What is granulomatosis with polyangiitis?

Granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) is a disease where the blood vessels are inflamed. This is called vasculitis. This inflammation causes damage to the organs of the body by decreasing their blood flow, which destroys their normal tissue. This is called necrosis.
The inflammation damages important organs of the body by limiting blood flow to those organs and destroying normal tissue. The organs afffected most commonly are the lungs and the kidneys.
Granulomatosis with polyangiitis is a disease that can involve any organ system, but specifically affects the upper and lower respiratory tract (nose, sinuses, windpipe and lungs), kidneys, and small blood vessels (capillaries, venules, arterioles and arteries) of the body.

Statistics on granulomatosis with polyangiitis

The disease is uncommon occuring in 0.4 per 100 000 people. Peak incidence is in the fifth decade of life, with an average age at diagnosis of 45 years however, the disease can occur in all age groups.
The male:female ratio is 2:1. The disease occurs mostly in caucasion people.

Risk factors for granulomatosis with polyangiitis

The cause of the disease is unknown, however, there is strong evidence that the disease is of an immunologic mechanism.

Progression of granulomatosis with polyangiitis

The complete syndrome usually quickly progresses to renal failure once the vascular phase begins. Nasal and pulmonary lesions are common in those with limited disease, these individuals may or may not have systemic involvement. These pulmonary lesions can improve or worsen spontaneously.

How is granulomatosis with polyangiitis diagnosed?

Blood tests can help determine diagnosis, and may show low red blood cell count (anaemia), and an elevated white blood cell count which is indicative of inflammation somewhere in the body.
If the kidneys are involved, the patient’s urine can be analysed under a microscope for protein, red blood cells, and structures called red blood cell casts. Blood tests investigating kidney function may be abnormal.
Patients may have a blood test that shows the presence of a type of antibody (a disease-fighting protein) called antineutophilic cytoplasmic antibodies. If this is present in the blood, it is highly indicative of the disease.
A chest x-ray may be performed if the lungs are involved.

Prognosis of granulomatosis with polyangiitis

If left untreated, 90% of patients will die within 2 years of diagnosis. With corticosteroid and cyclosporin treatment the 5-year-survival is 95%.
Causes of death include complications from underlying disease such as myocardial infarction, heart failure, respiratory failure or renal failure or complications from the immunosuppressant treatment given such as infection, malignancy.
Other complications include massive hemoptysis, respiratory failure, acute or chronic renal failure, deafness, blindness and neuropathy.
Early diagnosis and treatment is crucial in order to improve remission rate and avoid kidney disease and complications.

How is granulomatosis with polyangiitis treated?

With the appropriate treatment, the outlook is good for patients with granulomatosis with polyangiitis.
Current treatment consists of a combination of a corticosteroid (prednisone) and a cytotoxic agent. Cyclophosphamide is the drug of choice. Azathioprine is less effective but is a good alternative for those patients who may develop side-effects from cyclophosphamide. Methotrexate can also be used in this case.
After approximately two to three months of treatment, prednisone dose is slowly reduced so that the patient is on cyclophosphamide only. Cyclophosphamide therapy must continue until greater than one year after clinical remission of the disease. After this an alternative drug such as azathioprine or methotrexate can be used.

References

  1. Cotran, R.S., Kumar, V. & Robbins, S.L. 1999, Pathological Basis of Disease, W.B Saunders, Philadelphia.
  2. Kumar, P. & Clark, M. 1999, Clinical Medicine, W.B Saunders, London.
  3. National Institute of Allergy and Infectious Diseases. (June 2003), Wegener’s Granulomatosis, [Online], Available from: http://www.niaid.nih.gov/factsheets/wegerners.htm.
  4. The Merck Manual of Diagnosis and Therapy. (2004), Wegener’s Granulomatosis, [Online], Available from: http://www.merck.com/mrkshared/mmanual/section5/chapter50/50n.jsp