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Aortic aneurysm: Fluoroquinolones, genetic counseling

To the Editor: We read with interest the article by Cikach et al on thoracic aortic aneurysm.1 For medical management of this condition, the authors emphasized controlling blood pressure and heart rate and also avoiding isometric exercises and heavy lifting. In addition to their recommendations, we believe there is plausible evidence to advise caution if fluoroquinolone antibiotics are used in this setting.

Three large population-based studies, from Canada,2 Taiwan,3 and Sweden,4 collectively demonstrated a significant 2-fold increase in the incidence of aortic aneurysm and dissection presenting within 60 days of fluoroquinolone use compared with other antibiotic exposure. Moreover, a longer duration of fluoroquinolone use was associated with a significantly higher incidence of aortic aneurysm and dissection.3

Mechanistically, fluoroquinolones have been shown to up-regulate production of several matrix metalloproteinases, including metalloproteinase 2, leading to degradation of type I collagen.2,5 Type I and type III are the dominant collagens in the aortic wall, and collagen degradation is implicated in aortic aneurysm formation and expansion.

Fluoroquinolones are widely prescribed in both outpatient and inpatient settings and are sometimes used for long durations in the geriatric population.2 It is possible that these drugs have a propensity to increase aortic aneurysm expansion and dissection in older patients who already have aortic aneurysm. Accordingly, this might make the risk-benefit ratio unfavorable for using these drugs in these situations, and other antibiotics should be used, if indicated.

Furthermore, if fluoroquinolones are used in patients with aortic aneurysm, perhaps imaging studies of the aneurysm should be done more frequently than once a year to detect accelerated aneurysm growth. Finally, physicians should be aware of the possibility of increased aortic aneurysm expansion and dissection with fluoroquinolone use.

References
  1. Cikach F, Desai MY, Roselli EE, Kalahasti V. Thoracic aortic aneurysm: how to counsel, when to refer. Cleve Clin J Med 2018; 85(6):481–492. doi:10.3949/ccjm.85a.17039
  2. Daneman N, Lu H, Redelmeier DA. Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study. BMJ Open 2015; 5:e010077. doi:10.1136/bmjopen-2015-010077
  3. Lee C-C, Lee MG, Chen Y-S, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med 2015; 175:1839–1847. doi:10.1001/jamainternmed.2015.5389
  4. Pasternak B, Inghammar M, Svanström H. Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. BMJ Open 2018; 360:k678. doi:10.1136/bmj.k678
  5. Tsai W-C, Hsu C-C, Chen CPC, et al. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J Orthop Res 2011; 29(1):67–73. doi:10.1002/jor.21196
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Mark R. Goldstein, MD, FACP
NCH Physician Group, Center for Healthy Living, Naples, FL

Luca Mascitelli, MD
Comando Brigata Alpina “Julia”/Multinational Land Force, Medical Service, Udine, Italy

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thoracic aortic aneurysm, fluoroquinolones, metalloproteinase 2, collagen, Mark Goldstein, Luca Mascitelli
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Mark R. Goldstein, MD, FACP
NCH Physician Group, Center for Healthy Living, Naples, FL

Luca Mascitelli, MD
Comando Brigata Alpina “Julia”/Multinational Land Force, Medical Service, Udine, Italy

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Mark R. Goldstein, MD, FACP
NCH Physician Group, Center for Healthy Living, Naples, FL

Luca Mascitelli, MD
Comando Brigata Alpina “Julia”/Multinational Land Force, Medical Service, Udine, Italy

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To the Editor: We read with interest the article by Cikach et al on thoracic aortic aneurysm.1 For medical management of this condition, the authors emphasized controlling blood pressure and heart rate and also avoiding isometric exercises and heavy lifting. In addition to their recommendations, we believe there is plausible evidence to advise caution if fluoroquinolone antibiotics are used in this setting.

Three large population-based studies, from Canada,2 Taiwan,3 and Sweden,4 collectively demonstrated a significant 2-fold increase in the incidence of aortic aneurysm and dissection presenting within 60 days of fluoroquinolone use compared with other antibiotic exposure. Moreover, a longer duration of fluoroquinolone use was associated with a significantly higher incidence of aortic aneurysm and dissection.3

Mechanistically, fluoroquinolones have been shown to up-regulate production of several matrix metalloproteinases, including metalloproteinase 2, leading to degradation of type I collagen.2,5 Type I and type III are the dominant collagens in the aortic wall, and collagen degradation is implicated in aortic aneurysm formation and expansion.

Fluoroquinolones are widely prescribed in both outpatient and inpatient settings and are sometimes used for long durations in the geriatric population.2 It is possible that these drugs have a propensity to increase aortic aneurysm expansion and dissection in older patients who already have aortic aneurysm. Accordingly, this might make the risk-benefit ratio unfavorable for using these drugs in these situations, and other antibiotics should be used, if indicated.

Furthermore, if fluoroquinolones are used in patients with aortic aneurysm, perhaps imaging studies of the aneurysm should be done more frequently than once a year to detect accelerated aneurysm growth. Finally, physicians should be aware of the possibility of increased aortic aneurysm expansion and dissection with fluoroquinolone use.

To the Editor: We read with interest the article by Cikach et al on thoracic aortic aneurysm.1 For medical management of this condition, the authors emphasized controlling blood pressure and heart rate and also avoiding isometric exercises and heavy lifting. In addition to their recommendations, we believe there is plausible evidence to advise caution if fluoroquinolone antibiotics are used in this setting.

Three large population-based studies, from Canada,2 Taiwan,3 and Sweden,4 collectively demonstrated a significant 2-fold increase in the incidence of aortic aneurysm and dissection presenting within 60 days of fluoroquinolone use compared with other antibiotic exposure. Moreover, a longer duration of fluoroquinolone use was associated with a significantly higher incidence of aortic aneurysm and dissection.3

Mechanistically, fluoroquinolones have been shown to up-regulate production of several matrix metalloproteinases, including metalloproteinase 2, leading to degradation of type I collagen.2,5 Type I and type III are the dominant collagens in the aortic wall, and collagen degradation is implicated in aortic aneurysm formation and expansion.

Fluoroquinolones are widely prescribed in both outpatient and inpatient settings and are sometimes used for long durations in the geriatric population.2 It is possible that these drugs have a propensity to increase aortic aneurysm expansion and dissection in older patients who already have aortic aneurysm. Accordingly, this might make the risk-benefit ratio unfavorable for using these drugs in these situations, and other antibiotics should be used, if indicated.

Furthermore, if fluoroquinolones are used in patients with aortic aneurysm, perhaps imaging studies of the aneurysm should be done more frequently than once a year to detect accelerated aneurysm growth. Finally, physicians should be aware of the possibility of increased aortic aneurysm expansion and dissection with fluoroquinolone use.

References
  1. Cikach F, Desai MY, Roselli EE, Kalahasti V. Thoracic aortic aneurysm: how to counsel, when to refer. Cleve Clin J Med 2018; 85(6):481–492. doi:10.3949/ccjm.85a.17039
  2. Daneman N, Lu H, Redelmeier DA. Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study. BMJ Open 2015; 5:e010077. doi:10.1136/bmjopen-2015-010077
  3. Lee C-C, Lee MG, Chen Y-S, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med 2015; 175:1839–1847. doi:10.1001/jamainternmed.2015.5389
  4. Pasternak B, Inghammar M, Svanström H. Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. BMJ Open 2018; 360:k678. doi:10.1136/bmj.k678
  5. Tsai W-C, Hsu C-C, Chen CPC, et al. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J Orthop Res 2011; 29(1):67–73. doi:10.1002/jor.21196
References
  1. Cikach F, Desai MY, Roselli EE, Kalahasti V. Thoracic aortic aneurysm: how to counsel, when to refer. Cleve Clin J Med 2018; 85(6):481–492. doi:10.3949/ccjm.85a.17039
  2. Daneman N, Lu H, Redelmeier DA. Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study. BMJ Open 2015; 5:e010077. doi:10.1136/bmjopen-2015-010077
  3. Lee C-C, Lee MG, Chen Y-S, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med 2015; 175:1839–1847. doi:10.1001/jamainternmed.2015.5389
  4. Pasternak B, Inghammar M, Svanström H. Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. BMJ Open 2018; 360:k678. doi:10.1136/bmj.k678
  5. Tsai W-C, Hsu C-C, Chen CPC, et al. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J Orthop Res 2011; 29(1):67–73. doi:10.1002/jor.21196
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Cleveland Clinic Journal of Medicine - 85(9)
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Aortic aneurysm: Fluoroquinolones, genetic counseling
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thoracic aortic aneurysm, fluoroquinolones, metalloproteinase 2, collagen, Mark Goldstein, Luca Mascitelli
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