Laboratory and Other Studies for SLE Test Notes The most common anemia in SLE is from chronic

disease. Hemolytic anemia will usually have a positive direct Coombs' test, for either IgG or complement, or both. Complete blood count Both leukopenia and lymphopenia are found in SLE. Thrombocytopenia can be due to SLE or to antiphospholipid antibodies Although the ESR is commonly elevated, it is not specific Erythrocyte sedimentation rate for SLE An elevated creatinine may be a clue to renal lupus. Comprehensive metabolic panel Mild elevations in liver function tests occur in 30% SLE myositis presents with proximal muscle weakness. Creatine phosphokinase Creatine phosphokinase is usually elevated Glomerulonephritis usually presents with proteinuria, Urinalysis with or without hematuria. Erythrocytes or granular casts can be seen Anti-DNA or anti-Sm are specific for SLE. Low C3 and low C4 are common in SLE, but not specific. Serologies A negative ANA argues against SLE. Anti-RNP, anti-Ro/SSA, anti-La/SSB, and antiphospholipid antibodies may be found, but they are not specific for SLE Indicated in patients with laboratory findings suggestive Renal biopsy of lupus nephritis Other diagnostic studies depend upon specific manifestation of the disease

Systemic lupus erythematosus (SLE) is a chronic multisystemic disease of autoimmune origin SLE characteristically affects skin and joints, although any system can be involved SLE commonly affects women aged 20-45 years but may affect all age groups and both sexes American College of Rheumatology criteria for diagnosis of SLE suggest that four or more of the following must be present for the diagnosis to be made: malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, hematologic disorder, immunologic disorder, antinuclear antibody (ANA) Treatment options are vast and dictated by the severity of disease; options include the use of nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, hydroxychloroquine, and more aggressive medications, such as cyclophosphamide and mycophenolate mofetil SLE is a chronic autoimmune multisystem disease with a fluctuating course It most commonly affects the skin and joints, and is most common in women aged 20-45 years, but does occur in all adult age groups of both sexes and can involve any body system The diagnosis is made on clinical grounds and on the presence of antibodies to nuclear antigens and to doublestranded DNA The most common presentation is with a butterfly rash on the face, low-grade fever, and nondeforming arthritis In mild cases, symptoms can be controlled by rest, NSAIDs, and avoidance of sunlight

NSAIDs are useful for arthralgia and hydroxychloroquine for the rashes More severe cases with multisystem involvement need treatment with systemic corticosteroids and/or other immunosuppressive agents

These criteria were designed for standardizing the inclusion of patients in clinical trials; however, they are useful as general clinical guidelines in the initial assessment of patients with suspected SLE: Malar rash: fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds Discoid rash: erythematous, raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions Photosensitivity: skin rash as a result of unusual reaction to sunlight, by patient history or physician observation Oral ulcers: oral or nasopharyngeal ulceration, usually painless, observed by physician Arthritis: nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling, or effusion Serositis: (a) pleuritis - convincing history of pleuritic pain or pleural rub heard by a physician or evidence of pleural effusion, or (b) pericarditis - documented by electrocardiogram or pericardial rub or evidence of pericardial effusion Renal disorders: (a) persistent proteinuria greater than 0.5g/day or greater than 3+ (dipstick) if quantitation not performed, or (b) cellular casts - may be red cell, hemoglobin, granular, tubular, or mixed Neurologic disorder: (a) seizures in the absence of offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis, or electrolyte imbalance, or (b) psychosis in the absence of offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis, or electrolyte imbalance, (c) symptoms of stroke, (d) migrainous type headaches, (e) peripheral neuropathy, (f) transverse myelitis, (g) depression, (h) cognitive dysfunction Hematologic disorder: (a) hemolytic anemia with reticulocytosis, or (b) leukopenia <4000/mm 3total on two or more occasions, or (c) lymphopenia <1500/mm3on two or more occasions, or (d) thrombocytopenia <100,000/mm3in the absence of offending drugs Immunologic disorder: (a) anti-DNA: antibody to native DNA in abnormal titer, or (b) anti-Smith: presence of antibody to Smith nuclear antigen, or (c) positive finding of antiphospholipid antibodies based on: (1) an abnormal serum level of IgG or IgM anti-cardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for at least 6 months and confirmed by the absence ofTreponema pallidumimmobilization or fluorescent treponemal antibody absorption test Antinuclear antibody (ANA): an abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with 'drug-induced lupus' syndrome. Presence of positive ANA is a cardinal feature but is not specific for SLE

In addition: Constitutional symptoms: fatigue, fever, malaise, and weight loss Other skin rashes: including calcified nodules, vasculitis, leg ulceration, and scalp ulcers with or without alopecia Sicca syndrome (dry eyes/mouth) and Raynaud's phenomenon are common Cardiac involvement: pericardial rub in pericarditis and heart murmurs if there is endocarditis or valvular thickening/dysfunction Hypertension : systemic and pulmonary Other features: including lymphadenopathy, splenomegaly, venous and arterial thrombosis

The differential is extensive, and will depend upon which system(s) is (are) involved at presentation. It is important to distinguish systemic lupus erythematosus (SLE) from other multisystemic conditions, particularly rheumatoid arthritis, Sjgren's syndrome, fibromyalgia, and systemic infections. These are the only differentials cited in detail here. Rheumatoid arthitis

Rheumatoid arthritis is a chronic multisystem inflammatory disease of unknown etiology. Features Characteristic features are persistent inflammatory synovitis, usually involving peripheral joints in a symmetrical distribution Early in the disease, painful joint effusions restricting movement are common, as is prolonged morning stiffness. In late disease, characteristic deformities can occur (subluxation, dislocation, joint contractures) Systemic involvement may be marked, with fevers, anorexia, splenomegaly, pericarditis, vasculitis, and uveitis A raised rheumatoid factor occurs in 80% of cases after 2 years, (can be only 50% at onset), often with raised erythrocyte sedimentation rate and C-reactive protein level Radiographs usually reveal soft tissue swelling and osteopenia in early disease, whereas they later show joint space narrowing, erosion, and deformity as the articular surface is destroyed

Other differentials to consider include the following, however, these lists are not exhaustive: Arthralgia/arthropathy: rheumatoid arthritis, mixed connective tissue disorder, other arthropathies, fibromyalgia Fever and malaise: bacterial infections, viral infections, fungal infections, malignancy, endocarditis, fever of unknown origin, chronic fatigue syndrome, poisoning Chest symptoms: myocardial infarction, pulmonary embolism, adult respiratory distress syndrome (ARDS), chest infections including tuberculosis Neurologic: stroke (either hemorrhagic or ischemic), seizures, and other neurologic complaints Skin lesions: scleroderma, discoid lupus (can occur in absence of systemic disease), atopic dermatitis Renal symptoms: glomerulonephritis and other renal conditions Abdominal pain: abdominal blunt trauma, constipation, ischemic bowel, vasculitis Hematologic: hemolytic anemia, immune or thrombotic thrombocytopenia, lymphoma Vasculitis: other vasculitides

Diagnostic decision Diagnosis is based on clinical findings aided by results of laboratory tests The typical course of the disease shows exacerbations and remissions The mean length of time between onset of symptoms and diagnosis is 5 years

The American College of Rheumatology has produced criteria that are useful in the initial assessment of patients with suspected SLE. These guidelines list 11 criteria for the diagnosis of SLE, and a diagnosis can be made when four or more of these criteria are present: Malar rash Discoid rash Photosensitivity Oral ulcers Arthritis Serositis Renal disorders Neurologic disorder Hematologic disorder Immunologic disorder Antinuclear antibody

ummary of tests

Although the diagnosis should be made on grounds of history and examination, laboratory tests may be useful for confirmation. They may also be useful in evaluating a disease flare: Complete blood count : leukopenia is a good index of disease activity; also lymphopenia, anemia of chronic disease, evidence of hemolytic disease. Thrombocytopenia occurs in 30-50% of cases and may be severe (as a result of antiplatelet autoantibodies, antiphospholipid antibodies, or marrow suppression due to drugs or disease) Acute phase reactants - erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): may be elevated in disease activity. The ESR is usually elevated in active disease or inflammation and infection Complete chemistry panel : to evaluate electrolytes, liver and kidney function Autoantibody screen : presence of ANA is the cardinal feature in SLE and occurs in over 90% of cases, depending upon the titer of the ANA. Although ANA-negative SLE can rarely occur, a negative ANA will call the diagnosis into question. Measurement of ANA subtypes may also be performed Antibodies to double-stranded DNA (dsDNA): antibody to dsDNA is more specific for lupus and often correlates with disease activity and nephritis. DsDNA can be measured in two ways - quantitatively and qualitatively. The quantitative method is more sensitive and less specific, and is currently more commonly used Extractable nuclear antibodies (ENA panel): includes anti-Ro (SS-A), anti-La (SS-B), anti-Smith, and antiRNP antibodies. These antibodies are all commonly found in SLE but may also be positive in other autoimmune disease. Anti-Ro is associated also with Sjgren's syndrome and subacute cutaneous lupus erythematosus; in SLE, it is associated with increased photosensitivity. Anti-La is also associated with Sjgren's syndrome. Anti-Smith antibodies are highly specific but not sensitive for SLE - seen in 30%). AntiRNP is associated with SLE and can indicated susceptibility to muscle disease or overlap with sclerodermatous-type symptoms Antihistone antibodies: highly sensitive (>95%) for drug-induced lupus with the important exception of minocycline-induced lupus. Antibodies to histone are common in SLE (50-70%) and do not distinguish SLE from drug-induced SLE Measurement of other autoantibodies should be guided by clinical manifestations such as petechiae, anemia, neurologic involvement, thyroid abnormalities, and coagulopathy Antiphospholipid antibody (anticardiolipin antibody and lupus anticoagulant) is present in 30% of SLE patients and is associated with recurrent thromboembolism and miscarriage In SLE the patient's rheumatoid factor is positive in 40% of cases A complement screen should also be performed (C3, C4). C3 and C4 decrease in disease activity, with which they often correlate better than the ESR and CRP Urinalysis : pyuria, hematuria, proteinuria, granular casts occur with the onset of renal involvement Partial thromboplastin time : may be elevated (lupus anticoagulant or antiphospholipid antibody) Appropriate radiographs : for joint involvement Electrocardiogram : for cardiac involvement, if appropriate Chest X-ray : for pulmonary symptoms Additional tests may be performed for specific symptoms, e.g. neuropathic changes can be investigated with an electromyogram and nerve conduction velocities Further studies may be indicated e.g. renal biopsy if renal involvement is suspected, and echocardiogram for cardiac involvement, including pericardial effusion or involvement of the mitral valve in Libman sacks endocarditis