Granulomatosis with Polyangiitis (GPA)

February 2, 2017

Granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis, is a multisystem systemic necrotising non-caseating granulomatous vasculitis affecting small to medium sized arteries, capillaries and veins, with a predilection for the respiratory system and kidneys.

What is Vasculaties? Vasculitis is a general term that refers to inflammation of the blood vessels. When inflamed, the blood vessel may become weakened and stretch forming an aneurysm, or become so thin that it ruptures resulting in bleeding into the tissue. Vasculitis can also cause blood vessel narrowing to the point of closing off the vessel entirely. This can cause organs to become damaged from loss of oxygen and nutrients that were being supplied by the blood.

Granulomatosis with polyangiitis (Wegener’s) is believed to be an autoimmune disorder. This means the body’s immune defenses mistakenly attack the body’s own cells and tissues. In this case, the misdirected immune attack is aimed at the blood vessels. This triggers inflammation and damage.

In this disorder, small-sized blood vessels in the nose, sinuses, ears, lungs and kidneys become inflamed and damaged. Other areas may also be affected in some cases. It can also produce a type of inflammatory tissue known as a granuloma that’s found around the blood vessels. Granulomas can destroy normal tissue.

Three areas in the body are affected most commonly –

Upper airways (including the sinuses, trachea and nose) – In the upper airways, tissue destruction causes chronic (long-lasting) nasal and sinus problems. Many people with Granulomatosis with polyangiitis (Wegener’s) first see their doctors because of sinusitis, persistent runny nose or frequent bloody nose.
Lungs – In most people with Granulomatosis with polyangiitis (Wegener’s), inflammation targets the lungs as well. This causes a respiratory illness. Symptoms include coughing, shortness of breath, wheezing or coughing up blood.
Kidneys – Kidney damage affects most people with Granulomatosis with polyangiitis (Wegener’s). But in many cases, this damage is mild and does not cause any symptoms. In some people, however, the kidney damage is more severe. It may cause kidney failure.

Wegener’s granulomatosis is most common in middle-aged adults, with an average age of onset between 40 and 65 years. It is rare in children, but has been seen in infants as young as 3 months old. Whites are more likely than blacks to develop Wegener’s granulomatosis.

Causes

Experts do not know what causes Wegener’s granulomatosis. Most agree that it develops as a result of an initial inflammation-causing event that provokes an abnormal immune system reaction, leading to inflamed and constricted blood vessels and granulomas (inflammatory tissue masses).

Many scientists tend to believe that an initial infection may be the start of the whole event. Studies have shown that about 50% of patients with Wegener’s granulomatosis had an infection. Some people believe that there may be other contributory factors, such as:

Environmental toxins
A genetic predisposition
A combination of both

Risk Factors

According to one estimate, the frequency of Wegener’s granulomatosis is one in 30,000 to 50,000 individuals in the United States. However, because cases of Wegener’s granulomatosis often go unrecognized, the disorder is under-diagnosed making it difficult to determine its true frequency in the general population. Wegener’s granulomatosis predominately affects Caucasians.

Granulomatosis with polyangiitis can occur at any age. It most often affects people between the ages of 40 and 65.

Symptoms

Sinus and lung symptoms are most common in GPA. Other early symptoms include fever, night sweats, fatigue and a general ill feeling (malaise). For some people, the disease is limited to the respiratory system and doesn’t involve the kidneys. Kidney involvement usually doesn’t cause symptoms early in the course of the disease. It may be detected only by blood and urine tests. Over time, kidney failure and anemia often occur.

Wegener’s granulomatosis signs and symptoms can develop either gradually or suddenly. Initial symptoms can vary widely, and diagnosis may sometimes be delayed because of their non-specific nature. The first symptom in most patients is rhinitis – runny and stuffy nose.

Signs and symptoms may include –

Sinus pain and inflammation
Runny nose, with pus-filled discharge
Nosebleeds
Fever
General ill feeling (malaise)
Unintended weight loss
Ear infections
Cough
Chest pain
Coughing up blood
Shortness of breath
Joint aches and swelling
Blood in urine
Skin sores
Eye redness, burning or pain

Other common symptoms include –

Lungs – breathlessness, wheeze, dry cough or coughing up blood
Skin – rashes, ulcers, and necrosis (death of tissue)
Eyes – red (blood shot) eyes, painful, dry or gritty eyes, visual loss or other changes in vision
Nerves – loss of sensation, weakness, unusual painful symptoms in the hands and feet (hotness, pins and needles or “electric shocks”) and rarely paralysis or stroke
Bowels – Diarrhoea, bleeding and abdominal pain.

Complications

Complications most often occur when the disease is not treated. People with GPA develop tissue damage in the lungs, airways, and the kidneys. Kidney involvement may result in blood in the urine and kidney failure. Kidney disease can quickly get worse. Kidney function may not improve even when the condition is controlled by medicines. If untreated, kidney failure and possibly death occur in most cases.

Other complications may include –

Eye swelling
Lung failure
Coughing up blood
Nasal septum perforation (hole inside the nose)
Side effects from medicines used to treat the disease

Treatment

Medications –

Corticosteroids – such as prednisone may be prescribed for initial signs and symptoms. In a few cases this is the only medication needed.
Other immunosuppressive drugs – such as cyclophosphamide (Cytoxan), azathioprine (Imuran) or methotrexate (Rheumatrex) is prescribed as well in most cases. The aim is to stop the body’s immune system from overreacting.
Rituximab (Rituxan) – this medication, which was originally designed to treat non-Hodgkin’s lymphoma (a type of cancer), was later approved for rheumatoid arthritis treatment. Rituximab reduces the number of B cells in the body – B cells are involved with inflammation. If standard treatments are not effective some doctors may prescribe Rituximab.

Surgery – if the Wegener’s granulomatosis patient has suffered kidney failure the doctor may recommend a kidney transplant.

Alternative Treatment

Reference –

http://www.uveitis.org/docs/dm/wegeners_granulomatosis_diagnosis_management.pdf

http://www.encyclopedia.com/topic/Wegeners_Granulomatosis.aspx

http://www.medicalnewstoday.com/articles/187807.php

http://www.mayoclinic.org/diseases-conditions/granulomatosis-with-polyangiitis/home/ovc-20167226

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/wegeners-granulomatosis

http://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/vasculitis/granulomatosis-with-polyangiitis-(gpa)

https://umm.edu/health/medical/ency/articles/wegeners-granulomatosis

http://www.myvmc.com/diseases/wegeners-granulomatosis/

http://www.sciencedirect.com/science/article/pii/S0030665713000383