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608 - Vol. 69 / Ed 5 / in 2003
Section: Artigo Original Pages: 644 to 647
Otolaryngological manifestations of patients with dengue
Authors:
Cristiane K. Denis1,
Karina M. Cavalcanti1,
Roberto C. Meirelles2,
Brenda Martinelli3,
Daniella C. Valença3

Keywords: dengue, otolaryngological manifestations, epistaxis

Abstract: Dengue is an acute fever disease caused by an arbovirus, and transmitted by the mosquito Aedes aegypti. Clinical picture usually starts with classic manifestations such as fever, myalgia, epistaxis, sore throat, vertigo and tinnitus. This disease has became a serious health public problem, reaching incidence rates of 50 to 70% in Rio de Janeiro State. Aim: Our objective was to evaluate patients with dengue, presenting otolaryngological symptoms as the first clinical manifestation. Study design: Longitudinal Cohort. Material and method: Thirty patients with serologically confirmed Dengue were included in this prospective study. Results: The most important otolaryngological signs and symptoms were sore throat (60%), hyaline rhinorrhea (50%), nasal obstruction (46.6%), earache (36.6%), vertigo (20%), epistaxis (13.3%), tinnitus (6.6%), salivary gland diseases (6.6%) and bleeding gum (3.3%). Conclusions: In an epidemic situation, dengue must be suspected by the otolaryngologist, since this disease generally is followed by many otolaryngological manifestations.

INTRODUCTION

Dengue is considered the most important arbovirus disease that affects human beings, considering morbidity and mortality. It is a serious problem of public health in the world, especially in tropical countries 1.

It is an acute fever infectious disease caused by arboviruses that belong to family Flaviviridae and it is transmitted by mosquito Aedes aegypti2. To present, four serum types (1, 2, 3 and 4)2 are known.
Dengue has caused outbreaks for centuries, and the first description was made by Benjamin Rush2 in 1780, in Philadelphia, USA. In 1906, Bancroft2 discovered that the transmission was made by the vector of yellow fever, mosquito Aedes aegypti. As of 1954, Hammon et al.2 described a new disease caused by the virus - dengue, characterized by generalized hemorrhage and shock, named hemorrhagic dengue or dengue shock syndrome. In 1968, Scherer2 suggested to the World Health Organization (WHO) the classification of dengue into 4 types. In the 70's, the outbreak got more severe, especially in tropical countries 2.

In 1981, in Cuba, the first outbreak of hemorrhagic dengue was described in Central America, caused by serotype 22. In Brazil, there is report of an outbreak in Rio de Janeiro in 18462. In 1917, there was the description of an outbreak of dengue in Rio Grande do Sul 2. Epidemic episodes started in the city of Rio de Janeiro ands Niteroi, state of Rio de Janeiro, between 1922 and 19232. The first clinically and laboratory documented outbreak happened in 1981-93 in Boa Vista, state of Rondonia. Dengue reappeared four years later in the cities of Rio de Janeiro and Nova Iguacu, state of Rio de Janeiro 2. Later, outbreaks were recorded in the Brazilian states of Ceara, Alagoas, Pernambuco, Bahia, Minas Gerais, Tocantins, Sao Paulo and Mato Grosso do Sul. From 1990 to 1998, there were many notified cases of dengue, being over 300 cases of hemorrhagic dengue and 8 deaths only in Rio de Janeiro 2.

Dengue is currently one of the main public health problems in the world. WHO estimates that there are about 80 million people that get infected annually in 100 countries, in all continents, except for Europe1, 3. Out of the total, 550,000 require hospitalization and at least 20,000 will die of the disease. The recent introduction of dengue serotypes 3 and 4 is related with new outbreak episodes, associated with individual susceptibility and virulence, as well as immune response1.

Known as "break bone fever" owing to marked prostration and arthralgia 4, the most frequent clinical form is asymptomatic or not evident. There are three clinical forms: asymptomatic dengue, classical dengue and hemorrhagic dengue or dengue shock syndrome 3.

Classical dengue has sudden onset, with high temperature, followed by headache, prostration, arthralgia, anorexia, retro-orbital pain, nausea, vomiting, exanthema and cutaneous rash 4, 5. The presence of hepatomegalia and generalized abdominal pain normally indicates poor prognosis, with likely evolution to shock 2. It lasts 5 to 7 days, when in general there is remission of symptoms, but in some few cases there can be persistence of fatigue 4, 5. In hemorrhagic dengue, the initial symptoms are the same, but on the third or fourth day, the picture is aggravated by agitation, lethargy, rapid pulse, hypotension, spontaneous hemorrhagic manifestation, cyanosis and temperature decrease 2.

Pathophysiology of hemorrhagic dengue is characterized by plasma overflow, which is manifested by increasing values of hematocrit owing to blood concentration. Thrombocytopenia is another significant laboratory finding 2, 3.

Dengue does not have a specific treatment. The most important therapeutic measure is hydration, PO or IV in severe cases 3, 4. Fever and arthralgia are treated with paracetamol or the association of paracetamol and codeine at regular doses. Some authors also employ dipyrone, at regular doses 3.
The tendency is to have marked growth and expansion in areas where there is virus circulation. In 2003, the number of cases in Rio de Janeiro reached over 70,000, being difficult to control the hemorrhagic cases among them. Currently, the rates can reach 50% to 70% in the population of the state of Rio de Janeiro 3.

The purpose of the present study was to assess dengue patients who initially presented ENT signs and symptoms whose first medical care was provided by the Otorhinolaryngology ER Service.

MATERIAL AND METHOD

We conducted a prospective study focusing on patients with clinical manifestations compatible with dengue between December 2001 and April 2002, total of 135 days, in the Service of Otorhinolaryngology Policlínica de Botafogo - Rio de Janeiro.

We selected 30 patients with positive serology and blood affections compatible with viral infection. All patients were seen in the Otorhinolaryngology ER Service presenting ENT signs and symptoms.
The routine assessment included anamnesis, physical and ENT examination, and laboratory tests such as complete blood count, platelet count and serology for IgM and IgG for dengue. The serology test was ordered on day 6 after onset of symptoms. Whenever necessary, we ordered other tests such as coagulation test, paranasal sinuses x-rays, audiometry, impedanciometry, auditory brainstem response (ABR) and vestibular tests.

The hospitalization criteria were platelet count below 50,000/ml, dehydration, continuous vomiting, hemodynamic instability, hemorrhage or deep decrease in general status. Patients with hemorrhage and platelet count below 30,000/ml were submitted to blood replacement.

RESULTS

Among the 30 studied patients, 18 were female and 12 were male patients. The mean age was 33.7 years, standard deviation of ± 14.45.

General clinical manifestations included fever (96.6%), arthralgia (80%), headache (66.6%), retro-orbital pain (60%), cutaneous rash (26,6%), cutaneous pruritus (20%), nausea (13.3%) and vomiting (10%) (Table 1).

Otorhinolaryngological manifestations were: odynophagia (60%), coriza (50%), nasal obstruction (46.6%), otalgia (36.6%), vertigo (20%), epistaxis (13.3%), salivary gland affections (6.6%), tinnitus (6.6%) and gingival hemorrhage (3.3%) (Table 2).

The diagnosis of hemorrhagic dengue was made in 5 patients, and only one of them had to be submitted to plasma replacement. Seven patients were hospitalized under clinical and ENT supervision.


Table 1. General manifestations of dengue.

* Many patients with multiple manifestations.


Table 2. ENT manifestations of dengue.

* Many patients with multiple manifestations.



DISCUSSION

We frequently see patients that present fever, no findings in the physical examination or some mild hyperemia of the oropharynx and nasal mucosa, leading to suspicion of viral process. In case of an outbreak, the differential diagnosis of such viral episodes with dengue becomes extremely important.
Fever is a constant sign in dengue, normally it is high, sudden and many times uncontrollable 2, 5. Fever and malaise are normally related to the presence of high levels of serum cytokines, among them TNF, IL-6 and IFN4,6. In our study only one patient did not manifest fever.

Headache, normally of frontal location and retro-orbital pain are many times associated with nasal obstruction and rhinorrhea, mimicking an episode of acute sinusitis. Headache is the most frequent general manifestation, reaching 93% of the cases 2, 5. Headache and retro-orbital pain are present as one single manifestation, named retro-orbital headache and it is related to the viral multiplication in muscle tissues with impairment of the oculomotor nerve 2. The dengue virus has tropism by phagocytarian cells and the multiplication occurs in lymphatic and muscle tissues 2. In our study, the incidence of retro-orbital headache was of 66.6%, a little below what was described in the literature. In the General Emergency service the rate found was of 93%.

Cutaneous rash of dengue ranges from 12 to 33% of the exanthematic diseases 7, and it can be seen in 25% of the patients 2. Maculo-papular exanthema is present on the 2nd or 3rd day, starting from the trunk and disseminating to the neck and face, sparing the palm and plantar regions. During remission of the exanthema there is pruritus and cutaneous desquamation 4, 8. The incidence in our group of patients was of 26.6%.

Eighteen patients in our study complained of odynophagia that was characterized by itching and pain during swallowing. In the exam, we detected mild oropharynx hyperemia, with absence of secretions and purulent points, findings not compatible with the complaints. According to the technical report on dengue, acute pharyngitis can occur in one fourth of the patients3. In our series, it was detected in 60% of the patients, being the most frequent complaint. In view of a picture of odynophagia, differential diagnosis with dengue becomes important, since the use of regular drugs, such as anti-inflammatory drugs and salycilates, can aggravate the hemorrhagic process 5, 8.

Half of the patients presented viral acute rhinitis with coriza and hyperemia and edema of nasal mucosa. Normally, rhinitis is detected in the prodromic phase, as well as others exanthematous diseases 7, 8. Marked otalgia, normally unilateral, was observed in 36.6% of the cases, and there was no improvement with the use of analgesics. The otoscopy revealed increase in vascularization of malleus manubrium and mild hyperemia of the tympanic membrane.

Four patients presented epistaxis, three of them with hemorrhagic dengue and one with classical dengue. It is important to point out that the hemorrhagic phenomenon is not characteristic of hemorrhagic dengue 3, 5, 8. Epistaxis was treated with anterior packing. One of the patients presented gingival hemorrhage, with no significant complications. One of the patients with epistaxis and platelet decrease of 3,000/ml was submitted to plasma replacement. The hemorrhagic phenomena are resultant from the release of thromboplastin and complement activator protease by the infected macrophages 7. There is a process of coagulation and cell lysis with release of cytokines, TNF, IL-8, histamine, IL-2 by macrophages, basophils and lymphocytes, affecting the endothelial cells and contributing to thrombocytopenia and increase of vascular permeability, causing plasma overflow 2, 5.

Rotation vertigo was reported in 20% of the cases, persistent and recurrent, maintained in some cases up to 30 days after the end of viral infection. The findings of complementary tests such as audiometry, ABR and vestibular tests confirmed the diagnosis of vestibular neuronitis. In such cases, the proposed treatment was rest, use of sedation and flunarizine for 15 to 30 days. Vestibular neuronitis is detected in 36% of the patients with previous upper respiratory tract infection, and the etiology is probably viral 9.

Tinnitus occurred in two patients, one associated with vertigo episode. According to the literature, auditory symptoms are not common in vestibular neuronitis 9.

The observed salivary affections included sensation of bitter taste and increase of unilateral parotid gland. We believe they were consequences of dehydration or viral infection, leading to acute sialoadenitis. The sensation of bitter taste can affect 1.9% of the cases 2.

CONCLUSION

In the presence of dengue outbreak, any case of fever should be seen as a suspected case. Dengue has a significant physiopathogenesis and should not be seen as a simple virus affection. It can lead to severe complications, such as hemorrhagic shock, acidosis and death. The physicians should bear in mind the occurrence of ENT manifestations that start an episode of dengue.

Considering the increasing number of dengue cases in Brazil, with various clinical manifestations, especially otorhinolaryngological ones, we should value differential diagnosis always suspecting of cases with fever and no specific findings.

REFERENCES

1. Fonseca BA, Fonseca SN. Dengue virus infections. Curr Opin Pediatr 2002; 14(1):67-71.
2. Figueiredo LTM, Fonseca BAL. Dengue. In: Veronesi R, Focaccia R. Tratado de infectologia. São Paulo: Atheneu; 1996. p.203-12.
3. CONSELHO REGIONAL DE MEDICINA DO ESTADO DO RIO DE JANEIRO. Informe Técnico do Dengue. Rio de Janeiro: CREMERJ; 2002. p.15, 19, 27-9.
4. BRASIL. MINISTÉRIO DA SAÚDE - FUNDAÇÃO NACIONAL DE SAÚDE. Doenças infecciosas e parasitárias. Brasília, DF; 1999. p. 51-4.
5. Guzman MG, Kourí G. Dengue: an update. Lancet Diseases 2002; 2(1):33.
6. Libraty DH, Endy TP, Houng HS et al. Differing influences of virus burden and immune activation on disease severity in seco infections. J Infect Dis 2002; 1, 185(9): 1213-21.
7. Oliveira SA, Siqueira MM, Camacho LA et al. The aetiology of maculopapular rash diseases in Niterói, state of Rio de Janeiro, Brazil: implications for measles surveillance. Epidemiol Infect 2001; 127(3): 509.
8. Prado FC, Ramos J, Valle JR. Atualização terapêutica - manual prático de diagnóstico e tratamento. 19a ed. São Paulo: Artes Médicas; 1999. p. 49-50.
9. Sociedade Brasileira De Otorrinolaringologia. Consenso sobre vertigem - 1999. Rev Bras ORL 2000; 66(6) pt. 2.




1 Post-graduation in Otorhinolaryngology, Policlínica de Botafogo - RJ.
2 Coordinator of Post-Graduation in Otorhinolaryngology, Policlínica de Botafogo - RJ. Joint Professor, State University of Rio de Janeiro.
3 Post-graduate studies in Otorhinolaryngology under course, Policlínica de Botafogo - RJ.
Service of Otorhinolaryngology, Policlínica de Botafogo - Av. Pasteur, 72 2º andar Botafogo RJ 22290-190
Tel: (55 21)2543-1909 - E-mail: ckas@terra.com.br
Study presented at 36º Congresso Brasileiro de Otorrinolaringologia, held in Florianópolis SC, November 19 - 23, 2002.
Article submitted on February 24, 2003. Article accepted on August 08, 2003.
Indexations: MEDLINE, Exerpta Medica, Lilacs (Index Medicus Latinoamericano), SciELO (Scientific Electronic Library Online)
CAPES: Qualis Nacional A, Qualis Internacional C


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