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
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ABSTRACT
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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.
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INTRODUCTION
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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 occurred 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 patients 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 diagnoses 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 symptoms and signs.
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MATERIALS AND METHODS
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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 transcriptase–polymerase chain reaction result, a positive enzyme-linked immunosorbent (ELISA) assay result for specific dengue IgM in acute-phase serum, or a four-fold increase in dengue-specific hemagglutination inhibition titers in convalescent-phase serum.11,12 The assay for dengue IgM was performed using IgG/IgM capture ELISA kits (Panbio, Windsor, Queensland, Australia). The quality assurance of 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 Organization 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 progressive abdominal pain that was the dominant feature of the patient’s illness, and the pain was characterized by the presence of a peritoneal sign (e.g., rebound tenderness and/or muscle guarding).14 In patients with acute abdomen, a presumptive 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 diagnosis, which was made based on the observation of the evolutionary clinical course and laboratory data. Several patients with DHF and acute abdomen during the local dengue epidemic underwent invasive procedures including percutaneous drainage or surgery at the discretion of the attending physician 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, ecchymosis, 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 corresponding blood components are as follows: 50 mL (platelets/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 procedures and those not receiving invasive procedures. For comparison of differences between these two groups, the Mann-Whitney U test and Fisher’s exact test were used for assessments of continuous variables and dichotomous data, respectively. A two-tailed P < 0.05 was considered statistically significant.
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RESULTS
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Of 328 patients with DHF, 163 (49.7%) had general abdominal pain and 14 (4.3%) (diffuse peritonitis in five patients and localized peritonitis in nine patients) had acute 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 laboratory data of these 14 patients upon admission are summarized 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%) patients. 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 cholecystitis (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 including ultrasonography in 13 patients (additional computed tomography 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 calculus and another with acalculus cholecystitis) developed diffuse 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, percutaneous transhepatic gallbladder drainage (PTGBD), and appendectomy. Elective surgery was planned for each of the remaining 11 patients, but because of thrombocytopenia, medical 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 information for the three patients who underwent invasive procedures are summarized in Table 3.
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TABLE 3 Detailed information of the three patients with dengue hemorrhagic fever (DHF) and acute abdomen who underwent invasive procedures*
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All patients with DHF and acute abdomen in this series survived. However, three patients who underwent surgery or drainage experienced massive bleeding that mandated substantial transfusions. Transfused volumes of blood components 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.
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DISCUSSION
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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 salmonellosis, rickettsiosis, and leptospirosis. The pathogenesis of acute cholecystitis in DHF is not fully understood, but may result from localized microangiopathy in the gallbladder wall.22
Acute appendicitis was found in one patient who underwent appendectomy in this series. To our knowledge, no complicated acute appendicitis in patients with DHF/DSS has been previously reported.23 Thrombocytopenia was observed one day after surgery in this patient, and histopathologic analysis of the excised appendix showed a predominant infiltration of lymphocytes, which was not consistent with acute 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 complication in patients with DHF and clarify the relationship between the clinically diagnosed appendicitis and DHF in terms of pathogenesis. Further studies to elucidate more information on this respect are warranted. Information regarding appendicitis in patients with DHF, albeit rare, may help circumvent surgical intervention of appendicitis in DHF because the diagnosis of appendicitis is based on clinical findings.
Acute abdomen usually results from active bacterial infection.14 The clinically overlapping manifestations of dengue virus and bacterial infections make it difficult, if not impossible, 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 normal PT as observed in our patients may serve as an important clue to dengue illness because activation of internal pathway of coagulation was reported in patients with DHF.7,24 The blood-clotting process in hemostasis is initiated by the formation of thrombin from prothrombin, and there are two ways in which prothrombin activator can be formed: 1) by the extrinsic 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 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 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 essential for binding and activation of plasminogen. Thus, hemorrhagia in DHF results mainly from an inadequate factor XI/thrombin/TAFI feedback loop, which leads to an imbalance between coagulation and fibrinolysis.24
In view of the blood cultures negative for bacteria growth and the absence of histopathologic evidence of bacterial infection, we believe that the invasive procedures performed on the three patients in this series were unnecessary. Although 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 infections, and had significantly prolonged hospitalization.
This series underscores the importance of a careful differential diagnosis when treating a patient with acute abdomen in a dengue-endemic setting. Under such circumstances, a diligent search for the commonly encountered clinical manifestations of dengue illness that would otherwise be ignored cannot be overemphasized. When a patient’s clinical condition is stable, surgical or drainage interventions may be delayed, and if concurrent DHF and bacterial infections are suspected, the patient should be supportively treated for DHF, and antibiotic(s) should be additionally administrated for possible superimposing bacterial infections. Prolonged fever (> 5 days) and acute renal failure have been reported to be independent risk factors for concurrent bacterial infection in adult patients with DHF/DSS.8
Received April 9, 2005.
Accepted for publication November 8, 2005.
* Address correspondence to Jien-Wei Liu, Division of Infectious 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{at}adm.cgmh.org.tw 
Authors’ addresses: Boon-Siang Khor, Department of Emergency and Critical Medicine, Li-Shin Hospital, Ping-Chen, Taoyuan, Taiwan, Republic of China. Jien-Wei Liu and Ing-Kit Lee, Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, and School of Medicine, 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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ABSTRACT
INTRODUCTION
