A 44-year-old female with no known medical history is admitted to the intensive care unit (ICU) with septic shock, presumably from influenza. She is treated with mechanical ventilation, vasopressors, and broad-spectrum antimicrobials including oseltamivir, vancomycin, cefepime, flagyl, and azithromycin. Despite 5 days of treatment, she fails to improve. She has persistent fever to 38.9°C and requires norepinephrine and vasopressin to treat hypotension. Arterial blood gas (ABG) is 7.32/34/98 on FiO2 of 0.5. She is noted to have hepatosplenomegaly, but no rash, asymmetric lower extremity edema, or lymphadenopathy. Laboratory data reveal:
Chest x-ray reveals resolving bilateral patchy opacities and mild pulmonary edema. Point of care cardiac ultrasound shows hyperdynamic biventricular function. Culture data are negative to date.
Which of the following tests would BEST to confirm her diagnosis:A. Ferritin, triglycerides, fibrinogen, soluble IL-2 receptor levels
Correct Answer: A
Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition characterized by excessive immune activation of macrophages and T cells. This results in elevated levels of inflammatory cytokines including interferon gamma and tumor necrosis factor alpha. Etiologies include genetic mutations, infection, inflammatory disease, and malignancy. Genetic mutations are more common in children. Increasingly, there is evidence that HLH induced by infection is underdiagnosed in the ICU.
HLH may be diagnosed with five of the following eight criteria:
Alternatively, diagnosis may be made with a positive genetic testing. HLH remains a difficult diagnosis to make in the critically ill, as many of the symptoms are nonspecific and exist in a variety of inflammatory and infectious conditions including sepsis. HLH should be a part of the differential in patients with persistent fever, hepatosplenomegaly, elevated ferritin, cytopenia (without alternative explanation), and failure to improve with appropriate antimicrobials.
In this case, the patient has failed to improve on broad-spectrum antimicrobials. She has pancytopenia, hepatosplenomegaly, and persistent fever, making HLH a possible diagnosis. The next best test to confirm a diagnosis of HLH is to measure ferritin, triglycerides, fibrinogen, and soluble IL-2 receptor levels. Bone marrow biopsy may also be considered but is more invasive.
Platelet factor 4 is a diagnostic test for HIT type II, caused by antibodymediated destruction of platelets. The confirmatory test is a serotonin release assay. Peripheral smear and flow cytometry are not required to diagnose HLH. ANCA is a laboratory test used for the assessment of vasculitis.