Case report study of thalidomide therapy in 18 patients with severe arteriovenous malformations.
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
13
12
2021
accepted:
05
05
2022
medline:
1
6
2022
pubmed:
1
6
2022
entrez:
28
8
2024
Statut:
ppublish
Résumé
Arteriovenous malformations (AVMs) are fast-flow lesions that may be destructive and are the most difficult-to-treat vascular anomalies. Embolization followed by surgical resection is commonly used; however, complete resection is rarely possible and partial resection often leads to dramatic worsening. Accumulating data implicate abnormal angiogenic activity in the development of AVMs. Thalidomide has been reported as an inhibitor of vascular proliferation. Here, we report a prospective experimental observational study testing the effects of the angiogenesis inhibitor thalidomide on 18 patients with a severely symptomatic AVM that is refractory to conventional therapies. All patients experienced a rapid reduction in pain, cessation of bleeding, and ulcer healing. Cardiac failure resolved in all three affected patients. Reduced vascularity on arteriography was observed in two patients. One AVM appeared to be cured after 19 months of thalidomide and an 8-year follow-up. Eight AVMs were stable after a mean thalidomide cessation of 58 months, and four lesions recurred after 11.5 months. Combined treatment with embolization permitted dose reduction in five patients with clinical improvement. Grade 3 side effects were dose dependent, including asthenia (n = 2) and erythroderma (n = 2). The results suggest that thalidomide is efficacious in the management of chronic pain, bleeding and ulceration of extensive AVMs that are refractory to conventional therapy. Further clinical study is needed to confirm the safety and efficacy of thalidomide treatment in AVM.
Identifiants
pubmed: 39195866
doi: 10.1038/s44161-022-00080-2
pii: 10.1038/s44161-022-00080-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
562-567Subventions
Organisme : Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)
ID : P.C013.20
Organisme : Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)
ID : T.0247.19
Organisme : Koning Boudewijnstichting (King Baudouin Foundation)
ID : 2018-J1810250-211305
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Liu, A. S., Mulliken, J. B., Zurakowski, D., Fishman, S. J. & Greene, A. K. Extracranial arteriovenous malformations: natural progression and recurrence after treatment. Plast. Reconstr. Surg. 125, 1185–1194 (2010).
doi: 10.1097/PRS.0b013e3181d18070
Boon, L. M. & Vikkula, M. in Harper’s Textbook of Pediatric Dermatology 4th edn (eds Irvine, A. D., Hoeger, P. H. & Yan, A. C.) Ch. 118 (Wiley-Blackwell, 2019).
Young, E. J. & Fishman S. J. in Mulliken and Young’s Vascular Anomalies: Hemangiomas and Malformations 2nd edn (eds Mulliken, J. B., Burrows, P. E. & Fishman, S. J.) Ch. 15 (Oxford University Press, 2013).
Boon, L. M. & Vikkula M. in Mulliken and Young’s Vascular Anomalies: Hemangiomas and Malformations 2nd edn (eds Mulliken, J. B., Burrows, P. E. & Fishman, S. J.) Ch. 9 (Oxford University Press, 2013).
Revencu, N. et al. RASA1 mosaic mutations in patients with capillary malformation-arteriovenous malformation. J. Med. Genet. 57, 48–52 (2020).
doi: 10.1136/jmedgenet-2019-106024
Amyere, M. et al. Germline loss-of-function mutations in EPHB4 cause a second form of capillary malformation-arteriovenous malformation (CM-AVM2) deregulating RAS-MAPK signaling. Circulation 136, 1037–1048 (2017).
doi: 10.1161/CIRCULATIONAHA.116.026886
Shovlin, C. L., Hughes, J. M. B., Scott, J., Seidman, C. E. & Seidman, J. G. Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia. Am. J. Hum. Genet. 61, 68–79 (1997).
doi: 10.1086/513906
Shovlin, C. L. Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment. Blood Rev. 24, 203–219 (2010).
doi: 10.1016/j.blre.2010.07.001
Marsh, D. J. et al. Germline PTEN mutations in Cowden syndrome-like families. J. Med. Genet. 35, 881–885 (1998).
doi: 10.1136/jmg.35.11.881
Marsh, D. J. et al. PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum. Mol. Genet. 8, 1461–1472 (1999).
doi: 10.1093/hmg/8.8.1461
Kohout, M. P., Hansen, M., Pribaz, J. J. & Mulliken, J. B. Arteriovenous malformations of the head and neck: natural history and management. Plast. Reconstr. Surg. 102, 643–654 (1998).
doi: 10.1097/00006534-199809010-00006
Soulez, G., Gilbert, P., Giroux, M.-F., Racicot, J.-N. & Dubois, J. Interventional management of arteriovenous malformations. Tech. Vasc. Interv. Radiol. 22, 100633 (2019).
doi: 10.1016/j.tvir.2019.100633
Koshima, I. et al. Free perforator flap for the treatment of defects after resection of huge arteriovenous malformations in the head and neck regions. Ann. Plast. Surg. 51, 194–199 (2003).
doi: 10.1097/01.SAP.0000044706.58478.73
Wong, M. et al. Soft tissue reconstruction and facial reanimation with bilateral latissimus dorsi flaps after extensive resection of head and neck arteriovenous malformation: a case report. Ann. Plast. Surg. 83, 73–77 (2019).
doi: 10.1097/SAP.0000000000001878
Lee, B. B. et al. Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management. Int. Angiol. 32, 9–36 (2013).
pubmed: 23435389
Hammer, F. D., Boon, L. M., Mathurin, P. & Vanwijck, R. R. Ethanol sclerotherapy of venous malformations: evaluation of systemic ethanol contamination. J. Vasc. Interv. Radiol. 12, 595–600 (2001).
doi: 10.1016/S1051-0443(07)61482-1
Burrows, P. E., Mulliken, J. B., Fishman, S. J., Klement, G. L. & Folkman, J. Pharmacological treatment of a diffuse arteriovenous malformation of the upper extremity in a child. J. Craniofac. Surg. 20, 597–602 (2009).
doi: 10.1097/SCS.0b013e3181927f1e
McBride, W. G. Thalidomide embryopathy. Teratology 16, 79–82 (1977).
doi: 10.1002/tera.1420160113
D’Amato, R. J., Loughnan, M. S., Flynn, E. & Folkman, J. Thalidomide is an inhibitor of angiogenesis. Proc. Natl Acad. Sci. USA 91, 4082–4085 (1994).
doi: 10.1073/pnas.91.9.4082
Lebrin, F. et al. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat. Med. 16, 420–428 (2010).
doi: 10.1038/nm.2131
Buscarini, E. et al. Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia. Orphanet J. Rare Dis. 14, 28 (2019).
doi: 10.1186/s13023-018-0982-4
Zhu, W. et al. Thalidomide reduces hemorrhage of brain arteriovenous malformations in a mouse model. Stroke 49, 1232–1240 (2018).
doi: 10.1161/STROKEAHA.117.020356
Fink, E. C. & Ebert, B. L. The novel mechanism of lenalidomide activity. Blood 126, 2366–2369 (2015).
doi: 10.1182/blood-2015-07-567958
Burrows, P. E. Endovascular treatment of slow-flow vascular malformations. Tech. Vasc. Interv. Radiol. 16, 12–21 (2013).
doi: 10.1053/j.tvir.2013.01.003
Mulliken J. B. in Mulliken and Young’s Vascular Anomalies: Hemangiomas and Malformations 2nd edn (eds Mulliken, J. B., Burrows, P. E. & Fishman, S. J.) Ch. 23 (Oxford University Press, 2013).
Park, K. B. et al. Predictive factors for response of peripheral arteriovenous malformations to embolization therapy: analysis of clinical data and imaging findings. J. Vasc. Interv. Radiol. 23, 1478–1486 (2012).
doi: 10.1016/j.jvir.2012.08.012
Pugh, C. W. & Ratcliffe, P. J. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat. Med. 9, 677–684 (2003).
doi: 10.1038/nm0603-677
Carmeliet, P. & Jain, R. K. Angiogenesis in cancer and other diseases. Nature 407, 249–257 (2000).
doi: 10.1038/35025220
Lu, L. et al. Increased endothelial progenitor cells and vasculogenic factors in higher-staged arteriovenous malformations. Plast. Reconstr. Surg. 128, 260e–269e (2011).
doi: 10.1097/PRS.0b013e3182268afd
Komorowski, J. et al. Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells. Life Sci. 78, 2558–2563 (2006).
doi: 10.1016/j.lfs.2005.10.016
Grinspan, D. Significant response of oral aphthosis to thalidomide treatment. J. Am. Acad. Dermatol. 12, 85–90 (1985).
doi: 10.1016/S0190-9622(85)70014-X
Ghobrial, I. M. & Rajkumar, S. V. Management of thalidomide toxicity. J. Support. Oncol. 1, 194–205 (2003).
pubmed: 15334875
pmcid: 3134146
Couto, J. A. et al. Somatic MAP2K1 mutations are associated with extracranial arteriovenous malformation. Am. J. Hum. Genet. 100, 546–554 (2017).
doi: 10.1016/j.ajhg.2017.01.018
Nikolaev, S. I., Fish, J. E. & Radovanovic, I. Somatic activating KRAS mutations in arteriovenous malformations of the brain. N. Engl. J. Med. 378, 1561–1562 (2018).
doi: 10.1056/NEJMoa1709449
Van Damme, A., Seront, E., Dekeuleneer, V., Boon, L. M. & Vikkula, M. New and emerging targeted therapies for vascular malformations. Am. J. Clin. Dermatol. 21, 657–668 (2020).
doi: 10.1007/s40257-020-00528-w
Seront, E., Van Damme, A., Boon, L. M. & Vikkula, M. Rapamycin and treatment of venous malformations. Curr. Opin. Hematol. 26, 185–192 (2019).
doi: 10.1097/MOH.0000000000000498
Gabeff, R. et al. Efficacy and tolerance of sirolimus (rapamycin) for extracranial arteriovenous malformations in children and adults. Acta Derm. Venereol. 99, 1105–1109 (2019).
pubmed: 31386166
Lekwuttikarn, R., Lim, Y. H., Admani, S., Choate, K. A. & Teng, J. M. C. Genotype-guided medical treatment of an arteriovenous malformation in a child. JAMA Dermatol. 155, 256–257 (2019).
doi: 10.1001/jamadermatol.2018.4653
Edwards, E. A. Monitoring arteriovenous malformation response to genotype-targeted therapy. Pediatrics 146, e20193206 (2020).
doi: 10.1542/peds.2019-3206
Wu, J. J., Huang, D. B., Pang, K. R., Hsu, S. & Tyring, S. K. Thalidomide: dermatological indications, mechanisms of action and side-effects. Br. J. Dermatol. 153, 254–273 (2005).
doi: 10.1111/j.1365-2133.2005.06747.x
Lokhorst, M. M. et al. Development of a condition-specific patient-reported outcome measure for measuring symptoms and appearance in vascular malformations: the OVAMA questionnaire. Br. J. Dermatol. 185, 797–803 (2021).
doi: 10.1111/bjd.20429
Gagne, J. J., Thompson, L., O’Keefe, K. & Kesselheim, A. S. Innovative research methods for studying treatments for rare diseases: methodological review. BMJ 349, g6802 (2014).
doi: 10.1136/bmj.g6802