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Expanded Dengue Syndrome: Gastrointestinal Manifestations.

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Bangladesh Crit Care J March 2018; 6 (1): 34-39

Review Article

Expanded Dengue Syndrome: Gastrointestinal Manifestations

Ahmad Mursel Anam1, Farzana Shumy2, Raihan Rabbani3, M Mufizul Islam Polash4, Shihan Mahmud
Redwanul Huq5, Adnan Shareef6, Shahzadi Sayeeda Tun Nessa7, Mst. Arifa Sultana8, Mirza Nazim Uddin9
Abstract
Dengue, the most common and fastest emerging arboviral infection, has become a major public health concern
throughout the world. This mosquito-borne infection has got a wide variety of clinical presentation, ranging from mild
febrile illness to severe and fatal disease. However, reports of atypical or unusual features, involving multiple organ
systems, are on the rise. ‘Expanded dengue syndrome (EDS)' is a new category in the World Health Organization
(WHO) classification of dengue infection and includes atypical presentations of dengue. EDS, in the form of organ
dysfunction, may require management support from various disciplines for aggressive and effective measures.
Recognition of features of EDS is very important for targeting treatment option. Sometimes unnecessary surgery even
takes place under confusion as EDS may present in form of acute abdomen. Features of Dengue Haemorrhagic Fever
or Dengue Shock Syndrome are well-known to clinicians. Physicians, intensivists and surgeons should also be aware of
EDS, especially the gastrointestinal (GI) features and have a high degree of suspicion for early recognition and
appropriate management. This review intends to throw light on the various under-recognized unusual GI manifestations
of dengue/EDS for the benefit of the practicing physicians, intensivists and surgeons.
Key word: Expanded Dengue Syndrome, Atypical manifestation of dengue, Intensive Care Unit, Critically ill,
Bangladesh.

Introduction: distribution of vectors,4,5 and its incidence has jumped-up

Dengue is a self limiting, systemic arboviral infection. This about 30-folds in the last five decades.2 The number of actual
mosquito-borne (by Aedes aegypi and A. albopictus) disease cases of dengue infection are under reported6, but, it is
is caused by one of four single-stranded RNA viruses (dengue estimated that around 390 million dengue infections occur
virus type 1–4) of the genus flavivirus.1-3 Dengue is endemic every year, of which around 96 million manifest clinically,2,6,7
in more than a hundred countries, especially throughout the and about 3.9 billion people in 128 countries are at risk of
tropics.2,4 Its transmission is greatly influenced by local infection.8 According to the World Health Organization
weather, rainfall, mean temperature, urbanization and (WHO), approximately 500,000 cases per year develop severe
disease, and about 2.5% die.6,9 Most infections are
asymptomatic. However, after an average incubation period of
1. Dr. Ahmad Mursel Anam, MRCP(UK), Specialist, ICU, Square 4–6 days (range 3–14 days), widely variable clinical
Hospitals Ltd. Dhaka, Bangladesh manifestations, from flu-like illness to death at its most severe
2. Dr. Farzana Shumy, FCPS(Medicine), MRCP(UK), Medical form, may occur. Most patients present with fever,
Officer, Department of Internal Medicine, Bangabandhu Sheikh non-specific constitutional symptoms and features of plasma
Mujib Medical University, Dhaka, Bangladesh leakage.1-3 The infection can be easily detected and confirmed
3. Dr. Raihan Rabbani, FCPS(Medicine), Certified-American Board by different investigations from serum (Table 1)1,10. Dengue
of Internal Medicine, Consultant, Internal Medicine & Critical Care, infection, besides becoming widespread globally, is also
Square Hospitals Ltd. Dhaka, Bangladesh unfolding itself with unusual features and increased severity,
4. Dr. M Mufizul Islam Polash, MBBS, Clinical Staff, ICU, Square and thus emerging as a major threat to global health.1,11-14
Hospitals Ltd. Dhaka, Baangladesh
According to presence of plasma leakage, dengue infection is
5. Dr. Shihan Mahmud Redwanul Huq, MRCP(UK), Specialist, ICU, classified as dengue fever (no plasma leakage) and dengue
Square Hospitals Ltd. Dhaka, Bangladesh haemorrhagic fever (DHF). Depending on the level of
6. Dr. Adnan Shareef, MBBS, Clinical Staff, HDU, Square Hospitals thrombocytopenia and degree of hypotension, DHF is further
Ltd. Dhaka, Baangladesh divided into grades I to IV (Table 2).1 Dengue infection is
7. Dr. Shahzadi Sayeeda Tun Nessa, MBBS, Clinical Staff, ICU, considered severe when there is severe plasma leakage and/or
Square Hospitals Ltd. Dhaka, Baangladesh severe haemorrhage and/or severe organ impairment (Alanine
8. Dr. Mst. Arifa Sultana, MBBS, Clinical Staff, ICU, Square aminotransferase or Aspertate aminotranferase > 1000 U/L,
Hospitals Ltd. Dhaka, Baangladesh impaired consciousness, heart or other organ involved).10
9. Dr. Mirza Nazim Uddin, MRCP, Consultant, Internal Medicine &
‘Expanded dengue syndrome’ (EDS) is a new category in the
Critical Care, Square Hospitals Ltd. Dhaka, Bangladesh WHO classification of dengue infection and includes atypical
presentations of dengue, involving neurological, hepatic,
Corresponding Author : renal, cardiac and other isolated organ involvement. These
features have been increasingly reported in Dengue
Dr. Ahmad Mursel Anam, MRCP (UK)
Haemorrhagic Fever (DHF) or severe dengue, and also in
Specialist, ICU, Square Hospitals Ltd. Dhaka, Bangladesh
Email: murselanam@gmail.com dengue patients without the evidence of plasma leakage.

34
 Bangladesh Crit Care J March 2018; 6 (1): 34-39
These unusual manifestations may be associated with permeability are thought to result in thickening of the
co-infections, co-morbidities or complications of prolonged gallbladder wall. Acute acalculous cholecystitis in DHF is
shock.1,15 Often, EDS may present with severe disease, self-limiting; usually no intervention is required.14,28-30
requiring exhaustive investigations1,15 and demanding Surgical intervention is reserved for patients with diffuse
multi-disciplinary supports for aggressive and effective peritonitis.12
measures. Table 3 enlists the recognized conditions of EDS,
• Acute pancreatitis
but a number of sporadically reported features (e.g. acute
colonic pseudo-obstruction,16,17 spontaneous muscle
haematoma,18-20 spontaneous haemothorax,21,22
thyrotoxicosis23,24 etc) associated with DHF/severe dengue are
there also.
Pathogenesis
The mechanisms that lead to severe life-threatening
manifestations of dengue viral infection are not completely
understood. A number of hypotheses have been proposed,
namely, viral tropism to cell and organ systems, viral load and Fig. 2: Ultrasound showing swollen pancreas.
virulence, complement activation, transient autoimmunity, Acute pancreatitis in dengue infection presents with similar
host factors, neutralizing and non-neutralizing antibodies, features as with other causes. The exact pathogenesis is poorly
T-cell response, and soluble mediators etc, but pathogenesis is understood, but has been postulated to result either from direct
likely to be multi-factorial.25 Detailed discussion of invasion by the virus itself, causing inflammation and
pathogenesis is beyond the scope of this review, but in destruction of pancreatic acinar cells; or pancreatic damage
summary, it is evident that platelets and the vascular due to dengue shock syndrome (grades III and IV of DHF); or
endothelium are the two end-organs affected, leading to acute viral infection causing an autoimmune response to
bleeding manifestation and plasma leakage, respectively, pancreatic islet cells and development of oedema of the
leading to shock/DHF and organ dysfunction/EDS.14,25 ampulla of Vater with obstruction to the outflow of pancreatic
Gastro-Intestinal System manifestations of Expanded fluid. Raised pancreatic enzymes and edematous pancreas
Dengue Syndrome [Fig. 2] on ultrasound is evident.12,21,30 Though mortality is
high in other aetiogy, acute pancreatitis as EDS usually runs a
• Acute abdomen benign course.15
Abdominal pain is a feature of severe dengue.10 Although • Spontaneous splenic rupture
abdominal pain may present with other EDS, there are reports
of uncommon presentation with acute abdomen only.26 Some
of these patients even required surgical exploration for
exclusion of other presumptive differential diagnoses.
Mechanism for acute abdomen in EDS is not known, but
presumed to be non-specific peritonitis. Usually, conservative
measures are all that patient requires. 26,27
• Acute acalculous cholecystitis

Fig. 3: Plain CT-scan of abdomen showing splenic rupture

with haematoma in the spleen and haemoperitoneum
Fig. 1: Ultrasound showing grossly thickened edematous gall
bladder, with no evidence of calculi. Spontaneous splenic rupture is termed when non-traumatic
splenic rupture occurs in a histologically proven normal
Acute acalculous cholecystitis is usually manifested with right spleen15,32,33 It is a very rare and potentially fatal form of
upper quadrant pain. Altered liver function tests are usually EDS.15,32 It can occur in both acute and recovery phase of
present. Thickened (>3.5 mm) edematous gall-bladder wall DHF.34 The spleen, frequently being congestive, bears sub
[Fig. 1] with no stone, and positive sonographic Murphy’s capsular hematomas in 15% of cases.12,35 Left upper quadrant
sign (maximum tenderness of sonographically localized pain and shock is the usual manifestation.33 The exact
gall-bladder) is diagnostic for acute acalculous cholecystitis. mechanism is yet to understand completely, but hypothesised
The exact pathogenesis of acalculous cholecystitis is poorly as 1) increased intrasplenic tension caused by cellular
understood. However, in DHF, direct viral invasion with hyperplasia and engorgement, 2) compression by abdominal
plasma leakage and serous effusion from increased vascular

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Bangladesh Crit Care J March 2018; 6 (1): 34-39
muscles during sneezing, coughing or defecation, and 3) traumatic factors can alter the autonomic regulation of colonic
vascular occlusion causing thrombosis and infarction, function, causing colonic atony and pseudo-obstruction.42
interstitial and sub-capsular bleed, stripping of the capsule Nausea, vomiting, abdominal distension, and pain are
and finally capsular rupture. In dengue, it is thought to be due common symptoms at presentation. On examination, the
to a combination of coagulation factors and severe abdomen is tympanic, and bowel sounds are typically present.
thrombocytopenia, but again, the mechanism is not fully The most severe complication is caecal perforation, when the
clear.32,33,36 Imaging (USG, MRI or CT) of the abdomen can distension is greater than 9 cm radiographically. Supportive
easily identify this condition [Fig. 3].33,35 Splenic rupture management is usually the mainstay of successful therapy in
needs a high index of suspicion for diagnosis. It can occur in patients not exhibiting signs of perforation.42,43 The exact
both uncomplicated and complicated/severe dengue. Early cause of the syndrome in dengue infection is not completely
surgical intervention (splenectomy) and appropriate understood, but may be associated with post-viral
supportive management is required for successful outcome of dysautonomia. Hyponatraemia might also be the cause for the
patient.32,33,36 acute intestinal pseudoobstruction.16
• Splenic necrosis
This is another extremely rare EDS, reported only once till
date, that presented with left upper quadrant pain. The cause
remains unknown. Ultrasonography and Doppler findings of
splenomegaly with hypoechoic periphery and no colour flow
wass suggestive of splenic necrosis in the background of
DHF. No specific treatment was required.37
• Acute appendicitis
Although dengue fever itself can mimic acute appendicitis,
thought to be due to lymphoid hyperplasia and mesenteric
adenitis, DHF can occur concurrently with acute
appendicitis.38 The diagnosis is mainly based on clinical
grounds, i.e features of persistent right iliac fossa pain,
evidence of localized peritonism like guarding, and persistent
fever.38,39 Perforation of the inflamed appendix is potentially
fatal and can be complicated by the formation of an
appendicular mass.38 The patients need for careful evaluation,
including ultrasonography, even when the diagnosis of
dengue infection is confirmed. Delay in the diagnosis of
dengue infection can cause dengue shock syndrome or even Fig. 4: Abdominal radiograph showing dilated colon
death. Likewise, delaying or missing the diagnosis of acute Conclusion
appendicitis can result in serious complications.40 There is no
identified cause for acute appendicitis presenting EDS.41 Although reports of Expanded Dengue Syndrome are on the
rise, they are still under-recognized and under-reported. Only
• Acute colonic pseudo-obstruction a clinician with up-to-date information and high degree of
Few cases of acute colonic pseudo-obstruction (commonly suspicion can identify a case of EDS and take appropriate
known as Ogilvie’s Syndrome) has been reported.16,17 measures, prevent complications and avoid unnecessary
Ogilvie’s syndrome is a clinical condition with the symptoms, procedures. We should keep our eyes and mind open for such
signs, and radiographic appearance of acute large bowel unusual features of DHF and let others be aware of it, for the
obstruction [Fig. 4], without evidence of a mechanical ultimate benefit of patients and mankind.
cause.42,43 Infectious, metabolic, pharmacological, or Competing interests: None declared.

Table 1: Laboratory investigations for dengue10

Method Interpretation Serum collection time
Viral isolation Virus isolated At 1-5 days of fever
Genome detection Positive RT-PCR
(Reverse Transcriptase Polymerase Chain Reaction)
Antigen detection Positive NS1 Antigen
IgM seroconversion From negative IgM to positive IgM in paired sera Acute serum (days 1–5) and
convalescent serum (15–21 days
IgG seroconversion From negative IgG to positive IgG in paired sera or
after first serum)
4-fold increase IgG levels among paired sera

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 Bangladesh Crit Care J March 2018; 6 (1): 34-39
Table 2: WHO classification of dengue infection 1

Class Clinical Features Haemogram

Dengue fever Fever with two of the following: • WBC ≤5000 cells/mm3
• Headache/Retro-orbital pain. • Platelet count <150 000 cells/mm3
• Myalgia/Arthtralgia/bone pain. • Rising haematocrit (5% – 10% )
• Rash.
• Haemorrhagic manifestations.
• No evidence of plasma leakage

DHF I Fever and haemorrhagic manifestation (positive tourniquet • Platelet count <100 000 cells/mm3
test) and evidence of plasma leakage • HCT rise ≥20%

DHF II Grade I plus • Platelet count <100 000 cells/mm3

Spontaneous bleeding. • HCT rise ≥20%

DHF III Grade I or II plus • Platelet count <100 000 cells/mm3

(Dengue Shock Circulatory failure (weak pulse, narrow pulse • HCT rise ≥20%
Syndrome) pressure (≤20 mmHg), hypotension, restlessness).

DHF IV Grade III plus • Platelet count <100 000 cells/mm3

(Dengue Shock Profound shock with undetectable BP and pulse • HCT rise ≥20%
Syndrome)

Table 3: Atypical manifestations of dengue infection (EDS)1,11

System Involved Atypical Manifestation
Neurological • Febrile seizures in young children
• Encephalopathy
• Encephalitis/aseptic meningitis
• Intracranial haemorrhages/thrombosis
• Subdural effusions
• Mononeuropathies/polyneuropathies/Guillane-Barre Syndrome
• Transverse myelitis

Gastrointestinal/hepatic • Hepatitis/fulminant hepatic failure

• Acalculous cholecystitis
• Acute pancreatitis
• Hyperplasia of Peyer’s patches
• Acute parotitis

Renal • Acute renal failure

• Hemolytic uremic syndrome

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Bangladesh Crit Care J March 2018; 6 (1): 34-39

Cardiac • Conduction abnormalities

• Myocarditis
• Pericarditis

Respiratory • Acute respiratory distress syndrome

• Pulmonary haemorrhage

Musculoskeletal • Myositis with raised creatine phosphokinase (CPK)

• Rhabdomyolysis

Lymphoreticular/bone marrow • Infection associated haemophagocytic syndrome.

• Haemophagocytic lymphohistiocytosis (HLH)
• Idiopathic Thrombocytopenic Purura (ITP)
• Spontaneous splenic rupture
• Lymph node infarction

Eye • Macular haemorrhage

• Impaired visual acuity
• Optic neuritis

Others • Post-infectious fatigue syndrome

• Depression
• Hallucinations
• Psychosis
• Alopecia

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