PEMPHIGUS VULGARIS

PEMPHIGUS VULGARIS

PEMPHIGUS VULGARIS is a skin disorder characterized by vesicles that blister on a normal or reddened background of skin.

Pemphigus vulgaris is a rare (1/1000000) autoimmune intraepidermal blistering disease. This disease affects the skin, as well as the mucous membranes and is potentially life threatening. Pemphigus vulgaris is found mainly in people of Ashkenazi Jewish descent and the age of onset if 60 years.

Causes of Pemphigus Vulgaris

    • an autoimmune blistering disease

    • caused by abnormal autoimmune antibodies, IgG, which are produced against a specific component of the skin, desmoglein 3 within the epidermis of the skin

    • this reaction of antibody attacking a component of the skin, leads to the formation of fluid-filled vesicles or larger vesicles called bullae

    Pemphigus Vulgaris usually begins with oral lesions being evident first, then followed by skin blisters months later. The oral lesions are painful erosins that dissect into the oral mucosa. The skin lesions, which are know as large blisters called bullae vary in size from 1-3 cm in diamteter. These may easily rupture. The bullae have a very thin outer membrane which is very fragile. Pressure can cause the bullae to alter shape, with the fluid within the bullae moving deeper into lateral epidermis. These bullae are caused by autoimmune antibodies against intercellular skin proteins, leading to an auto-inflammatory response leading to damage of the skin and accumulation of fluid in the form of bullae and blisters. Nikolsky's sign describes that traction pressure that is applied to the skin will lead to bullae formation. Bullae rupture leads to erosion formation, which can last for months before healing. Healing consists replacing the erosions with brow! n pigmented skin. Scarring however, is rare. Death can occur either from infection of the lesions or from side-effects of prolonged steroid use, which is the treatment of choice. Mortality is around 5-15%.

     

    Picture of pemphigus in a dog, showing extensive ruptured bullae on an erythematous base/inflammed skin.

    Epidemiology of Pemphigus Vulgaris

  • Often effects patients aged 40-60 and of Jeweish or Mediterranean decent

  • Pemphigus is often associated with cancer, and other autoimmune diseases, such as myasthenia gravis

    • Appearance and Body Sites Affected by Pemphigus Vulgaris

  • Body sites affected:

  • mainly effects the MOUTH

  • lesions begin in the mouth, and then move to affect the rest of the body

  • also affects face and scalp

  • chest, armpits, and groin

  • Pressure on skin leads to lesion formation and also the extension of previous lesions

  • Lesions heal without scarring: however, changes in skin colour may be seen after lesions have left

  • May be FATAL if left untreated

    • Diagnosis of Penphigus Vulgaris

    Skin biopsy's usually show intraepidermal bulla, eosinophiul infiltrate and acantholysis, which refers to the separation of epidermal cells. Direct and indirect immunofluorescence, the presence of immunoglobulin G and complement C3 within the affected areas, and antibodies directed against desmoglein 3, a cellular adhesion molecule all aid in diagnosis. Prognosis is usually done by following antibody levels.

    Treatments for Pemphigus Vulgaris

    Treatment is aimed at stopping the formation of blisters. Prednisone is the mainstay of treatment. Adjuvant therapies, that are known to work effectively alongside prednisone in decreasing and suppressive the immune reaction that forms these blisters, includes cyclophosphamide, as well as other immunosuppressive agents. Intralesional steroids has recently been found to be much more effect than systemic treatment.

    • cyclophosphamide

    • prednisone (steroid) is the mainstay of treatment - acts by decreasing the autoimmune response towards the skiin

    • predinsone at a dose of 2-3 mg/kg body weight should be started initially, and then tapered/lowered to 1-1.5 mg/kg to clear the lesions - after, steroids should always be slowly stopped due to there many side effects

    • plasmapheresis - a procedure which removes antibodies within the body, therefore removing the IgG antibodies that are attacking the skin

    UPDATES: RECENT ADVANCES IN PEMPHIGUS VULGARIS CAUSES AND TREATMENTS

    Recently, the role of important immune cells interactions, specifically in the CD40/CD154 interaction have been implicated as a therapeutic mechanism in treating pemphigus. A study by Aoki-Ota et al., the was published in the Journal of Investigative Dermatology, revealed that the CD40/CD154 interaction is essential for pemphigus vulgaris, and that this is the interaction that causes the anti-Desmoglein IgG antibodies from being created. The group further showed that blockade of this interaction holds promise for treatments, through anti-CD154 monoclonal antibodies.

    Miyo Aoki-Ota, Mari Kinoshita, Takayuki Ota et al. Tolerance induction by the blockade of CD40/CD154 interaction in pemphigus vulgaris mouse model. Journal of Investigative Dermatology (2006) 126, 105-113.