Choosing wisely: Review and commentary on anti-nuclear antibody (ANA) testing

doi:10.1016/j.autrev.2015.12.002

Autoimmunity Reviews

Volume 15, Issue 3, March 2016, Pages 272-280

https://doi.org/10.1016/j.autrev.2015.12.002 Get rights and content

Abstract

Choosing Wisely®: Next Steps in Improving Healthcare Value is an initiative of the American Board of Internal Medicine (ABIM) Foundation. The driving forces for the Choosing Wisely (CW) campaign include rising and unstainable health care expenditures and evidence that there is lack of fiscal stewardship of health care resources. The American College of Rheumatology and the Canadian Rheumatology Association published their top five Choosing Wisely recommendations, the first of which pertained to antinuclear antibodies (ANA) and ANA subserology testing. Concerns about the wasteful use of these tests prompted an analysis of the expenditures attributable to ANA testing as a proportion of total health care expenditures and based on a financial model was in the range of 0.00125%. It is suggested that if the sole use of ANA testing is to add evidence to support a diagnosis when the pre-test probability is high, then the ANA test has limited clinical value. Accordingly, the goal of ANA testing needs to be reconsidered and expanded beyond an approach to simply confirming a diagnosis with ‘intention to treat’ to a goal of case finding of ‘pre- or early disease’ with an ‘intent to prevent’ disease. This an area where more significant inroads can be made in preventing end organ disease and thereby reducing health care expenditures HCE. One CW recommendation that bears emphasizing is that, with a few possible exceptions, repeat ANA or ANA subserology testing has little clinical value in monitoring disease activity or predicting a flare.

Section snippets

Introduction: a brief history of the choosing wisely initiative

Choosing Wisely®: Next Steps in Improving Healthcare Value is an initiative of the American Board of Internal Medicine (ABIM) Foundation whose primary goal is stated as “sparking conversations between health care providers and patients to ensure the right care is delivered at the right time” (http://www.choosingwisely.org/). Since its inception in 2012, more than 70 specialty societies in more than 12 countries have joined the campaign and a growing number have created lists of “Things

Are the ANA and ANA subserologies commonly ordered or provided by rheumatologists?

To adequately address this question, it is important to establish which ANA and ANA subserology testing is being referred to. Based on citations that the ANA indirect immunofluorescence (IIF) test is the “gold standard” screening test for SLE and other AARD [18], [19], it is made clear that the CW recommendations address this IIF assay as performed on HEp-2 substrates. At the outset, calling the use of the ANA IIF test into question seems rather paradoxical if not ironic because the

Is the ANA among the most expensive services ordered or provided?

The second of the three criteria leading to the ACR CW recommendations specified that ‘tests or procedures that were among the most expensive services ordered or provided’ should be identified [16]. The factors implicated in a thorough cost analysis of ANA or ANA subserology testing is complex and to thoroughly address this criterion is beyond the scope of this discussion. It is important to point out that the words “most expensive” has no apparent benchmark or comparator that can be used to

ANA subserologies (ENA profiles)

Another concern with the CW claims on ANA testing is that there appears to be a misconception that a positive ANA test is so sensitive that no further ANA subserology testing (i.e. anti-ENA) need be done [16]. Even with the caveats expressed in the CW publication (discussed below), such a wide sweeping statement is not entirely consistent with contemporary literature and evidence. First, it should have been clarified which immune mediated diseases (IMD) are attended by ANA testing and fell

Is there compelling evidence showing that ANA and ANA subserology testing does not provide meaningful benefit to at least some groups for whom the test or treatment is provided?

As an approach to addressing this third criterion, a key issue is the definition of ‘meaningful benefit’. This section of commentary proposes the question “What are the goals of ANA testing?” and posits that there should be two: 1) To confirm a diagnosis where the pre-test probability of the disease in question is relatively high, and 2) as a tool for “case finding” and establishing an early and accurate diagnosis where the pre-test probability is low.

Based on the wording, context and cited

Summary

The ACR and CRA CW recommendations on the use and abuse of ANA and ANA subserology have opened the door for dialogue and commentary on the clinical value and applications of these immunoassays. There appears to be significant misunderstanding about what the ANA test can actually achieve in clinical practice. If the sole use of the ANA test is to add evidence to support a diagnosis when the pre-test probability is high, the ANA test is not very useful. Save your money. One of the values of ANA

Abbreviations

Aab

autoantibodies

AARD

anti-nuclear antibody related diseases

IIM, ANA

antinuclear antibody

ACR

American College of Rheumatology

billion

CDN

Canadian

CRA

Canadian Rheumatology Association

CTD

connective tissue disease

choosing wisely

DFS

dense fine speckled

dsDNA

double-stranded DNA

ENA

extractable nuclear antigens

GDP

gross domestic product

HCE

health care expenditures; idiopathic inflammatory myopathies

IMD

immune mediated disease

million

MCTD

mixed connective tissue disease

OECD

Organization for Economic Cooperation

Take-home messages

•
Based on the CW recommendations on ANA and ANA subserology testing, there appears to be significant misunderstanding about what the ANA test can achieve in clinical practice.
•
The goal of ANA testing needs to be expanded beyond an approach to confirm a diagnosis with ‘intention to treat’ to incluide a goal of case finding of ‘pre- or early-AARD’ with an ‘intent to prevent’ disease.
•
In considering wasteful HCE, it is important to appreciate the VALUE PROPOSITION wherein increases in HCE are offset

Acknowledgements

The helpful discussions with Dr. Ann Clarke (University of Calgary), Michael Mahler, Ed Bass, Susan Copple and Patricia Swartwood (Inova Diagnostics Inc., San Diego, CA) are appreciated. It is acknowledged that the author (MJF) was identified as a “content expert” for the CRA CW publication [17].

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ReviewChoosing wisely: Review and commentary on anti-nuclear antibody (ANA) testing

Abstract

Section snippets

Introduction: a brief history of the choosing wisely initiative

Are the ANA and ANA subserologies commonly ordered or provided by rheumatologists?

Is the ANA among the most expensive services ordered or provided?

ANA subserologies (ENA profiles)

Is there compelling evidence showing that ANA and ANA subserology testing does not provide meaningful benefit to at least some groups for whom the test or treatment is provided?

Summary

Abbreviations

Take-home messages

Acknowledgements

Autoimmun Rev

Value Health

Autoimmun Rev

Am J Med

Mayo Clin Proc

Autoimmun Rev

Autoimmun Rev

J Biol Chem

J Autoimmun

Autoimmun Rev

Autoimmun Rev

Best Pract Res Clin Rheumatol

Rheum Dis Clin North Am

Rheum Dis Clin North Am

Autoimmun Rev

Clin Chim Acta

‘Choosing wisely’: a growing international campaign

BMJ Qual Saf

Focus on Health Spending: OECD Statistics 2015

Health Data: Health Expenditure and Financing

Choosing wisely: helping physicians and patients make smart decisions about their care

JAMA

Choosing wisely: changing clinicians, patients, or policies?

JAMA

Impact of patient requests on provider-perceived visit difficulty in primary care

J Gen Intern Med

Addressing requests by patients for nonbeneficial interventions

JAMA

Professionalism in medicine: results of a national survey of physicians

Ann Intern Med

And a diagnostic test was performed

N Engl J Med

Googling for a diagnosis—use of Google as a diagnostic aid: internet based study

BMJ

Watson will see you now: a supercomputer to help clinicians make informed treatment decisions

Clin J Oncol Nurs

Probabilistic machine learning and artificial intelligence

Nature

Medical professionalism in the new millennium: a physician charter

Ann Intern Med

Choosing wisely: the American College of Rheumatology's Top 5 list of things physicians and patients should question

Arthritis Care Res (Hoboken)

Choosing wisely: the Canadian Rheumatology Association's list of 5 items physicians and patients should question

J Rheumatol

ANA screening: an old test with new recommendations

Ann Rheum Dis

Position Statement, methodology of testing for antinuclear antibodies

The antinuclear antibody (ANA) test: last or lasting gasp?

Arthritis Rheum

Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing

Arthritis Rheum

Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies

J Immunol Res

Autoimmune diagnostics: the technology, the strategy and the clinical governance

Immunol Res

Interpretation of ANA indirect immunofluorescence test outside the darkroom using NOVA view compared to manual microscopy

J Immunol Res

Automated tests of ANA immunofluorescence as throughput autoantibody detection technology: strengths and limitations

BMC Med

Clinical and serological features of patients referred through a rheumatology triage system because of positive antinuclear antibodies

PLoS One

The clinical significance of the dense fine speckled immunofluorescence pattern on HEp-2 cells for the diagnosis of systemic autoimmune diseases

Clin Dev Immunol

Clinical disease activity and titers of anti-dsDNA antibodies measured by an automated immunofluorescence assay in patients with systemic lupus erythematosus

Lupus

Serology of lupus erythematosus: correlation between immunopathological features and clinical aspects

Autoimmune Dis

Anti-dsDNA antibodies are one of the many autoantibodies in systemic lupus erythematosus

Review
Choosing wisely: Review and commentary on anti-nuclear antibody (ANA) testing