Granulomatous angiitis leading to a pulmonary veno-occlusive disease-like picture

Abstract

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension characterised by extensive fibrotic occlusion of pulmonary veins. PVOD has a similar insidious presentation to idiopathic pulmonary arterial hypertension but responds poorly to conventional therapies and has a worse prognosis.The current study reports the case of a Caucasian female with a long history of progressive dyspnoea ultimately diagnosed as focal granulomatous venulitis leading to a pulmonary venoocclusive disease-like pathology. The present study highlights the challenges in diagnosing and treating this condition.KEYWORDS: Acute pulmonary oedema, bosentan, granulomatous venulitis, infliximab, pulmonary veno-occlusive disease, sildenafil CASE REPORT A 43-yr-old female was extensively investigated because of progressive exercise induced fatigue and breathlessness without wheeze or cough. The patient was otherwise well. She ceased smoking at the time of symptom onset, having accumulated a 25 pack-yr smoking history. There was no relevant family history or occupational and drug exposures. There were no abnormal examination findings early in the natural history of the disease. Arterial oxygen saturation (Sa,O 2 ) at rest was 97% on room air.A chest radiograph (CXR), electrocardiogram, echocardiogram and myocardial thallium scan were all unremarkable. Lung function tests demonstrated a mild degree of airflow obstruction with no reversibility: forced expiratory volume in one second (FEV1) 2.15 L (85% predicted); forced vital capacity (FVC) 2.84 L (94% pred); FEV1/FVC ratio 76%; mean forced expiratory flow between 25 and 75% FVC 61% pred; diffusing capacity of the lung for carbon monoxide (DL,CO) 94% pred. A histamine challenge showed a provocation concentration causing a fall in FEV1 of 20% of 0.825 mg?mL -1 , which is consistent with severe airway hyperresponsiveness. A provisional diagnosis of asthma prompted a 3-week trial of oral prednisolone and introduction of a corticosteroid/long-acting b 2 -agonist combination inhaler device. This intervention was ineffective and did not improve lung function tests. A cardiopulmonary exercise test was aborted due to severe fatigue at 87% of predicted workload. The maximal oxygen uptake (V9O 2, max) was 93% of predicted with no exercise induced fall in SaO 2 . The patient was then lost to follow-up.The patient re-presented with worsening breathlessness and tender, erythematous nodules on her legs consistent with a diagnosis of erythema nodosum 3 yrs later. The cutaneous lesions resolved spontaneously without any treatment. A ventilation/perfusion (V9/Q9) scan was normal. High-resolution computed tomography (HRCT) of the lungs showed mild expiratory gas trapping with patchy peripheral bronchocentric opacities and minor septal thickening, but no mediastinal lymphadenopathy. Her serum biochemistry and full blood count were normal, erythrocyte sedimentation rate (ESR) was elevated at 41 mm?h -1 (normal rate ,15 mm?h -1 ) and angiotensin-converting enzyme level was 21.5 IU?L -1 (norm...

Characteristics of Patients with Pulmonary Venoocclusive Disease Awaiting Transplantation

“…Histopathologically, it is characterized largely by occlusion of the pulmonary veins by fibrous tissue, although lesions affecting the arterial vasculature may also be observed. The pathogenesis of PVOD remains poorly understood, although several risk factors have been reported, including genetic factors (1)(2)(3), toxic exposures (4)(5)(6)(7)(8), hypercoagulability (9,10), infection (11)(12)(13), and autoimmune disorders (14)(15)(16)(17)(18)(19). Although the true prevalence and incidence of PVOD are unknown, data from the French National PAH registry estimate an annual incidence of 0.1 to 0.2 cases per million in the general population (20,21).…”

In search of markers of treatment failure and poor prognosis in IPAH - the value of mosaic lung attenuation pattern on thin-section CT scans

“…The authors suggest a clinically relevant hemodynamic effect of post-capillary occlusion in a setting of PAH-CTD, with PVOD-like pathology. PVOD-like pathology was described in PAH-CTD also by Overbeck et al [27] and in the course of fatal granulomatous angiitis by Dwyer et al [28]. …”

In search of markers of treatment failure and poor prognosis in IPAH – the value of mosaic lung attenuation pattern on thin-section CT scans

“…The authors suggest a clinically relevant hemodynamic effect of post-capillary occlusion in a setting of PAH-CTD, with PVOD-like pathology. PVOD-like pathology was described in PAH-CTD also by Overbeck et al [27] and in the course of fatal granulomatous angiitis by Dwyer et al [28]. The search for clinical markers of PVOD/PCH drew attention to the presence of lung pathology seen occasionally on CT scans in PAH.…”