musculoskeletal and connective tissue disorders
Systemic Lupus Erythematosus (SLE)
Treatment of SLE
Hydroxychloroquine(an antimalarial) for all patients with SLE Nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to antimalarials for mild disease Corticosteroids, immunosuppressants, and antimalarials for severe disease To simplify therapy, SLE should be classified as mild to moderate (eg, fever, arthritis, pleurisy, pericarditis, rash) or severe (eg, hemolytic anemia, severe thrombocytopenic purpura, massive pleural and pericardial involvement, diffuse alveolar hemorrhage or pneumonitis, nephritis, acute vasculitis of the extremities or gastrointestinal tract, florid central nervous system [CNS] involvement). is indicated for all patients with SLE regardless of disease severity because it decreases disease flares and decreases mortality ( Treatment references ); however, (See alsorecommendations for the management of SLEfrom the European League Against Rheumatism [EULAR].) Arthralgias are usually controlled with NSAIDs. However, chronic NSAID use is discouraged because of gastrointestinal adverse effects (eg, peptic ulcer disease) and potential coronary and renal toxicity (eg, interstitial nephritis, papillary necrosis). Topical agents (corticosteroids,tacrolimus) can be used for skin disease, usually under the guidance of dermatology. Antimalarials, such ashydroxychloroquine, are useful for joint and skin manifestations.Hydroxychloroquinereduces the frequency of SLE flares and decreases mortality, and is therefore used in virtually all patients with SLE. Dose is 5 mg/kg of actual body weight orally once a day. Baseline ophthalmologic examination should be done before starting therapy to exclude maculopathy because chronichydroxychloroquineuse increases the risk of toxic maculopathy. Ophthalmologic screening should be done yearly after the drug has been used for 5 years to assess for retinal toxicity. Alternatives include oralchloroquine250 mg once a day and oral quinacrine 50 to 100 mg once a day. (See alsorecommendationson screening forchloroquineandhydroxychloroquineretinopathy.)Hydroxychloroquinecan rarely cause skeletal or cardiac muscle toxicity. Methotrexate(15 to 20 mg orally or subcutaneously once a week),azathioprine(2 mg/kg orally once a day), ormycophenolatemofetil (1 to 1.5 grams orally twice a day) can be added tohydroxychloroquinein patients with uncontrolled mild to moderate disease who would otherwise be candidates for a course of corticosteroids. The ultimate goal is to maintain disease remission either without the need for corticosteroids or with only the lowest dose possible. (10 mg/kg IV every 2 weeks for 3 doses, then 10 mg/kg IV once a month or 200 mg subcutaneously once a week) should be considered if patients have uncontrolled disease or frequent flares, particularly for joint, skin, or nonsevere hematologic manifestations ( Treatment references ). It can be used in addition to Treatment includes induction therapy to control acute severe manifestations followed by maintenance therapy. Corticosteroids are first-line therapy. A combination of a corticosteroid and other immunosuppressants is typically used in active severe disease (ie, lupus nephritis with impaired renal function or CNS involvement). The complication for which there is the strongest evidence for treatment efficacy is Lupus Nephritis . alone ( Treatment references ). Vocloscorin in a dose of 23.7 mg orally twice a day in combination with Cyclophosphamideuse for more than 6 months is discouraged because of potential toxicities, including increased risk of cancer. Once disease control is achieved, patients are transitioned to eithermycophenolatemofetil (1 to 1.5 g orally 2 times a day) orazathioprine(0.5 to 1.5 mg/kg orally twice a day) for maintenance. Women of childbearing age for whomcyclophosphamideis being considered should be informed about the risk of gonadal toxicity and offered a fertility consult for ovarian protection or egg harvesting when possible. In CNS lupus, including Acute Transverse Myelitis , treatment recommendations are based on anecdotal evidence, and options include IV is an alternative option for refractory cases ( Treatment references ). Patients with end-stage renal disease can undergo kidney transplantation, as an alternative to dialysis, with a successful outcome, especially if their disease has been in remission. Improvement of severe SLE often takes 4 to 12 weeks. Thrombosis or embolism of cerebral, pulmonary, or placental vessels requires short-term treatment withheparinand longer treatment withwarfarin. If the diagnosis of antiphospholipid syndrome is confirmed, lifelong therapy (usuallywarfarin) is usually indicated. The initial target international normalized ratio is usually 2 to 3. (IgG1κ monoclonal antibody to type I interferon receptor), at a dose of 300 mg IV every 4 weeks, may be added to standard therapy for the management of moderate to severe systemic lupus erythematosus, particularly in those with severe skin disease. However, patients with active and severe neuropsychiatric or renal disease were not included in the pivotal trial ( Treatment references ). ]) to maintain remission ( Treatment references ). Treatment should be guided by clinical features primarily, although anti-dsDNA antibody titers or serum complement levels may be followed, particularly if they have correlated with disease activity in the past. However, anti-dsDNA antibody titers or serum complement levels may not parallel nonrenal disease flares. Other pertinent blood and urine tests may be used to assess specific organ involvement. , and bisphosphonate therapy (see Prevention ) should be considered in patients taking corticosteroids long term. (see Prevention ), and vaccines against common infections (eg, All patients should be closely monitored for atherosclerosis, and cardiovascular risk reduction is a key part of management ( Treatment ). Long-term anticoagulation is vital in patients with antiphospholipid antibodies and history of thrombosis (see also Pregnant women should remain onhydroxychloroquinethroughout their pregnancy, and low-doseaspirinis recommended as well. When clinical antiphospholipid syndrome is present, as manifested by prior thrombotic events, full anticoagulation therapy with low molecular weight or unfractionatedheparinis advised. If the pregnant woman has positive antiphospholipid syndrome antibodies and prior late-stage fetal loss or recurrent 1st trimester miscarriages, prophylactic low molecular weight or unfractionatedheparincan be considered during pregnancy and 6 weeks postpartum. When the patient has positive serologies but no prior obstetric or thrombotic events, recommendations are less clear. Co-management by a hematologist, an obstetrician, and a rheumatologist should be considered when managing these patients. Mycophenolatemofetil is teratogenic. Because of this teratogenicity and the known poor outcomes related to active SLE during pregnancy, women should ideally conceive after their disease has been in remission for 6 months or longer. If the patient needs to remain on immunosuppression (eg, ongoing maintenance therapy for lupus nephritis),mycophenolatemofetil is usually switched toazathioprineat least 6 months prior to conceiving. 1.Alarcón GS, McGwin G, Bertoli AM, et al: Effect ofhydroxychloroquineon the survival of patients with systemic lupus erythematosus: Data from LUMINA, a multiethnic US cohort (LUMINA L).Ann Rheum Dis66(9):1168–1172, 2007. doi: 10.1136/ard.2006.068676 2.Fanouriakis A, Kostopoulou M, Alunno A, et al: 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus.Ann Rheum Dis78(6):736-745, 2019. doi:10.1136/annrheumdis-2019-215089 3.Furie R, Rovin BH, Houssiau F, et al: Two-year, randomized, controlled trial ofbelimumabin lupus nephritis.N Engl J Med383(12):1117-1128, 2020. doi:10.1056/NEJMoa2001180 4.Rovin BH, Teng YKO, Ginzler EM, et al: Efficacy and safety ofvoclosporinversus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.Lancet397(10289):2070-2080, 2021. doi:10.1016/S0140-6736(21)00578-X. Erratum in:Lancet397(10289):2048, 2021. 5.Bajema IM, Wilhelmus S, Alpers CE, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices.Kidney Int93(4):789-796, 2018. doi:10.1016/j.kint.2017.11.023 6.Morand EF, Furie R, Tanaka Y, et al: Trial ofanifrolumabin active systemic lupus erythematosus.N Engl J Med382(3):211-221, 2020. doi:10.1056/NEJMoa1912196 