Oral manifestations of dengue virus infection: a scoping review for clinical dental practice

Abstract

Background

Dengue virus (DENV) infection, a mosquito-borne disease, presents a significant public health challenge globally, with diverse clinical manifestations. Although oral dengue manifestations are uncommon, they can serve as crucial diagnostic indicators and impact patient management in dental practice. This scoping review aims to map the evidence on the oral manifestations associated with DENV infection and their clinical implications for dental practice.

Methods

This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and was registered on PROSPERO (CRD42022337572). A comprehensive search was conducted across six electronic databases (MEDLINE, Web of Science, Scopus, Embase, Cochrane Library, and LILACS/BBO) up to June 2024. Eligible studies included case reports, case-control, cohort, and cross-sectional studies reporting oral manifestations in patients with DENV infection.

Results

A total of 41 studies were included, comprising 17 case reports, 15 retrospective cohort studies, 4 prospective cohort studies, and 5 cross-sectional studies. Gingival bleeding, oral ulceration, bilateral inflammatory increase in the parotid glands, and lingual hematoma were the most frequently reported oral manifestations. Less common manifestations included Ludwig’s angina, osteonecrosis of the jaw, and angular cheilitis. These findings suggest a broad spectrum of oral symptoms that could aid in the early identification and management of dengue patients.

Conclusions

This review highlights the importance of recognizing oral manifestations in dengue patients, which can facilitate early diagnosis and intervention, particularly in dengue-endemic regions. Dental professionals play a crucial role in identifying these symptoms and improving patient outcomes. Further research is needed to explore the pathophysiological mechanisms underlying these manifestations and to develop standardized protocols for clinical assessment and management.

Clinical relevance

This paper highlights the role of dental professionals in early dengue diagnosis, emphasizing oral manifestations like gingival bleeding. It promotes interdisciplinary care, improving patient outcomes and management in dengue-endemic regions.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12903-025-05504-6.

Introduction

Dengue is a mosquito-borne viral disease that has been rapidly increasing across the globe in recent years, with at least 390 million estimated annual cases [1]. Dengue virus is from the Flaviviridae family, and there are five different serotypes that can infect human beings (DENV-1, DENV-2, DENV-3, DENV-4, and DENV-5) [2]; However, the dengue disease has different epidemiological patterns worldwide, and often one serotype is transmitted to another region of the world through infected travelers, causing an alarming endemic from different serotypes of dengue. The primary infection vector for dengue virus (DENV) is the female mosquitoes of the species Aedes aegypti and A. albopictus [3]. These types of mosquitoes are prevalent in tropical and subtropical climates such as Southeast Asia, India, and Latin American countries [4].

DENV remains a critical public health challenge in Brazil, characterized by complex dynamics influenced by environmental, social, and virological factors. This disease has seen fluctuating patterns of incidence with periodic resurgences, notably post-Zika epidemic [5]. Recent data from 2023 highlights the introduction of new DENV lineages and a concerning increase in cases and fatalities, exacerbated by the overlapping impact of the COVID-19 pandemic [6, 7]. These developments emphasize the continued need for vigilant surveillance, vector control, and public health preparedness to manage and mitigate the impacts of dengue.

Most of the infections are estimated to be asymptomatic. Moreover, dengue fever can manifest mild flu-like symptoms, such as fever, nausea, muscle and joint pain, and headaches [8]. Although dengue fever is self-resolving, transitory thrombocytopenia is a common finding in blood screenings during the acute phase of the febrile illness. However, in the minority of the patients, complications emerge due to this reduction in the platelet count, evolving into more severe cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). These stages of severe dengue fever are potentially lethal to the host due to coagulation abnormalities, plasma leakage, severe bleeding, respiratory distress, and fluid loss leading to hypovolemic shock and multi-organ failure [9].

Although oral manifestations of the dengue virus are considered uncommon [10], dental professionals should be able to identify oral symptoms related to DENV and give an early diagnosis of infected patients undergoing dental procedures. Commonly reported manifestations include gingival bleeding, oral ulceration, lingual hematoma, and bilateral inflammatory swelling of the parotid glands. From this perspective, this scoping review aims to retrieve all relevant data regarding the oral manifestations of DENV and critically analyze the clinical implications to dental practice and the oral outcomes related to this viral disease, giving insight to dental professionals as to how to manage the patient infected with DENV.

Materials and methods

Protocol registration and research question

This scoping review is reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis extension for Scoping Reviews (PRISMA-ScR) [11, 12], and the protocol for this study was registered a priori on the PROSPERO database (registration code: CRD42022337572).

The research question was developed within the population-concept-context (PCC) framework for scoping reviews: What are the oral manifestations (Concept) associated with patients with dengue virus infection (Population), and what are their clinical implications for dental practice (Context)?

Eligibility and exclusion criteria

Eligible studies were original articles that reported any oral manifestation directly related to dengue infection and its clinical outcome. The design of the included studies was limited to case reports, case-control, cohort, and cross-sectional studies.

In order to extract patient-level data, exclusion criteria were applied to in vitro and ex vivo studies, animal studies, gray literature, literature reviews, short commentaries, letters to the editor, and congress abstracts.

Information sources and search strategy

A search strategy was elaborated based on the combination of MEDLINE MeSH (Medical Subject Headings) terms related to dengue virus infection and oral health, and they were adapted for the other databases, respecting their syntax rules (Supplementary file 1). A total of 6 electronic databases were systematically searched until June 20th, 2024: MEDLINE (via PubMed), Web of Science, Scopus, Embase, Cochrane Library, and LILACS/BBO. Additionally, the references of eligible studies were manually verified to increase the pool of studies.

Selection process

The selection process began with a systematic search, and the resulting references were uploaded to Mendeley (Elsevier, Amsterdam, NE) to remove duplicates. These references were then transferred to Rayyan online software (Qatar Computing Research Institute, Doha, QA) [13] for further evaluation. In this phase, two independent reviewers performed a blind review of titles and abstracts. Once this initial review was completed, the blind was removed, and discrepancies were resolved through consultation with a third researcher. This selection process was based on established eligibility criteria. Studies that met these criteria or those that could not be conclusively assessed from the title and abstract were chosen for full-text review. Additionally, a manual search of the references from these selected studies was conducted to find other pertinent studies that the initial search might have missed.

Data collection process

Two independent reviewers extracted data from the eligible studies using a standardized Excel sheet (Microsoft, Redmond, USA). Subsequently, a third reviewer performed a double-check of the extracted data. The following information was collected: study characteristics (e.g., author, publication year, country, and study type), participant characteristics (e.g., sample size, age, gender), details of the dengue infection (e.g., serotype, geographic distribution, and transmission vector), information about the clinical manifestation of DENV (e.g., symptomatology and oral manifestations), and the outcome as reported by the studies.

Results

Search strategy

Figure 1 presents a flowchart detailing the study selection process for this review. The final systematic search across all databases was completed in July 2024, resulting in 1240 records. After removing 411 duplicates, the remaining records were screened based on titles and abstracts, leading to the exclusion of 777 records that did not meet the eligibility criteria. This left 52 studies for detailed full-text analysis. Of these, eleven were excluded for various reasons, such as being literature reviews, not reporting oral manifestations, or being letters to the editor. Ultimately, 41 studies met all the criteria and were included in this review.

Fig. 1.

Search flowchart according to the PRISMA 2020 statement

Study characteristics

We identified 41 studies that addressed the oral manifestations of dengue. Among these, 41% (17/41) were clinical case reports [14–30], 37% (15/41) were retrospective cohort studies [31–45], 10% (4/41) were prospective cohort studies [46–49], and 12% (5/41) were cross-sectional studies [50–54]. The included studies in this review originate from a diverse range of countries, reflecting the global impact of dengue fever. India contributes the highest number of studies with 13 publications [17, 21–27, 29, 30, 36, 39, 40] followed by Brazil with 6 studies [19, 28, 38, 43, 45, 50], Pakistan with 4 studies [41, 48, 53, 54], Mexico [32, 52], Bangladesh [34, 46] and Taiwan [35, 37] with 2 studies each. Additionally, Sri Lanka [47] is represented by a prospective cohort study. Other contributions include 1 study each from Colombia [51], Fiji [31], Venezuela [14], the United States [15], Yemen [16], Honduras [44], Japan [18], Cuba [42], Bolivia [20], China [33], and France [49], highlighting the widespread concern and varied research efforts addressing oral manifestations of dengue across different regions and populations.

The sample described in Table 1 encompasses a diverse group of patients affected by dengue. The studies collectively include thousands of participants (n = 42.817), with individual study sample sizes varying from single case reports to large cohort studies involving thousands of patients. The mean age range of participants, where specified, varied widely from 8 to 44 years. However, all age groups were represented, reflecting the broad range affected by dengue. Both genders were included across the studies, showing a balanced perspective on how dengue impacts males and females.

Table 1.

Study characteristics and oral manifestations

Study characteristics		Participant characteristics			DENV characteristics			Oral manifestations
Author/Year	Study design	Sample size	Age	Gender	Serotype	Geographic distribution	Transmission vector
Fagbami et al., 1995	Retrospective cohort	426	All ages	Both genders	DENV-1 and DENV-2	Fiji	Aedes albopictus	Gingival bleeding
Desruelles et al., 1997	Retrospective cohort	39	All ages	Both genders	DENV-2	Mexico	Aedes aegypti	Pharyngitis Erythematous Diffuse, Glossitis Depapillated, Gingival Bleeding and Purpura of the Palate
Vasconcelos et al., 1998	Cross-sectional	1341	All ages	Both genders	DENV-2	Brazil	Aedes aegypti	Gingival bleeding and epistaxis
Torres et al., 2000	Case report	1	55 years	Man	DENV-1	Venezuela	Aedes aegypti	Bilateral inflammatory increase in the parotid glands
Ahmed et al., 2001	Prospective cohort	72	Average 8 years old		N/A	Bangladesh	Aedes aegypti	Gingival bleeding
Setlik et al., 2004	Case report	1	61 years	Woman	DENV-1, DENV-2 and DENV-3	United States	Aedes aegypti	Oral ulceration
Díaz-Quijanoa et al., 2005	Cross-sectional	891	Over 15 years old	Both genders	N/A	Colombia	Aedes aegypti and Aedes albopictus.	Gingival bleeding
Malavige et al., 2006	Prospective cohort	104	N/A	Both genders	N/A	Sri Lanka	Aedes aegypti	Oral candidiasis
Ramırez-Zepeda et al., 2009	Cross-sectional	241	Average 34 years old	Both genders	N/A	Mexico	Aedes aegypti	Gingival bleeding
Ribeiro et al., 2010	Retrospective cohort	4818	All ages	Both genders	DENV-1, DENV-2 and DENV-3	Brazil	Aedes aegypti	Gingival bleeding
Bhaskar et al., 2010	Retrospective cohort	128	Average 33 years old	Both genders	N/A	India	Aedes aegypti	Gingival bleeding
Kumar et al., 2010	Retrospective cohort	466	N/A	Both genders	N/A	India	Aedes aegypti	Gingival bleeding
Sarkar et al., 2011	Case report	1	N/A	Man	N/A	India	Aedes mosquito	Lingual hematoma causing upper airway obstruction
Mahboob et al., 2012	Prospective cohort	60	All ages	Both genders	N/A	Pakistan	Aedes mosquito	Oral mucous membrane congestion
Sheikh et al., 2012	Cross-sectional	109	All ages	Both genders	N/A	Pakistan	Aedes mosquito	Diffuse erythema, candidiasis and oral aphthae
Azfar et al., 2012	Cross-sectional	300	All ages	Both genders	N/A	Pakistan	Aedes mosquito	Erythema of the buccal mucosa and palate
Mithra et al., 2013	Case Report	1	N/A	Female	N/A	India	Aedes aegypti	Bilateral submandibular Lymphadenopathy, hemorrhagic plaques blue mucosa area of erosion tonsils inflamed. xerostomia and the tongue appeared to be coated.
Dubey et al., 2013	Case report	1	20-year-old	Male	N/A	India	Aedes aegypti	Gingival bleeding
Ahmed et al., 2013	Retrospective cohort	640	All ages	Both genders	DENV-1, DENV-2, DENV-3 and DENV-4	Pakistan	Aedes mosquito	Gingival bleeding
Khan et al., 2013	Case report	1	18 years	Male	N/A	India	Aedes aegypti	Gingival bleeding
Byatnal et al., 2013	Case report	1	50 years	Female	N/A	India	Aedes aegypti	Gingival bleeding
Pontes et al., 2014	Case report	1	18 years	Male	N/A	Brazil	Aedes aegypti	Gingival and lip reddish swelling
Bansal et al., 2014	Case report	1	40 years		N/A	India	Aedes aegypti	Gingival bleeding
Brito, 2014	Retrospective cohort	997	N/A	Both genders	N/A	Cuba	Aedes aegypti	Gingival bleeding
Indurkar and Sethi, 2015	Case report	1	46 years		N/A	India	Aedes aegypti	Osteonecrosis of the jaw
Pone et al., 2016	Retrospective cohort	145	Under 18 years	Both genders	N/A	Brazil	Aedes aegypti	Gingival bleeding
Al-Namnam et al., 2016	Case report	1	30 years	Both genders	N/A	Yemen	Aedes aegypti	Maxillary osteonecrosis, periodontitis with root resorption
Bhardwaj et al., 2016	Case report	1	19 years	Male	N/A	India	Aedes aegypti	Blisters in mouth, soreness on the gums, alveolar mucosa on soft palate, and difficulty in swallowing
Fernandez et al., 2016	Retrospective cohort	390	Average 21 years	Both genders	N/A	Honduras	Aedes aegypti	Gingival bleeding
Yamamoto, 2019	Case report	1	6 years	Male	DENV-1	Japan	Aedes aegypti	Submucosal hemorrhages on the hard palate and rose-colored spots on the soft palate
Barros et al., 2020	Retrospective cohort	1,003	All ages	Both genders	N/A	Brazil	Aedes aegypti	Ulcerative stomatitis
Fernandes, et al., 2020	Case report	1	29 year	Female	N/A	Brazil	Aedes aegypti	Gingival bleeding, maculopapular lesions, erythema, petechiae and ecchymoses
Cossaboom et al., 2020	Case report	5	65, 25, 22, 48 years Case 5: N/A	Male	N/A	Bolivia	Aedes aegypti	Gingival hemorrhage
Wang et al., 2021	Retrospective cohort	718	All ages	Both genders	N/A	China	Aedes aegypti	Dry mouth
Khan et al., 2021	Retrospective cohort	190	Under 15 years	Both genders	DENV-1	Bangladesh	Aedes aegypti	Mouth sores
Chang et al., 2021	Retrospective cohort	29,365	Average 44 years	Both genders	N/A	Taiwan	Aedes aegypti	Sjogren’s syndrome
Shang et al., 2021	Retrospective cohort	105	All ages	Both genders	N/A	Taiwan	Aedes aegypti	Gingival bleeding
Dronamraju et al., 2022	Case report	1	31 years	Female	N/A	India	Aedes aegypti	Ludwig’s angina
Randhawa et al.,2023	Retrospective cohort	84	Under 12 years	Both genders	N/A	India	Aedes aegypti	Oral mucosal changes
Fera et al., 2023	Prospective cohort	163	N/A	Both genders	N/A	France	Aedes aegypti	Mouth involvement including lip, tongue, cheek, angular cheilitis, pharyngitis, mouth ulcer and gingivitis
Das et al., 2024	Case report	2	30 years and 43 years	Male	DENV-1	India	Aedes aegypti	Oral/oro-pharyngeal pseudomembranous candidiasis

DENV-1: Dengue virus serotype 1; DENV-2: Dengue virus serotype 2; DENV-3: Dengue virus serotype 3; DENV-4: Dengue virus serotype 4; DF: Dengue fever; DHF: Dengue hemorrhagic fever; N/A: Not applicable

The distribution of DENV serotypes across the studies showed that DENV-2 was the most frequently reported, accounting for 20% (8/41) of the studies, followed by combinations of DENV-1 and DENV-2 at 5% (2/41) and DENV-1, DENV-2, and DENV-3 at 7% (3/41). A single study, reported all four serotypes (DENV-1 to DENV-4), while the serotype was unspecified in 66% (27/41) of the studies. Geographically, the studies were concentrated in tropical and subtropical regions as shown in Fig. 2. By continent, Asia accounted for 61% (25/41) of the studies, followed by South America with 22% (9/41), North America with 7% (3/41), Central America with 5% (2/41), Oceania and Europe with 2% (1/41) each; no studies were reported from Africa. Within countries, Brazil and India were the most represented countries. Regarding transmission vectors, Aedes aegypti was identified as the primary vector in 78% (32/41) of the studies, Aedes albopictus in 5% (2/41), and a combination of both vectors in 17% (7/41). These findings emphasize the global variability in DENV serotypes, the regional burden of disease, and the transmission dynamics.

Fig. 2.

Global map showing the distribution of DENV studies. Search flowchart according to the PRISMA 2020 statement

Table 1 presents a wide array of oral manifestations associated with DENV infections. Gingival bleeding emerged as the most frequently reported symptom (51%), documented in 21 studies across various countries. Other notable oral manifestations included oral ulcerations (10%), often severe enough to cause significant discomfort or complications; pharyngitis (10%); and oral/oropharyngeal pseudomembranous candidiasis (7%).

Additional symptoms, such as bilateral inflammatory swelling of the parotid glands, indicating systemic involvement, and lingual hematoma, which can obstruct the upper airways, were also reported. Other manifestations included hemorrhagic plaques, blue mucosa, submucosal hemorrhages on the hard palate, pink spots on the soft palate, and Ludwig’s angina, highlighting the diverse and often severe nature of oral involvement in dengue cases. Further documented findings, such as osteonecrosis of the jaw and angular cheilitis, underscore the importance of comprehensive oral examinations in patients with dengue.

Discussion

This scoping review identified 41 studies that discussed various aspects of oral manifestations related to DENV infection. Among these, 17 were clinical case reports, 15 were retrospective cohort studies, 4 were prospective cohort studies, and 5 were cross-sectional studies. The oral manifestations most frequently reported in the included studies were gingival bleeding, oral ulceration, bilateral inflammatory increase in the parotid glands, and lingual hematoma. Gingival bleeding emerged as the most common oral manifestation, reported in multiple studies across various countries, reflecting a potential diagnostic clue for DENV infection in clinical practice. Dengue is characterized by thrombocytopenia and coagulopathy, which increase bleeding tendencies, making the highly vascularized and easily irritated gingival tissues particularly susceptible to spontaneous bleeding [55–57]. Additionally, oral ulcers may arise from immune dysregulation triggered by DENV, involving the activation of inflammatory cytokines and immune cells that cause mucosal damage [58]. Systemic effects of dengue, such as dehydration and nutritional deficiencies, further exacerbate mucosal fragility, compounding the vulnerability of oral tissues [59]. The variation in clinical presentation, ranging from mild symptoms like gingival bleeding to more severe manifestations such as osteonecrosis of the jaw and Ludwig’s angina, highlights the complexity of oral involvement in dengue cases and the importance of early diagnosis and comprehensive management. These manifestations are likely due to the combination of direct viral effects, immune-mediated tissue damage, and systemic complications like thrombocytopenia and vascular leakage, which are hallmarks of severe dengue infection.

The findings align with previous reviews, such as the study by Pedrosa et al. (2017) [10], which also identified gingival bleeding as a prevalent oral manifestation of dengue fever. However, our review expands upon earlier work by including recent studies that report additional, previously undocumented oral symptoms. For instance, Ludwig’s angina has been associated with dengue due to the immunosuppressed state caused by the virus, which predisposes patients to severe infections [21]. Furthermore, new associations such as Sjögren’s syndrome, identified in recent studies [35], suggest potential autoimmune implications of DENV infections. These novel findings underscore the evolving understanding of the diverse oral manifestations associated with dengue and the need for continuous surveillance and research to understand the full spectrum of symptoms better.

The wide range of oral symptoms associated with DENV may stem from several factors, including the complexity of the disease’s pathophysiology, variability in patient immune responses, and differences in diagnostic practices across regions [60]. Misdiagnosis or delayed diagnosis of dengue, particularly in endemic areas with common febrile illnesses, may also contribute to the observed variability in reported symptoms [6]. For example, conditions such as Ludwig’s angina might initially be attributed to other causes until a definitive dengue diagnosis is made, reflecting a gap in clinical awareness and timely recognition of DENV’s impact on oral health [60]. It is essential for healthcare providers, especially dental professionals in dengue-endemic regions like Asia and South America, to be well-versed in the oral manifestations of dengue. This knowledge will facilitate early differential diagnosis and prompt intervention, potentially improving patient outcomes by preventing the progression to more severe stages of the disease.

This review highlights several controversies that warrant further investigation. The variability in reported oral manifestations, ranging from common symptoms such as gingival bleeding to rare findings like Ludwig’s angina and Sjögren’s syndrome, raises concerns about the consistency of diagnostic practices and reporting standards across regions and studies. While immune dysregulation and thrombocytopenia are proposed as explanations, the mechanisms underlying severe cases like osteonecrosis of the jaw remain speculative and require more robust evidence. Additionally, diagnostic gaps and potential misdiagnoses, particularly in endemic regions, emphasize the need for enhanced clinical awareness and education. These controversies underscore the need for large-scale, multicenter studies to validate findings, elucidate mechanisms, and develop standardized diagnostic and management protocols.

Dental professionals’ early identification of oral manifestations can significantly contribute to the early diagnosis of dengue, thereby improving patient outcomes. Recognizing symptoms such as gingival bleeding, oral ulceration, and mucosal changes as potential indicators of dengue can prompt timely referral for medical evaluation and appropriate management, which is crucial in preventing severe complications like DHF and DSS. This underscores the importance of comprehensive training and awareness among dental practitioners regarding the signs of DENV infection. Additionally, dentists should remain vigilant when considering potential diagnoses, as medications must be prescribed with caution. For patients with suspected dengue, the use of non-essential drugs—particularly anti-inflammatories, antibiotics, and medications with renal, hepatic, or hematologic toxicity—is not recommended, in accordance with World Health Organization guidelines [4].

It is important to highlight that this review expanded the literature search compared to the last published review by utilizing six databases. Although this review provides valuable insights into the oral manifestations of dengue, limitations must be acknowledged. The reliance on case reports and cohort studies introduces variability in the quality of evidence [61], and the geographic distribution of studies may not fully capture the global diversity of DENV’s clinical presentation. The exclusion of gray literature ensured the inclusion of high-quality, peer-reviewed evidence to enhance reliability and standardization. However, this decision may have introduced some publication bias. To address this, we conducted a manual reference search and adhered to a transparent methodology. Additionally, a quality assessment was not performed, as the primary objective of this scoping review was to map the available evidence. Future research should focus on large-scale, multicenter studies to validate these findings and explore the pathophysiological mechanisms underlying the oral manifestations of dengue.

Conclusions

In conclusion, the timely diagnosis of dengue through the recognition of oral manifestations is crucial in mitigating the impact of this disease. Dental professionals play a pivotal role in identifying early signs of DENV infection, especially in endemic regions. Future research should aim to elucidate the pathogenesis of oral manifestations associated with dengue and develop standardized protocols for clinical assessment and management. Enhanced education and awareness programs for healthcare professionals are recommended to strengthen early detection and improve patient care outcomes in the context of dengue fever.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

LPA, SKW, and ETC drafted the main manuscript and conducted the initial analysis. BCC and MAK reviewed the analysis and contributed to data extraction. NKW and SAK reviewed the final manuscript and provided support for the methodology.

Funding

This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.