Pemphigus Vulgaris

Pemphigus vulgaris (PV) is a rare and serious condition that causes painful blisters to develop on the skin as well as inside the mouth, nose, throat, anus and genitals.

The blisters are fragile and can easily burst open, leaving painful areas of raw unhealed skin.

The blisters can fade and flare up later, and it is impossible to predict how severe a flare-up might be.

What causes pemphigus vulgaris?

PV is what is known as an autoimmune condition. This means the immune system (the body's defence against infection) malfunctions and starts attacking healthy tissue.

In cases of PV, the immune system attacks cells found in a deep layer of skin as well as the cells found in the mucous membrane (the protective lining of the mouth, nostrils, throat, genitals and anus). This causes blisters to form in the affected tissue.

It is unclear why the immune system goes wrong in this way. PV could be caused by a combination of both genetic and environmental factors. What is known is that PV is not contagious and cannot be passed from one person to another.

Treating pemphigus vulgaris

There is currently no cure for PV, although the symptoms respond well to high doses of steroid medication (corticosteroids).

Using a high dose of steroids over a long period of time can cause serious side effects. When the symptoms have cleared, low doses are used in combination with other medicine. This is known as steroid-sparing therapy, and it prevents some of the dangerous side effects associated with long-term steroid use.

If long-term doses of corticosteroids are not effective, other treatment options may be considered, including:

• other medications, such as azathioprine, mycophenolate mofetil or, very rarely, rituximab infusion
• plasmapheresis
• intravenous immunoglobulin therapy

Complications

A possible complication of PV is the blisters becoming infected. In some cases, infection can quickly spread into the blood (sepsis) and affect the whole body, which can be life threatening.

Other complications include side effects associated with the long-term use of corticosteroids and immunosuppressants.

Who is affected?

PV is a rare condition. It is estimated that around 3 in every 100,000 people are diagnosed with PV.

Most cases first develop in older adults between the ages of 50 and 60, although PV can affect people of all ages, including children. Both sexes are affected equally.

PV is slightly more common in people of Jewish, Indian and Mediterranean descent.

Outlook

The outlook for people with PV has improved significantly since the introduction of steroids, although the complications associated with the condition can be life threatening.

Most people with PV experience flare-ups when symptoms are particularly bad and then periods when they experience no or very few symptoms (this is known as remission). In some people, the symptoms may go away permanently (complete remission).

However, living with a long-term painful condition can be distressing and affect you emotionally.

Aside from medication, there are also steps you can take to help you cope better, such as exercise and relaxation techniques.

The NHS also runs pain management courses designed to help people with long-term painful conditions learn to live with their pain. 

Read more about living with pain.

Causes

Pemphigus vulgaris (PV) is an autoimmune condition. An autoimmune condition causes the body's immune system to attack its own cells and organs by mistake.

Normally, the immune system only responds in this way to an invading germ or substance that it does not recognise, such as a virus or pollen.

In the case of PV, the immune system produces antibodies that damage the cells in the skin and mucous membranes (the lining of the mouth, nose, throat and genitals).

The antibodies attack proteins called desmogleins, which hold the cells together. This causes the cells to fall apart. Fluid-filled blisters or sores then develop in the spaces.

It is not known why some people develop this reaction.

Is PV inherited?

PV is not passed down through families, and it is very unusual for more than one person in a family to have PV.

However, recent evidence suggests that the genes a person inherits from their parents, while not directly causing PV, may make them more susceptible to the disease.

Two genetic mutations (where the instructions found in all living cells become scrambled in some way) called DR4 and DRw4 are common in people with PV.

Most experts believe it also takes an external factor or combination of factors to trigger PV. This could be a bacterial or viral infection, or something in the environment such as a pollutant.

Risk factors

Although PV may develop at any age, the majority of cases develop in people aged between 50 and 60.

PV has also been found to occur alongside certain other autoimmune diseases, such as myasthenia gravis, a rare long-term condition that causes certain muscles to become weak.

Tannins

Researchers in Italy reported in 2011 that a diet rich in tannins could make the symptoms of PV worse.

Tannins are found in a wide range of food and drink. There are particularly high levels of tannins in:

• red wine
• tea
• cherries
• strawberries
• tropical fruit

You may want to try avoiding these types of food and drinks to see if your symptoms improve.

Diagnosing

Because pemphigus vulgaris (PV) is so rare, many GPs have not come across it before.

If your GP suspects PV, you will need to be referred to a dermatologist (skin specialist). They will confirm the diagnosis and prescribe appropriate treatment.

PV should always be suspected in anyone who has sores inside the mouth that do not heal. The mouth is affected in many cases of PV and sores may also be seen in other places, such as the vagina or the skin.

Confirming the diagnosis

The diagnosis of PV can be confirmed by doing a skin biopsy, where a sample of an unbroken blister is sent to a laboratory. The sample is examined under a microscope to see whether the skin cells are breaking apart, which would indicate PV.

To confirm the diagnosis further, a technique called immunofluorescence can be used. In direct immunofluorescence, a skin biopsy is stained with dye to detect PV antibodies in the cells, whereas the levels of PV antibodies in the blood are measured with indirect immunofluorescence.

Coping with a diagnosis

Being told you have a rare chronic disease can be a bewildering, frightening and sometimes lonely experience.

You may want to find out as much as you can about the condition and how best to cope with it.

A good place to start is the Pemphigus Vulgaris Network, which is a UK support group for people with PV.

Treatment

Treatment for pemphigus vulgaris (PV) usually involves taking a combination of two types of medication – steroid medication (oral corticosteroids) and immunosuppressants.

Both of these types of medication can prevent your immune system damaging healthy tissue.

It can take a while to determine the best dose of these medications. There is often a fine balance to successfully controlling symptoms while limiting unpleasant side effects, so it may take some months until this balance can be achieved.

The aim of treatment is:

• to heal the blisters and prevent new ones forming – it usually takes up to eight weeks for the blisters to heal and two to three weeks to prevent new ones forming
• to reduce the medication gradually to the lowest possible dose that will still control the symptoms

Oral corticosteroids (steroid tablets)

Corticosteroids are usually effective at reducing the harmful activity of the immune system in a short space of time.

They contain synthetic versions of hormones that can block some of the chemical reactions of the immune system. By blocking these reactions, further damage to the skin can usually be prevented.

When corticosteroids were first introduced as treatment for PV in the early 1950s, it led to a big fall in the number of deaths from the condition.

First stage

You usually start on a high dose of prednisolone (60-100mg a day). The dose will depend on how serious your condition is.

If you need more than 100mg a day, pulse therapy is an option. Pulse therapy involves high doses of methylprednisolone plus cyclophosphamide through a drip in your arm. The sessions are given three days a month for at least six months.

Some people notice an improvement in their symptoms within days of taking corticosteroids. On average, it takes two to three weeks for the blistering to stop.

Second stage

Once your symptoms have been relieved, your medication is gradually reduced to the lowest possible dose that can still control your symptoms.

The lowest possible dose is used because corticosteroids have a wide range of unpleasant side effects, such as:

• weight gain
• acne
• mood changes – for example, you may become aggressive, irritable and short-tempered
• rapid mood swings – such as feeling very happy one minute and then very sad and weepy the next

Eventually, you may be able to come off corticosteroids altogether if your symptoms have disappeared and do not flare up when treatment is stopped. However, many people will always need to take a low dose of corticosteroids to keep their symptoms under control.

Long-term corticosteroid use increases the risk of developing a range of health conditions, such as:

• weakening of the bones (osteoporosis)
• the onset of diabetes or worsening of existing diabetes
• high blood pressure

Read more about corticosteroids, including how they work and their possible side effects.

Immunosuppressants

As their name suggests, immunosuppressants suppress or "dampen down" the immune system. By combining them with corticosteroids, it is often possible to reduce the dosage of the steroid medication.

This means you are less likely to experience side effects and long-term complications such as osteoporosis. This is known as steroid-sparing therapy.

The most commonly used immunosuppressants in the treatment of PV include:

• azathioprine
• mycophenolate mofetil
• cyclophosphamide

These medications are usually taken in tablet form. If one immunosuppressant does not seem to be effective, another one can be tried.

Immunosuppressants can make you more vulnerable to infection, so you will need to take precautions when taking them, such as:

• avoiding close contact with someone known to have an active infection, especially if it is chickenpox or shingles, as the virus that causes these two infections could make you feel very ill
• if possible, avoiding crowded places
• reporting any possible symptom of infection – such as a high temperature or swelling – to your GP or dermatologist immediately 

In addition, azathioprine can make your skin more vulnerable to the effects of sunlight, so you should wear sunscreen on bright days.

Immunosuppressants are not suitable for pregnant women as they can cause birth defects. If you are a sexually active woman, you should use a reliable method of contraception while taking this type of medication.

Add-on treatments

There are several other treatments that are sometimes used in combination with corticosteroids and immunosuppressants.

These include:

• tetracycline – a type of antibiotic that can be useful in preventing infections
• dapsone – a type of medication that can help prevent blisters becoming infected with bacteria
• colchicine – a medication that can reduce levels of inflammation in the body and help prevent new blisters forming

Rituximab

Rituximab is a new type of medication that works by targeting what are known as B cells. These are a type of white blood cell that the immune system uses to attack healthy skin tissue in cases of PV.

Research published in 2011 concluded that rituximab is an effective alternative in cases where conventional treatment is ineffective or causes serious side effects.

It is usually administered directly into your vein over the course of a few hours. However, it is still unclear what the most effective method of prescribing rituximab is.

Some doctors have tried using it once a week over the course of four weeks. Others have suggested it should be used six times over the course of two months, followed by four more doses once a month. Further research is needed.

It is common to experience flu-like symptoms when you are being treated with rituximab. These can include:

• headache
• fever or chills
• fatigue
• muscle pain

You may be given additional medication to prevent or lessen side effects, although the side effects should improve as your body gets used to the drug.

Current evidence suggests that around 1 in 14 people will experience more serious side effects after taking rituximab, typically an infection such as pneumonia or sepsis (infection of the blood, or blood poisoning).

A practical disadvantage of rituximab is that it is a relatively expensive medication and some clinical commissioning groups (CCGs) may be unwilling to fund treatment.

If you think you could benefit from rituximab, you should discuss this with your dermatologist.

Plasmapheresis and immunoglobulin therapy

Plasmapheresis or intravenous immunoglobulin therapy may be considered if high doses of corticosteroids are not effective.

These treatments are given in hospital and involve:

• plasmapheresis – where your blood is circulated through a machine that removes the plasma containing the harmful antibodies
• intravenous immunoglobulin therapy – where you are injected with normal antibodies from donated blood that temporarily change the way your immune system operates
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Complication

Secondary infections are a common complication of pemphigus vulgaris (PV).

The blisters caused by PV are vulnerable to bacterial infection. This is made worse by most of the medications used to treat the condition, as they weaken the immune system.

Symptoms of an infected blister include:

• the blister or surrounding skin becomes more painful and hot
• the blister is filled with yellow or green pus  
• there are red streaks leading away from the blister

It's important not to ignore an infected blister, as it could potentially lead to secondary impetigo (a contagious bacterial infection of the skin) if it splits open.

This could lead to further complications, such as cellulitis (a bacterial infection of the deeper layers of the skin) or sepsis (a life-threatening infection of the blood).

Contact your GP or dermatologist if you think you may have an infected blister. Antibiotics can be used to treat this complication.

Long-term corticosteroid use

If you are required to take corticosteroids on a long-term basis (more than three months), the side effects can include:

• further weight gain
• thinning skin that can bruise easily
• muscle weakness
• Cushing's syndrome – a combination of fatty deposits that develop in the face (moon face), stretch marks across the body and acne 
• the onset of diabetes or worsening of existing diabetes
• high blood pressure
• glaucoma – an eye condition where fluid gathers inside the eye
• cataracts – an eye condition where cloudy patches develop at the front of the eye
• delayed wound healing
• increased risk of infection

Most of these side effects should improve if you're able to reduce your dosage. However, osteoporosis can be a persistent problem, particularly in older people. 

People who take high doses of corticosteroids on a long-term basis are also at risk of stomach ulcers.

Osteoporosis

Osteoporosis (weakening of the bones) can make you more vulnerable to breaking a bone.

You may be referred for a type of X-ray called a dual energy X-ray absorptiometry (DEXA) scan. This can be used to assess how strong your bones are. 

Your GP can prescribe medication such as calcium and vitamin D supplements to help strengthen your bones. This can compensate for the effects of prednisolone.

Stomach ulcers

To protect against stomach ulcers, you may be prescribed a type of medication called a proton pump inhibitor (PPI). This reduces the amount of acid in your stomach, which will make you less vulnerable to developing stomach ulcers.

You will also probably have regular checks and tests for conditions such as diabetes, high blood pressure and glaucoma if you need to take oral corticosteroids on a long-term basis.

Immunosuppressants and cancer

There is evidence that taking an immunosuppressant on a long-term basis increases your risk of developing cancer, particularly skin cancer.

One study looked at people who were taking immunosuppressants to prevent their body rejecting a kidney transplant. It found that just over half of these people developed cancer, typically 15 years after they began treatment.

However, it is unclear whether a similar risk exists in cases of PV. It may well be the case that you are not required to take an immunosuppressant for 15 years or more.

As a precaution, it is recommended that you:

• quit smoking if you smoke
• avoid exposing your skin to too much sunlight
• never use sunbeds or sun lamps

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