Bismillah, [Granulomatosis with polyangiitis (GPA), the disease formerly known as Wegeners granulomatosis (WG)], =is a systemic disorder that involves both granulomatosis and polyangiitis. It is a form of vasculitis (inflammation of blood vessels) that affects small- and medium-size vessels in many organs. Damage to the lungs and kidneys can be fatal. It requires long-term immunosuppression. When referred to as Wegeners granulomatosis, it is named after Friedrich Wegener, who described the disease in 1936. Because of Wegeners association with the German Nazi party, professional bodies and journals have replaced his name with a descriptive name. 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 Churg–Strauss syndrome and microscopic polyangiitis.Although GPA affects small- and medium-size vessels, it is formally classified as one of the small vessel vasculitides in the Chapel Hill system. # Pathophysiology Inflammation with granuloma formation against a nonspecific inflammatory background is the classical tissue abnormality in all organs affected by 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. # Signs and symptoms Initial signs are extremely variable, and diagnosis can be severely delayed due to the nonspecific nature of the symptoms. In general, rhinitis is the first sign in most people. Kidney: rapidly progressive glomerulonephritis (75%), leading to chronic kidney failure Upper airway, eye and ear disease: Nose: pain, stuffiness, nosebleeds, rhinitis, crusting, saddle-nose deformity due to a perforated septum Ears: conductive hearing loss due to auditory tube dysfunction, sensorineural hearing loss (unclear mechanism) Oral cavity: strawberry gingivitis, underlying bone destruction with loosening of teeth, non-specific ulcerations throughout oral mucosa Eyes: pseudotumours, scleritis, conjunctivitis, uveitis, episcleritis Trachea: subglottal stenosis Lungs: pulmonary nodules (referred to as coin lesions), infiltrates (often interpreted as pneumonia), cavitary lesions, pulmonary haemorrhage causing haemoptysis, and rarely bronchial stenosis. Arthritis: Pain or swelling (60%), often initially diagnosed as rheumatoid arthritis Skin: nodules on the elbow, purpura, various others (see cutaneous vasculitis) Nervous system: occasionally sensory neuropathy (10%) and rarely mononeuritis multiplex Heart, gastrointestinal tract, brain, other organs: rarely affected. # Diagnosis 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. Cytoplasmic-staining ANCAs that react with the enzyme proteinase 3 (cANCA) in neutrophils (a type of white blood cell) are associated with GPA.[1] If the person has renal failure or cutaneous vasculitis, a biopsy is obtained from the kidneys. On rare occasions, thoracoscopic lung biopsy is required. On histopathological examination, a biopsy will show leukocytoclastic vasculitis with necrotic changes and granulomatous inflammation (clumps of typically arranged white blood cells) on microscopy. These granulomas are the main reason for the appellation of Wegeners granulomatosis, 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.[1] # Criteria In 1990, the American College of Rheumatology accepted classification criteria for GPA. These criteria were not intended for diagnosis, but for inclusion in randomised controlled trials. Two or more positive criteria have a sensitivity of 88.2% and a specificity of 92.0% of describing GPA.[9] 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: microhematuria or red cell casts Biopsy: granulomatous inflammation within 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: a granulomatous inflammation involving the respiratory tract, and a vasculitis of small to medium-size vessels. Several investigators have compared the ACR and Chapel Hill criteria.
Posted on: Mon, 15 Dec 2014 21:27:03 +0000
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