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Objectives To explore the safety and efficacy of rituximab in active SLE patient who developed a new onset lupus nephritis during pregnancy.Methods .Results Case presentationWe present the case of a 34-year-old with SLE treated initially with hydroxychloroquine (200 mg/daily) and low dose of glucocorticoids(GC). The autoimmune profile revealed positivity for double-stranded DNA, anti-Ro/SSA, anti-La/SSB, and antiphospholipid antibodies, with no prior history of pregnancy loss or thrombotic events. In May 2023, azathioprine 100 mg/daily was started following an acute hemolytic anemia episode.In May 2024, the patient underwent an unplanned pregnancy. During the 5-week referral, SELENA-SLEDAI scored 16 points due to the presence of constitutional symptoms, arthritis, mild anemia, lymphopenia, complement consumption and a new onset of proteinuria measured at 627 mg in a 24-hour collection. At week 12, the patient experienced a decrease in hemoglobin levels (7.8 mg/dL), an increase in 24-hours proteinuria (1256 mg) and in SELENA-SLEDAI till 20 points. This necessitated a rapid treatment escalation, including GC, azathioprine (150 mg/daily) and hydroxychloroquine (400 mg/daily). However, only hemoglobin levels improved, while SELENA-SLEDAI and proteinuria continued to rise, prompting the administration of anti-CD20 rituximab (RTX) 1 g in a single dose at week 23. At week 28, hemoglobin, complement and inflammatory markers showed rapid improvement, and proteinuria remained stable (figure 1–3).The delivery of a healthy male newborn occurred preterm at week 36 due to premature rupture of the membranes. Four weeks postpartum, 24-hours proteinuria decreased up to 627 mg, hemoglobin increased to 14 mg/dL, and SELENA-SLEDAI reduced to 8 points.Three months after delivery, a further rise of proteinuria (1930 mg/24 hours) necessitated a retreatment with RTX. However, on May 2025, due to the persistence of elevated proteinuria, kidney biopsy was performed and revealed a lupus nephritis class III with focal glomerulonephritis, and a modified NIH activity index of 5/24 [2+;1+;0(x2);0;1+(x2);0], modified NIH chronicity index of 1/12 (1+;0;0;0). After lactation interruption, mycophenolate mofetil 2 g/daily was started.Abstract PO:08:209 Figure 1–4Conclusions This is the first case of a patient receiving RTX for active SLE with new-onset lupus nephritis during pregnancy. RTX may represent a safe and effective therapeutic approach in this complex clinical scenario.