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

Autor: Sommer N; 1 Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany., Droege F; 2 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Gamen KE; 3 Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Geisthoff U; 4 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Philipps Universitðt Marburg, Marburg., Gall H; 1 Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany., Tello K; 1 Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany., Richter MJ; 1 Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany., Deubner LM; 1 Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany., Schmiedel R; 5 Morbus Osler Selbsthilfe, Hattingen., Hecker M; 1 Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany., Spiekerkoetter E; 6 Division of Pulmonary and Critical Care Medicine, Dept. of Medicine, Stanford University, Stanford, CA, USA., Wirsching K; 7 Department of Otorhinolaryngology, University Medical Center Regensburg, Regensburg., Seeger W; 1 Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.; 3 Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Ghofrani HA; 8 Department of Medicine, Imperial College London, UK., Pullamsetti S; 3 Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Jazyk: angličtina
Zdroj: Pulmonary circulation [Pulm Circ] 2019 Apr-Jun; Vol. 9 (2), pp. 2045894018805406. Date of Electronic Publication: 2018 Sep 27.
DOI: 10.1177/2045894018805406
Abstrakt: 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.
Databáze: MEDLINE
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