Granulomatosis with polyangiitis (GPA), formerly known as Wegener's 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 Wegener's granulomatosis, it is named after Friedrich Wegener, who described the disease in 1936. Because of Wegener's 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.
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.
Immunofluorescence pattern produced by binding of ANCA to ethanol-fixed neutrophils, from a person with GPA
Photo showing the sclerokeratitis associated with GPA
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.
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 granulomatousinflammation (clumps of typically arranged white blood cells) on microscopy. These granulomas are the main reason for the appellation of "Wegener's 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.
In generalised non-organ-threatening disease, remission can be induced with methotrexate and steroids, where the steroid dose is reduced after a remission has been achieved and methotrexate used as maintenance.
In case of organ-threatening disease, pulsed intravenous cyclophosphamide with steroids is recommended. Once remission has been achieved, azathioprine and steroids can be used to maintain remission.
In severe renal vasculitis, the same regimen is used but with the addition of plasma exchange.
In 2006, Alexander Woywodt (Preston, United Kingdom) and Eric Matteson (Mayo Clinic, USA) investigated Wegener's past, and discovered that he was, at least at some point of his career, a follower of the Nazi regime. In addition, their data indicate that Wegener was wanted by Polish authorities and that his files were forwarded to the United Nations War Crimes Commission. Furthermore, Wegener worked in close proximity to the genocide machinery in Łódź. Their data raise serious concerns about Wegener's professional conduct. They suggest that the eponym be abandoned and propose "ANCA-associated granulomatous vasculitis." The authors have since campaigned for other medical eponyms to be abandoned, too. In 2011, the American College of Rheumatology (ACR), the American Society of Nephrology (ASN) and the European League Against Rheumatism (EULAR) resolved to change the name to granulomatosis with polyangiitis.
^ abFalk RJ, Gross WL, Guillevin L et al. (2011). "Granulomatosis with polyangiitis (Wegener's): An alternative name for Wegener's granulomatosis". Ann. Rheum. Dis.70: 74. doi:10.1136/ard.2011.150714. PMID21372195.
^Silva, Fred; Jennette, J. Charles; Heptinstall, Robert H.; Olson, Jean T.; Schwartz, Melvin (2007). Hepinstall's pathology of the kidney. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 677. ISBN0-7817-4750-3.
^ abcdeBerden, A; Göçeroglu, A; Jayne, D; Luqmani, R; Rasmussen, N; Bruijn, JA; Bajema, I (January 2012). "Diagnosis and management of ANCA associated vasculitis.". BMJ344: e26. doi:10.1136/bmj.e26. PMID22250224.
^Tracy, CL; Papadopoulos, PJ; Bye, MR; Connolly, H; Goldberg, E; O'Brian, RJ; Sharma, GD; Talavera, F; Toder, DS; Valentini, RP; Windle, ML; Wolf, RE (10 February 2014). Diamond, HS, ed. "Granulomatosis with Polyangiitis". Medscape Reference. WebMD. Retrieved 16 March 2014.
^van der Woude FJ, Rasmussen N, Lobatto S, et al. (February 1985). "Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis". Lancet1 (8426): 425–9. doi:10.1016/S0140-6736(85)91147-X. PMID2857806.
^Leavitt RY, Fauci AS, Bloch DA, et al. (August 1990). "The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis". Arthritis Rheum.33 (8): 1101–7. doi:10.1002/art.1780330807. PMID2202308.
^Jennette JC, Falk RJ, Andrassy K, et al. (February 1994). "Nomenclature of systemic vasculitides. Proposal of an international consensus conference". Arthritis Rheum.37 (2): 187–92. doi:10.1002/art.1780370206. PMID8129773.
^Friedmann I (1982). "McBride and the midfacial granuloma syndrome. (The second 'McBride Lecture', Edinburgh, 1980)". The Journal of laryngology and otology96 (1): 1–23. doi:10.1017/s0022215100092197. PMID7057076.