Hughes–Stovin syndrome without peripheral venous thrombosis: Early recognition and successful immunosuppressive management—A case report and brief literature review

Abstract

Hughes–Stovin syndrome (HSS) is an exceptionally rare and potentially life-threatening systemic vasculitis characterized by the coexistence of pulmonary artery aneurysms and venous thrombosis. Its striking clinical overlap with Behçet disease has led to ongoing debate regarding whether HSS constitutes a distinct disease entity or instead represents a vascular variant within the Behçet spectrum. In the absence of standardized diagnostic criteria, diagnosis relies primarily on clinical suspicion supported by radiologic evidence. Early identification is crucial, as rupture of pulmonary aneurysms is frequently fatal.

We report a young male patient diagnosed with HSS who demonstrated favorable clinical and radiologic improvement following treatment with corticosteroids and mycophenolate mofetil. This case highlights the importance of considering HSS in young individuals presenting with unexplained pulmonary artery aneurysms, even in the absence of venous thrombosis. Prompt diagnosis, early initiation of immunosuppressive therapy, and coordinated multidisciplinary management are essential to mitigate the risk of catastrophic complications. This case is unusual in that HSS occurred in the absence of peripheral venous thrombosis and responded favorably to combined corticosteroid and mycophenolate mofetil therapy.

Highlights

• •Hughes–Stovin syndrome is a rare vasculitis with pulmonary artery aneurysms.
• •Venous thrombosis may be absent, adding to the diagnostic challenge.
• •Early diagnosis and aggressive immunosuppression can prevent fatal rupture.
• •This case showed marked radiologic improvement with steroids and mycophenolate.
• •HSS should be considered in young patients with unexplained pulmonary artery aneurysms.

1. Introduction

Hughes–Stovin syndrome (HSS) was first described in 1959 by British physicians John Patterson Hughes and Peter George Ingle Stovin, who reported four male patients with pulmonary artery aneurysms (PAA) associated with deep venous thrombosis (DVT)—two of their own cases and two previously published in the literature [1].

Approximately 90–100 cases have been reported in the literature, leaving the epidemiology, natural history, and optimal clinical management poorly defined. Most deaths result from massive hemoptysis due to pulmonary artery aneurysm rupture [2].

The precise etiology of HSS remains uncertain; however, it is widely considered a form of systemic vasculitis with a predilection for the pulmonary arteries and peripheral veins. Owing to considerable overlap in clinical and histopathological features, many authors regard HSS as an incomplete or atypical variant of Behçet disease (BD) [3].

Clinical manifestations stem from both thrombophlebitis and aneurysmal vascular involvement. Thrombotic events may affect the cerebral venous sinuses, cardiac chambers, or major veins, and can occasionally lead to pulmonary embolism. Pulmonary artery aneurysms may present with cough, dyspnea, chest pain, or life-threatening hemoptysis. Although classically limited to the pulmonary and bronchial arteries, aneurysms have also been reported in the carotid, iliac, hepatic, and aortic arterial beds. Traditionally, HSS has been described as progressing through three stages: (1) initial thrombophlebitis, (2) development of pulmonary artery aneurysms, and (3) aneurysmal rupture with massive hemoptysis [4].

Radiological imaging—particularly computed tomography pulmonary angiography (CTPA)—is pivotal in establishing the diagnosis, enabling visualization of aneurysms and associated thrombosis. To assist with standardized interpretation, the Hughes–Stovin Syndrome International Study Group developed a reference atlas that classifies pulmonary vasculitis into six progressive radiologic stages, ranging from aneurysmal wall enhancement and in-situ thrombosis to unstable leaking aneurysms, pulmonary artery pseudoaneurysms, and right-ventricular strain with or without intracardiac thrombus. This structured framework facilitates early detection and accurate characterization of vascular lesions, guiding timely intervention aimed at preventing catastrophic outcomes. In select, refractory, or high-risk cases, surgical or endovascular techniques—including embolization—may be required [5].

Here, we present a case of Hughes–Stovin syndrome manifesting with hemoptysis, review the diagnostic work-up and therapeutic approach, and discuss its clinical implications. This case contributes to the limited body of literature on HSS and underscores the importance of early recognition and multidisciplinary management to optimize outcomes.

2. Case presentation

A 20-year-old man presented to the respiratory clinic following an episode of mild hemoptysis one week earlier. His symptoms began with a 20-day history of dry cough that gradually progressed to productive cough with yellow sputum and a low-grade, undocumented fever. Empirical antibiotics led to temporary relief, but his cough subsequently worsened and mild hemoptysis developed. Past medical history was notable for a single episode of right knee pain with effusion during the preceding year and recurrent painful oral ulcers. The patient had a smoking history of one pack-year, and no history of trauma. He was admitted for further evaluation. He denied dyspnea, chest pain, night sweats, and anorexia but reported significant unintentional weight loss (>10 kg) within one month. On admission, vital signs were: temperature 37 °C, blood pressure 130/90 mmHg, heart rate 105 beats/min, respiratory rate 18/min, and oxygen saturation 98% on room air. Physical examination revealed marked cachexia and decreased breath sounds over the lower third of the right lung. Mild epigastric tenderness was noted. Laboratory investigations showed microcytic hypochromic anemia (hemoglobin 10.6 g/dL, hematocrit 32%, MCV 68 fL, MCHC 30 g/dL) and elevated inflammatory markers (erythrocyte sedimentation rate (ESR) 53 mm/h, C-reactive protein (CRP) 62 mg/L).

Chest X-ray (Fig. 1) demonstrated right hilar opacity. Non-contrast chest CT (Fig. 2) identified a right mass causing narrowing of the right lower bronchus, located in the apical segment of the right lower lobe and extending medially, measuring 4.5 × 4.6 × 9.8 cm. CTPA (Fig. 3) revealed a 5.2 × 5.1 × 3.7 cm aneurysm arising from the right lower lobe pulmonary artery, protruding into the parenchyma with mural thickening and a 1.2 cm circumferential thrombus. A second nearly thrombosed aneurysm measuring 3 cm in diameter was identified in the posterior segment of the same lobe. Doppler ultrasonography demonstrated no evidence of peripheral venous thrombosis. No aneurysms were identified in the abdominal aorta, iliac, or lower-extremity arteries. Abdominal ultrasound was unremarkable. Echocardiography showed preserved biventricular function with no structural abnormalities or pulmonary hypertension. Ophthalmologic evaluation was normal. Tuberculosis was excluded by three consecutive negative sputum smears for acid-fast bacilli. Sputum cultures showed no fungal growth, and hydatid serology was negative. Bronchoscopy demonstrated pulsatile external compression at the lateral orifice of the middle and basal segments of the right bronchial tree without endobronchial lesions or purulent secretions, consistent with a vascular etiology. Extended autoimmune testing including ANA, c-ANCA, p-ANCA, lupus anticoagulant, anti-cardiolipin, and β2-glycoprotein antibodies was negative.

Fig. 1.

— Posteroanterior chest radiograph showing a right hilar opacity corresponding to the right lower lobe pulmonary artery aneurysm.

Fig. 2.

— Non-contrast axial chest CT images showing a large right lower lobe mass causing narrowing of the right lower lobe bronchus and extending medially, consistent with a pulmonary artery aneurysm.

Fig. 3.

— Baseline computed tomography pulmonary angiography (CTPA) showing a large saccular aneurysm arising from the right lower lobe pulmonary artery with a circumferential mural thrombus. A second, nearly thrombosed aneurysm is seen in the posterior segment of the same lobe.

Given the differential diagnosis of pulmonary artery aneurysms without arteriovenous communications—including infectious etiologies (e.g., tuberculosis, syphilis), structural cardiac disease, pulmonary hypertension, trauma, and vasculitis—the clinical picture prompted consideration of idiopathic vasculitic syndromes, particularly Hughes–Stovin syndrome and Behçet disease. Serologic tests for HCV and HBsAg were negative; pathergy testing and HLA-B51 PCR were negative. Rheumatology consultation excluded Behçet's disease. Based on clinical, laboratory, and radiologic findings, a diagnosis of Hughes–Stovin syndrome was made. Digital subtraction angiography was recommended to assess suitability for embolization, but the patient declined. A multidisciplinary team initiated medical therapy. High-dose IV methylprednisolone (1 g/day × 3 days) resulted in significant symptomatic relief and a marked decline in inflammatory markers, including a reduction in CRP to 0.8 mg/dL. The patient was discharged on oral prednisolone (1 mg/kg/day), mycophenolate mofetil (2 g/day). Anticoagulation (apixaban) was used cautiously at a prophylactic dose given the absence of aneurysm instability.

Follow-up chest CT at four weeks (Fig. 4A) showed a reduction in aneurysm size: the major lesion decreased from 5.2 × 5.1 × 3.7 cm to 4.6 × 3.7 × 3.6 cm, and the second to 1.7 × 1.8 × 1.7 cm. Repeat CT after three months (Fig. 4B) demonstrated further interval reduction in aneurysm size (3.5 × 3.1 × 3.0 cm and 1.3 × 1.3 × 1.2 cm, respectively). Our patient remained clinically stable, with no recurrent hemoptysis and normalization of inflammatory markers. A six-month follow-up CT is planned.

Fig. 4A.

— non-contrast axial CT at 4 weeks showing interval reduction in the size of the right lower lobe pulmonary artery aneurysms.

Fig. 4B.

— Axial CT at 3 months with caliper measurements demonstrating further decrease in the diameter of the dominant aneurysm (approximately 35.1 × 31.1 mm).

3. Discussion

Hughes–Stovin syndrome is a rare systemic vasculitis characterized by the presence of pulmonary artery aneurysms and venous thrombosis, predominantly affecting young men [5]. Differential diagnoses of pulmonary artery aneurysms are broad and include malignancy, thromboembolic disease, infection, and congenital vascular anomalies [4,5]. A stepwise diagnostic approach was adopted, prioritizing exclusion of infectious and malignant causes before establishing a working diagnosis of Hughes–Stovin syndrome. Malignancy was considered less likely given the purely vascular morphology on CTPA and interval regression after immunosuppression. Pulmonary embolism was excluded radiologically. Fungal infection was excluded by negative sputum fungal cultures and the absence of radiologic features suggestive of invasive fungal disease, while hydatid disease was excluded serologically. Congenital anomalies were unlikely due to acute inflammatory presentation and systemic inflammation, and lack of prior respiratory symptoms.

Owing to its considerable overlap with Behçet disease—including shared vascular pathology—significant debate persists regarding whether HSS represents a distinct clinical entity or a vascular subtype of Behçet disease. Differentiation relies on clinical features: Behçet disease is typically associated with recurrent oral and genital ulcers, ocular inflammation, cutaneous lesions, and a positive pathergy test, whereas these manifestations are generally absent in HSS [6]. The absence of recurrent genital ulcers, ocular involvement, and a negative pathergy test over time made Behçet disease unlikely in our case.

Early recognition is essential to improve outcomes, as pulmonary artery aneurysm rupture remains the leading cause of mortality. No standardized diagnostic criteria exist; thus, diagnosis is based on clinical suspicion supported by imaging. Radiologic findings include unilateral or bilateral aneurysms, with or without intraluminal thrombi. Aneurysms may develop across the central vasculature, though they most commonly involve the pulmonary arteries. Venous thrombosis has been documented in the inferior vena cava, jugular, iliac, femoral, and cerebral venous sinuses [7].

The present case aligns with the classical demographic profile. The patient's recurrent oral ulcers raised suspicion for Behçet disease; however, the absence of genital ulceration, ocular involvement, cutaneous lesions, and negative pathergy and HLA-B51 testing supported the diagnosis of HSS. The absence of peripheral venous thrombosis is notable. Although peripheral thrombophlebitis has historically been considered a hallmark of HSS, several reports have documented cases with isolated pulmonary artery aneurysms without systemic thrombosis [8,9]. Our case adds to the growing number of HSS reports with isolated pulmonary artery involvement, suggesting that peripheral venous thrombosis, while common, may not be an obligatory component of the syndrome.

Management is not standardized, due to the syndrome's rarity. Current strategies are extrapolated from Behçet-related vascular disease and primarily include immunosuppressive therapy. High-dose corticosteroids remain the cornerstone, often combined with cytotoxic agents such as cyclophosphamide [10], which is frequently recommended in severe vascular Behçet disease and HSS; however, we opted for mycophenolate mofetil as a steroid-sparing agent given the patient's young age and the desire to minimize potential gonadotoxicity and long-term adverse effects. Immunosuppression was initiated only after reasonable exclusion of infectious etiologies.

Anticoagulation remains controversial: while it may be considered in cases with intracardiac thrombi or pulmonary embolism, it carries substantial risk when aneurysms are unstable [11]. In this case, prophylactic apixaban was chosen to reduce the risk of venous thromboembolism associated with hospitalization and relative immobilization, as the pulmonary artery aneurysms appeared radiologically stable, with no imaging features of leak or pseudoaneurysm.

Our patient responded favorably to high-dose corticosteroids and mycophenolate mofetil, demonstrating radiologic improvement. This supports the role of early aggressive immunosuppression in stabilizing vascular lesions. Long-term clinical and radiologic surveillance remains essential.

Our case highlights the importance of considering rare vasculitic syndromes in young patients with pulmonary artery aneurysms and hemoptysis, particularly when routine infectious and malignant evaluations are unrevealing.

This case has several limitations. First, Hughes–Stovin syndrome lacks standardized diagnostic criteria and histopathologic confirmation was not obtained. Second, the absence of venous thrombosis represents an atypical presentation. Third, the diagnosis remains clinical and radiologic, supported by exclusion of infectious, malignant, and autoimmune etiologies. These factors highlight the diagnostic challenges inherent to this rare syndrome.

4. Conclusion

Hughes–Stovin syndrome is an exceptionally rare and potentially fatal vasculitis that requires prompt recognition to avoid catastrophic outcomes. Although it shares clinical features with Behçet's disease, HSS remains a subject of debate within the spectrum of Behçet-related vasculitis; however, it is a useful working diagnosis in young patients presenting with pulmonary artery aneurysms and hemoptysis once infectious and autoimmune causes have been excluded. In the absence of standardized diagnostic criteria, a multidisciplinary approach integrating clinical assessment and radiologic evaluation is essential. Early initiation of immunosuppressive therapy can stabilize vascular lesions and reduce life-threatening complications. This case underscores the need for heightened clinical awareness and continued reporting to expand the current understanding of HSS and guide future management strategies.

To the best of our knowledge, reports of HSS without peripheral venous thrombosis remain limited, and this case adds to the evolving understanding that venous thrombosis may not be mandatory for the diagnosis of HSS.

CRediT authorship contribution statement

Kais Ebraheem: Writing – review & editing. Hanaen Hamed: Writing – original draft. Laila Alwan Alarrat: Writing – original draft. Batoul Taisan: Writing – original draft. Hussam Albardan: Writing – review & editing, Supervision. Ammar Alzein: Writing – review & editing, Supervision.

Statement for consent

Written informed consent was obtained from the patient for publication of this case and accompanying images.

Ethical approval

Ethical approval was not required for this single-patient case report according to the policy of Almouassat University Hospital.

Funding

No specific funding was received for this work.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.