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Regression of Cutaneous and Gastrointestinal Telangiectasia with Sirolimus and Aspirin in a Patient with Hereditary Hemorrhagic Telangiectasia

Vivian C. McAlister, MD
[+] Article and Author Information

From University Hospital, London, Ontario N6A 5A5, Canada.


Potential Financial Conflicts of Interest: None disclosed.


Ann Intern Med. 2006;144(3):226-227. doi:10.7326/0003-4819-144-3-200602070-00030
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Might doxycycline be useful in the treatment of hereditary hemorrhagic telangiectasia ?
Posted on June 17, 2006
Francisco José Fernández-Fernández
Service of Internal Medicine. Hospital Arquitecto Marcide
Conflict of Interest: None Declared

We read with interest the article by Dr. McAlister (1) on regression of cutaneous and gastrointestinal telangiectasia with sirolimus and aspirin, probably through the effects of these drugs on vascular endothelial growth factor (VEGF). This clinical observation opens the door to the investigation of various drugs directed against either VEGF or its receptor in the treatment of complicated hereditary hemorrhagic telangiectasia. However, at present, these agents, like sirolimus, have the disadvantage of their side effects. From a theoretical standpoint, it might be useful to evaluate less toxic drugs with a potential role in the angiogenesis. Doxycycline is thought to inhibit angiogenesis through the inhibition of matrix metalloproteinases, which are needed for the degradation of the extracellular matrix (2,3). This phase is followed by proliferation and migration of endothelial cells. VEGF stimulates expression of matrix metalloproteinases (4), and matrix metalloproteinases can facilitate the availability of tissue-bound VEGF. In a case report, doxycycline appeared to be beneficial in the treatment of a patient with pulmonary capillary hemangiomatosis (5), a process with dysregulated angiogenesis. Perhaps this antibiotic might also be useful in the treatment of hereditary hemorrhagic telangiectasia.

References

1.McAlister VC. Regression of cutaneous and gastrointestinal telangiectasia with sirolimus and aspirin in a patient with hereditary hemorrhagic telangiectasia. Ann Intern Med 2006;144:226-7.

2.Hanemaaijer R, Visser H, Koolwijk P, Sorsa T, Salo T, Golub LM, et al. Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. Adv Dent Res 1998;12:114- 8.

3.Moses MA. The regulation of neovascularization by matrix metalloproteinases and their inhibitors. Stem Cells 1997;15:180-9.

4.Lamoreaux WJ, Fitzgerald ME, Reiner A, Hasty KA, Charles ST. Vascular endothelial growth factor increases release of gelatinase A and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro. Microvasc Res 1998;55:29-42.

5.Ginns LC, Roberts DH, Mark EJ, Brusch JL, Marler JJ. Pulmonary capillary hemangiomatosis with atypical endotheliomatosis: successful antiangiogenic therapy with doxycycline. Chest 2003;124:2017-22.

Conflict of Interest:

None declared

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