Hypoxemia without Respiratory Distress: Hereditary Hemorrhagic Telangiectasia in a Child

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is an underrecognized genetic disorder of vascular development in pediatric patients. Its presentation can range from mild cutaneous findings to life-threatening hemorrhage from arteriovenous malformations. Clinical diagnosis can be challenging in the pediatric population as disease manifestations evolve over time and may be difficult to identify in younger patients. This case highlights how nonspecific symptoms and signs in the preanesthesia period can be misleading, potentially placing a patient with unrecognized HHT at risk for significant morbidity and mortality.

Introduction

Hereditary hemorrhagic telangiectasia (HHT) is an underrecognized genetic disorder of vascular development. ^{1 2} It is characterized by arteriovenous malformations (AVMs) that can be small, thin-walled, and close to the skin surface or gastrointestinal mucosa or much larger, within the brain, liver, and lungs. ³ The clinical presentation can range from mild cutaneous findings and recurrent nosebleeds to migraines, cyanosis, seizures, brain abscesses, and life-threatening hemorrhage. ^{4 5 6} HHT is classically diagnosed by meeting at least three of the four Curacao criteria: recurrent epistaxis, telangiectasias of the skin, visceral organs AVMs, and a positive family history. ⁴ Because of its unique pathophysiology, when an asymptomatic patient with HHT undergoes a surgical procedure with anesthesia, care is taken to reduce the risk of air embolization, rupture of possible AVMs, endocarditis, and death during the procedure. ^{7 8 9 10}

Although inheritance is autosomal dominant, first-degree relatives are often unaware of their diagnosis because the clinical findings can be subtle and seen in the general population. ² This may be especially true in pediatric patients, as the development of clinical signs progresses with age, and the disease may not have manifested itself. ¹¹ If a pediatric patient with unrecognized HHT undergoes anesthesia for a surgical procedure, this may place the patient at increased risk of HHT-associated complications.

The following case report describes an insidious presentation of pulmonary AVM during anesthesia in a pediatric patient subsequently discovered to have HHT.

Case Description

A 5-year-old African American girl patient with a reported previous history of hypoxemia attributed to viral pneumonitis and a family history of thromboembolism (but no reported history of epistaxis nor cutaneous telangiectasias) presented to an outside hospital surgical suite for a scheduled dental procedure (tooth extraction) under general anesthesia. To our knowledge, and upon thorough review of available outside medical records, other than a history and physical examination, no additional preoperative evaluation was performed including chest radiograph or laboratory work. She was induced with sevoflurane and propofol; shortly thereafter, the patient acutely desaturated to 70%. Respiratory interventions included oxygen, bronchodilator, and corticosteroid administration, which did not improve her condition. The procedure was aborted and after emergence, the patient remained desaturated to 90 to 93% range and was referred to our institution.

Upon admission to the pediatric intensive care unit, the patient was in no acute distress and hemodynamically stable. Her respiratory rate was 35 breaths/min, heart rate was 122 beats/min, and blood pressure was 102/80 mm Hg. Her initial pulse oximetry reading was 85% on room air. She was placed on 20 L/min humidified high-flow nasal cannula which increased her oxygen saturation level to 93% on 100% fractional inspired oxygen. The patient did not have any complaints. Her review of systems was positive for “migraine” headaches and her mother denied that the patient had any fever, rhinorrhea, and cough. The patient denied chest pain and respiratory distress.

On physical examination, her oral cavity was without erythema or ulcerations. Her lung fields were clear to auscultation bilaterally with a mild end-expiratory wheeze noted within the left lower lobe. She had S1, S2 heart sounds, did not have any murmurs, or jugular venous distension on cardiac examination. Her abdominal exam was soft, nontender, nondistended. She had no rashes, her capillary refill was less than 2 seconds, and digital clubbing was present.

Her chest radiography showed an ill-defined opacity in the left upper lingula ( Fig. 1 ). An arterial blood gas was obtained, which had a pH of 7.398, PCO ₂ of 29 mm Hg, PaO ₂ of 51 mm Hg, and a bicarbonate level of 17.7 mmol/L with a base deficit of −5.5. Her complete blood count revealed a leukocytosis of 12.9 K/μL, a hemoglobin of 17.1 g/dL, hematocrit of 48.5%, and a platelet count of 304 K/μL. Basic metabolic panel and a respiratory viral panel were unremarkable. An electrocardiogram was performed, which showed normal sinus rhythm with no evidence of ventricular strain.

Fig. 1.

Plain radiography of the chest that shows an ill-defined opacity (red arrow) of the left lower lung.

During her hospitalization, her respiratory support was unable to be weaned. Further history revealed a family history of an ill-defined venous thromboembolism to the pulmonary vasculature in the mother, maternal grandmother, and maternal aunt subsequently realized to be secondary to HHT. Upon further discussion with the patient's mother, though some of the affected members were told they had this disease, the family never received genetic counseling, did not appreciate the hereditary nature of the disease, and were never seen at an HHT center. An echocardiogram without saline agitation was normal. A chest computed tomography angiogram (CTA) showed a large left upper lobe lingular pulmonary AVM ( Fig. 2A , 2B ) and a brain CTA revealed an AVM in the right temporooccipital region.

Fig. 2.

Axial ( A ) and coronal ( B ) computed tomography images demonstrating large left upper lobe lingular arteriovenous malformation arising from the left upper lobar pulmonary arteries and draining into the left superior pulmonary vein, both of which are prominent.

An interdisciplinary panel of hematology, cardiology, pulmonology, and neuroradiology agreed that the patient met criteria for HHT clinically, thus genetic evaluation did not initially take place prior to intervention on her AVMs. She underwent coil embolization of three separate AVMs in the pulmonary vasculature. During general anesthesia, a bubble trap was used to prevent embolus, her tidal volumes were maintained between 6 and 7 mL/kg, and the positive end-expiratory pressure was set at 2 cm H ₂ O during the procedure. Cefazolin was administered for antibacterial prophylaxis. After coil embolization, her hypoxemia immediately resolved. In the setting of ongoing headaches, endovascular treatment of the cerebral AVM was completed later in her hospital course. Due to subsequent mild brain edema surrounding the coiled lesion, she was placed on a prolonged steroid taper and on levetiracetam for seizure prophylaxis. Upon follow-up in the ensuing months, her hypoxemia and headaches remained resolved. She ultimately was arranged to follow up with an HHT center.

Discussion

HHT (Rendu–Osler–Weber's syndrome) is an autosomal dominant genetic disorder of vascular development with an age reduced penetrance and variable expressivity. ^{3 4 5} The defect typically occurs in either the ENG (HHT 1) or ALK1 / ACVRL1 (HHT2) genes 85% of the time. ^{6 12} The vascular malformations appear during childhood, develop gradually as the child ages, and is associated with significant morbidity. ^{11 13} Epidemiologic studies of this condition suggest that it occurs with a prevalence rate of up to 1 in 8,000. ¹⁴

Determining this diagnosis in pediatric patients requires the presence of a first-degree relative with HHT and the associated clinical findings. ^{15 16} Clinical findings are related to the presence of telangiectasias and AVMs that affect various organ systems. ^{12 16} In children, the classic clinical characteristics are seen in the following incidences: mucocutaneous telangiectasias (79%), nasal telangiectasias (68%), epistaxis (63%), pulmonary AVMs (53%), hepatic AVMs (47%), and cerebral involvement (12%). ¹² Pulmonary AVMs typically are seen after puberty, but can occur during childhood, ¹⁷ and in ENG and ALK1 genotypes, can be seen 82 and 38% of the time, respectively. ¹² As these clinical findings may be subtle in pediatric patients, the diagnosis of HHT is challenging, potentially placing individuals at risk for avoidable complications. ^{11 18}

In this case, it was unrecognized that the patient had HHT and underwent general anesthesia despite having a family history of HHT and presence of digital clubbing on physical examination. In addition, pulmonary AVMs were present in this case of HHT, which requires special anesthetic considerations to avoid morbidity. If it was clearly known that the patient had a family history of HHT, increased clinical suspicion of this disease may have occurred. This highlights the importance of a thorough preanesthesia history and physical examination and emphasizes the importance of medical as well as genetic counseling for any family members who were diagnosed with HHT. While screening and providing genetic testing to future asymptomatic children is controversial, any patient diagnosed with HHT should at the very least understand the clinical implications, natural course of the disease, and the importance of screening if the patient's current and future children show symptoms. ¹⁶ This is especially crucial when the child may undergo invasive procedures such as anesthesia that may place the child at higher risk of complications.

During the preanesthesia period, if the history and physical examination suggest the presence of HHT (with the possibility of pulmonary or cerebral AVMs), procedure delay with expert consultation to allow for further evaluation should be considered. ¹⁰ If delay can occur, molecular genetic examination, especially in young individuals of family members with HHT, searching for the typically affected genes could be useful if the diagnosis cannot be made. ¹² Some authors also suggest pulmonary assessment with contrast echocardiography or computed tomography of the chest should take place for monitoring of silent AVMs, especially prior to invasive procedures. ^{12 16 17} If the patient must undergo anesthesia, steps should be taken to avoid the introduction of air emboli in the intravenous line due as pulmonary AVMs may have right-to-left shunting that can result in stroke. ^{8 10 19} For example, a bubble trap was utilized in this patient when she underwent anesthesia during her hospitalization at our institution. ²⁰ The anesthetic selected should avoid elevated blood pressures as it may result in AVM rupture. ¹⁰ Nasogastric tube placement should be performed under extreme caution as telangiectasias within the nasal mucosa may result in bleeding. ^{8 10} Hypoxemia is a possibility during positive pressure ventilation as increased intrathoracic pressure may increase right-to-left shunting. ²¹ If the patient requires positive pressure ventilation, decreasing mean airway pressure as much as possible and positional changes may assist this. ^{22 23} Endobronchial hemorrhage is a rare but possible complication due to pulmonary AVM rupture. ^{24 25} This can be managed with transcatheter embolization or if not immediately available, pulmonary isolation with a double-lumen endotracheal tube or bronchial blockade. ^{26 27} Finally, a right-to-left shunt through pulmonary AVMs may place the patient at risk of endocarditis and/or brain abscesses, thus antimicrobial prophylaxis should be considered. ⁸ Even after intervention on AVMs, silent ones can persist or develop overtime, thus, we suggest preoperative assessments for right-to-left shunts should take place and the aforementioned precautions should be utilized. ^{16 20}

Conclusion

In conclusion, patients with HHT have special anesthetic considerations. If this diagnosis is unrecognized, the risk of complications may be higher. In this case report, the importance of an accurate history and appropriate investigations is highlighted to minimize the risks associated with HHT and to ensure the delivery of high quality care.