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Case report study of thalidomide therapy in 18 patients with severe arteriovenous malformations

Nature Cardiovascular Research volume 1, pages 562–567 (2022)Cite this article

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Abstract

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.

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Fig. 1: Clinical aspects of AVMs.
Fig. 2: Patient 5 with AVM of the right upper eyelid.
Fig. 3: Patient 12 with AVM of the hand.

Data availability

All data generated and analyzed during this study are included in this published article.

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Acknowledgements

All authors but one (A.D.) are members of the VASCA Working Group of VASCERN, project no. 769036. We are grateful to all of the patients for their invaluable participation. This work is part of the thesis project of J.C., who was supported by a Fond de la Recherche Clinique (FRC) des Cliniques universitaires Saint-Luc. These studies were financially supported by Fonds de la Recherche Scientifique (FNRS) grants T.0247.19 (to M.V.) and P.C013.20 (to L.M.B.), and the Fund Generet managed by the King Baudouin Foundation (grant 2018-J1810250-211305) (to M.V.). The authors are grateful to J.B. Mulliken, P.E. Burrows and J. Dubois for their expert review of and suggestions for the manuscript; the nurse coordinator, O. Debue, for his excellent assistance in patient follow-up; and L. Niculescu and L. Huybrechts for their skilled secretarial help.

Author information

Author notes

  1. Deceased: Anne Jeanjean.

Authors and Affiliations

  1. Division of Plastic Surgery, Center for Vascular Anomalies, Cliniques universitaires Saint-Luc, UCLouvain, VASCERN VASCA European Reference Centre, Brussels, Belgium

    Laurence M. Boon, Valérie Dekeuleneer, Julien Coulie, Anne-Christine Bataille & Miikka Vikkula

  2. Human Molecular Genetics, de Duve Institute, UCLouvain, Brussels, Belgium

    Laurence M. Boon & Miikka Vikkula

  3. Division of Dermatology, Center for Vascular Anomalies, Cliniques universitaires Saint-Luc, UCLouvain, VASCERN VASCA European Reference Centre, Brussels, Belgium

    Liliane Marot & Anne-Christine Bataille

  4. Division of Vascular and Interventional Radiology, Center for Vascular Anomalies, Cliniques universitaires Saint-Luc, UCLouvain, VASCERN VASCA European Reference Centre, Brussels, Belgium

    Frank Hammer

  5. Division of Pediatric Radiology, Center for Vascular Anomalies, Cliniques universitaires Saint-Luc, UCLouvain, VASCERN VASCA European Reference Centre, Brussels, Belgium

    Philippe Clapuyt

  6. Department of Neurology, Center for Vascular Anomalies, Cliniques universitaires Saint-Luc, UCLouvain, VASCERN VASCA European Reference Centre, Brussels, Belgium

    Anne Jeanjean

  7. Department of Dermatology, Université de Caen Basse Normandie, CHU Caen, Caen, France

    Anne Dompmartin

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Contributions

L.M.B. and M.V. conceived and designed the study; L.M.B., J.C., V.D., L.M., A.-C.B. and A.J. followed the patients; F.H. and P.C. analyzed the radiological data; and A.D. L.M.B., J.C., V.D., L.M. and A.-C.B. analyzed the data. All authors contributed to writing the paper and reviewed the final manuscript.

Corresponding author

Correspondence to Laurence M. Boon.

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Nature Cardiovascular Research thanks Joyce M. C. Teng and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Extended data

Extended Data Table 1 Characteristics of patients before and after high-dose thalidomide medication
Full size table
Extended Data Table 2 Characteristics of patients before and after low-dose thalidomide medication
Full size table

Extended Data Fig. 1

Patient #1 with dramatic progressive aggravation of her AVM due to several partial surgical resection and embolization. (a) stage I AVM involving her upper lip at the age of 20. (b) stage IV AVM at the age of 50 now involving her entire central face and causing labial and palatal ulceration. (c) arteriography showing the extensiveness of her AVM. (D) 1 month after thalidomide initiation (d,e) showing cessation of mucosal bleeding of the lip, cessation of drooling and complete healing of her palate.

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Boon, L.M., Dekeuleneer, V., Coulie, J. et al. Case report study of thalidomide therapy in 18 patients with severe arteriovenous malformations. Nat Cardiovasc Res 1, 562–567 (2022). https://doi.org/10.1038/s44161-022-00080-2

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