A 74-year-old woman without relevant medical history presented with intermittent fever for more than one month. She also mentioned body weight loss about 18 kilograms and dry cough in recent half year. She did not travel in recent one year. She was admitted to local hospital and was transferred to our hospital for survey.
On physical examination at admission, her temperature was 37.3 C, heart rate 101 beats/min, respiratory rate 16 breaths/min, and blood pressure 142/54 mmHg. Pulmonary examination revealed accessory muscles use and bilaterally diffuse rales. Abdominal examination showed palpable spleen contour while palpation without muscles guarding or rebounding pain. The rest of the physical examination was unremarkable.
Laboratory examination revealed a total leukocyte count of 19,900 cells per muL and a platelet count of 133,000 per muL. Her alkaline phosphate was 481 U/L, serum total bilirubin 3.2 mg/dL, and lactate dehydrogenase 311 U/L. Her serum transaminases, internal normalized ratio (INR), and the activated partial thromboplastin time (aPTT) were all within normal range on initial presentation. Initial acid-fast stain of sputum, stool, and urine was negative. Chest X-ray showed multiple tiny nodules over bilateral lung field with alveolar infiltration over bilateral upper lobes, suspected as pulmonary tuberculosis with miliary tuberculosis (Figure 1(a)). Computed tomography from local hospital revealed multiple tiny nodules over bilateral lung fields, hepatosplenomegaly, and lymphadenopathy over omentum plus mediastinum, which indicated disseminated tuberculosis (Figures 2(a) and 2(b)).
On the 3rd day of hospitalization, progressive orthopnea developed with paradoxical respiration (Figure 1(b)). Oxyhemoglobin saturation by pulse oximetry (SpO2) was 83% in room air. Emergent intubation was performed, and she was transferred to the respiratory intensive care unit (RICU) for resuscitation. Serial laboratory examination revealed leukocytosis with left shifting, INR > 10 ratio, aPTT > 100 seconds, fibrinogen 137.2 mg/dL, ferritin 980 ng/mL, triglyceride 110 mg/dL, sIL-2 receptor > 5000 pg/mL, and PaO2/FiO2 of arterial blood gas 55.1. Chest X-ray revealed newly developed symmetrically alveolar infiltration over bilateral lung field. Severe septic shock with acute respiratory distress syndrome was diagnosed. HLH was suspected due to splenomegaly, decreased fibrinogen, elevated ferritin, and sIL-2 receptor. Bone marrow biopsy was needed for definite diagnosis but held because her condition was unstable, and her family also hesitated due to high risk. Early goal-directed therapy was initialized with empirical antibiotics of Tazocin. Besides, ventilator setting was lung protective strategy. In addition, serum markers were negative for HIV-1, HIV-2, hepatitis B surface antigen, hepatitis C virus IgG antibody, influenza virus type A antigen, influenza virus type B antigen, IgG and IgM antibodies to cytomegalovirus, and herpes simplex virus. The Epstein-Barr virus (EBV) capsid antigen IgG antibodies were positive while EBV early antigen and nuclear antigen IgG antibodies and EBV IgM antibodies were all negative, indicating prior infection. We did not check EBV DNA from the patient's serum by polymerase chain reaction (PCR). On the 4th day, we arranged bronchoscopy for bronchoalveolar lavage fluid, and the result showed positive acid-fast stain 4+ and no bacteria were found. PCR for DNA of tuberculosis was also positive. We shifted antibiotics to antituberculosis medication of HERZ (isoniazid, ethambutol, rifampin, and pyrazinamide) plus levofloxacin immediately. On the 12th day, definite culture showed Mycobacterium tuberculosis which was sensitive to all antituberculosis medication. Bone marrow aspiration on this day confirmed diagnosis of HLH, and blood smear showed phagocytosis of macrophages without granular formation and negative acid-fast stain. We diagnosed HLH by fulfilling 5 out of 8 criteria of HLH in 2004. On the 31st day, she was extubated and finally she was discharged from our hospital after following for 73 days.