Isolated granulomatous pulmonary artery vasculitis associated with Hughes–Stovin syndrome: a case report

Abstract

Background

Hughes–Stovin syndrome (HSS) is an exceptionally rare vasculitis, characterized by pulmonary artery aneurysms with in situ thrombosis and is increasingly regarded as part of the vascular Behcet spectrum. Diagnosis remains challenging due to its rarity, lack of validated diagnostic criteria, and overlap with other vasculitis.

Case summary

We describe a 71-year-old male who presented with progressive dyspnoea and chest pain. Serial imaging demonstrated rapid enlargement of a main pulmonary artery aneurysm from 5 mm to 68 × 55 mm over 18 months, prompting surgical repair. Histopathological examination of the resected pulmonary artery demonstrated granulomatous arteritis with multinucleated giant cells, transmural inflammation, and disruption of the elastic lamina, confirming isolated pulmonary artery vasculitis. In the context of pulmonary artery aneurysm, normal coagulation studies and systemic exclusion of alternative causes including Behcet disease, giant cell arteritis, Takayasu arteritis, infection, and malignancy, the findings were considered most consistent with HSS. Following multidisciplinary review, immunosuppression was commenced with corticosteroid and methotrexate before transition to tocilizumab and mycophenolate mofetil. Recurrent pulmonary thrombosis despite therapeutic apixaban required conversion to therapeutic enoxaparin. At latest follow-up, the patient remained clinically stable with no evidence of active vasculitis or recurrent aneurysm.

Conclusion

This case highlights a rare presentation of isolated granulomatous pulmonary artery vasculitis associated with HSS in an older patient. The case demonstrates the importance of cautious diagnostic classification and exclusion of alternative diagnoses through serial multimodal imaging, timely surgical intervention, prompt commencement of immunosuppression, and multidisciplinary care.

Learning points.

• Consider Hughes–Stovins syndrome in pulmonary artery aneurysm with thrombosis after excluding alternative vasculitides, infection, and malignancy.

• Histopathology, multimodal imaging, and multidisciplinary assessment are essential for diagnosing isolated pulmonary artery vasculitis.

• Early immunosuppression with selective surgical intervention may prevent recurrent and catastrophic aneurysm progression.

Introduction

We present a rare case of isolated pulmonary artery granulomatosis associated with Hughes–Stovin syndrome (HSS) in a 71-year-old male. The HSS International Study Group has proposed diagnostic criteria as CT-detected pulmonary artery (PA) aneurysms with adherent in situ thrombosis, vascular occlusive diseases with a normal coagulation profile, and the absence of an alternative explanation.¹ Histopathology demonstrated granulomatous arteritis with multinucleated giant cells, raising a broad differential diagnosis including giant cell arteritis, Takayasu arteritis, and isolated pulmonary artery vasculitis. Recent comprehensive reviews continue to emphasize the rarity of the condition, absence of validated diagnostic criteria, and increasingly considered part of the vascular Behcet disease spectrum.² This case highlights the challenges presented in isolated PA vasculitis, supporting a cautious approach to diagnosis.

Summary figure

Case timeline. (A) Main pulmonary artery. (B) Multidisciplinary team.

Time	Events
July 2021	Initial presentation with dyspnoea and undifferentiated chest pain Transthoracic echocardiogram (TTE): 6/7: Right ventricular systolic pressure (RVSP): 34 mmHg. Dilated proximal PA 45 mm.
Sep 2021	CT 7/9: Main PA 55 mm at bifurcation. Identification of PA aneurysm
Dec 2021	Cardiac MRI 8/12: PA aneurysm imaged with mid PA measuring 62 × 55 mm
Jan 2022	Angio 18/1: Minor coronary disease
Feb 2023	Cardiac MRI 1/2: Sudden enlargement of PA aneurysm 68 × 55 mm with associated chest pain
Mar 2023	Operation 1/3: Replacement of main PA and branch PA for expanding aneurysm. Histopathology showed large giant cells with well-formed granulomas in keeping with a large vessel vasculitis Intraoperatively, pulmonary embolism (PE) was discovered. Commenced on anticoagulation apixaban 5 mg twice daily (BD)
Apr 2023	PET 20/4: Increased uptake of pulmonary trunk and proximal branch PA consistent with post-operative changes. No signs of active vasculitis
May 2023	Readmitted with myopericarditis, confirmed by cardiac MRI, managed with colchicine
Nov 2023	PET: Ongoing increased FDG uptake in both branch PAs MDTb Meeting with immunology and cardiology Immunosuppression commenced to treat refractory disease: prednisone 60 mg, methotrexate 25 mg weekly
Jan 2024	Steroid side effects: mood, sleep disturbance, and weight gain Immunosuppression changed to mycophenolate 1 g BD and tocilizumab
Aug 2024	New exertional dyspnoea and tachycardia CTPA: Subsegmental PEs (while on anticoagulation apixaban 5 mg BD) Transitioned to enoxaparin 100 mg BD
Jan 2025	V/Q scan: Resolution of PE Nil signs of active vasculitis. Continues immunosuppression

Case presentation

A 71-year-old male with a medical history of gout and depression presented initially with vague symptomatology of progressive dyspnoea and undifferentiated chest pain with euvolemic status in July 2021. Initial transthoracic echocardiography in July 2021 revealed normal left ventricular function [Ejection Fraction (EF) 58%], normal right ventricular function [Triscuspid Annular Plane Systolic Excursion (TAPSE) 20 mm], estimated RVSP 34 mmHg, dilated proximal PA measuring 45 mm, and dilated right ventricular outflow tract (46 mm). Chest X-ray showed clear lung fields with no cardiomegaly or pneumothorax. Baseline 12-lead ECG revealed sinus rhythm at a rate of 83 bpm, PR interval (atrioventricular conduction interval) of 192 ms, QRS interval (ventricular depolarisation interval) of 84 ms, and normal axis with no conduction abnormalities. CT in September demonstrated a large PA aneurysm measuring 55 mm at the bifurcation (see Figure 2A). Due to persisting symptoms, cardiac MRI was performed in December 2021 and demonstrated a dilated main PA (62 × 55 mm) (see Table 1). Coronary angiography in January 2022 showed minor coronary disease. A lower limb Doppler in August 2022 demonstrated no Deep Vein Thrombosis (DVT).

Figure 2.

(A) CT chest September 2021 demonstrating MPA measuring 55 mm at the bifurcation. The right pulmonary trunk measures 29 mm in diameter, and the left pulmonary trunk measures 30 mm. (B) CTPA March 2023 showing bilateral PE involving right upper lobe segmental/subsegmental branches as well as left upper lobe segmental/subsegmental branches. (C, D) CTPA August 2024 sagittal and axial lung windows demonstrating an occlusive filling defect concerning for a pulmonary embolus identified within a first-order subsegmental branch of the anterior segment of the right upper lobe.

Table 1.

Pulmonary artery measurements at interval cardiac MRI (in mm)

	December 2021	August 2022	February 2023
Proximal MPA	56 × 51	57 × 53	57 × 52
Mid MPA	62 × 55	64 × 55	68 × 55
Distal MPA	58 × 48	59 × 49	59 × 49
Left PA	37 × 32	37 × 35	31 × 29
Right PA	41 × 33	45 × 32	41 × 36

In February 2023, he presented with chest pain, and repeat cardiac MRI detected rapid progressive interval growth of the dilated main PA (68 × 55 mm) (see Figure 1A and B). In March 2023, a decision was made for surgical repair of the rapidly expanding PA aneurysm, a decision largely driven by the rate of growth and concern for aneurysm rupture combined with symptoms of dyspnoea. The aorta and left coronary artery were being distorted by the size of the main PA. During the operation, the aorta was transected, and both PAs were divided at the exit from the pericardium. A 26 mm Vascutek tube graft was then anastomosed from hilum to hilum to connect the right and left PAs together. A 34 mm Vascutek tube graft was placed distally to the previous graft, and the proximal portion was anastomosed to the sinotubular junction of the native PA trunk, completing the RV-to-branch PA connection as a T-type graft. Intraoperatively, a PE was discovered, confirmed with CTPA (see Figure 2B), and anticoagulation with apixaban 5 mg BD was commenced. Histopathology of the resected aneurysmal tissue revealed granulomatous arteritis with multinucleated giant cells, transmural inflammation, and disrupted elastic lamina, confirming pulmonary arterial vasculitis (See Figure 1D, E, and F). No fibrinoid necrosis was seen. In the context of PA aneurysm formation, pulmonary arterial thrombosis, normal coagulation studies, and exclusion of alternative causes, these findings were considered most consistent with a clinical diagnosis of Hughes–Stovin syndrome. Classical Behcet disease was considered but not supported by the absence of mucocutaneous, ocular, or neurological manifestations.³

Figure 1.

(A, B) Cardiac magnetic resonance in February 2023 peri-operatively showing the severely dilated aneurysmal main pulmonary artery measuring a maximum of 68 × 55 mm in the mid pulmonary artery. (C) Cardiac magnetic resonance in November 2023 post-operatively showing the repaired dilated pulmonary aneurysm. (D) H&E stain demonstrating chronic inflammation with multinucleated giant cells. (E) Elastic stain showing disruption of the elastic lamina. (F) H&E stain demonstrating granulomatous arteritis showing transmural inflammation involving tunica intima, media, and adventitia.

Post-operatively, he recovered well with no initial signs of active vasculitis. However, he was readmitted in May 2023, diagnosed with myopericarditis, confirmed by cardiac MRI, and managed with colchicine, achieving clinical and biochemical improvement. For disease monitoring, serial FDG-PET scans were performed. The April 2023 PET scan demonstrated increased uptake at the sternotomy site, main pulmonary trunk, and bilateral PAs, consistent with post-operative changes related to the Dacron graft. These findings were managed conservatively. Autoimmune serology, including ANCA and anti-phospholipid antibodies, was negative. C-Reactive Protein (CRP) levels peaked during admission for myopericarditis (176 mg/L) but normalized by August 2023 (see Table 2).

Table 2.

Laboratory workup

Lab	Value
WCC	7.3
CRP	0.6
eGFR	82 mL/min
Coagulation studies	APTT 35
ANA	Not detected
ANCA	<10. Not detected
Anti-phospholipid antibodies	Negative
HIV	Negative
IgG4	Negative
HLAB-51	Negative
Syphilis	Negative
Hepatitis B/C	Negative
Blood culture	Negative

Follow-up November 2023 PET imaging showed persistent uptake at the pulmonary trunk and proximal branch PAs with no new parenchymal or systemic abnormalities. Cardiac MRI at this time demonstrated good integrity of the repaired PA system with no evidence of new aneurysm (see Figure 1C). Serial FDG-PET imaging was performed in line with our protocol for surveillance, where serial Standardised Uptake Values (SUVs) were documented. Interpretation of FDG-PET findings was challenging because the Dacron graft prosthesis may be inherently associated with persistent post-operative FDG uptake. The decision to initiate immunosuppression was not based solely on PET findings, but rather on a combination of prior histologically confirmed granulomatous arteritis, persistent arterial uptake on serial imaging, Multi-disciplinary Team (MDT) consensus, and concern regarding recurrence of a disease process that resulted in rapid aneurysm enlargement.

Following multidisciplinary discussion with consultant immunologists and cardiologists, prednisolone 60 mg daily and methotrexate 25 mg weekly were commenced, given the history of granulomatous arteritis resulting in a large PA aneurysm and potentially catastrophic consequences if there was to be disease recurrence. The patient experienced significant corticosteroid-related side effects, including insomnia, mood disturbance, hypomania, and Cushingoid features. Serial PET scans showed stable disease with only minor post-operative changes in the pulmonary trunk graft. Given the severity of his initial presentation with the rapidly expanding PA aneurysm, immunosuppression was maintained but transitioned to mycophenolate mofetil 1 g twice daily and tocilizumab in January 2024, with a tentative plan to switch to mycophenolate monotherapy for long-term prevention of vasculitis recurrence.

In August 2024, the patient reported new-onset exertional dyspnoea and intermittent tachycardia without any clear precipitant. V/Q scan revealed ventilation/perfusion mismatch in the right middle lobe and lingular segments and in the apical, posterior, and lateral accessory segments of the right upper lobe. CT pulmonary angiogram showed a subsegmental PE (see Figure 2C and D), despite therapeutic anticoagulation with apixaban 5 mg BD. Given concern for pulmonary thromboembolic disease and to allow more complete anticoagulation with Factor Xa level monitoring, apixaban was converted to enoxaparin 100 mg BD subcutaneously. The intensified anticoagulation was continued on haematology advice.

In January 2025, the patient reported improved exercise tolerance. Reassuringly, a ventilation-perfusion scan confirmed resolution of the PE. Formal pulmonary function testing showed mild airflow obstruction with post-bronchodilator reversibility. At the latest follow-up, he remains on mycophenolate and tocilizumab with no evidence of active vasculitis and continues on enoxaparin.

Discussion

The diagnosis in this case is consistent with HSS after systematic exclusion of alternative causes of PA aneurysm and vasculitis. The diagnosis was supported by the characteristic combination of rapidly enlarging PA aneurysm formation, pulmonary arterial thrombosis in the absence of an underlying coagulation disorder, and histologically confirmed granulomatous arteritis.

A broad range of differential diagnoses were systemically evaluated. Behcet’s disease was an important differential diagnosis because HSS is increasingly considered an incomplete or vascular predominant form of Behcet disease.² However, our patient had no oral or genital ulceration, ocular involvement, skin lesions, superficial thrombophlebitis, and neurological involvement. HLA-B51 and pathergy test were negative.

Giant cell arteritis (GCA) was considered given the granulomatous inflammation; however, disease involvement confined to the PA circulation without evidence of extracranial arterial involvement is not typical of GCA. Takayasu arteritis was considered unlikely given the patient’s age, sex, and absence of systemic large vessel disease.

Alternative causes of PA aneurysm and thrombosis were excluded. Autoimmune testing, including ANA, ENA, ANCA, rheumatoid factor, and anti-phospholipid antibodies, was negative, ruling out ANCA-associated vasculitis and anti-phospholipid syndrome. Serum IgG4 levels were normal, making IgG4-related disease unlikely. Infectious causes were excluded with negative blood cultures and serological testing. There was no radiological or histopathological evidence to suggest PA sarcoma. Pulmonary hypertension-related aneurysm was not supported by echocardiographic findings.

Although the pulmonary thrombotic events were initially managed as PE, the absence of deep vein thrombosis and presence of PA vasculitis raised the possibility of in situ thrombosis related to vascular inflammation in line with emerging evidence in HSS and similar conditions.^1,2 This distinction remains challenging and cannot be determined with certainty.

Taken together, this case is most consistent with HSS manifesting as isolated granulomatous PA vasculitis rather than classical Behcet disease. Although HSS is increasingly regarded as part of the vascular Behcet disease spectrum, the absence of oral or genital ulcers, Central Nervous System (CNS) manifestations, or HLA-B51 favours HSS as the appropriate clinical diagnosis in this patient.^2–5

Management

Surgical intervention is a careful decision balancing thrombosis risk against haemoptysis and aneurysm rupture risk. Surgery may be reasonable for isolated/localized aneurysms; however, HSS is often multifocal and bilateral, making surgery difficult and recurrence possible.² While surgery successfully treated the localized aneurysm in this case, PA involvement in HSS is frequently multifocal and bilateral, limiting surgical applicability. Surgical intervention should therefore be individualized and reserved for localized, rapidly enlarging, or rupture-prone aneurysms, with continued immunosuppression required to reduce recurrence risk.^2,6 Surgical intervention is often warranted in large (PA aneurysm diameter >5.5 cm) or rapidly expanding aneurysms (>0.5 cm in 6 months), as outlined by the international study group HSSISG, with CTPA central to assessment of aneurysm morphology and thrombotic complications.²

Recent reviews advocate immunosuppression as first-line therapy, typically corticosteroids with cyclophosphamide or steroid-sparing agents, while surgery and endovascular intervention are reserved for localized aneurysms at high risk of rupture.^2,7 Some case reports describe successful outcomes with high-dose corticosteroids, while others have reported cyclophosphamide to stabilize or even regress PA aneurysms.⁸ More recent evidence supports the use of IL-6 inhibitors like tocilizumab, particularly as immunosuppressive agents, given their efficacy in large vessel vasculitis such as giant cell arteritis.⁹ TNF-α inhibitors have also shown promise, including sustained remission in refractory cases following treatment with high-dose steroids, cyclophosphamide, and azathioprine.^2,10 We note that our patient’s PA histopathology was virtually indistinguishable from that seen in typical giant cell arteritis; there is a paucity of data to strongly advise one treatment modality over another in HSS, but given our patient’s microscopic findings, evidence-based treatments for GCA were considered appropriate.

The effectiveness of early commencement of immunotherapy has been demonstrated in, thus far, the largest published cohort of 57 cases, with mortality rates lowered by 17.5% receiving single agent and 68% in combination regimens utilizing steroids and other immunosuppressive agents.¹¹ Thus, highlighting the importance of the early introduction of immunosuppressants in our case to prevent worsening vasculitis or enlargement of the PA aneurysm.

Conclusion

This case highlights a rare presentation of HSS characterized by isolated granulomatous PA vasculitis, rapidly progressive PA aneurysm formation, and pulmonary arterial thrombosis. The diagnosis was supported by characteristic vascular findings together with systematic exclusion of alternative vasculitides, infection, and malignancy. Although HSS shares pathological and clinical overlap with vascular Behcet disease, the absence of classical Behcet manifestations in this patient supports HSS as the most appropriate clinical diagnosis. The case demonstrates the importance of cautious diagnostic classification and exclusion of alternative diagnoses through serial multimodal imaging, timely surgical intervention, prompt commencement of immunosuppression, and multidisciplinary care.

Lead author biography

James Healy is a Cardiology Advanced Trainee at St Vincent’s Hospital, Sydney. He completed Basic Physician Training at Royal Prince Alfred Hospital, Sydney. He has a keen interest in inflammatory mechanisms of atherosclerosis, sudden cardiac death, transplant cardiology, and right heart diastology.

Author contributions

James Healy (Conceptualization, Data curation, Formal analysis, Writing—original draft, Writing—review & editing [lead]), Nicolás Urriola (Formal analysis, Methodology, Writing—review & editing [supporting]), Ian Nicholson (Writing—review & editing [supporting]), and Rajesh Puranik (Conceptualization, Writing—original draft, Writing—review & editing [supporting])

Consent: The authors confirm that written consent for submission and publication of this case report, including images, has been obtained from the patient in line with the Committee on Publication Ethics (COPE) guidance.

Funding

None declared.

Data availability

The data underlying this article cannot be shared publicly for the privacy of individual that participated in the study.