CASE REPORT article
Front. Pharmacol.
Sec. Obstetric and Pediatric Pharmacology
Hydroxychloroquine Withdrawal Triggers Pregnancy-Associated Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: A Case Report and Exploration of the Complement-EndMT Axis
Chun-Fei Wang
Yu-fei Zhang
Li Zhang
Xue-Feng Jiao
Qiang Wei
West China Second University Hospital, Sichuan University, Chengdu, China
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Abstract
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 weeks, culminating in a planned cesarean delivery. At the three-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.
Summary
Keywords
complement system, Drug adherence, Endothelial-mesenchymal transition, Hydroxychloroquine, Pregnancy, pulmonary arterial hypertension, systemic lupus erythematosus
Received
31 December 2025
Accepted
17 February 2026
Copyright
© 2026 Wang, Zhang, Zhang, Jiao and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Qiang Wei
Disclaimer
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