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.[7]
GPA treatment depends on the severity of the disease.
Plasma exchange is also used in severe cases with damage to the lungs, kidneys, or intestines.[9]
The
affect 3 cases per 100,000 people in the United States and equally affects men and women.[10] GPA has infrequently been reported in minors.[11]
Signs and symptoms
Typical saddle nose damage due to granulomatosis with polyangiitis.
Initial signs are highly variable, and diagnosis can be severely delayed due to the nonspecific nature of the
hole in the septum of the nose.[7][14] Inflammation of the outer layers of the eye (scleritis and episcleritis[15][16]) 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.[6]
dysfunction, sensorineural hearing loss (unclear mechanism)
Oral cavity: strawberry gingivitis, underlying bone destruction with loosening of teeth, non-specific ulcerations throughout the lining of the mouth[17]
Lungs: pulmonary nodules (referred to as "coin lesions"), infiltrates (often interpreted as pneumonia), cavitary lesions, bleeding in the lungs causing a person to cough up blood, and rarely bronchial stenosis.
endothelial cells. In theory, this phenomenon could cause extensive damage to the vessel wall, in particular of arterioles.[12]
Diagnosis
Immunofluorescence pattern produced by binding of ANCA to ethanol-fixed neutrophils, from a person with GPA
Granulomatosis with polyangiitis is usually suspected only when a person has had unexplained symptoms for a long period of time. Determination of
neutrophils (a type of white blood cell) are associated with GPA.[12] Involvement of the ears, nose, and throat is more common in granulomatosis with polyangiitis than in the similar condition microscopic polyangiitis.[7]
If the person has signs of kidney involvement or
microscopy. These granulomas are the main reason for the name granulomatosis with polyangiitis, although it is not an essential feature. Nevertheless, necrotizing granulomas are a hallmark of this disease. However, many biopsies can be nonspecific and 50% provide too little information for the diagnosis of GPA.[12]
Classification
Granulomatosis with polyangiitis is part of a larger group of vasculitic syndromes called systemic vasculitides or necrotizing vasculopathies, all of which feature an autoimmune attack by an abnormal type of circulating antibody termed ANCAs (antineutrophil cytoplasmic antibodies) against small and medium-size blood vessels. Apart from GPA, this category includes eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis.[1] Although GPA affects small- and medium-size vessels,[20] it is formally classified as one of the small vessel vasculitides in the Chapel Hill system.[2]
The left apical region is opacified in a case of granulomatosis with polyangiitis.
Nasal or oral inflammation:
painful or painless oral ulcers or
purulent
or bloody nasal discharge
Lungs: abnormal chest X-ray with:
nodules,
infiltrates or
cavities
Kidneys: urinary sediment with:
microscopic hematuria
or
red cell
casts
Biopsy: granulomatous inflammation
Photo showing the sclerokeratitis associated with GPAwithin the arterial wall or
in the perivascular area
According to the Chapel Hill Consensus Conference (CHCC) on the nomenclature of systemic vasculitis (1992), establishing the diagnosis of GPA demands:[22]
Oral and intravenous cyclophosphamide are both effective for induction of GPA remission. Oral cyclophosphamide at a dose of 2 mg/kg/day was the standard treatment for many years; this regimen resulted in complete remission in more than 75% of people with GPA but is associated with significant toxicities including
Pneumocystis jirovecii pneumonia is a common complication and prophylaxis against this pathogen is recommended.[8]
Rituximab may be substituted for cyclophosphamide to induce remission since it is similarly effective and has a comparable side effect profile.
mycophenolate mofetil are used.[27]TNF inhibitors, such as etanercept, appear to be ineffective and are not recommended for routine use.[8]
Limited disease
In generalized non-organ-threatening disease, remission can be achieved with a combination of methotrexate and corticosteroids, where the steroid dose is reduced after a remission has been achieved and methotrexate is used as maintenance therapy. Treatment measures for localised GPA of the nose and sinuses includes nasal irrigation, nasal corticosteroids, and antibiotics if infection occurs.[14] If perforation of the nasal septum occurs (or saddle nose deformity), then surgical repair is recommended.[14]
Cochrane review did not confirm fewer relapses with trimethoprim/sulfamethoxazole treatment.[8][9]
Prognosis
Before modern treatments, the 2-year survival was under 10% and average survival five months.[13][28] Death usually resulted from uremia or respiratory failure.[13] The revised Five-factor score is associated with 5-year mortality from GPA and is based on the following criteria: age greater than 65 years, cardiac symptoms, gastrointestinal involvement, chronic kidney disease, and the absence of ears, nose, and throat symptoms.[7]
With corticosteroids and
chronic kidney failure, hearing loss, and deafness.[12] The risk of relapse is increased in people with GPA who test positive for anti-PR3 ANCA antibodies and is higher than the relapse risk for microscopic polyangiitis.[7]
Today, medication toxicity is managed more carefully and long-term remissions are possible. Some affected individuals are able to lead relatively normal lives and remain in remission for 20+ years after treatment.[29]
European League Against Rheumatism (EULAR) resolved to change the name to granulomatosis with polyangiitis, given Wegener's association with the Nazi Party.[35]
