Pulmonary vasculitis mimicking chronic thromboembolic disease

Abstract

A 29-year-old female patient presented with chest pain, breathlessness and syncope on the background of constitutional symptoms, oral ulceration and a rash. Multiple investigations were performed, including a CT pulmonary angiogram (CTPA) that was initially felt to show imaging features consistent with a diagnosis of chronic thromboembolic disease (CTED). The patient was referred to a tertiary pulmonary hypertension centre and the possibility of pulmonary vasculitis was raised. Subsequent positron emission tomography (PET)-CT revealed imaging features supporting this diagnosis. The patient was treated with intravenous cyclophosphamide infusions, following which her symptoms improved. A repeat PET-CT 6 months after treatment showed resolution in pulmonary artery and mediastinal uptake, but persistence of pulmonary artery occlusions on a repeat CTPA. A final diagnosis of pulmonary vasculitis secondary to Behçet’s disease was made. This case report aims to raise awareness of the imaging features of CTED and its mimics.

Background

Chronic thromboembolic disease (CTED) and chronic thromboembolic pulmonary hypertension (CTEPH) are significantly under-diagnosed conditions where pulmonary artery webs and occlusions can lead to pulmonary hypertension and progressive right ventricular failure. Untreated CTEPH carries a poor prognosis and can be fatal. It is estimated that only approximately 20% of patients with CTEPH are diagnosed; some go undiagnosed, others are misdiagnosed.¹ Radiology is crucial to diagnosis and radiologists need to become increasingly aware of the CT findings. Surgery with pulmonary endarterectomy can be considered curative for most. There is also treatment available with balloon pump angioplasty and licenced medical treatment with riociguat.² Radiologically there are rare mimics of CTEPH including pulmonary artery sarcomas, thrombus in-situ (most commonly seen in congenital heart disease) and pulmonary vasculitis.³ It is important that these are appreciated, both so the correct diagnosis is achieved but also so major surgery is either not undertaken unnecessarily or planned as part of a secondary treatment. We present such a case.

Case presentation

A 29-year-old Caucasian woman presented with a 6-month history of right sided chest pain, progressive breathlessness, exertional syncope and some peripheral oedema. She also reported a 2-year history of increasing morning ankle and knee pain with sicca symptoms, fatigue, hair loss, recurrent oral ulceration, episodes of per rectal bleeding, limb pustular rash and 1.5 stone weight loss. She had no significant medical history. Her mother had rheumatoid arthritis.

On examination, there was reduced air entry at the lung bases, a systolic murmur in the pulmonary region, right ankle swelling and a pustular rash on her arms. Jugular venous pressure was mildly elevated.

Investigations

Initial blood tests revealed a microcytic anaemia, deranged liver function tests (LFT) with a raised alkaline phosphatase of 238 and alanine transaminase of 129 and a raised C reactive protein (CRP) of 85. There was a positive D-dimer. Renal function was normal.

Immunological tests showed antinuclear antibody, anti-neutrophil cytoplasmic antibody and human leucocyte antigen B5 to be negative. Complement tests were normal. Results of an antiphospholipid screen were later available and showed negative anticardiolipin antibodies with equivocal lupus anticoagulant.

Skin biopsy revealed non-specific ulceration only.

The presenting clinical features of dyspnoea, chest pain and ankle swelling raised the possibility of pulmonary embolism, potentially chronic given the duration of symptoms and possible features of right heart failure. For this reason, a CT pulmonary angiogram (CTPA) was performed, which showed circumferential thickening of the left main pulmonary artery (initially erroneously thought to represent laterally adherent chronic thrombus) and complete occlusion of several lobar and segmental arteries in the right lower and middle lobe (figures 1 and 2).

Figure 1.

Axial slice from presentation CT pulmonary angiogram showing circumferential wall thickening of the left main pulmonary artery (arrow).

Figure 2.

Coronal slice from presentation CT pulmonary angiogram showing circumferential thickening of left main pulmonary artery (arrowhead) and occlusion of right lower lobe artery (arrow).

The pulmonary artery occlusions are essential radiological features of CTEPH and CTED. However, following referral to a tertiary pulmonary hypertension service, the possibility of an underlying pulmonary vasculitis was raised on the basis of the pulmonary artery wall thickening. A positron emission tomography-CT was subsequently performed, which showed increased uptake through the mediastinum and pulmonary arteries (figure 3).

Figure 3.

Axial slice from presentation positron emission tomography-CT scan shows high tracer uptake in the left main pulmonary artery (arrow), corresponding with wall thickening seen on presentation CT pulmonary angiogram.

Echocardiogram showed a mildly dilated right atrium, a borderline pulmonary artery acceleration time and trivial tricuspid regurgitation. There was no right ventricular dilatation and a right ventricular systolic pressure of 28 mm Hg. Right heart catheterisation was performed and revealed a mean pulmonary artery pressure of 20 mmHg and pulmonary vascular resistance of 1.6 Wood units.

Differential diagnosis

Chronic respiratory symptoms, coupled with the CTPA findings, led to an initial differential diagnosis of CTED. The sicca symptoms, arthralgia, rash and ulceration would be atypical—although the possibility of two diagnoses should always be considered. This principle differential was revised on subsequent multidisciplinary discussion at the tertiary pulmonary hypertension centre, and following a PET-CT, a diagnosis of pulmonary vasculitis was made. Pulmonary artery sarcoma can also have similar imaging findings and was, therefore, included in the differential.

Treatment

The patient was initially treated with enoxaparin then switched to warfarin. Prednisolone 35 mg was commenced alongside bone protection. Following the results of the antiphospholipid screen, she was switched to rivaroxaban.

She was finally commenced on intravenous cyclophosphamide treatment infusions, then given azathioprine maintenance.

Outcome and follow-up

The case was referred to a further specialist cardiothoracic centre, who agreed that imaging showed pulmonary artery occlusions at a lobar level and that overall the appearances were suggestive of a ‘burnt out’ vasculitis rather than CTED/CTEPH.

A diagnosis of pulmonary vasculitis secondary to Bechet’s disease was eventually made.

Her CRP, anaemia and abnormal LFTs normalised with anticoagulation and prednisolone. However, oral ulcers, arthritis and constitutional symptoms persisted.

Following cyclophosphamide infusions, the arthritis, rash and ulcers improved but the dyspnoea and chest pain broadly persisted.

A repeat PET-CT 6 months after presentation showed resolution of the pulmonary artery and mediastinal uptake (figure 4). A repeat CTPA also showed improvement of the pulmonary artery thickening on the left, although there were substantial persistent right sided pulmonary artery occlusions (figure 5).

Figure 4.

Axial positron emission tomography-CT slice performed 6 months after initial scans, following treatment with intravenous cyclophosphamide, showing resolution of previously demonstrated high tracer uptake in the left main pulmonary artery (arrow).

Figure 5.

Axial slice from repeat CT pulmonary angiogram performed 6 months after initial scans, following treatment with intravenous cyclophosphamide, showing resolution of previously demonstrated wall thickening of left main pulmonary artery (arrow).

Discussion

CTEPH is a rare, potentially fatal but curable disease. Untreated there is a poor prognosis dependent on pulmonary artery pressure and right ventricular function. Worldwide CTEPH is significantly under-diagnosed. Using observed incidence rates for CTEPH post-acute pulmonary embolic disease it is estimated that only 7%–29% of patients worldwide with CTEPH are currently identified correctly.¹

CTPA features of CTPEH include generic CT features of pulmonary hypertension (pulmonary artery dilatation, right ventricle dilatation/hypertrophy) with additional chronic pulmonary artery thrombus and webs. The webs and occlusions appear different to acute pulmonary emboli and can be easily overlooked. In CTED there is no pulmonary hypertension and the generic features of pulmonary hypertension may be absent, but the webs and occlusions are present.^{4 5}

There are technical factors and disease mimics that can lead to a false positive diagnosis of CTEPH/CTED. These include breathing and contrast streak artefact, thrombus in situ (most commonly seen in congenital heart disease), pulmonary artery sarcoma, fibrosing mediastinitis and pulmonary vasculitis.

Hagan et al ⁶ previously described two cases where the initial diagnosis of CTED was made, with both patients having pulmonary endarterectomy surgery. At surgery both cases demonstrated unexpected fibrous pulmonary arteries which histologically were due to a large vessel vasculitis. In the first of their cases, despite surgery and medical treatment for the vasculitis, some of the pulmonary arteries remained occluded and narrowed. Isolated pulmonary vasculitis has also been described as rare causes of pulmonary hypertension and pulmonary artery aneurysms.^{7 8}

In both our case and the cases by Hagan there were areas of circumferential wall pulmonary artery wall thickening not typically seen in CTEPH/CTED. This is a useful sign and led to further investigation with PET-CT. Making the diagnosis of pulmonary vasculitis before (potentially unnecessary) pulmonary endarterectomy surgery is clearly crucial.

Pulmonary manifestations of Behçet’s disease have been described in 1%–10% of cases,⁹ with pulmonary vasculitis thought to represent the underlying pathologic process. This most commonly manifests as pulmonary artery aneurysms, but can lead to a variety of pulmonary sequelae, including thrombosis, infarction and haemorrhage.¹⁰ Medical treatment with immunosuppression is successful in improving symptoms and radiological features, with only a minority of patients requiring more invasive treatment such as embolisation or lobectomy.¹¹ An important consideration in patients with vasculitides presenting with respiratory symptoms is that this may be secondary to either pulmonary artery vasculitis or thrombosis alone. The treatment approach will differ, hence careful assessment is required.

Learning points.

• Pulmonary vasculitis may mimic chronic thromboembolic disease (CTED). Unrecognised there is the potential for unplanned or unnecessary surgery.

• Radiologists should be alert to the diagnosis and a key CT pulmonary angiogram (CTPA) finding is circumferential pulmonary artery wall thickening.

• Radiologists need to continue to be alert to the CTPA findings of chronic thromboembolic pulmonary hypertension and CTED to improve diagnostic rates for this potentially fatal but curable condition.