Granuloma formation in ANCA-associated vasculitides
ABSTRACT Granuloma formation is a key pathologic finding in two of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: Wegener's granulomatosis (WG) and Churg-Strauss syndrome (CSS). So far, no animal models have been established convincingly reproducing both vasculitic and granulomatous features typical of WG and CSS. In biopsies, granulomatous lesions are found both at distant extravascular sites and in the vicinity of inflamed vessels, e.g. in the lung. Intriguingly, WG-granulomata appear to display features of tertiary lymphoid tissue. Cartilaginous and osseous destruction is caused by granulomatous inflammation invading adjacent tissues. Rhinosinusitis is regularly encountered in WG and CSS. Septal perforation, saddle nose deformity, middle and inner ear symptoms, and granulomatous invasion of the palate, orbita, meninges, or the pituitary gland may complicate WG. Both common (e.g. FCGR3B copy number) and distinct (e.g. HLA-DP, IL-10.2) genetic factors have been identified in AAV potentially favouring inflammation and autoimmunity. The HLA-DPB1/RING1/RXRB region constitutes a quantitative trait locus for ANCA-positive WG with the strongest association to be reported up to now. A profound alteration of the T-cell response including Th1 and Th17 responses, anomalously NK-receptor-expressing 'NK-like' T cells, and dysfunctional regulatory T cells could facilitate and sustain granuloma formation and autoimmunity.
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Article: L20. Memory T-cells in vasculitis.La Presse Médicale 02/2013; DOI:10.1016/j.lpm.2013.01.019 · 1.17 Impact Factor
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ABSTRACT: The antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) are a group of primary vasculitides that affect predominantly small- to medium-sized blood vessels. AAV include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Disease severity is dictated by the location and extent of the blood vessels affected. If left untreated, systemic forms of AAV are often fatal. The advent of immunosuppressive therapy (cyclophosphamide plus glucocorticoids) has revolutionised the prognosis for patients with AAV, transforming the course of the disease from fatal to one that can be managed, though not without significant treatment-related toxicity. Recently, the monoclonal antibody rituximab was approved for the treatment of GPA and MPA, providing the first major alternative to cyclophosphamide for induction therapy of AAV. This review explores the emerging role of rituximab in the management of this complex disorder.
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ABSTRACT: Inflammatory diseases of the nose and paranasal sinus are commonly encountered in diagnostic histopathology. This review describes the possible manifestations of the common diseases as well as highlighting some of the uncommon causes of sinonasal inflammation which may have importance for treatment and prognosis. The diagnosis of fungal sinusitis is primarily histological. It is important to distinguish between invasive and non-invasive fungal sinusitis, the latter including allergic fungal sinusitis characterized by ‘allergic mucin’ and scanty fungal hyphae. Nasal eosinophilia is a feature of both allergic and non-allergic rhinosinusitis and a wide range of secondary changes in inflammatory polyps may lead to diagnostic confusion. Nasal biopsies are often taken from perforations or inflammatory masses to confirm or exclude granulomatous diseases. There is a broad differential diagnosis for granulomatous sinonasal disease and pathologists should appreciate the diagnostic histological and clinical features of these conditions.Diagnostic Histopathology 06/2010; DOI:10.1016/j.mpdhp.2010.03.008