SUMMARY is no family history of any significance.

 

 

SUMMARY

 
Dengue fever became
more frequent in southeast Asia, but involvement of neurological complication
such as encephalopathy is rare. Dengue encephalopathy results from
multisystem impairment with hepatic failure, shock and coagulopathy leading
to cerebral insult. Dengue encephalopathy causes extensive immune activation;
stimulate ferritin production as an acute phase reactant and results hyperferritinaemia.
Dengue encephalopathy associated with hyperferritinaemia is indeed a rare
clinical scenario of dengue fever. We present a case of dengue without
haemorrhagic fever with hepatic failure, thrombocytopenia and
hyperferritinaemia in an adult male, leading to dengue encephalopathy. He was
conservatively managed with adequate supportive care as per international
standards and discharged after 11 days. After four weeks, on follow up, his
Laboratory investigation revealed restored liver function, Platelet count and
ferritin level.
 

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BACKGROUND

 
Being
an epidemic arboviral disease, Dengue fever became more frequent in southeast
Asia. Around 2.5 billion people live in dengue-risk region and about 100
million new cases each year worldwide. Dengue virus is single stranded RNA
virus which belongs to Flaviviridae family. Dengue fever
has broad clinical features ranging from asymptomatic infection to life
threatening dengue haemorrhagic fever and dengue shock.1  Dengue encephalopathy is well reported,
though unusual, entity with prevalence of 0.5 % to 6.2%. Dengue
encephalopathy results from the multisystem impairment such as hepatic
failure, shock and coagulopathy which leads to cerebral insult by extensive
immune activation.2
 
Hyperferritineamia
can be precipitate by external stimulus like virus which impaired cytotoxic
function of NK cells and T lymphocytes. These will results exaggerated immune
system by decreased clearance of infected and antigen presenting cells from
the circulation. Higher than 500 µg/L of
ferritin level was reported as hyperferritineamia. In children ferritin
level ware reported as laboratory marker for dengue and severity of disease.
Ferritin releases shows favourable defence mechanism by extensive immune
activation.3  We present a rarer clinical picture of
dengue fever with hepatic failure, thrombocytopenia and dengue encephalopathy
associated hyperferritinaemia.
 

CASE
PRESENTATION

 
A
previously healthy 35 year old male, presented with chief complains of high
grade fever with rigor, generallized myalgia, diffused abdominal pain mainly
in epigastric region and non projectile vomiting of 5 days duration. On the
examination, he was conscious and oriented.  He was clinically and hemodynamically stable.
His laboratory investigation (table 1) revealed normal heamogram. Liver
function test revealed elevated liver enzymes.  Lactate dehydrogenase (LDH) and ferritn
levels were extremely high. He had deranged prothrombine time 19 seconds. Dengue
was confirmed by etiological work up which revealed positive dengue IgM and
NS1 antigen test.
 
He
had no past history of dengue and did not have any co-morbidity. He was a
businessman and lived with his family. There is no family history of any
significance.
 
Table 1 Laboratory
investigations at the time admission

Laboratory

Value

Reference value

Haemoglobin

15.9

13.5-17.5
gm/dl

Total
white cell count

8400

4000-10000/cu
mm

Platelet
count

275000

150000
– 45000/cu mm

Total bilirubin

1.88

150
mg/dl

Fibrinogen

130

150-400
mg/dl

C
– reactive protein

8

90 folds, table 2), LDH and ferritin level; moreover
patient developed thrombocytopenia with decreased platelet counts (14000). He
underwent for Chest radiograph which revealed another complication of pleural
effusion. Cardiovascular system revealed normal functioning. Ultrasound of
abdomen showed hepatosplenomegaly with mild ascites and pseudo thickened GB
wall.  Computed tomography of brain was
normal. Based on all of these investigations a provisional diagnosis of dengue
encephalopathy associated with hyperferritineamia was made.
 
Table 2 Laboratory profile of the patient during
the course of illness

Days of illness

PC
(per cu mm)

ALT (U/L)

AST (U/L)

LDH (U/L)

PT (sec)

Ferritin(ng/ml)

Day-2

14000

3295

8825

9968

21.1

54000

Day-3

47000

3976

12848

13415

24.6

125000

Day-4

81000

3976

8093

9088

22.5

Day-5

86000

1735

3020

3352

18.2

78415

Day-6

84000

1096

1400

1896

15.8

40302

Day-7

67000

766

692

1333

15.1

19315

Day-8

45000

571

429

1176

15.8

Day-9

57000

450

289

722

14.4

5269

Day-13

200000

100

108

230

520

Day-

 

 

 

 

 

 

Normal
value

(150000-450000)

(0-40)

(0-40)

(0-250)

(11-13.5)

(70-435)

PC:
Platelet count, ALT: Alanine aminotransferase, AST: Aspartate
aminotransferase, LDH: lactate dehydrogenase, PT: Prothrombine time

TREATMENT

Our patient showed dengue encephalopathy associated with acute
hepatic dysfunction and hyperferritinaemia at the time of admission. On 3 day
of hospitalization, he was found restless, hypoxic and went in coma. He was
intubated and put on mechanical ventilation and started with injectable N –
acetyl cystine with saline, oral lactulose, rifaxamin, L- ornithine L-
aspartate. He was managed with adequate supportive care as per international
standards.  Subsequently he was
heamodynamically stable. Laboratory improvements are presented as graphs in
fig. 1 and 2.
 

OUTCOME
AND FOLLOW-UP  

 
The
patient’s laboratory abnormalities were started improving from 4th
day of hospitalization. His complication of pleural effusion was resolved on
the 5th day of hospitalization. On day 7 of hospitalization, he
was conscious and oriented and he was extubated. His laboratory investigation
revealed resolving thrombocytopenia by improving level of platelet count as
well as restored hepatic function by reduced liver enzymes and ferritin level
was drastically decreased.  He was
discharged on 11th day of hospitalization. At the time of
discharge, he was sentient and oriented with improving laboratory studies.
Follow up with laboratory study after three days of discharge revealed good
improvement in his hepatic function as well as in ferritin level. LDH found
within the normal (table 2).  After four
weeks of follow up, his liver function and ferritin levels were completely
resolved.
 

DISCUSSION

 
Dengue
is single stranded RNA virus which belongs to Flaviviridae family. Dengue fever has broad clinical features
ranging from asymptomatic infection to life threatening dengue haemorrhagic
fever and dengue shock.1   Dengue virus is tagged as non-neurotropic
virus but well reported neurological manifestation such as encephalopathy,
transverse myelitis syndrome and many more. Severe dengue infection results
multisystem impairment with acute hepatic failure, shock and coagulopathy
leading to cerebral insult. Dengue encephalopathy is well reported, though
unusual, entity with prevalence of 0.5 % to 6.2%.2
 
We
confirmed that hyperferritanemia was not associated with heamophagocytic
lymphohistiosis (HLH) by clinical investigations. In our case only few
criteria of HLH was observed those were hepatospenomegaly, elevated
transaminases, coagulopathy and hyperferritinaemia. Rest of criteria such as
raised C reactive protein, depleted erythrocyte sedimentation rate (ESR),
hypofibrinogenaemia, cytopenia, hypertriglyceridaemia was not observed. Thus
we hypothesized that hyperferritinaemia is associated to dengue fever not
because of HLH.
 
In our case, on
day 3 of hospitalization, patient developed dengue encephalopathy with
hepatic failure, thrombocytopenia, hyperferritinaemia and further elevated
LDH level. Hepatic involvement is common in dengue fever but hepatic failure
is rare.4  Hepatic failure associated with elevated
hepatic enzyme 5 folds is common but more than 10 folds are not very common.4  We observed hepatic enzyme elevation more
than 90 folds.  Dengue hepatitis results by direct or
sub-sequential replication of dengue virus in hepatocytes and Kupffer cells.
Those cause hepatic injury, stimulate apoptosis, microvascular stenosis and
develop Councilman – Rocha Lima bodies which results hepatic failure.
Unregulated host immune response may cause hepatic dysfunction. In dengue,
AST elevated sooner and gain a higher peak than ALT. The similar elevation
pattern, we observed in our case.5
 
Elevated LDH
level is due to increased proliferation of macrophages dengue fever.
Hypothesis states that Increased LDH release is indication of congestive
liver or hepatic shock as degree of LDH release is marker of hypoxia.6  
 
Development of
thrombocytopenia in case was due to dengue virus which affects directly or
indirectly bone marrow progenitor cells and suppress their function to reduce
the proliferative potential of haematopoietic cells and perfuse platelets and
occupy translational machinery for viral replication. Platelet utilization
occurs in dengue fever due to diffused intravascular coagulation, platelet
destruction due to elevated apoptosis, lysis by complement system and by involvement
of ant platelet antibodies. World Health Organization (WHO) defined
thrombocytopenia as rapid decline in platelet count which is