Systemic Sclerosis Associated Pulmonary Arterial Hypertension with Venous Involvement – a Novel ABCC8 Pathogenic Variant

Discussion

PAH with venous/capillary involvement (formerly referred to as pulmonary veno-occlusive disease [PVOD] /capillary hemangiomatosis) is a rare, severe form of PH, with an incidence of 0.1-0.5 cases/million/year. This condition comprises a fibroproliferative process of pulmonary venous and capillary compartments, with small vein occlusion caused by smooth muscle hypertrophy and collagen deposition.

The diagnosis of PVOD is challenging due to its non-specific presentation, often mimicking PAH. Moreover, histological confirmation via lung biopsy is contraindicated due to the significant risk of hemorrhage. Certain clinical and imaging features can facilitate a presumptive diagnosis, which include typical findings on CCTA – centrilobular ground-glass opacities, septal lines, and mediastinal lymphadenopathy, severely reduced DLCO on PFTs, and low oxygen saturation nadir during the 6MWT. PVOD manifests in two forms: hereditary, which is associated with autosomal recessive biallelic mutations in the EIF2AK4 gene, and sporadic, which presents later in life and more frequently in males. Several risk factors are linked to sporadic PVOD, including prior exposure to chemotherapy (particularly alkylating agents),^, tobacco, and organic solvents such as trichloroethylene.^,

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