Oral manifestations of dengue fever

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194 © 2018 Sahel Medical Journal | Published by Wolters Kluwer - Medknow INTRODUCTION Many systemic and infectious diseases show their significant presence in the oral cavity. [1] Infectious diseases include bacterial, viral, fungal, and protozoal diseases. Viral diseases include primary and secondary herpes, varicella, shingles, infectious mononucleosis, herpangina, rubeola, rubella, mumps, and HIV and occur in the form of vesicles, ulcers, erythema, petechiae, purpura, and Koplik’s spot. [2] Dengue is a life‑threatening viral illness caused by dengue virus (DENV), which is a single‑stranded RNA virus belong to the genus Flavivirus, [3] and it is usually epidemic in the postmonsoon period (August–November). [4] There are four serotypes, i.e., DENV1–4. These four serotypes are transmitted to humans by mosquitoes, principally by the Aedes aegypti, and other species such as Aedes albopictus, Aedes polynesiensis, and Aedes scutellaris complex. [5] They usually breed in stagnant water; water was collected in containers, water‑based air coolers, and tyre dumps which create a favorable environment for the vectors in large cities. [6] The purpose of this study was to assess the oral manifestations in patients with dengue fever. MATERIALS AND METHODS This cross‑sectional study was carried out in the inpatient Department of General Medicine, Indira Gandhi Government General Hospital and Postgraduate Institute, Pondicherry, from October to November 2017. Serologically diagnosed 50NS1 antigen‑positive cases Oral manifestations of dengue fever Sethuraman Govindaraj, Ramesh Jayaraman 1 , M. Jonathan Daniel, Saravanan Subbiah 2 , Srinivasan Subramanian Vasudevan, Jimsha Vannathan Kumaran Departments of Oral Medicine and Radiology and 2 Public Health Dentistry, Mahatma Gandhi Postgraduate Institute of Dental Sciences Pondicherry, 1 Department of Medicine, Geriatrics and Endocrinology, Indira Gandhi Government General Hospital and Postgraduate Institute Pondicherry, Puducherry, India ABSTRACT Background: Dengue is a life‑threatening viral infection which has become an epidemic in India in the postmonsoon period (August–November). It mostly associated with nonspecific fever and rashes, arthralgia, myalgia, and thrombocytopenia in severe cases. Objective: This study aimed to study the oral manifestations of dengue fever and to observe the various features of oral presentation then to validate the significance and importance of oral manifestation in the diagnosis of dengue fever. Materials and Methods: Patients meeting the inclusion criteria were subjected to detailed history, oral examination, and relevant investigations. Results: Intraoral manifestations were present in 24 (48%) patients, anf these included petechiae (29.2%), bleeding gums (16.6%), ulcer (4.2%), dryness of mouth (4.2%), and combined features (45.8%). Extraoral manifestations were present in 4% of the cases. Conclusion: This study highlights the thrombocytopenia related oral haemosrrhagic manifestations of dengue fever. Keywords: Dengue fever, oral manifestation, petechiae Corresponding Author: Dr. Sethuraman Govindaraj, Department of Oral Medicine and Radiology, Mahatma Gandhi Postgraduate Institute of Dental Sciences Pondicherry, Puducherry, India. E‑mail: [email protected] Cite this article as: Govindaraj S, Jayaraman R, Daniel MJ, Subbiah S, Vasudevan SS, Kumaran JV. Oral manifestations of dengue fever. Sahel Med J 2018;21:194-8. This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] Access this article online Quick Response Code: Website: www.smjonline.org DOI: 10.4103/smj.smj_28_18 Original Article [Downloaded free from http://www.smjonline.org on Friday, June 14, 2019, IP: 197.157.252.242]

Transcript of Oral manifestations of dengue fever

Page 1: Oral manifestations of dengue fever

194 © 2018 Sahel Medical Journal | Published by Wolters Kluwer - Medknow

INTRODUCTION

Many systemic and infectious diseases show their significant presence in the oral cavity.[1] Infectious diseases include bacterial, viral, fungal, and protozoal diseases. Viral diseases include primary and secondary herpes, varicella, shingles, infectious mononucleosis, herpangina, rubeola, rubella, mumps, and HIV and occur in the form of vesicles, ulcers, erythema, petechiae, purpura, and Koplik’s spot.[2]

Dengue is a life‑threatening viral illness caused by dengue virus (DENV), which is a single‑stranded RNA virus belong to the genus Flavivirus,[3] and it is usually epidemic in the postmonsoon period (August–November).[4] There

are four serotypes, i.e., DENV1–4. These four serotypes are transmitted to humans by mosquitoes, principally by the Aedes aegypti, and other species such as Aedes albopictus, Aedes polynesiensis, and Aedes scutellaris complex.[5] They usually breed in stagnant water; water was collected in containers, water‑based air coolers, and tyre dumps which create a favorable environment for the vectors in large cities.[6]

The purpose of this study was to assess the oral manifestations in patients with dengue fever.

MATERIALS AND METHODS

This cross‑sectional study was carried out in the inpatient Department of General Medicine, Indira Gandhi Government General Hospital and Postgraduate Institute, Pondicherry, from October to November 2017. Serologically diagnosed 50NS1 antigen‑positive cases

Oral manifestations of dengue feverSethuraman Govindaraj, Ramesh Jayaraman1, M. Jonathan Daniel, Saravanan Subbiah2,

Srinivasan Subramanian Vasudevan, Jimsha Vannathan KumaranDepartments of Oral Medicine and Radiology and 2Public Health Dentistry, Mahatma Gandhi Postgraduate Institute of Dental

Sciences Pondicherry, 1Department of Medicine, Geriatrics and Endocrinology, Indira Gandhi Government General Hospital and Postgraduate Institute Pondicherry, Puducherry, India

A B S T R A C T

Background: Dengue is a life‑threatening viral infection which has become an epidemic in India in the postmonsoon period (August–November). It mostly associated with nonspecific fever and rashes, arthralgia, myalgia, and thrombocytopenia in severe cases. Objective: This study aimed to study the oral manifestations of dengue fever and to observe the various features of oral presentation then to validate the significance and importance of oral manifestation in the diagnosis of dengue fever. Materials and Methods: Patients meeting the inclusion criteria were subjected to detailed history, oral examination, and relevant investigations. Results: Intraoral manifestations were present in 24 (48%) patients, anf these included petechiae (29.2%), bleeding gums (16.6%), ulcer (4.2%), dryness of mouth (4.2%), and combined features (45.8%). Extraoral manifestations were present in 4% of the cases. Conclusion: This study highlights the thrombocytopenia related oral haemosrrhagic manifestations of dengue fever.

Keywords: Dengue fever, oral manifestation, petechiae

Corresponding Author: Dr. Sethuraman Govindaraj, Department of Oral Medicine and Radiology, Mahatma Gandhi Postgraduate Institute of Dental Sciences Pondicherry, Puducherry, India. E‑mail: [email protected]

Cite this article as: Govindaraj S, Jayaraman R, Daniel MJ, Subbiah S, Vasudevan SS, Kumaran JV. Oral manifestations of dengue fever. Sahel Med J 2018;21:194-8.

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

For reprints contact: [email protected]

Access this article online

Quick Response Code:Website: www.smjonline.org

DOI: 10.4103/smj.smj_28_18

Original Article

[Downloaded free from http://www.smjonline.org on Friday, June 14, 2019, IP: 197.157.252.242]

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were included in the study by convenience sampling. Patients with platelet disorders, autoimmune disorders, bone marrow disease, trauma, and other infectious disease were excluded from the study. A written permission to carry out the study was obtained on 23‑10‑2017 from Medical superintendent of Indira Gandhi Government General Hospital & Post Graduate Institute. An informed consent was obtained. A detailed history was recorded; extraoral and intraoral examinations and relevant blood investigations were done. Intraoral examination was done using plane mouth mirrors under artificial illumination. Instruments and supplies were sterilized using autoclave every day before the survey. The data were entered on a pro forma containing demographic variables, chief complaint, and extraoral and intraoral sites and then analyzed using SPSS‑20 (IBM, Armonk, NY, United States of America). Frequency and percentage were used for various forms of manifestations. Student’s t‑test was used for comparison of mean among patients based on petechial status. Pearson correlation test was applied to assess the correlation between petechial count and platelet count. The level of statistical significance was set at P < 0.05.

RESULTS

A total of fifty patients were enrolled in the study. There were 34 males and 16 females. The male: female ratio was 2:1 [Table 1]. Intraoral manifestations were present in 24 (48%) patients, of which petechiae were seen in 29.2% of the patients, bleeding gums in 16.6%, ulcer in 4.2%, dryness of mouth in 4.2%, and combined features in 45.8%. Extraoral manifestations were present in 2 (4%) patients, with rashes as cutaneous features. Both extraoral and intraoral manifestations were found in 6 (12%) patients and in 18 (36%) patients only fever with no intra and extraoral findings [Table 2]. Of the fifty cases, thrombocytopenia was present in 38 (76%) patients. Thrombocytopenia with petechiae was observed in 18 (36%) cases and without petechiae was noted in 20 (40%) cases [Table 3]. On comparing the mean platelet count among patients based on petechial status, a low mean platelet count was observed among 20 patients with petechiae (64900±2880) compared to cases without petechiae (97500±6289). This difference in observation was found to be statistically significant (P = 0.03). There was no correlation between petechial count and mean platelet count.

DISCUSSION

Dengue fever is a rapidly growing public health problem, especially in the tropical and subtropical

countries. The incubation period after the mosquito bite is between 3 and 8 days. During the febrile period, the patient may experience severe headache, retro‑orbital pain, myalgia, arthralgia, nausea, and vomiting. More than 50% of the infected patients reported having a rash during this period that initially is macular or maculopapular and becomes diffusely erythematous. Minor hemorrhagic manifestations such as petechiae, epistaxis, and gingival bleeding occur in some patients.[7]

Severe dengue is life‑threatening from bleeding (dengue hemorrhagic fever), Dengue shock syndrome, or severe organ impairment (hepatic, renal, cardiac, pulmonary, and brain). The bleeding results from microangiopathy, while platelet number is insufficient to block the bleeding points. Shock results from capillary plasma leakage from vascular to extracellular spaces. Organ failure is presumably due to microangiopathy

Table 1: Age- and gender distribution of dengue patientsAge (years) Gender Total, n (%)

Male (n) Female (n)11‑20 7 4 11 (22)21‑30 8 3 11 (22)31‑40 7 5 12 (24)41‑50 11 2 13 (26)>51 1 2 3 (6)Total (%) 34 (68) 16 (32) 50 (100)

Table 3: Distribution of dengue patients according to platelet count and petechial statusPlatelet count Gender Total

(n=50), n (%)Male (n) Female (n)Normal platelet count without petechiae

6 4 10 (20)

Normal platelet count with petechiae

1 1 2 (4)

Thrombocytopenia with petechiae

11 7 18 (36)

Thrombocytopenia without petechiae

16 4 20 (40)

Total (%) 34 (68) 16 (32) 50 (100)

Table 2: Manifestations of dengue feverForms N (%) Features, n (%)Extraoral 2 (4) Rashes 2 (100)Intraoral 24 (48) Petechiae 7 (29.2)

Bleeding gums 4 (16.6)Ulcer 1 (4.2)Dryness of mouth 1 (4.2)Combined 11 (45.8)

Both extraoral and intraoral

6 (12) Combined features of rashes, petechiae, bleeding gums, ulcers, lips encrusting, dryness of mouth

No extraoral 42 (84) ‑No intraoral 20 (40) -

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resulting in impaired perfusion. While dengue fever is relatively inconsequential, severe dengue has a significant fatality rate.[8] The World Health Organization criteria exist for the classification of dengue into three clinical categories. Infection with DENV causes three clinical syndromes with undifferentiated viral syndrome, classic dengue fever, dengue hemorrhagic fever, and Dengue shock syndrome. However, there is a significant overlap between these three categories.[1,9]

A total of 50 cases of dengue were enrolled in our study with a male‑to‑female ratio of 2:1. Several other studies by Mahboob et al.[5] and Azfar et al.[3] have reported a similar gender variation and occurrence being more common in male. Most of our patients belonged to the age group of 20–40 years with the mean age of 33 years. This was similar to studies of Azfar et al.[3] and Saleem and Shaikh[10] In the present study, all the cases presented with fever, headache, arthralgia, and myalgia and some cases with vomiting and cough. The incubation period normally ranges from 4 to 7 days, after which the patients may experience an acute onset of fever followed by specific signs and symptoms.

Patients with cutaneous manifestations alone were noted in 4% of the cases in the present study [Figure 1]. Whereas in other studies by Mahboob et al.,[5] Thomas et al.,[7] and Azfar et al.,[3] these values were 77%, 46.8%, and 65%, respectively. This difference could possibly because of the rashes were present during 24–48 h of febrile period. Most of the patients which we examined were at the 5th–6th day of fever. The various hypotheses for cutaneous manifestation include as follows:1. Viral replication which occurs primarily in

macrophages although dendritic cells (Langerhans cell) in the skin may be the early target of infection

2. Direct infection of the skin by DENV3. Immunological and chemically mediated,

mechanism indeed by interaction of the virus with the host.

However, de Andino et al. concluded that the absence of evidence for direct viral involvement or for immune complex in the skin lesions could be due to viral‑host interaction including release of unidentified chemical mediators in the skin and that the rashes have nothing to do with the direct viral invasion or with the presence of immune complexes.[7]

In the present study, the oral manifestations were seen in 48% of the cases. Whereas in other studies conducted by Mahboob et al.[5] and Azfar et al.,[3] it was found to be 66% and 43.6%, respectively. The most common oral presentation was petechiae which were found to be present in 29.2% of the cases and seen in the posterior part of hard palate [Figure 2] followed by soft palate, buccal mucosa, labial mucosa, and tongue [Figure 3] which is similar to presentation reported by Bhardwaj et al.[1] and Mithra et al.[9] These lesions were reddish‑to‑purple discoloration caused by blood from vessels leaking into the connective tissue. Purpuric lesions do not blanch when pressure is applied and are classified by the size as petechiae (<0.3 cm), purpura (0.4–0.9 cm), and ecchymosis (>1 cm).[11]

Bleeding gums were noted in 16.7% of the patients which were present during the 2nd and 3rd days of fever. The bleeding was spontaneous in nature which is similar to a study reported by Khan et al.[12,13] The major cause of hemorrhagic manifestations is plasma leakage and abnormal hemostasis. Abnormal hemostasis includes capillary fragility, thrombocytopenia, impaired

Figure 1: Cutaneous manifestation in the form of rashes and purpuric spots Figure 2: Oral manifestations in the form of petechiae in hard palate

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Figure 4: Ulcer in corner of mouth with vesicles formation

platelet function, and disseminated intravascular coagulation (DIC).[1,9]

Ulcer was present in 1 patient out of 50 patients examined. There was a history of vesicles before ulcer formation with the corner of the mouth as the site of involvement. It occurred during the 3rd day of fever which is similar to the reports of Bhardwaj et al.[1] and Mithra et al.[9] Dryness of mouth was present in 4.2% of the patients, mostly due to dehydration. Combination of petechiae, bleeding gums, ulcer, dryness of mouth, and lip encrusting [Figure 4] was present in 45.8% of the patients who presented with intraoral manifestations alone. Both extraoral manifestation and intraoral manifestations were found in 12% of the patients presenting with combined features of rashes, petechiae, bleeding gums, ulcer, dryness of mouth, and lip encrusting.

Thrombocytopenia was present in 76% of the overall cases, wherein petechiae were associated with 47.4% of the cases. Petechiae were commonly associated with thrombocytopenia as compared to patient with normal platelet count. This association is because of leakage of small blood vessels due to thrombocytopenia into the surrounding tissue which presents in the form of petechiae.[14] Several hypotheses have been suggested to elucidate the mechanism involved for thrombocytopenia in dengue which includes DENV, which could directly or indirectly affect bone marrow progenitor cells by inhibiting their function to reduce the proliferative capacity of hematopoietic cells. Indeed, there is evidence that DENV can induce bone marrow hypoplasia during the acute phase of the disease. Beside platelet counts, the functional disruption of these cells is associated with a significant

deregulation of the plasma kinin system and the immunopathogenesis of dengue. In addition, DENV infection induces platelet consumption due to DIC, platelet destruction due to increased apoptosis, lysis by the complement system, and by the involvement of antiplatelet antibodies.[15]

According to the study, petechiae were most commonly present. Although they are not a constant feature in dengue fever, laboratory investigations have to be done to substantiate its significance.

In a patient with a recent history of dengue, dentist should check for recovery of oral signs and symptoms. Usually, the lesions heal uneventfully within 2 weeks. If any surgical intervention is required in such patient (i.e., extraction and flap procedure), it is important to undergo blood investigation to assess the platelet count.

CONCLUSION

This study highlights the thrombocytopenia related oral haemosrrhagic manifestations of dengue fever.

Financial support and sponsorshipNil.

Conflicts of interestThere are no conflicts of interest.

REFERENCES

1. Bhardwaj VK, Negi N, Jhingta P, Sharma D. Oral manifestations of dengue fever: A rarity and literature review. Eur J Gen Dent 2016;5:95‑8.

2. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial

Figure 3: Oral manifestation in the form of petechiae in tongue

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Pathology. 3rd ed. Philadelphia: Saunders; 2009. p. 240‑64.3. Azfar NA, Malik LM, Jamil A, Jahangir M, Tirmizi N, Majid A, et al.

Cutaneous manifestations in patients of dengue fever. J Pak Assoc Dermatol 2012;22:320‑4.

4. Raj AS, Munshi S, Shah BH. A study on clinical presentation of dengue fever in children. IJSR 2016;5:2272‑5.

5. Mahboob A, Iqbal Z, Javed R, Taj A, Munir A, Saleemi MA, et al. Dermatological manifestation in dendue fever. J Ayub Med Abbottabad 2012;24:52‑4.

6. Colledge NR, Walker BR, Ralston SH. Davidson’s Principles & Practice of Medicine. 21st ed. Edinburg; New York: Elsevier; 2011. p. 318‑9.

7. Thomas EA, John M, Kanish B. Mucocutaneous manifestations of dengue fever. Indian J Dermatol 2010;55:79‑85.

8. Eapen CE, Elias E, Goel A, John JT. Hypothesis of mechanism of thrombocytopenia in severe dengue, providing clues to better theraphy to save lives. Curr Sci 2015;108:168‑9.

9. Mithra R, Baskaran P, Sathyakumar M. Oral presentation in dengue

hemorrhagic fever: A rare entity. J Nat Sci Biol Med 2013;4:264‑7.10. Saleem K, Shaikh I. Skin lesions in hospitalized cases of dengue

fever. J Coll Physicians Surg Pak 2008;18:608‑11.11. Glick M. Burket’s Oral Medicine. 12th ed. Shelton: PMPH; 2015.12. Khan S, Gupta ND, Maheshwari S. Acute gingival bleeding as a

complication of dengue hemorrhagic fever. J Indian Soc Periodontol 2013;17:520‑2.

13. Pedrosa MS, de Paiva M, Oliveira L, Pereira S, da Silva C, Pompeu J, et al. Oral manifestations related to dengue fever: A systematic review of the literature. Aust Dent J 2017;62:404‑11.

14. Soares de Lima AA, Falcao de Oliveira Melo NS, Dias Gil FB. Oral manifestation of thrombocytopenia in immunosuppressed patient – Report of case. J Oral Diagn 2016;01:e8.

15. de Azeredo EL, Monteiro RQ, de‑Ol iveira Pinto LM. Thrombocytopenia in dengue: Interrelationship between virus and the imbalance between coagulation and fibrinolysis and inflammatory mediators. Mediators Inflamm 2015; 2015:313842.

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