Steroid-responsive pulmonary nodules in a patient with hemophagocytic lymphohistiocytosis.
Ting C, Kraus C, Marshall D, Parikh S, Woolley R, Gildersleeve R, Harrison M, and Kelly BA. Steroid-responsive pulmonary nodules in a patient with hemophagocytic lymphohistiocytosis. Am J Respir Crit Care Med 2018; 197:A3393.
Am J Respir Crit Care Med
Hemophagocytic lymphohistiocytosis (HLH) is a rare sequela of common viral and bacterial infections. We report a case of a man presenting with multiple pulmonary nodules leading to a diagnosis of HLH. Description: 61 year-old male with a past medical history of hypertension who presented to an outside hospital with a chief complaint of fatigue and generalized weakness of several weeks duration. Workup was notable for oliguric acute kidney injury, pancytopenia, and multiple bilateral pulmonary nodules on computed tomography (CT) of the thorax. Extensive infectious and autoimmune workup was unrevealing except for positive IgG and IgM for Epstein-Barr virus. Renal biopsy demonstrated diffuse glomerulosclerosis. Bone marrow biopsy and flow cytometry was negative for primary hematologic malignancy. Transbronchial biopsy of a pulmonary nodule demonstrated lymphohistiocytic inflammation. Given persistent oliguria the patient was started on intermittent hemodialysis. He was started on empiric steroids with symptomatic improvement and transferred to our institution for further evaluation. Initial lab workup revealed worsening pancytopenia. He was noted to have intermittent high-grade fevers with thorough infectious workup not suggestive of a source. Repeat CT imaging demonstrated splenomegaly and near complete resolution of the previous pulmonary nodules. Given his constellation of high grade fevers, peripheral cytopenias, splenomegaly, and steroid-responsive pulmonary nodules, the decision was made to treat empirically for HLH with etoposide and dexamethasone. Further directed workup was notable for a ferritin level of 2629ng/mL, hypertriglyceridemia, and soluble IL-2 receptor level greater than 30 times the reference range. The patient experienced marked improvement after initiation of therapy with recovery of renal function and improvement in his peripheral cytopenias within one week of initiating therapy. Discussion: Hemophagocytic lymphohistiocytosis is a syndrome of uncontrolled macrophage-mediated cytotoxic inflammation that is most frequently diagnosed in children, but can occur in adults of all ages. Pulmonary involvement is estimated to occur in 40% of cases with severity ranging from asymptomatic pulmonary nodules to acute respiratory distress syndrome. Its acquired forms are most commonly triggered by infections such as Epstein-Barr virus in our patient. Patients often die of multi-organ failure and overwhelming infections secondary to neutropenia, and delays in diagnosis contribute to its high morbidity and mortality. Etoposide and dexamethasone remain the mainstay treatment, though many cases of HLH will ultimately require hematopoietic stem cell transplantation. Conclusion: Pulmonary involvement with steroid responsive nodules in the setting of cytopenias and hyperinflammation in critically ill patients can be an important clue in the diagnosis of HLH.