What are the guideline sources, guidelines and references for Systemic lupus erythematosus ?
Guideline sources The following summarized guidelines for the evaluation and management of systemic lupus erythematosus are prepared by our editorial team based on guidelines from the American College of Rheumatology (ACR 2023), the European League Against Rheumatism (EULAR 2022; 2019), the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2021), the European Dialysis and Transplant Association (ERA-EDTA/EULAR 2020), the British Society for Rheumatology (BSR 2018), the Pan-American League of Associations of Rheumatology (PANLAR 2018), the Canadian Rheumatology Association (CRA 2018), and the Treat-to-target (T2T 2014). 1 2 3 4 5 6 7 8 9 10 11 11 12 12 12 Definition SLE is a chronic autoimmune disease with a heterogeneous clinical course and progressive involvement of multiple organs. 10 Epidemiology https://web.pathway.md/diseases/rec2VahxSujBKEc4x 1/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway SLE is caused by a complex interaction between genetic (SNP polymorphisms, deficiency of C1q and C4), epigenetic (DNA hypomethylation), hormonal (X chromosome and estrogen), immunoregulatory (T and B cell rewiring) and environmental factors (UV exposure, smoking). 12 Pathophysiology In the United States, the estimated incidence of SLE ranges from 4.9 to 7.4 cases per 100,000 person-years, while the estimated prevalence ranges from 72.8 to 178 persons per 100,000 population. 11 Disease course Autoantibody production, immune complex formation, and inflammatory T cell activation result in inflammation and end-organ damage (particularly in the skin, kidneys, heart, lungs, and brain), which causes increased morbidity and mortality. 12 Prognosis and risk of recurrence The 10-year survival rate of patients with SLE is approximately 70%. The all-cause standard mortality rate is increased 2.6 fold in patients with SLE, and the risk of mortality is increased by 4.98, 4.67, and 2.25 fold for infections, renal disease, and CVD, respectively. 11 12 Guidelines 1. Screening and diagnosis Clinical manifestations: recognize that clinical manifestations in SLE may be due to disease activity (inflammation or thrombosis), damage, drug toxicity or the presence of comorbidity. B Diagnosis: diagnose SLE based on a combination of clinical features and the presence of at least one relevant immunological abnormality. Obtain blood tests (including serological markers) in case of clinical suspicion of SLE. B Show 3 more 2. Classification and risk stratification Assessment of disease activity: Classify disease activity into the following categories according to the occurrence of flares B : https://web.pathway.md/diseases/rec2VahxSujBKEc4x 2/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway Situation Guidance Clinically stable disease with no life- threatening organ involvement, mainly manifesting as arthritis, mucocutaneous lesions and mild pleuritis Mild More serious manifestations Moderate Organ- or life-threatening disease. B Severe 3. Diagnostic investigations Initial evaluation: As per EULAR 2019 guidelines, screen for antiphospholipid syndrome in all patients with SLE at diagnosis. A As per BSR 2018 guidelines, elicit a thorough history and review of systems, perform full clinical examination and monitoring of vital signs, obtain urinalysis, laboratory tests, assessment of health status and quality of life, and measurement of disease activity and damage using standardized SLE assessment tools in patients with SLE. B Show 2 more As per CRA 2018 guidelines, elicit a thorough history and perform a complete physical examination at baseline. B Show 2 more Anti-Ro/La antibodies: measure anti-Ro and anti-La antibodies prior to pregnancy or during the first trimester in women with SLE. B Screening for chronic infections: As per EULAR 2022 guidelines, screen for HBV infection in all patients eligible for treatment with conventional synthetic, biological, or targeted synthetic DMARDs, immunosuppressants, or corticosteroids (according to dose and duration). B Show 3 more As per EULAR 2019 guidelines, assess for the following general and disease-related risk factors for infections in patients with SLE: advanced age/frailty B diabetes mellitus B renal involvement B immunosuppressive/biological therapy B use of corticosteroids. A As per PANLAR 2018 guidelines, screen for HBV and HCV infections in patients with high-risk behaviors for virus acquisition. Consider screening for hepatitis B infection before initiating https://web.pathway.md/diseases/rec2VahxSujBKEc4x 3/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway immunomodulatory treatments. B Evaluation for osteonecrosis: Consider avoiding screening for osteonecrosis in adult and pediatric patients with SLE who do not have clinical symptoms suggestive of osteonecrosis. D Consider radiographs as the initial imaging modality to screen for osteonecrosis, rather than MRI or bone scan with single photon emission-CT. C Evaluation of cardiac risk: As per EULAR 2019 guidelines: Obtain regular assessment in patients with SLE for traditional B and disease-related risk factors for CVD, including: persistently active disease B increased disease duration B medium/high titers of antiphospholipid antibodies B renal involvement, especially persistent proteinuria and/or GFR < 60 mL/min B chronic use of corticosteroids. B Consider initiating preventative strategies as in the general population, including low-dose aspirin and/or lipid-lowering agents, in patients with SLE based on their individual cardiovascular risk profile. C As per BSR 2018 guidelines, assess modifiable risk factors including hypertension, dyslipidemia, diabetes, high BMI and smoking at baseline and at least annually in patients with SLE. B As per CRA 2018 guidelines: Assess for cardiovascular comorbidities including obesity, smoking status, arterial hypertension, diabetes, and dyslipidemia at the time of diagnosis of SLE. Reassess comorbidities periodically according to current recommendations in the general population. B Avoid carotid ultrasound as part of routine cardiovascular risk assessment, except in highly selected cases where expertise is available. D Evaluation of fracture risk: Consider assessing for risk of osteoporosis and fractures every 1-3 years with a detailed history, physical exam, and measurement of bone mineral density in patients with other risk factors as per recommendations for the general population. C Consider screening for 25-hydroxyvitamin D deficiency as part of the assessment for risk for osteoporosis and fractures. C 4. Medical management General principles: As per EULAR 2019 guidelines, consider treating flares of SLE according to the severity of organ involvement by adjusting ongoing therapies (corticosteroids, immunomodulating agents) https://web.pathway.md/diseases/rec2VahxSujBKEc4x 4/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway to higher doses, switching or adding new therapies. C As per BSR 2018 guidelines: Consider initiating hydroxychloroquine B , methotrexate B , and short courses of NSAIDs for symptomatic control in patients with mild non-organ-threatening disease include. C Obtain thorough evaluation to exclude other etiologies, including infection, in patients presenting with severe SLE, including renal and neuropsychiatric manifestations. Initiate treatment according to the underlying etiology (inflammatory and/or thrombotic) with immunosuppression and/or anticoagulation, respectively. B As per PANLAR 2018 guidelines: Individualize treatment. Emphasize the active involvement of patients and their family members in the overall therapeutic plan. B Provide comprehensive treatment that includes photo-protection, management of osteoporosis, cardiovascular and metabolic comorbidities, prevention of infection, psychological support and pregnancy counseling. B As per T2T 2014 guidelines, decide on management of SLE based on shared decisions between the informed patient and the clinician. E Show 3 more Goals of treatment: As per EULAR 2019 guidelines, aim for remission or low disease activity and prevention of flares in all organs, maintained with lowest possible dose of corticosteroids. B As per PANLAR 2018 guidelines, target remission or low disease activity, and aim to achieve this as soon as possible after the diagnosis is made, and to maintain this for as long as possible. B As per T2T 2014 guidelines, set treatment goals of SLE aiming at ensuring long-term survival, preventing organ damage, and optimizing health-related quality-of-life, by controlling disease activity and minimizing comorbidities and drug toxicity. E Show 2 more Hydroxychloroquine: As per EULAR 2019 guidelines: Initiate hydroxychloroquine in all patients with SLE B , unless contraindicated, at a dose not exceeding 5 mg/kg/real body weight. B Obtain ophthalmological screening (by visual fields examination and/or spectral domain-optical coherence tomography) at baseline, after 5 years and yearly thereafter, in the absence of risk factors for retinal toxicity. B As per PANLAR 2018 guidelines, initiate hydroxychloroquine in all patients with SLE, except those who refuse or who have absolute contraindications to its use. Chloroquine remains an alternative for some countries where hydroxychloroquine is not available. B Corticosteroids: https://web.pathway.md/diseases/rec2VahxSujBKEc4x 5/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway As per EULAR 2019 guidelines, consider initiating corticosteroids at doses and route of administration depending on the type and severity of organ involvement. C Show 3 more As per BSR 2018 guidelines: Consider initiating prednisolone at a low dose of 7.5 mg/day for maintenance therapy in patients with SLE. C Administer higher doses of prednisolone (up to 0.5 mg/kg/day) in patients with moderate SLE. B As per PANLAR 2018 guidelines, limit corticosteroid exposure by employing the lowest possible dose for the shortest period of time possible. B Immunosuppressants: As per EULAR 2019 guidelines, consider adding any of the following agents in patients not responding to hydroxychloroquine alone or in combination with corticosteroids, or unable to reduce corticosteroids below doses acceptable for chronic use: methotrexate C azathioprine C mycophenolate. C Show 2 more As per BSR 2018 guidelines, initiate immunosuppressive agents to control active disease, B reduce the risk of long-term damage accrual B and as corticosteroid-sparing agents. B Show 4 more Biologics: As per EULAR 2019 guidelines: Consider initiating add-on therapy with belimumab in patients with inadequate response to standard-of-care (combination of hydroxychloroquine and corticosteroids with or without immunosuppressive agents), defined as residual disease activity not allowing tapering of corticosteroids and/or frequent relapses. B Consider initiating rituximab in patients with organ-threatening disease refractory or with intolerance/contraindications to standard immunosuppressive agents. C As per BSR 2018 guidelines, consider initiating belimumab C or rituximab in patients refractory disease C , or on a case-by-case basis in patients failed to respond to other immunosuppressive drugs due to inefficacy or intolerance. C Intravenous immunoglobulin: consider administering IVIG C in patients with refractory cytopenias or TTP, C rapidly deteriorating acute confusional state or catastrophic variant of antiphospholipid syndrome. 5. Nonpharmacologic interventions https://web.pathway.md/diseases/rec2VahxSujBKEc4x 6/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway Sun protection: advise using high-sun protection factor UVA and UVB sunscreen B , avoiding sun exposure and wearing protective clothing for the management and prevention of UV radiation- induced skin lesions in patients with SLE. B 6. Therapeutic procedures Plasmapheresis: consider performing plasmapheresis C in patients with refractory cytopenias or TTP, C rapidly deteriorating acute confusional state or catastrophic variant of antiphospholipid syndrome. 7. Specific circumstances Pregnant patients: As per BSR 2018 guidelines: Recognize that the presence of antiphospholipid antibodies is associated with thrombotic events, damage, and adverse outcomes in pregnancy. B Reevaluate antiphospholipid antibodies, if previously negative, before pregnancy or surgery, or in the presence of a new severe manifestation or vascular event. B Screen for anti-Ro and anti-La antibodies before pregnancy because of the risk of neonatal lupus (including congenital heart block). B As per PANLAR 2018 guidelines, obtain a complete history, physical, and laboratory evaluation (including antiphospholipid antibodies at baseline) immediately prior to pregnancy, during each trimester of pregnancy, and when flare is suspected during pregnancy. B Show 2 more Patients with lupus nephritis: As per KDIGO 2021 guidelines, define response to treatment in patients with lupus nephritis as follows: Situation Guidance Reduction in proteinuria < 0.5 g/g (50 mg/mmol) measured as the protein- creatinine ratio from a 24-hour urine collection (proteinuria < 0.5 g/1.73 m /day or < 300 mg/m /day based on a 24-hour urine specimen in pediatric patients) Complete response Stabilization or improvement in kidney function ( 10-15% of baseline) Within 6-12 months of initiating therapy, but could take > 12 months Partial response https://web.pathway.md/diseases/rec2VahxSujBKEc4x 7/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway Reduction in proteinuria by at least 50% and to < 3 g/g (300 mg/mmol) measured as the protein-creatinine ratio from a 24-hour urine collection Stabilization or improvement in kidney function ( 10-15% of baseline) Within 6-12 months of initiating therapy Failure to achieve a partial or complete response within 6-12 months of initiating therapy. B No kidney response As per EULAR 2020 guidelines, set the following as goals of treatment in lupus nephritis: patient survival long-term preservation of kidney function prevention of disease flares prevention of organ damage management of comorbidities improvement in disease-related quality of life. B Show 7 more As per EULAR 2019 guidelines, ensure early recognition of signs of renal involvement and, when present, perform diagnostic renal biopsy to ensure optimal outcomes. B Show 5 more As per BSR 2018 guidelines, initiate mycophenolate mofetil or cyclophosphamide in most cases of lupus nephritis and for refractory, severe non-renal disease. B As per PANLAR 2018 guidelines, administer hydroxychloroquine and corticosteroids, in addition to an immunosuppressant (cyclophosphamide, mycophenolate mofetil, or tacrolimus) for induction of remission in patients with SLE-related kidney disease. B Show 2 more As per T2T 2014 guidelines, ensure early recognition and treatment of renal involvement in patients with SLE. E Show 2 more Patients with diffuse alveolar hemorrhage: treat patients with SLE-related diffuse alveolar hemorrhage with intravenous corticosteroids plus cyclophosphamide and/or IVIGs and/or therapeutic plasma exchange and/or rituximab. B Patients with pericarditis: consider administering colchicine plus standard of care (hydroxychloroquine and corticosteroids) in patients with acute SLE-related pericarditis. C Patients with neuropsychiatric manifestations: As per EULAR 2019 guidelines: https://web.pathway.md/diseases/rec2VahxSujBKEc4x 8/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway Consider obtaining neuroimaging, CSF analysis, assessing risk factors (type and timing of the manifestation in relation to the onset of lupus, patient age, non-neurological lupus activity, presence of antiphospholipid antibodies), excluding confounding factors in order to facilitate attribution of neuropsychiatric manifestations to SLE. C Initiate the following for the treatment of SLE-related neuropsychiatric disease: corticosteroids/immunosuppressive agents for manifestations considered to reflect an inflammatory process B antiplatelet/anticoagulants for atherothrombotic/antiphospholipid antibodies-related manifestations. B As per BSR 2018 guidelines, consider administering IVIG C and performing plasmapheresis C in patients with rapidly deteriorating acute confusional state. As per PANLAR 2018 guidelines, consider administering corticosteroids plus cyclophosphamide (over corticosteroids alone or corticosteroids plus rituximab) for the treatment of severe neurologic manifestations in patients with SLE. C Patients with hemolytic anemia: Consider administering high-dose corticosteroids in patients with severe autoimmune hemolytic anemia. C Consider initiating rituximab for patients with life-threatening autoimmune hemolytic anemia and/or for patients in whom high-dose corticosteroid treatment fails. C Patients with thrombocytopenia: As per EULAR 2019 guidelines, administer high-dose corticosteroids (including pulses of IV methylprednisolone) and/or IV IgG for acute treatment of lupus thrombocytopenia. B Show 2 more As per BSR 2018 guidelines, consider administering IVIG C and performing plasmapheresis C in patients with refractory cytopenias or TTP. C As per PANLAR 2018 guidelines: Consider administering high-dose corticosteroids in patients with lupus with severe lupus thrombocytopenia. C Administer IVIGs with or without corticosteroids, or rituximab plus corticosteroids, in patients with severe lupus thrombocytopenia who meet one of the following criteria: thrombocytopenia refractory to high-dose corticosteroids life-threatening bleeding requirement for urgent surgery active infections. B Patients with antiphospholipid syndrome: As per EULAR 2019 guidelines: Consider administering primary prophylaxis with antiplatelet agents in patients with SLE with high-risk antiphospholipid antibodies profile (persistently positive medium/high titers or multiple https://web.pathway.md/diseases/rec2VahxSujBKEc4x 9/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway positivity), especially if other atherosclerotic/thrombophilic factors are present, after balancing the bleeding hazard. C Use the same therapeutic approach for secondary prevention (thrombosis, pregnancy complication/loss) as recommended for primary antiphospholipid syndrome. B As per BSR 2018 guidelines, consider administering IVIG C and performing plasmapheresis C in patients with catastrophic variant of antiphospholipid syndrome. As per PANLAR 2018 guidelines, initiate extended anticoagulation therapy with a vitamin K antagonist for patients with antiphospholipid syndrome and venous thrombotic disease. B Show 3 more As per T2T 2014 guidelines, offer the same treatment options in patients with SLE-related antiphospholipid syndrome as in primary antiphospholipid syndrome. E Patients with musculoskeletal manifestations: As per BSR 2018 guidelines, consider administering intra-articular corticosteroids injections in patients with arthritis. C As per PANLAR 2018 guidelines: Consider standard of care alone (hydroxychloroquine and corticosteroids) over adding other immunosuppressant in adult patients with musculoskeletal manifestations of SLE. C Consider adding either methotrexate, leflunomide, belimumab or abatacept to patients with musculoskeletal manifestations that fail to respond to standard of care. C Patients with cutaneous manifestations: As per EULAR 2019 guidelines: Initiate the following options as first-line therapy of skin disease in SLE: topical agents: corticosteroids, calcineurin inhibitors B antimalarials: hydroxychloroquine, quinacrine A systemic corticosteroids. B Consider adding the following agents in patients with non-responsive disease or requiring high-dose corticosteroids: methotrexate C retinoids C dapsone C mycophenolate. C As per BSR 2018 guidelines, consider offering topical corticosteroids in patients with cutaneous manifestations. C As per PANLAR 2018 guidelines: Administer hydroxychloroquine alone in patients with cutaneous manifestations, rather than adding another immunosuppressant. B Consider adding methotrexate, azathioprine, cyclosporine A, cyclophosphamide, or belimumab to patients who fail to respond to standard of care. C https://web.pathway.md/diseases/rec2VahxSujBKEc4x 10/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway 8. Patient education Patient education: educate adult and pediatric patients with SLE (in particular, patients who have a history of corticosteroid exposure) regarding the symptoms of osteonecrosis (including progressive or sudden deep joint pain that is worse with weight-bearing). B 9. Preventative measures Routine immunizations: As per ACR 2023 guidelines, consider offering high-dose or adjuvanted influenza vaccination, rather than regular-dose influenza vaccination, in 65 years old patients with rheumatic or musculoskeletal diseases and in 18-65 years old patients with rheumatic or musculoskeletal diseases on immunosuppressive medications. C Show 17 more As per CRA 2018 guidelines, provide influenza immunization with an inactivated vaccine on an annual basis in adults and children with SLE. B Prophylaxis for Pneumocystis jirovecii pneumonia: consider administering prophylaxis against P. jirovecii pneumonia in patients initiating high-dose corticosteroids, especially in combination with immunosuppressants and depending on the risk-benefit ratio. C 10. Follow-up and surveillance Indications for specialist referral: refer all adult patients with suspected SLE to an SLE specialist, most often a rheumatologist, to confirm diagnosis and facilitate ongoing care. B Serial clinical and laboratory monitoring: As per BSR 2018 guidelines, monitor patients with SLE regularly for disease manifestations, drug toxicity and comorbidities. B Obtain close monitoring for toxicities in patients taking immunosuppressive drugs by regular laboratory tests and clinical assessment in accordance with drug monitoring guidelines. B Show 2 more As per CRA 2018 guidelines: Consider assessing disease activity and end-organ damage annually with a validated measure for adult and pediatric patients with SLE. C Obtain follow-up laboratory monitoring depending on the patient's clinical status. Such monitoring may include CBC, estimated GFR, urinalysis, urine protein-creatinine ratio, CRP and/or ESR, C3, C4, and anti-dsDNA antibodies. B As per T2T 2014 guidelines, obtain regular long-term monitoring and review and/or adjustment of therapy in patients with SLE. E Cervical cancer screening: consider annual cervical cancer screening rather than screening every 3 years at least until 69 years of age for all female adult patients with SLE who are or have https://web.pathway.md/diseases/rec2VahxSujBKEc4x 11/13 6/24/23, 3:14 PM Systemic lupus erythematosus Pathway been sexually active, regardless of sexual orientation. C References 1. Caroline Gordon, Maame-Boatemaa Amissah-Arthur, Mary Gayed et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology Oxford). 2018 Jan 1;57 1):e1-e45. Open 2. Antonis Fanouriakis, Myrto Kostopoulou, Alessia Alunno et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019 Jun;78 6 736 745. Open 3. Antonis Fanouriakis, Myrto Kostopoulou, Kim Cheema et al. 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 Jun;79 6 713 723. Open 4. Pons-Estel BA, Bonfa E, Soriano ER et al. First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology PANLAR . Ann Rheum Dis. 2018 Jul 25. Open 5. Ronald F van Vollenhoven, Marta Mosca, George Bertsias et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014 Jun;73 6 958 67. Open 6. Kidney Disease: Improving Global Outcomes KDIGO Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100 4S S1 S276. Open 7. Keeling SO, Alabdurubalnabi Z, Avina-Zubieta A et al. Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus. J Rheumatol. 2018 Oct;45 10 1426 1439. Open 8. Anne R Bass, Eliza Chakravarty, Elie A Akl et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2023 Jan 4. Online ahead of print. Open 9. George E Fragoulis, Elena Nikiphorou, Mrinalini Dey et al. 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2022 Nov 3;ard-2022 223335. Open 10. Ali A, Sayyed Z, Ameer MA et al. RETRACTED ARTICLESystemic Lupus Erythematosus: An Overview of the Disease Pathology and Its Management. 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EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022 Jun;81 6 768 779. Open 16. Martin Aringer, Karen Costenbader, David Daikh et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019 Sep;71 9 1400 1412. Open 17. Expert Panel on Neurological Imaging, Vikas Agarwal, Lubdha M Shah et al. ACR Appropriateness Criteria Myelopathy: 2021 Update. J Am Coll Radiol. 2021 May;18 5S S73 S82. Open https://web.pathway.md/diseases/rec2VahxSujBKEc4x 13/13