Acute acalculous cholecystitis secondary to dengue fever.

Abstract

Patients with dengue fever usually present with typical symptoms such as fever, frontal headache, retro-ocular pain, myalgia, arthralgia, nausea, vomiting, rash, leucopaenia and thrombocytopaenia. However, they can also manifest with atypical symptoms. Acute acalculous cholecystitis is an atypical manifestation of dengue fever. In dengue endemic areas such as Brunei Darussalam, it is imperative that typical and atypical presentations of dengue fever are recognised so that early diagnosis can be made. We report a case of an 18-year-old Malay lady who presented with fever, cough, abdominal pain, and generalised myalgia. She was found to have acute acalculous cholecystitis secondary to dengue fever.

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Acute acalculous cholecystitis
secondary to dengue fever
Farah HISAMONIE KOH 1, Hartini MISLI 2, Vui Heng CHONG 2
1 Medical School, Queensland University, Australia, 2 Department of Medicine,
RIPAS Hospital, Brunei Darussalam
ABSTRACT
Patients with dengue fever usually present with typical symptoms such as fever, frontal headache,
retro-ocular pain, myalgia, arthralgia, nausea, vomiting, rash, leucopaenia and thrombocytopaenia.
However, they can also manifest with atypical symptoms. Acute acalculous cholecystitis is an atypical
manifestation of dengue fever. In dengue endemic areas such as Brunei Darussalam, it is imperative
that typical and atypical presentations of dengue fever are recognised so that early diagnosis can be
made. We report a case of an 18-year-old Malay lady who presented with fever, cough, abdominal
pain, and generalised myalgia. She was found to have acute acalculous cholecystitis secondary to den-
gue fever.

Keywords: Cholecystitis, complications, dengue haemorrhagic fever
INTRODUCTION
Dengue fever is a mosquito-borne viral dis-
ease transmitted by the infected female
Aedes aegypti mosquitoes and is endemic in
the tropical and subtropical countries, includ-
ing Brunei Darussalam. 1 Patients typically
present with fever, frontal headache, retro-
ocular pain, myalgia, arthralgia, nausea, vom-
iting, rash, leucopaenia and thrombocytopae-
nia. 2, 3 Atypical presentations are infrequent,
and if unrecognised, may potentially result in
delayed diagnosis leading to potentially catas-
trophic consequences. 2 We report a case of
an 18-year-old Malay lady who presented
with abdominal pain, and generalised myal-
gia. She was found to have acute acalculous
cholecystitis (AAC) secondary to dengue fe-
ver.
Case Report
Brunei Int Med J. 2011; 7 (1): 45-49
Correspondence author: Vui Heng CHONG
Department of Medicine, RIPAS Hospital,
Bandar Seri Begawan BA 1710,
Brunei Darussalam
Tel+673 2242424 Ext 5235, +673 8778218
E-mail: chongvuih@yahoo.co.uk
CASE REPORT
An 18-year-old Malay lady with no known
past medical history presented to RIPAS Hos-
pital with a three-day history of fever, cough,
abdominal pain, and generalised myalgia. She
also complained of loss of appetite. Her sister
and brother had been recently diagnosed with
dengue fever. There was no history of rash
and recent travel. On examination, she was
alert and appeared well. She had a tempera-
ture of 40.1oC, with a blood pressure of 95/60
mmHg, pulse rate 112 per min and respira-
tory rate of 22 per min. There was no pallor,

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or lymphadenopathy. Examination of the ab-
domen revealed mild epigastric and right up-
per quadrant tenderness. There was no re-
bound tenderness, guarding, masses, or-
ganomegaly or ascites. Bowel sounds were
present. Her respiratory, cardiovascular, neu-
rological and ear, nose and throat examina-
tions were unremarkable.

Laboratory and haematological inves-
tigations on admission were as follows: total
white cell counts 3.2 x 109/L (4.0 to 11.0)
with 76.5% neutrophils (40 to 75) and 13.1%
lymphocytes (15 to 41), haemoglobin 12.0 g/
dL (12.0 to 16.0), platelets 81 x 109/L (150 to
450), haematocrit 36.8% (36 to 46),
prothrombin time 14.3 seconds (9.9 to 12.9),
APTT 38.4 seconds (25.6 to 41.5), INR 1.29
(0.8 to 1.2), C-reactive protein (CRP) 0.95
mg/dL (0 to 0.50). Liver function test and
electrolyte panel were normal. Blood culture,
peripheral blood film for malarial parasite,
serology for viral hepatitis A, B and C were all
negative. Chest radiography was normal. Se-
rology for dengue was positive with dengue
IgM antibodies.
The patient was given intravenous
fluids and was started on regular intravenous
antibiotics consisting of amoxicillin-clavulanic
acid (augmentin, 1.2gm t.i.d) and metronida-
zole (500mg t.i.d). Daily full blood count
showed a decreasing trend of platelets from
81 to the nadir point of 26 X109/L and she
was given four units of platelets.

On the third day of admission, an ul-
trasound scan of her abdomen was done to
evaluate the right upper quadrant pain, sus-
pected to be cholecystitis. The scan showed a
thickened and oedematous gall bladder
(8mm, normal <3mm). No stones or sludge
were seen and the common bile duct and he-
patic ducts were normal. There was also as-
cites and left pleural effusion. The scan was
consistent with a diagnosis of AAC and this
was attributed to the dengue infection.

The patient was continued on conser-
vative treatment with intravenous fluids and
was later given an additional four units of
platelets. Her fever settled within 24 hours of
admission with resolution of her abdominal
HISAMONIE KOH et al. Brunei Int Med J. 2011; 7 (1): 46
Fig. 1: Ultrasound scan shows marked thickening of the gallbladder
and pericholecystic fluid in the absence of any stones or sludge.

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pain on the third day. The platelet level came
up to 321 x 109/L on the ninth day of admis-
sion. She was discharged well on the ninth
day with oral metronidazole (400mg t.i.d) for
10 days. She defaulted her clinic follow up
appointment but had remained well when she
was contacted via telephone.
the whole range of symptoms. It is also inter-
esting to note that our patient had manifested
with an atypical manifestation despite the
mild degree of her dengue fever. Hence, it is
imperative that clinicians are familiar with
both the typical and atypical manifestations. 4
Atypical presentations (Table 1) are infre-
quent, and if unrecognised, may potentially
lead to catastrophic illness. 2

AAC has been reported to account for
approximately 10% of all cases of acute
cholecystitis. 6 Patients with AAC present with
fever, right upper quadrant abdominal pain,
positive Murphy’s sign, and abnormal liver
function tests. Ultrasonographic findings for
diagnosis of AAC include thickening of the
gallbladder wall over 3mm, gallbladder disten-
tion, localised tenderness, pericholecystic fluid
and sludge. 4

AAC is traditionally known to occur in
the critically ill patients with mortality as high
as 90%. 6 A variety of clinical conditions is
associated with AAC which includes burns,
HISAMONIE KOH et al. Brunei Int Med J. 2011; 7 (1): 47
DISCUSSION
Dengue fever is endemic in tropical and sub-
tropical countries in Southeast Asia, the Pa-
cific, East and West Africa, the Caribbean and
the Americas. 1 In Brunei Darussalam, there
has been an outbreak of dengue fever with
the main focus located at the water village
(Kampong Ayer) in Bandar Seri Begawan. Our
patient was also from the water village.
Therefore in our setting, any patients admit-
ted from Kampong Ayer with fever and
thrombocytopenia needs to have dengue in-
fection excluded.

Most presented with typical symptoms
as did our patient. However, it is important to
realise that not every patient will manifest
Table 1: Atypical manifestations of dengue infection


System

Gastrointestinal







Manifestations
Acalculous cholecystitis, acute pancreatitis, acute parotitis
febrile diarrhoea, hepatitis / fulminant hepatic failure

Cardiovascular Conduction abnormalities
Atrioventricular blocks (first degree AV block, Mobitz type I second degree
AV block, complete heart block, atrial fibrillation, sinus node dysfunction
(sinus bradycardia, sinoatrial exit block), ectopic ventricular ectopic
Myocarditis, pericarditis

Acute respiratory distress syndrome, pulmonary haemorrhage Respiratory

Neurological

Encephalopathy, encephalitis, septic meningitis, intracranial haemorrhages,
thrombosis, mononeuropathies, polyneuropahties, Guillian-Barre syndrome,
myelitis

Renal

Lympho-reticular

Musculosckeletal

Adapted from Gulati S and Maheshwari A. 1
Haemolytic anaemia, renal failure
Spontaneous splenic rupture, lymph node infarction, haemophagocytosis
Myositis, rhabdomyolysis

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childbirth, cholesterol emboli, coronary heart
disease, diabetes mellitus, immunosuppres-
sion, major trauma, mechanical ventilation,
medications (e.g. opiates), multiple transfu-
sions, nonbiliary surgery, sepsis/hypotension,
total parenteral nutrition, and vasculitis. 7-13
AAC can also occur in outpatients with no evi-
dence of acute illness or trauma. It is also
interesting to note certain infections have
been reported to be associated with AAC. 4, 14
Dengue infection has been reported to be as-
sociated with AAC in up to 7.6% in a study
from Taiwan. In our local setting, to our
knowledge, this is the only case of AAC asso-
ciated with dengue fever.

The exact pathogenesis of AAC is un-
known, but cholestasis and increased bile vis-
cosity from prolonged fasting, spasms of the
ampulla of Vater, infection, endotoxaemia,
microangiopathy and ischaemia-reperfusion
injury have been suggested. Dengue virus
has been shown to be present in the brains of
patients with neurological manifestations.
Whether, the virus itself has any direct effect
on the pathogenesis of AAC is unknown. In
dengue fever, the main pathophysiological
changes of AAC could be due to increased
vascular permeability, causing plasma leakage
and serous effusion with high protein content,
which then causes thickening of the gallblad-
der wall. 1 A thickened wall can lead to motil-
ity problem. The associated hypoalbuminemia
may be an important contributory factor.

AAC needs to be diagnosed early and
requires prompt management, especially in
critically ill patients. Management includes
starting broad spectrum antibiotics after blood
cultures have been obtained. The definitive
therapy for AAC is cholecystectomy with
drainage of any associated abscess via percu-
taneous cholecystostomy.
6 AAC in dengue
fever is usually self-limiting, and the gall blad-
der wall thickness usually returns to normal.
Thus, management is conservative with anti-
biotic therapy. Cholecystectomy is usually not
indicated in dengue patients unlike other sub-
sets of patients. It is however indicated if
there are complications like gangrene and
perforation.1

In conclusion, AAC can manifest in
dengue fever. In dengue endemic areas, it is
important that typical and atypical presenta-
tions of dengue fever are recognised.
HISAMONIE KOH et al. Brunei Int Med J. 2011; 7 (1): 48
Table 2: Infections associated with acute acalculous cholecystititis.


Genus Organism

Virus Hepatitis A, Cytomegalovirus, Ebstein Barr virus, Dengue

Bacteria Salmonella species, Vibro cholera, Escherichia coli, Klebsiella species,
Staphylococcus species, Serratia marcesens, Leptospira species,
Mycobacterium avium-intracellulare

Parasites Isospora bellis, Microsporidia, Cryptosporidium, Malaria

Fungus Candida species

Adapted from Chong VH and Goh SK. 14

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HISAMONIE KOH et al. Brunei Int Med J. 2011; 7 (1): 49
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