Gazal G, Alsalhani AB, Tarakji B, Nassani MZ. Evidence-based review and clinical practice recommendations for the diagnosis and management of common oral mucosal lesions. World J Exp Med 2026; 16(1): 115535 [DOI: 10.5493/wjem.v16.i1.115535]
Corresponding Author of This Article
Mohammad Zakaria Nassani, DDS, PhD, Associate Professor, Department of Restorative and Prosthetic Dental Sciences, College of Dentistry, Dar Al Uloom University, Northern Ring Road, Exit 7, Al Falah District, Riyadh 13314, Saudi Arabia. mznassani@dau.edu.sa
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Dentistry, Oral Surgery & Medicine
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Minireviews
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Mar 20, 2026 (publication date) through Mar 20, 2026
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World Journal of Experimental Medicine
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2220-315x
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Gazal G, Alsalhani AB, Tarakji B, Nassani MZ. Evidence-based review and clinical practice recommendations for the diagnosis and management of common oral mucosal lesions. World J Exp Med 2026; 16(1): 115535 [DOI: 10.5493/wjem.v16.i1.115535]
Giath Gazal, Department of Oral and Maxillofacial Surgery, Aleppo University, Aleppo 12212, Syria
Anas B Alsalhani, Department of Dentistry, Vision Colleges, Riyadh 13226-3830, Saudi Arabia
Anas B Alsalhani, Department of Histology and Pathology, Faculty of Dentistry, University of Hama, Hama 12345, Syria
Bassel Tarakji, Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
Mohammad Zakaria Nassani, Department of Restorative and Prosthetic Dental Sciences, College of Dentistry, Dar Al Uloom University, Riyadh 13314, Saudi Arabia
Author contributions: Gazal G and Nassani MZ conceptualized and designed the study; Gazal G drafted the original manuscript; Alsalhani AB, Tarakji B, and Nassani MZ critically revised the manuscript; All authors conducted the literature review and participated in the analysis and interpretation of data; All authors read and approved the final submitted version.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Corresponding author: Mohammad Zakaria Nassani, DDS, PhD, Associate Professor, Department of Restorative and Prosthetic Dental Sciences, College of Dentistry, Dar Al Uloom University, Northern Ring Road, Exit 7, Al Falah District, Riyadh 13314, Saudi Arabia. mznassani@dau.edu.sa
Received: October 20, 2025 Revised: November 19, 2025 Accepted: January 20, 2026 Published online: March 20, 2026 Processing time: 147 Days and 9.9 Hours
Abstract
Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions.
Core Tip: This minireview provided general dental practitioners with a practical, evidence-based guide for the diagnosis and management of common oral mucosal lesions. It introduced a clinical classification framework based on lesion appearance, site, and risk, together with evidence-based first-line and adjunctive treatment options. Diagnostic pathways, severity-based escalation protocols, and integrative herbal therapies were also outlined. By integrating conventional and validated complementary therapies into a single decision-support framework, this minireview aimed to enhance diagnostic accuracy, support safe and effective management, and bridge conventional and integrative strategies in the care of patients with oral mucosal lesions.
Citation: Gazal G, Alsalhani AB, Tarakji B, Nassani MZ. Evidence-based review and clinical practice recommendations for the diagnosis and management of common oral mucosal lesions. World J Exp Med 2026; 16(1): 115535
Oral mucosal lesions involve a wide range of conditions, including benign lesions, reactive lesions, immune-mediated diseases, and potentially malignant disorders[1,2]. The diagnosis and management of oral lesions present a continuing clinical challenge in general dental practice. This is mainly due to overlapping presentations, variations in severity, and a lack of structured treatment protocols[3,4]. In the United Kingdom the incidence of oral white lesions such as leukoplakia and oral lichen planus is substantial, largely among adults aged 40 years and above with risk factors including tobacco use, alcohol consumption, and systemic immunosuppression[1,5,6]. Moreover, ulcers, candidiasis, and burning mouth syndrome (BMS) are among the most frequently encountered oral lesions, yet their diverse etiologies often complicate early diagnosis and intervention[7,8].
While hospital-based oral medicine departments offer advanced management, the vast majority of patients first present to general dental practitioners (GDPs), highlighting the need for a simplified yet evidence-based diagnostic and therapeutic protocol[9,10]. Several United Kingdom clinical guidelines, including those from the British National Formulary (BNF), National Institute for Health and Care Excellence (NICE), and Public Health England, offer isolated treatment recommendations, but no single, integrated protocol currently exists to guide GDPs through assessment, diagnosis, and treatment escalation[11,12].
This review attempted to bridge this gap by synthesizing evidence from a wide range of peer-reviewed literature and United Kingdom clinical guidelines to create a comprehensive clinical ladder for the treatment of common oral mucosal lesions. It provided structured classification tables and pharmacologic and herbal therapies and implemented an escalation management approach based on severity of the condition. This unified protocol was designed to support GDPs in making informed, stepwise decisions regarding oral lesion care, ultimately improving diagnostic accuracy, treatment outcomes, and timely referrals[11-15].
METHODOLOGY
This evidence-informed narrative review was conducted to develop a comprehensive, clinically applicable protocol for the diagnosis and management of common oral mucosal lesions in general dental practice. A narrative synthesis approach was employed to integrate diverse evidence types, including clinical guidelines, randomized controlled trials (RCTs), systematic reviews, and observational studies, across a range of oral mucosal conditions, populations, and care settings. This flexible approach allowed the incorporation of research evidence, clinical reviews, and clinical guidelines relevant to primary dental care.
Literature search strategy
A targeted and exploratory literature search was performed across major biomedical databases, including PubMed, Scopus, and Web of Science (ISI-indexed journals), covering January 2014 to June 2025. Endorsed clinical guidelines, including the BNF[12] and the NICE[13], were also incorporated.
Search terms were derived from the main diagnostic and management categories represented in the clinical summary tables (Tables 1, 2, 3, 4, and 5). Core keywords and Boolean combinations included: Conditions: “Oral mucosal lesions” OR “oral ulceration” OR “leukoplakia” OR “erythroplakia” OR “oral lichen planus” OR “oral candidiasis” OR “traumatic ulcer” OR ‘burning mouth syndrome” OR “geographic tongue” OR “xerostomia”. Combined with: “Diagnosis” OR “management” OR “treatment’ OR “clinical protocol” OR “general dental practice” OR “guidelines” OR “evidence-based dentistry.”
Table 1 Clinical classification of common oral mucosal lesions based on appearance, site, and risk profile.
Urgent referral for any persistent red or red-white patch (erythroplakia/erythroleukoplakia), non-healing ulcer > 3 weeks, or unexplained lump on lip/oral cavity
This approach was not systematic or comprehensive but rather purposeful and integrative and designed to capture clinically relevant evidence and prioritize practical applicability over exhaustive literature retrieval in a general dental context. A total of 47 peer-reviewed and guideline-based sources were included following relevance screening.
Inclusion/exclusion criteria
Studies were included if they were peer-reviewed, English-language publications published between January 2014 and June 2025 and addressed the diagnosis or management of oral mucosal lesions in general dental practice, including clinical guidelines, RCTs, systematic or scoping reviews, narrative reviews, or observational studies. Case reports, non-English publications, animal or in vitro studies, and publications before 2014 were excluded.
Data selection and synthesis and evidence grading
All references were appraised using a simplified GRADE approach: Grade A (high): Consistent findings from ≥ two RCTs, systematic reviews/meta-analyses, or national guidelines; Grade B (moderate): Cohort, cross-sectional, audit, or pre-post intervention studies; and Grade C (low): Narrative reviews, expert consensus, textbooks, or pilot studies.
The selected literature encompassed a broad spectrum of inflammatory, infectious, immune-mediated, traumatic, and potentially malignant oral mucosal conditions. Studies were prioritized based on clinical relevance, diagnostic clarity, and applicability to general dental practice.
Data were extracted, synthesized narratively, and organized into five structured tables summarizing: (1) Clinical classification of oral mucosal lesions by appearance, site, and risk profile (Table 1); (2) First-line and adjunctive treatments (Table 2); (3) Diagnostic pathways (Table 3); (4) Escalation protocols for GDPs (Table 4); and (5) Herbal and traditional remedies with published scientific support (Table 5).
All therapeutic recommendations in Tables 2, 3, 4, and 5 were anchored to current national guidelines[12-15], conferring Grade A certainty for core pharmacological interventions. Off-label uses were designated with risk-benefit language and specialist supervision advice. Dosing regimens, treatment durations, follow-up triggers, and escalation thresholds have been standardized and quantified throughout. Red-flag biopsy criteria were quoted verbatim from NICE NG12[12-15] and integrated into Table 4. Each clinical recommendation in Tables 2, 3, 4, and 5 is annotated with its evidence grade (A-C), enabling readers to assess confidence and certainty in the guidance.
RESULTS
Overall, 47 references were identified and included in this narrative review. The findings were synthesized into a practical clinical framework designed to support GDPs in the diagnosis and management of common oral mucosal lesions. The evidence was organized into five key domains covering lesion classification, treatment modalities, systemic considerations, severity-based management pathways, and complementary therapeutic options and presented across five structured tables that summarize the diagnostic and therapeutic approaches. These results demonstrated the range of oral mucosal conditions encountered in general dental practice and reveal how evidence-based and integrative strategies can be applied in everyday clinical decision making.
Table 1 presents the classification of oral mucosal lesions. It shows a structured diagnostic overview that aids GDPs in differentiating between lesions of traumatic, reactive, infectious, immune-mediated, and potentially malignant origins. Each lesion type is matched with characteristic symptoms and a diagnostic pathway, such as clinical examination, biopsy, or serological testing. For example, leukoplakia, often a white non-removable lesion, requires biopsy due to its premalignant potential[2,16-18]. On the other hand, frictional keratosis typically resolves with the removal of local irritants and does not necessitate histopathological examination. Such stratification allows early detection and timely referral for high-risk cases like erythroplakia or lupus-associated lesions[9,19-21].
Table 2 outlines the therapeutic protocols tailored for specific oral lesions, grounded in United Kingdom clinical practice. It highlights the use of National Health Service (NHS)-approved medications such as Betnesol for aphthous ulcers and Dermovate or Protopic for oral lichen planus[1,12-15]. The table also incorporates appropriate mouthwashes, like Corsodyl and Difflam, for symptom control. Importantly, the inclusion of biopsy guidance for each lesion type ensures that potentially malignant conditions are not missed[2]. The therapeutic recommendations align with evidence-based protocols and offer GDPs a clear framework to manage oral lesions systematically and safely within primary care[1,9,10].
The third table broadens the scope of this review by addressing systemic and secondary conditions that influence the health of the oral mucosa, including oral candidiasis, BMS, geographic tongue, and xerostomia. These conditions often present in conjunction with local or systemic factors, requiring a broader diagnostic approach.
For BMS the recommended management follows a two-phase protocol: Initial evaluation focuses on ruling out fungal infections and nutritional deficiencies. If symptoms persist after exclusion of these factors, treatment shifts toward neuropathic pain modulation using agents such as low-dose amitriptyline[7,15,22-24]. Oral candidiasis is managed with topical antifungals, such as Nystatin and Daktarin, and escalated to systemic fluconazole when necessary[1,8,12]. This layered strategy ensures comprehensive patient care while limiting overtreatment in cases that are self-limiting or nutritional in origin.
Table 4 introduces a practical “ladder” of oral medicine that aligns treatment intensity with lesion severity, providing a rational and auditable escalation pathway for GDPs. Mild conditions, such as frictional keratosis and traumatic ulcers, can be confidently managed in primary care with irritant removal, symptomatic relief, and patient education[1,9,13,25,26]. In contrast, moderate-to-severe cases, including erosive lichen planus, persistent candidiasis, or erythroplakia, require biopsy, potent topical immunosuppressants, and prompt onward referral[20,27,28]. Referral criteria have been explicitly aligned with NICE NG12[13] and RCPath tissue pathways[14]. Red-flag triggers [persistent red or red-white patches (erythroplakia/erythroleukoplakia), non-healing ulcers lasting longer than 3 weeks, and unexplained lumps on the lip or in the oral cavity] mandate urgent specialist assessment within 14 days. Integration of Emery and Vedsted[29] and Grimes et al[30] highlights the evidence-based intent of dentist-first triage while underscoring potential risks, emphasizing the critical importance of safety netting. This Grade A framework remains internationally applicable through the universal 2-week referral principle, irrespective of local pathway variations, and effectively bridges primary and specialist care[13,14].
The inclusion of Table 5 acknowledges the growing interest in evidence-based herbal therapies as supportive treatments. Substances like chamomile, honey, and turmeric have shown anti-inflammatory and antimicrobial properties in clinical studies and are well-suited for minor lesions such as aphthous ulcers[21-23]. Aloe vera and black seed oil have demonstrated benefits in the management of oral lichen planus, offering patients additional options with fewer systemic side effects[31,32]. Importantly, the protocol advises that such remedies are adjunctive and not replacements for pharmacological or surgical interventions, thereby maintaining clinical standards while embracing integrated care where appropriate.
DISCUSSION
This protocol-based review highlighted the importance of a structured, evidence-driven approach for the diagnosis and management of oral mucosal lesions in general dental practice.
The selected lesions encompass a spectrum from common benign conditions, such as aphthous and traumatic ulcers, to immune-mediated disorders like oral lichen planus, and potentially malignant lesions such as leukoplakia and erythroplakia. This scope ensures coverage of the conditions in which misdiagnosis has the most serious consequences. By contrast, salivary gland disorders and craniofacial pain syndromes were excluded as these are less common in GDP practice and often require advanced investigations beyond primary care, such as imaging or immunological testing. Excluding such conditions preserved the practical focus of the review and avoided diluting its clinical applicability.
Overall, this review provided a comprehensive yet practical guide to assist GDPs in navigating the complexity of oral mucosal conditions. The classification system presented in Table 1 simplifies diagnosis by organizing lesions according to their clinical appearance, site, and associated symptoms. This system when combined with targeted first-line therapies grounded in United Kingdom NHS guidelines (Table 2) enables efficient and confident treatment selection[2,4,9]. Moreover, the inclusion of systemic and adjunctive considerations such as hematinic deficiencies, candidal infections, and neuropathic causes (Table 3) expands diagnostic accuracy and encourages a holistic evaluation[12-15]. Escalation of care is guided by the severity-based protocol (Table 4), enabling GDPs to transition confidently from conservative management to immunomodulatory therapy or urgent referral when red-flag features are present[9,10,13]. All high-risk triggers are directly mapped to NICE NG12[13] and RCPath tissue pathways[14] and reinforced by national audits[29,30], ensuring specialist review within 14 days for suspected malignancy. This structured, evidence-informed approach (Grade A) facilitates robust clinical decision-making, minimizes diagnostic delay, reduces uncertainty in primary care, and empowers GDPs to manage the majority of benign and moderate lesions safely and effectively all while maintaining an auditable, medico-legally defensible pathway.
Table 5 introduces scientifically supported herbal treatments as complementary options[31-37], particularly in chronic or refractory lesions, offering both clinical and patient-centered benefits[38-41]. A crucial element in managing mucosal diseases is the accurate differentiation of similar-appearing lesions; for instance, leukoplakia presents as a non-removable white plaque with dysplastic potential requiring biopsy[2,42] while oral lichen planus manifests with characteristic bilateral Wickham striae and often coexists with pain or erythema[1,43]. In contrast, candidiasis though also white is typically removable and responds to antifungal therapy[12,24], serving as a useful diagnostic clue. In persistent aphthous ulcers the use of silver nitrate for chemical cauterization accelerates healing by coagulating proteins, sealing nerve endings, and reducing microbial colonization, offering rapid symptomatic relief[44].
Moreover, low-level laser therapy has demonstrated significant effectiveness in reducing pain and accelerating healing time in recurrent aphthous stomatitis, offering a promising non-pharmacological treatment modality for symptomatic relief[45]. The therapeutic ladder for oral lichen planus typically begins with high-potency topical corticosteroids such as clobetasol propionate 0.05% (Dermovate®), which suppresses proinflammatory cytokines, and escalates to calcineurin inhibitors like tacrolimus 0.03% (Protopic®), which blocks T cell activation via interleukin 2 inhibition. Both therapies can be alternated or combined in resistant cases[1,12,46]. Topical adjuncts like chlorhexidine gluconate 0.2% (Corsodyl®) act as antiseptics, benzydamine hydrochloride 0.15% (Difflam®) offers analgesia and anti-inflammation, and lidocaine 2% gel (Acuvisc®) provides mucosal anesthesia. Artificial saliva substitutes such as Glandosane® are vital in managing xerostomia, especially when due to medications or autoimmune conditions[1,12,15].
In addition to conventional treatments, several herbal therapies have shown promise through mechanisms supported by recent evidence. Nigella sativa (black seed oil) and curcuma longa (turmeric) exhibit potent anti-inflammatory and antioxidant effects[35,37]. Aloe vera, Matricaria chamomilla (chamomile), and Commiphora myrrha (Murrah) promote mucosal repair and symptom relief[31,36,41]. Honey supports wound healing and antimicrobial defense[20]. Tea tree oil combats fungal colonization[33,34]. Capsaicin reduces neuropathic pain through transient receptor potential vanilloid 1 receptor desensitization[39].
In cases of BMS, especially when no local cause is found, systemic evaluation and neuropathic management become central[22,23]. Amitriptyline, a tricyclic antidepressant, plays a key role in managing BMS by modulating pain pathways through serotonin-norepinephrine reuptake inhibition and sodium channel blockade, supporting its use as a second-line agent following exclusion of nutritional deficiencies such as vitamin B12, folic acid, and ferritin[1,12,47]. Taken together, these findings support a clinically rational, patient-centered, and evidence-informed protocol for oral mucosal care in dental settings.
This review presented a practical, evidence-based protocol to support GDPs in the diagnosis and management of common oral mucosal lesions. By integrating clinical classification with pharmacological, adjunctive, and herbal options, the protocol seeks to enhance early detection, ensure timely intervention, and minimize misdiagnosis and unnecessary referrals. Despite its clinical utility several limitations must be acknowledged. The recommendations rest on current NHS guidelines and the best available literature, which remains subject to future evolution. Included studies vary considerably in design, sample size, and population, contributing to heterogeneity that may affect reproducibility. Herbal and supportive therapies, although promising, often rely on preliminary or small-scale trials rather than large, multicenter RCTs, introducing moderate imprecision and potential publication bias. The narrative synthesis approach, while appropriate for this broad, practice-focused review, precludes formal meta-analysis and quantitative pooling of effect sizes. Off-label uses of certain agents lack long-term oral mucosal safety data, and implementation success depends on equitable access to diagnostic tools and laboratory services not uniformly available across dental settings. While the core conventional recommendations align closely with NICE and BNF guidance and carry high certainty, ongoing research is essential to strengthen the evidence base for adjunctive and herbal approaches and to refine integrated management strategies for common oral mucosal lesions.
GDPs are encouraged to adopt a protocol-driven approach for assessing oral lesions and escalating treatment based on severity and response. A biopsy should be considered for non-healing white or red patches. Hematinic screening is recommended in unexplained mucosal conditions. Herbal therapies may be offered as adjuncts, not replacements, to conventional care. Amitriptyline should be reserved for confirmed neuropathic cases of BMS after exclusion of local and systemic causes. Ongoing research and audit are necessary to validate and refine this approach across clinical environments.
CONCLUSION
This minireview offered GDPs a practical, evidence-based protocol for the diagnosis and management of common oral mucosal lesions. While firmly anchored in current guidelines, its recommendations have limitations. Future research and clinical audits are needed to validate and refine these recommendations.
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