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.
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MAKING THE DIAGNOSIS
Diagnosing SLE may prove problematic because of the remarkable variety of relapsing and remitting clinical features, mimicry of similar conditions, and lack of a simple, definitive diagnostic test. Initial diagnosis of SLE depends on the disease manifestation, published criteria, and exclusion of alternative diagnoses. Confirmation requires careful clinical assessment, based on a thorough medical history and complete physical examination, along with specific laboratory testing.^1,16 Biopsy results indicative of lupus nephritis in the presence of ANA or anti-dsDNA antibodies also confirm the diagnosis of SLE.²⁴

Although created for research purposes, ACR classification criteria for SLE, published in 1982 and revised in 1997, have been used for more than 30 years to diagnose lupus (see www.rheumatology.org/Practice-Quality/Clinical-Support/Criteria/ACR-Endorsed-Criteria). In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group revised the 1997 ACR classification criteria to address major flaws and to improve clinical precision.²⁴ According to SLICC, a definitive diagnosis requires the presence of at least four of 17 criteria, including at least one clinical and one immunologic criterion.²⁴ The SLICC revisions have resulted in fewer misclassifications and provide greater sensitivity but lower specificity in the identification of SLE in comparison to the 1997 ACR criteria.²⁴ To date, no one set of criteria allows for early diagnosis of SLE.

MANAGEMENT OPTIONS
Treatment must be tailored to the patient’s specific organ system involvement. Effective therapy hinges on controlling symptoms and reducing underlying inflammation.²⁵ Four classes of drugs are used: NSAIDs, antimalarial drugs, corticosteroids, and cytotoxic drugs (see Table 3). Most patients benefit from NSAIDs to alleviate minor arthritis and arthralgia symptoms, but the risk for peptic ulcers and nephrotoxicity should be addressed; this may require the concomitant use of gastroprotective agents such as proton pump inhibitors.²⁵ Antimalarials are effective for musculoskeletal symptoms that do not respond to NSAIDs and for cutaneous rashes.¹ The current antimalarial drug of choice is hydroxychloroquine (200 to 400 mg/d po), which has been shown to control SLE manifestations by reducing and preventing disease flares.^1,11,26 It is well tolerated and can be used for the duration of treatment.^11,26 Patients should be informed that this drug’s onset of action is one month.²⁶ In rare cases, this drug can cause retinal toxicity; therefore, SLE patients receiving hydroxychloroquine should be referred to an ophthalmologist for a baseline eye examination and yearly assessments to monitor for this rare adverse effect.^25,26

Low-dose corticosteroids, such as oral prednisolone or methylprednisolone, are employed when NSAIDs and antimalarials fail to control arthritis or cutaneous SLE eruptions.²⁵ Major systemic manifestations that occur during a disease flare—such as severe arthritis, hemolytic anemia, glomerulonephritis, alveolar hemorrhage, pericarditis, pleurisy, or CNS involvement—necessitate high-dose IV corticosteroids in conjunction with immunosuppressive agents.^1,11,25 These high-dose glucocorticoids should be gradually withdrawn as soon as remission is achieved.¹¹ Long-term suppressive therapy with oral corticosteroids in addition to other agents is often needed to preserve organ function.²⁵

The major adverse effects of long-term glucocorticoids are osteoporosis, hypertension, hyperlipidemia, glucose intolerance, and susceptibility to infection. It is recommended that patients taking prednisolone 7.5 mg/d or more undergo a bone mineral density scan every two years.²⁵ Those with T scores below –2.5 should be prescribed bisphosphonates.²⁵

Immunosuppressive agents, such as cyclophosphamide, mycophenolate mofetil, and azathioprine, are used in conjunction with corticosteroids or when syndromes are resistant to corticosteroids.¹ Collaboration between primary care, rheumatology, and nephrology is advisable for patients requiring immunosuppressive or disease-modifying pharmacologic agents.

Two new treatments for SLE are the immunologic agents belimumab and rituximab.⁷ Belimumab, a monoclonal human antibody, is the first medication in the past 50 years that has been approved by the FDA for antibody-positive SLE patients with active lupus unresponsive to standard treatment.^7,27 Rituximab is an anti-CD20 monoclonal antibody, approved by the FDA for non-Hodgkin lymphoma, chronic lymphocytic leukemia, and RA, and is now considered an option for SLE refractory to conventional treatment regimens.^7,27 The efficacy of belimumab and rituximab, and the spectrum of indications for their use, are still under study, but these new therapeutic agents hold promise for the treatment of patients with refractory SLE.

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Systemic Lupus Erythematosus: The Devastatingly Deceptive Disease

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