Pulmonary Veno-Occlusive Disease: An 80-Year-Old Mystery

Abstract

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension which occurs in 0.1-0.2 people per million. Its etiology is still poorly understood but is related to several risk factors. The histopathology of PVOD is characterized by intimal fibrosis narrowing or the occlusion of small pulmonary veins or venules. A definitive diagnosis requires a surgical biopsy, which is a risky procedure. Thus, the diagnosis must be based on high clinical suspicion and the results of various diagnostic tests, mainly high-resolution computed tomography, pulmonary function tests, bronchoalveolar lavage, and right heart catheterization. The definitive treatment is limited to lung transplantation. Several pulmonary arterial hypertension-specific agents may cause pulmonary edema in PVOD. However, the cautious use of such medications in selected patients, and surgical or mechanical supports, may successfully bridge patients to transplantation. Given the scant knowledge regarding this entity, future studies with a focus on elucidating the etiology and establishing the optimal treatment are required, as is further development in diagnosis.

Challenges in pulmonary hypertension: managing the unexpected

“…A rare case of PH associated with pulmonary veno-occlusive disease The diagnosis and treatment of pulmonary veno-occlusive disease (PVOD) presents a challenge to the practising clinician, primarily because the condition remains poorly understood and is difficult to distinguish from idiopathic PAH (IPAH) [25][26][27]. It is estimated that PVOD accounts for 5-10% of cases initially misdiagnosed as IPAH [25,28].…”

“…Thus, all disorders related to PAH are classified within group 1 (PAH) of the WHO classification system, with PVOD categorised as a subgroup of group 1 [30]. However, despite this similarity, there are distinctive clinical, genetic, environmental and phenotypic features that differentiate PVOD from PAH subtypes such as IPAH, including predisposing factors [25,26,31,32]. Recently, genetic studies have shown that PVOD occurs sporadically or is inherited in families due to recessive mutations of the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene which encodes the GCN2 protein [31].…”

“…Recently, genetic studies have shown that PVOD occurs sporadically or is inherited in families due to recessive mutations of the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene which encodes the GCN2 protein [31]. In addition, environmental factors such as a heavier smoking habit (greater tobacco exposure) have been reported to occur at a higher frequency in PVOD than in IPAH patient populations [25,33]. At a clinical level, the haemodynamic presentation of PVOD is similar to IPAH, particularly with respect to wedge pressure, which is invariably normal in both disease conditions [33].…”

Clinical case of delayed systemic sclerosis and pulmonary arterial hypertension diagnostics

“…This condition remains poorly understood and accounts for 5-10 % of cases initially misdiagnosed as IPAH. Haemodynamic presentation of PVOD is similar to IPAH, particularly with respect to wedge pressure, which is invariably normal in both disease conditions [19,20], that was reflected in the ESC/ERS guideline PH 2009 [12]. In updated clinical classification (Nice 2018) PVOD was determined as PAH with overt sings of venous / capillaries (PVOD/PCH) involvement [13].…”

Pulmonary Veno-Occlusive Disease as a Cause of Pulmonary Arterial Hypertension

“…Pulmonary veno-occlusive disease (PVOD) represents an uncommon form of pulmonary arterial hypertension (PAH) characterized by progressive obliteration of the pulmonary venules, elevation of pulmonary arterial pressures, and increased pulmonary vascular resistance, leading to right ventricular failure and death (1)(2)(3). PVOD shares similar characteristics with idiopathic PAH, which can easily lead to misdiagnosis among these two entities.…”