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.
13. Popescu A, Kao AH. Neuropsychiatric systemic lupus erythematosus. Curr Neuropharmacol. 2011;9(3):449-457.
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.
15. Hahn BHH. Chapter 378: Systemic lupus erythematosus. In: Kasper DL, Fauci AS, Hauser SL, et al, eds. Harrison’s Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill; 2015.
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.
17. Cappelli S, Bellando Randone S, Martinovic D, et al. “To be or not to be,” ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum. 2012;41(4):589-598.
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.
19. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-939.
20. Magrey M, Abelson A. Laboratory evaluation of rheumatic diseases. Cleveland Clinic Center for Continuing Education 2010. www.cleveland clinicmeded.com/medicalpubs/diseasemanagement/rheumatology/laboratory-evaluation-rheumatic-diseases/. Accessed July 19, 2016.
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.
23. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526-1533.
24. Petri M, Orbai A, Alarcón G, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686.
25. Ioannou Y, Isenberg DA. Current concepts for the management of systemic lupus erythematosus in adults: a therapeutic challenge. Postgrad Med J. 2002;78:599-606.
26. Dall’Era M, Wofsy D. Treatment of systemic lupus erythematosus. In: Imboden JB, Hellmann DB, Stone JH, eds. Current Diagnosis & Treatment: Rheumatology. 3rd ed. New York, NY: McGraw-Hill; 2013.
27. Stohl W, Hilbert DM. The discovery and development of belimumab: the anti-BLyS–lupus connection. Nat Biotechnol. 2012;30(1):69-77.
28. Lateef A, Petri M. Unmet medical needs in systemic lupus erythematosus. Arthritis Research & Ther. 2012;14(suppl 4):S4.
29. Bertsias G, Ioannidis JP, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics. Ann Rheum Dis. 2008;67(2):195-205.

DIFFERENTIAL DIAGNOSES
The differential diagnosis for SLE includes rheumatoid arthritis (RA), septic arthritis, mixed connective tissue disease (MCTD), Sjögren syndrome, systemic sclerosis (SSc), polymyositis (PM), fibromyalgia, and drug-induced lupus. Symmetrical, inflammatory, polyarticular arthritis with a predilection for the wrist and MCP joints occurs in both RA and SLE.^1,15 And, because the initial articular features of SLE are symmetric arthralgias, patients with SLE are frequently misdiagnosed with RA. The absence of destructive bony erosions on radiographs and large joint effusions, along with the joint reducibility in SLE, can help distinguish it from RA.¹⁶ Asymmetric arthritis, which can be a presenting feature in both RA and SLE, is more commonly seen in the latter. ANA and rheumatoid factor test results can be positive in both disorders, but antibodies to anti-cyclic citrullinated peptides, with a 95% specificity for RA but absent in SLE, distinguish RA from SLE.^1,16

Patients with MCTD display an array of overlapping features of SLE, PM, and SSc, making the diagnosis difficult.¹⁷ Although MCTD can evolve into other connective tissue diseases, such as SLE, it is nonetheless considered a distinct entity.¹⁷ High titers of anti-U1 ribonucleoprotein (anti-U1RNP) antibodies are indicative of MCTD. Anti-U1RNP is rarely detected in SLE and almost never seen in other rheumatic diseases.¹⁷ Typical manifestations of MCTD are Raynaud phenomenon, swollen fingers (referred to as “sausage digits”), and protuberant polyarthritis.¹⁷

Anti-SSA/Ro and anti-SSB/La antibodies, although detectable in SLE patients, are more commonly associated with Sjögren syndrome. In addition, patients with Sjögren syndrome frequently demonstrate signs of keratoconjunctivitis sicca and xerostomia.¹⁶

The clinical features of fibromyalgia include diffuse musculoskeletal pain that readily mimics SLE arthralgias. The 2011 modification of the 2010 American College of Rheumatology (ACR) preliminary diagnostic criteria for fibromyalgia serves as a reliable tool for diagnosing patients with nonspecific, diffuse pain.¹⁸ This 2011 modification includes 19 pain locations and the six self-reported symptoms: fatigue, impaired sleep, headaches, depression, poor cognition, and abdominal pain.¹⁸

SSc, also known as scleroderma, is characterized by skin thickening and/or CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia). The presence of anti-Scl-70 and anti-centromere antibodies are noted as well.¹⁶

Finally, a suspicion of SLE mandates an evaluation for drug-induced lupus by assessing the patient’s exposure to culprit medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, minocycline, and tumor necrosis factor inhibitiors.^1,11 Four key features point toward drug-induced lupus:
• The female-to-male ratio is nearly equivalent.
• Nephritis and central nervous system (CNS) manifestations are not commonly present.
• Anti–double-stranded DNA (anti-dsDNA) antibodies and hypocomplementemia are absent.
• The clinical features and laboratory abnormalities return to baseline once the offending agent is removed.¹

Anti-histone antibodies are present in approximately 75% of patients with drug-induced lupus but can also be seen in patients with SLE.¹¹

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Systemic Lupus Erythematosus: The Devastatingly Deceptive Disease

References

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