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.
- Sommer, N.
- Droege, F.
- Gamen, K. E.
- Geisthoff, U.
- Gall, H.
- Tello, K.
- Richter, M. J.
- Deubner, L. M.
- Schmiedel, R.
- Hecker, M.
- Spiekerkoetter, E.
- Wirsching, K.
- Seeger, W.
- Ghofrani, H. A.
- Pullamsetti, S.
Keywords
- ALK-1 mutation
- Fk506
- Morbus Osler
- Vegf
- tacrolimus