Hughes-Stovin Syndrome

Hughes-Stovin syndrome is a rare vasculitis characterised by multiple pulmonary artery aneurysms with systemic venous thrombosis, mainly in young men aged 20 to 40 years. It is regarded as a vascular variant of Behçet disease by many, since overlapping features (oral ulcers, uveitis, pathergy) are found in some.

Fewer than 40 to 50 cases have been reported, mostly from the Middle East, Mediterranean, Asia and North Africa. The thrombosis is of the venous system (deep veins of the legs, inferior vena cava, hepatic veins, cerebral venous sinuses, right heart), and the aneurysms are in the pulmonary arteries (lobar and segmental), the bronchial arteries and, occasionally, systemic arteries.

Pathophysiology. Perivascular inflammation of the vasa vasorum causes neutrophilic and lymphocytic infiltration, destruction of the elastic lamina and media of the pulmonary arteries, and aneurysm formation. Thrombosis occurs on inflamed endothelium (in situ, rather than embolic). Aneurysms can rupture into the bronchus, producing massive, often fatal haemoptysis.

Fever, cough, haemoptysis (nearly all, from streaks to massive), dyspnoea, pleuritic chest pain, weight loss and malaise, with leg swelling and pain from deep vein thrombosis. Others have headache and papilloedema from cerebral venous thrombosis, abdominal pain from hepatic vein thrombosis, or right heart thrombus. Oral and genital ulcers, uveitis and skin lesions occur in an overlap with Behçet disease.

Haemoptysis of any degree in a young man with venous thrombosis needs urgent imaging, and the diagnosis should not be treated as pulmonary embolism with anticoagulation.

• CT pulmonary angiography: single or multiple saccular or fusiform aneurysms of the lobar or segmental pulmonary arteries (often bilateral), sometimes with thrombosed lumen and wall enhancement, together with consolidation and ground glass from haemorrhage. Filling defects in vessels may represent thrombus or aneurysm contents.
• Venous imaging: Doppler of the leg veins, CT venography or MR venography of the inferior vena cava, hepatic veins and cerebral veins.
• Echocardiography for right heart thrombus and pulmonary pressure.
• Exclusion of other aneurysm causes: tuberculosis (Rasmussen aneurysm), syphilis, bacterial endocarditis, fungal infection, Marfan syndrome, Takayasu arteritis and trauma.
• Inflammatory markers (raised C-reactive protein and sedimentation rate), HLA-B51, antiphospholipid antibodies, and pathergy test and clinical features of Behçet disease.
• Avoid pulmonary angiography with catheters through the aneurysm, and avoid pulmonary artery catheters.

Differential diagnosis.

• Behçet disease with pulmonary artery involvement
• Pulmonary embolism with infarction
• Mycotic pulmonary artery aneurysm and septic emboli
• Tuberculosis with Rasmussen aneurysm
• Pulmonary vasculitis (granulomatosis with polyangiitis) with haemorrhage
• Takayasu arteritis

• Immunosuppression is the main treatment, and should be started early: methylprednisolone 1 g intravenously daily for 3 days, followed by prednisolone 1 mg/kg daily with taper over 3 to 6 months, together with cyclophosphamide 600 mg/m2 (or 10 to 15 mg/kg) intravenously monthly for 6 to 12 months, then azathioprine 2 mg/kg daily (after thiopurine methyltransferase testing) for maintenance.
• Refractory or relapsing disease: infliximab 5 mg/kg intravenously at weeks 0, 2 and 6, then every 8 weeks, or adalimumab 40 mg subcutaneously every 2 weeks. Tocilizumab is reported in single cases.
• Anticoagulation is controversial: it risks fatal bleeding from aneurysms, so avoid it until immunosuppression has been started and aneurysm stability is shown, and use it for extensive thrombosis only with specialist advice. Anticoagulants are contraindicated with active haemoptysis.
• Interventional treatment for haemoptysis, symptomatic or growing aneurysms: transcatheter embolisation (coils, plugs, glue) of the affected artery, bronchial artery embolisation for bronchial sources, and covered stents. Surgery (lobectomy, aneurysm resection) has high mortality and is used when embolisation fails.
• Massive haemoptysis: airway protection, selective intubation, tranexamic acid 1 g intravenously every 8 hours, and urgent embolisation.
• Treat infection before and during immunosuppression (tuberculosis screening, hepatitis B screening, Pneumocystis prophylaxis with co-trimoxazole 960 mg three times weekly during high dose steroid).
• Treat venous thrombosis related complications, and eye, mouth and skin disease with the relevant specialist.

Complications and prognosis. Massive haemoptysis (the leading cause of death), rupture of aneurysm, recurrent thrombosis, and cerebral venous thrombosis. Mortality is 20 to 50% in published series, and is lower with early immunosuppression and embolisation.

Monitoring. CT angiography at 3 and 6 months, then every 6 to 12 months, with inflammatory markers monthly in the first 6 months, and monitoring of blood counts and infection on immunosuppression.

Referral and escalation. Refer to a rheumatology and vasculitis centre, interventional radiology and cardiothoracic surgery. Refer urgently for haemoptysis.