Table of Content - Volume 14 Issue 1 - April 2020
HLH criteria as a marker of severity in dengue
Shubhangi Agrawal1, Sharad Agarkhedkar2*, Pramod Jog3
1Resident, 2Professor and Head, 3Professor, Department of Paediatrics, At DY Patil medical college and Research Center, Pimpri, Pune. Email: shubhangiagrawal@hotmail.com, agarkhedkar@gmail.com, dr_pramodjog@yahoo.co.in
Abstract Background: Dengue fever, a benign syndrome caused by several arthropod borne viruses, is characterized by biphasic fever, myalgia or arthralgia, rash, leukopenia and lymphadenopathy. Severe dengue (also known as Dengue Haemorrhagic Fever) was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. This review will cover the current understanding of the risk factors associated with poor outcome in dengue.so This study is aimed to know the association between severity of dengue by using HLH criteria. Hemophagocytic lymphohistiocytosis is a rare hyperinflammatory disorder related to macrophage activation and usually presents as prolonged fever and a sepsis-like syndrome. Two types of HLHs are seen: The primary (familial) form is a fatal autosomal recessive disorder that typically affects young children, whereas the secondary or reactive form is associated with viral, bacterial, fungal, or parasitic infections as well as with connective tissue disorders and malignancy. The importance of the association between HLH and infection lies in the fact that both forms of HLH may be preceded by infection. Aims and Objective: To study HLH criteria as a marker of severity in Dengue. Materials and Methods: 93 patients under age of 12 years diagnosed with dengue(NS1 positive) were studied and their fever days, splenomegaly, lymphadenopathy, cytopenia- Hb, Neutropenia, Platlet count, Serum ferritin, serum triglycerides, AST and ALT were noted as a part of HLH criteria. Bone Marrow examination for hemophagocytes was not included in the study due to refusal for consent. Results: Out of 9 patients, 66 were diagnosed with Dengue fever, 10 were diagnosed with Dengue fever with warning signs and 17 were diagnosed as Severe Dengue or Dengue Hemorrhagic fever. Out of 17 patients with severe dengue, 8/17(47.05%) or 8/66(12.12%) were diagnosed with Secondary Hemophagocytic Lymphohistiocytosis by clinical and laboratory investigations. Out of 8 patients diagnosed with Secondary HLH, 5 patients required ICU admission, 1 patient recovered and 2 patients died. All patients diagnosed with dengue fever recovered and out of 10 patients diagnosed with Dengue fever with warning signs, 9 patients recovered and 1 patient required ICU admission. Conclusion: In this study we have concluded that the patients diagnosed with Secondary Hemophagocytic Lymphohistiocytosis as a complication of Severe Dengue fulfills the criteria proposed by Histiocytic Society in 2004. Key Word: dengue.
INTRODUCTION Dengue fever, a benign syndrome caused by several arthropod borne viruses, is characterized by biphasic fever, myalgia or arthralgia, rash, leukopenia and lyphadenopathy. Severe dengue (also known as Dengue Haemorrhagic Fever) was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today, severe dengue affects most Asian and Latin American countries and has become a leading cause of hospitalization and death among children and adults in these regions. Dengue haemorrhagic fever is a severe, often fatal febrile disease caused by dengue viruses. It is characterised by capillary permeability, abnormalities of hmostasis and in severe cases, a protein losing shock syndrome (Dengue Shock Syndrome). Severe manifestations, including a unique plasma leakage syndrome, a coagulopathy sometimes accompanied by bleeding, and organ impairment, occur relatively late in the disease course, presenting a window of opportunity to identify the group of patients likely to progress to these complications. However, as yet, differentiating this group from the thousands of milder cases seen each day during outbreaks remains challenging, and simple and inexpensive strategies are urgently needed in order to improve case management and to facilitate appropriate use of limited resources. This review will cover the current understanding of the risk factors associated with poor outcome in dengue.so This study is aimed to know the association between severity of dengue by using HLH criteria. Hemophagocytic lymphohistiocytosis is a rare hyperinflammatory disorder related to macrophage activation and usually presents as prolonged fever and a sepsis-like syndrome.2,4 Two types of HLHs are seen: The primary (familial) form is a fatal autosomal recessive disorder that typically affects young children, whereas the secondary or reactive form is associated with viral, bacterial, fungal, or parasitic infections as well as with connective tissue disorders and malignancy. The importance of the association between HLH and infection lies in the fact that both forms of HLH may be preceded by infection.
MATERIALS AND METHODS Type of study: cross sectional observational study. Place of study: Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune Period of study: August 2017 to August 2019 Ethical clearance: Ethics clearance will be obtained before the start of the study Source of data: The study will be a cross sectional observational study conducted on all Children’s with dengue IgM in the age group less than 12 years in paediatric ward from August 2017 to august 2019. Inclusion Criteria:
Exclusion Criteria
Sample size: 93 cases All participants age less than 12 years and Considering the baseline prevalence / propotion of 2.23% (8/358) and 10% acceptable difference @ 95% CI. Calculated sample size using Winpepi software will be 93 cases considering 5-7% non respondent rate Final 100 cases will be sample for this study.
Method of study For the children <12 years with dengue NS1 positive blood sample will be taken for IgM levels. Children with inceased IgM titers will be considered for the study and further will be evaluated for:
RESULTS In our study, 55 patients were males and 38 females. Out of 93 patients, 66 were diagnosed with Dengue fever, 10 were diagnosed with Dengue fever with warning signs and 17 were diagnosed as Severe Dengue or Dengue Hemorrhagic fever. Out of 17 patients with severe dengue, 8/17(47.05%) or 8/66(12.12%) were diagnosed with Secondary Hemophagocytic Lymphohistiocytosis by clinical and laboratory investigations. Out of 8 patients diagnosed with Secondary HLH, 5 patients required ICU admission, 1 patient recovered and 2 patients died. All patients diagnosed with dengue fever recovered and out of 10 patients diagnosed with Dengue fever with warning signs, 9 patients recovered and 1 patient required ICU admission.
TABLE 1
DISCUSSION In 1952 Farquhar and Clarieaux described Haempophagocytic Lymphohistiocytosis (HLH). HLH is a potentially life threatening condition due to release of cytokines due to uncontrolled clonal proliferation of T Lymphocytes. In 2004, revised criteria for diagnosis for HLH was proposed. Five out of eight criteria are required for diagnosis for HLH. In 2012, Priyanka Pal, Prabhas prasun Giri et al.1 studied the outbreak of dengue in 2012 at Institute of child health, Kolkata, West Bengal, they studied 358 cases of Dengue aged less than 15 years. Out of which, 8 patients were diagnosed with secondary HLH as per the guidelines stated by Histiocytic Society in 2004. In 2018, Kankananarachchi, Pratheep N et al.2 studied 12 cases of secondary HLH caused by Dengue at Lady Ridgeway Hospital and Teaching center Karapitiya, Sri Lanka from October 2016 to November 2017. Patients were aged from 10 months to 11 years. Nine were females. In our study, 93 cases of Dengue were studied. Out of which 9 cases were diagnosed with Secondary HLH. All the patients in out study fulfilled at least 5 out of 8 criteria’s. Bone marrow examination was not included in our study due to refusal for consent.
CONCLUSION In this study we have concluded that the patients diagnosed with Secondary Hemophagocytic Lymphohistiocytosis as a complication of Severe Dengue fulfills the criteria proposed by Histiocytic Society in 2004.
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