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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 2  |  Page : 80-84

Frequency of systemic involvement in patients with acute dengue fever - the expanded dengue syndrome: A retrospective review from a tertiary care hospital in Karachi


1 Department of Medicine, Patel Hospital, Karachi, Pakistan
2 Department of Medicine, Liaquat National Hospital, Karachi, Pakistan
3 Department of Emergency Medicine, Indus Hospital, Karachi, Pakistan

Date of Submission30-Mar-2020
Date of Decision14-Sep-2020
Date of Acceptance18-Oct-2020
Date of Web Publication30-Dec-2020

Correspondence Address:
Dr. Ayesha Khalil
Department of Medicine, Patel Hospital, Street 18, Gulshan Iqbal IV, Karachi 75300
Pakistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJAMR.IJAMR_32_20

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  Abstract 


Background: Dengue is globally the most common arboviral disease. As the primary immunopathological target in dengue is the endothelium, presentations beyond the typical triad of fever, myalgias, and thrombocytopenia are increasingly encountered. Severe systemic organ involvement can occur even without evidence of dengue hemorrhagic fever (DHF). These manifestations of dengue have been termed the “expanded dengue syndrome” by WHO. Aim: To observe the types and frequency of organ involvement in patients admitted with acute dengue fever. Methods: This is a retrospective cross-sectional study. Records of patients above 18 years admitted with acute dengue fever from December 2016 to December 2017 were reviewed. Patients fulfilling WHO criteria for probable or confirmed acute dengue fever were included. Patients with definite laboratory evidence of other systemic infections and patients with autoimmune or hematological disease were excluded. Data were obtained for 129 patients and analyzed using IBM-SPSS-21. Frequencies of clinical manifestations and organ involvement were noted. Results: Gastrointestinal manifestations occurred in 89% of patients. Transaminitis, organomegaly, and serositis were common. About 19% had pulmonary involvement, and 9% of patients had neurological features. Renal dysfunction, dyselectrolytemia, ophthalmic, muscular, and lymphoreticular abnormalities were also seen. Conclusion: Systemic involvement in dengue is not uncommon, and organ dysfunction can occur in the absence of severe DHF. Recognition of myriad range of organ involvement is crucial for optimal management.

Keywords: Dengue, dengue fever, severe dengue


How to cite this article:
Khalil A, Ishaque S, Khatri A, Muhammad AJ. Frequency of systemic involvement in patients with acute dengue fever - the expanded dengue syndrome: A retrospective review from a tertiary care hospital in Karachi. Int J Adv Med Health Res 2020;7:80-4

How to cite this URL:
Khalil A, Ishaque S, Khatri A, Muhammad AJ. Frequency of systemic involvement in patients with acute dengue fever - the expanded dengue syndrome: A retrospective review from a tertiary care hospital in Karachi. Int J Adv Med Health Res [serial online] 2020 [cited 2021 Apr 10];7:80-4. Available from: https://www.ijamhrjournal.org/text.asp?2020/7/2/80/305453


  Introduction Top


Dengue is globally the most common arboviral disease.[1] The primary immunopathological target in dengue is the endothelium causing myriad systemic features.[1] These have been termed the “expanded dengue syndrome” by the World Health Organization (WHO).[2] Severe organ involvement can occur even without evidence of dengue hemorrhagic fever (DHF) and maybe the presenting feature of the disease.[3]


  Methods Top


This was a retrospective cross-sectional study. After approval from the Ethical Review Committee (ERC No. 73), records of patients above 18 years with acute dengue fever between December 2016 and December 2017 admitted to a postgraduate teaching center were reviewed. Patients who fulfilled the WHO case definition for probable dengue or confirmed dengue fever were included.[2] Patients with definite confirmation of other systemic infections, pregnant patients and those with preexisting or newly diagnosed autoimmune or hematological disease were excluded.

Case records of 793 patients were reviewed; 158 cases met WHO diagnostic criteria for probable or confirmed acute dengue infection.[2] Cases meeting exclusion criteria and those with incomplete information were excluded; data were obtained for 129 patients and entered on a pro-forma. Data were analyzed using IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp for Windows. Frequencies of clinical manifestations and organ involvement were noted. Multiorgan dysfunction (MODS) was defined as two or more of renal, pulmonary, hepatic, neurologic, or hemodynamic compromise; acute renal impairment as increase in serum creatinine of 0.3 mg/dl within 48 h; neurological impairment as impaired Glasgow coma scale (GCS), focal deficits or fits in the absence of any other cause, liver dysfunction as transaminase increase >5 times above normal, pulmonary dysfunction as the need for oxygen or ventilator support. Chi-square test was applied to test the association of MODS with gender, comorbidities, warning signs, grade of illness,and major bleeding. Patients were divided into two age groups, <45 and >45 years. Student's t-test was applied to test the association of MODS with age, duration of illness, and hospital stay.


  Results Top


Demographic and clinical details of included patients are presented in [Table 1]. Frequency of organ involvement in these patients is presented in [Table 2].
Table 1: Demographic/clinical characteristics and outcome of 129 patients with acute dengue

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Table 2: Frequency of systemic involvement

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Vomiting was present in 81 patients (62.8%). Among patients with GI bleed, platelet count was <10,000/μl in five, <20,000/μl in three. Only one patient with GI bleed had deranged prothrombin time. Among 10 patients with ultrasonography-reported cholecystitis, one patient had a gall bladder calculus, rest were reported as the distended, thick-walled gallbladder or acalculous cholecystitis; only one did not have accompanying ascites. Swollen pancreas was reported in one patient on ultrasonography, but amylase, lipase or abdominal computed tomography imaging were not ordered in any patient. Mean alanine aminotransferase (ALT) was 290 IU/L (highest 3070 IU/L). Mean aspartate aminotransferase (AST) was 776 IU/L (highest 15,741 IU/L). Twelve female patients (9.3%) and 22 (17%) male patients had >5 times increase in transaminases. An increase in bilirubin (>2 mg/dl) ranged from 2.31 to 17 mg/dl with a mean of 5.06 mg/dl.

All patients had thrombocytopenia. Leukopenia (<4.0 × 103/μl) ranged from 0.3 to 2.9 × 103/μl (mean 5.5 × 103); leukocytosis (>11,000/μl) ranged from 11.1 to 32.3 × 103/μl (mean 18.6 × 103). Eighty-eight (68.2%) patients had a rapid drop in platelet count. Minor bleeding (skin, nose, and mucosa) occurred in 14 (10.8%), major bleeding in 20 (15.5%): eight of these patients had platelet counts <10,000/μl and four had counts below 25,000/μl. Lymphadenopathy was bilateral cervical in one, right inguinal in one, and hilar lymphadenopathy on chest radiography in one.

In those with renal impairment, mean serum creatinine was 2.3 mg/dl. One patient required dialysis. Hypokalemia (serum potassium <3.5 mmol/l) ranged from 2.7 to 3.3 mmol/l, mean value 3.2 mmol/l; paralysis was noted in none of these. Hyponatremia (serum sodium <132 mmol/l) occurred, mean value 129 mmol/l. Five patients (3.8%) had hyperkalemia (serum potassium >5.1 mmol/l) ranging from 5.2 to 7.8 mmol/l (mean 6.1 mmol/l): three of these had acute renal impairment.

Notably, fits did not occur in any patient with a history of epilepsy. Facial palsy was noted in two patients, hemiplegia (power <3/5 on MRC scale) in two and absent reflexes (without weakness) in one. Two patients had behavioral changes. One patient had meningitis with signs of meningeal irritation and GCS 10/15. Cerebrospinal fluid examination was done in two patients showing elevated protein but normal cell count and glucose levels. Brain imaging and EEG were performed in three patients and were within normal limits.

Three patients had rhinitis or sore throat and tonsillar enlargement. Two patients required intubation

Red-eye and troublesome lacrimation occurred. No vision loss was noted

Sixteen patients (12.4%) had multi-organ involvement. Statistical analysis of MODS in relation to other variables is given in [Table 3].
Table 3: Association of multiorgan dysfunction with other variables

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  Discussion Top


Recurrent vomiting, abdominal pain, and abdominal tenderness are among dengue warning signs.[2] These were common in our patients. A study reported acalculous cholecystitis in 52% of patients having abdominal pain with dengue fever.[4] Acute bilateral parotitis with demonstration of the dengue virus in saliva has been reported.[5] We noted no parotid involvement. A study reported AST and ALT elevations in 86% and 46%, respectively, with elevations >1000 IU/L in 1.01%.[6] Transaminitis was similarly common in our data and 4.6% of patients had values >1000 IU/L. In DHF, fatal fulminant hepatic failure is due to a massive infection of hepatocytes and Kupffer cells with minimal cytokine response.[7] No patient in our series developed fulminant hepatic failure. Pancreatitis can manifest rarely and conservative treatment is effective.[8] Pancreatitis was not confirmed in any of our patients. Spontaneous rupture of the spleen has been reported during the viremic phase.[9] It presents with abdominal pain.

Prerenal involvement due to increased capillary permeability and third spacing is common, especially in patients with preexisting renal disease.[10] In our study, none of the patients with impaired renal function had any past renal problems. Prerenal cause could not be attributed to any of our patients as only three had evidence of third-spacing and none of them was hypotensive. Rhabdomyolysis secondary to cytokine storm can occur in acute dengue with attendant renal complications.[11] Screening urinalysis has been suggested for patients with severe dengue and creatinine kinase levels if urine is positive for heme.[10] IgA nephropathy and hemolytic-uremic syndrome were reported in a 48-year-old man.[12],[13] In patients who manifest renal impairment, deposits of IgG, IgM and C3 and glomerular basement membrane thickening are found.[14]

Protean neurological manifestations have been reported in 0.5%–7.4% of patients with dengue.[1],[15] Dengue virus crosses the blood-brain barrier; neurological features result from direct damage, capillary sludging, or metabolic impairment. As dengue virus antigens cross-react with other encephalitis viruses, postinfectious immune-mediated injury has been postulated.[4] Encephalopathy and encephalitis both occur. Prognosis is variable, but mortality is high. In our series, nine patients demonstrated clinical features of encephalitis (altered consciousness, altered behavior, focality, or seizures).

Acute pure motor quadriplegia and acute transient muscle dysfunction with myalgia, hyporeflexia, and raised muscle enzymes have been reported.[16] Dengue virus can directly damage myocytes.[17] Simultaneous myositis and myocarditis may occur.[4] Paralysis due to hypokalemia with or without hypomagnesemia has been reported.[18] Hypokalemic paralysis occurs during defervescence.[19] While myalgia was very common in our study (76.7%), and 13.1% had hypokalemia, no patient had hypokalemic paralysis. Two patients in our series manifested limb weakness and decreased tone without hypokalemia, and one patient had absent reflexes without muscle weakness. However, muscle enzymes were not sent in any patient. No patients in our series had any clinical, biochemical, electrocardiography, or echocardiography evidence of myocarditis.

Isolated involvement of the 2nd, 3rd, 6th cranial nerves and long thoracic and phrenic nerves have been described.[20] Two of our patients demonstrated facial nerve palsy. Guillain-Barre syndrome (GBS), brachial neuritis, and neuralgic amyotrophy syndrome have been reported in the convalescent period.[4] There were no cases of GBS noted in our series. Parainfectious and postinfectious acute transverse myelitis has been reported. Magnetic resonance imaging (MRI) spinal cord may be normal or reveal high-intensity signal.[4] Postinfectious acute cerebellitis has been reported.[21] For this study, follow-up case records were not reviewed, so any parainfectious neurology cannot be ascertained. Hemorrhagic stroke can occur in the absence of bleeding from any other site, usually in the convalescent period. Ischemic stroke is less common. Carod-Artal has cogently described dengue associated subtypes of stroke.[4] MRI may demonstrate central nervous system involvement, but findings are not specific to dengue. Brain imaging was performed in five of our patients and showed no abnormality.

Neuro-ophthalmic dengue can present as maculopathy, retinal hemorrhages or optic neuropathy, causing blurring of vision or scotomas. Occurrence during convalescent phase suggests immune-mediated damage. Response to intravenous steroids is reported.[22] Vasculitis has also been reported. Most ocular manifestations recover spontaneously within 8–12 weeks.[23] Uveitis can occur several months after acute dengue infection.[24] It responds to treatment with topical steroids, cycloplegics, and ocular hypotensive agents. In our series, eleven patients (8%) had red-eye; four (3%) had troublesome lacrimation. Visual loss was reported by none.

ARDS, pulmonary hemorrhage, pneumonitis, and pleural effusion have been reported with DHF and DSS.[25] ARDS is thought to be due to increased permeability of the alveolar-capillary membrane. Pleural effusion, lung infiltrates, pulmonary edema, and ARDS all were noted in our study.

In our data, MODS correlated significantly with increasing age, diabetes, and hypertension but not with asthma or major vascular disease. It correlated significantly with rapidly decreasing platelet count, but there was no significant relation with other warning signs of persistent vomiting and abdominal pain.


  Conclusion Top


Dengue can cause serious organ involvement and MODS syndrome, even in the absence of severe DHF. Recognition of these complications is imperative to expedite diagnosis and management.

Acknowledgment

We gratefully acknowledge research help by Resident, Department of Medicine, Patel Hospital Dr. Rabia Malik, MBBS (literature review, data analysis), and elective research assistants Dr. Ali Shah, MBBS (data collection) and Dr. Samurna Sabir, MBBS (data collection).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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Carod-Artal FJ. Neurological manifestations of dengue viral infection. Res Rep Trop Med 2014;5:95-104.  Back to cited text no. 15
    
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    Tables

  [Table 1], [Table 2], [Table 3]



 

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