Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension
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 telang...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-11-01
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| Series: | Pulmonary Circulation |
| Online Access: | https://doi.org/10.1177/2045894018805406 |
| _version_ | 1811330604766068736 |
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| author | N Sommer F Droege KE Gamen U Geisthoff H Gall K Tello MJ Richter LM Deubner R Schmiedel M Hecker E Spiekerkoetter K Wirsching W Seeger HA Ghofrani S Pullamsetti |
| author_facet | N Sommer F Droege KE Gamen U Geisthoff H Gall K Tello MJ Richter LM Deubner R Schmiedel M Hecker E Spiekerkoetter K Wirsching W Seeger HA Ghofrani S Pullamsetti |
| author_sort | N Sommer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T16:04:51Z |
| format | Article |
| id | doaj.art-cb41cf216c6e4f02b323bc7fe6b8401d |
| institution | Directory Open Access Journal |
| issn | 2045-8940 |
| language | English |
| last_indexed | 2024-04-13T16:04:51Z |
| publishDate | 2018-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj.art-cb41cf216c6e4f02b323bc7fe6b8401d2022-12-22T02:40:25ZengWileyPulmonary Circulation2045-89402018-11-01910.1177/2045894018805406Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertensionN Sommer0F Droege1KE Gamen2U Geisthoff3H Gall4K Tello5MJ Richter6LM Deubner7R Schmiedel8M Hecker9E Spiekerkoetter10K Wirsching11W Seeger12HA Ghofrani13S Pullamsetti14Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University Duisburg-Essen, Essen, GermanyMax Planck Institute for Heart and Lung Research, Bad Nauheim, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Philipps Universitðt Marburg, MarburgExcellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, GermanyExcellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, GermanyExcellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, GermanyExcellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, GermanyMorbus Osler Selbsthilfe, HattingenExcellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, GermanyDivision of Pulmonary and Critical Care Medicine, Dept. of Medicine, Stanford University, Stanford, CA, USADepartment of Otorhinolaryngology, University Medical Center Regensburg, RegensburgMax Planck Institute for Heart and Lung Research, Bad Nauheim, GermanyDepartment of Medicine, Imperial College London, UKMax Planck Institute for Heart and Lung Research, Bad Nauheim, GermanyPulmonary 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.https://doi.org/10.1177/2045894018805406 |
| spellingShingle | N Sommer F Droege KE Gamen U Geisthoff H Gall K Tello MJ Richter LM Deubner R Schmiedel M Hecker E Spiekerkoetter K Wirsching W Seeger HA Ghofrani S Pullamsetti Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension Pulmonary Circulation |
| title | Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension |
| title_full | Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension |
| title_fullStr | Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension |
| title_full_unstemmed | Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension |
| title_short | Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension |
| title_sort | treatment with low dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension |
| url | https://doi.org/10.1177/2045894018805406 |
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