CE/CME

Systemic Lupus Erythematosus: The Devastatingly Deceptive Disease

Clinician Reviews. 2016 August;26(8):38-46

References

1. Hellmann DB, Imboden JB. Rheumatologic & immunologic disorders. In: Papadakis M, McPhee SJ, Rabow MW, eds. Current Medical Diagnosis & Treatment. 53rd ed. New York, NY: McGraw-Hill; 2014:786-836.
2. Bertsias G, Cervera R, Boumpas DT. Systemic lupus erythematosus: pathogenesis and clinical features. In: Bijlsma JWJ, ed. EULAR Textbook on Rheumatic Diseases. London: BMJ Group; 2012:476-505.
3. Dall’Era M. Chapter 21. Systemic lupus erythematosus. In: Imboden JB, Hellmann DB, Stone JH, eds. Current Diagnosis & Treatment: Rheumatology. 3rd ed. New York, NY: McGraw-Hill; 2013.
4. Lupus Foundation of America. What is lupus? www.lupus.org/answers/entry/what-is-lupus. Accessed July 19, 2016.
5. Furst DE, Clarke AE, Fernandes AW, et al. Incidence and prevalence of adult systemic lupus erythematosus in a large US managed-care population. Lupus. 2012;22(1):99-105.
6. Pons-Estel GL, Alarcón GS, Scofield L, et al. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum. 2010;39(4):257-268.
7. Lisnevskaia L, Murphy G, Isenberg D. Systemic lupus erythematosus. Lancet. 2014;384(9957):1878-1888.
8. Mok CC, Kwok RC, Yip PS. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus. Arthritis Rheum. 2013;65(8):2154-2160.
9. Merola JF, Bermas B, Lu B, et al. Clinical manifestations and survival among adults with SLE according to age at diagnosis. Lupus. 2014;23(8):778-784.
10. Font J, Cervera R, Ramos-Casals M, et al. Clusters of clinical and immunologic features in systemic lupus erythematosus: analysis of 600 patients from a single center. Semin Arthritis Rheum. 2004;33(4):217-230.
11. Kiriakidou M, Cotton D, Taichman D, Williams S. Systemic lupus erythematosus.Ann Intern Med. 2013;159(7):2-16.
12. Wolff K, Johnson R, Saavedra A. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, NY: McGraw-Hill; 2013:334-342.
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14. Chen PY, Chang CH, Hsu CC, et al. Systemic lupus erythematosus presenting with cardiac symptoms. Am J Emerg Med. 2014;32(9):1117-1119.
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16. Wallace DJ. Diagnosis and differential diagnosis of systemic lupus erythematosus in adults. UpToDate. www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-systemic-lupus-erythematosus-in-adults. Accessed July 19, 2016.
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18. Bennett RM, Friend R, Marcus D, et al. Criteria for the diagnosis of fibromyalgia: validation of the modified 2010 preliminary American College of Rheumatology criteria and the development of alternative criteria. Arthritis Care Res (Hoboken). 2014;66(9):1364-1373.
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21. Copple SS, Sawitzke AD, Wilson AM, et al. Enzyme-linked immunosorbent assay screening then indirect immunofluorescence confirmation of antinuclear antibodies: a statistical analysis. Am J Clin Pathol. 2011;135(5):678-684.
22. Von Feld JM; American College of Rheumatology. Antinuclear antibodies (ANA). 2015. www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Antinuclear-Antibodies-ANA. Accessed July 19, 2016.
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LABORATORY WORK-UP
Laboratory abnormalities associated with SLE include anemia, leukopenia, lymphopenia, thrombocytopenia, hypocomplementemia, and proteinuria. A typical work-up includes a routine complete blood count (CBC) with differential, serum creatinine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinalysis with microscopy, and serologic ANA titer.^1,16,19 A CBC with differential may reveal hematologic abnormalities, such as anemia of chronic disease (most commonly) or autoimmune hemolytic anemia, as well as leukopenia and thrombocytopenia due to circulating autoantibodies.³ An elevated ESR and CRP indicate the severity of the systemic inflammation and/or infection. Urinalysis is effective for detecting lupus with renal diseaseand may reveal proteinuria due to renal dysfunction.²

A positive ANA titer indicates widespread activation of the immune system targeted against nuclear and cytoplasmic subparticles. The vast majority of patients with SLE will develop a positive ANA with a high titer at some point during the course of their disease.¹⁶ The ANA is highly sensitive for SLE (93% to 95%) but lacks specificity (57%).²⁰The most common tests for ANA are enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA). ELISA is more sensitive in detecting ANA, while IFA is the gold standard due to its high specificity.²¹ Some laboratories may use immunoassay as a screening tool for ANA and then use IFA to confirm positive or equivocal results.²¹ Positive ANA results can be seen in patients with other rheumatologic diseases and in up to 15% of all healthy persons, but with low or borderline titers.²² For these reasons, ANA testing alone is a poor predictor of SLE.

When either the ANA test results are positive or are negative but a strong clinical suspicion for SLE remains, clinicians should order tests for antibodies to extractable nuclear antigens (ENA panel; see Table 2).^3,16 Anti-dsDNA and anti-Smith (anti-Sm) antibodies are both specific for SLE, and levels of anti-dsDNA reflect disease activity in many patients.^1,19 In contrast, anti-dsDNA antibodies are found in fewer than 0.5% of healthy individuals and patients with other autoimmune conditions.¹⁹ Among patients with high levels of anti-dsDNA antibodies and clinically inactive disease, 80% will have active disease within five years after elevated antibodies are detected.¹⁹

Autoantibodies, including ANA, anti-SSA/Ro, anti-SSB/La, and antiphospholipid antibodies, are usually detectable for many years prior to the onset of symptomatic SLE, while others, such as anti-Sm and anti-U1RNP, appear just months before the diagnosis.²³ Patients with positive ANA results who do not meet criteria for SLE are still at risk for lupus and other autoimmune diseases, because complex autoimmune changes occur years before the diagnosis of SLE.²³ These patients should be followed closely.

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Systemic Lupus Erythematosus: The Devastatingly Deceptive Disease

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