Dengue: Spectrum of Systemic Manifestations

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Dengue: Spectrum of Systemic Manifestations Poster No.: C-0235 Congress: ECR 2016 Type: Educational Exhibit Authors: P. KANNAN, R. SETH, H. K. THAKRAR, M. Seth, M. thakur ; 1 1 1 1 2 2 2 MUMBAI, MAHARASHTRA/IN, Mumbai/IN Keywords: Emergency, Ultrasound, CT, MR, Diagnostic procedure, Infection, Tropical diseases DOI: 10.1594/ecr2016/C-0235 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 34

Learning objectives To describe the various manifestations we have encountered in dengue patients To suggest a diagnosis of dengue at radiology in patients with atypical symptoms To aid in early management and to take appropriate therapeutic decisions Background Dengue is a mosquito borne viral disease caused by arbovirus. It is transmitted by the female Aedes aegypti mosquito. The disease is widespread in the tropics, with local variations caused by temperature and unplanned rapid urbanization. It starts during the rainy season when breeding of vector mosquitoes is generally abundant. Dengue cases in India are more during July to September. There are 4 distinct, but closely related serotypes that cause dengue (DEN-1, DEN-2,DEN-3 AND DEN-4). Infection provides lifelong immunity against that serotype, but partial and temporary immunity to other subtypes. Subsequent infection with other serotypes can cause severe dengue infection. The mortality is around 1-2 % [1]. Dengue should be suspected when a high fever is accompanied by 2 of the following symptoms: severe headache, nausea, vomiting or rash. After an incubation period of 4-10 days, symptoms usually last for 2-7 days. The disease spectrum varies from asymptomatic or mild infection, through varying thrombocytopenia and vascular leakage that is typical of dengue haemorrhagic fever(dhf), to a severe shock syndrome and multi organ failure. WHO case definitions for dengue shock [2] Fever, or history of acute fever, lasting 2-7 days, occasionally biphasic Hemorrhagic tendencies, evidenced by at least one of the following A positive tourniquet test Petechiae, ecchymoses, or purpura Bleeding from the mucosa, gastrointestinal tract, injection sites, or other locations Hematemesis or melena Thrombocytopenia (100000/mm3 or less) Page 2 of 34

Evidence of plasma leakage due to increased vascular permeability, manifested by at least one of the following; A rise in hematocrit #20% above the average for age, sex and population A drop in hematocrit following volume replacement equal to or greater than 20% of the baseline Signs of plasma leakage such as pleural effusion, ascites or hypoproteinemia All four of the above PLUS evidence of circulatory failure, manifested by: Rapid weak pulse, and Narrow pulse pressure (<20mmHg) OR Hypotension for age, and Cold, clammy skin, and restlessness Findings and procedure details ABDOMINAL MANIFESTATIONS CASE 01: A 25 year old female presented with severe onset of acute abdominal pain. There was a history of fever for 5 days prior to this and she had tested positive for dengue. Her total counts were marginally high with mildly abnormal liver function tests. On clinical examination, there was severe tenderness in the right upper quadrant with positive Murphy's sign. Study: An initial ultrasound showed minimal free fluid in the abdomen. In view of severe persisting pain, a CT-abdomen was done (Fig. 1, Fig. 2). CT abdomen showed moderate low dense gall bladder wall thickening. No GB calculus was seen on USG or CT. The liver was mildly enlarged and somewhat heterogeneous. Moderate free fluid was seen in the pelvis. Page 3 of 34

Fig. 1 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 4 of 34

Fig. 2 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 A diagnosis of Acalculous Cholecystitis was made with associated hepatitis. Acalculous cholecystitis should be suspected in a case of DF presenting with abdominal pain, fever, a positive Murphy's sign, mild elevation of transaminases and a thickened gallbladder wall without stones on ultrasonography. In DF patients with acute acalculous cholecystitis, the course of DF could be self-limiting and the gallbladder wall could return to normal after several days. Cholecystectomy in a case of dengue fever complicated by acalculous cholecystitis is rarely required and hence the patient should be closely observed for signs of perforation. Adequate Page 5 of 34

hydration, antipyretics and platelet-transfusion in cases with severe thrombocytopenia may be all they need. [3] [4] Dengue fever should be strongly considered in patients that present with signs of cholecystitis in dengue endemic areas especially when radiological findings show no stones and the platelet count is low. As acute acalculous cholecystitis is known to have a fulminant course, a high index of suspicion and close monitoring of such patients is required. [5] Liver injury due to dengue infection is not uncommon and has been described since 1970. It is mostly associated with dengue hemorrhagic fever and its magnitude is not related to the severity of the disease. Viral strains DEN-1 and DEN-3 exhibit liver tropism. Liver injury in dengue is a positive predictive factor for DHF. [6] Early diagnosis in our patient was critical to preventing DHF by early institution of fluid therapy, continuous surveillance and other supportive measures. CHEST MANIFESTATIONS CASE 02: A 60 year old female patient came with breathlessness and 2 episodes of hemoptysis. Study: HRCT chest showed patchy areas of consolidation and ground glass opacities in both lungs (Fig. 3, Fig. 4). In view of the post monsoon season with a spurt in dengue infections, the possibility of pulmonary hemorrhage was considered and a diagnosis of dengue was suggested. Serological testing was positive for dengue. The patient was treated conservatively. Page 6 of 34

Fig. 3 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 7 of 34

Fig. 4 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 In a follow up HR CT chest after 2 weeks, there was a significant regression in the ground glass opacities and consolidations. The patient showed good clinical improvement (Fig. 5, Fig. 6). Page 8 of 34

Fig. 5 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 9 of 34

Fig. 6 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Pulmonary hemorrhage occurs as part of DHF. A fter the initial period of infection, the patient develops thrombocytopenia and hemoconcentration with petechiae,purpura and ecchymosis. Hemoptysis has been reported in 1.4 % of dengue infections. It is thought to be a multifactorial process with abnormalities in the coagulation cascade,thrombocytopenia,platelet dysfunction and disseminated intravascular coagulation. [7] In our patient the diagnosis of dengue was made after the CT. Early supportive measures are crucial to prevent progress of the disease. Remedial measures enabled our patient to make an early recovery. Hence a high index of suspicion is necessary, especially in the post monsoon period. CASE 03: 30 year old patient admitted with fever and abdominal pain. Her laboratory investigations were positive for dengue and she had a thrombocytopenia with a platelet count of 30,000. She was referred for CT abdomen,in view of pain. Study Page 10 of 34

The CT abdomen was normal. Right pleural effusion was noted (Fig. 7). Fig. 7 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 In a large series involving CT in patients with dengue, CT findings of lower respiratory involvement were uncommon. When present, pleural effusion was the most common finding and is seen in 55% of patients. [8,9] Pleural effusion is part of the serositis induced by dengue infection and is secondary to capillary leakage and hydrostatic pressure imbalance. Institution of adequate fluid is essential to prevent progress of the disease. CASE 04: A 35 year old female came with high grade fever and chest pain. Her chest X ray showed small patchy opacities. Her WBC count was 20,000 with a mildly decreased platelet count of 1 lakh/c.mm. In view of the monsoon period, she was also tested for dengue which was positive. She was referred for a CT chest in view of pain. Study: Page 11 of 34

HRCT Chest shows multiple small patchy areas of consolidation (Fig. 8, Fig. 9). In view of the raised WBC count, the possibility of an associated bacterial pneumonia was considered and was started on antibiotics with adequate fluid therapy and other supportive measures. She responded well and was afebrile by day 3 and the pain subsided. Fig. 8 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 12 of 34

Fig. 9 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 A diagnosis of mild dengue infection with a concomitant bacterial pneumonia was made. Co-infection has been shown to worsen the outcome of dengue, if not appropriately treated. Lee et al observed that 5.5% of the patients among 774 patients presenting with DHF/dengue shock syndrome (DSS) showed bacteremia. [10] [11] Co-infection has been shown to worsen the outcome of dengue infection. Immunological mechanisms have been implicated, namely cytokines, tumor necrosis factor and interferon which are known to be increased in dengue. Patients with prolonged fever, unusual dengue manifestations and altered consciousness should be investigated for co-infection. This could help the start of antibiotics which can be life saving. Infections with S. typhi, Shigella sonei,hepatitis viruses, flu and chikungunya viruses, malaria and leptospira have been noted in literature. [12] [13] CNS MANIFESTATIONS CASE 05: Page 13 of 34

25 year old male with fever since 3 days and disorientation of acute onset He was positive for dengue with a platelet count of 1,50,000/c.mm. A possibility of dengue associated encephalopathy / encephalitis was raised. Study: The initial CT brain was normal (Fig. 10). Fig. 10 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 The patient became comatose with convulsions after 24 hours and was sent for a follow up CT which showed extensive hemorrhage in the left paraventricular white matter with ventricular extension and moderate hydrocephalus with generalised cerebral edema and multiple white matter hypodensities (Fig. 11, Fig. 12, Fig. 13, Fig. 14). Page 14 of 34

Fig. 11 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 15 of 34

Fig. 12 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 16 of 34

Fig. 13 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Neurological maniofestations in DF are usually secondary to vascular leak.presentation as hemorrhagic encephalitis is rare. CNS involvement is more commonly seen with serotypes 2 and 3 and occur in 0.5-21 % of patients. [14] It is usually due to multisystem dysfunction. Dengue has classically been thought to be non neurotropic; however anti-dengue IgM antibody in CSF in some patients suggests possible cerebral invasion. The number of studies describing the imaging features of dengue is limited.solomon et al.[15] reported a series of nine cases of dengue encephalitis, wherein all patients were positive for dengue serology, but virus/antibody was found in the CSF in only two patients. In their study, seven patients did not show the classic clinical features of dengue. Few case reports have described involvement of bilateral gangliocapsular location, mid brain, and spinal cord on MRI. [17] SOFT TISSUE MANIFESTATIONS CASE 06: 30 year old male with sudden onset swelling left pectoral region with mild pain Page 17 of 34

There was no history of trauma or previous coagulopathy and he was not on any medication.clinical examination showed a soft fluctuant lesion suggestive of a cystic lesion. Study: Plain CT scan of chest showed mildly hyperdense lesion in the left pectoral region with fluid-fluid level, raising suspicion of hemorrhage. (Fig. 14) Fig. 14 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Post contrast CT shows an active spurt of blood into the lesion. There was no evidence of underlying vascular malformation (Fig. 15). Page 18 of 34

Fig. 15 References: Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 A provisional diagnosis of soft tissue hematoma secondary to possible dengue was made. He subsequently tested positive for dengue. Aspiration showed blood without evidence of infection. The patient settled down within a week with progressive decrease in the swelling. Soft tissue and muscle hematomas are a rare complication of dengue fever. Very few cases have been reported in literature. Ammer et al. [18], Ganeshwaran et al. [19] and Ganu et al. [20] reported cases of DHF with muscle hematomas in the psoas, rectus muscle and iliopsoas, respectively. Spontaneous hematomas are ususally seen with an underlying pathology like aneurysms or with bleeding diathesis. It is important to keep a diagnosis of dengue fever in mind, in the appropriate season, so that early treatment and appropriate life saving measures can be started. Images for this section: Page 19 of 34

Fig. 1 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 20 of 34

Fig. 2 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 21 of 34

Fig. 3 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 22 of 34

Fig. 4 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 23 of 34

Fig. 5 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 24 of 34

Fig. 6 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 25 of 34

Fig. 7 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 26 of 34

Fig. 8 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Fig. 9 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 27 of 34

Fig. 10 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 28 of 34

Fig. 11 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Fig. 12 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 29 of 34

Fig. 13 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 30 of 34

Fig. 14 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Fig. 15 Nirman Hitech Diagnostic Centre, Mumbai, India, 2015 Page 31 of 34

Conclusion Imaging is important to evaluate the varying manifestations of severe DF. In our study, we have suggested a possible diagnosis of dengue in two patients in view of the postmonsoon period. Early diagnosis of capillary leak is important for adequate patient management with supportive measures and fluid therapy to prevent progression of dengue-shock syndrome. Personal information P. Kannan, Dept of Radiology, Nirman Diagnostic Centre, Mumbai, India R. Seth, Dept of Radiology, Nirman Diagnostic Centre, Mumbai, India H.K. Thakrar, Dept of Radiology, Nirman Diagnostic Centre, Mumbai, India M. Seth, Dept of Radiology, Nirman Diagnostic Centre, Mumbai, India M. Thakur, Dept of Radiology, Nirman Diagnostic Centre, Mumbai, India References [1] Rajapakse S. Dengue shock. Journal of Emergencies, Trauma and Shock. 2011;4(1):120-127. doi:10.4103/0974-2700.76835. [2] 2nd Edition. World Health Organization; 19977. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. [3] Beniwal P, Kumar S, Gulati S, Garg S. Acalculous Cholecystitis in Dengue Fever. Indian Journal for the Practising Doctor. Indian Journal for the Practising Doctor. Vol. 3, No. 4 (2006-08 - 2006-09) [4] Lal D, Tewani R, Sharma H And Jain S. Acalculous Cholecystitis In Primary Dengue Fever Patients. International Journal Of Food And Nutritional Sciences. Vol.3, Iss.1, JanMar 2014 [5] Nasim A. Dengue Fever Presenting as Acute Acalculous Cholecystitis. Journal of the College of Physicians and Surgeons Pakistan 2009, Vol. 19 (8): 531-533 Page 32 of 34

[6] MOURAO, Maria Paula Gomes et al. Dengue hemorrhagic fever and acute hepatitis: a case report. Braz J Infect Dis [online]. 2004, vol.8, n.6 [cited 2015-12-09], pp. 461-464. [7] Marchiori E, Ferreira JLN, Bittencourt CN, et al. Pulmonary hemorrhage syndrome associated with dengue fever, High-resolution computed tomography findings: a case report. Orphanet Journal of Rare Diseases. 2009;4:8. doi:10.1186/1750-1172-4-8. [8] Rodrigues RS, Brum ALG, Paes MV, Po voa TF, Basilio-de-Oliveira CA, et al. (2014) Lung in Dengue: Computed Tomography Findings. PLoS ONE 9(5): e96313. doi:10.1371/journal.pone.0096313 [9] Rodrigues RS, Brum ALG, Paes MV, et al. Lung in Dengue: Computed Tomography Findings. Costa C, ed. PLoS ONE. 2014;9(5):e96313. doi:10.1371/ journal.pone.0096313. [10] Lee IK, Liu JW, Yang KD. Clinical characteristics and risk factors for concurrent bacteremia in adults with dengue hemorrhagic fever. Am J Trop Med Hyg 2005; 72:221-6 [11] Chai LY, Lim PL, Lee CC, et al. Cluster of Staphylococcus aureus and dengue coinfection in Singapore.Ann Acad Med Singap 2007; 36:847-50 [12] Jeevan MK, Rajendran R, Thangaratham PS, et al. Dual infection by dengue virus and Plasmodium vivax in Alappuzha District, Kerala, India. Jpn J Infect Dis 2006; 59:211-2 [13] Kaur H, John M. Mixed infection due to leptospira and dengue. Indian J Gastroenterol 2002; 21:206 [14] Nadarajah J, Madhusudhan KS, Yadav AK, Gupta AK, Vikram NK. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection. Indian J Radiol Imaging 2015; 25:52-5 [15] Solomon T, Dung NM, Vaughn DW, Kneen R, Thao LT, Raengsakulrach B, et al. Neurological manifestations of dengue infection. Lancet 2000; 355:1053-9 [16] Kamble R, Peruvamba JN, Kovoor J, Ravishankar S, Kolar BS. Bilateral thalamic involvement in dengue infection. Neurol India 2007; 55:418-9. [17] Acharya S, Shukla S, Thakre R, Kothari N, Mahajan SN. Dengue encephalitis-a rare entity. J Dent Med Sci 2013; 5:40-2. [18] Ammer AM, Arachichi WK, Jayasingha PA. Psoas hematoma complicating dengue hemorrhagic fever: A case report. Galle Med J 2009; 14:83-4. [19] Ganeshwaran Y, Seneviratne SM, Jayamaha R, De Silva AP, Balasuriya WK. Dengue fever associated with a hematoma of the rectus abdominis muscle. Ceylon Med J 2001; 46:105-6. Page 33 of 34

[20] Ganu S, Mehta Y. Femoral compressive neuropathy from iliopsoas hematoma complicating Dengue haemorrhagic fever. Asian Pac J Trop Med 2013; 6:419-20 Page 34 of 34