In the first segment of this two-part column (
“Beware the Bite of ‘the Wolf,’” January 2013), we reviewed the basics of systemic lupus erythematosus (SLE) and the wide-ranging effects it has on various systems in the body. We discussed potential signs and symptoms, and specific ocular complications that include keratoconjunctivitis sicca, episcleritis/scleritis, uveitis, retinal vasculopathy and optic neuropathy.1,2
Because SLE varies in its clinical presentation, it may masquerade as other conditions—particularly rheumatoid arthritis and other autoimmune connective tissue diseases. In this second column, we discuss the diagnostic work-up, treatment and management of SLE.
When to Suspect Lupus
The American College of Rheumatology (ACR) has established 11 diagnostic criteria to help clinicians identify SLE. Four of these are needed to establish a formal diagnosis of SLE.1,3,4 (See “List of ACR Criteria for SLE.”) Given the complexity and heterogeneity of the disease, it is prudent for clinicians to consult rheumatologists and other subspecialists to investigate for each criterion when SLE is suspected.
List of ACR Criteria for SLE1,3,5
1. Malar (cheeks and nose) rash.
2. Discoid (red, raised) rash.
3. Photosensitivity (sun-related) rash.
4. Oral ulcers.
5. Arthritis.
6. Serositis (pleuritis or pericarditis).
7. Renal disorder (urinalysis and glomerular filtration rate abnormalities).
8. Neurological disorder (seizure or psychosis).
9. Blood disorder (e.g., hemolytic anemia, leuko/lymphopenia, thrombocytopenia).
10. Immunologic disorder (e.g., positive anti-Smith antibody, anti-phospholipid antibodies, anti-double-stranded DNA).
11. Abnormal anti-nuclear antibodies.
*Four of the 11 above criteria are needed for a formal diagnosis of SLE
Diagnostic Work-up for SLE
Diagnosis of SLE is tricky, to say the least. As a multi-system disease, it may take some time before symptoms manifest in various parts of the body—and until it does, the patient and/or clinician may not even be aware that this dangerous disease is lurking right beneath the surface. SLE, in particular, is a disease that doesn’t usually develop rapidly but rather evolves slowly over time.
Further complicating the process, there is no single diagnostic test for lupus—patients often have to undergo an extensive battery of laboratory tests, sometimes more than once. These are different for every patient and vary significantly during the course of the disease. Serial evaluation of a patient’s laboratory tests, along with the history and physician’s observations, determine the diagnosis of SLE, its course and the appropriate treatment regimen.
Several of the ACR criteria are easily identified by history and physical examination, as well as common diagnostic, radiologic (chest X-ray) and lab tests. In addition to routine blood and urine tests, clinicians often use autoantibody testing to help diagnose and evaluate SLE. In the interest of brevity, we will describe just a few of the key auto-antibody tests:1,3,5,6
- Anti-nuclear antibody (ANA). Patients with SLE tend to have high titers of ANA; this test is positive in close to 100% of all people with active SLE. However, it’s important to remember that these test results alone are not enough to confirm SLE, as a high ANA can be present in many healthy individuals as well as those with other connective tissue diseases.
- Anti-Smith antibody (Anti-Sm). While just 30% to 40% of patients with SLE have a positive anti-Sm test, it is highly specific for SLE and is rarely found in patients with other rheumatic diseases.
- Anti-double stranded DNA antibody (Anti-dsDNA). High results on this test indicate active SLE; it is not found in patients with other rheumatic diseases.
- Anti-Sjögren syndrome A and anti-Sjögren syndrome B (anti-SSA and anti-SSB). Found in primary Sjögren’s syndrome, anti-SSA and anti-SSB tests may also be positive in patients with SLE.
- Anti-chromatin antibodies. These antibodies may be present in patients with SLE who are positive for ANA but negative for anti-dsDNA.
- Antiphospholipid antibodies (APLs). One or more APLs are frequently seen with autoimmune disorders—the most common are anticardiolipin antibodies and the lupus anticoagulant. APLs are present in 50% of people with lupus, and their presence can help confirm a diagnosis. Positive test results help identify women with SLE who are at risk for blood clots, miscarriage or preterm birth.
Case Report
History
Our SLE patient’s SD-OCT
revealed parafoveal thinning and contamination of the inner/outer
segment junction line in both eyes.
A 42-year-old white female presented with a chief complaint of bilateral blur and visual dimming. The onset of these symptoms was gradual. Her systemic history was remarkable for SLE, which was being treated with 200mg Plaquenil BID. She had been receiving this pharmacotherapy for six years, and reported occasional flare-ups with fair control of the condition.
Diagnostic data
Her best-corrected visual acuity measured 20/40 OD and OS. Clinical examination showed retinal pigment epithelium disturbances located within the central macular region of each retina.
Spectral-domain OCT revealed parafoveal thinning and contamination of the inner/outer segment junction line in both eyes.
Autofluorescence imaging revealed a “bull’s eye” pattern. Threshold 10-2 perimetry revealed moderately dense central defects OD/OS consistent with the patient’s visual function.
Management
Consultation with the patient’s rheumatologist was obtained. After trying both nonsteroidal and steroid therapies, the patient was eventually switched to Benlysta, a novel immunomodulatory agent.
Treatment Approaches
The goals for treating a patient with SLE are to minimize complications by reducing tissue inflammation, preventing flare-ups and easing symptoms. Treatment plans are individualized for each patient, based on age, health, symptoms and lifestyle.1,3
A wide variety of medical therapies are now available for SLE, increasing the potential for enhanced patient outcomes. Patients living with SLE are treated with nonsteroidal anti-inflammatory drugs, antimalarial agents, glucocorticoids and immunosuppressive drugs.1,3,6,7
Autofluorescence imaging revealed a “bull’s eye” pattern.
Intravenous immunoglobulins may be used to control systemic lupus erythematosus with organ involvement or vasculitis.
Although the mechanism by which these products help is not well understood, it is thought that they reduce antibody production or promote the clearance of immune complexes from the body.8,9
Some of the more commonly used medications used to treat symptoms include Cytoxan (cyclophosphamide, Bristol-Myers Squibb), Imuran (azathioprine, Prometheus Laboratories), Rheumatrex (methotrexate, DAVA Pharmaceuticals) and CellCept (mycophenolate mofetil, Genentech).6-9
In addition, some agents—including Plaquenil (hydroxychloroquine, Sanofi-Aventis), prednisone and aspirin—have been FDA approved specifically for the treatment of SLE.
A monoclonal antibody-based treatment, Benlysta (belimumab, Human Genome Sciences), is the first new medication approved for lupus in more than 50 years.10 When added to standard therapy, this intravenous drug can reduce the level of SLE activity, such as joint pain, in patients whose disease is auto-antibody positive, according to the FDA.
Newer drug therapies hold promise, and are potentially more effective and less toxic than traditional treatments. Astute eye care providers should monitor for systemic lupus erythematosus in patients with and without ocular manifestations. Additionally, you must properly screen for unwanted ocular side effects of treatments, especially in patients who use corticosteroids or antimalarial agents.
1. Siegel RM, Lipsky PE. Autoimmunity. In: Firestein GS, Budd RC, Harris Ed, et al. (eds.). Kelley’s Textbook of Rheumatology. 8th ed. Philadelphia: Saunders Elsevier; 2009.
2. Arevalo JF, Lowder CY, Muci-Mendoza R. Ocular manifestations of systemic lupus erythematosus. Curr Opin Ophthalmol. 2002 Dec;13(6):404-10.
3. Male D, Brostoff J, Roth DB, Roitt I. Immunology. 8th ed. Philadelphia: Elsevier Saunders; 2012.
4. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Handout on health: systemic lupus erythematosus. Available at:
www.niams.nih.gov/health_info/lupus. Accessed December 27, 2012.
5. Sivaraj RR, Durrani OM, Denniston AK, et al. Ocular manifestations of systemic lupus erythematosus. Rheumatology (Oxford). 2007 Dec;46(12):1757-62.
6. Read RW. Clinical mini-review: systemic lupus erythematosus and the eye. Ocul Immunol Inflamm. 2004 Jun;12(2):87-99.
7. Wiseman MH, Weinblatt ME, Louie JS. Treatment of Rheumatic Diseases: A Companion to Kelley’s Textbook of Rheumatology. 2nd ed. Philadelphia: W.B. Saunders; 2000.
8. Ruiz-Irastorza G, Khamashta MA. Hydroxychloroquine: the cornerstone of lupus therapy. Lupus 2008 Apr;17(4):271-3.
9. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010 Jan;69(1):20-8.
10. Hill E. Belimumab earns FDA approval for lupus. Medscape News. March 15, 2011. Available at:
www.medscape.com/viewarticle/738729. Accessed December 11, 2012.
