Clinical manifestations and diagnosis of systemic lupus erythematosus in adults

AUTHORS:

Daniel J Wallace, MD

Dafna D Gladman, MD, FRCPC

SECTION EDITOR:

David S Pisetsky, MD, PhD

DEPUTY EDITOR:

Siobhan M Case, MD, MHS

translate:

Wu Xiangni, attending physician

All of our topics are updated based on newly published evidence and thepeer review process.

The literature review is valid until: 2023-10.

The last update date of the topic: 2023-06-16.

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Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that can affect almost all organs. A distinctive feature of the disease is immune abnormalities, especially the production of large amounts of antinuclear antibodies (ANA).

Patients may present with different clinical characteristics, ranging from mild joint and skin lesions to life-threatening kidney, blood system or central nervous system lesions. SLE is clinically heterogeneous and lacks diagnostic features or tests, making it difficult for clinicians to diagnose. Patients may present with only some clinical features of SLE, which may be similar to other autoimmune, infectious, or hematological diseases, making diagnosis more difficult.

SLE is usually diagnosed based on clinical and laboratory findings after other conditions have been ruled out. There are currently no diagnostic criteria for SLE, and clinicians usually use the SLE classification criteria as a guide to identify some prominent clinical features at the time of diagnosis. Serological test results are important in suggesting SLE, and some antibodies are highly correlated with SLE, such as anti-double-stranded DNA (dsDNA) antibodies and anti-Smith (Sm) antibodies.

This topic will review the clinical manifestations and diagnostic methods of SLE. Other topics related to SLE in adults include:

●(See "Overview of Treatment and Prognosis of Systemic Lupus Erythematosus in Adults" )

●(See "Epidemiology and pathogenesis of systemic lupus erythematosus")

●(See "Overview of Cutaneous Lupus Erythematosus")

●(See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus")

●(See "Diagnosis and Classification of Lupus Nephritis")

●(See "Lupus nephritis: Treatment of membranous lupus nephropathy")

●(See "Initial and subsequent treatment of focal or diffuse lupus nephritis")

●(See "Hematological manifestations of systemic lupus erythematosus")

●(See "Gastrointestinal manifestations of systemic lupus erythematosus")

●(See "Coronary heart disease in patients with systemic lupus erythematosus")

●(See "Noncoronary cardiac manifestations of systemic lupus erythematosus in adults" )

●(See "Nervous system and neuropsychiatric manifestations of systemic lupus erythematosus")

●(See "Manifestations of systemic lupus erythematosus affecting the peripheral nervous system")

●(See "Contraceptive methods for women with systemic lupus erythematosus")

●(See "Pregnancy in women with systemic lupus erythematosus")

●(See “Embodied Lupus”)

clinical manifestations

Main clinical features and organ involvement

Systemic symptoms — Most patients with SLE will experience systemic symptoms during the course of the disease, such as fatigue, fever, and weight loss.

●Fatigue – Fatigue is the most common complaint, with an incidence of 80%-100%, and can sometimes make patients incapacitated. Fatigue is not clearly associated with other measures of disease activity and is often more closely associated with depression, sleep disturbance, and coexisting fibromyalgia [1-5].

●Fever–Fever may be a sign of active disease and is seen in more than 50% of SLE patients[< a i=3>6]. However, in clinical practice, it is often difficult to distinguish fever caused by exacerbation of long-term lupus symptoms from fever caused by other causes, such as infection, drug reaction, or malignancy. There are currently no specific clinical features that clearly distinguish fever caused by SLE from fever caused by other causes. The medical history may help determine the cause of the fever. For example, if a patient develops fever while receiving moderate or high doses of corticosteroids, new infection should be strongly suspected, especially in the absence of other signs of active disease. If fever does not resolve with NSAIDs, acetaminophen, and/or low- to moderate-dose corticosteroids, Suspect an infectious or drug-related etiology, as these drugs are effective in most fevers caused by active SLE [7]. Additionally, if a patient has a low white blood cell count in addition to a fever, it is more likely to have active lupus rather than an infection. Infection should be clearly ruled out in SLE patients who develop fever.

The main cause of patient complications is serious infection and this should be considered in all immunocompromised SLE patients who present with fever. (See ‘Clinical manifestations’ above)

●Myalgia–Myalgia is also common in SLE patients, but severe myasthenia or myositis is relatively uncommon. Myalgia and weakness are discussed separately. (See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus," section on 'Muscle involvement' )

●Weight changes – People with SLE often experience weight changes that may be related to the disease or its treatment. Patients with SLE often experience weight loss before diagnosis. Unintentional weight loss may be caused by loss of appetite, side effects of medications (especially diuretics and occasionally hydroxychloroquine), and gastrointestinal disorders (e.g. , gastroesophageal reflux, abdominal pain, peptic ulcer disease, or pancreatitis) (see "Gastrointestinal manifestations of systemic lupus erythematosus"). The cause of weight gain in SLE patients may be water and sodium retention caused by hypoalbuminemia, such as hypoalbuminemia caused by nephrotic syndrome or protein-losing enteropathy, or increased appetite caused by the use of glucocorticoids. (See "Overview of macroalbuminuria and nephrotic syndrome" and "Gastrointestinal tract in systemic lupus erythematosus" Manifestations", section on 'Protein-losing enteropathy')

Arthritis and joint pain — Arthritis and joint pain occur in more than 90% of SLE patients and are often among the earliest manifestations[8]. The incidence of arthritis is 65%-70%, accompanied by significant inflammation, and is often migratory, polyarticular, and symmetrical. Arthritis is moderately painful, usually does not cause erosion, and rarely causes deformity (Picture 1A-B). However, SLE patients occasionally develop deformative erosive arthritis, similar to rheumatoid arthritis (RA) [9]. The clinical features and treatment of arthritis and arthralgia in patients with SLE are discussed separately. (See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus," section on 'Joint involvement')

Mucocutaneous involvement — Most patients with SLE will develop skin and mucosal lesions during the course of the disease. There are huge differences in the types of skin lesions. The most common lesion is facial rash, which is characteristic of acute cutaneous lupus erythematosus (also known as butterfly rash). It manifests as erythema distributed on the patient's cheeks (cheeks and bridge of nose, but not involving nasolabial folds), and appears after sun exposure. appears (Picture 2A-B). Some patients may develop discoid lesions, in which inflammation is more severe and often scarring (Picture 3A-B). SLE patients also frequently develop photosensitive skin lesions. The different cutaneous manifestations in patients with SLE are discussed separately. (See “Overview of cutaneous lupus erythematosus”)

Many patients develop oral and/or nasal ulcers, which are usually painless compared with herpetiform chancre blisters. Nasal ulcers may lead to perforation of the nasal septum. Many patients with SLE also experience non-scarring alopecia during the course of the disease. People with discoid lupus erythematosus may develop scarring alopecia. (See "Overview of cutaneous lupus erythematosus," section on 'Discoid lupus erythematosus')

Cardiac involvement and vascular manifestations — A variety of cardiac and vascular abnormalities may occur in patients with SLE.

●Many patients with SLE will develop heart disease, and the pericardium, myocardium, valves, conduction system, and coronary arteries may be affected. The most common cardiac manifestation in patients with SLE is pericarditis (which may be accompanied by effusion), and approximately 25% of patients will develop pericarditis during the course of the disease[10]. Verrucous endocarditis is usually asymptomatic but may cause valvular insufficiency and emboli formation (Picture 4). Myocarditis is less common but can be serious. People with SLE are also at increased risk of developing coronary artery disease. (See "Noncoronary cardiac manifestations of systemic lupus erythematosus in adults" and "Noncoronary cardiac manifestations of systemic lupus erythematosus in adults" Coronary heart disease")

Infants born to women with SLE who express anti-Ro/SSA and anti-La/SSB antibodies may develop neonatal lupus, which can cause varying degrees of heart block and may be noted in utero, and /or may present with congenital heart block, see elsewhere. (See "Epidemiology, pathogenesis, clinical manifestations, and diagnosis of neonatal lupus")

●Raynaud’s phenomenon – Raynaud’s phenomenon in SLE patients is a vasospasm process caused by cold, with an incidence of up to 50% ()"Clinical Manifestations and Diagnosis of Raynaud's Phenomenon"]. Raynaud's phenomenon is discussed in detail elsewhere. (See 11]. Raynaud's phenomenon is characterized by intermittent acral pallor followed by cyanosis and erythroderma [6)[Picture 5

●Vasculitis – The prevalence of vasculitis in patients with SLE has been estimated to be 11%-36% in large cohort studies[]. The main clinical manifestation of vasculitis is skin lesions, with an incidence rate of 89%. The remaining 11% of patients with vasculitis have visceral involvement, such as peripheral nerves, lungs, pancreas, and kidneys. 13). For example, a large case series of 670 patients with SLE found an incidence of vasculitis of 11% [" Evaluation of vasculitic skin lesions in adults”]. In patients with SLE, inflammation may occur in both large and small blood vessels, thus clinically manifesting a series of vasculitis. Small vessel disease is most common and often presents as skin lesions, but medium-sized vessels and large vessels may also be involved. Cutaneous small vessel vasculitis may manifest as palpable purpura, petechiae, papulonodular lesions, livedo reticularis, panniculitis, splinter hemorrhages, and superficial ulcers (see 12

Other specific types of vasculitic lesions in SLE include mesenteric vasculitis, hepatic vasculitis, pancreatic vasculitis, coronary artery vasculitis, pulmonary vasculitis, and retinal vasculitis, as well as peripheral or central nervous system vasculitis. There are also a small number of reports of aortitis, which is similar to Takayasu arteritis [14]. (See "Overview of cutaneous lupus erythematosus" and "Gastrointestinal manifestations of systemic lupus erythematosus," on Section on 'Autoimmune hepatitis' and "Gastrointestinal manifestations of systemic lupus erythematosus", section on 'Acute pancreatitis' > and "Gastrointestinal manifestations of systemic lupus erythematosus", section on 'Mesenteric vasculitis/ischemia' and )"Retinal vessels associated with systemic disease and infection inflammation", section on 'Systemic immune-mediated causes'and "Manifestations of systemic lupus erythematosus affecting the peripheral nervous system"

●Thromboembolic disease – Thromboembolic disease may complicate the condition of patients with SLE, especially those with antiphospholipid antibodies . Thromboembolic disease can affect the venous and arterial circulation, but the exact mechanism is unknown [15,16]. For example, a large observational cohort study of 554 patients with newly diagnosed SLE found an 11% incidence of arterial thrombotic events (ATE) and venous thrombotic events (ATE) during a median follow-up of 6.3 years. event, VTE) thrombotic events occurred in 33% of cases [16]. Antimalarials may prevent thromboembolic disease in patients with SLE [17].

Renal involvement — Approximately 50% of SLE patients will develop clinically significant renal involvement, which is an important cause of complications and death[18]. Therefore, regular screening for lupus nephritis via urinalysis, quantitative proteinuria analysis, and estimated GFR is an important component of the ongoing management of patients with SLE. Patients may develop several types of glomerulonephritis, and a kidney biopsy can help determine the type and extent of kidney involvement. The clinical manifestations of lupus nephritis vary greatly, ranging from asymptomatic hematuria and/or proteinuria to severe nephrotic syndrome and rapidly progressive glomerulonephritis with loss of renal function. Some people with lupus nephritis also develop high blood pressure. (See "Diagnosis and classification of lupus nephritis")

Gastrointestinal involvement — Gastrointestinal symptoms occur in many SLE patients, with an incidence of up to 40%. Most gastrointestinal symptoms are caused by adverse drug reactions and viral or bacterial infections [19]. SLE-related gastrointestinal abnormalities can involve virtually any organ adjacent to the gastrointestinal tract and include esophagitis, intestinal pseudo-obstruction, protein-losing enteropathy, lupus hepatitis, acute pancreatitis, mesenteric vasculitis or ischemia, and peritonitis. The gastrointestinal manifestations of SLE are discussed separately. (See "Gastrointestinal manifestations of systemic lupus erythematosus")

Pulmonary involvement — Many people with SLE will develop symptoms secondary to pulmonary involvement during the course of the disease. Pulmonary manifestations of SLE include pleurisy (possibly with effusion), pneumonia, interstitial lung disease, pulmonary hypertension, lung reduction syndrome, and alveolar hemorrhage. Respiratory symptoms must be distinguished from infection, especially in patients receiving immunosuppressive therapy. Patients with the presence of antiphospholipid antibodies or lupus anticoagulants are at increased risk for thromboembolic disease. (See "Pulmonary manifestations of systemic lupus erythematosus in adults")

Neurological and neuropsychiatric involvement — Neuropsychiatric involvement in patients with SLE includes a variety of neurological and psychiatric manifestations, such as stroke, seizures, cognitive impairment, delirium, psychotic symptoms, and/or peripheral neuropathy. Other less common problems include movement disorders, cranial neuropathy, myelitis, and meningitis. (See “Neurological and Neuropsychiatric Manifestations of Systemic Lupus Erythematosus” and “Systems Affecting the Peripheral Nervous System” manifestations of sexual lupus erythematosus")

A minority of patients with SLE (20%) may develop thromboembolic events, often related to antiphospholipid antibodies or lupus anticoagulants [20] . Arterial thromboembolism may cause focal neurological symptoms such as stroke or seizures and/or more generalized cognitive deficits [20]. (See "Clinical manifestations of antiphospholipid syndrome")

Hematological abnormalities — Many SLE patients will develop hematological abnormalities, and all three systems may be affected. Anemia of chronic disease (also known as inflammatory anemia and chronic inflammatory anemia) is the most common type of anemia in SLE patients. Leukopenia is common in SLE patients, with an incidence of approximately 50% [21]. Leukopenia may result from lymphopenia and/or secondary neutropenia and is often associated with clinically active disease. The toxicity of immunosuppressive drugs can also cause neutropenia. Mild thrombocytopenia is also a common hematologic abnormality. Occasionally, patients with SLE develop severe thrombocytopenia and require treatment. Autoimmune hemolytic anemia is also relatively rare, but can be serious and require immediate treatment. The hematologic manifestations of SLE are discussed separately. (See "Hematologic manifestations of systemic lupus erythematosus")

People with active SLE often have enlarged lymph nodes, often involving the neck, armpits, and groin. SLE patients may also develop splenomegaly, especially in patients with active SLE. (See "Hematological manifestations of systemic lupus erythematosus," section on 'Lymph node enlargement, splenomegaly, and elevated blood cell counts')) a>

Ocular involvement — All ocular structures may be affected in patients with SLE, with the most common manifestation being keratoconjunctivitis sicca due to secondary Sjögren's disease[22) "Retinal vasculitis associated with systemic disease and infection", section on 'Systemic immune-mediated causes' ). The second most common ocular lesion in patients with lupus is retinal vasculopathy manifesting as cotton wool spots. (See "Clinical manifestations of Sjogren's syndrome: exocrine gland disease" ] (see

Other less common ophthalmic manifestations in patients with SLE include optic neuropathy, choroidopathy, episcleritis, scleritis, and anterior uveitis (iritis, iridocyclitis). (See "Optic neuropathy", section on 'Systemic autoimmune diseases'and "Episcleritis ” and “Clinical manifestations and diagnosis of scleritis” and “Grape The etiology, clinical manifestations and diagnosis of inflammation", section on 'Systemic inflammatory diseases')

Orbital tissues may also be involved in SLE, such as the lacrimal gland (often causing dryness), extraocular muscles, and other orbital tissues, causing pain, proptosis, eyelid swelling, and diplopia[23]. In addition, the drugs have specific toxicities to the eyes of patients with SLE, including glucocorticoid-induced glaucoma and nephrotoxicity caused by antimalarial therapy.

Other related diseases and complications — SLE patients may have multiple comorbidities due to underlying diseases or related treatments.

●Immunodeficiency– Hereditary angioedema is a rare genetic disease caused primarily by C1 inhibitor deficiency. The disease can be accompanied by some inflammatory and autoimmune diseases, including SLE[24]. (See "Hereditary angioedema (due to C1 inhibitory factor deficiency): Pathogenesis and diagnosis" )

SLE can also occur in patients with other types of complement (such as C2) deficiencies. Manifestation often depends on whether the defect is homozygous or not. Patients with complete C4 deficiency and C1q deficiency often develop SLE[25]. Inherited C4 deficiencies are discussed separately. (See "Hereditary disorders of the complement system", section on 'C4 deficiency') Acquired low immunoglobulin levels may also occur in patients with SLE [26].

●Antiphospholipid syndrome–40% of SLE patients have antiphospholipid antibodies [27)"Clinical manifestations of antiphospholipid syndrome"and "Diagnosis of antiphospholipid syndrome"]. However, the incidence of antiphospholipid syndrome is much lower. (See

●Fibromyalgia – In patients with SLE and several other systemic rheumatic diseases, the prevalence of fibromyalgia is higher than High in the general population [28]. (See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus," section on 'Fibromyalgia')

●Osteonecrosis – Osteonecrosis manifests as severe joint pain in patients with SLE and has an estimated risk of 3%-40% [29]. It is currently believed that the increased risk is related to underlying medical conditions and concomitant use of glucocorticoids. (See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus," section on 'Osteonecrosis')

●Osteoporosis – Osteoporosis is a common complication of SLE and is discussed separately. (See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus," section on 'Osteoporosis')

●Infection – Up to 50% of patients with SLE will develop serious infectious complications, especially of the skin, respiratory and urinary systems []. Therefore, in immunocompromised patients, fever can be attributed to SLE only after infection has been reasonably excluded. 35-38]. Opportunistic infections (including infections caused by fungi) may be related to immunosuppressive therapy and are a common cause of death [33]. The vast majority (about 80%) of infections are caused by pathogenic bacteria [34]. A large study of 33,565 patients with SLE in the Medicaid database, 7113 of whom had lupus nephritis, found that the incidence of serious infections requiring hospitalization was 10.8 per 100 person-years in SLE patients, compared with 10.8 per 100 person-years in the lupus nephritis subgroup. 23.9/100 person-years [6,30-33

Risk factors for infection include active SLE [39], long-term disease impairment, neutropenia, lymphopenia, low Complementemia, hypogammaglobulinemia, renal involvement, neuropsychiatric manifestations, and use of glucocorticoids and other immunosuppressive drugs [33,40] . National cohort studies show increased risk of infection among black Americans and men; antimalarial drugs have been found to be protective [34]. Viral infections are also common, including parvovirus B19 (which can cause lupus-like syndrome), Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, and human papillomavirus. Patients with SLE are at higher risk of developing mycobacterial infections, including non-tuberculous mycobacteria [30,33].

●Other autoimmune diseases – There is an increased prevalence of thyroid disease in patients with SLE, usually Hashimoto’s thyroid inflammation. It has been reported that patients with SLE also develop myasthenia gravis at the same time. The prevalence of autoimmune diseases is higher among relatives of SLE patients [41-43]. (See "Clinical manifestations of myasthenia gravis", section on 'Epidemiology')

Evaluate

When to Suspect SLE — The initial diagnosis of SLE depends on the clinical pattern of presentation and other diagnostic exclusions. The clinical manifestations of SLE are heterogeneous, so for some patients, the diagnosis of SLE can be relatively simple and straightforward based on a series of clinical manifestations and supporting laboratory test results. Others develop isolated problems or rare disease features that make diagnosis more difficult. Demographics should also be considered when evaluating patients for the presence of SLE, as the disease occurs primarily in young women of childbearing age. In addition, SLE is more common in certain racial and ethnic groups than in whites, especially blacks, Asians, and Hispanics [44]. (See "Epidemiology and pathogenesis of systemic lupus erythematosus," section on 'Epidemiology')

For example, a young woman presenting with fatigue, arthralgia, and pleuritic chest pain, and a physical examination reveals hypertension, cheek rash, pleural friction rub, multiple joint tenderness and swelling, and mild peripheral edema is more likely to be diagnosed. SLE. Laboratory testing may reveal leukopenia, anemia, elevated serum creatinine levels, hypoalbuminemia, proteinuria, active findings on urine sediment microscopy, hypocomplementemia, and a positive ANA test (including anti-dsDNA antibodies and anti-dsDNA antibodies). Sm antibody). Another patient may have fatigue and joint pain, have a positive ANA test, but have no evidence of organ involvement. Such patients may develop the characteristic multisystem features of SLE over the subsequent months to years. (See ‘Clinical manifestations’ above)

Therefore, initial evaluation requires a detailed history and physical examination, as well as specific laboratory tests to identify characteristic manifestations of SLE or features suggestive of other diagnoses. Patients with shorter duration of symptoms require close follow-up because the frequency of different features of SLE varies depending on the stage of the disease [45-49].

History and Physical Examination — We will conduct a thorough history, paying special attention to the following signs and symptoms:

●Systemic symptoms, such as fever, fatigue, swollen lymph nodes, or weight loss

●Photosensitive skin lesions, such as cheek rash

●Painless oral or nasal ulcers

●Patchy alopecia or forehead/peripheral alopecia

●Raynaud phenomenon

●Joint pain or swelling, which may be migratory or symmetrical

●Dyspnea or pleuritic chest pain suggestive of serositis

●Chest pain suggestive of pericarditis

●Edema of lower limbs

●Neurological symptoms, such as seizures or psychotic symptoms

●Recurrent spontaneous abortion (see "Pregnancy in women with systemic lupus erythematosus")

●Use of drugs related to drug-induced lupus (see "Drug-induced lupus")

The clinical manifestations of SLE are variable, so it is helpful to consider the frequency of these features at onset (Table 1).

A comprehensive physical examination is required because SLE can affect any organ system. Relevant physical examination findings are as follows:

●Lesions consistent with cheek rash or discoid lesions

●Scarring or non-scarring patchy alopecia

●Oral or nasopharyngeal ulcers, nasal septum perforation

●Polyarthritis, usually symmetrical

●Metacarpophalangeal joint subluxation and rheumatoid-like swan neck deformity of the hand

●Decreased or abnormal breath sounds may indicate pleural effusion, pneumonia, or interstitial lung disease

●Lower limb edema and hypertension

Laboratory tests — We perform the following routine laboratory tests, which may provide useful diagnostic information:

● Complete blood count and differential count, which may show leukopenia, mild anemia, and/or thrombocytopenia

●Serum creatinine test, elevated levels may indicate renal dysfunction

●Urinalysis (including urine sediment examination), which may reveal hematuria, pyuria, proteinuria, and/or cellular casts

●Serum protein electrophoresis may reveal hypergammaglobulinemia suggesting a systemic inflammatory response.

In addition to the above routine laboratory tests, we will also conduct the following laboratory tests. If the results are abnormal, the diagnosis of SLE will be supported:

●ANA detection, preferably indirect immunofluorescence assay

●Anti-dsDNA antibody detection

Antiphospholipid antibodies, including lupus anticoagulant antibodies, IgG and IgM anticardiolipin antibodies, and IgG and IgM anti-β2 glycoprotein 1 antibodies

●C3 and C4 or CH50 complement levels

●Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels

●Urine protein/creatinine ratio

Almost all SLE patients will have a positive ANA test during the course of the disease (see "Detection and clinical significance of antinuclear antibodies"). If the ANA test is positive, other specific antibodies should be tested, such as anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, and anti-U1 ribonucleoprotein (RNP) antibodies, as detailed below. In some laboratories, if a certain ANA is positive by indirect immunofluorescence, other such ANAs commonly present in SLE patients will naturally be tested. However, positive ANA test results must also be interpreted in conjunction with other clinical or experimental findings. Indirect immunofluorescence method found that almost 15% of Americans are ANA positive (at least 1:80), but only 10% actually have autoimmune diseases [50< a i=4>]. For details on ANA testing and interpretation of results, see other topics. (See "Detection and clinical significance of antinuclear antibodies")

●Anti-dsDNA and anti-Sm antibodies have high specificity for SLE, but the sensitivity of anti-Sm antibodies is very low[51,52]. About 70% and 30% of SLE patients have anti-dsDNA and anti-Sm antibodies respectively. (See "Antibodies against double-stranded (ds)DNA, Sm, and U1RNP")

●About 30% and 20% of SLE patients have anti-Ro/SSA and anti-La/SSB antibodies respectively, but these two antibodies are more commonly associated with Sjögren's disease[ 51]. (See "Anti-Ro/SSA and anti-La/SSB antigen antibody systems")

●About 25% of SLE patients have anti-U1 RNP antibodies, but these antibodies also appear in patients with other diseases, and high levels of antibodies basically appear in patients with mixed connective tissue disease (MCTD) in [51,52]. (See "Antibodies against double-stranded (ds)DNA, Sm, and U1RNP")

●Anti-ribosomal P protein antibody has high specificity for SLE, but low sensitivity. Specificity for specific organ system involvement or disease manifestations is also very low. (See "Anti-ribosomal P protein antibodies", section on 'Clinical applications of anti-ribosomal P protein antibodies')

If the initial ANA test result is negative but clinical suspicion of SLE is high, additional antibody testing may be needed. This is partly due to differences in the sensitivity and specificity of different ANA detection methods. For details on ANA testing technology and some of the reasons for differences in test results, see separate topics. (See below‘ANA-negative lupus’)

More information on interpreting ESR and CRP abnormalities in patients with SLE is provided separately. (See "Overview of treatment and prognosis of systemic lupus erythematosus in adults," section on 'Laboratory evaluation')

We perform the following laboratory tests on selected patients:

●Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies– in In patients with primary presentation of arthralgia or arthritis, RF and anti-CCP antibodies may help rule out RA. The diagnostic utility of RF is low because 20%-30% of SLE patients are RF-positive. However, anti-CCP antibodies are much more specific for RA and are more useful in identifying RA-related arthritis. (See "Diagnosis and evaluation of rheumatoid arthritis: biomarkers", section on 'Rheumatoid factor' and "Diagnosis and evaluation of rheumatoid arthritis: biomarkers", section on 'anti-citrullinated peptide antibodies')

●Serological testing for infection – For short-term cases with predominantly arthralgia or arthritis (e.g., less than 6 weeks) For patients, we perform serological testing to determine whether they are infected with human parvovirus B19. For patients with multi-system clinical manifestations, we also perform HBV and HCV serology testing. In areas where Lyme disease is endemic, we will also send samples for Borrelia (Borrelia) serology testing. In appropriate clinical circumstances, testing for Epstein-Barr virus infection may also be warranted. (See "Diagnosis of Lyme disease")

●creatine kinase (CK)–Elevated CK may indicate myositis, which is relatively uncommon in patients with SLE . Myositis can also suggest other diagnoses, such as MCTD, polymyositis (PM), or dermatomyositis.

●Collect 24 hours of urine – If a random urine sample has a protein/creatinine ratio >0.05g/mmol, 24 hours should be collected Hourly urine samples, because random urine samples may not reflect the true amount of proteinuria [53] (See "Evaluation of urinary protein excretion and evaluation of pure non-nephrotic range proteinuria in adults", section on '24-hour urine collection vs random urine collection'< a i=6>)

Additional tests in selected patients — In some cases, a biopsy of the affected organ (eg, skin or kidneys) may be necessary. Typical histological findings of each affected organ in patients with SLE are discussed in the relevant topic for the specific affected site. (See "Diagnosis and classification of lupus nephritis"and "Overview of cutaneous lupus erythematosus")

The need for additional testing is usually determined based on the clinical presentation and the likelihood of associated differential diagnoses. For example:

●Evaluate with an electrocardiogram for chest pain that may be caused by pericarditis or myocardial ischemia

●Assess for pulmonary embolism in patients with pleuritic chest pain and dyspnea

Measure carbon monoxide diffusing capacity to evaluate suspected pulmonary hemorrhage and estimate the severity of interstitial lung disease

Diagnostic imaging may have some value but is not currently used routinely unless indicated by relevant symptoms, clinical manifestations, or laboratory abnormalities. For example:

●Plain radiographs, if performed when there is joint swelling, can reveal bone erosions that are uncommon in SLE patients, unlike affected joints in RA[54].

●Musculoskeletal ultrasound, such as to detect synovitis and tenosynovitis of the hands and wrists when there is joint pain[55,56].

●Renal ultrasound, such as to assess kidney size and rule out urinary tract obstruction (when there is evidence of impaired renal function).

●Chest radiography, if used for suspected pleural effusion, interstitial lung disease, and cardiomegaly.

●Echocardiography, if used in patients with suspected pericardial involvement, to assess the source of emboli or to noninvasively estimate pulmonary artery pressure; and to evaluate suspected valvular pathology (eg, verrucous vegetations).

●CT, such as for abdominal pain, suspected pancreatitis, and interstitial lung disease.

●MRI, if used for focal neurological dysfunction or cognitive dysfunction.

Classification Criteria Several classification criteria for SLE have been developed to classify patients at the time of study enrollment. These standards help clinicians systematically document key disease features, but issues with sensitivity and specificity limit diagnostic applications.

●2019 EULAR/ACR standards – European League of Rheumatology Associations (EULAR, formerly known as the European League Against Rheumatism)/ The American College of Rheumatology (ACR) SLE classification criteria are designed to improve detection of early or new-onset SLE and to increase sensitivity and specificity compared with previous criteria (Table 2A-B)[57,58]. SLE classification requires the patient to have a positive ANA. Other criteria include 7 clinical manifestations (i.e., systemic symptoms, hematological symptoms, neuropsychiatric symptoms, mucocutaneous symptoms, serosal symptoms, musculoskeletal symptoms, renal symptoms), and 3 immunological manifestations (i.e., antiphospholipid antibodies, Complement proteins and SLE-specific antibodies), each item is scored from 2 to 10 points, and a score of ≥10 is considered SLE. In a validation cohort that included patients with early-stage disease, the sensitivity and specificity of the EULAR/ACR criteria were 96.1% and 93.4%, respectively, while the Systemic Lupus International Collaborating Clinics (SLICC) criteria were 96.7 % and 83.7%, and the ACR standard is 82.8% and 93.4%.

A study combined the derivation cohort and the validation cohort, with a total of 1197 patients with SLE and 1074 patients without SLE but with various SLE-like diseases, to evaluate the efficacy of the EULAR/ACR classification criteria. The study showed that ANA The sensitivity and specificity of positivity are 99.5% and 19.5% respectively[59]. The sensitivities of specific criteria vary widely, but the specificities are consistent and high (eg, at least 80%).

●2012 SLICC Standards – The classification standards proposed by SLICC in 2012 are intended to make up for the inherent shortcomings of the 1997 ACR classification standards (]. For example, a major limitation of the 1997 ACR criteria is that patients with biopsy-confirmed lupus nephritis may still not meet the criteria. Other problems with the ACR criteria include the potential overlap of closely related skin features (eg, cheek rash and photosensitivity); the failure to include other cutaneous manifestations (eg, maculopapular or polyannular rashes); and the omission of many neurologic manifestations of SLE. (eg, myelitis). The ACR criteria also do not incorporate relevant immunological information, such as low serum levels of complement components. 60)[Table 3

According to the SLICC criteria, SLE is defined as meeting at least 4 of 17 criteria, including at least 1 of 11 clinical criteria and 1 of 6 immunological criteria, or the patient has biopsy-proven nephritis consistent with SLE. , and have ANA or anti-dsDNA antibodies.

An analysis of 690 patients with SLE or other rheumatic diseases validated the SLICC criteria. This initial validation found that the revised SLICC criteria were more sensitive but less specific than the 1997 ACR classification criteria (sensitivity 97% vs 83%, specificity 84% vs 96%).

Although the SLICC criteria are more sensitive than the ACR criteria, they may delay the diagnosis of SLE in many patients, and some patients may not be classified as SLE based on SLICC. These conditions were confirmed in a study that included two large cohorts of SLE patients divided into 3 groups who met SLICC criteria before, simultaneously with, or after the use of ACR criteria and subsequently compared. ]. Among patients who were subsequently diagnosed by SLICC criteria, the diagnostic delay was mostly due to the classification of both cheek rash and photosensitivity as acute cutaneous components of SLE and thus being scored by only one criterion. 61

●1997 ACR Criteria – The SLE classification criteria of the American Rheumatism Association (ARA; now ACR) are based on Developed by cluster analysis, this type of analysis has been performed primarily in academic research centers and among white American patients [62-64].

According to ACR criteria, a patient can be classified as SLE if 4 or more manifestations occur continuously or simultaneously during the observation period (regardless of how long) (Table 3 a>)[62,63]. Positive antiphospholipid antibodies have replaced the positive lupus erythematosus cell test used in the old standards [62]. When used to exclude other rheumatic diseases, the sensitivity and specificity of these criteria are approximately 96%.

Diagnosis If an experienced clinician finds that a patient has a series of characteristic symptoms and signs and the serological test results support SLE, he or she can diagnose SLE according to his or her own judgment after ruling out other diagnoses. The presentation of SLE varies widely, so its diagnosis is often difficult. Although the classification criteria were developed for research purposes, many clinicians refer to these criteria when diagnosing SLE. (See ‘Classification criteria’ above)

There is currently no "diagnostic standard". The general diagnostic method we use will be introduced below, which takes into account the 1997 version of the ACR standards and the 2012 version of the SLICC standards (Table 3Table 3)‘Classification criteria’ above). (See Table 2A) or the 2019 EULAR/ACR classification standard (

It should be noted that the general diagnostic methods we use are not sufficient to distinguish various clinical manifestations or the subtleties of some clinical features, nor are they a substitute for clinical judgment. Therefore, patients with suspected SLE are often suitable for referral to experienced rheumatologists [65].

Our diagnostic criteria

Confirmed SLE - After excluding other diagnoses, if the patient meets the 1997 ACR criteria, the 2012 SLICC criteria (Table 3) or the 2019 edition According to EULAR/ACR standards, we will diagnose SLE (Table 2A). As mentioned above, the ACR criteria require patients to meet at least 4 of 11 criteria. SLICC criteria require patients to meet at least 4 of 17 criteria, including at least 1 of 11 clinical criteria and 1 of 6 immunological criteria, or < a i=6>Patient has biopsy-proven nephritis consistent with SLE and has ANA or anti-dsDNA antibodies. According to EULAR/ACR criteria, diagnosis of SLE requires a positive ANA (≥1:80) and a score of ≥10 points. This value has been validated in many cohorts. (See ‘Classification criteria’ above)

Probable SLE — Some patients do not meet the classification criteria for SLE, but we still diagnose SLE. Including insufficient number of ACR or SLICC criteria met, or the presence of other SLE manifestations that are not included in both classification criteria.

Generally speaking, we also diagnose patients with SLE if they meet 2 or 3 ACR or SLICC criteria and have at least 1 other feature that may be related to SLE but is not specific to SLE. Some of these features include [66]:

●Optic neuritis, aseptic meningitis

●Glomerular hematuria

●Pneumonia, pulmonary hemorrhage, pulmonary hypertension, interstitial lung disease

●Myocarditis, verrucous endocarditis

●Abdominal vasculitis

●Raynaud phenomenon

●Elevated acute phase reactants (e.g., ESR and CRP)

Suspected SLE — We consider patients with suspected SLE who have at least 1 or 2 of the other features listed above but meet only 1 ACR/SLICC criterion. Suspected or suspected SLE is also called primary lupus or latent lupus, which means the patient meets ≤3 ACR or SLICC criteria [67].

Patients with suspected or suspected SLE are usually treated similarly to SLE patients, with treatment based on their main symptoms and manifestations. Over time, symptoms in these patients may persist, progress to definite SLE or related connective tissue diseases, or even resolve. In addition, these patients may gradually become seropositive, allowing a more definite diagnosis of SLE. But the antibodies may "disappear" in patients who receive high doses of prednisone, making it more difficult to diagnose the underlying disease.

Undifferentiated connective tissue disease — Patients with other features less suggestive of SLE may have undifferentiated connective tissue disease (UCTD). UCTD refers to a patient whose symptoms and signs suggest systemic autoimmune disease, but does not meet the ACR criteria for SLE and cannot be clearly diagnosed as another connective tissue disease[68 ]. (See "Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes")

For patients diagnosed with UCTD at presentation, several case series have summarized the clinical outcomes [69-73]. After 10 years of follow-up, it was found that all symptoms and signs disappeared in up to 1/3 of the patients. However, 40%-60% of patients still have initial clinical manifestations, and 5%-30% of patients progress and meet the classification criteria of a certain disease, such as SLE, RA, scleroderma or inflammatory myopathy (myositis) [ 69-73] (see "Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes")‘Laboratory tests’ above). Therefore, patients with UCTD should be closely followed, encouraged to report new symptoms, and undergo regular laboratory testing to evaluate emerging clinical features or laboratory findings. The above laboratory tests should be performed. (See

ANA-negative lupus — ANA-negative SLE was discovered as early as the 1970s, but it was subsequently discovered that the ANA testing method can affect test results. It was estimated that at that time, 5% of SLE patients were determined to be ANA negative by indirect immunofluorescence [74]. However, the reason for this negative result is that the substrate used to detect ANA by indirect immunofluorescence is rodent non-human tissue [75]. When human cell line extracts were used as substrates for anti-Ro/SSA antibody detection, anti-Ro/SSA antibodies were detected in many of these patients.

The researchers then replaced rodent tissue sections with HEp2 cells (human cell line) as a substrate for indirect immunofluorescence detection of ANA, and found that there were even fewer SLE patients who were negative for ANA. However, in rare cases, the presence of anti-Ro/SSA antibodies may indicate a systemic autoimmune disease despite a negative ANA test by indirect immunofluorescence. For example, a study in Sweden tested ANA on 4025 sera, and indirect immunofluorescence method found that 64 patients were ANA negative, and these patients all had anti-Ro/SSA antibodies[76]. Among these 64 patients, 12 had SLE and 5 had cutaneous lupus erythematosus.

Clinicians should be familiar with the technique used to test ANA as this can affect test results. For example, ANA negativity determined by indirect immunofluorescence has a clinical role because it significantly reduces the likelihood of SLE. On the other hand, for patients with strong clinical suspicion of SLE but solid-phase immunoassay showing ANA negative results, indirect ANA testing with Hep-2 cells should be used, given that initial ANA testing using solid-phase immunoassay will increase the risk of false-negative results. Immunofluorescence assay was performed again. ANA testing methods are discussed separately. (See "Detection and clinical significance of antinuclear antibodies")

Other factors that may influence ANA negativity in patients with SLE include the duration of the disease and the treatment the patient receives [77]. Our experience is that patients with early-stage disease have a lower probability of ANA-negative SLE. In addition, patients with chronically ill and/or treated SLE may gradually lose ANA reactivity and become negative on serological tests.

Differential diagnosis The clinical manifestations of SLE are diverse, so the scope of differential diagnosis is also relatively wide. This topic will not be a comprehensive list of possible alternative diagnoses, but some will be described.

●RA – Early RA may be difficult to differentiate from arthritis in SLE because both conditions cause joint tenderness and swelling (Table 4). In patients with more destructive RA, features such as swan neck deformity, ulnar deviation, and soft tissue laxity may be observed later in life, but some patients with SLE may also develop these features. However, joint deformities in patients with SLE are often reversible and are rarely found to be erosive on plain X-rays, which is an important differential feature.

SLE patients may also develop some extra-articular manifestations of RA, including serositis, sicca, subcutaneous nodules, anemia, and fatigue. These features are more common in patients with RA who have more severe or advanced disease. The presence of serological abnormalities such as anti-CCP antibodies further supports the diagnosis of RA and is helpful for identification. It should be noted that up to half of RA patients may be ANA positive. About 1/3 of SLE patients may have RF. In addition, 5%-10% of SLE patients may have anti-CCP antibodies [78]. (See "Diagnosis and Differential Diagnosis of Rheumatoid Arthritis")

●Rhupus syndrome – “Rhupus syndrome” is used to describe patients who have features of both SLE and RA. It is still controversial whether Rhupus syndrome is an independent disease clinically and immunologically, whether there is overlap between SLE and RA or whether it is a subtype of SLE. In addition to serological findings consistent with SLE and RA, some patients classified as Rhupus syndrome may also have erosive arthropathy, which is not typical of SLE. (See "Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes", section on 'Early undifferentiated systemic rheumatic diseases' )

●MCTD – MCTD is characterized by the coexistence of SLE, systemic sclerosis (SSc) and PM. and high titers of anti-U1 RNP antibodies. However, the diagnosis of MCTD is often complicated because many of the typical features of the disease often occur within a few years. In addition, some patients with MCTD may progress to another connective tissue disease during the clinical course, including SLE [79]. (See "Clinical Manifestations and Diagnosis of Mixed Connective Tissue Diseases")

●UCTD – As mentioned above, patients with UCTD have symptoms and signs suggestive of systemic autoimmune disease, but do not meet certain criteria. Classification criteria for definite connective tissue diseases (eg, SLE or MCTD). These patients may have symptoms such as arthritis, joint pain, and Raynaud's phenomenon, and their serological findings are difficult to distinguish from early SLE. Most patients with UCTD never have clear symptoms and their disease is mild[80]. (See "Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes")

●SSc–Raynaud’s phenomenon and gastroesophageal reflux are often present in patients with SSc; however, these manifestations are not specific, and patients with SLE or healthy Individuals may also exist. In contrast, acrosclerosis, telangiectasia, calcinosis, and malignant hypertension with acute renal failure are more consistent with SSc (rather than SLE). In addition, most patients with SSc are ANA positive, but positive serology results for anti-dsDNA and anti-Sm antibodies, which are more specific for SLE, are usually not seen. However, SSc patients usually express antibodies against the Scl-70 antigen (topoisomerase I) or antibodies against centromere proteins. In cases with overlapping manifestations of SSc and SLE (eg, patients with MCTD), differentiation between the two disorders is particularly difficult. (See "Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults")

●Sjögren’s disease – Patients with Sjögren’s disease may have extraglandular manifestations of SLE, such as neurological and pulmonary abnormalities. However, patients with Sjögren's disease should have objective manifestations of keratoconjunctivitis sicca and xerostomia, as well as characteristic findings on salivary gland biopsy (which are not typical of SLE). Patients with Sjögren's disease often express antibodies against Ro and La antigens. In addition, some patients may have both SLE and Sjögren's disease. (See "Diagnosis and Classification of Sjogren's Syndrome")

●vasculitis–medium- and small-vessel vasculitis (e.g., polyarteritis nodosa, granulomatosis with polyangiitis, or Microscopic polyangiitis, etc.) may present with overlapping features of SLE, including systemic symptoms, skin lesions, neuropathy, and renal dysfunction. However, patients with these vasculitis are usually ANA negative and antineutrophil cytoplasmic antibodies (antibody to neutrophil cytoplasmic antigens (ANCA)) are usually positive. (See "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis" and " Clinical manifestations and diagnosis of polyarteritis nodosa in adults")

●Behçet syndrome – Almost all patients with Behçet syndrome have aphthous ulcers, and may also appear in patients with SLE. Other overlapping features include inflammatory eye disease, neurological disease, vascular disease, and arthritis. However, aphthous sores in people with Behçet syndrome are usually painful, and people with Behçet syndrome are usually male and ANA negative. In addition, the involvement of both large and small vessels is more characteristic of Behçet syndrome than SLE. (See "Clinical manifestations and diagnosis of Behçet syndrome")

●Dermatomyositis and PM–Patients with SLE may present with low-grade myositis, whereas patients with dermatomyositis and PM typically present with higher-grade myositis. Marked proximal muscle weakness. Approximately 30% of patients with dermatomyositis and PM are ANA positive, while almost all patients with SLE are ANA positive. Patients with dermatomyositis may have characteristic cutaneous findings, including Gottron's papules, positive rash, and photodistributive poikiloderma (including shawl sign and V-shaped sign). Patients with dermatomyositis and PM do not have the typical clinical manifestations of SLE, such as oral ulcers, arthritis, nephritis, and hematological abnormalities. Patients with dermatomyositis or PM may also express myositis-specific antibodies, such as anti-Jo-1 antibodies. (See "Clinical manifestations of dermatomyositis and polymyositis in adults")

●Adult-onset Still's disease – Adult-onset Still's disease is common in patients with SLE disease, AOSD), such as fever, arthritis or joint pain, and swollen lymph nodes. However, patients with AOSD often have leukocytosis (compared with leukopenia in patients with SLE), and these patients are usually ANA negative. Patients with AOSD are also more likely to have significantly elevated serum ferritin concentrations. (See "Clinical manifestations and diagnosis of Still's disease in adults")

●Kikuchi disease–Kikuchi disease is a benign histiocytic necrotizing lymphadenitis that is usually self-limiting. Clinical features at presentation include lymphadenopathy, fever, myalgia, arthralgia, and (relatively uncommon) hepatosplenomegaly. The disease has been reported to be associated with SLE, but its clinical course is usually benign, with spontaneous remission often occurring within 4 months. Kikuchi disease is diagnosed based on lymph node biopsy showing histiocytic infiltration. (See "Kikuchi disease")

●Serum sickness – SLE patients often have many of the clinical features of serum sickness, such as fever, lymphadenopathy, rash, and joint pain. Additionally, during severe disease episodes, complement (including C3 and C4) measurements may be reduced, as in SLE. However, ANA is usually negative and the disease course is usually self-limiting, unlike SLE. (See "Serum sickness and serum sickness-like reactions")

●Fibromyalgia – People with SLE may experience widespread joint pain, myalgia, and fatigue, much like those with fibromyalgia. However, patients with fibromyalgia do not develop other typical features of SLE, such as photosensitivity dermatitis, arthritis, and multisystem organ involvement. However, patients with systemic rheumatic diseases are more likely to develop fibromyalgia than the general population. It has been reported that at least 22% of SLE patients also have fibromyalgia [81]. (See "Clinical manifestations and diagnosis of fibromyalgia in adults" and "Chronic widespread ( Overview of central) pain", section on 'Systemic lupus erythematosus and Sjogren's syndrome')

●Infection – Some viral infections can cause the same symptoms and signs as SLE, including cytomegalovirus and Epstein-Barr virus. In addition, Epstein-Barr virus infection may cause ANA positivity [82,83]. Human parvovirus B19 can cause influenza-like symptoms and hematologic abnormalities (eg, leukopenia and thrombocytopenia) in patients with SLE, who may develop joint pain or arthritis.

Other viral infections that may cause multisystem involvement include HIV, HBV, and HCV. However, many of these viruses can be diagnosed through serological tests. Bacterial infections such as Salmonella or tuberculosis should sometimes be considered.

●Multiple sclerosis (MS)–SLE patients may develop cranial neuropathy, which must be differentiated from MS, but this This situation is relatively rare. MS is characterized by unilateral optic neuritis and pyramidal syndrome, as well as MRI-detected lesions suggestive of spatial and temporal dissemination. (See "Evaluation and Diagnosis of Multiple Sclerosis in Adults")

●Malignancy – Leukemia or myelodysplastic syndrome may have hematological and systemic symptoms similar to those seen in SLE. However, SLE can be distinguished based on monoclonal expansion of B cells and T cells (determined by immunophenotyping analysis), mononucleosis, or macrocytosis. Patients with lymphoma often present with other manifestations, such as splenomegaly, lymphadenopathy, or elevated lactate dehydrogenase (LDH) levels. People with angioimmunoblastic T-cell lymphoma can be identified by findings in an excisional biopsy of tissue, usually a lymph node.

●Thrombotic thrombocytopenic purpura–Although patients with thrombotic thrombocytopenic purpura (TTP) and SLE Fever and thrombocytopenia may occur, but patients with TTP also present with microangiopathic hemolytic anemia, acute renal insufficiency, fluctuating neurological manifestations, and/or low ADAMSTS13 levels. (See "Diagnosis of immune thrombotic thrombocytopenic purpura")

●Other–Some patients with mental disorders (eg, bipolar disorder, substance use disorder) will have leukopenia and ANA positivity, which may Mistaken for SLE, but the symptoms may actually be caused by drugs/medications. Therefore, these patients should be evaluated for the presence of other clinical symptoms consistent with SLE. (See “Drug-induced lupus” and “Drug-induced neutropenia and agranulocytosis”)

Links to Society Guidelines. Links to society guidelines and government guidelines for some countries and regions can be found in other topics. (See “Society guideline links: Systemic lupus erythematosus”)

Patient Education UpToDate provides two types of patient education materials: "Basic" and "Advanced." The basic chapter is easy to understand and is equivalent to a 5th-6th grade reading level (in the United States). It can answer 4-5 key questions that patients with a certain disease may want to know; the basic chapter is more suitable for people who want to understand the overview of the disease and who like to read short and easy-to-read books. data patients. The advanced chapter is longer and has more in-depth and detailed content; it is equivalent to the reading level of grades 10-12 (in the United States) and is suitable for patients who want to understand more deeply and can accept some medical terminology.

The following are patient education materials related to this topic. We recommend that you print or email this to your patient. (You can also find more related topic content by searching for "patient education" and keywords.)

●The Basics (see "Patient Education: Lupus (The Basics)")

●高级篇(参见 “Patient education: Antinuclear antibodies (ANA) (Beyond the Basics)”和 “Patient education: Systemic lupus erythematosus (Beyond the Basics)”)

Summary and recommendations

●Clinical manifestations – Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Its clinical manifestations and serum The clinical manifestations vary widely and can affect almost all organs. It often remits and relapses many times, with varying severity. (See ‘Introduction’ above)

The main clinical manifestations of SLE include:

•Systemic symptoms – Most patients with SLE will experience systemic symptoms during the course of the disease, such as fatigue, fever, and weight loss. (See ‘Systemic symptoms’ above)

•Arthritis and joint pain – More than 90% of SLE patients will develop arthritis and joint pain, which is often the earliest manifestation. one. (See ‘Arthritis and joint pain’ above)

•Mucocutaneous involvement–Many patients also develop skin and/or mucosal lesions. (See ‘Mucocutaneous involvement’ above)

•Cardiovascular involvement – Heart disease is common in patients with SLE, and the pericardium, myocardium, valves, conduction system, and coronary arteries may be affected. Patients with SLE may also develop a number of vascular abnormalities, including Raynaud's phenomenon, vasculitis, microvascular angina, and thromboembolic disease. (See ‘Cardiac involvement and vascular manifestations’ above)

•Renal involvement – Approximately 40% of patients will develop clinically apparent renal involvement, which is an important factor in the development of complications and death reason. (See ‘Renal involvement’ above)

•Gastrointestinal involvement – Gastrointestinal abnormalities can involve almost any organ adjacent to the gastrointestinal tract. But the vast majority of symptoms are related to adverse drug reactions or infections. (See ‘Gastrointestinal involvement’ above)

•Pulmonary involvement–Pulmonary manifestations of SLE include pleurisy (possibly effusion), pneumonia, interstitial lung disease, and pulmonary hypertension , lung reduction syndrome and alveolar hemorrhage. (See above‘Pulmonary involvement’)

•Neuropsychiatric involvement – Neuropsychiatric involvement in SLE patients includes a variety of neurological and psychiatric manifestations, such as cognitive dysfunction, Qualitative cerebral syndrome, delirium, psychotic symptoms, seizures, headache and/or peripheral neuropathy. (See above'Nervous system and neuropsychiatric involvement')

•Hematologic abnormalities – Hematologic abnormalities include anemia, leukopenia, and thrombocytopenia. Patients also develop enlarged lymph nodes and splenomegaly. (See ‘Hematological abnormalities’ above)

●Evaluation – The following symptoms and signs should be of particular concern during the history and physical examination (see above 'Evaluation'):

•Photosensitive skin lesions such as cheek rash or discoid lesions.

•Painless mouth or nose ulcers

•Patchy alopecia or frontal/peripheral alopecia

•Raynaud phenomenon

•Joint pain or swelling, which may be migratory or symmetrical

•Symptoms of serositis/pericarditis

•Fatigue/pain/fever

We also ask about the use of medications related to drug-induced lupus (e.g., hydralazine). (See "Drug-induced lupus")

●Laboratory tests – We will perform a complete blood count and differential count, serum creatinine level testing, and a urinalysis. We also test for antinuclear antibodies (ANA) [and if positive, other specific autoantibodies such as anti-dsDNA, anti-Smith (Sm) antibodies], antiphospholipid antibodies, C3 and C4 or CH50 complement levels, and erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels, and urine protein/creatinine ratio. (See ‘Laboratory tests’ above)

●Additional testing in selected patients – Additional testing, such as diagnostic imaging or biopsy of affected organs, may be needed; should The decision to perform such testing is based on the patient's clinical presentation and the likelihood of relevant differential diagnoses. (See ‘Other tests in selected patients’ above)

●Classification criteria – Classification criteria for SLE have been developed and are used to classify patients for research. These standards help clinicians systematically document key disease characteristics. (See ‘Classification criteria’ above)

●Diagnosis – There are currently no “diagnostic criteria” and our general approach to diagnosing SLE is as follows (see above'Our diagnostic criteria'):

•Confirmed SLE – After excluding other diagnoses, if the patient meets the 1997 American College of Rheumatology (ACR) criteria, the 2012 edition of systemic According to the Lupus International Clinical Assistance Group (SLICC) classification criteria (Table 3) or the 2019 version of the European League of Rheumatology Associations (EULAR)/ACR criteria, we SLE will be diagnosed (Table 2A). (See above'Diagnosed SLE' and 'Classification criteria')

•Proposed SLE – Some patients do not meet the classification criteria for SLE, but we still diagnose them with SLE. They meet an insufficient number of ACR or SLICC criteria or have additional SLE manifestations not covered by either classification criteria. (See above‘Proposed diagnosis of SLE’)

In general, we also diagnose SLE if a patient meets 2 or 3 ACR or SLICC criteria and has at least 1 other feature that may be related to SLE but is not specific to SLE. Some of these features include:

- Optic neuritis, aseptic meningitis

-Glomerular hematuria

-Pneumonia, pulmonary hemorrhage or pulmonary hypertension, interstitial lung disease

-Myocarditis, verrucous endocarditis (Libman-Sacks endocarditis)

-Abdominal vasculitis

-Raynaud phenomenon

-Elevated acute phase reactants (e.g., ESR and CRP)

•Suspected SLE–for patients with at least 1 or 2 of the above rare features but only 1 ACR/SLICC criterion , we considered the suspected diagnosis to be SLE. (See above‘Suspected diagnosis of SLE’)

•Undifferentiated connective tissue disease—Other patients with fewer features suggestive of SLE may have undifferentiated connective tissue disease (UCTD). (See ‘Undifferentiated connective tissue diseases’ above)

•ANA-negative SLE – Indirect immunofluorescence testing found that less than 5% of SLE patients were ANA-negative. (See above‘ANA-negative lupus’)

Acknowledgments The editorial staff of UpToDate would like to thank Peter Schur, MD, for his contribution to an earlier version of this topic.

references

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Contributor Disclosures

Daniel J Wallace, MDGrant/Research/Clinical Trial Support: Eli Lilly and Company [Lupus]; Exagen Diagnostics [Lupus]; GlaxoSmithKline [Lupus]. Consultant/Advisory Boards: Amgen [Vasculitis]; Eli Lilly and Company [Lupus]; GlaxoSmithKline [Lupus]; Horizon [Sjögren's syndrome, lupus]; Kyverna [Sjögren's syndrome, lupus]; Merck Serono [Lupus]; Nektar [Sjögren's syndrome, lupus]; Novartis [Sjögren's syndrome, lupus]. Speaker's Bureau: AstraZeneca [Lupus]; Aurinia [Lupus]; GlaxoSmithKline [Lupus]. All of the relevant financial relationships listed have been mitigated.Dafna D Gladman, MD, FRCPCGrant/Research/Clinical Trial Support: AbbVie [Psoriatic arthritis]; Amgen [Psoriatic arthritis]; Bristol-Myers Squibb [Psoriatic arthritis]; Celgene [Psoriatic arthritis]; Eli Lilly [Psoriatic arthritis]; Galapagos [Psoriatic arthritis]; Gilead [Psoriatic arthritis]; Janssen [Psoriatic arthritis]; Novartis [Psoriatic arthritis]; Pfizer [Psoriatic arthritis]; UCB [Psoriatic arthritis]. Consultant/Advisory Boards: AbbVie [Psoriatic arthritis]; Amgen [Psoriatic arthritis]; AstraZeneca [SLE]; Bristol-Myers Squibb [Psoriatic arthritis]; Celgene [Psoriatic arthritis]; Eli Lilly [Psoriatic arthritis]; Galapagos [Psoriatic arthritis]; Gilead [Psoriatic arthritis]; GSK [SLE]; Janssen [Psoriatic arthritis]; Novartis [Psoriatic arthritis]; Pfizer [Psoriatic arthritis]; UCB [Psoriatic arthritis]. All of the relevant financial relationships listed have been mitigated.David S Pisetsky, MD, PhDConsultant/Advisory Boards: BMS [Lupus]; DILIsym [Drug-induced liver injury]; Immunovant [Lupus]; Nottingham Ningbo GRADE Centre [Rheumatoid arthritis]. All of the relevant financial relationships listed have been mitigated.Siobhan M Case, MD, MHSNo relevant financial relationship(s) with ineligible companies to disclose.