Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension.

Abstract

Pulmonary arterial hypertension (PAH) can be found in patients suffering from a loss-of-function mutation of the gene encoding for the activin receptor-like kinase 1 (ALK-1), a bone morphogenetic protein (BMP) type 1 receptor. Interestingly, ALK-1 mutations also lead to hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease characterized by arteriovenous malformations (AVMs) leading to potentially life-threatening bleeding complications such as epistaxis. Current therapeutic options for both diseases are limited and often only temporary or accompanied by severe side effects. Here, we report of a patient with a mutation of the ALK-1 gene suffering from both HHT and PAH. Recently, it was shown that tacrolimus increased ALK-1 signaling and had beneficial effects in selected end-stage PAH patients. We thus hypothesized that treatment with tacrolimus may prevent disease progression in this patient. Surprisingly, treatment with low-dose tacrolimus dramatically improved his HHT-associated epistaxis but did not attenuate progression of PAH.

• Authors: N Sommer, F Droege, K E Gamen, U Geisthoff, H Gall, K Tello, M J Richter, L M Deubner, R Schmiedel, M Hecker, E Spiekerkoetter, K Wirsching, W Seeger, H A Ghofrani, S Pullamsetti
• Journal: Pulmonary circulation (Pulm Circ) 2019 Apr-Jun Vol. 9 Issue 2 Pg. 2045894018805406 ISSN: 2045-8932 [Print] United States
• PMID: 30260738 (Publication Type: Journal Article)