Pediatric Blood & Cancer | 2021
Hemophagocytosis in bone marrow aspirates in multisystem inflammatory syndrome in children
Abstract
To the Editor: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects people of all ages. Although it is known that children have a milder course of illness compared to adults, it has been observed that a severe newly described clinical picture called multisystem inflammatory syndrome in children (MIS-C) has been reported.1–6 Herein we describe unique cases of MIS-C with hemophagocytosis on bone marrow aspirates. CASE 1: A 4-year-old boy referred to our hospital with the diagnosis of Kawasaki disease. He had no known exposure to SARS-CoV-2. He was hospitalized with the complaint of fever and severe abdominal pain. His clinical characteristics and laboratory findings are given in Supplemental Tables S1 and S2 and Figure S1. His nasopharyngeal swab SARS-CoV-2 RT-PCR test was negative twice on first and fourth day of fever. Intravenous immunoglobulin (ivIg) (2 g/kg/day) and acetylsalicylic acid were started. He had headache and nuchal rigidity. Lumbar puncture was performed. Cerebrospinal fluid (CSF) findings were normal. Although he had ivIg treatment, he still had fever and abdominal pain, bone marrow aspiration (BMA) had been applied to exclude hematologic malignancy. On admission, his SARS-CoV-2 IgG level was high (8.9). His clinic was compatible with MIS-C, methylprednisolone (2 mg/kg/day) and anakinra (4 mg/kg/day) were administered. He was started on antibiotics (vancomycin, ceftriaxone, and clarithromycin), favipiravir, and enoxaparin (1mg/kg/day). BMAwas re-evaluated in our center and revealed hemophagocytosis with no malignancy (Figure 1, panelsA,B).On the seconddayof the treatment, hehadnoneed for respiratory support and rashes regressed. On the fifth day diffuse edema on his body and organomegaly resolved. Thrombocytopenia and lymphopenia recovered; thrombocyte count was 247 000/mm3; ALC was 2500/mm3. Ferritin and D-dimer level decreased and cardiac enzymes improved. CASE 2: A 3-year-old girl admitted with fever of 4 days. Her clinical characteristics and laboratory findings are given in Tables S1 and S2 and Figure S1, panel B. Rashes on her trunk are shown in Figure S2. Her nasopharyngeal swab SARS-CoV-2 RT-PCR test was negative on admission and SARS-CoV-2 IgGwas positive (9.1). Shewas hospitalized with the diagnosis of MIS-C and started on ivIg (2 g/kg/day), methylprednisolone (2mg/kg/day), anakinra (4mg/kg/day), and enoxaparin (1 mg/kg/day). Her platelet (44 000/mm3) and hemoglobin (9.3 g/dL) levels were decreased further, and ferritin level increased. BMA, applied to rule out hematologicmalignancy, showedhemophagocytosis with increased number of free histiocytes was (Figure 1, panelsC,D).On the fifth dayof the treatment, diffuse edemaand rashes resolved. Thrombocytopenia and lymphopenia improved; thrombocyte count was 154 000/mm3; ALC 2600/mm3. Ferritin and D-dimer levels decreased. She was well with improved laboratory findings after the 10-day hospital stay. CASE 3: A 17-year-old boy with a sensorineural hearing loss was admitted to a hospital with a 7-day history of fever, abdominal pain, and vomiting. Lumbar puncturewasperformeddue to severeheadache and CSF findings were normal. He had respiratory distress, hypotension, and low left ventricular function (ejection fraction 33%), and was admitted to the intensive care unit. Thoracic computed tomography was consistent with COVID-19 pneumonia and pericardial effusion (Supplemental Figure S3). During the 10-day hospitalization, his tracheal aspirate SARS-CoV-2 RT-PCR test was negative three times. He was referred to our center for potential extracorporeal membrane oxygenation therapy. His clinical characteristics and laboratory findings are summarized in Supplemental Tables S1 and S2 and Supplemental Figure S1, panel C). SARS-CoV-2 IgG was positive (8.9). He was started on ivIg, steroid, anakinra, enoxaparin, and antibiotics. Despite these treatments, he had very high D-dimerand ferritin levels, and persistent fever. BMA was performed to rule out malignancy and revealed hemophagocytosis and increased number of free histiocytes (Figure 1, panels E,F). On the 10th day of treatment, his organomegaly resolved. He was hospitalized for 2 months for respiratory support. He was discharged with no need for any support. Recent reports suggest that the cytokine storm caused by SARSCoV-2 has significant similarities with the clinical and laboratory findings of hemophagocytic lymphohistiocytosis (HLH) and macrophageactivating syndrome (MAS).6–8 Cases have raised concerns about a hyperinflammatory process associated with COVID-19 in children, defined as MIS-C.1–5 Most children had fever lasting more than 4 days, and common presenting symptoms such as rashes, conjunctival injection, gastrointestinal symptoms, and lethargy. Cardiac manifestations especially left ventricular failure and organomegaly may occur. High levels of inflammatory markers (e.g. C-reactive protein, erythrocyte sedimentation rate, procalcitonin, and ferritin) are observed. Many patients have lymphopenia and thrombocytopenia. Although clinical and laboratory findings of MIS-C resemble HLH and MAS, Lee et al.7 reported that ferritin levels were significantly higher in MAS group compared with MIS-C. Both HLH and MIS-C are conditions in which patients deteriorate rapidly and