Abstract
INTRODUCTION: This case outlines the diagnostic and therapeutic complexity of pulmonary hypertension (PH) in a young woman with systemic autoimmune disease. Initially presenting with digital vasculopathy and Raynaud’s like symptoms, she developed myositis, interstitial lung disease, and post-capillary pulmonary hypertension, raising questions about classification and treatment strategy. Serological and imaging findings were consistent with antisynthetase syndrome, though her phenotype remained incomplete. Her disease course was complicated by comorbidities, prolonged steroid use, pulmonary embolism, and medication intolerances. This case highlights the diagnostic uncertainty in overlap autoimmune presentations and the challenges of managing cardiopulmonary complications when conventional pathways are confounded by patient-specific factors. CASE DESCRIPTION: A 28-year-old woman with asthma, morbid obesity, and past DVT was referred in 2022 with digital pain and suspected Raynaud’s. She had a positive ANA, PMSCL 75 and 100, and later PL-12 and Ro-52 antibodies. Examination revealed a shallow digital ulcer but no signs of sclerodactyly. MRI confirmed myositis in bilateral gastrocnemius despite a normal EMG, possibly affected by early steroid treatment. CT thorax showed ground glass opacities; BAL was negative for infection, and lung function showed impaired gas transfer. She was diagnosed with antisynthetase syndrome and pulsed with IV methylprednisolone, followed by mycophenolate (MMF) and rituximab. Despite treatment, she remained breathless with progressive weight gain and steroid dependency. Right heart catheterisation revealed post-capillary pulmonary hypertension (PH). VQ scan and invasive pulmonary angiography showed peripheral bilateral pulmonary embolism suggestive of chronic thromboembolic pulmonary hypertension (CTEPH). A heterozygous prothrombin gene mutation was identified; anticoagulation with warfarin was initiated. Digital ulcers remained difficult to treat. Bosentan was trialled but stopped due to INR instability and intolerance. Iloprost was poorly tolerated. Subsequent imaging suggested organising pneumonitis, which responded to steroids, but steroid tapering led to worsening fatigue and functional decline By 2025, lung function was stable but impaired. Sleep studies were arranged for suspected obstructive sleep apnoea (OSA). She remains on MMF and rituximab with shared care between rheumatology and respiratory. DISCUSSION: This case underscores the complexity of diagnosing and managing pulmonary hypertension in autoimmune disease. The patient initially presented with evolving features of antisynthetase syndrome, Raynaud’s, ILD, and myositis but lacked the full classical picture. PH emerged later, with catheter findings confirming a post-capillary (group 4) pattern, characterised by raised wedge pressure and low PVR. This distinction was clinically crucial, ruling out vasodilator therapy and shifting focus toward fluid optimisation, anticoagulation, and disease-modifying treatment. The suspected CTEPH added further diagnostic uncertainty. While the VQ scan was suggestive, CTPA did not show evidence of thromboembolic disease, and she needed invasive pulmonary angiography to confirm diagnosis of pulmonary embolism. Morbid obesity complicated both diagnosis (incomplete imaging, poor breath-holding) and management (exclusion of DOACs and vigilance use of steroids). This real-world limitation frequently challenges textbook decision making. Her lung disease showed features consistent with organising pneumonitis likely inflammatory and steroid-responsive, yet repeated attempts at tapering led to clinical deterioration. This highlights the difficulty in distinguishing between chronic disease and low-grade active inflammation, particularly in patients with overlapping features. Vasculopathy, a major burden in her case, remained resistant to therapy. Endothelin receptor antagonists and prostanoids were trialled but poorly tolerated. Despite broad immunosuppression, disease activity persisted, compounded by psychosocial and functional limitations. This case reflects how classification frameworks can fall short in complex overlap disease. It emphasises the need for integrated decision-making, recognising that ideal management often must be balanced against feasibility, safety, and patient-specific barriers. KEY LEARNING POINTS: 1. Pulmonary hypertension in autoimmune disease requires invasive haemodynamic confirmation. Group 4 PH (post-capillary) should not be treated with vasodilators. 2. Antisynthetase syndrome may present with incomplete features; PL-12 is a less common antibody associated with anti-synthetase syndrome. 3. ILD with organising pneumonitis-like features may respond to steroids, but careful assessment is needed to guide tapering and avoid flares. 4. Real-world management is often shaped by comorbidities, obesity, psychiatric burden, and drug intolerance may restrict both diagnostics and treatments. 5. Refractory vasculopathy remains a significant challenge in connective tissue disease, often persisting despite adequate immunosuppression.