Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + TEXTBOOK PRESENTATION Download Section PDF Listen +++ ++ SLE classically presents in a young woman with fatigue and arthritis, commonly of the hands. There are often suspicious findings in the history such as an episode of pleuritis or undiagnosed anemia. + DISEASE HIGHLIGHTS Download Section PDF Listen +++ ++ SLE is a systemic autoimmune disease primarily affecting women of childbearing age. Various groups are more prone to disease. Female:male ratio is about 9:1. About 5% of patients report a first-degree relative with the disease. Women of color are most commonly affected. Almost every organ can be involved, although the joints, skin, serosa, and kidneys are most commonly affected. The pathogenesis of the disease is related to the formation of autoantibodies to a number of nuclear antigens. The ANA is the most common. The most common features of SLE, both at presentation and later in follow-up, are listed in Table 27-7. ++Table Graphic Jump LocationTable 27-7.Clinical manifestations of SLE at onset and during disease.View Table||Download (.pdf)Table 27-7. Clinical manifestations of SLE at onset and during disease. Signs and Symptoms Prevalence at Onset Prevalence at any Time Arthralgia 77% 85% Rashes 53% 78% Constitutional 53% 77% Kidney involvement 38% 74% Arthritis 44% 63% Raynaud phenomenon 33% 60% CNS involvement (most commonly headache) 24% 54% GI (most commonly abdominal pain) 18% 45% Lymphadenopathy 16% 32% Pleurisy 16% 30% Pericarditis 13% 23% CNS, central nervous system; GI, gastrointestinal; SLE, systemic lupus erythematosus. + EVIDENCE-BASED DIAGNOSIS Download Section PDF Listen +++ ++ The diagnosis of SLE, especially in people with mild disease, can be difficult. The ACR has developed criteria to standardize the diagnosis for research purposes. The criteria are: Malar rash Discoid rash Photosensitivity Oral ulcers Arthritis (nonerosive arthritis) Serositis (pleuritis or pericarditis) Kidney disorder (proteinuria or cellular casts) Neurologic disorder (headache, seizures, or psychosis without other cause) Hematologic disorder (hemolytic anemia or any cytopenia) Immunologic disorder (anti-ds-DNA, anti-SM, or antiphospholipid antibodies) Positive ANA The diagnosis of SLE requires the presence of 4 or more of these criteria. Although the same reservations about using diagnostic criteria clinically that were discussed above in the section on RA apply here, the SLE criteria are frequently used. Newer diagnostic criteria have also been developed by the Systemic Lupus International Collaborating Clinics (SLICC) group. These criteria, referenced at the end of the chapter, give somewhat greater primacy to serologic and pathologic evidence of SLE. A patient may fulfill the criteria with biopsy-proven SLE nephritis and the presence of ANA or anti-ds-DNA antibodies. The test characteristics for the diagnostic criteria are given in Table 27-8. Also included in this table are the test characteristics for the various individual criteria. Satisfaction of the ACR criteria or the presence of the anti-Sm antibody is highly supportive of the diagnosis of SLE. Failure to fulfill the SLICC criteria or the absence of ANA argue strongly against SLE. Autoantibodies Measuring autoantibodies in SLE provides important diagnostic information. ANA and anti-ds-DNA ANA is the most sensitive test for SLE. It is nonspecific. Anti-ds-DNA and anti-Sm are highly specific. They are also associated with the presence of lupus nephritis. ANA does not vary with disease activity while anti-ds-DNA does. A negative ANA essentially rules out SLE. A positive anti-ds-DNA or anti-Sm essentially rules in SLE. Staining patterns are often reported with the ANA. These patterns correlate, to some extent, with the other specific antibodies discussed below and their use has, to a great extent, been supplanted by these tests. In general, the meanings of the staining patterns are as follows: Homogeneous: Seen in SLE, RA, and drug-induced lupus Peripheral: Most specific pattern for SLE Speckled: Least specific pattern. Commonly seen with low titer ANAs in people without rheumatic disease Nucleolar: Common in patients with scleroderma and Raynaud phenomenon. Other serologies are helpful because they tend to be associated with various subsets of disease. Anti-RNP: Associated with Raynaud phenomenon and myositis and highly sensitive for mixed connective tissue disease. Anti-SSA/Ro and anti-SSB/La: Associated with Sjögren syndrome and photosensitivity Anti-ribosomal P: Highly specific for SLE Table 27-9 outlines a variety of serologies that may be obtained in persons in whom rheumatologic disease is suspected. Complement Complement levels are helpful in tracking the activity of SLE but are nonspecific. C3, C4, and CH50 levels tend to decline during episodes of lupus activity. ++Table Graphic Jump LocationTable 27-8.Test characteristics for the ACR and SLICC criteria and individual criteria in the diagnosis of SLE.View Table||Download (.pdf)Table 27-8. Test characteristics for the ACR and SLICC criteria and individual criteria in the diagnosis of SLE. Finding Sensitivity Specificity LR+ LR− ACR criteria 83% 96% 21 0.18 SLICC criteria 97% 84% 6.1 0.04 Oral ulcers 44% 92% 6.0 0.61 Nonscarring alopecia 32% 96% 7.4 0.71 Serositis 35% 97% 12.6 0.66 Kidney disorder 33% 96% 9.1 0.70 Leukopenia 46% 95% 8.9 0.57 Anti-ds-DNA 57% 96% 13.9 .044 ANA 96% 45% 1.7 .077 Anti-Sm 26% 99% 20.0 0.75 Low complement 59% 93% 7.9 0.44 ACR, American College of Rheumatology; ANA, antinuclear antibody; SLICC, The Systemic Lupus International Collaborating Clinics; SLE, systemic lupus erythematosus.Data from Petri M, Orbai AM, Alarcón GS et al: Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus, Arthritis Rheum. 2012 Aug;64(8):2677–2686. ++Table Graphic Jump LocationTable 27-9.Common serologies in rheumatologic diseases.View Table||Download (.pdf)Table 27-9. Common serologies in rheumatologic diseases. Antibody Clinical Association Anti-ds-DNA Nephritis in SLE Anti–Smith SLE Anti-RNP Raynaud phenomenon and myositis in SLE Anti Ribosomal P High specificity for SLE Anti SSA/Ro, Anti SSB/La Sjögren syndrome and skin disease in SLE Anti-histone antibodies Drug-induced lupus Anti-Jo-1 Polymyositis/dermatomyositis Anti-DNA topoisomerase I (Scl-70), anti-RNA polymerase I and III Systemic sclerosis (scleroderma) ANCA Many vasculitic diseases including granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis Anti-U1 RNP antibodies Mixed connective tissue disease Anti-GBM Anti-GBM antibody (Goodpasture disease) ANCA, anti-neutrophil cytoplasmic antibody; anti-GBM, anti-glomerular basement antibodies; SLE, systemic lupus erythematosus. + TREATMENT Download Section PDF Listen +++ ++ Similar to RA, the treatment of SLE is complicated and the purview of the rheumatologist. In general, NSAIDs, corticosteroids, and immunosuppressants are the mainstays of therapy. NSAIDs are generally used for symptomatic relief of inflammatory symptoms with careful monitoring because of their potential nephrotoxic effects. Corticosteroids and hydroxychloroquine are commonly used in long-term therapy and high-dose corticosteroids are used for disease exacerbations. Cyclophosphamide, mycophenolate mofetil, and azathioprine are the most commonly used immunosuppressants in SLE. They are used most widely for the treatment of lupus nephritis.