Anti-neutrophil cytoplasmic antibody (ANCA) testing at Groote Schuur Hospital: Adherence to indications for testing

Appropriate use of laboratory investigations is increasingly important in resource-constrained environments. We receive the anti-neutrophil cytoplasmic antibody (ANCA) testing practices in a tertiary hospital in South Africa

Use of Plasmapheresis and Immunosuppressants to Treat Diffuse Alveolar Hemorrhage in a Patient with Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a systemic granulomatous inflammatory disease characterized by small-to-medium vessel vasculitis due to Central Anti-Neutrophil Cytoplasmic Antibody (C-ANCA). GPA commonly involves the lungs and the kidneys. Among the pulmonary manifestations, diffuse alveolar hemorrhage (DHA) is a rare presentation of GPA that can present with hemoptysis leading to acute onset of anemia and hemodynamic instability. An active diagnostic workup including serologic titer of C-ANCA, imaging, intensive care, and aggressive immunosuppression is the key to DAH management. We report a case of DAH secondary to GPA that presented with hemoptysis leading to severe anemia, initially resuscitated symptomatically and started on plasmapheresis with pulse steroids and cyclophosphamide. Timely diagnosis and management led to a remarkable recovery of the pulmonary symptoms and imaging findings of DAH

ANCA-associated vasculitis

The vasculitides are a heterogeneous group of conditions typified by their ability to cause vessel inflammation with or without necrosis. They present with a wide variety of signs and symptoms and, if left untreated, carry a significant burden of mortality and morbidity. The ANCA-associated vasculitides (AAV) are three separate conditions - granulomatosis with polyangiitis (GPA - formerly known as Wegener’s granulomatosis); microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA - previously known as Churg-Strauss Syndrome). This review examines recent developments in the pathogenesis and treatment of AAV

Clinical and epidemiological Studies in ANCA-associated vasculitis

Objectives:This thesis aims to provide an overview of the epidemiology of AAV in southern Sweden, to evaluate different classification criteria in AAV. In addition we study if infection is a risk factor for later development of AAV comparing patients with AAV with a matched population cohort and to examine the occurrence of severe infections as an outcome in AAV. Methods:All adult patients diagnosed with AAV between 1997 and 2019 in the study area of 14 municipalities in Southern Sweden were identified and classified according to EMA algorithm and to the recently published ACR/EULAR classification criteria. Changes in the incidence and prevalence of AAV were studied over 23 years. Using a non-AAV age, sex and place of residence matched population the association of prior infections and later development of AAV was analysed with a logistic regression model. Events of severe infections after AAV diagnosis were identified and studied, incidence rate of severe infections was calculated. Results:Stable incidence with 30 cases per million inhabitants and rising prevalence are observed under the study period. Incidences are rising with age. The prevalence of 469/million in 2015 is the highest ever reported. Classification with the new ACR/EULAR criteria shows good agreement with earlier criteria (96% EGPA, 85% GPA, 75% MPA) but even with a classification based on ANCA serology alone (PR3 99%, MPO 84%). Infection, especially in the respiratory tract, is associated with later development of AAV. A history of prior infections is more likely in MPO-positive cases. In patients with AAV, severe infection occurs in 40% of cases after the onset of AAV. The incidence rate of severe infection is 9.1 per 100 person-years of follow-up but significantly higher during the first year with 22.1 per 100 person-years. High age and high diesaese activity independently predict the occurrence of severe infection. Conclusion:The incidence of AAV is stable in our area. The prevalence has increased substantially during the last decades, which can be attributed to better treatment and management and therefore increased survival. An ANCA based classification of AAV produces similar results as the new ACR/EULAR classification criteria. MPO-positive AAV is associated with prior infection. Severe infections are common problem in AAV especially in the first year, they are among the leading causes of death in vasculitis patients

The immunopathology of ANCA-associated vasculitis.

The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control