Abstract

Background:Anti-neutrophil cytoplasmic antibodies (ANCAs) are valuable laboratory markers used in the detection of medium and small-vessel vasculitis: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis. Historically, and in our own centre, ANCAs are screened for using indirect immunofluorescence (IIF) with antigen-specific immunoassays being performed on IIF-ANCA positive results. While highly sensitive, IIF has a low specificity compared to antigen-specific immune-assay for MPO and PR3. Anecdotally, positive IIF ANCA results often trigger rheumatology referrals. A 2017 International consensus statement has recommended ten clinical indications for requesting ANCA, and suggested high quality immunoassays are the preferred screening method, without the categorical need for IIF.Objectives:This service evaluation explores the local impact and implications of adopting the 2017 International Consensus on ANCA testing by evaluating new patient referrals to a single UK rheumatology centre.Methods:New out-patient referrals to a single consultant rheumatologist at one UK centre were collected over 40-months (2016-19) and prospectively coded by referral indication from the clinical letter prior to clinical assessment. Data collected included: anonymised baseline demographics, referral source, key features for referral, and diagnosis following assessment. Referral text was coded using clinical reasoning theory, to identify up to four ‘key-features’ of the referral, typed by the clinician as free text. This included clinical findings, suspected diagnosis, ANCA testing (MPO/PR3 status), other autoantibodies, arthralgia, synovitis, or other important features (e.g. rash, Raynaud’s phenomenon). Diagnosis at the visit was coded against established rheumatological diagnoses. We retrospectively identified any patient where ANCA/ MPO/PR3 formed a key part of the referral, using electronic text search tools.Results:A total of 1748 referrals were seen, 177 (10.1%) were excluded due to incomplete data. This left 1547 for analysis, of these 18 (1.2%) had been referred with an ANCA IIF positive result as a key component for the referral. The 18 ANCA positive were predominantly female (16/18) and had a mean age of 49 (SD 16.6). The majority of referrals were initiated primary care (16/18); the remaining referrals were from haematology and ophthalmology. The majority (17/18, 94%) tested negative for MPO and PR3, 1/18 (6%) was PR3 antibody positive (known inflammatory bowel disease). Retrospectively, none of the ANCA requests would have met the 2017 gating criteria for testing. In total 13/18 patients were given an additional diagnosis: Fibromyalgia 6 (28%); Soft tissue rheumatism 4 (22%); undifferentiated inflammatory arthritis 1; reactive arthritis 1; biomechanical joint pain 1; probable connective tissue disease 1.Conclusion:This service evaluation shows that routine outpatient referrals with positive IIF ANCA represent a small but significant proportion of referrals to our centre (1.2%). The vast majority of these would be filtered out with a gating strategy. This evaluation demonstrates the low specificity of IIF ANCA without any suggestive clinical symptoms. By adopting MPO/PR3 immune-assays as the primary screening method, the vast majority of these referrals (17/18, 94%) would have tested ‘negative’, reducing uncertainty for patients and primary care clinicians. None of these patients were diagnosed with vasculitis. These data support adoption of the 2017 Consensus Statement across our, and other units, to reduce unnecessary referrals, uncertainty, and cost. Our electronic requesting system allows for the introduction of an ANCA gating strategy. These data can be used to educate primary care teams regarding indications and interpretation of ANCA testing.

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