Information for Patients

Pemphigus is a group of potentially life-threatening disorders characterized by blisters in mucous membranes and skin. The blistering in pemphigus happens because of an immune response resulting in autoantibodies attacking the “glue” that holds mucous membranes or skin cells together. This process is called “acantholysis” and is not fully understood. Pemphigus patients develop mucosal erosions and/or blisters, erosions, or small bumps that fill with pus or fluid.

The four major types of pemphigus include pemphigus vulgaris, pemphigus foliaceus, IgA pemphigus, and paraneoplastic pemphigus. The most common form of pemphigus is pemphigus vulgaris; however, in some areas of the world, pemphigus foliaceus is more prevalent. Pemphigus vulgaris is generally more severe than pemphigus foliaceus. Pemphigus vulgaris usually involves a lot of blisters and erosions. In pemphigus foliaceus, blistering is more superficial than pemphigus vulgaris.

The different forms of pemphigus are distinguished by their clinical features, associated autoantigens, and laboratory findings. Benign familial pemphigus, or Hailey-Hailey, is a genetic condition caused by cell mutation. It is not autoimmune like the other forms mentioned.

A pemphigus diagnosis is based on consistent clinical, histological, and direct immunofluorescence findings where autoantibodies are against cell surface antigens. Laboratory studies help distinguish pemphigus from other blistering and erosive diseases.

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.

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.

Key features: Grouped blisters with crusts in the epidermis when autoantibodies attack desmocollin 1

Subtypes: Subcorneal pustular dermatosis-type IgA pemphigus (Sneddon-Wilkinson disease), intraepidermal neutrophilic IgA dermatosis

  • The subcorneal pustular dermatosis type of IgA pemphigus is clinically similar to Sneddon-Wilkinson disease.
  • Immunofluorescence studies are necessary to distinguish these diseases.

IgA pemphigus is characterized by “pimples” or blisters. The vesicles and pustules are usually, but not always, accompanied by patches of redness. A herpes, ring-shaped, or circular pattern may be present.

The trunk and nearby extremities are common sites for IgA pemphigus. The scalp, the skin in and around the ear, and skin-on-skin areas are less common sites. A desire to itch may or may not be present. Mucous membranes are usually not affected.

Key features: Extensive oral and skin blistering associated with underlying malignancies when autoantibodies weaken cell adhesion and inflammatory cells infiltrate the skin, damaging the structure of adjacent cells

  • Life-threatening lung involvement consistent with bronchiolitis obliterans also may be seen.
  • Paraneoplastic pemphigus is the rarest form of the pemphigus types.

Paraneoplastic pemphigus is an autoimmune multi-organ syndrome associated with neoplastic disease. Typically, patients suffer from severe and critical mucosal involvement with extensive, stubborn inflammation of the mucous linings. The skin indicators vary, and include blisters, erosions, and lichen-type lesions that may resemble other autoimmune blistering diseases, erythema multiforme, graft versus host disease, or lichen planus.

Pemphigus vulgaris is the most common form of pemphigus and occurs all over the world. Its frequency is influenced by geographic location and ethnicity. Pemphigus vulgaris occurs between 0.1 and 2.7 per 100,000 people per year. Studies have found certain populations (e.g., people of Jewish ancestry, particularly Ashkenazi Jews, and inhabitants of India, Southeast Europe, and the Middle East) are at a greater risk for pemphigus vulgaris.

In some places (e.g., North Africa, Turkey, and South America), pemphigus foliaceous is more common than pemphigus vulgaris.

Typically, pemphigus vulgaris and nonendemic pemphigus foliaceous typically occur in adults between 40-60 years old. Pemphigus is pretty rare in children (except for endemic pemphigus foliaceous, which affects children and young adults in endemic areas). Neonatal pemphigus is a rare form of pemphigus that happens when an affected mother’s autoantibodies are transferred to the fetus.

Some studies indicate women in Tunisia are four times more likely to have pemphigus foliaceous than men. However, one study identified a 19:1 ratio of males to females in an one location in Columbia.

Epidemiological information on IgA pemphigus is limited. It may occur at any age and might be more common in females. Paraneoplastic pemphigus is very rare and more common in middle-aged adults, but some children have been diagnosed with it.

Why autoantibodies attack cell adhesion is still intensively debated. Several reasons have been proposed, including events that cause cell separation and damage to adhesive molecule function. One theory suggests acantholysis results from autoantibody-caused disruption of cellular signals leading to a cell’s structural collapse and shrinkage.

Autoantibodies that attack a variety of cell surface antigens have been identified in patients with pemphigus.

Desmogleins are the antigens most studied in pemphigus vulgaris and pemphigus foliaceous. Desmogleins are components of desmosomes, key components for cell-to-cell adhesion.

Like other autoimmune diseases, what causes the pemphigus diseases is not really understood. Researches believe genetic and environmental factors may influence the diseases.

Some suggest that ultraviolet radiation could lead to pemphigus foliaceous and pemphigus vulgaris activity. Pemphigus has even developed following burns or electrical injury. Others have suggested viral infections, certain food compounds, ionizing radiation, and pesticides may trigger or worsen the disease.