people in Australia who have some form of EB and over 500,000 worldwide. It occurs in all racial and ethnic groups and affects males and females equally. EB may not always be evident at birth. Milder cases of EB may become apparent when a child crawls, walks, runs or when young adults become more physically active. Patients living with EB are faced with daily challenge, as no cure exists and current therapies under development have faced both safety and technical challenges. EB is an area of unmet medical needs with current management focusing on relieving patient pain, stopping infections and providing dressings which are passive and do not address the symptoms associated with EB including severe scarring, infections and development of squamous cell carcinoma. Urgent research is needed to develop therapies that address these symptoms and for that we need your funding support.

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