Systemic lupus erythematosus: clinical approach
文摘
科学
2024-07-10 07:00
澳大利亚
If you would like to view past exciting content, please click on the following link.Systemic lupus erythematosus (SLE), commonly known as lupus, is a chronic autoimmune disease that can impact virtually any organ system. Individuals with this condition develop autoantibodies and immune complexes that cause tissue damage, often affecting the skin, blood, kidneys, joints, and nervous system.When a patient presents with symptoms indicative of SLE, a thorough history and physical examination should be conducted. Typically, patients report general symptoms such as fatigue, fever, malaise, and weight loss, alongside specific complaints like skin photosensitivity, joint pain, pleuritic chest pain, and neurological or psychiatric issues, including cognitive impairments or seizures.During the physical examination, notable signs include a distinctive malar rash, or butterfly rash, characterized by erythema on the nose and cheeks that spares the nasolabial folds. Another significant dermatological sign is the discoid rash, a chronic erythematous rash occurring in sun-exposed areas that may scar. Additional findings may include painless oral and nasal ulcers, symmetric swelling and tenderness of small joints (particularly in the hands and wrists), reduced breath sounds, or a pericardial friction rub. These signs should raise the suspicion of SLE.The next step involves laboratory testing, which should include a complete blood count (CBC), comprehensive metabolic panel (CMP), antinuclear antibody test (ANA), anti-double-stranded DNA, anti-Smith antibodies, antiphospholipid antibodies, and complement levels (C3 and C4). Additionally, a urinalysis and urine spot protein-to-creatinine ratio should be performed to evaluate for proteinuria.Lab results may show anemia, leukopenia, or thrombocytopenia in the CBC, and elevated creatinine levels in the CMP. Positive ANA, potentially accompanied by other specific antibodies, and possibly reduced complement levels are typical findings. The urinalysis might reveal blood, protein, and cellular casts, while an increased urine spot protein-to-creatinine ratio can indicate kidney involvement.Diagnosis of SLE relies on the Classification Criteria for SLE, primarily used for research purposes but also applicable clinically due to the multifaceted nature of lupus. A positive ANA titer of at least 1:80 is necessary for further evaluation using additional criteria, which involve a weighted scoring of various signs, symptoms, and lab results, with a total score of 10 or more supporting a lupus diagnosis.To confirm SLE, both clinical and immunologic domains are considered. Clinical domains include Constitutional symptoms (e.g., fever), Neuropsychiatric symptoms (e.g., delirium, psychosis, seizures), Mucocutaneous manifestations (e.g., hair loss, oral ulcers, skin rashes), Musculoskeletal manifestations (e.g., arthritis), Serosal manifestations (e.g., effusions, pericarditis), Renal involvement (e.g., proteinuria, nephritis), and Hematologic abnormalities (e.g., leukopenia, thrombocytopenia, hemolysis). Each symptom and finding contributes to a comprehensive assessment of the patient.In the immunologic domain, individuals with systemic lupus erythematosus (SLE) often exhibit specific antibodies, such as anti-double stranded DNA and anti-Smith antibodies. Abnormalities in complement proteins, like decreased levels of C3 or C4, are also common. Additionally, patients might test positive for antiphospholipid antibodies, including lupus anticoagulant, anti-cardiolipin, and anti-Beta 2 glycoprotein 1 antibodies.It’s important to note that the presence of antiphospholipid antibodies might also indicate antiphospholipid antibody syndrome, an autoimmune disorder associated with various forms of thrombosis and pregnancy complications like fetal loss and preeclampsia, independent of lupus.A useful mnemonic for remembering key lupus manifestations is SOAP BRAIN MD. "S" represents serositis (such as pericarditis, pleuritis, peritonitis); "O" for oral or nasal ulcers; "A" for arthritis in two or more joints; "P" for photosensitivity; and "B" for blood disorders, including various cytopenias and malignancies."R" indicates renal involvement, typically lupus nephritis due to immune complexes in the glomerular basement membrane. "A" stands for a positive ANA test; "I" refers to other immunologic phenomena or antibodies; "N" for neurologic and psychiatric conditions such as headaches, seizures, and mood disorders; and "MD" highlights skin manifestations—Malar rash and Discoid rash.If a patient meets the diagnostic criteria, diagnose SLE. However, if the criteria are not met, consider alternative diagnoses. For those diagnosed, assessing for renal involvement is crucial. This includes checking for proteinuria or cellular casts in urinalysis, elevated serum creatinine, or a decreased estimated glomerular filtration rate.Should there be signs of renal involvement, suspect lupus nephritis and proceed with a renal biopsy. If the biopsy confirms immune complex-mediated glomerulonephritis, diagnose lupus nephritis, categorized into six classes each having distinct prognostic and therapeutic implications.Treatment generally begins with hydroxychloroquine, but for severe nephritis (classes III, IV, or V), treatment involves glucocorticoids combined with mycophenolate mofetil or cyclophosphamide. In cases of proteinuria, start an ACE inhibitor or angiotensin receptor blocker to protect the kidneys. For persistent hypertension, additional antihypertensive treatments or lifestyle modifications may be necessary.A clinical pearl to remember: patients without renal involvement at diagnosis can still develop lupus nephritis later, necessitating regular monitoring of urine and serum creatinine levels.For lupus patients without renal complications, evaluate the overall severity of the disease, which can range from mild to severe, based on the clinical presentation. This assessment helps tailor management strategies accordingly.For patients presenting with mild systemic lupus erythematosus (SLE), characterized by mild skin and joint symptoms combined with mild cytopenia (platelet count between 50,000 and 100,000), the initial treatment strategy involves hydroxychloroquine. If the patient responds well, indicating symptom improvement or resolution, this management should be continued. However, if there is an inadequate response, consider adding an NSAID or a low-dose glucocorticoid to the treatment regimen. It’s crucial to use glucocorticoids for the shortest possible duration and at the lowest effective dose to achieve remission, followed by a gradual tapering and potential discontinuation.Shifting to moderate disease severity, patients may exhibit more extensive skin or joint involvement, or moderate cytopenias (platelet count between 20,000 and 50,000), along with other organ involvement like serositis, which may manifest as small pleural or pericardial effusions, or gastrointestinal issues such as hepatitis or enteritis, without threatening organ function. Treatment should start with hydroxychloroquine and a glucocorticoid. If the patient responds well to treatment, begin to taper the glucocorticoid with the aim of discontinuation. If the response is inadequate, consider introducing an additional immunosuppressive agent such as azathioprine, mycophenolate mofetil, or a calcineurin inhibitor like cyclosporine or tacrolimus.For patients with severe disease, characterized by organ-threatening conditions such as severe neurological or renal manifestations, very low platelet counts (below 20,000), or large pericardial or pleural effusions, initiate treatment with hydroxychloroquine, a high-dose glucocorticoid, and either mycophenolate mofetil or cyclophosphamide. Monitor the patient’s response, and if it is adequate, gradually reduce the glucocorticoid dosage with the goal of discontinuation. If the response is inadequate, consider switching between immunosuppressive agents, for example from mycophenolate mofetil to cyclophosphamide or vice versa. Additionally, some patients may benefit from alternative treatments such as rituximab.It’s important to emphasize that hydroxychloroquine remains a cornerstone in the management of all lupus patients due to its role in reducing flare-ups, preventing organ damage, and improving long-term survival. Hydroxychloroquine should be maintained even during remission and is safe during pregnancy. However, due to the risk of retinal toxicity associated with hydroxychloroquine, patients should undergo annual ophthalmologic evaluations to monitor eye health.1. **Diagnosis**: If you suspect lupus, utilize the classification criteria for SLE to confirm the diagnosis.2. **Renal Assessment**: Determine the extent of renal involvement. If present, order a renal biopsy to check for lupus nephritis.3. **Treatment Initiation for Lupus Nephritis**: If the biopsy confirms lupus nephritis, start with hydroxychloroquine and consider adding other immunosuppressive medications based on the severity and response.4. **Severity Assessment**: Determine the severity of the disease to guide treatment: - **Mild Disease**: Initiate treatment with hydroxychloroquine. If the response is inadequate, add an NSAID or low-dose glucocorticoid. - **Moderate Disease**: Begin with hydroxychloroquine and glucocorticoids. If there's an inadequate response, introduce an additional immunosuppressive medication like azathioprine, mycophenolate mofetil, or calcineurin inhibitors. - **Severe Disease**: Treat with hydroxychloroquine, high-dose glucocorticoids, and another potent immunosuppressive agent like mycophenolate mofetil or cyclophosphamide. Consider switching agents if the initial response is inadequate.Throughout the treatment process, continuous assessment and adjustment based on patient response are essential. Hydroxychloroquine remains a cornerstone of treatment for all severity levels due to its efficacy in reducing flares and promoting long-term well-being. It's also important to monitor for potential side effects and adjust the therapy accordingly."The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults" Rheumatology (Oxford) (2018)"American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis" Arthritis Care Res (Hoboken) (2012)"2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus" Arthritis Rheumatol (2019)"2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis" Ann Rheum Dis (2020)"2019 update of the EULAR recommendations for the management of systemic lupus erythematosus" Ann Rheum Dis (2019)"The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults" Rheumatology (Oxford) (2018)"Systemic Lupus Erythematosus: Diagnosis and Treatment" Am Fam Physician (2023)"Antiphospholipid syndrome" Hematology Am Soc Hematol Educ Program (2013)"International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)" J Thromb Haemost (2006)"Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus" Arthritis Rheum (2012) - - - - - - - END - - - - - - -
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