Hughes–Stovin syndrome presenting with massive pulmonary artery aneurysms: a case report

Abstract

Background

Hughes–Stovin syndrome (HSS) is an exceedingly rare vasculitis characterized by the combination of thrombophlebitis and multiple pulmonary or bronchial artery aneurysms. It predominantly affects young men, is often considered a variant of Behçet's disease, and carries a poor prognosis due to the high risk of fatal hemoptysis from aneurysm rupture. This case report highlights the classic diagnostic and therapeutic challenges of this condition.

Case presentation

A 20-year-old Arab male smoker presented with a 20-day history of progressive cough, hemoptysis, recurrent oral aphthous ulcers, and significant weight loss. He did not meet the International Study Group criteria for Behçet's disease. Laboratory findings indicated marked systemic inflammation. While a chest radiograph suggested a hilar abnormality, contrast-enhanced computed tomography (CT) pulmonary angiography revealed multiple pulmonary artery aneurysms, the largest measuring 5.2 cm, confirming the diagnosis of HSS. The patient was treated with high-dose intravenous corticosteroids, followed by oral prednisolone, mycophenolate mofetil, and prophylactic apixaban. Despite initial improvement, he experienced a relapse of hemoptysis during steroid tapering. At a 4-week follow-up, his symptoms had resolved, inflammatory markers had normalized, and the largest aneurysm showed a reduction in size. The patient was subsequently scheduled for endovascular coiling.

Conclusions

HSS is a life-threatening condition that must be considered in young patients with hemoptysis and thrombosis, particularly when clinical features are suggestive but incomplete for Behçet's disease. CT angiography is essential for diagnosis. Treatment centers on aggressive immunosuppression to halt aneurysm progression, requiring a delicate balance with anticoagulation. Endovascular intervention is often necessary for large aneurysms to prevent a fatal outcome.

Background

Hughes–Stovin syndrome (HSS) is an extremely rare disorder of unknown etiology, characterized by the combination of thrombophlebitis and multiple pulmonary and/or bronchial artery aneurysms [1, 2]. The condition predominantly affects young men, typically between the second and fourth decades of life, and often follows a clinical course in three phases: symptoms of thrombophlebitis, formation of large pulmonary aneurysms, and finally, aneurysmal rupture leading to massive, often fatal, hemoptysis [1, 3].

The pathogenesis remains unclear, but the current consensus is that HSS represents a form of vasculitis. Due to significant clinical, radiological, and histopathological overlap, many authorities consider it to be a rare cardiovascular manifestation or an incomplete form of Behçet's disease (BD), distinguished primarily by the absence of characteristic mucocutaneous ulcers, ocular lesions, and a positive pathergy test [3, 4]. The diagnosis is one of exclusion, made in patients presenting with the characteristic aneurysm–thrombosis combination after other causes have been ruled out. Management is challenging and centers on immunosuppressive therapy to control the underlying vasculitis and stabilize aneurysm growth, though the prognosis remains poor [1]. We report the case of a 20-year-old male with HSS to highlight the classic diagnostic features and the complexities of its management.

Case presentation

A 20-year-old Arab male smoker with no significant past medical history presented with a 20-day history of cough that progressed from dry to productive with yellowish sputum and hemoptysis. He reported recurrent painful oral aphthous ulcers, epigastric pain, post-tussive vomiting, and an unintentional weight loss of more than 10 kg in the preceding month. He denied genital ulcers, ocular involvement, joint pain, neurological symptoms, or urinary complaints. The family history was significant only for type I diabetes in a sibling.

On examination, the patient was cachectic (BMI 17.9 kg/m²), afebrile, with a heart rate of 105 bpm, blood pressure of 130/90 mmHg, respiratory rate of 18/min, and SpO₂ of 98% on room air. Chest auscultation revealed decreased breath sounds in the right lower lung field. Abdominal examination demonstrated mild epigastric tenderness and a palpable spleen tip. No lymphadenopathy, skin lesions, genital ulcers, or neurological deficits were noted.

Initial laboratory investigations revealed marked inflammation with an elevated C-reactive protein (CRP) level of 62 mg/dL. Further workup showed hemoglobin of 10.6 g/dL and an erythrocyte sedimentation rate (ESR) of 53 mm/h. Renal and liver function tests were within normal limits. An extensive infectious workup was negative, including three sputum samples for acid-fast bacilli and negative serology for hydatid disease and viral hepatitis. Pathergy test and HLA–B51 were negative.

A chest radiograph suggested a right hilar abnormality (Fig. 1). A non-contrast chest CT revealed a rounded opacity in the right lower lobe, raising suspicion of vascular pathology (Fig. 2). A subsequent contrast-enhanced CT pulmonary angiography was performed. Bronchoscopy demonstrated a pulsatile extrinsic compression of the right lower lobe bronchi. The CT pulmonary angiography with 3D reconstruction confirmed multiple pulmonary artery aneurysms, the largest measuring 5.2 × 5.1 × 3.7 cm in the right lower lobe (Figs. 3, 4). Echocardiography showed normal cardiac structure and function without evidence of pulmonary hypertension.

Fig. 1.

Chest X-ray (PA view) showing right hilar abnormality

Fig. 2.

Non-contrast chest CT showing a rounded opacity in the right lower lobe region. A coronal view–aorta level. B coronal view–heart level. C coronal view—diaphragm level. D Axial view

Fig. 3.

Contrast-enhanced CT pulmonary angiography (axial cuts) demonstrating pulmonary artery aneurysms in the right lower lobe

Fig. 4.

A 3D CT pulmonary angiography reconstruction showing the morphology and distribution of the aneurysms. B Diagram showing the distribution of the aneurysms. (The diagram is the author's own work)

Given the presence of oral aphthosis and pulmonary artery aneurysms in the absence of other major criteria for Behçet's disease, the patient did not fulfill the International Study Group criteria. A diagnosis of Hughes–Stovin syndrome was established.

The patient was treated with intravenous methylprednisolone 1 g/day for 3 days, followed by oral prednisolone 1 mg/kg/day (with a planned taper), mycophenolate mofetil 2 g/day, and prophylactic apixaban 2.5 mg twice daily. His clinical course was complicated by a relapse of hemoptysis during the steroid taper, which required a temporary increase in the corticosteroid dose. At the 4-week follow-up, the hemoptysis had resolved, CRP had normalized, and a repeat CT scan showed a reduction of the largest aneurysm to 4.6 × 3.7 × 3.6 cm (Fig. 5). The course was further complicated by an episode of pneumonia, which was successfully treated with moxifloxacin. The patient was subsequently scheduled for endovascular coiling of the aneurysm (Fig. 6).

Fig. 5.

As a 4-week follow-up, CT showed a reduction of the largest aneurysm to 4.6 × 3.7 × 3.6 cm. A mediastinal window. B lung window

Fig. 6.

Timeline

Discussion

We report a classic case of Hughes–Stovin syndrome in a young male, presenting with the quintessential triad of recurrent oral aphthosis, deep vein thrombosis, and multiple pulmonary artery aneurysms. This case serves as a critical reminder of the diagnostic and therapeutic tightrope walked in managing this rare, life-threatening vasculitis. Our experience underscores three pivotal aspects: the syndrome's position within the spectrum of Behçet's disease, the critical role of advanced imaging, and the nuanced balance between immunosuppression and anticoagulation in a disease fraught with both thrombotic and hemorrhagic risks.

The pathogenesis of HSS is believed to center on a neutrophilic vasculitis affecting the vasa vasorum of large arteries, leading to weakening of the vessel wall and aneurysm formation, concurrent with a hypercoagulable state [1, 3]. The most significant clinical challenge lies in differentiating HSS from its close relative, Behçet's disease. Our patient’s presentation—featuring major vascular involvement and oral aphthosis in the absence of genital ulcers, ocular lesions, or a positive pathergy test—epitomizes the "incomplete" BD phenotype that defines HSS [4]. This overlap suggests that HSS is not a distinct entity but rather a variant or severe cardiovascular manifestation of BD, a concept gaining wider acceptance [3, 7]. The differential characteristics are summarized in Table 1.

Table 1.

Key differentiating features between Hughes–Stovin syndrome and Behçet's disease

Feature	Hughes–Stovin syndrome	Behçet's disease
Core manifestations	Pulmonary artery aneurysms, peripheral thrombophlebitis	Recurrent oral/genital ulcers, skin lesions, uveitis
Pulmonary involvement	Hallmark (Aneurysms are common)	Less common (5–10% of cases), but aneurysms are the most severe manifestation
Systemic involvement	Often limited or absent	Widespread (articular, neurological, gastrointestinal, vascular)
Pathergy test	Typically negative	Positive in 60–70% of patients (geographic variation)
HLA–B51 association	Weak or absent	Strong association (40–80% of patients)
Diagnostic approach	Diagnosis of exclusion; based on clinical/radiological findings	Fulfillment of International Study Group or ICBD criteria

As demonstrated in our case, the diagnostic journey from a non-specific chest X-ray to a definitive CT pulmonary angiography is typical. CT angiography is the undisputed gold standard, not only for confirming the presence and extent of aneurysms but also for monitoring treatment response, as evidenced by the measurable reduction in aneurysm size in our patient [5, 8]. A critical diagnostic pitfall is the misidentification of the underlying thrombotic phenomena as simple pulmonary embolism. Initiating full therapeutic anticoagulation in this context without concomitant immunosuppression can be disastrous, potentially accelerating aneurysm rupture by counteracting the fragile inflammatory pseudo-aneurysm wall [4, 9]. This underscores the necessity of considering HSS in any young patient with hemoptysis and radiographic evidence of thrombosis.

The management of HSS is a paradigm of balancing competing risks. The primary driver of morbidity and mortality is the inflammatory vasculitis; thus, aggressive immunosuppression is the cornerstone of therapy [1, 6]. Our initial regimen of high-dose intravenous corticosteroids followed by a steroid-sparing agent (mycophenolate mofetil) aligns with established guidelines for severe vascular BD, from which HSS management is often extrapolated [10]. The initial favorable response, marked by normalized inflammatory markers and aneurysm regression, validates this approach.

However, the relapse of hemoptysis during steroid tapering offers a crucial clinical lesson. It highlights the disease's refractory nature and the absolute requirement for long-term, sustained immunosuppression. This relapse pattern is well-documented and often necessitates the early introduction of steroid-sparing agents like azathioprine, cyclophosphamide, or, as in our case, mycophenolate mofetil [6, 11].

The use of anticoagulation in HSS remains one of its most contentious aspects. The presence of thrombosis tempts its use, yet the risk of fatal hemorrhage counsels against it. Our decision to use a prophylactic dose of apixaban reflects a middle-ground approach reported in some recent cases [12]. We posit that in the presence of active, high-burden thrombosis, the benefits of prophylactic anticoagulation may outweigh the risks, but only when coupled with potent, concurrent immunosuppression to control the underlying vasculitis and stabilize the aneurysmal walls. This cautious strategy appeared successful in our patient, as no hemorrhagic complications occurred, and the thrombotic burden was controlled.

Medical management alone is often insufficient for large, life-threatening aneurysms. Endovascular embolization has emerged as the preferred first-line intervention over high-mortality surgical resection [1, 13]. The decision to proceed with coiling in our patient, whose dominant aneurysm was initially > 5 cm, was therefore prudent. This approach provides a means to securely exclude the aneurysm from the circulation, mitigating the immediate threat of rupture while medical therapy addresses the systemic disease.

Limitations and strengths

A limitation of this report is its nature as a single case study, which precludes broad generalizations. Furthermore, the complexity of the case was compounded by an intercurrent pneumonia, a known risk in immunocompromised patients, underscoring the challenges of managing intense immunosuppression. The strengths of this report lie in the comprehensive diagnostic workup, the clear demonstration of a treatment response on imaging, and the detailed documentation of a clinical relapse, which provides valuable insight into the disease's natural history.

Conclusion

Hughes–Stovin syndrome is a rare but catastrophic vasculitis that demands a high index of suspicion. This case reinforces its position within the Behçet's disease spectrum and highlights the critical importance of CT angiography for diagnosis and follow-up. Successful management requires a nuanced, dual-pronged strategy: aggressive, sustained immunosuppression to control the underlying vasculitis, and a carefully considered, often prophylactic, approach to anticoagulation to manage thrombotic risk. As evidenced by our patient's course, medical therapy can induce remission, but a relapsing pattern is common. For large, unstable aneurysms, endovascular intervention is an essential, life-saving adjunct to medical therapy, forming the definitive step in preventing a fatal hemorrhage.

Author contributions

AAB and NF and SF were responsible for drafting the manuscript. MA was responsible for reviewing the manuscript.

Funding

Not applicable.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

The Ethics Committee of Damascus University does not require ethical approval for case reports or case series, as per institutional policy.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interest

The authors declare that they have no competing interest.