Review: More Investigation Needed to Understand Pathogenesis of Sch-PAH

A deeper understanding of schistosome-associated pulmonary arterial hypertension (Sch-PAH) pathogenesis, course, and treatment is needed given the uncertainty that still surrounds the condition, according to a review published in Frontiers in Cardiovascular Medicine.

PAH occurs in about 5% to 15% of patients with the severe hepatosplenic form of schistosomiasis, particularly due to Schistosoma mansoni, makingschistosomiasis a well-recognized cause of PAHand Sch-PAH one of the most common causes of the disorder worldwide.

Although the clinical, laboratory, and hemodynamic profiles presented by patients with Sch-PAH are similar to those observed in patients with other etiologies, data on the pathogenic mechanisms underlying Sch-PAH are limited, and the condition is still underdiagnosed and undertreated. This presents challenges to the recognition and management of the condition, and patients still die prematurely from right heart failure.

Previous data indicate that schistosomiasis affects more than 230 million people in parts of the Middle East, South America, Southeast Asia, and in Sub-Saharan Africa especially. Given the prevalence of the condition, it is therefore worth investigating this helminthiasis in people with PAH, the authors of the current review note, which aimed to summarize existing knowledge about Sch-PAH, with a focus on the pathogenesis of the condition.

Schistosomiasis is a parasitic disease caused by trematode flukes of the genus Schistosoma. The flukes use man and other mammals and aquatic and amphibian snails as definitive hosts and intermediate hosts, respectively. The differences in schistosome species are important predictors of clinical presentations of the infection.

Upon entering a definitive host, cercarial larvae travel to the liver where they grow into adult worms and follow paths to the mesenteric venules of the colon (S mansoni), small intestine (Schistosoma japonicum), or pelvic plexus (Schistosoma haematobium) and lay eggs.

Although the exact pathogenesis of Sch-PAH remains unknown, mechanical obstruction of lung vasculature by embolized eggs, pulmonary vascular inflammation and remodeling, and portopulmonary hypertension–like pathophysiology have been suggested as the most likely pathogenic mechanisms for the condition. Research also suggests that a diffuse and heterogeneously distributed pulmonary proliferative vasculopathy is an important mechanism underlying the pathogenesis of Sch-PAH and that inflammatory mechanisms may be at play.

Currently, PAH therapies target 1 or more of 3 major pathways involved in disease progression: the nitric oxide pathway, which includes phosphodiesterase type 5 inhibitors and soluble guanylyl cyclase stimulators; the endothelin-1 pathway, which includes receptor antagonists; and the prostacyclin pathway, which includes prostacyclin analogs and the nonprostanoid IP-receptor agonist selexipag. Although a deeper understanding of PAH pathophysiology has warranted combination therapy, targeting the NO, ET-1, and PG12 pathways, as the contemporary standard for treatment among patients with PAH, the approach requires investigation among patients with Sch-PAH.

Further data on therapeutic strategies of patients with Sch-PAH may improve symptoms and rates of survival, the review authors concluded.

Reference

Ferrari TCA, Albricker ACL, Gonçalves IM, Freire CMV. Schistosome-Associated Pulmonary Arterial Hypertension: A Review Emphasizing Pathogenesis. Front Cardiovasc Med. Published online October 5, 2021. doi:10.3389/fcvm.2021.724254