Granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), is a long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels. It is a form of vasculitis (inflammation of blood vessels) that affects small- and medium-size vessels in many organs but most commonly affects the upper respiratory tract and the kidneys. Therefore, the signs and symptoms of GPA are highly varied and reflect which organs are supplied by the affected blood vessels. Typical signs and symptoms include nosebleeds, stuffy nose and crustiness of nasal secretions, and inflammation of the uveal layer of the eye. Damage to the heart, lungs and kidneys can be fatal. Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), is a long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels. It is a form of vasculitis (inflammation of blood vessels) that affects small- and medium-size vessels in many organs but most commonly affects the upper respiratory tract and the kidneys. Therefore, the signs and symptoms of GPA are highly varied and reflect which organs are supplied by the affected blood vessels. Typical signs and symptoms include nosebleeds, stuffy nose and crustiness of nasal secretions, and inflammation of the uveal layer of the eye. Damage to the heart, lungs and kidneys can be fatal. The cause of GPA is unknown. Genetics have been found to play a role in GPA though the risk of inheritance appears to be low. GPA treatment depends on the severity of the disease. Severe disease is typically treated with a combination of immunosuppressive medications such as rituximab or cyclophosphamide and high-dose corticosteroids to control the symptoms of the disease and azathioprine, methotrexate, or rituximab to keep the disease under control. Plasma exchange is also used in severe cases with damage to the lungs, kidneys, or intestines. The number of new cases of GPA each year is estimated to be 2.1-14.4 new cases per million people in Europe. GPA is rare in Japanese and African-American populations but occurs more often in people of Northern European descent. GPA is estimated to affect 3 cases per 100,000 people in the United States and equally affects men and women. Initial signs are highly variable, and diagnosis can be severely delayed due to the nonspecific nature of the symptoms. In general, irritation and inflammation of the nose is the first sign in most people. Involvement of the upper respiratory tract, such as the nose and sinuses, is seen in nearly all people with GPA. Typical signs and symptoms of nose or sinus involvement include crusting around the nose, stuffiness, nosebleeds, runny nose, and saddle-nose deformity due to a hole in the septum of the nose. Inflammation of the outer layers of the eye (scleritis) and conjunctivitis are the most common signs of GPA in the eye; involvement of the eyes is common and occurs in slightly more than half of people with the disease. The cause of GPA is unknown, although microbes, such as bacteria and viruses, as well as genetics have been implicated in its pathogenesis. Classic microscopic features of GPA include inflammation of blood vessels associated with poorly formed granulomas, necrosis, and many giant cells. Bacterial colonization with Staphylococcus aureus has been hypothesized as an initiating factor of the autoimmunity seen in people with GPA. Several genes involved in the immune system including PTPN22, CTLA4, and human leukocyte antigen genes may influence the risk of developing GPA. It is now widely presumed that the anti-neutrophil cytoplasmic antibodies (ANCAs) are responsible for the inflammation in GPA. The typical ANCAs in GPA are those that react with proteinase 3, an enzyme prevalent in neutrophil granulocytes. In vitro studies have found that ANCAs can activate neutrophils, increase their adherence to endothelium, and induce their degranulation that can damage endothelial cells. In theory, this phenomenon could cause extensive damage to the vessel wall, in particular of arterioles. Granulomatosis with polyangiitis is usually suspected only when a person has had unexplained symptoms for a long period of time. Determination of anti-neutrophil cytoplasmic antibodies (ANCAs) can aid in the diagnosis, but positivity is not conclusive and negative ANCAs are not sufficient to reject the diagnosis. More than 90% of people who have GPA test positive for ANCA. Cytoplasmic-staining ANCAs that react with the enzyme proteinase 3 (cANCA) in neutrophils (a type of white blood cell) are associated with GPA. Involvement of the ears, nose, and throat is more common in granulomatosis with polyangiitis than in the similar condition microscopic polyangiitis.