Journal of Vasculitis

The review seeks to summarise the current ideas in regard to the pathogenesis of ANCA-associated vasculitis and to examine in detail how epidemiological and genetic factors fit with the modern paradigm. The recent literature has been reviewed. The AASV appear to involve initiation by both T cells and B cells followed by a neutrophil dominated inflammatory phase in which ANCA may actually be involved. The alternative complement pathway may play a role. The genetic background is reviewed with genes identified that potentially encode proteins that are involved in the regulation of the immune system, other genes may be involved in the control of the inflammatory phase. With regard to environmental factors the two that stand out are a latitude gradient, presumably vitamin D and silica an agent known to be associated with both autoantibody production and autoimmune disease. A model which includes these factors is outlined.

DIL is an autoimmune mediated vasculitis against certain drugs. Such drugs may induce autoantibodies in some patients leading to a clinical syndrome similar to systemic lupus erythematosus. Over 100 drugs with mostly hydralazine, procainamide, quinidine, isoniazid, and diltiazem may often cause increased levels of ANA in serum while some patients with these antibodies may develop clinical symptoms of SLE such as rash, serositis, or arthritis suggesting drug-induced disease. Although DIL and SLE share clinical similarities that may lead to a diagnostic dilemma, these two entities have crucial disparities in pathogenetic, immunologic and clinical features. DIL occurs due to the interactions between the drug and DNA or histones that make them immunogenic. DIL is rare but recognition of this syndrome clinically and serologically is crucial because DIL resolves completely within few weeks after withdrawal of the causative agent. Prompt withdrawal is required because continued use may lead to lifethreatening severe cases. This article reviews the pathogenetic mechanisms, clinical manifestations and brings up to date the diagnosis with approach to treatment of DIL.

Background: ANCA-associated small vessel vasculitides (AAV) are prone to cycles of relapse and remission. Renal involvement manifests as glomerulonephritis with microscopic haematuria, red blood cell casts, proteinuria and variable decrease in renal function. Remission of renal vasculitis is defined as stabilization in serum creatinine (Creat) and resolution of haematuria while controversy exists about persistence of haematuria (during apparent disease-remission) since it may indicate smouldering disease-activity or should be considered as renal flare.
Objective: To clarify the course of haematuria after diagnosis and induction therapy and its possible predictive value of long term renal function.
Design: Retrospective cohort study. Participants: 96 consecutive AAV-patients with renal involvement diagnosed and treated with systemic AAV between 1st of January 2000 to 31th December 2007 were followed for 60 months. Main measures: Collected data were Creat, CRP (mg/ml), eGFR ml/min/1.73 m2, creatinine-excretion in collected 24 h urine (Ucreat/24 h), proteinuria (Uprot), ratio of proteinuria/ creatinine in 24 h urine (Uprot/creat) and haematuria. Data were analysed for the complete study population and compared for MPO-ANCA and PR3-ANCA.
Key results: At twelve months after diagnosis, haematuria was no longer detectable in 92% of all patients. In the PR3-ANCA group, haematuria disappeared after 13 months, while in the MPO-ANCA group haematuria persisted in 19% of the patients. On average, haematuria disappeared almost simultaneously with stabilisation of the renal function.
Conclusion: Haematuria persists for many months after diagnosis and disappears usually simultaneously with stabilisation of kidney function. There was no relation between persistence of haematuria for over 12 months and renal function during follow up. Haematuria probably acts as a sensitive marker for absence of inflammatory glomerular disease activity in most patients with systemic AAV and renal involvement. It is disappearance coincide with stabilisation of renal function and remission of the disease in almost all patients. However, if it persists, it is not predictive for worsening renal function nor for relapse. Proteinuria does not seem to be a reliable marker for renal disease remission.