Original Article. Vol. 28 No. 2 Thai Adult Dengue Hemorrhagic Fever:- Sorakhunpipitkul L, et al.

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1 Original Article Vol. 28 No. 2 Thai Adult Dengue Hemorrhagic Fever:- Sorakhunpipitkul L, et al. 99 Thai Adult Dengue Hemorrhagic Fever During : Seven Cases Presented with Severe Multiorgan Failure and Successfully Treated with High Dose of Corticosteroids and Intravenous Immunoglobulin G Ladda Sorakhunpipitkul, M.D., Sompone Punyagupta, M.D., MPH&TM, Tanomsri Srichaikul, M.D., M.Sc. (Med), Supattra Tribuddharat, M.D., M.Sc. ABSTRACT During January 2008-February 2010, 157 adult patients who were admitted to Vichaiyut Hospital and Medical Center with acute phase of dengue hemorrhagic fever (DHF) were analyzed. Seven cases presented with very severe life-threatening complications. Among all, there were four cases presented with severe multiorgan failure during early first four days. The most significant organ failures were shock in cases, acute respiratory distress syndrome (ARDS) in cases, cardiac involvement in 4 cases, neurological involvement in cases, severe hepatitis in 4 cases, acute renal failure in 2 cases, disseminated intravascular coagulopathy (DIC) in cases and severe bleeding in 4 cases. Hemophagocytic syndrome (HPCS) was recognized in four cases in which 2 cases developed shock. Seven cases received high doses of corticosteroids and 5 cases received intravenous immunoglobulin G (IVIgG). Five cases survived with complete recovery. Two cases had delayed treatment and fatal outcome; one case with severe intracranial bleeding and the other case had co-infection with scrub typhus. (J Infect Dis Antimicrob Agents 2011;28:99-10.) INTRODUCTION Dengue hemorrhagic fever (DHF) was first recognized among the Thai children in with significant fatalities. 2 In 1987, Nimmannitya and colleaques reported that 18 DHF children were presented with jaundice and neurological symptoms, and 10 cases had fatal outcome. In , Apollo Hospital in India 4 reported that 109 cases of severe DHF *Department of Medicine, Vichaiyut Hospital and Medical Center, Bangkok 10400, Thailand. Received for publication: April 1, Reprint request: Ladda Sorakhunpipitkul, M.D., Department of Medicine, Vichaiyut Hospital and Medical Center, Bangkok 10400, Thailand. annra@gmail.com Keywords: Dengue hemorrhagic fever, adult, multiorgan failure, cortocosteroids, immunoglobulin G 99

2 100 J INFECT DIS ANTIMICROB AGENTS May-August 2011 required Pediatric ICU. They had persistant shock in 9 cases, acute respiratory distress (ARDS) in 10 cases, neurological symptoms in 24 cases and diastolic cardiac dysfunction in cases. Six cases died from refractory shock, four of them had ARDS and disseminated intravascular coagulopathy (DIC) and 2 cases had DIC. In 2004, Wichmann and colleagues 5 reported that 219 DHF patients, child patients had encephalopathy and 20 patients (9 children and 11 adults) had severe liver involvement. During , Kittiprapan 6 reported that 4 cases of dengue shock syndrome and 2 cases died from multiorgan failure. Later adult DHF was commonly found with a higher rate of unusual clinical manifestations. In 1975, Srichaikul and colleagues 7 reported that among 9 adult DHF cases, cases developed DIC and two cases had fatal outcomes. In 1995, Chan et al 8 from Singapore reported that there were 4 adult dengue deaths, cases of severe bleeding and 1 case of acute pulmonary edema and shock. They emphasized the increasing incidence of fatality rates in adult DHF. In 2007, Punyaguta 9 retrospectively studied 75 adults DHF, one case had cerebral hemorrhage. Recenty In 2008, Srichaikul and colleagues 10 reported that an adult DHF with hemophagocytic syndrome (HPCS) and multiorgan failure was successfully treated with intravenous methylprednisolone and a high dose of intravenous immunoglobulin G (IVIgG). This study was aimed to analyze DHF patients presented with severe multiorgan failure included in clinical manifestation, diagnosis, treatment and outcome and to find out of indicators and factors that might improve fatalities outcome in these patients. MATERIALS AND METHODS During January 2008 and February 2010; retrospective analysis of 220 adults clinically diagnosed as dengue fever or DHF were admitted to Vichaiyut Hospital and Medical Center in Bangkok. From this analysis, dengue fever and DHF at convalescent phase were excluded. Therefore 157 adult DHF cases who had acute dengue were included. One hundred and fifty patients of these presented with grade IorII DHF and seven of these presented with dengue shock syndrome with at least two organ involvement were founded. The diagnosis was based on WHO criteria with either positive non-structural 1 (NS 1 ) antigen or dengue IgM antibody type specific or positive polymerase chain reaction (PCR) were reviewed. The study was analyzed that seven cases presented with dengue shock syndrome (DSS) with multiorgan involvement and life threatening complications will be reported. RESULTS Age and sex of the 157 adults with DHF, 8 males and 74 females were presented in Table 1. The ages were between 15 to 70 years old and over. Sixty-nine cases (44%) ranged in age from 15 to 0 years and only 10 cases (9%) aged over 60 years. Severe multiorgan failure was recognized in 7 cases (Table 2, ). HPSC was found in 4 cases, shock in cases, ARDS in cases, cardiac involvement in 4 cases, neurological involvement in cases, gastrointestinal bleeding in 2 cases and 4 cases with severe hepatitis (transaminase enzyme of over >500 unit). Two cases had renal failure and one of them required hemodyalysis. Two out of three cases with DIC presented with bleeding tendency; one experienced intracerebral hemorrhage and GI bleeding, and the other case had only GI bleeding. Both cases required blood transfusion. Two other cases had bleeding per vagina and they also required blood transfusion. The severe multiorgan failure was detected in five cases during the first four days of admission.

3 Vol. 28 No. 2 Thai Adult Dengue Hemorrhagic Fever:- Sorakhunpipitkul L, et al. 101 Table 1. Demographic data of 157 adult DHF patients hospitalized during January 2008 and February Sex Age (yrs) > 70 Total Male Female T otal case (%) 69 (44) 44 (28) 21 (1) 1 (8) 6 (4) 4 () 157 (100) Table 2. Severe multiorgan failure in 7 Adults DHF. Manife stations Numbe r of cases Hemophagocytic syndrome 4 Shock ARDS Cardiac: cardiomyopathy/myocarditis / 1 CNS: convulsion/alteration of conscious 1/ 1 cerebral hemorrhage 1 GI: severe vomiting/severe abdominal pain / 2 severe hepatitis (transaminase enzyme >500μ) 4 Acute renal failure 2 DIC Bleed per vagina/gi bleeding 2/ 2 All seven cases were treated with high dose dexamethasone, 2 of them also received pulse methylprednisolone and 5 cases also received IVIgG and all of them received fully supportive treatment for the complications. Hemophagocytic syndrome was recognized in 4 cases; 2 of them developed shock and ARDS, another case had ARDS, myocarditis, seveve hepatitis and DIC, the other case had DIC. Two of these four cases recovered and were discharged after 7-8 days of hospitalization. The other two cases who had renal failure and DIC had fatal outcome; one case with severe intracranial bleeding and the other case 101 had co-infection with scrub typhus. The diagnosis and proper treatment was delayed in both cases. Five of seven patients who received corticosteroids and/or IVIgG fully recovered. DISCUSSION From this study, it is obvious that the natural courses of adult DHF are quite different from the children namely severe multiorgan failure is not uncommon features in adult DHF. In this study, there were at least 7 out of 157 cases (4.5%) that experienced multiorgan failure. The pathogenesis of

4 102 J INFECT DIS ANTIMICROB AGENTS May-August 2011 Table. Clinical features of 7 adult DHF with severe multiorgan failure. No Sex Complicatio n Clinical Featur e Rx Start on Da y Ou t Days o f Age (yrs) on Da y S HPC Shoc k ARD S Cardia c CN S GI RF DI C Bleedin g Dex a P M IV Ig G com e Hospitalizatio n 1 F D D2-6 D5 D- 7 S F D D4 D5-7 D8 S 9 4 F D D6-8 - D5-6 F M D D- 7 - D7 F M D D4-7 - D7 S F D D S M D D6 - - S 6 16 MP = methylprednisolone, RF= renal failure, S = survive, F = fatal

5 Vol. 28 No. 2 Thai Adult Dengue Hemorrhagic Fever:- Sorakhunpipitkul L, et al. 10 this phenomenon is not clearly understood; however, severe hyperimmune reaction is probably the most possible cause. This is supported by the demonstration of HPCS in all 4 severe cases. It is well supported that the benefit of high dose of corticosteroids and IVIgG is shown in this report as well as in our previous study. 10 In 2010, PL Goh 11 from Singapore reported that one case of fatal perimyocarditis. In this study one patient who experienced myocarditis with sinus bradycardia was successfully treated with high dose dexamethasone and IVIgG. Five out of seven patients survived the early severe multiorgan failure emphasizing the significance of early diagnosis as well as proper treatment with corticosteroids and/or IVIgG administration. Two patients died because the diagnosis and treatment were delayed. In conclusion, this study of adult DHF reveals that early diagnosis and treatment with immunomodulator drugs will save lives in severe cases with multiorgan failure. References 1. Thongcharoen P. Hemorrhagic Fever. Bangkok: Aksornsamai Press, Nimmannitya S, Halstead SB, Cohen SN, Margiotta MR. Dengue and chikungunya virus infection in man in Thailand, I. Observations on hospitalized patients with hemorrhagic fever. Am J Trop Med Hyg 1969;18: Nimmannitya S, Thisyakorn U, Hemsrichart V. Dengue haemorrhagic fever with unusual manifestations. Southeast Asian J Trop Med Public Health 1987;18: Kamath SR, Ranjit S. Clinical features, complications and atypical manifestations of children with severe forms of dengue hemorrhagic fever in South India. Indian J Pediatr 2006;7: Wichmann O, Hongsiriwon S, Bowonwatanuwong C, Chotivanich K, Sukthana Y, Pukrittayakamee S. Risk factors and clinical features associated with severe dengue infection in adults and children during the 2001 epidemic in Chonburi, Thailand. Trop Med Int Health 2004;9: Kittiprapan W. Dengue shock syndrome in pediatric patients at Buddhachinaraj Hospital. Buddhachinaraj Med J 2010;27: Srichaikul T, Punyagupta S, Nitiyanant P, Alkarawong K. Disseminated intravascular coagulation in adult Dengue haemorrhagic fever: Report of three cases. Southeast Asian J Trop Med Public Health 1975;6: Chan KP, Lau GK, Doraisingham S, Chan YC. Adult dengue deaths in Singapore. Clin Diagn Virol 1995;4: Punyagupta S. Dengue hemorrhagic fever in adults, an emerging problem in Thailand: a retrospective study of 75 adult dengue infection in J Infect Dis Antimicrob Agents 2009;26: Srichaikul T, Punyagupta S, Kanchanapoom T, Chanokovat C, Likittanasombat K, Leelasiri A. Hemophagocytic syndrome in Dengue hemorrhagic fever with severe multiorgan complications. J Med Assoc Thai 2008;91: Goh PL. Dengue perimyocarditis: a case report. Hong Kong J Emerg Med 2010;17: