Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013
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Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013. / Ellis, Esther M; Sharp, Tyler M; Pérez-Padilla, Janice; González, Liza; Poole-Smith, B Katherine; Lebo, Emmaculate; Baker, Charlotte; Delorey, Mark J; Torres-Velasquez, Brenda; Ochoa, Eduardo; Rivera-Garcia, Brenda; Díaz-Pinto, Hector; Clavell, Luis; Puig-Ramos, Anabel; Janka, Gritta E; Janka-Schaub, Gritta; Tomashek, Kay M.
In: PLOS NEGLECT TROP D, Vol. 10, No. 8, 08.2016, p. e0004939.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013
AU - Ellis, Esther M
AU - Sharp, Tyler M
AU - Pérez-Padilla, Janice
AU - González, Liza
AU - Poole-Smith, B Katherine
AU - Lebo, Emmaculate
AU - Baker, Charlotte
AU - Delorey, Mark J
AU - Torres-Velasquez, Brenda
AU - Ochoa, Eduardo
AU - Rivera-Garcia, Brenda
AU - Díaz-Pinto, Hector
AU - Clavell, Luis
AU - Puig-Ramos, Anabel
AU - Janka, Gritta E
AU - Janka-Schaub, Gritta
AU - Tomashek, Kay M
PY - 2016/8
Y1 - 2016/8
N2 - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness.METHODOLOGY/PRINCIPAL FINDINGS: After a cluster of pediatric dengue-associated HLH patients was identified during the 2012-2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008-2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012-2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p ≤ 0.02).CONCLUSIONS/SIGNIFICANCE: During this cluster of dengue-associated HLH cases that was temporally associated with the 2012-2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury.
AB - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness.METHODOLOGY/PRINCIPAL FINDINGS: After a cluster of pediatric dengue-associated HLH patients was identified during the 2012-2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008-2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012-2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p ≤ 0.02).CONCLUSIONS/SIGNIFICANCE: During this cluster of dengue-associated HLH cases that was temporally associated with the 2012-2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury.
KW - Journal Article
U2 - 10.1371/journal.pntd.0004939
DO - 10.1371/journal.pntd.0004939
M3 - SCORING: Journal article
C2 - 27556807
VL - 10
SP - e0004939
JO - PLOS NEGLECT TROP D
JF - PLOS NEGLECT TROP D
SN - 1935-2735
IS - 8
ER -
