Wegener's Granulomatosis - Granulomatosis with Polyangiitis
Wegener's granulomatosis, also called granulomatosis with polyangiitis, is a vasculitis of autoimmune origin, that is, a disease that occurs with diffuse inflammation of the blood vessels of the body, caused by the inappropriate production of autoantibodies and, in ultimately leads to a restriction of blood flow in the affected organs.
Wegener's granulomatosis is an uncommon disease, affecting 1 in 30,000 people, which affects the whole body, but mainly attacks the blood vessels of the kidneys, lungs and respiratory tracts. The inflammation caused by the disease produces a type of inflammatory tissue called a granuloma, a kind of microscopic tumor in the form of granules. Hence the name Wegener's granulomatosis. The granulomas destroy the vessels, prevent the blood supply to the organs and cause necrosis of the affected tissues.
Wegener's granulomatosis is an autoimmune disease, that is, the inflammation of the vessels is caused by a disorder in our immune system that ends up attacking our vessels inappropriately. The reason that this deregulation of the immune system occurs, causing our body to begin to self-destruct, is still unknown.
Wegener's granulomatosis can occur at any age, but mainly affects individuals between 30 and 50 years. It is more common in whites than in blacks and occurs more in men than in women.
Wegener is a very serious disease, which if untreated, has a very high mortality rate. Before the advent of more modern treatments with immunosuppressants, the median survival was only 5 months, and 90% of the patients died with less than 1 year of diagnosis.
The clinical picture varies greatly from patient to patient. Some have disease restricted to a single organ while others may have a very dramatic multi-systemic condition.
Wegener's granulomatosis usually begins indolently, with mild and nonspecific symptoms such as tiredness, loss of appetite, low fever and dismay. The first specific symptoms usually occur in the upper airways with rhinitis and sinusitis. The picture may resemble that of a flu, but the duration of the symptoms is much greater.
After a mild start, vasculitis shows a rapid worsening of symptoms. Sinusitis worsens and does not respond to any conventional treatment. Nasal discharge may become bloody and deformities and ulcerations in and out of the nasal cavity may arise.
Wegener's lung injury
The involvement of the lung in Wegener's granulomatosis is typical. Up to 1/3 of the patients with pulmonary lesion present a mild condition. The other 2/3, however, suffer from a more serious illness.
The main symptoms of Wegener's pulmonary vasculitis are coughing, shortness of breath and expectoration with streaks of blood. In 5% to 10% of cases, vasculitis of the airways is very serious and leads to a large pulmonary hemorrhage with a massive expectoration of blood.
In the photo beside it is possible to see a lung with necrosed ulcers caused by the vasculitis of Wegener's granulomatosis.
If left untreated the lung injury can be fatal.
Wegener's kidney damage
The kidneys are other organs often affected by Wegener's granulomatosis. The typical lesion is a necrotizing glomerulonephritis.
The clinical picture of Wegener's glomerulonephritis is characterized by acute renal failure, manifested by a rapid and sudden elevation of creatinine associated with arterial hypertension and hematuria (blood in the urine).
Renal vasculitis leads to destruction of the functioning tissue of the kidneys, and if not treated in time, makes the patient dependent on hemodialysis.
The simultaneous involvement of the kidneys and lungs, called the lung-kidney syndrome, is not uncommon. Whenever a patient presents with bloody expectoration associated with hematuria or sudden elevation of creatinine, Wegener's granulomatosis is one of the main differential diagnoses.
Other lesions of Wegener's granulomatosis
In addition to respiratory and renal symptoms, Wegener's granulomatosis can still affect several other organs:
Vasculitis of the skin may manifest as blisters, rashes, ulcers and bleeding
Through blood tests it is possible to detect a typical Wegener autoantibody, called anti-neutrophil cytoplasmic antibody, or simply ANCA. The presence of this autoantibody is important for the diagnosis since it is present in up to 90% of the cases, but alone it is not enough.
Close the Wegener's diagnosis requires a biopsy, removal of a piece of affected tissue for microscopic evaluation. Nasopharyngeal or skin biopsies are easier to perform, but there is not always visible lesion to get samples. Often it is necessary to use a more invasive procedure to perform lung or kidney biopsies.
As it is a disease of immune origin and potentially very serious, the treatment is made on the basis of strong immunosuppressants. There is no cure for Wegener, however, the natural history of the disease has changed a lot in the last 20-30 years.
The main drugs used are high-dose corticosteroids and cyclophosphamide. Other drugs that may also be used are azathioprine, leflunomide, methotrexate, or rituximab.
The use of the antibiotic Bactrim, for reasons not yet well understood, also seems to help in the control of the disease, besides preventing opportunistic infections by immunosuppression.
In severe cases with rapid loss of renal function and pulmonary hemorrhage, plasmapheresis is indicated for the immediate removal of excess circulating autoantibodies.
With current immunosuppressive drugs, about 75% of patients can achieve complete remission of the disease. Of these, 30% present relapses over time, requiring a return of immunosuppression. If more than 90% of patients died in the first year, mortality in 5 years is less than 20%.
