18 Management of musculoskeletal involvement in SLE

Case 1. A young female with SLE and relapsing-remitting arthritis

A 14-year-old Caucasian girl presented to her physician with malar and trunk photosensitivity rashes in Summer 2010. In October 2010, she developed fever, pleurisy, polyarthritis and mild proteinuria (<0.5 g/day). Laboratory tests showed positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA, anti-U1RNP, anti-Sm and decreased C3. A diagnosis of systemic lupus erythematosus (SLE) was made and she was treated with IV pulses of methylprednisolone (MPN), 500 mg x 3, then oral prednisone starting from 25 mg/day, then tapered to 5 mg per day plus hydroxychloroquine (HCQ) 400 mg/day. After almost one-year prednisone was withdrawn due to clinical remission¹; unfortunately, in 2017–2018, she experienced three episodes of SLE articular and skin flares; thus, prednisone was reintroduced (25 mg/day than tapered to 15 mg/day always plus HCQ). It must be mentioned that she experienced recurrent genital herpes simplex, 1–2 episodes/year, starting from 2015. In June 2018, she had a new hospital admission due to polyarthritis (DAS28 7.16), fever, malar rash, fatigue and lymphadenopathy, and muscular weakness. She had high C-reactive protein (CRP) 18.3 mg/l, lymphopenia 700/mm³, C3 0.83 mg/dl, increased anti-dsDNA 1.096 KIU/L and creatin kinase (CK) 965 U/L. Muscular MRI showed mild oedema at proximal muscle of the limbs. At that time, she was on prednisone 25 mg/day and HCQ 400 mg/day. [The best therapeutic options in this case will be discussed with the participants at the workshop.] However, we increased the daily dosage of prednisone and we added belimumab.^{2 3} After belimumab initiation we observed a progressive decline in SLEDAI-2K score and in DAS-28 score, a decrease in the prednisone dose taken by the patient, a decrease in anti-dsDNA serum levels and an increase in C3 and C4 serum levels. Regarding safety, we did not observe infusion reactions.

References

Zen M, et al. Defining the targets in SLE management: insights and unmet gaps. Ann Rheum Dis. 2022 Nov;81(11):1483–1485. doi: 10.1136/ard-2022-222991. Epub 2022 Aug 25. PMID: 36008131. Zen M, et al. Early and late response and glucocorticoid-sparing effect of belimumab in patients with systemic lupus erythematosus with joint and skin manifestations: results from the belimumab in real life setting study-joint and skin (BeRLiSS-JS). J Pers Med. 2023 Apr 20;13(4):691. doi: 10.3390/jpm13040691. Gatto M, et al. Early disease and low baseline damage as predictors of response to belimumab in patients with systemic lupus erythematosus in a real-life setting. Arthritis Rheumatol. 2020 Aug;72(8):1314–1324. doi: 10.1002/art.41253. Epub 2020 Jun 12.

Case 2. A patient with persistent arthritis leading to Jaccoud's arthropathy

A 32-year-old Caucasian female started to complain fever and headache in July 2010. In August 2010, she developed subacute lupus on upper arms, leukopenia and thrombocytopenia, arthritis, with mild arthritis at hands and wrists. Blood tests showed leukopenia (WBC 3,467/mm³), low C3 (0.79 g/L), increase gamma-globulins (24.2%), positive ANA, anti-dsDNA, anti-SSA, anti-P-ribosomal, and rheumatoid factor. The diagnosis of SLE was made and she was treated with prednisone 25 mg per day, progressively tapered to 5 mg/day, and HCQ 400 mg with improvement of her clinical manifestations. She went well until 2014, with the exception of mild but persistent inflammatory arthralgias.¹ In May 2015 she developed skin and joint flares with subacute cutaneous lupus and arthritis at hands and wrists with mild Jaccoud's deformities, leukopenia (WBC 2.320/mm³), increase in anti-dsDNA (199 KIU/L), decrease in C3. Notably, she had SLEDAI-2K: 7, CLASI activity: 10, DAS28: 4.58, SLICC-DI: 1. At that time she was on prednisone 25 mg and HCQ 400 mg. The best therapeutic options in this case will be discussed with the participants at the workshop. We increased the prednisone dose and started belimumab in June 2015. In May 2017 she developed a new flare with diffuse subacute lupus on upper arms, chest and back after sun exposition and persistent arthritis, leukopenia (WBC 3.722/mm³), increased anti-dsDNA (134 KIU/L), decreased complement levels (C3 0.79 g/l). She had SLEDAI-2K: 10, CLASIa: 11, DAS28: 4.52, SLEDAS:² 5.96, SLICC-DI: 0, PGA: 1.3. We continued belimumab and added mycophenolate mofetil (2 g/day) and this approach was effective. In august 2020 at the time of the 70th belimumab administration she presented mild skin involvement (few little red lesions on left arm), a worsening of Jaccoud's joint deformities with inflammatory arthralgias and right wrist arthritis, positive anti-dsDNA (96 KUI/L), and leukopenia (WBC 2900 mm³); C3 and C4 within normal range; SLEDAI-2K 5; SLEDAS 8.05; CLASIa 2; DAS28 3.56; SLICC-DI 1 (no new damage). She was on prednisone 5 mg/day, belimumab 640 mg IV every 4 weeks, chloroquine 250 mg/day, MMF 2 g/day. Since she was not at target according to the treat-to-target strategy,^{1 3} in September 2020 we administered rituximab with a good result and in February 2021 we restarted belimumab.

References

Gatto M, et al. New therapeutic strategies in systemic lupus erythematosus management. Nat Rev Rheumatol. 2019 Jan;15(1):30–48. doi: 10.1038/s41584-018-0133-2. Jesus D, et al. Derivation and validation of the SLE disease activity score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity. Ann Rheum Dis. 2019 Mar;78(3):365–371. doi: 10.1136/annrheumdis-2018-214502. Epub 2019 Jan 9. Jesus D, et al. Systemic lupus erythematosus disease activity score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity. Ann Rheum Dis. 2021 Dec;80(12):1568–1574. doi: 10.1136/annrheumdis-2021-220363. Epub 2021 Aug 18.

Learning Objectives

Discuss the different treatment approach in SLE patients with relapsing-remitting or persistent arthritis Discuss how to treat patients with arthritis to the target and how to manage biologic treatment in SLE