Over several months, Mr. Jones, a 46-year-old insurance agent, gradually developed a low-grade fever, sinus symptoms, and a cough with unintentional weight loss with several weeks of foot numbness.  The tests his doctor ordered revealed a cavity on chest x-ray, deteriorating kidney function, a positive C-ANCA (antineutrophil cytoplasmic antibodies), and granulomatous vasculitis via lung biopsy.  With his accurate diagnosis of Wegener’s granulomatosis, Mr. Jones was successfully treated with Rituximab (Rituxan) IV infusion and corticosteroids.

In 1936, at the University in Breslau, Friedrich Wegener linked symptoms of granuloma and vasculitis of the upper and lower respiratory tract with other tissues, which in 1954, became a definite criterion the disease known as Wegener’s granulomatosis (WG).  When the walls of certain arteries become inflamed, vasculitis occurs due to the fact that the blood vessels become narrowed, inadequately supply oxygen rich blood to tissue, thus making the tissue vulnerable for ischemia and even failure.  Currently, the etiology of WG is still unclear.  It is not common and occurs in approximately 1 in 20,000 to 30,000 people per year, most commonly appearing between the ages of forty to fifty, but possible at any age.

Wegener’s granulomatosis can affect small arteries of many organs.  When the walls of certain arteries become inflamed, vasculitis occurs due to the fact that the blood vessels become narrowed, inadequately supply oxygen rich blood to tissue, thus making the tissue vulnerable for ischemia and even failure.  Note worthily, the onset of WG may be gradual with few symptoms or sudden and vastly severe.  However, about 90% of patients seem to have shown symptoms of recurrent severe sinusitis, that fail to respond to standard therapeutic treatment, inflammation of the ear or eyes with hearing or loss of vision complications, cough, hemoptysis (blood stained spit), fever, weight loss, fatigue, and joint pain. Furthermore, kidney and nerve tissue are also commonly involved (generalized WG).  Some patients can have limited organs involvement such as upper respiratory tract or eye involvement (limited WG).  Prognosis of limited WG is much better than generalized WG.

ANCA are specific antibodies for antigens in cytoplasmic granules and monocyte lysosomes.  These antibodies can be detected with indirect immunofluorescence microscopy.  Two major patterns of staining are present: cytoplasmic ANCA ( c-ANCA) and peri-nuclear ANCA (p-ANCA).  Specific immunochemical assays demonstrate the c-ANCA is mainly antibodies to protein 3, and p-ANCA is antibodies to myeloperoxidase.

ANCA-associated vasculitis is the most common primary systemic small –vessel vasculitis to occur in adult.  ANCA-associated with vasculitis includes Wegener’s granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome.  They have unique clinical manifestations, organ involvement and are associated with different ANCA.  Microscopic polyangiitis is the most common ANCA-associated vasculitis.  The kidney is the most commonly affected organs in 90 percent of patients who have this type of vasculitis.  Patients could present with variable combinations of renal problems, skin rash, cough, hemoptysis or even abdominal pain.  Most patients have positive p-ANCA (MPO-ANCA).  The most common age of onset is 40-60 years and is more common in men.

Compared to 1958, when patients with WG had only an 18% chance of survival, the treatment and outcome of WG has come a long way.  In the 1970’s the biggest milestone in the treatment of WG occurred due to the emergence of cyclophosphamide (Cytoxan), which increased survival dramatically to over 90%.  Currently, based on disease activity and organ involvement, Cytoxan is used to send the WG into remission, while Methotrexate or Imuran can be prescribed for limited WG or later as a maintenance treatment for generalized WG.  Rituximab (Rituxan), a biologic agent, IV infusion weekly for 4 weeks, with corticosteroids, is as effective as Cytoxan to induce remission of WG and microscopic polyangiitis.

Unfortunately, there is no known cure for WG or other ANCA-associated vasculitis.  However, we do know that an early diagnosis and appropriate treatment is effective to induce remission.  Even though relapses are common, they can be caught early for effective treatment.

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