Cryptic brain abscess ‐ do not forget hereditary hemorrhagic teleangiectasia!
Authors: Ivan Krečak, Bojan Gardijan, Jasminka Brkičić, Robert Grubišić‐Čabo, Velka Gverić‐Krečak
Journal: American Journal of Hematology (2021)

Hereditary hemorrhagic teleangiectasia (HHT) or Osler-Weber-Rendu disease is an autosomal dominant genetic disorder of the vasculature which typically manifests in adulthood as recurrent epistaxis, mucocutaneous teleangiectasias/arteriovenous malformations (AVMs) and iron-deficient anemia (IDA).1 Hereditary hemorrhagic teleangiectasia is diagnosed according to Curaçao criteria; (1) spontaneous and recurrent epistaxis, (2) mucocutaneous telangiectasias (lips, oral cavity, face, and fingers), (3) visceral AVMs (brain, liver, pulmonary, spine, etc.), and (4) HHT in a first degree relative.1 Patients with ≥3 or more criteria have “definite” HHT, whereas those with two criteria are labeled as “suspected” HHT.1-3 However, HHT is one of the most underrecognized disorders, possibly due to the fact that nosebleeds and mucocutaneous changes are often quite subtle. In addition, patients can have variable clinical presentations even within affected family members, with some of them, for example, struggling only with gastrointestinal bleedings.1-3 Because of the high frequency of IDA, HHT patients are often managed by hematologists. On the other hand, due to high prevalence of neurological complications, such as cerebral or spinal AVMs, ischemic stroke or brain abscesses,4-6 these patients are also frequently encountered by neurologists and/or neurosurgeons. Here, we present an illustrative case of a patient with an undiagnosed HHT who initially presented with a brain abscess. A 55-year-old female patient was admitted to the neurology department due to headache, confusion, mild left-sided hemiparesis and elevated axillary temperature (38.2°C). Her somatic status was otherwise normal; she was normotensive (120/80 mmHg), eupneic (respiratory rate 12/min), heart murmur and lung crackles were absent, and there was no lymphadenopathy or hepatosplenomegaly present. Meningeal signs were negative. Mucocutaneous changes were not recorded nor was family history obtained at admission. Apart from the subtle and self-limited nosebleed caused by the nasopharyngeal swab for severe acute respiratory distress coronavirus 2 detection (which was negative), the patient reported no bleeding diathesis. There was also no history of head trauma, prior respiratory infections or dental problems. Her white blood cells were slightly elevated (12.1 × 109/L); however, C-reactive protein was normal (1.7 mg/L). She had IDA (hemoglobin 103 g/L, serum iron 3.4 μmol/L). Contrast-enhanced computed tomography (CT) of the brain revealed a ring-enhancing mass in the right parieto-occipital region surrounded by vasogenic edema, consistent with an abscess (Figure 1(A)). Chest x-ray and panoramic radiograph were normal and there were no signs of urinary tract infection. An urgent craniotomy with pus evacuation was performed and the viridans streptococci was isolated from the abscess. No perioperative bleeding complications were recorded. The patient was treated with intravenous ceftriaxone for a total of 6 weeks and the neurological symptoms gradually improved. Interestingly, blood cultures were repeatedly negative and echocardiography ruled out endocarditis and intracardial right-to-left shunts. In good health, the patient was eventually discharged from the hospital. Three weeks later, she was hospitalized at the internal medicine ward due to left femoral vein thrombosis, right-sided pulmonary embolism and severe IDA (hemoglobin 77 g/L), which were successfully treated with dalteparin sodium and parenteral iron. Clinical examination and gastrointestinal endoscopy revealed multiple small teleangiectasias/angiodysplasias of the skin, lips, pharynx (Figure 1(B)–(D)), esophagus, stomach and duodenum. Contrast-enhanced chest and abdominal CT ruled out the presence of pulmonary and/or hepatal AVMs. The patient then admitted she had recurrent self-limited epistaxis and chronic IDA from childhood. Her deceased mother also had IDA and recurrent epistaxis, whereas her uncle was diagnosed with HHT and passed away several years ago due to ischemic stroke. Thus, she fulfilled the diagnostic criteria for HHT.1-3 Interestingly, even though both the patient and her mother had recurrent epistaxis and IDA from childhood, HHT was not timely recognized, possibly due to subtle mucocutaneous changes and self-limited nosebleeds which were not considered by the patient to have a major impact on her quality of life. Finally, some patients may be aware of the disease presence; however, in the absence of major symptoms they prefer not to have HHT diagnosed, in order to avoid the stigma of being a genetic disorder carrier. These reasons may be more prevalent in younger adults and in smaller communities.7 In approximately one-fourth of brain abscesses, the source of infection cannot be identifed; thus, these cases are classified as “cryptic.”7 Notably, brain abscesses can be found in 1% of HHT patients and are typically caused by peridontal infections and septic emboli to the brain due to transitory bacteremia and right-to-left shunting in pulmonary AVMs.4-6 On the other hand, our case illustrates that, on rare occasions, brain abscesses may occur in HHT regardless of the presence of pulmonary AVMs. In recent years, contrast echocardiography emerged as an extremely sensitive procedure for the detection of pulmonary AVMs; thus, it may reveal pulmonary AVMs not detectable on contrast-enhanced CT scans and guide embolotherapies.8, 9 Therefore, careful clinical and diagnostic evaluation for HHT should be considered for all patients presenting with “cryptic“ brain abscesses, as timely identification of these patients may be important for guiding future therapeutic interventions, that is, dental antibiotic prophylaxis and IDA management.10 Finally, this case stands to raise the awareness about HHT and highlights the importance of good history taking and detailed physical exam when approaching patients suffering from recurrent epistaxis, IDA, AVMs and/or neurological symptoms. The authors declare no conflict of interest. The patient provided consent for this publication. The General Hospital of Šibenik-Knin County, Croatia, does not require ethical approval for reporting individual cases or case series. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions