Background The continuation of hydroxychloroquine (HCQ) during pregnancy in patients with systemic lupus erythematosus (SLE) is a cornerstone of management, proven to mitigate maternal disease flares. However, its precise role in preventing the devastating cardiopulmonary complication of pregnancy-associated pulmonary arterial hypertension (PAH) remains inadequately defined, and the underlying pharmacological mechanisms remain largely elusive. Case presentation We detail the case of a 31-year-old primigravida with a 15-year history of well-controlled SLE, who self-discontinued HCQ at 8 weeks of gestation. At 27 + 4 weeks, she presented with significant exertional dyspnea. Diagnostic evaluation confirmed severe PAH (estimated PASP 107 mmHg) with right heart strain, alongside serological evidence of active SLE, including hypocomplementemia. A multidisciplinary therapeutic protocol was immediately instituted, comprising the reinstatement of HCQ and the administration of intravenous methylprednisolone. This intervention resulted in a marked reduction in pulmonary arterial pressure to a moderate range (PASP 73 mmHg), stabilizing the patient’s condition sufficiently to prolong gestation to 31 + 1 week, culminating in a planned cesarean delivery. At the 3-month postpartum assessment, echocardiography documented sustained improvement, with PAH decreased to a mild grade (PASP 40 mmHg). Conclusion This case provides compelling in vivo evidence that non-adherence to HCQ constitutes a pivotal, modifiable risk factor for the onset of SLE-associated PAH in the gravid state, and that pharmacological reintroduction can arrest and partially reverse this pathogenic trajectory. We attribute the vascular protective effects of HCQ to the inhibition of complement activation along the C5a-MAPK/ERK signaling axis. Targeting this pathway disrupts pathological endothelial-mesenchymal transition (EndMT) and mitigates subsequent pulmonary vascular remodeling. Stringent HCQ adherence should be standard of care. Furthermore, complement monitoring guides precision pharmacotherapy to prevent PAH in susceptible SLE pregnancies.
Zhang et al. (2026) studied this question.