musculoskeletal and connective tissue disorders
Systemic Lupus Erythematosus (SLE)
Diagnosis of SLE
Clinical criteria Cytopenias Autoantibodies SLE should be suspected in patients, particularly young women, with any of the symptoms and signs. However, early-stage SLE can mimic other connective (or nonconnective) tissue disorders, including Rheumatoid Arthritis (RA) if arthritic symptoms predominate. Laboratory testing may differentiate SLE from other connective tissue disorders. Routine testing should include the following: Antinuclear antibodies (ANA) and anti–double-stranded (ds) DNA (anti-dsDNA) Complete blood count (CBC) Urinalysis Chemistry profile including renal and liver enzymes In clinical practice, some clinicians rely on the classification criteria for SLE developed by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR; see table). Patients are eligible for these criteria only if they have a positive ANA ≥ 1:80. The 2019 EULAR/ACR classification criteria include clinical and immunologic domains, and each criterion is assigned a weight of 2 to 10. If the patient's score is 10 or more, and at least one clinical criterion is fulfilled, disease is classified as SLE. However, a positive ANA does not indicate a diagnosis of lupus. A positive ANA test in the presence of fatigue and generalized myofascial pain without other clinical or laboratory findings is rarely significant. The fluorescent test for ANA is the best initial test for SLE in patients who have compatible symptoms and signs; positive ANA tests (usually in high titer:>1:80) occur in>98% of people with SLE. However, positive ANA tests can also occur in rheumatoid arthritis, other connective tissue disorders, autoimmune thyroid disease, cancers, and even in the general population. The false-positive rate varies from about 3% with ANA titers of 1:320 to about 30% for ANA titers of 1:40 among healthy controls. Drugs such ashydralazine,procainamide, and tumor necrosis factor-alpha antagonists can produce positive ANA results as well as a lupus-like syndrome; the ANA eventually becomes negative if the drug is stopped. Positive ANA should prompt more specific testing such as anti-dsDNA antibodies; high titers of anti-dsDNA are highly specific for SLE but occur in < 70% of people with SLE. The ANA test is very sensitive, but it is not specific for SLE; thus, evidence of other autoantibodies is used to aid in diagnosis. They include Ro (SSA), La (SSB), Smith (Sm), ribonucleoprotein (RNP), and dsDNA. Ro is predominantly cytoplasmic; anti-Ro antibodies are occasionally present in ANA-negative SLE patients presenting with chronic cutaneous lupus. Anti-Ro is the causal antibody for neonatal lupus and congenital heart block. Anti-Sm is highly specific for SLE but, like anti-dsDNA, is not sensitive. Anti-RNP occurs in patients with SLE, mixed connective tissue disease, and occasionally other systemic autoimmune disorders and systemic sclerosis. Overview of Leukopenias (usually lymphopenia) is common. Other tests help monitor disease severity and determine the need for treatment. Serum complement levels (C3, C4) are often depressed in active disease and are usually lowest in patients with active nephritis. Erythrocyte sedimentation rate (ESR) is elevated frequently during active disease. C-reactive protein levels are not necessarily elevated; high levels raise the concern for infection and/or serositis. Screening for renal involvement begins with urinalysis. Red blood cell (RBC) and/or white blood cell casts suggest active Lupus Nephritis . Urinalysis should be done at regular intervals (eg, every 3 to 6 months), even for patients in apparent remission, because kidney disease is usually asymptomatic. Proteinuria can be estimated by the urine protein/creatinine ratio or measured in a 24-hour urine collection. Renal biopsy is indicated in patients whose protein excretion is > 500 mg/day and who have hematuria (thought to be glomerular) or RBC casts and is helpful in evaluating the status of renal disease (ie, active inflammation vs postinflammatory scarring) and in guiding therapy. Patients with chronic renal insufficiency and mostly sclerotic glomeruli are not likely to benefit from aggressive immunosuppressive therapy. 