Am. J. Trop. Med. Hyg., 74(5), 2006, pp.

901–904
Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

DENGUE HEMORRHAGIC FEVER PATIENTS WITH ACUTE ABDOMEN: CLINICAL

EXPERIENCE OF 14 CASES
BOON-SIANG KHOR, JIEN-WEI LIU,* ING-KIT LEE, AND KUENDER D. YANG
Division of Infectious Diseases, Department of Internal Medicine, and Department of Pediatrics, Chang Gung Memorial
Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan, Republic of China

Abstract. Among 328 patients with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 14 (4 men and
10 women, median age 44 years) had acute abdomen. DHF/DSS was initially suspected in only 2 of these 14 patients.
Presumptive diagnoses of acute cholecystitis (6 acalculus and 4 calculus cholecystitis) were made in 10 patients, non-
specific peritonitis in three patients, and acute appendicitis in one patients. Cholecystectomy, percutaneous transhepatic
gallbladder drainage, and appendectomy were performed in three patients. Transfused blood in the three patients who
underwent invasive procedures and the 11 patients who received supportive treatment included packed red blood cells
(24 versus 0 units; P ⳱ 0.048), fresh frozen plasma (84 versus 0 units; P ⳱ 0.048), and platelets (192 versus 180 units;
P ⳱ 0.003). Patients who underwent invasive procedures also had prolonged time in the hospital (median ⳱ 11 versus
7 days; P ⳱ 0.015). To avoid unnecessary invasive procedure–related morbidity and mortality, this report underscores
the importance of a careful differential diagnosis in patients with acute abdomen in a dengue-endemic setting.

INTRODUCTION Windsor, Queensland, Australia). The quality assurance of

Dengue virus is a mosquito-borne flavivirus and the most
prevalent arbovirus in tropical and subtropical regions of the
globe. Dengue is widely distributed in many countries in
southeast and southern Asia, Central and South America, and
the Western Pacific regions.1 Dengue epidemics have oc-
curred in Taiwan since the early part of the 20th century,2–6
and a dengue epidemic with a substantial number of patients
with dengue hemorrhagic fever (DHF) occurred from June
2002 to the end of 2002.7,8 In this epidemic, among other
clinical manifestations, a variety of gastrointestinal symptoms
and signs, including acute abdomen, were observed in pa-
tients with DHF.7–10 Acute abdomen in these patients made
the clinical situation bewildering and diagnosis of the etiology
and patient management challenging. We herein report diag-
noses and treatments involving 14 patients with DHF and
acute abdomen. This report may offer valuable information
to clinicians who are inexperienced in dealing with patients
with DHF who show such atypical but not uncommon symp-
toms and signs.
MATERIALS AND METHODS
This is a retrospective study of patients with DHF and
acute abdomen in a dengue epidemic in southern Taiwan.
Among 328 patients with the diagnosis of DHF admitted to
the Chang Gung Memorial Hospital-Kaohsiung between
June 2002 and December 2002, those with acute abdomen
were included for analyses. The diagnosis of dengue fever
(DF) was made based on either a positive reverse tran-
scriptase–polymerase chain reaction result, a positive en-
zyme-linked immunosorbent (ELISA) assay result for spe-
cific dengue IgM in acute-phase serum, or a four-fold increase
in dengue-specific hemagglutination inhibition titers in con-
valescent-phase serum.11,12 The assay for dengue IgM was
performed using IgG/IgM capture ELISA kits (Panbio,
the diagnostic tests was confirmed by the Center for Disease
Control, Taiwan. The diagnostic criteria for DHF in patients
with laboratory confirmed DF and the severity of DHF was
categorized in accordance with the World Health Organiza-
tion definitions.13 Grade III DHF and grade IV DHF were
grouped as dengue shock syndrome (DSS).13
Acute abdomen was defined as a sudden onset of progres-
sive abdominal pain that was the dominant feature of the
patient’s illness, and the pain was characterized by the pres-
ence of a peritoneal sign (e.g., rebound tenderness and/or
muscle guarding).14 In patients with acute abdomen, a pre-
sumptive diagnosis referred to the tentative diagnosis made
by the attending physician upon patient’s admission, and a
definitive diagnosis referred to the patient’s discharge diag-
nosis, which was made based on the observation of the evo-
lutionary clinical course and laboratory data. Several patients
with DHF and acute abdomen during the local dengue epi-
demic underwent invasive procedures including percutaneous
drainage or surgery at the discretion of the attending physi-
cian based on the presumptive diagnosis he or she made.
Transfusions were required in the included patients because
of either DHF-associated bleeding alone (e.g., petechia, ec-
chymosis, gum bleeding, and gastrointestinal bleeding) and/or
additional invasive procedure–related bleeding. The volume
per unit of transfused material in Taiwan varies from one
blood component to another. Specifically, the volumes of cor-
responding blood components are as follows: 50 mL (plate-
lets/unit), 250 mL (packed red blood cells [PRBC]/unit), and
125 mL (fresh frozen plasma [FFP]/unit).
The included patients with DHF and acute abdomen were
divided into two groups: patients receiving invasive proce-
dures and those not receiving invasive procedures. For com-
parison of differences between these two groups, the Mann-
Whitney U test and Fisher’s exact test were used for assess-
ments of continuous variables and dichotomous data,
respectively. A two-tailed P < 0.05 was considered statistically
significant.

* Address correspondence to Jien-Wei Liu, Division of Infectious RESULTS

Diseases, Department of Internal Medicine, Chang Gung Memorial
Hospital-Kaohsiung Medical Center, 123 Ta Pei Road, Niao Sung
Hsiang, Kaohsiung Hsien 833, Taiwan, Republic of China. E-mail:
88b0@adm.cgmh.org.tw
Of 328 patients with DHF, 163 (49.7%) had general ab-
dominal pain and 14 (4.3%) (diffuse peritonitis in five
patients and localized peritonitis in nine patients) had acute

901
902
abdomen. These 14 patients (12 with DHF and 2 with DSS)
included four men and 10 women with a median age of 44
years (range ⳱ 15–68). The clinical manifestations and labo-
ratory data of these 14 patients upon admission are summa-
rized in Table 1 and Table 2, respectively. Leukopenia was
found in 5 (35.7%) patients, atypical lymphocytosis in 9
(64.3%) patients, and thrombocytopenia in 14 (100%) pa-
tients. No leukocytosis was found in these patients at their
hospitalizations. Among patients with data available, 7 (7/7,
100%) had prolonged activated partial thromboplastin times
(APTTs) and normal prothrombin times (PTs), 11 (11/13;
84.6%) had elevated serum aspartate aminotransferase, and 8
(8/11; 72.7%) had abnormally high alanine aminotransferase.
On admission, the presumptive diagnosis of acute cholecys-
titis (6 acalculus and 4 calculus cholecystitis) was made in 10
patients, non-specific diffuse peritonitis in three patients, and
acute appendicitis in one patient. Imaging procedures includ-
ing ultrasonography in 13 patients (additional computed to-
mography in 5 patients) and abdominal plain film in 1 patient
with acute appendicitis did not show any evidence of pus or
blood accumulation in the abdominal cavity in any of these
patients. All patients received empirical antibiotic treatment
for acute abdomen at admission. Two of the patients with
presumptively diagnosed acute cholecystitis (one with calcu-
lus and another with acalculus cholecystitis) developed dif-
fuse peritonitis and shock. Only 2 (14.2%) of the 14 included
patients were suspected of having DHF at admission. All 14
patients with acute abdomen were considered candidates for
surgery. Invasive procedures were performed in three
(21.4%) patients which included cholecystectomy, percutane-
ous transhepatic gallbladder drainage (PTGBD), and appen-
dectomy. Elective surgery was planned for each of the re-
maining 11 patients, but because of thrombocytopenia, medi-
cal treatment was instituted first. At follow-up, the acute
abdomen in these 11 patients improved and their peripheral
platelet counts normalized, which made scheduled surgical
interventions no longer necessary. Blood cultures of these
patients were negative for bacterial growth. Detailed infor-
mation for the three patients who underwent invasive proce-
dures are summarized in Table 3.
All patients with DHF and acute abdomen in this series
survived. However, three patients who underwent surgery or
TABLE 1
Symptoms/signs of 14 patients with dengue hemorrhagic fever (DHF)
and acute abdomen*
Symptom/sign
Fever
Myalgia
Nausea and/or vomiting
Chills
Skin rashes
Diarrhea
Headache
Dizziness
DHF-associated bleeding
Murphy’s sign
Diffuse peritonitis
Shock
* An individual patient might have more than one symptom and/or sign.
† Acute cholecystitis in two patients (one with calculus cholecystitis and another with
acalculus cholecystitis), and non-specific diffuse peritonitis in three patients.
‡ Both had dengue shock syndrome (one patient with acute calculus cholecystitis subse-
quently underwent a cholecystectomy and the other with acute acalculus cholecystitis re-
ceived supportive management).
KHOR AND OTHERS
TABLE 2
Laboratory data of 14 patients with dengue hemorrhagic fever and
acute abdomen*
Variable n/N (%)
Thrombocytopenia† 14/14 (100)
Median (range) (× 109 cells/L) 1.7 (0.70–8.6)
Peripheral WBC count
Leukopenia‡ 5/14 (35.7)
Atypical lymphocytosis§ 9/14 (64.3)
Prolongation of APTT¶ 7/7 (100)
Prolongation of PT# 0/7 (0)
Elevated AST (> 40 U/L) 11/13 (84.6)
Elevated ALT (> 40 U/L) 8/11 (72.7)
* n ⳱ No. of patients; N ⳱ No. of patients with data available; WBC ⳱ white blood cells;
APTT ⳱ activated partial thromboplastin time; PT ⳱ prothrombin time; ALT ⳱ alanine
aminotransferase; AST ⳱ aspartate aminotransferase.
† Thrombocytopenia was defined as a platelet count < 100 × 109 cells/L.
‡ Leukopenia was defined as a peripheral WBC count < 4.0 × 109 cells/L.
§ Atypical lymphocytosis was defined as a peripheral atypical lymphocyte count > 5% of
the WBC count.
¶ Prolongation of the APTT was defined as > 20% than that of the control.
# Prolongation of the PT was defined as > 3 seconds than that of the control.
drainage experienced massive bleeding that mandated sub-
stantial transfusions. Transfused volumes of blood compo-
nents in the 3 patients who underwent invasive procedures
and the 11 who did not included PRBC (24 versus 0 units;
P ⳱ 0.048), FFP (84 versus 0 units; P ⳱ 0.048) and platelets
(192 versus 180 units; P ⳱ 0.003). In addition, patients who
underwent invasive procedures had prolonged hospital stays
(median ⳱ 11 days, range ⳱ 9–19) compared with those with
received only medical treatment (median ⳱ 7 days, range ⳱
3–9), with a P ⳱ 0.015.
DISCUSSION
In addition to acute abdomen, the included patients in this
series had a variety of symptoms and signs such as fever,
chills, myalgia, headache, rashes, and petechia, which were
similar to those found in patients with DHF without acute
abdomen.7,8 However, the predominant acute abdomen in
these patients was the overwhelming concern and distracted
clinicians from the typical clinical manifestations of dengue
illness that would have been noticed. Acute cholecystitis, an
increasingly reported manifestation in patients with DHF/
DSS, is not unique in dengue illness; it has been sporadically
reported in salmonellosis, rickettsiosis, and leptospirosis.15–19
If one considers reports indicating a thickened gallbladder
wall observed sonographically in as many as 90% of patients
with DHF,9,10,20,21 acute cholecystitis may be much more
common in patients with DHF than in patients with salmo-
nellosis, rickettsiosis, and leptospirosis. The pathogenesis of
No. of patients (%) acute cholecystitis in DHF is not fully understood, but may
14 (100) result from localized microangiopathy in the gallbladder
5 (35.7) wall.22
5 (35.7) Acute appendicitis was found in one patient who under-
4 (28.6)
3 (21.4) went appendectomy in this series. To our knowledge, no com-
3 (21.4) plicated acute appendicitis in patients with DHF/DSS has
2 (14.3) been previously reported.23 Thrombocytopenia was observed
1 (7.1) one day after surgery in this patient, and histopathologic
14 (100)
10 (71.4)
analysis of the excised appendix showed a predominant infil-
5† (35.7) tration of lymphocytes, which was not consistent with acute
2‡ (14.3) bacterial appendicitis.23 However, it is not possible on the
basis of this single case of appendicitis in a patient with DHF
to clearly generalize an evolutionary course of such a com-
plication in patients with DHF and clarify the relationship
between the clinically diagnosed appendicitis and DHF in
 DHF AND ACUTE ABDOMEN 903

† Normal platelet count was found in patient 3 at admission at noon with fever and acute abdomen. He underwent an appendectomy that night; persistent bleeding from the surgical wound and thrombocytopenia (PLT ⳱ 2.8 × 109 cell/L) as well as leukopenia
* PLT ⳱ platelets; WBC ⳱ white blood cells; PT ⳱ prothrombin time; APTT ⳱ activated partial thromboplastin time; PRBC ⳱ packed red blood cells; FFP ⳱ fresh frozen plasma; PTGBD ⳱ percutaneous transhepatic gallbladder drainage. Volumes:
Survived
Survived

Survived
terms of pathogenesis. Further studies to elucidate more in-

Outcome
formation on this respect are warranted. Information regard-
ing appendicitis in patients with DHF, albeit rare, may help
circumvent surgical intervention of appendicitis in DHF be-
cause the diagnosis of appendicitis is based on clinical find-

lymphoid follicle
finding of the excised

infiltration with
Mononuclear cell ings.
Histopathologic

infiltration of
lymphocytes
Acute abdomen usually results from active bacterial infec-

Predominant
tissue

formation tion.14 The clinically overlapping manifestations of dengue

–
virus and bacterial infections make it difficult, if not impos-
Detailed information of the three patients with dengue hemorrhagic fever (DHF) and acute abdomen who underwent invasive procedures*

sible, to distinguish these infection entities from each other.8

Thrombocytopenia, an universally encountered hematologic
disorder in patients with DHF, may also be seen in patients
with bacterial sepsis. However, a prolonged APTT and a nor-
Catheter exit site bleeding;

transfusion of platelets,
transfusion of platelets,

Surgical wound bleeding;

substantial transfusion

mal PT as observed in our patients may serve as an important

units; FFP, 84 units;
Massive bleeding with

including PRBC, 24

clue to dengue illness because activation of internal pathway

platelets, 108 units
invasive procedure
Complication of

of coagulation was reported in patients with DHF.7,24 The

blood-clotting process in hemostasis is initiated by the forma-
tion of thrombin from prothrombin, and there are two ways in
48 units
36 units

which prothrombin activator can be formed: 1) by the extrin-

sic pathway that begins with trauma to the vascular wall or to
the tissue outside blood vessels, or 2) by the intrinsic pathway
that begins with the blood itself. In patients with DHF, the
intrinsic pathway of coagulation cascade is triggered by
Cholecystectomy
Invasive procedure

Appendectomy

thrombin (initially formed by tissue factor pathway that is

then rapidly inhibited) activating coagulation factor XI via
positive feedback.24 Factor XI generates additional thrombin
PTGBD

by activation of factors IX and X. Patients with DHF have a

comparatively low level of thrombin-activatable fibrinolysis
inhibitor (TAFI). The function of TAFI is to down-regulate
fibrinolysis by removing C-terminal lysine residues that are
Acute appendicitis
cholecystitis and
TABLE 3

essential for binding and activation of plasminogen. Thus,

Acute acaculus
Acute calculus

septic shock

cholecystitis
at admission
Presumptive

hemorrhagia in DHF results mainly from an inadequate fac-

diagnosis

tor XI/thrombin/TAFI feedback loop, which leads to an im-

balance between coagulation and fibrinolysis.24
In view of the blood cultures negative for bacteria growth
and the absence of histopathologic evidence of bacterial in-
fection, we believe that the invasive procedures performed on
Grade III

Grade II
Grade II
Severity of

the three patients in this series were unnecessary. Although

DHF

the two patients who underwent surgical intervention and the

one who received PTGBD in this series survived, all required
otherwise avoidable substantial blood transfusions, and were
at increased risk for potential transfusion-associated infec-
cells/L; WBC, 4.9

cells/L; WBC, 1.7

× 109 cells/L; PT,

× 109 cells/L; PT,

7.0 × 109 cells/L;

11.5 sec; APTT,

10.4 sec; APTT,

tions, and had significantly prolonged hospitalization.

APTT, 34.8 sec
cells/L;† WBC,
Initial laboratory

PLT, 19.5 × 109

This series underscores the importance of a careful differ-

PT, 10.2 sec;
9

PLT, 4.7 × 109

PLT, 1.9 × 10

ential diagnosis when treating a patient with acute abdomen

data

46.3 sec

42.6 sec

in a dengue-endemic setting. Under such circumstances, a

PRBC/unit ⳱ 250 mL; FFP/unit ⳱ 125 mL; PLT/unit ⳱ 50 mL.

diligent search for the commonly encountered clinical mani-

festations of dengue illness that would otherwise be ignored
(WBCs ⳱ 3.7 × 109 cells/L) were found the following day.

cannot be overemphasized. When a patient’s clinical condi-

tion is stable, surgical or drainage interventions may be de-
Hypertension

layed, and if concurrent DHF and bacterial infections are

Underlying

mellitus
disease

Diabetes

suspected, the patient should be supportively treated for

–

DHF, and antibiotic(s) should be additionally administrated

for possible superimposing bacterial infections. Prolonged fe-
ver (> 5 days) and acute renal failure have been reported to
be independent risk factors for concurrent bacterial infection
Age (years),

26, M

in adult patients with DHF/DSS.8

68, F

54, F
sex

Received April 9, 2005. Accepted for publication November 8, 2005.

Authors’ addresses: Boon-Siang Khor, Department of Emergency
Patient

and Critical Medicine, Li-Shin Hospital, Ping-Chen, Taoyuan, Tai-

no.

wan, Republic of China. Jien-Wei Liu and Ing-Kit Lee, Division of

1

3
904 KHOR AND OTHERS
Infectious Diseases, Department of Internal Medicine, Chang Gung
Memorial Hospital-Kaohsiung Medical Center, and School of Medi-
cine, Chang Gung University Taiwan, Kweishan, Taoyuan, Taiwan,
Republic of China. Kuender D. Yang, Department of Pediatrics,
Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan,
Republic of China.
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