Granulomatosis with polyangiiti

Granulomatosis with polyangiitis (GPA) is a rare disease which causes the walls of the blood vessels to become inflamed (swollen).

It's a serious condition that can eventually lead to tissue damage and organ failure and can be fatal if left untreated.

However, there are effective treatments which mean most people can live relatively normal lives with the condition.

Until recently, GPA used to be called Wegener's granulomatosis.

Signs and symptoms

The inflammation of the blood vessels (known as vasculitis) caused by GPA mainly affects the nose, sinuses, ears, lungs and kidneys, although other organs can be affected too, including the brain, skin, nerves, heart and bowels.

This means the condition can have a wide range of symptoms, such as:

• a persistent unexplained fever
• night sweats
• fatigue (extreme tiredness) and weakness
• a general ill feeling
• loss of appetite and weight loss
• joint pain and soreness
• persistent ear infections and reduced hearing
• frequent sinusitis
• recurrent nosebleeds and crusts around the nose
• chest pain, cough and shortness of breath
• coughing up blood or blood in the phlegm
• blood in the urine

Some people with GPA may also be at risk of developing blood clots in their legs (deep vein thrombosis) or lungs (pulmonary embolism).

When to seek medical advice

If you have any of the above symptoms that are persistent or troublesome see your GP. They can arrange appropriate tests if they suspect GPA is the cause and, if appropriate, arrange referral to a specialist centre for treatment.

If you have been diagnosed with GPA and suddenly develop any of the above symptoms, see your GP immediately because you are probably experiencing a relapse (return of the condition).

What causes GPA?

The exact cause of GPA is unknown. It is thought that GPA is likely to be an autoimmune disease, which means the body's immune system mistakenly attacks its own tissues.

As with other autoimmune disorders, it's probable that people with GPA have a gene that makes them more likely to develop the condition. GPA is then probably triggered by an additional factor, such as an infection with bacteria or a virus.

Genes alone are not responsible for the condition, as it's very unusual for GPA to occur in two people in the same family.

Who is affected

Around 500 men and women are diagnosed with GPA each year in the UK.

Symptoms can start at any age, including in childhood, although the condition usually first appears in middle-aged or elderly people.

How GPA is diagnosed

Your doctor may suspect GPA if you feel unwell, have a persistent fever and have lost weight, and one or more of the following areas of your body is affected:

• your nose, ears and sinuses – for example, you have persistent earache, nosebleeds or sinusitis
• lungs – for example, you have difficulty breathing or are coughing up blood, or your chest X-ray shows lung abnormalities
• kidneys – for example, there is blood or protein in your urine

Blood tests may be done to test levels of ANCAs (antineutrophil cytoplasmic antibodies). These are antibodies thought to be involved in the process that leads to the blood vessels becoming inflamed.

However, this test can sometimes come back negative in people with GPA and positive in people who don’t have the condition, so it can't be relied upon on its own to diagnose the condition.

A tissue sample of the affected area may also be removed (a biopsy) and looked at under the microscope for evidence of inflammation. In GPA, white blood cells clump together to form tiny lumps called granulomas.

Computerised tomography (CT) scans and magnetic resonance imaging (MRI) scans may also be carried out to assess the condition of any organs or areas of the body that may be affected.

How GPA is treated

The aim of treatment for GPA is firstly to bring the condition under control (known as inducing remission), and then try to prevent the condition relapsing (known as maintaining remission).

For most people, this can be achieved using a number of different medications, which may need to be taken for a number of years. Medication administration is supervised through specialist centres in close liaison with your GP and is tailored to each individual patient.

Inducing remission

To begin with, you will usually need high doses of medication to dampen down your immune system and bring the inflammation under control.

Typically, you will be given a steroid medication called prednisolone to reduce the inflammation in addition to a medication called cyclophosphamide, which weakens your immune system.

Steroid medication is either given intravenously alongside this, or is taken by mouth (orally) on a daily basis.

Cyclophosphamide is normally given intravenously (directly into a vein) every two to three weeks.

In milder cases, an alternative oral immune-suppressing medication called methotrexate may be given instead of cyclophosphamide.

This treatment will continue – with your steroid dose gradually reduced over time – until you achieve remission, which in most people takes around three to six months.

Cyclophosphamide and steroids are powerful medications, so make sure you discuss the possible side effects with your doctor. Read more about the side effects of steroid medication.

Maintaining remission

Once remission is achieved, your treatment with cyclophosphamide will be stopped and you will be given a milder immune-suppressing medication such as methotrexate or azathioprine.

Your steroid medication may also be stopped, or you may continue taking it at a low dose.

This stage of treatment will usually last between two and five years and will also involve frequent check-ups to look for signs of a relapse.

Other treatments

Although the medications described above are effective for most people, some people with GPA will need alternative or additional treatment.

For example, you may be given long-term treatment with antibiotics alongside your other medications to prevent potentially serious infections, as the medications used to treat GPA can increase your chances of picking up an infection.

If you have severe GPA, cyclophosphamide is not suitable for you, or your condition relapses despite therapy, you may be offered a medication called rituximab instead. This medication works by destroying certain cells produced by the immune system that are thought to play a role in the inflammation of the blood vessels.

In particularly severe cases affecting the kidneys, a procedure called plasma exchange (plasmapheresis) may be recommended. 

During this procedure, you will be connected to a machine that removes some of your blood. A blood component called plasma will then be separated from the blood cells and removed, before the remaining blood cells are returned to your body. This process can remove some of the antibodies thought to contribute to the inflammation in GPA.

Once the disease is under control, some people may also need surgical treatment. For example, surgery may be needed to correct any nose deformities, narrowing of the airways or obstruction of the tear ducts that can occur as a result of the tissue damage caused by GPA.

If damage to the kidneys means they are no longer able to work properly, a kidney transplant may be needed.

Outlook

Although GPA can be life-threatening, early diagnosis and modern treatments can significantly improve the outlook.

Most people are able to achieve remission with medical treatment, although about half of people with GPA will have a relapse at some point. This usually happens within a few years of stopping treatment.

If you do have a relapse, you will usually need to start taking medication again or increase the doses of any medication you are already taking.

Most people with GPA are able to lead normal lives, although – in addition to taking medication regularly – you will need to have regular check-ups to monitor your progress and check for signs of a relapse.

Complications, if they occur, are often the result of a delay in diagnosis and a lack of treatment. If left untreated, people with GPA may develop severe inflammation in the respiratory tract and kidneys, which can eventually lead to life-threatening lung and kidney failure.