Systemic lupus erythematosus Investigation and management Initial evaluation Elicit a thorough history and perform a complete physical examination at baseline. B Obtain baseline laboratory tests, possibly including, but not limited to: CBC, CK, liver enzymes creatinine and eGFR, urinalysis, urine microscopy, urine protein-creatinine ratio CRP, ESR, complements (C3, C4) anti-dsDNA, antinuclear antibodies, antibodies to extractable nuclear antigens lupus anticoagulant, anticardiolipin, anti- -2-glycoprotein I lipid profile. B Consider assessing disease activity with validated instrument of disease activity during baseline and followup visits. C Screening for chronic infections PANLAR Q Does the patient have high-risk behaviors for acquisition of hepatitis B or C? Q Is immunomodulatory therapy planned? Yes to any Screen for HBV and HCV infections in patients with high-risk behaviors for virus acquisition. Consider screening for hepatitis B infection before initiating immunomodulatory treatments. B No to all 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 General principles 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 Hydroxychloroquine PANLAR Q Is hydroxychloroquine contraindicated? No 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 Yes Patients with lupus nephritis PANLAR Q Does the patient have adult-onset lupus nephritis? Yes 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 Consider using high-dose corticosteroids plus mycophenolate mofetil or cyclophosphamide, rather than high-dose corticosteroids alone, as induction therapy in patients with childhood lupus nephritis. Recognize that cost and availability may favor cyclophosphamide, despite the risk of gonadal toxicity. C Consider using mycophenolate mofetil or azathioprine, rather than cyclophosphamide, as maintenance therapy in patients with childhood lupus nephritis who responded, partially or completely, to induction therapy. Recognize that cost and availability may favor azathioprine. C No Patients with pericarditis Q Does the patient have lupus-associated pericarditis? Yes No Consider administering colchicine plus standard of care (hydroxychloroquine and corticosteroids) in patients with acute SLE-related pericarditis. C No Patients with diffuse alveolar hemorrhage Q Does the patient have lupus-associated diffuse alveolar hemorrhage? Yes 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 No Patients with neuropsychiatric manifestations PANLAR Q Does the patient have lupus-associated neuropsychiatric manifestations? Yes Consider administering corticosteroids plus cyclophosphamide (over corticosteroids alone or corticosteroids plus rituximab) for the treatment of severe neurologic manifestations in patients with SLE. C No Patients with hemolytic anemia Q Does the patient have lupus-associated hemolytic anemia? Yes Consider administering high-dose corticosteroids in patients with severe autoimmune hemolytic anemia. C No Patients with hemolytic anemia Q Does the patient have life-threatening hemolytic anemia? Q Did the patient fail high-dose glucocorticoid treatment for hemolytic anemia? Yes to any Consider initiating rituximab for patients with life-threatening autoimmune hemolytic anemia and/or for patients in whom high-dose corticosteroid treatment fails. C No Patients with thrombocytopenia PANLAR Q Does the patient have severe lupus-associated thrombocytopenia? Yes Consider administering high-dose corticosteroids in patients with lupus with severe lupus thrombocytopenia. C No Patients with thrombocytopenia PANLAR Q Is thrombocytopenia refractory to high-dose glucocorticoids? Q Does the patient have life-threatening bleeding? Q Does the patient require urgent surgery? Q Does the patient have an active infection infection? Yes to any 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 No Patients with antiphospholipid syndrome PANLAR Q Does the patient have antiphospholipid syndrome? Q Does the patient have venous thrombolic disease? Yes to all Initiate extended anticoagulation therapy with a vitamin K antagonist for patients with antiphospholipid syndrome and venous thrombotic disease. B Use standard (INR 2.0-3.0) over high-intensity (INR 3.0-4.0) anticoagulation for patients with SLE and antiphospholipid syndrome with venous thrombotic disease. B No Patients with antiphospholipid syndrome PANLAR Q Does the patient have antiphospholipid syndrome? Q Does the patient have a history of stroke? Yes to all Select extended high-intensity (INR 3.0-4.0) over standard intensity (2.0-3.0) anticoagulation or low-dose aspirin therapy for patients with antiphospholipid syndrome and stroke. B No Patients with musculoskeletal manifestations PANLAR Q Does the patient have lupus-associated musculoskeletal manifestations? Yes 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 No Patients with cutaneous manifestations PANLAR Q Does the patient have lupus-associated cutaneous manifestations? Yes 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 No Serial clinical and laboratory monitoring 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, eGFR, urinalysis, urine protein-creatinine ratio, CRP and/or ESR, C3, C4, and anti-dsDNA antibodies. B