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Objectives Rhupus—an overlap of SLE and rheumatoid arthritis—features symmetrical erosive polyarthritis, fixed deformities, and SLE serologies (anti-dsDNA, anti-Smith, RF ± anti-CCP). Prevalence is ~0.01–2% (largest Asian series: 51/3,733 = 1.4%), with more frequent hematologic abnormalities in Asian cohorts. We present a Chinese Rhupus case with recurrent leukopenia and severe thrombocytopenia refractory to multiple therapies, highlighting the response to rituximab. Prior reports support the benefit of rituximab in SLE-associated thrombocytopenia.Methods A 57-year-old Chinese woman with Rhupus (diagnosed 2010, with high RF, anti-CCP, and anti-dsDNA) presented with inflammatory arthritis, sicca symptoms, recurrent leukopenia, ANA 1:1280 (speckled), anti-RibP/Ro-52, and low-titer antiphospholipid antibodies (β2-GPI, cardiolipin). Management included MTX 25 mg weekly (since 2010), leflunomide (2014–2018, leukopenia), sulfasalazine 2 g/day (2018–2020, leukopenia), hydroxychloroquine (since 2018), intermittent glucocorticoid tapers, and biologics—tocilizumab 162 mg weekly (2021–2024, inadequate response) and upadacitinib 15 mg/day (stopped July 2025 for thrombocytopenia).During hospitalization in the rheumatology clinic, physical examination showed a positive squeeze test at PIP3 and MCP1–3 of the right hand and MCP1–2 of the left hand. Laboratory results were: ESR 99 mm/h; CRP 21 mg/L; hemoglobin 10.2 g/dL; thrombocytopenia with platelets 33 × 103/µL; ANA 1:1280 (speckled); anti-dsDNA low; and low-level cardiolipin and β2-glycoprotein I antibodies. Disease activity: DAS28-CRP 5.76; patient VAS 54 mm.Initial HRCT showed indeterminate malignancy-suspicious changes, prompting oncology referral; contrast-enhanced CT ultimately indicated NSIP. Given high RA activity with thrombocytopenia, rituximab 1000 mg IV (two-dose regimen) was started. Ongoing therapy: methylprednisolone 4 mg/day, hydroxychloroquine 200 mg/day; maintenance rituximab planned at 6 months.Results After the first infusion, platelets rose to 44 × 10 3/µL; after the second, to 85 × 103/µL. Inflammatory markers improved (ESR 55 mm/h; CRP 10 mg/L) with clinical improvement (VAS 20 mm; DAS28-CRP 3.2). Treatment was well tolerated.Abstract PO:04:106 Figure 1Conclusions Cytopenias are common in Rhupus/SLE and may be more pronounced in Asian populations. This case supports the potential role of rituximab in Rhupus complicated by severe thrombocytopenia, demonstrating prompt clinical and laboratory responses after failure of multiple DMARDs/biologics.