25 Refractory musculoskeletal manifestations

Musculoskeletal involvement is one of the most common clinical manifestations of systemic lupus erythematosus (SLE), being the first presenting symptom in around 50–70% of cases and affecting up to 95% of patients at some point. The most prevalent manifestations are arthralgia and arthritis (95%), follow by myalgia/myositis (17%), tenosynovitis and bursitis (12%). Deformities arise in 5–15% of patients with no radiographic erosions, as the hallmarks of Jaccoud’s arthropathy, whereas radiographic erosions may be detected in less than 5% of patients suggesting the overlap between rheumatoid arthritis and SLE referred as rhupus syndrome. Other comorbidities may be present as musculoskeletal involvement, such as: fibromyalgia (6–32%), fragility fractures (8–12%) and avascular osteonecrosis (2–12%).1–4 Recent insights from US studies show that in large numbers of lupus patients with arthralgia, despite subclinical synovitis, clinical assessment underestimates the level of joint and tendon inflammation compared to ultrasound and magnetic resonance imaging. This has implications for therapeutic choice, evaluation of response or treat-to-target protocols. While prevalence of subclinical synovitis is agreed, it is not yet clear whether it should be treated, however imaging studies suggest potential changes to the classification, assessment and management of patients with inflammatory musculoskeletal lupus. SLE manifestations are considered refractory when patients are unresponsive to-or disease relapses despite-treatment with corticosteroids, antimalarials and/or immunosuppressants. Other key issues are that recurrent flares of disease activity are associated with poor long-term outcomes and longstanding overreliance on corticosteroid therapy, which contributes substantially to damage accrual and patient mortality. Hydroxychloroquine and corticosteroids remain first-line therapies for musculoskeletal manifestations of SLE; however, patients with refractory musculoskeletal disease may require further management with immunosuppressive (methotrexate, leflunomide) or biologic (belimumab, abatacept, rituximab) agents for inflammatory disease control. Mycophenolate mofetil and, to a lesser degree, azathioprine have shown efficacy in the treatment of inflammatory myositis in SLE patients and have demonstrated a steroid sparing effect. Despite current therapy, musculoskeletal manifestations are major contributors to poor quality of life and work instability. There remains an unmet clinical need in SLE, particularly in patients with disease refractory to conventional immunosuppressive therapies. Learning Objectives Explain the main musculoskeletal manifestations in patients with SLE Describe potential changes to the classification of musculoskeletal manifestations Describe the current recommendations for the treatment of refractory musculoskeletal manifestations Discuss new trends in research on new therapies for musculoskeletal manifestations in patients with SLE References Pons-Estel BA, Catoggio LJ, Cardiel MH, et al. The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among ‘Hispanics’. Medicine (Baltimore) 2004;83(1):1–17. Zoma A. Musculoskeletal involvement in systemic lupus erythematosus. Lupus 2004;13(11):851–3. Mahmoud K, Zayat A, Vital EM. Musculoskeletal manifestations of systemic lupus erythmatosus. Curr Opin Rheumatol 2017;29(5):486–92. 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;77(11):1549–57.