FPIN's Clinical Inquiries

Antibody Testing for Systemic Lupus Erythematosus



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Am Fam Physician. 2011 Dec 15;84(12):1407-1409.

Clinical Question

What is the role of antibody testing in the diagnosis of systemic lupus erythematosus (SLE)?

Evidence-Based Answer

Antibody testing plays an important role when assessing patients, but should not be used alone to diagnose SLE. (Strength of Recommendation: C, based on expert opinion.) The antinuclear antibody (ANA) test is the most commonly used screening test for SLE. The presence of anti-DNA, anti-Sm, and antiphospholipid antibodies is more specific for diagnosing SLE.

Evidence Summary

The diagnosis of SLE is made in patients who meet four of the 11 criteria outlined by the American College of Rheumatology (ACR).1,2  Table 1 shows the revised ACR classification criteria for SLE.1,2 Two of the criteria are the presence of antibodies (i.e., ANA and either antibody to DNA antigen [anti-DNA], antibody to Sm nuclear antigen [anti-Sm], or anticardiolipin antibody). Therefore, positive values on antibody tests can represent one-half of the criteria for a diagnosis of SLE.

Initial evaluation for suspected autoimmune disease often includes an ANA test, which is positive in 95 percent of patients with SLE.3 The ANA test has a false-negative rate of only 5 percent, but the specificity is low because many healthy patients and those with chronic liver disease, a neoplasm, or active infection also may have a positive test. Consequently, a positive ANA test result can be used only as part of the diagnosis.46 A prospective blind comparison of the sera of 213 patients in India was performed to determine the best screening dilution to distinguish between healthy persons and those with SLE.7 A dilution of 1:80 maximized the sensitivity and specificity. Using this standard, testing was positive for ANA in 95.3 percent of those with SLE and in 4.3 percent of those without SLE. This study was limited by age, sex, ethnicity, and environmental factors, which can affect ANA testing.

In patients with a suspected rheumatologic disorder, anti-DNA, anti-Sm, and antiphospholipid antibodies are more specific than ANA for diagnosing SLE. A retrospective study of 127 patients with various connective tissue disorders found elevated titers of anti-DNA antibody (82 percent), anti-Sm antibody (60 percent), and antiphospholipid antibody (62 percent) in the 50 patients with SLE who had an ANA titer of at least 1:128, but not in patients with other connective tissue disorders.8 In this study, 80 percent of all patients with SLE tested positive for at least two of three antibodies, whereas patients with other connective tissue disorders had no more than one positive test result.

The antichromatin antibody is under investigation as an additional marker for SLE. In a retrospective study of 78 patients with SLE, antichromatin antibody had a sensitivity of 64 percent and a specificity of 99 percent.9

Recommendations from Others

The ACR revised criteria for the classification of SLE have become the standard for categorizing SLE around the world.10 An alternative to the ACR classification is the Boston Weighted Criteria system. In one study, these criteria identified 190 of 271 patients with SLE, whereas the ACR criteria identified 171 of 271.11 The Boston Weighted Criteria have a sensitivity of 93 percent and a specificity of 69 percent for diagnosing SLE.11

Table 1.

ACR Criteria for the Classification of Systemic Lupus Erythematosus

Criterion Definition

Malar rash

Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds

Discoid rash

Erythematous, raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions

Photosensitivity

Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation

Oral ulcers

Oral or nasopharyngeal ulceration, usually painless, observed by physician

Nonerosive arthritis

Involving two or more peripheral joints, characterized by tenderness, swelling, or effusion

Serositis

Pleuritis: convincing history of pleuritic pain or rubbing heard by a physician or evidence of pleural effusion

or

Pericarditis: documentation on electrocardiography, rubbing, or evidence of pericardial effusion

Renal disorder

Persistent proteinuria: greater than 0.5 g per day or greater than 3+ if quantitation not performed

or

Cellular casts: may be red blood cell, hemoglobin, granular, tubular, or mixed

Neurologic disorder

Seizures: in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, electrolyte imbalance)

or

Psychosis: in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, electrolyte imbalance)

Hematologic disorder

Hemolytic anemia: with reticulocytosis

or

Leukopenia: lymphocyte count less than 4,000 per μL (4 × 109 per L) on two or more occasions

or

Lymphopenia: lymphocyte count less than 1,500 per μL (1.5 × 109 per L) on two or more occasions

or

Thrombocytopenia: platelet count less than 100 × 103 per μL (100 × 109 per L) in the absence of offending drugs

Immunologic disorder

Anti-DNA: antibody to native DNA in abnormal titer

or

Anti-Sm: presence of antibody to Sm nuclear antigen

or

Positive finding of antiphospholipid antibodies based on one of the following:

An abnormal serum level of immunoglobulin G or immunoglobulin M anticardiolipin antibodies

A positive test result for lupus anticoagulant using a standard method

A false-positive serologic test result for syphilis known to be positive for at least six months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test

Antinuclear antibody

An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus


note: For the purpose of identifying patients in clinical studies, a person is considered to have systemic lupus erythematosus if at least four of the 11 criteria are present, serially or simultaneously, during any interval of observation.

ACR = American College of Rheumatology.

Adapted with permission from Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1274, with additional information from reference 2.

Table 1.   ACR Criteria for the Classification of Systemic Lupus Erythematosus

View Table

Table 1.

ACR Criteria for the Classification of Systemic Lupus Erythematosus

Criterion Definition

Malar rash

Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds

Discoid rash

Erythematous, raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions

Photosensitivity

Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation

Oral ulcers

Oral or nasopharyngeal ulceration, usually painless, observed by physician

Nonerosive arthritis

Involving two or more peripheral joints, characterized by tenderness, swelling, or effusion

Serositis

Pleuritis: convincing history of pleuritic pain or rubbing heard by a physician or evidence of pleural effusion

or

Pericarditis: documentation on electrocardiography, rubbing, or evidence of pericardial effusion

Renal disorder

Persistent proteinuria: greater than 0.5 g per day or greater than 3+ if quantitation not performed

or

Cellular casts: may be red blood cell, hemoglobin, granular, tubular, or mixed

Neurologic disorder

Seizures: in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, electrolyte imbalance)

or

Psychosis: in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, electrolyte imbalance)

Hematologic disorder

Hemolytic anemia: with reticulocytosis

or

Leukopenia: lymphocyte count less than 4,000 per μL (4 × 109 per L) on two or more occasions

or

Lymphopenia: lymphocyte count less than 1,500 per μL (1.5 × 109 per L) on two or more occasions

or

Thrombocytopenia: platelet count less than 100 × 103 per μL (100 × 109 per L) in the absence of offending drugs

Immunologic disorder

Anti-DNA: antibody to native DNA in abnormal titer

or

Anti-Sm: presence of antibody to Sm nuclear antigen

or

Positive finding of antiphospholipid antibodies based on one of the following:

An abnormal serum level of immunoglobulin G or immunoglobulin M anticardiolipin antibodies

A positive test result for lupus anticoagulant using a standard method

A false-positive serologic test result for syphilis known to be positive for at least six months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test

Antinuclear antibody

An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus


note: For the purpose of identifying patients in clinical studies, a person is considered to have systemic lupus erythematosus if at least four of the 11 criteria are present, serially or simultaneously, during any interval of observation.

ACR = American College of Rheumatology.

Adapted with permission from Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1274, with additional information from reference 2.

Address correspondence to Kacey Gibson, DO, at kacey.gibson@macdill.af.mil. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations to disclose.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official, or as reflecting the views of the U.S. Air Force Medical Service or the U.S. Air Force at large.


Copyright Family Physicians Inquiries Network. Used with permission.

REFERENCES

1. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1271–1277.

2. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.

3. Hietarinta M, Lassila O. Clinical significance of antinuclear antibodies in systemic rheumatic diseases. Ann Med. 1996;28(4):283–291.

4. Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol. 2000;53(6):424–432.

5. von Mühlen CA, Tan EM. Autoantibodies in the diagnosis of systemic rheumatic diseases. Semin Arthritis Rheum. 1995;24(5):323–358.

6. Harley JB. Autoantibodies are central to the diagnosis and clinical manifestations of lupus. J Rheumatol. 1994;21(7):1183–1185.

7. Ghosh P, Dwivedi S, Naik S, et al. Antinuclear antibodies by indirect immunofluorescence: optimum screening dilution for diagnosis of systemic lupus erythematosus. Indian J Med Res. 2007;126(1):34–38.

8. Moses S, Barland P. Laboratory criteria for a diagnosis of systemic lupus erythematosus. JAMA. 1979;242(10):1039–1043.

9. Braun A, Sis J, Max R, et al. Anti-chromatin and anti-C1q antibodies in systemic lupus erythematosus compared to other systemic autoimmune diseases. Scand J Rheumatol. 2007;36(4):291–298.

10. Petri M, Magder L. Classification criteria for systemic lupus erythematosus: a review. Lupus. 2004;13(11):829–837.

11. Costenbader KH, Karlson EW, Mandl LA. Defining lupus cases for clinical studies: the Boston Weighted Criteria for the classification of systemic lupus erythematosus. J Rheumatol. 2002;29(12):2545–2550.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net/?o=1025).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or e-mail: questions@fpin.org.

A collection of FPIN's Clinical Inquiries published in AFP is available at http://www.aafp.org/afp/fpin.


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