Tropical Medicine and International Health volume 12 no 9 pp 10871095 september 2007

doi:10.1111/j.1365-3156.2007.01891.x

Atypical manifestations of dengue

Sameer Gulati and Anu Maheshwari
Maulana Azad Medical College, New Delhi, India

Summary

As the spread of dengue and dengue haemorrhagic fever is increasing, atypical manifestations are also on the rise, although they may be under reported because of lack of awareness. This review compiles descriptions of atypical manifestations of dengue, such as dengue encephalitis, dengue myocarditis, dengue hepatitis and dengue cholecystitis. keywords dengue fever, dengue haemorrhagic fever, dengue encephalitis, dengue myocarditis, dengue hepatitis, dengue cholecystitis

Introduction Dengue, the most common arboviral disease transmitted globally, is caused by four antigenically distinct dengue virus serotypes (DEN 1, DEN 2, DEN 3 and DEN 4). The dengue virus, a member of avivirus group in the family Flaviviridae, is a single stranded enveloped RNA virus, 30 nm in diameter, which can grow in a variety of mosquitoes and tissue cultures. The four serotypes possess antigens that cross-react with Yellow Fever, Japanese encephalitis and West Nile viruses. The infection is transmitted by infected female Aedes mosquitoes. Dengue is a worldwide condition spread throughout the tropical and subtropical zones between 30 N and 40 S. It is endemic in South-East Asia, the Pacic, East and West Africa, the Caribbean and the Americas (Gubler & Clark 1995; Gubler 1997). Dengue haemorrhagic fever (DHF) epidemics occur annually with major outbreaks occurring every 3 years. Factors responsible for dengues spread include explosive population growth, unplanned urban overpopulation with inadequate public health systems, poor vector control and increased international recreational, business and military travel to endemic areas. Indeed dengue and DHF is fast emerging as a global health problem. Dengue infections (Tables 1 and 2) may be asymptomatic, may lead to undifferentiated fever (or viral syndromes), dengue fever or DHF (World Health Organization, 1997). Mild dengue disease is characterized by biphasic fever, several types of skin rash, headache, retro orbital pain, photophobia, cough, vomiting, myalgia, arthralgia, leukopenia, thrombocytopenia and lymphadenopathy, while DHF is an often fatal disease characterized by haemorrhages and shock syndrome. Other common symptoms include sore throat, altered taste sensation, colicky pain and abdominal tenderness, consti-

pation, dragging pain in the inguinal region and general depression (Table 3). Classical dengue fever is rare among indigenous people as most of the adults are immune. In these areas both mild dengue illness and DHF occur mainly in children, but cases in young as well as older adults have been reported. DHF is usually associated with secondary dengue infection but can appear during a primary infection, especially in infants who possess maternal IgG dengue antibody. With increasing reports of dengue in adults, neonatal dengue including DHF because of vertical transmission have been reported (Chye et al. 1997). A second attack of DHF is very rare: it has been shown to occur in about 0.5% of cases in a study over a 16-year period at Childrens Hospital in Bangkok (Nimmannitya et al. 1990). As dengue and DHF are assuming global proportions, more and more atypical presentations appear, which might be under reported because of lack of awareness. The present review briey consolidates the atypical manifestations of dengue (Figure 1). Atypical manifestations of dengue The endothelium is the target of the immunopathological mechanisms in dengue and DHF. The hallmark is vascular permeability and coagulation disorders. These mechanisms can explain varied systemic involvement. Atypical neurological manifestations of dengue The relationship between DHF and neurological disturbances was rst described in 1976 (Solomon et al. 2000; Pancharoen & Thisyakorn 2001). Encephalopathy in DHF is an atypical manifestation and may appear in various forms, including depressed sensitivity, convulsions, neck rigidity, pyramidal signs, headache, papilloedema, 1087

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Table 1 Case denition of dengue fever (http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/) Probable case Acute febrile illness with two or more of following Headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopenia. and Supportive serology OR Occurrence at the same time and location as other conrmed cases of dengue fever A case conrmed by laboratory criteria i.e.: Isolation of dengue virus from serum or autopsy samples; or Demonstration of fourfold or greater change in reciprocal IgG or IgM antibody titers to one or more dengue virus antigens in paired serum samples; or Demonstartion of dengue virus antigen in autopsy tissue, serum or cerebrospinal uid samples by immunohistochemistry, immunouorescence or ELISA; or Detection of dengue virus genomic sequences in autiopsy tissue, serum or cerebro spinal uid by polymerase chain reaction

Conrmed case

Table 2 WHO classication of dengue fever. (http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/) DF DHF DF Grade Symptoms Fever with two or more of following: Headache Retro orbital pain Myalgias Arthralgias Above signs plus positive tourniquet sign Above signs plus spontaneous bleeding Above signs plus circulatory failure (weak pulse, hypotension, restlessness) Profound shock with undetectable BP and pulse Laboratory Leucopenia, occasionally thrombocytopenia may be present. No e o plasma loss.

DHF DHF DHF* DHF*

I II III IV

Thrombocytopenia < 100 000; Hct rise 20% Thrombocytopenia < 100 000; Hct rise 20% Thrombocytopenia < 100 000; Hct rise 20% Thrombocytopenia < 100 000; Hct rise 20%

DHF, dengue haemorrhagic fever; DF, dengue fever; DSS, dengue shock syndrome. *DHF III and IV also called as DSS.

myoclonus and behavioural disorders. Post-infectious sequelae are mainly amnesia, dementia, manic psychosis, Reyes syndrome and meningo encephalitis. Neurological involvement may occur because of intracranial haemorrhage, cerebral oedema, hyponatremia, cerebral anoxia, fulminant hepatic failure with portosystemic encephalopathy, renal failure or release of toxic products. Pathophysiology of neurological involvement may include the following factors: direct tissue lesion caused by the virus because of its neurotropicity, capillary haemorrhage, disseminated intravascular coagulation and metabolic disorders (Lum et al. 1996). A number of patients with DHF and concurrent neurological symptoms have been described as case reports or as part of minor series of patients with unusual manifestations (Kho et al. 1981; Nimmannitya et al. 1987; Patey et al. 1993; Row et al. 1996; Thakare et al. 1996; Hommel et al. 1998; Strobel et al. 1999; Solomon et al. 2000; Pancharoen & Thisyakorn 2001). During the 2-year study period in a prospective casecontrol study carried out in a hospital in Vietnam, patients with dengue-associated encephalo1088

pathy accounted for 0.5% of all patients admitted with DHF (Cam et al. 2001). Another study from Vietnam found dengue viruses in 4.2% of the patients with central nervous system (CNS) infections (Solomon et al. 2000). In one of the studies dengue virus was observed in the cerebrospinal uid (CSF) in ve of six patients presenting with encephalitis, indicating that the virus may cross the bloodbrain barrier and directly invade the brain (Lum et al. 1996). Studies in mice had already shown virusinduced cytokine mediated breakdown of bloodbrain barrier. Dengue viral antigens have been demonstrated by immunohistochemistry in CNS biopsies from ve fatal cases of dengue infection associated with encephalitis; inltration of infected macrophages could be one of the pathways by which the virus may enter the brain in dengue-induced encephalitis (Miagostovich et al. 1997). Testing for both dengue and Japanese encephalitis antibodies should be carried out in areas endemic for either because of antigenic cross reactivity (Innis et al. 1989). Unfortunately, as yet there are no data to show dengue viral replication in CNS of patients without neurological

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Table 3 Atypical manifestations of dengue System Neurological Manifestations Encephalopathy Encephalitis aseptic meningitis Intracranial haemorrhages thrombosis Mononeuropathies polyneuropathies GuillaneBarre Syndrome Myelitis Hepatitis fulminant hepatic failure Acalculous cholecystitis Acute pancreatitis Febrile diarrhea Acute parotitis Hemolytic uremic syndrome Renal failure Myocarditis Conduction abnormalities Pericarditis ARDS Pulmonary hemorrhage Myositis Rhabdomyolysis Spontaneous splenic rupture Lymph node infarction Refrences Kho et al. (1981), Row et al. (1996), Thakare et al. (1996), Cam et al. (2001) Lum et al. (1996), Hommel et al. (1998) Luiz Jose de Souza et al. Brazilian Journal of Infectious Diseases vol.9 no.3 Salvador June 2005 Soares et al. (2006) Leao et al. (2002) Lawn et al. (2003) Sharma et al. (2006), Goh & Tan (2006), Wu et al. (2003) Jusuf et al. (1998), Chen et al. (2004) Helbok et al. (2004) Torres et al. (2000) Wiersinga et al. (2006) Hommel et al. (1999), Wiwanitkit (2005a,b) Promphan W et al. (Promphan et al. 2004) Veloso et al. (2003), Khongphatthallayothin et al. (2000), Chuah (1987) Nagaratnam et al. (1973) Sen et al. (1999), Thong (1998), Lum et al. (1995) Setlik et al. (2004), Liam et al. (1993) Kalita et al. (2005) Gunasekera et al. (2000), Davis & Bourke (2004) Imbert et al. (1993), Redondo et al. (1997), Miranda et al. (2003) Rao et al. (2005)

Gastrointestinal Hepatic

Renal Cardiac

Respiratory Musculoskeletal Lymphoreticular

Figure 1 Clinical spectrum of dengue fever (http://www.who.int/csr/resources/ publications/dengue/Denguepublication/ en/)

involvement. The severity of neurological disease caused by different dengue serotypes has been examined in a number of studies. Dengue serotypes 2 and 3 have been primarily reported to cause neurological symptoms (Lum et al. 1996; Row et al. 1996; Hommel et al. 1998). Magnetic resonance imaging is superior to computed tomography scans when demonstrating CNS lesions (Gilman 1998a,b). MRI in a cohort of patients with dengueassociated neurological involvement revealed cerebral

oedema in most patients; encephalitis-like changes were less common; and one patient had intracranial haemorrhage (Cam et al. 2001). Japanese encephalitis co-infection had MRI ndings consistent with this infection (Kalita & Misra 2006). Globus pallidus involvement has also been reported (Misra et al. 2006). Strictly speaking, encephalitis can only be diagnosed on histological conrmation. However, brain biopsy and necropsy is not possible in many areas where dengue 1089

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occurs. Most published postmortem series are on patients who died from DHF rather than from CNS afictions and the lesions have been rather non-specic (oedema, vascular congestions and focal haemorrhages) (Burke 1968). Dengue virus serotype 4 has been detected by immunohistochemistry and by RT-PCR in inferior olivary nucleus of medulla and granular layers of cerebellum. Immunoreactivity has been observed in endothelial cells, astrocytes, neurones and microglia. Extended immunohistochemical studies have shown the virus positive cells located mostly with Virchow Robin space of medium size and small veins, inltrating the white and grey matter are often close to neurones displaying cytopathic features (Ramos et al. 1998). Reported neurological manifestations other than encephalitis encephalopathy include mononeuropathies, polyneuropathies, GuillainBarre Syndrome and transverse myelitis (Patey et al. 1993; Soares et al. 2006). Spinal cord involvement due to dengue virus including transverse myelitis (Solomon et al. 2000; Leao et al. 2002), post infectious myelopathy (Fraser et al. 1978) and acute disseminated encephalomyelitis (Yamamoto et al. 2002) are rare. Preferential grey matter involvement was found in a patient with dengue myelitis (Kunishige et al. 2004). This grey matter involvement preferentially corresponded to anterior horn cell involvement similar to poliomyelitis. However, the ndings with sensory levels in this patient were unlikely to be poliomyelitis. CSFblood barrier dysfunction has been shown in patients with myelitis and GuillainBarre Syndrome (Soares et al. 2006). Atypical gastrointestinal manifestations of dengue Gastrointestinal manifestations of dengue are increasingly being identied and reported, such as hepatitis, fulminant hepatic failure, acalculous cholecystitis, acute pancreatitis, acute parotitis and febrile diarrhoea. Any patient presenting with acute abdomen in dengue endemic areas should be evaluated for dengue fever and dengue-related acute acalculous cholecystitis; acute pancreatitis and acute hepatitis should be promptly recognized. Dengue virus antigen is found in Kupfer cells and sinusoidal lining cells in the liver. Isolation of dengue virus type I from the liver was made by Nogueira et al. (1988) in Rio de Janeiro during the 1986 epidemic. Detection of dengue antigen virus in hepatocytes suggests that such cells can support viral replication (Miagostovich et al. 2002). Hepatic manifestations can be characterized by manifestations of acute hepatitis with pain in the hypochondrium, hepatomegaly, jaundice and raised aminotransferase levels. In hepatitis the levels of these enzymes peak on the ninth day after onset of symptoms and gradually return to 1090

normal levels within 3 weeks. Histopathological ndings include centrilobular necrosis, fatty alterations, hyperplasia of the Kupfer cells, acidophil bodies and monocyte alteration of the portal tracts. In most cases hepatic involvement prolongs the clinical course of this selflimiting viral infection but it does not constitute a sign of worse prognosis (Nimmannitya 1987; Miagostovich et al. 2002). The presence of jaundice in these patients is multifactorial. It can be due to hepatic aggression caused by the dengue virus and or hypoxia and tissue ischaemia in cases of shock. Jaundice occurs in 1262% of patients with dengue shock syndrome (Mohan et al. 2000). Increased levels of alkaline phosphatase and bilirubin are found in a smaller proportion of cases (Kuo et al. 1992). In a study, 1585 serologically conrmed cases of dengue were analysed for changes in aminotransferase levels (De Souza et al. 2004) and showed that there was a greater elevation in AST than ALT levels, which may be explained by AST being released from the damaged monocytes (Chung et al. 1992). This information may be useful in differential diagnosis of acute hepatitis especially in dengue endemic areas. Liver damage, and consequently increases in aminotransferase levels, were more frequent among females and in patients with DHF. Similar ndings have been found in a number of other studies also (Nimmannitya 1987; Kuo et al. 1992; Mohan et al. 2000). From 1973 to 1982, the observed hepatic involvement in dengue infection in Thailand and Malaysia was mild and it manifested solely as increase in aminotransferase levels. But after this period several cases of fulminant hepatitis with high mortality have been reported (Lawn et al. 2003). Severe haemorrhage, shock, metabolic acidosis and disseminated intravascular coagulation may contribute to severe changes in liver. It should be remembered that even chronic liver disease, alcoholic steatonecrosis and hepatotoxic drug use (e.g. salicyclates, acetaminophen etc.) during dengue infection may predispose to and may even increase liver injury. Acute liver failure is a severe complicating factor in dengue infection predisposing to life threatening haemorrhage, disseminated intravascular coagulation and encephalopathy. The increase in aminotransferases has been associated with increased disease severity and might serve as an early indicator of dengue infection. Acute pancreatitis is a rare complication of dengue fever. There are isolated case reports highlighting pancreatic involvement in dengue fever (Jusuf et al. 1998; Chen et al. 2004). One hundred and forty-eight children with DHF and abdominal pain were enrolled in a study to look for sonographic evidence of pancreas involvement. Enlarged pancreas and increase serum amylase and lipase levels were found in 29% of the patients (Setiawan et al. 1998). Pancreas involvement might be due to the direct viral

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invasion or might be due to hypotension in DHF. We could not nd any case series or report investigating the pancreatic histological ndings in dengue to document direct viral invasion. This might be due to difculty in obtaining samples. Thus more denitive studies are required to determine pathogenesis and which subset of dengue patients develops pancreatitis. Acalculous cholecystitis is equally rare in dengue fever (Beniwal et al. 2000; Wu et al. 2003; Goh & Tan 2006; Sharma et al. 2006). Patients present with right upper quadrant abdominal pain, fever, positive Murphy sign, abnormal liver function tests and thickened gall bladder wall without stones on abdominal ultrasonography. Differential diagnosis of acalculous cholecystitis other than dengue fever includes burns, trauma, vasculitis, postsurgical conditions and certain infections such as salmonellosis, leptospirosis, rickettsiosis and cytomegalovirus infections in immunocompromised patients. The exact pathogenesis of acalculous cholecystitis is not known, but prolonged fasting, spasms of ampulla of vater, infection, endotoxemia, microangiopathy and ischaemia reperfusion injury have been suggested as possible causes of cholestasis and increased bile viscosity. The main pathophysiological changes in dengue fever could be due to increased vascular permeability causing plasma leakage and serous effusion with high protein content which causes thickening of gall bladder wall (Gubler et al. 1998). There is a signicant association between thickening of gall bladder wall and severity as well as progression of dengue fever (Setiawan et al. 1995). The course of the disease is usually selflimiting and the gall bladder wall thickness usually returns to normal. Thus cholecystectomy is usually not advised in dengue patients unlike other subsets of patients. Rapid progression of acalculous cholecystitis to gangrene and perforation has been reported and therefore prompt recognition and intervention are required for these complications. Surgical intervention is reserved for patients with diffuse peritonitis. Two dengue patients have been reported to present with febrile diarrhoea followed by haemorrhagic skin lesions (Helbok et al. 2004). Dengue fever was suspected early mainly because of characteristic accompanying leucopenia and thrombocytopenia. Both patients had a benign clinical course. Bilateral parotid gland enlargement in an immunocompetent patient with dengue infection and evidence of dengue virus in saliva has been described as a unique case (Torres et al. 2000). Atypical cardiovascular manifestations of dengue fever Cardiac manifestations of dengue are uncommon but cardiac rhythm disorders such as atrioventricular blocks,

atrial brillation, sinus node dysfunction and ectopic ventricular beats have been reported during episodes of DHF (Chuah 1987; Khongphatthallayothin et al. 2000; Veloso et al. 2003; Promphan et al. 2004). Most are asymptomatic and have a benign self limiting course with resolution of infection. These arrythmias have been attributed to viral myocarditis, but an exact mechanism has not been elucidated. In most of the reported cases there were no documented electrolyte disturbances or signicant Chest X ray or echocardiography ndings. Pericardial involvement has also been attributed to dengue infection along with myocarditis (Nagaratnam et al. 1973). Atypical renal manifestations of dengue Acute renal failure is rare in dengue fever and it mainly presents as shock induced acute tubular necrosis. It has been observed as a complication of dengue fever in French Guiana (Hommel et al. 1999) and was found to occur in 0.3% of cases in a series of 6154 patients with DHF (Wiwanitkit 2005a). Descriptions of glomerular changes observed in DHF are scarce. They include a variety of signs including IgG, IgM and or C3 deposition and thickening of the glomerular basement membrane (Boonpucknavig et al. 1976). Acute renal failure and multiple organ failure can also be a manifestation of rhabdomyolysis (Gunasekera et al. 2000). The role of immune complex in development of renal failure in dengue infection is still unclear. Wiwanitkit discovered that the diameter of dengue virus immunoglobulin complex is much smaller than the diameter of glomerulus. Thus he postulated that immune complex can be entrapped only if a previous glomerular lesion causes narrowing of the glomeruluss diameter, and concluded that the immune complex does not play a signicant role in pathogenesis of renal failure in dengue infection (Wiwanitkit 2005b). Renal failure because of haemolytic uraemic syndrome has been described in an isolated case report where renal biopsy revealed thrombotic microangiopathy with glomerular and arteriolar microthrombi. Electron microscopy demonstrated presence of microtubuloreticular structures suggesting a viral infection. This patient was treated with plasmapheresis, haemodialysis and anti-hypertensive drugs (Wiersinga et al. 2006). Atypical respiratory manifestations of dengue Dengue haemorrhagic fever can result in acute respiratory distress syndrome (ARDS) (Lum et al. 1995; Thong 1998; Sen et al. 1999). Dengue virus antigen is found in alveolar lining cells of the lung. Increased permeability of the alveolar-capillary membrane results in the oedema in 1091

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the alveoli and interstitial spaces which lead to pulmonary dysfunction (Lum et al. 1995). Dengue shock syndrome is reported to be third leading cause of ARDS in the paediatric intensive care setting in a dengue endemic area (Goh et al. 1998). Early restoration of adequate tissue perfusion is critical to prevent progression of dengue shock syndrome to ARDS. However, equal care must be exercised to avoid excessive uid infusion after adequate volume replacement because uid overload may result in ARDS. This complication requires early recognition and management for good results. Pulmonary haemorrhage with or without haemoptysis has also been reported in DHF (Liam et al. 1993; Setlik et al. 2004). Lymphoreticular complications of dengue Dengue virus antigen is found predominantly in cells of the spleen, thymus and lymph nodes. In DHF, lymphadenopathy is observed in half of the cases and splenomegaly is rarely observed in small infants. Splenic rupture and lymph node infarction in DHF are rare. The spleen which is frequently congestive, bears sub capsular hematomas in 15% of cases (Bhamarapravati et al. 1967). There are only three reported cases of splenic rupture in DHF (Imbert et al. 1993; Redondo et al. 1997; Miranda et al. 2003). Physicians should be aware of this fatal complication in areas endemic to dengue. A case of splenic rupture can be misdiagnosed because of misinterpretation of the shock syndrome as in a case of dengue shock syndrome dengue shock syndrome. Splenectomy can be curative. A case of lymph node infarction in association with disseminated intravascular infarction in a serologically proven case of dengue fever has been reported (Rao et al. 2005). Multiple sections of the infarcted and the surrounding non-infarcted lymph nodes failed to reveal any predisposing condition. However the parahilar vessels showed thrombotic occlusion, which must have been responsible for infarction. As malignant lymphoma is the commonest cause of lymph node infarction, this disease should be ruled out using immunohistochemistry. A 2-year follow up is required to rule out development of malignant lymphoma beyond which the risk is negligible. Atypical musculoskeletal complications of dengue fever Dengue fever has been described classically as break bone fever as it causes severe muscle, joint and bone pain. Rhabdomyolysis is not well characterized in DHF. There are a handful of case reports recognizing this complication (Gunasekera et al. 2000; Davis & Bourke 2004). Direct 1092

invasion of muscle by virus has not been demonstrated and the most likely cause appears to be myotoxic cytokines, particularly TNF. Studies of muscle biopsy specimens have revealed a range of ndings from mild lymphocytic inltrate to foci of severe myonecrosis (Malheiros et al. 1993). Davis et al. suggest that urinalysis be performed in all patients with severe DHF as a screening tool and that serum creatinine phosphokinase levels be measured if urinalysis is positive for haeme. This will go a long way in recognizing this underreported entity. Rhabdomyolysis can lead to acute renal failure and electrolyte disturbances, if unrecognized. However, if recognized early, these complications can be easily prevented. Patients with dengue might present with pure motor weakness. Creatinine phosphokinase is elevated in most and electromyography and muscle biopsy is consistent with myositis. Patients usually show satisfactory improvement (Misra et al. 2006). Kalita et al. (2005) have pointed out that in an area endemic with dengue, dengue-related acute pure motor quadriplegia because of myositis should be considered in the differential diagnosis of acute accid paralysis. Myalgias associated with dengue fever are usually short lived, but prolonged myalgias after resolution of infection have been reported (Finsterer & Konqchan 2006). These myalgias resolved with a course of corticosteroids. Conclusion Dengue can have varied and multisystemic presentations. The atypical manifestations described here might be unrecognized and underreported. However, it is imperative to know all these manifestations for clinical diagnosis and appropriate management, especially given the global health problem which dengue presents. References
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Miagostovich MP, Santos FB, De Simone TS et al. (2002) Genetic characterization of dengue virus type 3 isolates in the State of Rio de Janeiro, 2001. Brazilian Journal of Medical and Biological Research 35, 14. Miranda LEC, Miranda SJC & Rolland M (2003) Case Report: Spontaneous Rupture of the Spleen Due to Dengue Fever. Brazilian Journal of Infectious Diseases 7, 423425. Misra UK, Kalita J, Syam UK et al. (2006) Neurological manifestations of dengue virus infection. Journal of the Neurological Sciences. 15, 244. Epub 2006 Mar 9. Mohan B., Patwari AK, Anand VK et al. (2000) Hepatic dysfunction in childhood dengue infection. Journal of Tropical Pediatrics 46, 4043. Nagaratnam N, Sripala K & De Silva N. (1973) Arbovirus (Dengue type) as a cause of acute myocarditis and pericarditis. British Heart Journal 35, 204206. Nimmannitya S. (1987) Clinical spectrum and management of dengue haemorrhagic fever. Southeast Asian Journal of Tropical Medicine and Public Health 18, 392397. Nimmannitya S, Thisyakorn U & Hemsrichart V (1987) Dengue haemorrhagic fever with unusual manifestations. Southeast Asian Journal of Tropical Medicine and Public Health 18, 398 406. Nimmannitya S, Kalaayanarooj S, Nisalak A et al. (1990) Second attack of Dengue Hemorrhagic fever. Proceedings of the International Symposium on Dengue and Dengue Hemorrhagic Fever, Bangkok. Nogueira RMR, Miagostovich MP, Schatzmayr HG et al. (1988) Virological study of a dengue type 1 epidemic in Rio de Janeiro. Memorias do Instituto Oswaldo Cruz 83, 219 225. Pancharoen C & Thisyakorn U (2001) Neurological Manifestations in Dengue Patients. Southeast Asian Journal of Tropical Medicine and Public Health 32, 341345. Patey O, Ollivaud L, Breuil J et al. (1993) Unusual neurologic manifestations occurring during dengue fever infection. American Journal of Tropical Medicine and Hygiene 48, 793 802. Promphan W, Sopontammarak S, Pruekprasert P et al. (2004) Dengue myocarditis. Southeast Asian Journal of Tropical Medicine and Public Health 35, 611613. Ramos C, Sanchez G, Pando RH et al. (1998) Dengue virus in the brain of a fatal case of haemorrhagic dengue fever. Journal of Neurovirology 4, 465468. Rao IS, Loya AC, Ratnakar KS et al. (2005) Lymph node infarction- a rare complication associated with disseminated intravascular coagulation in a case of dengue fever. BMC Clinical Pathology 12, 5. Redondo MC, Ros A, Cohen R et al. (1997) Hemorrhagic dengue with spontaneous splenic rupture. Clinical Infectious Diseases 25, 12621263. Row D, Weinstein P, Murray-Smith S et al. (1996) Dengue fever with encephalopathy in Australia. American Journal of Tropical Medicine and Hygiene 54, 253255.

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Tropical Medicine and International Health S. Gulati & A. Maheshwari Atypical manifestations of dengue

volume 12 no 9 pp 10871095 september 2007

Corresponding Author: Sameer Gulati, Maulana Azad Medical College, New Delhi, India. E-mail: drsameergulati@gmail.com

Revue: Manifestations atypiques de la dengue Alors que la propagation de la dengue et de la evre hemorragique de la dengue saccrot, les manifestations atypiques sont egalement en augmentation ` bien quelles pourraient etre encore sous rapportees a cause du manque de prise de conscience. Cette revue compile des descriptions sur les ` manifestations atypiques de la dengue, telles que: lencephalite de la dengue, la myocardite de la dengue, lhepatite de la dengue et la cholecystite de la dengue. ` mots cles evre de la dengue, evre hemorragique de la dengue, encephalite de la dengue, myocardite de la dengue, hepatite de la dengue, cholecystite ` de la dengue

Revision: Manifestaciones atpicas del dengue A medida que aumenta la dispersion del dengue y de la ebre hemorragica del dengue, las manifestaciones atpicas tambien van en aumento, aunque podran estar por debajo de la cifra real debido a una falta de concienciacion. Esta revision recoge descripciones de manifestaciones atpicas del dengue, tales como la encefalitis, miocarditis, hepatitis o colecistitis por dengue. palabras clave ebre del dengue, dengue hemorragico, encefalitis por dengue, miocarditis por dengue, hepatitis por dengue, colecistitis por dengue

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