Orthodeoxia without Platypnea in Hereditary Hemorrhagic Telangiectasia
Introduction Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominant hereditary disease presenting as a vascular dysplasia of multiple organs. The prevalence rate in all races suggested in some population studies is 1 in 10,000, and 2 mutations have been identified, occurring in 85% of cases: type 1 is related to a mutation in the endoglin gene (ENG, chromosome 9q34.1), and type 2 is related to a mutation in the activin receptor-like kinase 1 gene (ACVRL 1, ALK1, chromosome 12q31.34), with a mild phenotype and late onset . Potential neurologic complications of HHT are attributed to pulmonary arteriovenous malformations (PAVMs) and include embolic stroke and cerebral abscess. Platypnea-orthodeoxia, defined as dyspnea and hypoxemia when adopting an upright position and resolving during decubitus, has been attributed to PAVMs.
Case Report A 38-year-old male with a previous history of pulmonary coil embolization during adolescence was transferred to our facility with a one-week history of persistent headaches and multiple family histories of HHT, manifested as mucocutaneous telangiectasia, bleeding disorders, and cerebral arteriovenous malformations. Vital signs showed orthostatic tachycardia and severe orthodeoxia; however, platypnea was not described. A physical examination revealed finger clubbing, peripheral cyanosis, and cutaneous telangiectasias.
An arterial blood gas (ABG) analysis reported pH: 7.42, pCO2: 26.1, and PO2: 45.1, and laboratory data exhibited polycythemia. Computed tomography of the chest evidenced hyperexpanded lung fields with increased interstitial markings and diaphragmatic flattening. Coil embolisation devices were observed in both the lower lobes. Additionally, areas of mild upper lobes paraseptal emphysema and multiple dilated vascular channels in both lower lobes were prominent. A magnetic resonance image of the brain showed a cerebral lesion, highly suspicious of cerebral abscess.
Treatment The patient was clinically diagnosed with HHT and a triple antibiotic therapy was initiated. Right parietal craniotomy for excision and drainage of cerebral abscess was performed. Following abscess management, a transthoracic echocardiogram revealed a probable right-to-left shunt on agitated saline test, suggestive of pulmonary origin. PAVMs were closed using Amplatzer Vascular Plugs 4 and Micro Vascular Plug System. A significant decrease in orthodeoxia was achieved. No peripheral cyanosis was noted, and imaging tests after PAVMs closure revealed considerable improvement. The patient was discharged with follow-up tests and was encouraged to contact family members for screening.
Discussion While genetic tests are presently available, the diagnosis of HHT remains clinical and is based on the Curacao criteria which include epistaxis as well as telangiectasia in the lips, oral cavity, fingers, or nose; visceral, pulmonary, hepatic, cerebral, or spinal AVMs; and affected first-degree relative. In patients with HHT, cerebral abscesses arise in the presence of uncontrolled right-to-left shunt, facilitating septic thrombus embolization through PAVMs. Bacteria could easily break through the cerebral or pulmonary capillary blood barrier, resulting in recurrent and severe cerebral abscesses. Platypnea-orthodeoxia has been related to PAVMs due to a right-to-left shunt that strengthens desaturation in the upright position. Orthodeoxia, in this setting, may be related to gravity's effect on the redistribution of pulmonary blood flow to PAVMs located in lung bases (53-70%). Santhirapala, in a prospective 8-year study, evaluated 257 patients with PAVMs attributed to HHT, and 29% demonstrated orthodeoxia; nevertheless, none of them described platypnea. Some hypotheses suggest that compensatory mechanisms such as polycythemia and postural orthostatic tachycardia may be able to maintain sufficient tissue oxygen delivery during orthodeoxia, explaining the absence of acute platypnea. These literature findings correlate completely with the orthodeoxia and compensatory mechanisms observed in our patient. Pulmonary angiography is considered the gold standard diagnosis for screening and precise localization of PAVMs. Vascular plugs are effective devices for occlusion of high-flow abnormal vessels in which traditional devices could be technically challenging to use. Ethanol embolotherapy as well has proved to be curative by a combination of a direct denuding effect on the vascular wall and clumping of damaged erythrocytes and denatured proteins, which result in complete obliteration of the vessel lumen preventing recurrences. PAVMs underline the necessity of immediate closure to prevent cerebral septic embolism and significantly decrease orthodeoxia. Compensatory pathophysiologic mechanisms such as polycythemia and orthostatic tachycardia in patients diagnosed with HHT and PAVMs could decrease the manifestation of platypnea, separating orthodeoxia into a single entity. For this reason, the concept of platypnea-orthodeoxia syndrome needs further revision. Patients presenting with refractory hypoxemia should warn physicians to initially evaluate their oxygen saturation measurements during standing and decubitus position, even though platypnea may not be present.
Keywords Hereditary hemorrhagic telangiectasia, Pulmonary arteriovenous malformations, orthodeoxia