Chest
Volume 141, Issue 6, June 2012, Pages 1598-1600
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The Intersection of Genes and Environment: Development of Pulmonary Arterial Hypertension in a Patient With Hereditary Hemorrhagic Telangiectasia and Stimulant Exposure

https://doi.org/10.1378/chest.11-1402Get rights and content

Pulmonary arterial hypertension (PAH) is a rare complication of hereditary hemorrhagic telangiectasia (HHT). The triggers that promote the development of PAH in HHT remain poorly understood. We present the case of a 45-year-old woman with decompensated right-sided heart failure secondary to newly diagnosed PAH. The clinical diagnosis of HHT was confirmed on the basis of recurrent spontaneous epistaxis, multiple typical mucocutaneous telangiectasia, and the presence of pulmonary arteriovenous malformation. There was also a suggestive family history. The patient was discovered to have active and extensive stimulant abuse in addition to HHT. We concluded that there may be a temporal relationship between exposure to stimulants and development of PAH in a host with underlying gene mutation. This case highlights the paradigm of PAH development after environmental exposure in a genetically susceptible host.

Section snippets

Case Report

A 45-year-old white woman presented with a 1-year history of progressive dyspnea and reduced exercise tolerance. She reported worsening lower-extremity swelling, abdominal distention, and a 20-pound weight gain, which improved after aggressive diuresis. She was referred to the Stanford PH clinic for further evaluation.

Her medical history was significant for three episodes of cryptic GI bleeding requiring blood transfusion and for spontaneous nose bleeds. Family history was noncontributory,

Discussion

HHT is a clinical diagnosis consisting of epistaxis, mucocutaneous telangiectases, visceral AVMs, and a family history of HHT.2 Genetic mutations may impact PAH progression and prognosis. In HHT associated with PAH, carriers of ACVRL1 mutations present at a younger age and have worse outcome than patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations.3 Also, compared with ACVRL1, endoglin mutations are less frequent and may confer a lower risk of PAH development.3

We believe

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Zamanian has served as a consultant to United Therapeutics Corporation; Gilead; Actelion Pharmaceuticals, Inc; and Ikaria, Inc. Drs de Jesus Perez, Ayala, Kudelko, and Haddad have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of

References (4)

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    Our results agreed with previous studies showing that RV pressure is unaffected by MA in rats and mice (Chen et al., 2017a; Liu et al., 2013; Wang et al., 2013). While MA is among risk factors for pulmonary hypertension, it may act as a “second hit” to an underlying genetic (i.e. mutations) or non-genetic (i.e. Human Immunodeficiency Virus (HIV)) conditions (Ayala et al., 2012; Orcholski et al., 2017, 2018). Our understanding of the mechanisms behind MA-associated hypertension is still lacking.

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    Six studies were excluded because they were pediatric cases [17–22]. Eight studies were excluded because they did not report individual hemodynamic parameters, side effects, or follow-up intervals necessary to evaluate the effect of pulmonary vasodilator therapy on the subject/s reported [13,23–29]. One study was excluded because the subject developed PAH following dexfenfluramine use [30].

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Funding/Support: Dr Zamanian has received support from United Therapeutics Corporation; Actelion Pharmaceuticals, Inc; and Gilead. Dr de Jesus Perez receives grant support from the National Institutes of Health [Grant NIH K12 HL089989-04].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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