What conditions can cause a positive Antinuclear Antibody (ANA) test without Systemic Lupus Erythematosus (SLE)?

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From the Guidelines

A positive Antinuclear Antibody (ANA) test can be caused by conditions other than Systemic Lupus Erythematosus (SLE), including other autoimmune diseases and healthy individuals.

Conditions that can cause a positive ANA test without SLE

  • Other autoimmune diseases, such as inflammatory myopathies, Sjögren’s syndrome, and mixed connective tissue disease 1
  • Healthy individuals, with up to 25% of sera from apparently healthy individuals being ANA positive, depending on demographics and assay variables 1

Important considerations

  • The indirect immunofluorescence assay (IIFA) is the gold standard technique for ANA detection, but it lacks specificity and can yield false positives 1
  • A positive ANA test should be interpreted in the context of clinical suspicion and other laboratory tests, such as anti-dsDNA and anti-ENA antibodies 1
  • The pattern and highest dilution of ANA reactivity should be reported, and testing for anti-dsDNA antibodies is advised when there is clinical suspicion of SLE 1

From the Research

Conditions Causing a Positive ANA Test without SLE

A positive Antinuclear Antibody (ANA) test can be caused by several conditions other than Systemic Lupus Erythematosus (SLE). Some of these conditions include:

  • Acute and chronic infections, as identified in a study published in the Journal of immunoassay & immunochemistry 2
  • Primary antiphospholipid syndrome (APS), as found in a multicenter retrospective study published in Joint bone spine 3
  • Non-autoimmune inflammatory diseases, as mentioned in the study published in the Journal of immunoassay & immunochemistry 2
  • Fibromyalgia, as diagnosed in 14 out of 44 patients in a study published in the Journal of clinical rheumatology 4
  • Seronegative rheumatoid arthritis, as diagnosed in 4 out of 44 patients in the same study 4
  • Myasthenia gravis, as diagnosed in 1 out of 44 patients in the study published in the Journal of clinical rheumatology 4

Other Factors to Consider

Other factors that can contribute to a positive ANA test without SLE include:

  • Widespread pain, which was the most common reason for ordering ANA testing in a retrospective study published in The American journal of medicine 5
  • Low pretest probabilities for ANA-associated rheumatic disease, which can lead to unnecessary testing and a poor predictive value of a positive ANA test, as found in the study published in The American journal of medicine 5
  • The presence of other antibodies, such as anti-Ro antibodies, which can be associated with ANA negative SLE, as reported in a case study published in the Asian Pacific journal of allergy and immunology 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

ANA testing in the presence of acute and chronic infections.

Journal of immunoassay & immunochemistry, 2016

Research

The 'rule out lupus' rheumatology consultation: clinical outcomes and perspectives.

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 1995

Research

The clinical utility of a positive antinuclear antibody test result.

The American journal of medicine, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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