Farela Neves, J

Gouveia, C

Santos, J

Varandas, L

Venâncio, P

Repositório do Centro Hospitalar de Lisboa Central, EPE

LETTER TO THE EDITORHemophagocytic lymphohistiocytosis secondary to Falciparummalaria in a 5 year-old boyJoana Almeida Santos & João Farela Neves &Paulo Venâncio & Catarina Gouveia & Luís VarandasReceived: 11 May 2014 /Accepted: 20 May 2014 /Published online: 1 June 2014# Springer-Verlag Berlin Heidelberg 2014Dear Editor,A previously healthy 5-year-old Portuguese boy presentedto our Emergency Department (ED) with a history of4 days of high fever and painful abdomen. He had beenliving in Mozambique (Matola) for the last year and didn’theld malaria prophylaxis. At the time of admission, hewas febrile and jaundiced, and a splenomegaly was no-ticed on physical examination. Initial laboratory datashowed leucopenia, thrombocytopenia, high liver enzymes,direct hyperbilirubinemia, and elevated C-reactive protein.The diagnosis of malaria was confirmed by the presenceof Plasmodium falciparum trophozoites in thin and thickblood films and by positive Plasmodium antigenemia.Despite a parasitemia of <1 %, he was admitted andtreated with IV quinine and clindamycin with diagnosisof severe malaria according to WHO criteria (Table 1). Onthe following days, his clinical condition deteriorated,presenting with high fever, hypotension, mucosal bleeding,pleural effusion, and ascites. Laboratory workout revealeddisseminated intravascular coagulation, pancytopenia, cho-lestatic hepatitis, hypoalbuminemia, as well aselevated ferritin (5,890 ng/mL) and soluble CD25 (sIL2R=4,352 U/mL). Other co-infections were excluded(Table 1).Despite the diagnosis of Falciparum malaria-associatedhemophagocytic lymphohistiocytosis (HLH), he did not re-ceive HLH-directed therapy and was treated withantimalaric drugs and supportive measures: packed red cells,platelets, fresh frozen plasma, cryoprecipitate, purified con-centrate of fibrinogen, as well as inotropic support withdopamine (day 2 - 4). His clinical and laboratory conditionslowly improved (Table 1). He was discharged home 12 daysafter being hospitalized.A hereditary cause for HLH was not investigated due theprompt improvement without HLH-targeted therapy.HLH is a potentially fatal hyperinflammatory conditioncaused by a highly stimulated but ineffective immune re-sponse [1]. It has been described as a familial disorder (dueto defects in Nk citotoxicity) and as a sporadic one [2]. Thelatter has been associated with infections, malignancies, orrheumatologic disorders [3].Infection-associated HLH can be triggered by virus,bacteria, fungi, or protozoa [1–4], but P. falciparum hasrarely been reported as a cause of HLH [5–7], especial-ly in children [10].A deranged immune response is the cause of HLH, andthe associated cytokine storm is responsible for the major-ity of the clinical and laboratory abnormalities [1–4]. Theclinical diagnosis is established fulfilling five of the eightHLH-2004 criteria [1]. Noteworthy are the facts thathemophagocytosis is not required for establishing the di-agnosis, that ferritin levels above 10,000 ng/mL are highlyspecific for HLH and that very high levels of sIL2Rα arealmost never seen outside HLH [3].J. A. Santos (*) : P. VenâncioPediatric Department, Hospital Dona Estefânia, Centro HospitalarLisboa Central, EPE Rua Jacinta Marto, 1169-045 Lisbon, Portugale-mail: joanaasantos@gmail.comC. Gouveia : L. VarandasPediatric Infectious Diseases Unit, Hospital Dona Estefânia, CentroHospitalar Lisboa Central, EPE Rua Jacinta Marto, Lisbon, PortugalJ. F. NevesPrimary Immunodeficiencies Unit and Pediatric Intensive Care Unit,Hospital Dona Estefânia, Centro Hospitalar Lisboa Central, EPERua Jacinta Marto, Lisbon, PortugalJ. F. NevesCEDOC, Chronic Diseases Study Centre, Faculty of MedicalSciences, New University of Lisbon, Lisbon, PortugalL. VarandasInstituto de Higiene e Medicina Tropical, Faculty of MedicalSciences, New University of Lisbon, Lisbon, PortugalAnn Hematol (2015) 94:161–163DOI 10.1007/s00277-014-2118-9The authors believe that despite being rarely described,HLH-associated malaria should be suspected in patients withseveremalaria and unexpectedmultiorgan failure. Experimen-tal studies have demonstrated that several soluble exoantigensof P. falciparum induce inappropriate macrophage activationand a Th1-stimulated hypercytokinemia with excessive pro-duction of the TNF-α and INF-γ [8], which are some of themajor cytokines responsible for HLH. This has also been welldescribed with other infectious agents, such as EBV [9].Most cases of malaria-induced HLH reported in literaturehave responded completely to antimalarial therapy alone[5–7], as observed in our case. Nevertheless, like in EBV-associated HLH [10], in the rare cases where there is progres-sion of HLH despite appropriate antimalarial therapy, a step-wise approach can probably be applied, in order to allowdisease control without jeopardizing the infection control.Conflict of Interest The authors declare that they have no conflictof interest.References1. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, ImashukuS, Ladisch S, McClain K, Webb D, Winiarski J, Janka G (2007)HLH-2004: diagnostic and therapeutic guidelines forhemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48(2):124–1312. Janka GE (2007) Familial and acquired hemophagocyticlymphohistiocytosis. Eur J Pediatr 166(2):95–1093. Filipovich AH (2011) The expanding spectrum of hemophagocyticlymphohistiocytosis. Curr Opin Allergy Clin Immunol 11(6):512–5164. Canna SW, Behrens EM (2012) Making sense of the cytokine storm:a conceptual framework for understanding, diagnosing, and treatinghemophagocytic syndromes. Pediatr Clin N Am 59(2):329–3445. Rehman JU, Bhabri N, Waleed A, Maulawi A, Aslam M (2012)Falciparum malaria in a patient with sickle cell trait withhemophagocytosis and secondary pancytopenia. Ann Hematol 91(8):1329–13306. Ohnishi K, Mitsui K, Komiya N, Iwasaki N, Akashi A,Hamabe Y (2007) CLINICAL case report: falciparum malariawith hemophagocytic syndrome. Am J Trop Med Hyg 76(6):1016–1018Table 1 Laboratory data performed on admission day (day 1), during hospitalization (between days 2 and 3), and at discharge (day 12)Laboratory evaluation Day 1 Day 2–3 Day 12Hemoglobin (g/dL) 13.6 8.9 11.7WBC (×109/L) 3.8 3.8 9.6ANC (×109/L) 1.99 0.94 4.22Platelet count (×109/L) 21 9 502PT (s)/INR/APTT (s) 11.1/0.97/37 16.6/1.45/53.3 10.8/0.95/30.8Fibrinogen (g/L) – 0.6 1.5D-dimer (μg/mL) – 13.288 2.382CRP (mg/L) 73.9 81.3 2.9AST/ALT/LDH (U/L) 147/84/1063 139/76/1411 53/53/510GGT/ ALP (U/L) 281/605 190/626 141/622T-Bil/D-Bil (mg/dL) 10.53/6.09 10.91/6.71 2.33/0.87Triglycerides (mg/dL) 91 306 197Albumin (g/L) – 21 36BUN/creatinine (mg/dL) 34/0.46 51/0.62 12/0.20Na (mEq/L) 129 135 139Ferritin (ng/mL) – 5890 734sCD25 (U/mL) – 4352 –Plasmodium falciparum Positive antigenemiaTrophozoites onperipheral blood smearParasite density 0 %Positive antigenemiaTrophozoites onperipheral blood smearNegativeantigenemiaEBV, CMVand PVB19 serology,blood cultures, O&P testNegativeNormal range—hemoglobin, 11.5–13.5 g/dL; WBC, 5–15×109 /L; ANC, 1.5–8×109 /L; platelet count, 200–450×109 /L; PT, 10.1–12.1 s; INR, 0.91–1.11; APTT, 26–36 s; fibrinogen, 1.57–4 g/L; D-dimer, <0.23 μg/mL; CRP, <5 mg/L; AST 15–60 U/L; ALT, <39 U/L; LDH, 110–295 U/L; GGT, <22U/L; ALP, 86–362 U/L; T-Bil, 0.3–1.2 mg/dL;D-Bil, 0–0.2 mg/dL; triglycerides, <150 mg/dL; albumin, 35–52 g/L; BUN, 10.8–38.4 mg/dL; creatinine,0.16–0.39 mg/dL; Na, 136–145 mEq/L; ferritin, 24–336 ng/mL; sCD25, <1,000 U/mL. Bold numbers - abnormal valuesWBC white blood cell, ANC absolute neutrophil count, PT prothrombin time, INR international normalized ratio, APTT activated partial thromboplastintime, CRP C-reactive protein, AST aspartate aminotransferase, ALT alanine aminotransferase, LDH lactate dehydrogenase, GGT gamma-glutamyltransferase, ALP alkaline phosphatase, T-Bil total bilirubin, D-Bil direct bilirubin, BUN blood urea nitrogen, Na sodium, sCD25 soluble CD25, EBVEpstein–Barr virus, CMV Cytomegalovirus, PVB19 human parvovirus B19, O&P ova and parasite (stool) test162 Ann Hematol (2015) 94:161–1637. Sermet-Gaudelus I, Abadie V, Stambouli F, Hennequin C,Lenoir G, Gendrel D (2000) Haemophagocytic syndrome inPlasmodium falciparum malaria. Acta Paediatr 89(3):368–3698. Kwiatkowski D, Hill AV, Sambou I, Twumasi P, Castracane J,Manogue KR, Cerami A, Brewster DR, Greenwood BM (1990)TNF concentration in fatal cerebral, non-fatal cerebral, anduncomplicated Plasmodium falciparum malaria. Lancet 336(8725):1201–12049. Usmani GN, Woda BA, Newburger PE (2013) Advances in under-standing the pathogenesis of HLH. Br J Haematol 161(5):609–62210. Imashuku S (2011) Treatment of Epstein-Barr virus-relatedhemophagocytic lymphohistiocytosis (EBV-HLH); update 2010. JPediatr Hematol Oncol 33(1):35–39Ann Hematol (2015) 94:161–163 163

Hemophagocytic Lymphohistiocytosis Secondary to Falciparum Malaria in a 5 Year-Old Boy

http://repositorio.chlc.min-saude.pt/bitstream/10400.17/2034/1/Ann%20Hematol%202015_161.pdf

Hemophagocytic Lymphohistiocytosis Secondary to Falciparum Malaria in a 5 Year-Old Boy

Abstract

Similar works

Full text

Available Versions

Repositório do Centro Hospitalar de Lisboa Central, EPE