Pemphigus vulgaris

Overview

Pemphigus is a group of rare skin disorders that cause blisters and sores on the skin or mucous membranes, such as in the mouth or on the genitals.

The two main types are pemphigus vulgaris and pemphigus foliaceus. Pemphigus vulgaris usually starts in your mouth. It can be painful. Pemphigus foliaceus affects the skin and tends to be more itchy than painful. Pemphigus can occur at any age, but it's most often seen in people who are middle-aged or older.

Pemphigus is not to be confused with bullous pemphigoid, another blistering skin condition. Usually a chronic condition, pemphigus is best controlled by early diagnosis and treatment. Treatment may include medications and therapies similar to those used for severe burns.
Symptoms & causes

 

Pemphigus vulgaris is an autoimmune disorder that involves blistering of the skin and mucous membrane. The blisters, which usually begin on your face and scalp and later erupt on your chest and back, usually aren't painful. They tend to be crusty and itchy. It occurs almost exclusively in middle-aged or older people. Many cases begin with blisters in the mouth, followed by skin blisters that may come and go. In most cases, the exact cause of pemphigus vulgaris is unknown.It has rarely been observed in multiple members of the same family.

Symptoms

Signs and symptoms for Pemphigus vulgaris are:

  • Abnormal blistering of the skin
  • Abnormality of the oral cavity
  • Acantholysis
  • Atypical scarring of skin
  • Autoimmunity
  • Feeding difficulties in infancy
  • Dysphagia
  • Recurrent cutaneous abscess formation
  • Urticaria
  • Weight loss
  • Abnormality of metabolism/homeostasis
  • Autosomal dominant inheritance

Lesions also may occur in the upper esophagus. Cutaneous bullae typically arise from normal-appearing skin, rupture, and leave a raw area and crusting. Itching is usually absent. Open skin lesions often become infected. If large portions of the body are affected, fluid and electrolyte loss may be significant.

Causes

Pemphigus vulgaris is an autoimmune disorder. The immune system produces antibodies against specific proteins in the skin and mucous membranes. These antibodies create a reaction that cause skin cells to separate. The exact cause is unknown.

Although it is rare, some cases of pemphigus vulgaris are caused by certain medications. Medications that may cause this condition include:

  • Blood pressure medications called ACE inhibitors
  • Chelating agents such as penicillamine, which remove certain materials from the blood

While in many cases the exact cause of pemphigus vulgaris remains unknown, several potentially relevant factors have been identified.

Diagnosis

Because it is a rare disease, diagnosis is often complicated and takes a long time. Early in the disease patients may have erosions in the mouth or blisters on the skin. These blisters can be itchy or painful. Theoretically, the blisters should demonstrate a positive Nikolsky's sign, in which the skin sloughs off from slight rubbing, but this is not always reliable. The gold standard for diagnosis is a punch biopsy from the area around the lesion that is examined by direct immunofluorescent staining, in which cells are acantholytic, that is, lacking the normal intercellular connections that hold them together. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein desmoglein.

Pemphigus vulgaris is easily confused with impetigo and candidiasis. IgG4 is considered pathogenic. The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to antibiotic treatment. Eosinophils tend to be found within the blisters and provide an important clue supporting bullous pemphigoid as the diagnosis.

Two physical signs in pemphigus vulgaris are helpful:

  • Lateral pressure on skin adjacent to a blister causes epidermal detachment (Nikolsky's sign).
  • Pressure on a blister can cause the blister to extend to adjacent skin (Asboe-Hansen sign).

 

  • Biopsy with direct immunofluorescence testing
  • Serum antibodies (eg, to desmoglein-3) can be used for diagnosis and for differentiating from pemphigus foliaceus; serial titers can help follow disease activity.

Prognosis

Before systemic corticosteroids were used, pemphigus vulgaris was usually fatal; most patients died within 5 yr of disease onset. Even with treatment, pemphigus vulgaris is a serious disease with an inconsistent and unpredictable response to treatment, a prolonged course, and virtually inevitable adverse drug effects.

Treatment

Treatment is aimed at reducing symptoms and preventing complications. Severe cases are treated similarly to severe burns

  • Corticosteroids, oral or IV
  • Sometimes immunosuppressants
  • Sometimes plasmapheresis and IV immunoglobulin (IVIG)

The primary aim of treatment is to decrease blister formation, prevent infections and promote healing of blisters and erosions. Oral corticosteroids are the mainstay of medical treatment for controlling the disease. Since their use, many deaths from pemphigus vulgaris have been prevented (mortality rate dropped from 99% to 5-15%) Systemic corticosteroid therapy is effective in reducing or eliminating the clinical manifestations of pemphigus vulgaris, although doses of prednisone may have to be as high as 400 mg. daily for patients with severe involvement. Topical corticosteroids can be used as an adjunct therapy if the bullae are confined to oral mucosa. Glucocorticoids 2 to 3 mg/kg of body weight of prednisone until cessation of new blister formation and disappearance of Nikolsky's signs. Then rapid reduction to about half the initial dose until patient is almost clear, followed very slow tapering of dose to minimal effective maintenance dose. Clinical, for improvement of skin lesions and development of drug-related side effects. Laboratory monitoring of pemphigus antibody titers and for hematologic and metabolic indicators of glucocorticoid- and/or immunosuppressive-induced adverse effects.

Resources

  • NIH
  • Mayo Clinic