Granulomatous Polyangiitis Research Articles

Fallbericht einer granulomatös-nekrotisierenden Sialadenitis

This article presents the case of a 43-year-old male patient with recurrent painful swelling of the right submandibular gland. Submandibulectomy was performed. Histological investigations showed an intense granulomatous inflammation with severe destruction of the parenchyma. The inflammatory infiltrate consisted of abscesses with neutrophilic and eosinophilic granulocytes and ill-defined granulomas with multinucleated giant cells. Some of the blood vessels showed evidence of vasculitis. After further clinical and serological investigations with highly elevated levels of cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and antiproteinase-3 antibodies, a rare limited disease of granulomatous polyangiitis (Wegener granulomatosis) was finally diagnosed. Such a manifestation of the disease is exceedingly rare; therefore, only single case reports have so far been described. The certain establishment of the diagnosis seems to be challenging because of the lack of involvement of the respiratory tract and the kidneys. In this case a histological assessment and clinical findings are mandatory for the correct diagnosis.

The Role of Environmental Factors in the Pathogenesis of Anti-Neutrophil Antibody Associated Vasculitis

This review seeks to critically examine the environmental factors reported to be associated with anti-neutrophil antibody associated systemic vasculitis. The published literature was searched in a systematic fashion. From this emerges strong evidence for a latitude gradient in the case of granulomatous polyangiitis and eosinophilic granulomatous polyangiitis; both appear more common at high latitudes. Microscopic polyangiitis does not demonstrate this. Latitude affects ultraviolet radiation exposure and the relationship of increased incidence of granulomatous polyangiitis and eosinophilic polyangiitis with decreased ultraviolet radiation exposure is much stronger. The most plausible explanation is vitamin D levels, a hormone known to be vital for normal immune function and largely synthesised in humans secondary to ultraviolet radiation exposure. Case control studies demonstrate a consistent relationship to silica exposure a substance well known to have profound immunological effects. The genetic risk factors for these diseases will be considered and a model of how genes and environment may interact to produce these diseases discussed. Low vitamin D levels, silica exposure, other environmental triggers may interact with genes that influence the immune and inflammatory response to initiate and sustain these diseases. As such, the broad concepts developed about the etiopathogenesis of the anti-neutrophil antibody associated vasculitides shows many parallels to other autoimmune diseases. Much more information is required about both genes and the environment, but the model helps define the questions that need to be answered

THU0218 Hematological malignancies (other than lymphoma) in patients with granulomatous polyangiitis (wegener)

BackgroundPrevious studies have suggested an increased risk of hematological malignancies in patients with granulomatous polyangiitis (GPA) (Wegener). In a Swedish study of GPA the risk for leukemia was 6-fold increased...

Unusually indolent MPO-ANCA: associated vasculitis-report of two cases.

Vasculitis associated with antineutrophil cytoplasmic antibodies specific to myeloperoxidase generally presents as a life- and organ-threatening disease that evolves over several months. It is a syndrome in which prompt diagnosis and therapy are important both in terms of short-term survival and long-term organ damage. Two cases with quite a different course, sustained and indolent with limited progression over many years, are described in this report. They are compared to cases in the literature. Indolent cases of granulomatous polyangiitis associated with antineutrophil cytoplasmic antibodies against proteinase-3 are well recognised, but these two cases of microscopic polyangiitis are almost unique.

Nucleotide-binding oligomerization domain containing 2: Structure, function, and diseases

ObjectivesTo systematically review literature about the structure and function of nucleotide-binding oligomerization domain containing 2 (NOD2) and its disease association. MethodsThe English literature was searched using keywords “NOD2” and “disease”. Relevant original and review articles were reviewed. ResultsNOD2 is an intracellular protein and shares similar molecular structure with NOD1, pyrin, and cryopyrin. There are more than 100 NOD2 gene mutations, some of which have been linked to diseases such as Crohn disease, Blau syndrome, and NOD2-associated autoinflammatory disease (NAID). The NOD2 variants located in the leucine-rich repeat (LRR) region are susceptible to Crohn disease, and the variants in the nucleotide-binding domain (NBD) and in between the NBD and LRR are associated with Blau syndrome and NAID, respectively. No disease association with the gene variants has been found in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis/psoriatic arthritis, adult sarcoidosis, granulomatous polyangiitis, or multiple sclerosis. The potential association of the NOD2 variants with graft-versus-host-disease remains controversial. NOD2 functions mainly through RICK or RIP2 to activate p38 mitogen-activated protein kinases and NF-κB, resulting in inflammatory response, and enhanced autophagic activity. Biologic therapy may be beneficial for NOD2-associated diseases, and new drug development may be realized based upon the signaling pathways. ConclusionsNOD2 gene mutations are associated with several diseases, and some of the mutations are of diagnostic value in Blau disease and NAID. To understand the NOD2 function, disease association, and its pathogenesis is important given the ever increasing clinical significance of NOD2.

Rituximab in Membranous Nephropathy

Rituximab, a B cell–depleting anti-CD20 chimeric monoclonal antibody, is Food and Drug Administration approved in the United States for the treatment of certain lymphomas, rheumatoid arthritis, and granulomatous and microscopic polyangiitis. It has been used additionally in a wide variety of

Rituximab in induction therapy for anti-neutrophil cytoplasmic antibody (ANCA) vasculitis

Anti-neutrophil cytoplasmic antibodies (ANCA) have been associated with a spectrum of vasculitis that includes granulomatous polyangiitis (formerly known as Wegener's granulomatosis), microscopic polyangiitis, the Churg-Strauss syndrome, primary pauciimmune necrotizing and crescentic glomerulonephritis and related forms of vasculitis. In vitro, in vivo and clinical evidence support the conclusion that ANCA participate in the pathophysiology of this disease spectrum. Rituximab is a potent tool that can interrupt B cell-mediated immunity without major compromise of T cell-mediated immunity. Thus, it has great appeal as a tool to interrupt antibody-mediated autoimmune disease. The results of two prospective randomized trials confirm that rituximab can be effective as part of induction therapy for active ANCA-associated vasculitis. The safety profile for rituximab appears favourable relative to cyclophosphamide and steroids. However, there remain many patients who require individualized adjustments of ancillary therapy, as breakthrough disease, relapses and infectious complications do occur. Based on our current knowledge, rituximab should now be incorporated as part of induction therapy in many patients with ANCA-associated vasculitis. However, more work is needed to determine how rituximab may best be integrated into the overall immunosuppression of these patients.