Dokazi infestacije helmintima i učinak terapije antihelminticima kod dece ispitivane zbog eozinofilije
Sažetak
Uvod/Cilj. Uzrok eozinofilije često ostaje nerasvetlјen. Cilj rada bio je da se analiziraju uzrok i terapijski pristup kod dece sa eozinofilijom u pedijatrijskoj bolnici tercijarnog stepena zbrinjavanja. Metode. Retrospektivno je analizirana medicinska dokumentacija dece koja su ispitivana zbog eozinofilije (naznačene šifrom D72.1 na osnovu Međunarodne klasifikacije bolesti) u Univerzitetskoj dečjoj klinici u Beogradu, Srbija, u periodu od decembra 2011. do decembra 2022. Dijagnozu eozinofilije imalo je ukupno 105 dece (62 dečaka; odnos dečaci:devojčice iznosio je 1:4) uzrasta od mesec dana do 16,5 godina (medijana 7,7 godina). Posle isključenja 15 dece zbog pogrešno postavljene dijagnoze samo na osnovu relativnog broja eozinofila, preostalih 90 dece grupisano je prema težini eozinofilije (blaga, umerena ili teška). Rezultati. Serološkom analizom potvrđena je toksokarijaza kod šest (6,7%) bolesnika, dok je kod dvoje dece (2,2%) dokazana infestacija nematodama (Ascaris lumbricoides, odnosno Enterobius vermicularis). Kod 32 (35,6%) dece sa eozinofilijom, kao i kod troje dece bez prave eozinofilije, helmintijaza je dijagnostikovana ex juvantibus. Eozinofilija je na kraju objašnjena
alergijskim/atopijskim stanjima [19 (21,1%)], reakcijama na lekove [četiri (4,4%)], bakterijskim infekcijama [devet (8,9%)], hematološkim problemima [pet (5,5%)], autoimunskim bolestima [tri (3,3%)], nepovezanim urođenim stanjima (jedno dete) ili kao izolovan nalaz [sedam (7,8%)]. Pored toga, kod jednog deteta s dijagnozom eozinofilije ali ne i povišenim apsolutnim brojem eozinofila postavljena je dijagnoza eozinofilnog ezofagitisa. Ukupno 56 (53,3%) dece dobilo je terapiju antihelminticima: 9 (90,9%) sa teškom eozinofilijom, 19 (51,4%) sa umerenom, 23 (53,5%) sa blagom i 5 (33,3%) dece bez prave eozinofilije. Većina (42) dece dobila je samo mebendazol, dok je preostalih 14 (osmoro sa teškom, troje sa umerenom i troje sa blagom) takođe prvobitno lečeno mebendazolom, ali su kasnije, zbog perzistentnosti eozinofilije, lečeni albendazolom. Kod sve dece lečene antihelminticima, eozinofilija i ostali relevantni nalazi (ako ih je bilo) povukli su se u roku od nekoliko dana do nekoliko nedelja od početka lečenja. Zaklјučak. Naši rezultati u celini govore u prilog preporuke da neobjašnjena eozinofilija bilo kog stepena težine iziskuje standardizovani dijagnostički pristup. Takođe, rezultati potkreplјuju potencijalnu racionalnu osnovu za primenu antihelmintika ex juvantibus kod jednog broja dece sa eozinofilijom bez očiglednog etiološkog razjašnjenja.
Reference
Valent P, Klion AD, Roufosse F, Simon D, Metzgeroth G, Leifer-man KM, et al. Proposed refined diagnostic criteria and classi-fication of eosinophil disorders and related syndromes. Allergy 2023; 78(1): 47–59.
Costagliola G, Marco SD, Comberiati P, D’Elios S, Petashvili N, Di Cicco ME, et al. Practical approach to children presenting with eosinophilia and hypereosinophilia. Curr Pediatr Rev 2020; 16(2): 81–8.
Schwartz JT, Fulkerson PC. An approach to the evaluation of persistent hypereosinophilia in pediatric patients. Front Im-munol 2018; 9: 1944.
Jackson DJ, Akuthota P, Roufosse F. Eosinophils and eosino-philic immune dysfunction in health and disease. Eur Respir Rev 2022; 31(163): 210150.
Ness TE, Erickson TA, Diaz V, Grimes AB, Rochat R, Anvari S, et al. Pediatric eosinophilia: a review and multiyear investiga-tion into etiologies. J Pediatr 2023; 253: 232–7. e1.
Noordin R, Yunus MH, Tan Farrizam SN, Arifin N. Serodiag-nostic methods for diagnosing larval toxocariasis. Adv parasi-tol 2020; 109: 131–52.
Weatherhead JE, Hotez PJ, Meija R. The global state of hel-minth control and elimination in children. Pediatr Clin North Am 2017; 64(4): 867–77.
Ma G, Holland CV, Wang T, Hofmann A, Fan CK, Maizels RM, et al. Human toxocariasis. Lancet Infect Dis 2018; 18(1): e14–24.
Rostami A, Ma G, Wang T, Koehler AV, Hofmann A, Chang BCH, et al. Human toxocariasis – A look at neglected disease through an epidemiological ’prism’. Infect Genet Evol 2019; 74: 104002.
Hahn JW, Lee K, Shin JI, Cho SH, Turner S, Shin JU, et al. Global incidence and prevalence of eosinophilic esophagitis, 1976-2022: a systematic review and meta-analysis. Clin Gas-troenterol Hepatol 2023; 21(13): 3270–84. e77.
Cetinkaya PG, Aytekin ES, Esenboga S, Cagdas D, Sahiner UM, Sekerel BE, et al. Eosinophilia in children: characteristics, eti-ology and diagnostic algorithm. Eur J Pediatr 2023; 182(6): 2833–42.
Burris D, Rosenberg CE, Schwartz JT, Zhang Y, Eby MD, Abonia JP, et al. Pediatric hypereosinophilia: characteristics, clinical manifestations, and diagnoses. J Allergy Clin Immunol Pract 2019; 7(8): 2750–8. e2.
Moller D, Tan J, Gauiran DTV, Medvedev N, Hudoba M, Car-ruthers MN, et al. Causes of hypereosinophilia in 100 consecu-tive patients. Eur J Haematol 2020; 105(3): 292–301.
Wardlaw AJ, Wharin S, Aung H, Shaffu S, Siddiqui S. The causes of a peripheral blood eosinophilia in a secondary care setting. Clin Exp Allergy 2021; 51(7): 902–14.
Mori F, Caffarelli C, Caimmi S, Bottau P, Liotti L, Franceschini F, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS) in children. Acta Biomed 2019; 90(3–S): 66–79.
Gabrielli S, Tasić-Otašević S, Ignjatović A, Fraulo M, Trenkić-Božinović M, Momčilović S, et al. Seroprevalence and risk factors for Toxocara canis infection in Serbia during 2015. Food-borne Pathog Dis 2017; 14(1): 43–9.
Peju M, Deroux A, Pelloux H, Bouillet L, Epaulard O. Hypereo-sinophilia: biological investigations and etiologies in a French metropolitan university hospital, and proposed approach for diagnostic evaluation. PLOS One 2018; 13(9): e0204468.
Sviben M, Čavlek TV, Missioni EM, Galinović GM. Seropreva-lence of Toxocara canis infection among asymptomatic chil-dren with eosinophilia in Croatia. J Helminthol 2009; 83(4): 369–71.
Manini MP, Marchioro AA, Coli CM, Nishi L, Falavigna-Guilherme AL. Association between contamination of public squares and seropositivity for Toxocara spp. in children. Vet Parasitol 2012; 188(1–2): 48–52.
Ristić M, Miladinović-Tasić N, Dimitrijević S, Nenadović K, Bogunović D, Stepanović P, et al. Soil and sand contamination with canine intestinal parasite eggs as a risk factor for human health in public parks in Niš (Serbia). Helminthologia 2020; 57(2): 109–19.
Cabral Monica T, Evers F, de Souza Lima Nino B, Pinto-Ferreira F, Breganó JW, Ragassi Urbano M, et al. Socioeconomic factors associated with infection by Toxoplasma gondii and Toxocara canis in children. Transbound Emerg Dis 2022; 69(3): 1589–95.
Fortini MB, Erickson TA, Leining LM, Robinson KM, Carey MN, Smith SJ, et al. Review of toxocariasis at a children’s hospital prompting need for public health interventions. Pediatr Infect Dis J 2023; 42(10): 862–6.
Maraghi S, Rafiei A, Hajihossein R, Sadjjadi SM. Seroprevalence of toxocariasis in hypereosinophilic individuals in Ahwaz, south-western Iran. J Helminthol 2012; 86(2): 241–4.
Delai RR, Freitas AR, Kmetiuk LB, Merigueti YFFB, Ferreira IB, Lescano SAZ, et al. One Health approach on human sero-prevalence of anti-Toxocara antibodies, Toxocara spp. eggs in dogs and sand samples between seashore mainland and island areas of southern Brazil. One Health 2021; 13: 100353.
Seo M, Yoon SC. A seroepidemiological survey of toxocariasis among eosinophilia patients in Chungcheongnam-do. Korean J Parasitol 2012; 50(3): 249–51.
Hartl S, Breyer MK, Burghuber OC, Ofenheimer A, Schrott A, Ur-ban MH, et al. Blood eosinophil count in the general popula-tion: typical values and potential confounders. Eur Respir J 2020; 55(5): 1901874.
Phuc LDV, Hai TX, Loi CB, Quang HH, Vinh LD, Le TA. The kinetic profile of clinical and laboratory findings and treatment outcome of patients with toxocariasis. Trop Med Int Health 2021; 26(11): 1419–26.
Bourgoin G, Callait-Cardinal MP, Bouhsira E, Polack B, Bourdeau P, Roussel Ariza C, et al. Prevalence of major digestive and respiratory helminths in dogs and cats in France: results of a multicenter study. Parasit Vectors 2022; 15(1): 314.
Groh M, Rohmer J, Etienne N, Abou Chahla W, Baudet A, Chan Hew Wai A, et al. French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syn-dromes. Orphanet J Rare Dis 2023; 18(1): 100.