Systemic Lupus Erythematosus Đánh giá ban đầu

Clinical Presentation

The clinical presentation varies in different patients and the disease activity varies over time in a single patient with flares resulting in damage from inflammation. Most patients have arthralgia of the hand. 

Cardiac manifestations of systemic lupus erythematosus include endocarditis, myocarditis, and pericarditis. Constitutional symptoms include fatigue, fever, and weight loss. Dermatological manifestations include alopecia, butterfly rash, livedo reticularis, mucous membrane lesions, photosensitivity, purpura, Raynaud’s phenomenon, urticaria, and vasculitis. Gastrointestinal symptoms include abdominal pain, nausea and vomiting, and oral ulcers. Hematologic signs are anemia, leukopenia, and thrombocytopenia. Musculoskeletal manifestations include arthralgia, arthritis, and myositis. Neuropsychiatric manifestations include cognitive dysfunction, cranial neuropathies, peripheral neuropathies, psychosis, seizures, strokes, and transverse myelitis. Pulmonary manifestations include pleurisy, pulmonary hypertension, pneumonitis, and serositis. Renal manifestations include casts, hematuria, nephrotic syndrome, and proteinuria. Reticuloendothelial manifestations include hepatomegaly, lymphadenopathy, and splenomegaly. 

Systemic Lupus Erythematosus_Initial Assessment 1

Systemic Lupus Erythematosus_Background

Specific Manifestations of Systemic Lupus Erythematosus

Lupus Nephritis

Patients suspected of having lupus nephritis should immediately undergo a renal biopsy to confirm the diagnosis, evaluate severity, and determine prognosis and therapy. 

The indications for renal biopsy in systemic lupus erythematosus patients include an unexplained increase in serum creatinine in the absence of alternative causes (eg sepsis, hypovolemia, medications) and confirmed proteinuria of ≥1 g/24 hr or reproducible proteinuria of ≥0.5 g/24 hr plus glomerular hematuria and/or cellular casts. 

The goal of treatment is to achieve proteinuria is <0.5-0.7 g/24 hr by 12 months, with improvement seen at 3 months and at least 50% reduction in proteinuria by 6 months.

For induction of treatment, Mycophenolate and low-dose intravenous Cyclophosphamide are the recommended first-line treatment in patients with class III-IV disease. Consider giving the same regimens or using high-dose intravenous Cyclophosphamide in those at high risk of renal failure or those with adverse prognostic factors.

For patients with pure class V disease, Mycophenolate is the recommended first-line induction treatment. Alternative options include Cyclophosphamide and calcineurin inhibitors (eg Tacrolimus, Ciclosporin, Voclosporin) in combination with Mycophenolate. Rituximab may also be considered for nonresponders to first-line agents. 

The initial combination of treatment regimens with three consecutive pulses of intravenous Methylprednisolone then followed by oral Prednisone helps increase efficacy and decrease cumulative corticosteroid dose. 

Patients with severe nephrotic syndrome or incomplete renal response without a decreased glomerular filtration rate (GFR), uncontrolled hypertension and/or kidney biopsy with a high chronicity index can be given Mycophenolate combined with low-dose calcineurin inhibitor. 

Hydroxychloroquine may also be considered as initial therapy, with regular ophthalmological screening. 

Belimumab may be used for the treatment of active lupus nephritis in combination with standard immunosuppressive therapies. It should be used in combination with corticosteroids and Mycophenolate or Cyclophosphamide for induction, or Azathioprine or Mycophenolate for maintenance. 

Azathioprine or Mycophenolate should be used for maintenance immunosuppressive treatment. Mycophenolate maintenance therapy is recommended for patients given Mycophenolate during the treatment induction. Azathioprine or Mycophenolate is the recommended maintenance therapy for patients given Ciclosporin as an initial treatment agent. Maintenance treatment with a calcineurin inhibitor may also be considered in class V lupus nephritis at its lowest effective dose. 

For the treatment of refractory disease, Mycophenolate, Ciclosporin, and calcineurin inhibitors as monotherapy or combination therapy are recommended. Studies showed that Rituximab, Obinutuzumab, Belimumab/Mycophenolate, Belimumab/Rituximab, and high-dose IVIg are viable alternative treatment options.

Monitoring of lupus nephritis includes a blood pressure check and laboratory tests such as urinalysis, protein/creatinine ratio, serum creatinine, C3/C4, and anti-DNA levels. 

Please see Lupus Nephritis disease management chart for further information.

Neuropsychiatric SLE (NPSLE)

Monitor systemic lupus erythematosus patients for neurological and/or psychiatric manifestations as in non-NPSLE patients. It usually appears within 1 year from the time of diagnosis but may also appear before or at the time of diagnosis. 

Diagnostic work-up may include lumbar puncture, nerve conduction studies (NCS), neuropsychological assessment of cognitive function, cerebrospinal fluid analysis, electroencephalography (EEG), and neuroimaging such as T1/T2 MRI, diffusion-weighted imaging, or gadolinium-enhanced T1 sequences. 

Manifestations indicating an inflammatory process are treated with corticosteroids and/or immunosuppressants while atherothrombotic or antiphospholipid-related manifestations are treated with antiplatelets or anticoagulants. 

Patients found to have NPSLE should be referred to a team of psychiatrists, psychologists, neurologists, and rheumatologists. 

Skin Disease

The initial management of skin diseases in patients with systemic lupus erythematosus includes the use of topical agents (corticosteroids, calcineurin inhibitors) or antimalarials (Hydroxychloroquine, Quinacrine) with or without systemic corticosteroids. Consider adding Methotrexate, Mycophenolate, Dapsone, or retinoids to unresponsive patients or those who need high-dose corticosteroids. 

Hematological Disease

Lupus thrombocytopenia can be acutely treated with moderate to high doses of corticosteroids (including intravenous pulse dosing of Methylprednisolone) in combination with immunosuppressants and/or IVIg. Azathioprine, Mycophenolate, or Ciclosporin can be used for maintenance therapy. Refractory patients can be given Rituximab or Cyclophosphamide. 

Comorbidities of Systemic Lupus Erythematosus

Cardiovascular Disease

Regularly evaluate patients with systemic lupus erythematosus for traditional and disease-related risk factors for cardiovascular disease (eg persistently active disease, increased disease duration, chronic use of corticosteroids, persistent proteinuria and/or GFR of <60 mL/min, and medium or high titers of antiphospholipid). Vascular events may be reduced with a blood pressure maintained at <140/90 mmHg in patients with systemic lupus erythematosus. Patients may be given low-dose Aspirin and/or lipid-lowering agents based on their individual cardiovascular risk profile. 

Infectious Diseases

Evaluate patients with systemic lupus erythematosus for general and disease-related risk factors for infection (eg advanced age, frailty, renal disease, diabetes mellitus, use of corticosteroid, and immunosuppressive therapy). Early diagnosis and treatment of infection or sepsis and general preventive measures (eg immunizations) are recommended.

Antiphospholipid Syndrome

Antiplatelet agents as primary prophylaxis may be given to patients with systemic lupus erythematosus with a high-risk antiphospholipid profile, especially if with other atherosclerotic or thrombophilic factors, after considering potential for bleeding. Management for secondary prevention (thrombosis, pregnancy loss or complication) should be the same as for primary antiphospholipid syndrome. 

Malignancies

Malignancies may include non-Hodgkin's lymphoma, thyroid, lung, cervical, and vulval cancer. Perform cancer screening and manage according to the established guidelines for the specific conditions. 

Screening

The diagnosis of systemic lupus erythematosus is based on clinical symptoms and laboratory findings. 

Antinuclear antibodies (ANAs) are present in approximately 95% of patients with systemic lupus erythematosus. A negative test indicates a low clinical probability of systemic lupus erythematosus; a positive test alone has a poor diagnostic value without the clinical features of autoimmune rheumatic disease. 

The entry criterion in the diagnosis of systemic lupus erythematosus is an ANA titer of ≥1:80 on HEp-2 cells or an equivalent positive test is measured at least once. It is recommended to test immunofluorescence on HEp-2 cells or a solid-phase ANA screening immunoassay with at least equivalent performance. If the patient is ANA negative, an alternative entry criterion could be low complement levels and/or the presence of antiphospholipid antibodies. 

2019 European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus

The 2019 EULAR or ACR Classification Criteria for systemic lupus erythematosus follows these statements:

• A criterion is not included if there is an explanation other than systemic lupus erythematosus
• It is sufficient for a criterion to occur on at least one occasion
• Criteria need not be present all at the same time
• Only the criterion with the highest weight within each domain will be counted
• Classify as systemic lupus erythematosus if the total score is ≥10 with at least one clinical criterion and the entry criterion is met and if the total score is <10, the inclusion of ACR-97 photosensitivity or a combination of clinical and immunological features can be used to diagnose systemic lupus erythematosus 

Clinical Domains and Criteria

• Constitutional
  • Fever (temperature >38.3°C) is given a score of 2 points
• Hematologic
  • Leukopenia (white blood cell count <4000/mm³) is given a score of 3 points
  • Autoimmune hemolysis (presence of elevated indirect bilirubin, elevated lactate dehydrogenase [LDH], low haptoglobin, reticulocytosis, and positive Coombs’ [direct antiglobulin] test) is given a score of 4 points Thrombocytopenia (platelet count <100,000/mm³) is given a score of 4 points
• Mucocutaneous
  • Non-scarring alopecia (observed by a clinician) is given a score of 2 points
  • Oral ulcers (observed by a clinician) is given a score of 2 points
  • Subacute cutaneous or discoid lupus (observed by a clinician) is given a score of 4 points
  • Acute cutaneous lupus (malar or generalized maculopapular rash observed by a clinician) is given a score of 6 points
• Musculoskeletal
  • Joint involvement (either synovitis involving ≥2 joints or tenderness in ≥2 joints and at least 30 minutes of morning stiffness) is given a score of 6 points
• Neuropsychiatric
  • Delirium (change in consciousness with decreased ability to focus; symptoms developing over hours to <2 days or fluctuating throughout the day; either acute or subacute change in cognition or change in behavior, mood, or affect) is given a score of 2 points
  • Psychosis (hallucinations and/or delusions without insight and no delirium) is given a score of 3 points
  • Seizure (primary generalized seizure, or partial or focal seizure) is given a score of 5 points
• Renal
  • Proteinuria (>0.5 g/24 hour by 24-hour urine or equivalent spot urine protein-to-creatinine ratio) is given a score of 4 points
  • Class II or V lupus nephritis on renal biopsy is given a score of 8 points
  • Class III or IV lupus nephritis on renal biopsy is given a score of 10 points
• Serosal
  • Pleural or pericardial effusion (with imaging evidence) is given a score of 5 points
  • Acute pericarditis (≥2 of the following: Pericardial chest pain, pericardial rub, electrocardiography with new widespread ST elevation or PR depression, or new or worsened pericardial effusion on imaging) is given a score of 6 points

Immunologic Domains and Criteria

• Antiphospholipid antibodies
  • Anti-cardiolipin antibodies (IgA, IgG, or IgM) at medium or high titer OR         
  • Anti-beta-2 glycoprotein 1 antibodies (IgA, IgG, or IgM) OR
  • Lupus anticoagulant positive is given a score of 2 points
• Complement proteins
  • Low C3 OR low C4 is given a score of 3 points
  • Low C3 AND low C4 is given a score of 4 points

Systemic Lupus Erythematosus_Initial Assessment 3

• SLE-specific antibodies
  • Anti-dsDNA antibody in an immunoassay with demonstrated ≥90% specificity for systemic lupus erythematosus versus relevant disease controls OR
  • Anti-Smith antibody is given a score of 6 points

Systemic Lupus Erythematosus_Initial Assessment 2

Disease Activity Indices

Several reliable and validated measuring tools are available for assessing the disease activity in systemic lupus erythematosus. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group (BILAG) are the indices more commonly used and most completely validated

Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)

SLEDAI is a global index for assessing disease activity in the preceding 10 days. It is used for both clinical and research purposes. It consists of twenty-four items which include specific manifestations from nine organ systems with a total score of 105. Other versions of this index include SELENA-SLEDAI, SLEDAI 2000, and Mex-SLEDAI.

British Isles Lupus Assessment Group (BILAG)

BILAG assesses nine organ systems and evaluates relapse occurrences. BILAG 2004 consists of several questions assessed on a 0-4 scale in which 0 is given for not present, 1 is given for improving, 2 is given for same, 3 is given for worse, and 4 is given for new event. Responses are then combined into five states of disease activity which are as follows:

• A: Very active disease needing immunosuppressants, medium- or high-dose corticosteroids or high-dose anticoagulation
• B: Moderate disease activity needing a lower dose of corticosteroid, antimalarials, or NSAIDs
• C: Little disease activity needing only symptomatic treatment
• D: No disease activity at the time but previously present
• E: No current or previous disease activity

Physician Global Assessment (PGA)

PGA is a visual analog scale (VAS) reflecting the physician's judgment of the overall disease activity of systemic lupus erythematosus. The most common visual analog scale tool ranges from 0-3 where 0 is given for none, 1 is given for mild, 2 is given for moderate, and 3 is given for severe. A flare is indicated by an increase in the score of ≥1 since the last patient visit. Reliability is affected by the scale used thus the need for standardization of scoring.   

European Consensus Lupus Activity Measurement (ECLAM)  

ECLAM measures disease activity in the previous month. It evaluates ten organ systems and two laboratory values (eg erythrocyte sedimentation rate [ESR] and complement levels). It consists of 33 items evaluated from 0.5 to 2 based on the type of involvement and a combined global score that ranges from 0 to 17.5.