A 10-year-old Chinese boy was transferred to the pediatric intensive care unit (PICU) of our hospital with AHF, PH, and hypertension. Ten months prior to this admission, he presented to the local healthcare providers with "chest pain," increased erythrocyte sedimentation rate (ESR: 39-52 mm/h), and C-reactive protein (CRP: 22.6-29.1 mg/L), and chest computed tomography (CT) scan demonstrated calcified left hilar lymph nodes. Chest pain improved after antibiotic therapy for 1 week (no detail regarding the medications).
On this admission, he returned to the local hospital with a 2-week history of cough, chest tightness, and shortness of breath. He was diagnosed with AHF, PH, and hypertension and transferred to our hospital. The patient had received routine vaccinations including Bacillus Calmette-Guerin (BCG). His growth and development were normal.
Physical examination on admission showed the following: heart rate 120/min, respiratory rate 26/min, and blood pressure (BP) 159/103 mmHg in his right arm, 124/93 mmHg in his left arm, 87/55 mmHg in his right leg, and 121/106 mmHg in the left leg. Distended jugular veins and weak left radial artery pulsation were found. Class IV systolic murmur in the precordial region was heard. There was no enlargement of liver and spleen. Laboratory evaluations revealed increased N-terminal pro-brain natriuretic peptide (NT-proBNP: 19052 pg/mL), CRP (8.45 mg/L), ESR (32 mm/h), serum creatinine (86 mumol/L), and urea (15.68 mmol/L) with decreased blood potassium (2.9 mmol/L), sodium (128 mmo1/L), and hemoglobin (84 g/L). The purified protein derivative (PPD) skin test and interferon-gamma release assay (IGRA) result were strongly positive. However, all microbiological analyses including TB culture and pathogenic microorganism sequencing were negative. Serum immunoglobulin and complements (C3 and C4) were normal. Antinuclear antibody (ANA) and antineutrophil cytoplasmic antibody (ANCA) were negative. Echocardiography revealed reduced left ventricular ejection fraction (LVEF: 40%) with left heart dilatation, PH (75 mmHg), and moderate mitral insufficiency. Chest x-ray showed significant cardiomegaly (Figure 1A). Chest CT showed calcified left hilar lymph nodes, enlarged mediastinal lymph nodes, patchy and slightly high-density shadows in both lungs, and a small amount of bilateral pleural effusion. CT angiography (CTA) showed occlusion of the proximal left subclavian artery and stenosis of the lumen of the descending and upper abdominal aorta with extensive thickening of the vascular wall (Figures 1B,C). Whole exome sequencing did not indicate any abnormal mutations. Based on the radiological findings and laboratory examinations, he was diagnosed as TB-associated TA complicated with AHF and PH.
The boy was initially treated with bed rest, oxygen inhalation, milrinone, diuretics, captopril, bosentan, and antibiotics including anti-TB medications. He developed hemoptysis on day 8. Intravenous methylprednisolone pulse (IVMP) therapy (10 mg/kg/day) was given on days 22-24, followed by 1 mg/kg of daily oral prednisone. Metoprolol was added on day 28. However, subxiphoid and right upper abdominal pain was recurrent during hospitalization and worsened on day 29. AHF, PH, BP, heart rate, cardiac function, chest tightness, and shortness of breath did not improve notably. On day 32, intravenous tocilizumab (TCZ) was initiated at a dose of 8 mg/kg following the 0-, 2-, and 4-week regimen (Figure 2). Coughing and hemoptysis resolved. Chest tightness, shortness of breath, abdominal pain, BP (115/82 mmHg on the right arm) and heart rate (102 beats/min), LVEF (45%), and PH (47 mmHg) were slightly improved after three doses of TCZ. He was discharged on day 60.
The child was re-admitted on day 66 due to worsening HF with lower LVEF (30%), higher PH (70 mmHg), and normal CRP and ESR. During this admission, his BP fluctuated from 175/105-123/74 mmHg, and hemoptysis recurred. Repeated CTA on day 77 and day 92 showed complete occlusion of the descending aorta with large thrombus (76 mm in length) (Figures 1D,E) and extensive collateral circulation (twisted and dilated right intrathoracic artery, numerous open collateral vessels in the neck and upper mediastinum) (Figures 1F,G). In addition to the same medications as the first admission, subcutaneous low-molecular-weight heparin was started on day 78. IVMP therapy (10 mg/kg/day) was administered again on days 93-95.
The patient developed seizure and loss of consciousness while afebrile on day 99. Seizure was controlled with intravenous diazepam. Cranial magnetic resonance angiography (MRA) showed narrowed lumen of the anterior, middle, and posterior cerebral arteries. Brain MR imaging revealed strong signals on T2 fluid-attenuation inversion recovery (FLAIR) images of the cortical and subcortical areas of both the occipital lobes and right frontal-parietal lobe (Figure 1H). After failing to respond to another two doses of TCZ, intravenous infliximab was given for two doses on day 98 and day 112, and IVMP therapy (10 mg/kg/day) again on days 114-116. However, there were still no signs of improvement, and his renal function worsened. Given the complete occlusion of the aorta with large thrombus and aggravating life-threatening HF without response to any medication, balloon angioplasty was performed and catheter-directed thrombolysis with urokinase and heparin was started on day 127. Four days after surgery, the patient worsened suddenly with increased shortness of breath, decreased heart rate, and dropping of oxygen saturation to 60%. The patient died on day 133 (Figure 2).