A 36-year-old unemployed, married female, height 163 cm, weight 56 kg, of Han nationality, with a 20-year history of epilepsy presented to Fujian provincial hospital on Dec 17, 2019 with high fever for 15 days, upper abdominal pain, muscle soreness in the limbs for 7 days and shortness of breath for 4 days. Her highest armpit temperature was 41 C, accompanied by sore throat and chills. She had visited Zhongshan hospital affiliated to Xiamen university where she received oseltamivir, imipenem and cilastatin for 4 days due to leukopenia (WBC 1.44 x 109/L) and patchy shadows on lung CT (Figure 1A), and was referred to our hospital due to progressive multiple patchy haze in bilateral lungs (Figure 1B) and dyspnea. She was taking lamotrigine (50 mg/d) and escitalopram (10 mg/d) regularly, and had no seizures in the past 3 years. She had no symptoms of dry cough or night sweats, and was otherwise healthy.
The patient had ARDS, with a respiratory rate (RR) of 36 times per min and pulse oxyhemoglobin saturation (SpO2) of 85% under 10 L/min oxygen supplied by an oxygen storage mask when she was referred to our emergency department. In addition, the patient had a heart rate (HR) of 110 beats per min, non-invasive blood pressure (BP) of 96/60 mmHg, and body temperature of 38.6 C. The patient was referred to the ICU, where she received sedation and invasive mechanical ventilation (VC mode, VT 360 ml, PEEP 10 cmH2O, FiO2 100%) at 10 pm on December 7, 2019.
The patient was fully evaluated after admission to the ICU. On that night, blood gas analysis showed (FiO2 100%): pH of 7.376, PaO2 of 74.4 mmHg, PCO2 of 59.4 mmHg, and oxygenation index (PaO2/FiO2) of 74.4. Blood tests showed that the white blood cell count (WBC), percentage of neutrophils (NE) and lymphocytes (L) were 3.8 x 109/L, 45.1 and 50.7%, respectively. Procalcitonin (PCT) and C-reactive protein (CRP) were 0.25 ng/ml and 24.3 mg/L, respectively. Total bilirubin (Tbil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 80.97 mumol/L, 143 and 296 U/L, respectively. Yellow sclera, medium abdominal distention and liver enlargement were noted on physical examination. Therefore, femoro-femoral veno-venous extra-corporeal membrane oxygenation (V-V ECMO) and prone position were performed to improve oxygenation and lung-protective ventilation at night. The initial treatment parameters of ECMO was pump rotational speed 3,200 rpm, blood flow rate 4.0 L/min, sweep gas flow 2.5 L/min. Methylprednisolone 40 mg q8h and Meropenem 1 g q6h were empirically initiated along with negative fluid balance after taking blood and sputum samples.
The patient's oxygenation improved and blood gas analysis showed (FiO2 30%): pH of 7.47, PaO2 of 138 mmHg, PCO2 of 36 mmHg, and oxygenation index (PaO2/FiO2) of 460. Computed tomography showed multiple patchy shadows and consolidation in the dorsal region of bilateral lungs, as well as moderate pleural effusion (Figures 2A,B), enlarged liver and spleen, and moderate effusion in the abdominal cavity (Figures 2C,D). Therefore, extended prone position and physical vibration were performed on the chest to re-expand the collapsed lung. In addition, we detected numerous self-antibodies, viral antibodies and tumor markers (Table 1). On day 7, the patient's condition improved gradually and ECMO was removed, and she was weaned off the ventilator on the next day. However, fever recurred and the blood test results were as follows: 1.7 x 109/L WBC, 60.7% NE, 32.9% L. Auto-antibodies, viral antibodies and tumor markers were negative (Table 1). So the patient underwent a whole-body PET-CT for infection screening. The results showed multiple nodular hyper-metabolic foci in the liver and lungs, slightly increased metabolism including bone marrow (Figures 3A-C). Subsequently, the patient underwent a contrast-enhanced ultrasound biopsy of the upper border of the right lobe of the liver (Figures 4A,B). Figure 4A shows irregular hyper-enhancement in the arterial phase of the lesion, with a transient abnormal enhancement area (white arrow) in the middle. Figure 4B shows the abnormal enhancement area in the delayed phase with low enhancement in contrast-enhanced ultrasound.
The histopathological examination showed Langhans giant cells and fusion granulomas with caseous necrosis in the liver tissue (Figures 5A,B). Acid-fast staining revealed mycobacterial accumulation in the cytoplasm (Figure 5C). We transferred the patient to Fuzhou Pulmonary Hospital on January 19, 2020, for further diagnosis and treatment according to the requirements and regulations of the local health institution. One week later, the second-generation sequencing results of cerebrospinal fluid specimens indicated M. tuberculosis, the biopsy of the anterior basal segment of the right lower lobe and the posterior segment of the right upper lobe showed granulomatitis with necrosis and acid-fast staining, but PAS staining and Gram staining were negative, and the ascites and bronchoalveolar lavage fluid were also negative. Therefore, a definitive diagnosis of subacute blood disseminated pulmonary tuberculosis, tuberculous meningitis, and hepatic tuberculosis was made. The patient was treated with isoniazid 300 mg/day, ethambutol 800 mg/day, pyrazinamide 1.5 g/day and rifampicin 600 mg/day for 2 months at the Fuzhou Pulmonary Hospital, and discharged with a plan to continue long-term anti-mycobacterial tuberculosis therapy. The patient has fully recovered now.