What is pemphigus vulgaris?
Pemphigus vulgaris is a rare autoimmune disease that is characterised by blisters and erosions on the skin and mucous membranes, most commonly inside the mouth. It is the most common subtype of pemphigus, accounting for 70% of all pemphigus cases worldwide although it is extremely rare in New Zealand (about one case per million). The other two main subtypes of pemphigus are pemphigus foliaceus and paraneoplastic pemphigus.
What causes pemphigus vulgaris?
Pemphigus vulgaris is an autoimmune blistering disease, which basically means that an individual's immune system starts reacting against his or her own tissue.
The building block cells of the epidermis are called keratinocytes. These cells are cemented together at special sticky spots called desmosomes. In pemphigus vulgaris immunoglobulin type G (IgG) autoantibodies bind to a protein called desmoglein 3, which is found in desmosomes in the keratinocytes near the bottom of the epidermis. The result is the keratinocytes separate from each other, and are replaced by fluid, the blister.
Who gets pemphigus vulgaris?
Pemphigus vulgaris affects people of all races, age and sex. It appears most commonly between the ages of 50-60 years, and is more common in Jews and Indians presumably for genetic reasons.
What are the signs and symptoms of pemphigus vulgaris?
Most patients first present with lesions on the mucous membranes such as the mouth and genitals. Several months' later blisters on the skin may develop or in some cases mucosal lesions are the only manifestation of the disease.
The most common mucosal area affected is the inside of the mouth but others include the conjunctiva, oesophagus, labia, vagina, cervix, penis, urethra and anus. Common features of oral mucosal pemphigus include:
- 50-70% of patients get oral lesions
- blistering superficial and often appears as erosions
- widespread involvement in the mouth
- painful and slow to heal
- may spread to the larynx causing hoarseness when talking
- may make it difficult to eat or drink
Skin lesions appear as thin walled flaccid blisters filled with clear fluid that easily rupture causing painful erosions. Erosions in the skin folds may develop into vegetative lesions which are granular and crusty looking (known as pemphigus vegetans).
Tests for pemphigus vulgaris
Diagnosis generally requires a skin biopsy, which shows typical features of rounded-up separated keratinocytes (called acantholytic cells) within the blisters just above the basal layer of the epidermis. Suprabasal clefting may be reported. See pathology of pemphigus vulgaris.
Pemphigus is confirmed by direct immunofluorescence staining of the skin biopsy sections to reveal antibodies.
In most cases, circulating antibodies can be detected by a blood test (indirect immunofluorescence test). The level of antibodies fluctuates and may reflect the effectiveness of treatment.
The severity of pemphigus can be scored using PDAI: Pemphigus Disease Area Index. For details, see Table 3, Pemphigus Disease Area Index. Other systems described are listed below.2
- PAAS: Pemphigus Area and Activity Score
- PAS: Pemphigus Activity Score
- ABSDIS: Autoimmune Bullous Skin Disorder Intensity Score
- Saraswat oral pemphigus scoring
- Pemphigus vulgaris lesion severity score
- Harman pemphigus grading
- Kumar scoring system
- Mahajan scoring system
Treatment of pemphigus vulgaris
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%). They are not a cure for the disease but improve the patient's quality of life by reducing disease activity. Unfortunately higher doses of corticosteroids may result in serious side effects and risks. Other immune suppressive drugs are used to minimise steroid use. These include:
- Mycophenolate mofetil
- Intravenous immunoglobulin
- The TNFα inhibitor, infliximab
- Anti-CD20 monoclonal antibody (rituximab)
At optimal therapy patients may still continue to experience mild disease activity.
Appropriate wound care is particularly important, as this should promote healing of blisters and erosions.
Patients should minimize activities that may traumatise the skin and mucous membranes during active phases of the disease. These include activities such as contact sports and eating or drinking food that may irritate or damage the inside of the mouth (spicy, acidic, hard and crunchy foods).
There is future hope that future treatment for pemphigus will be more specific with fewer side effects. Investigators have engineered specific chimeric autoantibody receptor T-cells to eliminate Desmoglein-3-specific B cells in mice.