Severe dengue associated with aseptic meningitis, acute kidney injury, and sudden sensorineural hearing loss: A case report

Renan GM Diniz, Elaine C dos Santos, Gabriel CL Chagas, Elizabeth F Daher

1Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, Ceará, Brazil

2Department of Intensive Care Unit, Fortaleza General Hospital, Fortaleza, Ceará, Brazil

3Post-Graduation Program in Medical Sciences, Department of Internal Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil

ABSTRACT

KEYWORDS: Dengue; Aseptic meningitis; Acute kidney injury;Sensorineural hearing loss; Deafness

1. Introduction

Dengue is the most important arboviral disease affecting humans in terms of morbidity and mortality[1,2]. Usually, it presents as an acute febrile illness[3,4]. Neurological complications are rare,and there is only one report of sudden sensorineural hearing loss(SSNHL) [1,3-6].

In this study, we report a case of aseptic meningitis, acute kidney injury (AKI), and SSNHL in a 42-year-old man with severe dengue.This case report was approved by the Ethics Committee of Fortaleza General Hospital. The authors obtained written informed consent from the patient.

2. Case report

A 42-year-old man from northeastern Brazil with history of alcoholism and smoking was presented to our emergency department with generalized tonic-clonic seizures. Three days before admission, he had an episode of excessive alcohol intake,followed, on the next day, by fever, severe headache, anorexia,vomiting, watery diarrhea, and abdominal pain. One day before admission, he suddenly developed dizziness, generalized tonicclonic seizures, and impaired consciousness.

On arrival, the patient presented Glasgow Coma Scale score of seven, blood pressure of 129/74 mmHg, heart rate of 128 beats/ min,and respiratory rate of 24 breaths/min with signs of respiratory distress and bilateral rhonchi at lung bases. During examination,he presented generalized tonic-clonic seizure. Blood glucose was normal, so diazepam was given followed by loading dose of phenytoin and thiamine. He underwent intubation and mechanical ventilation due to refractory status epilepticus. Head CT scan did not show significant abnormalities related to impaired consciousness or status epilepticus. Relevant laboratory investigations are summarized in Table 1. Arterial blood gas analysis showed a pH of 7.25(reference range: 7.35-7.45), PaCOof 28.2 mmHg (reference range:35-45 mmHg), HCOof 14 mEq/L (reference range: 22-26 mEq/ L),and lactate of 3.8 mmol/L (reference range: 0.5-1.6 mmol/L). In the first six hours, his urine output was 300 mL. Urinalysis revealed numerous red blood cells (RBCs) (reference range: 0-2 cells/ hpf),white blood cell (WBC) count of 10-12/hpf (reference range:0-4/ hpf), associated with granular and RBC casts.

As meningoencephalitis was considered as a possible diagnosis,ceftriaxone and acyclovir were prescribed. Lumbar puncture was contraindicated due to thrombocytopenia. Fresh frozen plasma and buffy coat transfusions were prescribed. Acute tubular necrosis due to rhabdomyolysis was suggested, and daily hemodialysis was started due to refractory metabolic acidosis. Serologies for cytomegalovirus,dengue, hepatitis A, B and C viruses, herpes simplex virus, human immunodeficiency virus, leptospirosis, parvovirus, syphilis, and toxoplasmosis were requested.

Due to clinical manifestations and some positive hemolytic markers, thrombotic thrombocytopenic purpura (TTP) was considered a possible diagnosis. Thus, blood sample was collected for ADAMTS-13 activity assay, and plasmapheresis was initiated.On the fourth day, kidney function improved after 3 dialysis sessions, and dialysis was discontinued. On the fifth day, he was transferred to the intensive care unit (ICU) to continue monitoring.Due to persistent fever, ceftriaxone was replaced empirically with meropenem considering its superior cerebrospinal fluid (CSF)activity, and ampicillin was added considering Listeria monocytogenes susceptibility. Electroencephalogram showed no epileptiform activity. On the fifth day, his platelet counts increased to 73 000/mm(reference range: 150 000-450 000/mm), and lumbar puncture was performed. CSF showed negative Gram stain, glucose of 57 mg/dL(reference range: 40-70 mg/dL), protein of 661.8 mg/dL (reference range: 15-50 mg/dL), RBC count of 320/mm(reference value:0/ mm), WBC count of 230/mm(reference range: 0-5/mm) with 60% lymphocytes (reference value: 0%), and lactate of 49 mg/dL(reference range: 10-20 mg/dL). On the eighth day, plasmapheresis was discontinued, and extubation was performed due to global improvement. Three days later, he was discharged from ICU.

Previously collected blood, urinary and CSF cultures were all negative. ADAMTS-13 activity assay was 66% (reference range:≥70%), not suggestive of TTP. Anti-dengue IgM serology was positive. Anti-CMV IgM, HAV IgM, HBs antigen, HBs IgM, HBc IgM/IgG, HCV IgM, HSV 1 and 2 IgM, fourth-generation antigen/antibody combination HIV-1/2 assay, leptospirosis IgM, parvovirus IgM, toxoplasmosis IgM, and VDRL were negative. So, the diagnosis of dengue was established.

Table 1. Hematologic and biochemical findings during hospitalization.

Despite recovery from coma, neurological evaluation was normal,except for partial deafness. Audiometry was performed and revealed moderate to severe SNHL on the right side and hearing loss on the left (Figure 1A). CT of mastoids did not show abnormalities. Family denied deafness before hospitalization.

The patient was discharged after 37 days still with hearing loss,but with important improvement of his general condition and of his blood test results. A six-month follow-up visit showed normal neurologic evaluation, except for persistent deafness (Figure 1B).

3. Discussion

3.1. Aseptic meningitis

Between 0.5% and 5.4% of dengue patients present neurological manifestations, with encephalopathy and encephalitis as the most common[3,5,6]. Meningitis is rare, especially in adults[5,6].

Clinical findings are similar to other causes of aseptic meningitis,including acute onset fever, vomiting, headache, altered consciousness, and nuchal rigidity[4,6].

Lumbar puncture should be done, and CSF analyzed for cell count,glucose and protein concentrations, and detection of viral RNA,NS1 antigen or dengue IgM antibodies[3,5,6]. Specific IgM and IgG antibodies were found in CSF in five to seven days after onset of neurological manifestations[5]. However, absence of IgM detection in CSF does not exclude dengue[3,5].

Our patient presented fever, vomiting, headache, impaired consciousness, and seizures. Neuroimaging study did not reveal structural lesions related to status epilepticus. CSF analysis showed lymphocytic pleocytosis and mild protein increase. CSF analysis for dengue infection was not possible due to laboratory limitations,but with combined clinical history and positive dengue serology,diagnosis of dengue-associated aseptic meningitis was established.Furthermore, dengue should be a differential diagnosis of acute febrile disease with neurological manifestations in patients from or with recent travel to dengue-endemic areas[3-5].

3.2. Acute kidney injury

Incidence of AKI in patients with dengue varies from 0.9% to 30.7%[7,8]. Etiopathogenesis is multifactorial, including direct cytopathic effects, systemic inflammation, hemodynamic instability,rhabdomyolysis, hemolysis and acute glomerulitis[2].

Figure 1. A 42-year-old man with history of alcoholism and smoking presented fever, vomiting, headache, impaired consciousness, and seizures. (A) Pure tone audiometry showed moderate to severe SNHL on the right side and hearing loss on the left. (B) A six-month follow-up pure tone audiometry showed persistent moderate to severe SNHL on the right side and hearing loss on the left.

Dengue-associated rhabdomyolysis might be due to direct viral cytotoxicity or proinflammatory myotoxic cytokines[2]. In this case, the leading factor for development of AKI was likely rhabdomyolysis, secondary to seizures, ethanol intoxication, fever and/or dengue infection. Our patient fully recovered kidney function.

3.3. Sudden sensorineural hearing loss

Sudden sensorineural hearing loss is SNHL that occurs within 72 hours with loss of at least 30 decibels in at least three consecutive frequencies on audiometry, in the absence of prior otological history[1].

Viruses can cause SSNHL by cochleitis or neuritis, viral reactivation within inner ear, or autoimmunity to inner ear antigens[1,9].

Infection by West Nile virus, also a member of the Flaviviridae family, may result in mild to severe bilateral sensorineural hearing loss[9]. Although, there is only one report of a patient with dengue infection that developed SSNHL[1]. In our case, it was not identified other cause for SSNHL besides dengue. Although no cause-effect relationship can be established, our finding supports the association between dengue and development of SSNHL.

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Authors’ contributions

RGMD, ECS, GCLC and EFD developed the theoretical formalism.RGMD and ECS followed the patient during hospitalization and acquired the exact data. RGMD, ECS, GCLC and EFD analyzed the data. RGMD, ECS and GCLC wrote the manuscript. GCLC designed the figure. RGMD, ECS, GCLC and EFD contributed to critical revision of the manuscript.