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BMJ Case Rep. 2010; 2010: bcr06.2009.1949.
Published online 2010 January 13. doi:  10.1136/bcr.06.2009.1949
PMCID: PMC3029086
Unusual association of diseases/symptoms

Skin rash, headache and abnormal behaviour: unusual presentation of intracranial haemorrhage in dengue fever

Abstract

Dengue viral infections are one of the most important mosquito borne diseases in the world. The dengue virus is a single stranded RNA virus belonging to the Flaviviridae family. There are four serotypes (DEN 1–4) classified according to biological and immunological criteria. Patients may be asymptomatic or their condition may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide and 2.5 billion people are at risk. At present, dengue is endemic in 112 countries. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. We present an interesting case of dengue fever with headache, skin rash and abnormal behaviour who had a massive intracranial haemorrhage with fatal outcome.

Background

This case conveys some important messages:

  • The unusual presentation of a common disease can occur and can be fatal if ignored
  • Absence of fever at presentation is striking
  • Headache and abnormal behaviour may symptomatic of a serious pathology such as intracranial haemorrhage
  • In an endemic area for dengue fever, diagnostic tests need to be done for appropriate management.

Case presentation

A 19-year-old unmarried female Burmawi patient presented with a 3 day history of headache and abnormal behaviour associated with skin rash. The patient’s family denied any history of fever or similar illness in the family. The examination revealed a young woman, ill looking, but conscious and confused. She was ambulatory and had a petechial rash over the arms and feet (fig 1). The general physical examination was normal, with temperature of 37.2 °C and pulse rate of 70 beats/min. The systemic examination did not reveal any focal neurological deficit, although vision could not be tested as the patient was confused. Investigations revealed normal chest x-ray, normal electrocardiogram, and normal urine analysis. Complete blood counts revealed a platelet count of only 21 000/cm3 and haemoglobin of 17 g/dl, with haematocrit of 52% (normal up to 45%) and a normal white cell count. Serum chemistry revealed lactic dehydrogenase of 614 IU (normal up to 220 IU) and creatinine kinase of 2000 IU/ml (normal up to 190 IU/ml). Liver enzymes were increased threefold, but serum bilirubin, serum creatinine, blood urea nitrogen and coagulation profile were normal, as were d-dimer and fibrinogen values. Erythrocyte sedimentation rate was 21 mm in the first hour, and ultrasonography of the abdomen was normal. Computed tomography (CT) scan of the brain was performed and showed a large occipital haemorrhage with midline shift and cerebral oedema (fig 2).

Figure 1
Petechial rash on hands and forearms.
Figure 2
Computed tomography scan showing occipital lobe haemorrhage, cerebral oedema, and midline shift.

Investigations

The patient was diagnosed with dengue haemorrhagic fever (DHF) on the results of following investigations:

  • Dengue serology including IgM, IgG
  • Reverse transcriptase polymerase chain reaction (RT-PCR) for dengue virus
  • Enzyme linked immunosorbent assay (ELISA) for NS1 antigen.

Differential diagnosis

Dengue fever

  • Infectious mononucleosis
  • Chickengunya viral infections
  • Coxsackie and other enteroviral infections
  • Rickettsial infections
  • Rubella
  • Parvovirus B19 infections
  • Leptospirosis
  • Influenza.

DHF

  • Leptospirosis
  • Chikengunya viral infections
  • Kawasaki disease
  • Yellow fever
  • Hanta viral infections
  • Other viral haemorrhagic fevers
  • Meningococcal septicaemia.

Treatment

  • Intravenous fluids
  • Platelet transfusions
  • Fresh frozen plasma

Outcome and follow-up

The patient was admitted to the intensive care unit, and received intravenous mannitol and mechanical ventilation in addition to supportive care, but died before any neurosurgical intervention could be undertaken.

Discussion

The presentation of this patient with skin rash, thrombocytopenia and elevated liver and muscle enzymes prompted us to perform dengue serology as dengue fever is endemic in our region. It was positive for IgM and IgG. The ELISA for NS1 viral antigen was also requested on admission in addition to RT-PCR, and the positive results confirmed the diagnosis. The patient was diagnosed with DHF with elevated haematocrit, thrombocytopenia, elevated liver and muscle enzymes, and intracranial haemorrhage. She was admitted to intensive care but succumbed to her intracranial haemorrhage 3 days later in spite of supportive care and an improvement in platelet count.

Dengue viral infections are one of the most important mosquito borne diseases in the world. The dengue virus is a single stranded RNA virus belonging to the Flaviviridae family.1 There are four serotypes (DEN 1–4), classified according to biological and immunological criteria.

Patients may be asymptomatic or their condition may give rise to undifferentiated fever, dengue fever, DHF, or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide and 2.5 billion people are at risk. Ninety per cent of DHF cases involve children <15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited.

Clinical features of DHF are summarised as follows:

General

  • High fever, intermittent
  • Severe headache (especially retro-orbital)
  • Flushing
  • Myalgia and arthralgia
  • Vomiting
  • Anorexia
  • Acute abdominal pain.

Bleeding manifestations

  • Epistaxis
  • Bleeding from gums
  • Petechiae and ecchymosis
  • Haematemesis and maelena
  • Spotting or menorrhagia in females.

Features of plasma leakage

  • Circulatory disturbances (low blood pressure, tachycardia, narrow pulse pressure, and poor capillary refill time)
  • Periserositis (pleural effusions, ascites sometimes pericarditis).

Complications

  • Encephalopathy and encephalitis
  • Liver failure
  • Myocarditis
  • Disseminated intravascular coagulation leading to massive bleeding.

World Health Organization classification of dengue fever

Case definition of DHF

A patient with the following four criteria:

  • Acute sudden onset of high fever for 2–7 days
  • Haemorrhagic manifestations with at least a positive tourniquet test
  • Platelet count <100 000/cm3
  • Haemoconcentration
  • or other evidence of plasma leakage—for example, ascites, pleural effusions, low level of serum protein/albumin

Encephalopathy is a rare complication of dengue virus infection and may occur as a consequence of intracranial haemorrhage, cerebral oedema, hyponatraemia, cerebral anoxia, fulminant hepatic failure with portosystemic encephalopathy, microcapillary haemorrhage or release of toxic products. Intracranial haemorrhage as the only presentation of dengue is rare.2,3 There are case reports of subarachnoid haemorrhage in dengue fever.4 The timely diagnosis is important as the outcome is dismal. There are few case reports with intracranial haemorrhage with variable outcome.5 Our case had abnormal behaviour at presentation which we attribute to raised intracranial tension, although cases of mania6 and other features of dengue encephalitis have been reported.7 The haemorrhage was due to thrombocytopenia and absence of focal neurological deficit due to occipital location of the haemorrhage. Our case emphasises the importance of high suspicion of intracranial haemorrhage in areas endemic for dengue fever, even in the absence of fever.

Learning points

  • A diagnosis of dengue fever needs to be considered in areas endemic for dengue.
  • Absence of fever on presentation does not rule out dengue fever.
  • Headache associated with dengue fever needs to be considered as serious when platelet count falls below 20000/mm3.
  • Abnormal behaviour may be the manifestation of a serious intracranial event.
  • Imaging procedures such as CT must be performed in cases with suspicion of intracranial haemorrhage.

Acknowledgments

We are grateful to Miss Mecciya Hadi for her support and encouragement.

Footnotes

Competing interests: None.

Patient consent: Patient/guardian consent was obtained for publication.

REFERENCES

1. Guzman MG, Kouri G. Dengue: an update. Lancet Infect Dis 2002; 2: 33–42 [PubMed]
2. Kumar J, Kumar A, Gupta S, et al. Neurological picture. Dengue haemorrhagic fever: an unusual cause of intracranial haemorrhage. J Neurol Neurosurg Psychiatry 2007; 78: 253. [PMC free article] [PubMed]
3. de Souza LJ, Martins AL, Paravidini PC, et al. Hemorrhagic encephalopathy in dengue shock syndrome: a case report. Braz J Infect Dis 2005; 9: 257–61 [PubMed]
4. Jensenius M, Berild D, Ormaasen V, et al. Fatal subarachnoidal haemorrhage in a Norwegian traveller with dengue virus infection. Scand J Infect Dis 2007; 39: 272–4 [PubMed]
5. Kumar R, Prakash O, Sharma BS. Intracranial hemorrhage in dengue fever: management and outcome A series of 5 cases and review of literature. Surg Neurol 2009; 72: 429–33 [PubMed]
6. Mendhekar DN, Aggarwal P, Aggarwal A. Classical mania associated with dengue infection. Indian J Med Sci 2006; 60: 115–6 [PubMed]
7. Ferreira ML, Cavalcanti CG, Coelho CA, et al. Neurological manifestations of dengue: study of 41 cases. Arq Neuropsiquiatr 2005; 63: 488–93 [PubMed]

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