Unusual Manifestations of Dengue Fever

Unusual Manifestations of Dengue Fever

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  Unusual Manifestations ofDengue Fever
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  Case Report CASE I AForty-year old gentleman, a known hypertensive and diabetic, presented with complaints of fever for 7 days associated with severe headache, bodyache and redness all over the body. He noticed purpuric spots over the forearm and chest one day prior to admission and also developed nausea, vomiting and bleeding from gums simultaneously. Investigations done prior to admission revealed a platelet count of 1. 2 L/cumm on 4/9/08 and 22,000/cumm on 6/9/08. USG abdomen revealed right pleural effusion. He was brought to IAH for further management. On examination, he was conscious, oriented, afebrile, tachycardic (HR-102/min), hypotensive ( BP-80/50 mm Hg)and had a RR-22/min. He had an erythematous macular rash all over the body and purpuric spots on both arms and chest. Systemic examination revealed tender hepatomegaly (1.5-2 cms below the costal margin). Rest of the examination was essentially normal. Following hospitalisation, he was resuscitated with i/v fluids and hypotension improved. Investigations revealed thrombocytopenia (platelet count-4,000/cumm), PCV- 43.3%, left lower zone plate atelectasis was noted on chest X-ray, USG abdomen revealed hepatomegaly, contracted gall bladder with edematous gall bladder wall, ascites and bilateral pleural effusion. The LFT on 6/9/08 was deranged, total bil. – 1.25mg/ dL, direct bil. -0.99 mg/dL, AST– 590 IU/L, ALT – 291 U/ L, ALP-429 U/L, SGGTP – 273 U/L and KFT showed normal serum urea, creatinine, serum albumin of 2. 5gm/ dL, serum calcium – 7.5 mg/dL. The LFTs deteriorated significantly on 9/9/08, AST rose to 13,560 IU/L, ALT- 3,370 U/L, ALP – 460 U/L, GGTP- 319U/L, Plasma ammonia was 123. All markers for viral hepatitis, Leptospira serology andANAwere negative. IgM dengue serology was initially non reactive but was strongly reactive later. A repeat Chest X Ray revealed bilateral lower zone infiltrates. The patient remained dyspnoeic and was put on noninvasive ventilation initially, but later had to be intubated and put on mechanical ventilation. During the hospital course, he also received I/V antibiotics (Piperacillin, Tazobactam and Vancomycin), platelet transfusions and insulin infusion. Patient’s condition gradually improved and he was extubated on 12/09/08. LFTs improved (serum total bilirubin – 0.73 mg/dL, AST 40 U/L, ALT- 59 U/L, SGGTP- 59 U/L, S.ALP-102U/L) after 2 weeks. In view of the absence of other demonstrable causes, the acute hepatitic picture was thought to be due to Dengue hemorrhagic fever. He was discharged in a stable condition after 19 days. CASE II A twenty-four year old gentleman, presented with complaints of fever with chills since 8 days. He was admitted in St. Stephen’s hospital where investigations revealed a progressive decline in platelet count ( from 37,000/cumm to 1,000/cumm), LFTs were also deranged and Dengue serology was negative. He developed a right intraocular haemorrage and CT head showed retinal detachment and proptosis right orbit, confirmed on an MRI orbit. He was treated with Piperacillin-Tazobactam, Artesunate, Ciprofloxacin, Doxycycline, Amoxycillin and platelet transfusion, and referred to IAH for further management. Platelet count on 69 Apollo Medicine, Vol. 7, No. 1, March 2010 UNUSUAL MANIFESTATIONS OF DENGUE FEVER Vijay Kumar Aneja*, Gitanjali Kochar** and Neelam Bisht*** *Senior Consultant, **Attending Physician, ***Associate Consultant, Department of Internal Medicine, Indraprastha Apollo Hospitals, Sarita Vihar , New Delhi 110 076, India. Correspondence to: Dr Vijay Kumar Aneja,Senior Consultant Internal Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110076, India. 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. We report two such cases of dengue hemorrhagic fever with hepatitis, intraocular hemorrhage, ARDS and myocarditis. Key words: Dengue, Dengue haemorrhagic fever, Unusual manifestations.
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  Apollo Medicine, Vol.7, No. 1, March 2010 70 Case Report the day of presentation was 74,000/cumm. There was no significant past medical history and no known drug allergy. On examination, he was conscious, oriented, dyspneic, afebrile, pulse rate-102/min, reg, BP- 150/100 mm Hg, RR- 44/min, pain score – 0/10, SPO2 86% on room air, Icterus was present, but no cyanosis, clubbing or peripheral lymphadenopathy was found. Breath sounds were decreased at bases and mild tenderness was present in the epigastrium. Rest of the systemic examination was essentially normal. Right eye had proptosis with tenderness and hemorrhage. On admission, patient was put on non invasive ventilatory support ( BiPaP) for respiratory distress. Initial investigations revealed anemia (Hb-8.6 gm/dL), leucocytosis TLC-30,400/cmm, Platelet count (1.51 lac/ cumm), coagulation profile-normal, deranged LFT (Sr. total Bilirulbin – 8.14 mg/dL, D.Bil – 6.19 mg/dL, AST- 239 IU/L, ALT–34U/L, S. ALP – 120U/L, S.GGTP – 158 U/L), features suggestive of ARDS on the Chest X Ray. IgM dengue serology was reactive, Ultrasound abdomen revealed splenomegaly with ascites and pleural effusion, 2D Echo – decreased Ejection Fraction – 45%, mild global LV hypokinesis and mildly dilated LV with overall mildly decreased global LV systolic function. Preliminary cultures were negative and in view of the clinical profile, ARDS and myocarditis were thought to be due to Dengue hemorrhagic fever with superadded sepsis. Treatment was started with dobutamine infusion, IV antibiotics (Vancomycin, Meropenem), Artesunate and IV fluids. The patient gradually started responding to the treatment and respiratory distress improved. Dobutamine was gradually tapered off, BiPaP support was discontinued. MRI brain and orbit revealed a proptosed, irregular and disrupted right eye ball with a dislocated lens, irregularity and detachment of retina and choroid with irregular scleral and episcleral thickening, with indistinct optic nerve head, retrobulbar fat stranding and oedema. Bilateral symmetrical basal ganglia signal alteration - ? Toxic, hepatic encephalopathy. An ophthalmological opinion was taken and right eye evisceration was done on 31/10/09 in view of the extensive ocular damage and no chances of vision restoration. The post operative period remained uneventful except for diarrhoea for which treatment was commenced with Chloramphenicol, Ciprofloxacin and Metrogyl. Stool routine, culture sensitivity and hanging drop examination were negative. A repeat 2D Echo on 01/11/09 revealed an Ejection fraction of 60%, no RWMA and SVR-1321 dynes sec/cm- 5. Patient gradually showed symptomatic and clinical improvement. Investigations at the time of discharge showed improvement in leucocyte count (TLC–8500/ cumm and LFT (T. Bil.-2.6 mg/dL, D.Bil –1.6 mg/dL, AST – 194 IU/L, ALT-197 U/L, S.ALP – 165 U/L, S.GGTP – 254 U/L). Patient was discharged in a stable condition after 2 weeks. Over the next 4 weeks, LFT has improved to normal. REVIEW OF LITERATURE Dengue, the most common arboviral disease transmitted globally, is caused by four antigenically distinct dengue virus serotypes (DEN 1, DEN 2, DEN 3 & DEN [4]. The dengue virus, a member of flavivirus group in the family Flaviviridae, is a single stranded enveloped RNAvirus, 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 Pacific, East and West Africa, the Caribbean and the Americas. Dengue haemorrhagic fever (DHF) epidemics occur annually with major outbreaks occurring every 3 years. Factors responsible for dengue’s 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 may be asymptomatic, may lead to undifferentiated fever (or viral syndromes), dengue fever or DHF. 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. Case definition of dengue fever (Table 1 & 2) Probable case Acute febrile illness with two or more of the following Headache, retro-orbital pain, myalgia, arthralgia, rash, hemor- rhagic manifestations, leucopenia and Supportive serology OR Occurrence at the same time and location as other confirmed cases of dengue fever
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  Case Report 71 ApolloMedicine, Vol. 7, No. 1, March 2010 Confirmed case A case confirmed 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 Demonstaration of dengue virus antigen in autopsy tissue, serum or cerebrospinal fluid samples by immunohistochemistry, immunofluorescence or ELISA; or Detection of dengue virus genomic sequences in autopsy tissue, serum or cerebrospinal fluid by polymerase chain reaction UNUSUAL 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 first described in 1976. Encephalopathy in DHF is an atypical manifestation and may appear in various forms, including depressed sensitivity, convulsions, neck rigidity, pyramidal signs, headache, papilloedema, myoclonus and behavioural disorders. Post-infectious sequelae are mainly amnesia, dementia, manic psychosis, Reye’s syndrome and meningoencephalitis. 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 [1]. 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 [2]. During the 2-year study period in a prospective case-control study carried out in a hospital in Vietnam, patients with dengue-associated encephalopathy accounted for 0.5% of all patients admitted with DHF Another study from Vietnam found dengue viruses in 4.2% of the patients with central nervous system (CNS) infections. In one of the studies dengue virus was observed in the cerebrospinal fluid (CSF) in five of six patients presenting with encephalitis, indicating that the virus may cross the blood-brain barrier and directly invade the brain. Dengue viral antigens have been demonstrated by immunohistochemistry in CNS biopsies from five fatal cases of dengue infection associated with encephalitis; infiltration of infected macrophages could be one of the pathways by which the virus may enter the brain in dengue-induced encephalitis. Testing for both dengue and Table 1. WHO classification of dengue fever DF/DHF Grade Symptoms Laboratory DF Fever with two or more of following: Leucopenia, occasionally thrombocytopenia Headache may be present. No e/o plasma loss. Retro orbital pain Myalgias Arthralgias DHF I Above signs plus positive Thrombocytopenia <100 000; tourniquet sign Hct rise 20% DHF II Above signs plus spontaneous Thrombocytopenia <100 000; bleeding Hct rise 20% DHF* III Above signs plus circulatory failure Thrombocytopenia <100 000; (weak pulse, hypotension, Hct rise 20% restlessness) DHF* IV Profound shock with undetectable Thrombocytopenia <100 000; BP and pulse Hct rise 20% DHF-dengue haemorrhagic fever; DF-dengue fever; DSS-dengue shock syndrome. *DHF III and IV also called as DSS.
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  Apollo Medicine, Vol.7, No. 1, March 2010 72 Case Report Japanese encephalitis antibodies should be carried out in areas endemic for either because of antigenic cross reactivity [3,4]. Dengue serotypes 2 and 3 have been primarily reported to cause neurological symptoms. Reported neurological manifestations other than encephalitis/encephalopathy include mononeuropathies, polyneuropathies, Guillain-Barré Syndrome and transverse myelitis. Spinal cord involvement due to dengue virus including transverse myelitis post-infectious myelopathy [5] and acute disseminated encephalomyelitis [6] are rare. Preferential grey matter involvement was found in a patient with dengue myelitis[6]. This grey matter involvement preferentially corresponded to anterior horn cell involvement similar to poliomyelitis. However, the findings with sensory levels in this patient were unlikely to be poliomyelitis. CSF-blood barrier dysfunction has been shown in patients with myelitis and Guillain-Barré syndrome. Atypical gastrointestinal manifestations of dengue Gastrointestinal manifestations of dengue are increasingly being identified 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. in Rio de Janeiro during the 1986 epidemic. Detection of dengue antigen virus in hepatocytes suggests that such cells can support viral replication. 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 normal levels within 3 weeks. Histopathological findings 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 self-limiting viral infection but it does not constitute a sign of worse prognosis. 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 12-62% of patients with dengue shock syndrome [8]. In a study, 1585 serologically confirmed cases of dengue were analysed for changes in aminotransferase levels 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. 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 findings have been found in a number of other studies also [8]. 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. 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., salicylates, 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. Acute pancreatitis is a rare complication of dengue fever. There are isolated case reports highlighting Table 2. Atypical manifestations of dengue System Manifestations Neurological Encephalopathy Manoneuropathies/ polyneuropathies/Guillane- Barre Syndrome Myelitis Gastrointestinal/ Acalculous cholecystitis hepatic Acute pancreatitis Acute parotitis Renal Hemolytic uremic syndrome Renal failure Cardiac Myocarditis Conduction abnormalities Pericarditis Respiratory ARDS Pulmonary hemorrhage Musculoskeletal Myositis Rhabdomyolysis Lymphoreticular Spontaneous splenic rupture Lymph node infarction
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  Case Report 73 ApolloMedicine, Vol. 7, No. 1, March 2010 pancreatic involvement in dengue fever [9,10]. 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. Pancreas involvement might be due to the direct viral invasion or might be due to hypotension in DHF. Acalculous cholecystitis is equally rare in dengue fever [11]. 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, post-surgical 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. There is a significant association between thickening of gall bladder wall and severity as well as progression of dengue fever. The course of the disease is usually self-limiting 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 [12]. Dengue fever was suspected early mainly because of characteristic accompanying leucopenia and thrombo-cytopenia. 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. Atypical cardiovascular manifestations of dengue fever Cardiac manifestations of dengue are uncommon but cardiac rhythm disorders such as atrioventricular blocks, atrial fibrillation, sinus node dysfunction and ectopic ventricular beats have been reported during episodes of DHF [13,14]. 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 significant Chest X ray or echocardio- graphy findings. Pericardial involvement has also been attributed to dengue infection along with myocarditis [15]. 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 and was found to occur in 0.3% of cases in a series of 6154 patients with DHF. Acute renal failure and multiple organ failure can also be a manifestation of rhabdomyolysis [16]. 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 glomerulus’s diameter, and concluded that the immune complex does not play a significant role in pathogenesis of renal failure in dengue infection. 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. Atypical respiratory manifestations of dengue Dengue haemorrhagic fever can result in acute respiratory distress syndrome (ARDS). Dengue virus antigen is found in alveolar lining cells of the lung. Increased permeability of the alveolar-capillary membrane results in the oedema in the alveoli and interstitial spaces which lead to pulmonary dysfunction [16]. Dengue shock syndrome is reported to be third leading cause of ARDS in the paediatric intensive care setting in a dengue endemic area. Early restoration of adequate tissue perfusion is critical to prevent progression of dengue shock syndrome to ARDS. However, this complication requires early recognition and management for good results. Complete clinical evaluation is needed to diagnose and establish the cause of ARDS. Treatment
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  Apollo Medicine, Vol.7, No. 1, March 2010 74 Case Report consists of ventilator and haemodynamic support besides treating the primary aetiological agent. In our case, a diagnosis of ARDS was made on the basis of chest X-ray findings in the presence of dengue hemorrhagic fever in accordance with WHO definition (Fig. 1). In the absence of any other pathogen/cause identified, we believe that DHF was the cause of ARDS in our patient.We suggest that clinicians in areas where dengue fever is endemic should be made aware of this unusual complication of DHF. Pulmonary haemorrhage with or without haemoptysis has also been reported in DHF. 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. There are only three reported cases of splenic rupture in DHF [18]. 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 coagulation in a serologically proven case of dengue fever has been reported. Multiple sections of the infracted 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.A2-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. Direct 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 findings from mild lymphocytic infiltrate to foci of severe myonecrosis. 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. 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 and Kalita 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 flaccid paralysis. Myalgias associated with dengue fever are usually short lived, but prolonged myalgias after resolution of infection have been reported. These myalgias resolved with a course of corticosteroids. Fig.1. Adult respiratory distress syndrome (ARDS) Fig.2. Vitreous hemorrhage
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  Case Report 75 ApolloMedicine, Vol. 7, No. 1, March 2010 Ocular lesions in severe dengue hemorrhagic fever (DHF) Visual disturbances in dengue fever are uncommon but may result in permanent visual impairment. Retinal haemorrhages, microinfarctions and optic neuritis were previously reported in a tourist with dengue fever.There have been several reports of ocular complications of dengue fever in the recent literature [19]. The pathogenesis and treatment options of dengue-related ocular complications are hitherto poorly established. It is probable that the pathogenesis of these ocular manifestations is directly related to the immunopathogenesis of dengue fever. Inflammatory changes in vascular endothelium resulting in vascular leakage, haemorrhage and ischaemia can be seen in cells infected with dengue virus. Ocular manifestations reported in DHF are subconjunctival hemorrhage, intraretinal haemorrhage, macular haemorrhage,vitreous hemorrhage (Fig.2), Roth spots, cotton wool spots, retinal oedema, disc oedema (Fig.3), or choroidal effusion. Macular hemorrhages have been postulated to reflect both thrombocytopenia as well as local capillary changes.Pale centered hemorrhages (Roth spots) have been noted in only one earlier report. A characteristic maculopathy has only rarely been reported and may be due to actual infection of macular tissue. This maculopathy may manifest as reduced visual acuity, abnormal visual fields or electrophysiological studies. Good recovery is the norm but exceptions have been seen in patients with macular hemorrhages. 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 1. Gubler DJ. Dengue and dengue hemorrhagic fever: its history and resurgence as a global health problem. In: DJ Gubler, G Kuno, eds. Dengue and Dengue Hemorrhagic Fever. CAB International, Willingford, UK, 1997; 1-22. 2. Patey O, Ollivaud L, Breuil J, et al. Unusual neurologic manifestations occurring during dengue fever infection. American Journal of Tropical Medicine and Hygiene 1993; 48: 793-802. 3. Miagostovich MP, Ramos RG, Nicol AF, et al. Retrospective study on dengue fatal cases. Clinical Neuropathology 1997; 16: 204-208. 4. Innis BL, Nisalak A, Nimmannitya S, et al. An enzyme- linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis cocirculate. American Journal of Tropical Medicine and Hygiene 1989; 40: 418-427. 5. Fraser HS, Wilson WA, Rose E, et al. Dengue fever in Jamaica with shock and hypocomplementaemia, haemorrhagic, visceral and neurological complications. West Indian Medical Journal 1978; 27: 106-116. 6. Yamamoto Y, Takasaki T, Yamada K, et al. Acute disseminated encephalomyelitis following dengue fever. Journal of Infection and Chemotherapy 2002; 8: 175-177. 7. Nogueira RMR, Miagostovich MP, Schatzmayr HG, et al. Virological study of a dengue type 1 epidemic in Rio de Janeiro. Memorias do Instituto Oswaldo Cruz 1988; 83: 219-225. 8. Mohan B, Patwari AK, Anand VK, et al. Hepatic dysfunction in childhood dengue infection. Journal of Tropical Pediatrics 2000; 46: 40-43. 9. Chen TC, Pernq DS, Tsai JJ, et al. Dengue Hemorrhagic Fever complicated with pancreatitis and seizure. Journal Fig.3. Serial photographs of the right eye showing optic disc swelling 3 (a) and 7 (b) days after onset of dengue fever. Optic atrophy is evident 1 month later (c).
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  Apollo Medicine, Vol.7, No. 1, March 2010 76 Case Report of the Formosan MedicalAssociation 2004; 103: 865-868. 10. Jusuf H, Sudjana P, Djumhana A, et al. DHF with complication of acute pancreatitis related hyperglycemia: a case report. Southeast Asian Journal of Tropical Medicine and Public Health 1998; 29: 367-369. 11. Beniwal P, Kumar S, Gulati S, et al. Acalculous cholecystitis in dengue fever. Indian Journal for the Practising Doctor 2000; 3 (4): 2006-08 - 2006-2009. 12. Helbok R, Dent W, Gattringer K, et al. Imported dengue fever presenting with febrile diarrhea: report of 2 cases. Wiener Klinische Wochenschrift 2004; 116 (suppl 4): 58-60. 13. Chuah SK. Transient ventricular arrhythmia as a cardiac manifestation in dengue haemorrhagic fever: a case report. Singapore Medical Journal 1987; 28: 569-572. 14. Promphan W, Sopontammarak S, Pruekprasert P, et al. Dengue myocarditis. Southeast Asian Journal of Tropical Medicine and Public Health 2004; 35: 611-613. 15. Nagaratnam N, Sripala K, De Silva N. Arbovirus (Dengue type) as a cause of acute myocarditis and pericarditis. British Heart Journal 1973; 35: 204-206. 16. Lum LCS, Thong MK, Cheah YK & Lam SK. Dengue- associated adult respiratory distress syndrome. Annals of Tropical Paediatrics 1995; 15: 335-339. 17. Setlik RF, Ouellette D, Morgan J, et al. Pulmonary hemorrhage syndrome associated with an autochthonous case of dengue hemorrhagic fever. Southern Medical Journal 2004; 97: 688-691. 18. Redondo MC, Ríos A, Cohen R, et al. Hemorrhagic dengue with spontaneous splenic rupture. Clinical Infectious Diseases 1997; 25: 1262-1263. 19. Haritoglou C, Scholz F, Bialasiewicz A , Klauss V. Ocular manifestation in dengue fever. Ophthalmologie 2000; 97: 433-436.