Not a very common

1. JOURNAL CLUB
By
Dr Ammara Rafique
FCPS II Trainee
NICH

2. Hemophagocytic
Lymphohistiocytosis Syndrome in
Dengue Hemorrhagic Fever

3. S. Raju & Shantaraman Kalyanaraman
&K.Swaminathan
Department of Pediatrics,
Krishna Hospitals,
Tamilnadu, India.
Indian J Pediatr April 2014.

4. Objectives

5. To evalute the incidence of Hemophagocytic
Lymphohistiocytosis Syndrome in Dengue
Hemorrhagic Fever

6. Hemophagocytic Lymphohistiocytosis (HLH) is a life
threatening clinical event associated with dengue fever
and is associated with high mortality.
infections like epstein barr virus (EBV), cyto-megalo
virus (CMV), dengue, brucellosis and visceral
leishmaniasis have also been reported in children.

7. Infection induces an inappropriate macrophage proliferation
in the marrow, spleen, liver, skin and spinal cord,
resulting in
uncontrolled hemophagocytosis of blood cells especially
erythroid cells in the marrow, a pathologic hallmark of
HLH.

9. Diagnosis of HLH in
Dengue

10. The diagnosis of HLH in dengue is based on the guidelines
of the FHL Study Group of the Histiocytic Society - HLH
2004 based on clinical and laboratory criteria, including
bone marrow aspiration.

11. Haemophagocytic Lymphohistiocytosis
(HLH) 2004 Diagnostic Criteria.

12. haemophagocytic lymphohistiocytosis (HLH) 2004
diagnostic criteria.
The diagnosis of HLH can be established if one of either 1 or 2 below
is fulfilled
1 . A molecular
diagnosis
consistent with
HLH
2. Diagnostic criteria
for HLH fulfilled (five
of eight criteria
below)

13. Diagnostic criteria for HLH fulfilled (five of
eight criteria)
1. Fever
2. Splenomegaly
3. Cytopenia affecting at least two of the three lineages in the peripheral blood
Haemoglobin <90 g/l Platelets <100 ¥ 10^9/l Neutrophils <1·0 ¥ 10^9/l
4. Hypertriglyceridaemia and/or hypofibrinogenaemia Fasting triglycerides 3·0 mmol/l (i.e. 265 mg/dl)
Fibrinogen 1·5 g
5. Haemophagocytosis in bone marrow, spleen or lymph nodes
6. Low/absent natural killer cell activity
7. Hyperferritinaemia Ferritin >500 mg/l
8. High soluble interleukin 2 receptor levels sIL-2R 2400 U/ml

15. DHF World Health
Organization (WHO) criteria

16. DHF World Health Organization (WHO)
criteria
• Fever or recent
history of fever
lasting 2–7 days.
• Any
hemorrha
gic
manifestat
ion.
positive
torniquete
test
• Thrombocytopenia
(platelet count of
<100,000/mm3).
• Evidence
of
increased
vascular
permeabili
ty

17. MATERIALS &
METHODS

18. Two hundred and twelve children, received at the
Pediatrics Department, Krishna Hospitals ,South India,
between November 2011 through January 2013, for
treatment of dengue were evaluated as per WHO
guidelines
The children were diagnosed clinically, confirmed by
ELISA for dengue, classified as dengue fever (DF) or
dengue hemorrhagic fever (DHF) and put on intensive
pediatric care as per standard WHO protocol.

19. Those of these children who were refractory to
treatment were evaluated for
splenomegaly
worsening blood cell counts
rising ESR
coagulation profile
rising titres of hepatic enzymes
electrolyte levels
serum triglycerides, ferritin, and fibrinogen.

20. Children with major co-morbidities were not included in the
study
The selected children were classified as suspected
hemophagocytic lymphohistiocytosis if they satisfied 4 of 7
clinical and laboratory criteria in the Diagnostic Guidelines
for HLH ,
Suspected HLH were advised bone marrow evaluation

21. RESULTS

22. Of 212 children evaluated for dengue fever, 31 children were
classified as suspect HLH and advised bone marrow
evaluation.
Out of 31 children, 23 (10.85 %) had marrow features of
hemophagocytosis and were labeled as HLH secondary to
dengue.
Of these 23 children, 11(47.82 %) were males (mean age 26
mo) and 12(52.17 %) were females (mean age 24.9 mo).
All 23 children had high fever, with a mean duration of fever
prior to diagnosis of HLH being 13.96 d (13.91 d in male and
14.01 d in female).

23. In these 23 children,
20(86.95 %) had malena,
4(17.39 %) had hematuria,
3(13.04 %) had altered consciousness,
all 23(100 %) had organomegaly with
isolated splenomegaly in 10 (43.48 %)
and hepatosplenomegaly in 13 (56.52 %).
Worsening blood cell counts
(erythropenia 78.26 %, leucopenia 34.78 % and thrombocytopenia
100 %),
rising ESR (100 %),

24. Coagulation profile (prolonged PT and INR in 86.96 %),
rising titres of hepatic enzymes [high transaminases in 100
% with a mean aspartate amino transferase (AST) of
1,397.0 IU/L and alanine transaminase (ALT) of 1,780.0
IU/L], electrolyte levels
triglycerides
(high in 95.65 % with a mean of 269.80 mg/dL),
ferritin
(high in 60.87 % with a mean of 600.69 μg/dL)
decreased fibrinogen levels
(34.78 %) were documented

25. The bone marrow aspirations were performed in 27
children of whom 23 had classical hemophagocytosis in the
marrow.
Of these 23 children, 19 received IVIG, and all of them
recovered,

26. while of the remaining 4 children who did not receive IVIG,
one child recovered with conventional treatment
three died of complications
One due to cardiopulmonary
two due to encephalopathy

27. An elevated hematocrit ≥20% above mean
Presence of pleural effusion or ascites
Hypoproteinemia or hypoalbuminemia

28. Clinical & lab presentation in
HLH due to Dengue

32. Discussion

33. • clinical diagnosis is central to early diagnosis of this
complication with a classical triad of clinical,laboratory
and bone marrow presentation.
• bone marrow hemophagocytosis,a hallmark of
activated macrophages is not specific for HLH.
• Its absence does not exclude a diagnosis of HLH.

34. • Early recognition is essential for preventing mortality.
• IVIG has a definite role in the treatment of HLH,hence
early recognition of clinical signs,laboratory indicators
and marrow analysis can reduce mortality.

35. Thanks