Matoshri College of Pharmacy, Eklahare, Nashik
Mouth ulcers, also known as aphthous ulcers, are one of the most common oral mucosal disorders affecting a significant proportion of the global population. These lesions are often painful, recurrent, and can interfere with normal eating, speaking, and swallowing. Although generally self-limiting, they can severely affect the quality of life and may indicate underlying systemic disorders. The exact etiology of mouth ulcers is multifactorial, involving nutritional deficiencies, trauma, stress, immunological dysregulation, and genetic predisposition. Conventional management relies on symptomatic relief with topical anesthetics, corticosteroids, and systemic agents, while newer approaches include nanotechnology-based delivery systems, mucoadhesive formulations, and natural herbal remedies. This review comprehensively explores the epidemiology, etiology, pathophysiology, clinical features, and advances in therapeutic management of mouth ulcers. Future perspectives and research trends are also discussed to highlight novel treatment strategies.
Oral health plays a crucial role in overall human well-being, as the oral cavity serves as the primary gateway for food intake, communication, and social interaction [1]. Disorders of the oral cavity not only impair these essential functions but may also contribute to systemic complications. Among these conditions, mouth ulcers (aphthous ulcers) represent one of the most frequently encountered oral mucosal lesions worldwide [2]. A mouth ulcer is defined as a localized loss of the mucosal epithelium that results in painful, shallow, and round or oval lesions with an erythematous halo [3]. These ulcers often occur on the non-keratinized mucosa, such as the inside of the cheeks, lips, tongue, and floor of the mouth. Clinically, they present as small lesions that may be solitary or multiple, recurrent, and self-limiting in nature [4].
The significance of mouth ulcers extends beyond mere discomfort. They can interfere with routine activities such as chewing, speaking, and swallowing, thereby reducing patient quality of life [5]. In some cases, recurrent ulcers may serve as indicators of systemic conditions including gastrointestinal disorders, autoimmune diseases, hematological deficiencies, and infectious diseases [6]. Therefore, a comprehensive understanding of mouth ulcers is important for clinicians, dentists, and pharmacists to ensure accurate diagnosis and effective treatment. The scope of this review is to present a detailed overview of mouth ulcers, covering aspects from epidemiology and etiology to pathophysiology, diagnosis, and management strategies. The review also emphasizes novel and emerging therapies, including natural remedies and nanotechnology-based drug delivery systems. Finally, the paper discusses future perspectives in the prevention and treatment of mouth ulcers.
2. Epidemiology of Mouth Ulcer
Mouth ulcers are among the most common oral mucosal conditions worldwide, with a reported prevalence ranging between 5–25% of the general population depending on geographic region and diagnostic criteria [7]. The condition is most frequently observed in younger individuals, with peak incidence in the second and third decades of life [8]. Although mouth ulcers can occur at any age, recurrent aphthous stomatitis (RAS) is particularly common in adolescents and young adults, while the frequency tends to decrease with advancing age [9].
2.1 Global Prevalence
Studies indicate that the prevalence of recurrent aphthous ulcers varies across different populations. For example, epidemiological surveys suggest that the prevalence is higher in developed countries, with approximately 20% of individuals in Europe and North America experiencing recurrent lesions [10]. In contrast, prevalence rates in Asian and African populations appear somewhat lower, ranging between 5–10% [11]. These variations may be attributed to differences in dietary habits, genetic factors, socioeconomic status, and healthcare accessibility.
2.2 Gender Distribution
Epidemiological evidence shows that mouth ulcers exhibit a slight female predominance, possibly due to hormonal influences and stress-related factors [12]. Women often report higher recurrence during menstruation or pregnancy, suggesting that sex hormones play a contributory role in the disease course [13].
2.3 Age Distribution
Children and adolescents are more prone to recurrent aphthous stomatitis than older individuals. Reports indicate that up to 40% of teenagers may experience at least one episode of mouth ulceration during their lifetime [14]. Conversely, the incidence declines progressively in older adults, possibly due to changes in immune function and mucosal resilience [15].
2.4 Lifestyle and Socioeconomic Factors
Lifestyle patterns, including diet, smoking, stress, and oral hygiene practices, strongly influence the epidemiology of mouth ulcers. Non-smokers appear to have a higher prevalence of aphthous ulcers compared to smokers, a phenomenon often explained by the keratinizing effect of tobacco on the oral mucosa [16]. In addition, individuals from lower socioeconomic backgrounds show higher risk due to poor nutrition, micronutrient deficiencies, and limited access to healthcare services [17].
2.5 Regional and Ethnic Variations
Epidemiological research also highlights significant differences among ethnic groups. For example, a higher prevalence has been noted among Caucasian populations compared to African or Asian ethnicities [18]. Such differences may be attributed to genetic predisposition, environmental exposures, and dietary patterns.
2.6 Recurrence and Chronicity
A notable feature of recurrent aphthous ulcers is their chronic, relapsing nature. Epidemiological surveys suggest that nearly 30–50% of affected individuals experience recurrent episodes multiple times per year, with some patients developing chronic, persistent ulceration lasting weeks [19].
3. Etiology and Risk Factors of Mouth Ulcer
The development of mouth ulcers, particularly recurrent aphthous stomatitis (RAS), is considered multifactorial, involving a complex interaction of genetic, environmental, nutritional, microbial, and immunological factors [20]. While the exact etiology remains unclear, several risk factors have been consistently associated with the occurrence and recurrence of these lesions.
3.1 Local Trauma
Mechanical trauma is one of the most common triggers for mouth ulcers. Injuries from accidental biting of the cheek, sharp tooth edges, braces, or ill-fitting dentures can damage the oral mucosa and lead to ulcer formation [21]. Even minor injuries may precipitate ulcers in susceptible individuals with predisposing factors such as stress or nutritional deficiencies [22].
3.2 Nutritional Deficiencies
Deficiencies in iron, folic acid, and vitamin B12 have been strongly linked to recurrent mouth ulcers [23]. These nutrients are essential for DNA synthesis, cell division, and repair of oral mucosal tissues. Inadequate intake or poor absorption of these vitamins may impair epithelial integrity and increase susceptibility to ulceration [24]. Additionally, deficiencies in zinc and other micronutrients have also been implicated [25].
3.3 Stress and Hormonal Factors
Psychological stress has been widely recognized as a significant precipitating factor for aphthous ulcers [26]. Stress-induced immunological changes, such as alterations in T-cell response and cytokine release, may contribute to mucosal damage [27]. Hormonal fluctuations, particularly in women during menstrual cycles, pregnancy, and menopause, also influence the incidence and severity of ulcers [28].
3.4 Genetic Predisposition
A strong genetic component is evident, as mouth ulcers tend to occur more frequently among individuals with a positive family history of recurrent ulceration [29]. Twin studies and genetic association studies suggest that certain HLA (human leukocyte antigen) types are associated with increased susceptibility [30].
3.5 Food and Dietary Allergies
Certain foods, including citrus fruits, chocolate, coffee, nuts, and spicy foods, may act as triggering agents for ulcer formation [31]. In sensitive individuals, these dietary factors may initiate immune-mediated reactions that cause epithelial breakdown [32].
3.6 Microbial Factors
Although mouth ulcers are not considered infectious, microbial organisms such as Helicobacter pylori, Streptococcus sanguinis, and viruses (HSV, EBV) have been associated with their pathogenesis [33]. Alterations in the oral microbiome may also contribute to mucosal inflammation and ulcer recurrence [34].
3.7 Systemic Conditions and Diseases
Mouth ulcers may occur as a secondary manifestation of systemic diseases such as Crohn’s disease, celiac disease, Behçet’s syndrome, HIV infection, and hematological disorders [35]. In such cases, they often present as chronic, recurrent, and severe lesions, requiring systemic therapy rather than topical treatment [36].
3.8 Medications
Certain medications are known to induce or exacerbate mouth ulcers. These include nonsteroidal anti-inflammatory drugs (NSAIDs), beta-blockers, nicorandil, and cytotoxic agents used in chemotherapy [37]. Drug-induced ulcers are typically dose-dependent and resolve upon discontinuation of the causative agent [38].
3.9 Lifestyle and Environmental Triggers
Lifestyle factors such as smoking cessation, alcohol consumption, poor oral hygiene, and lack of sleep are also linked to mouth ulcer development [39]. Interestingly, smokers tend to experience fewer aphthous ulcers due to the protective keratinization effect of tobacco on the mucosa; however, ulcers may appear more frequently after quitting smoking [40].
4. Pathophysiology of Mouth Ulcer
The pathophysiology of mouth ulcers, particularly recurrent aphthous stomatitis (RAS), is multifactorial and involves a complex interplay of immune dysregulation, mucosal barrier disruption, microbial triggers, and genetic susceptibility [41]. Although the precise mechanism remains unclear, several models have been proposed to explain how these ulcers develop and persist.
4.1 Initiation Phase
Mouth ulcers usually begin with a triggering factor such as local trauma, stress, nutritional deficiency, or microbial imbalance. These triggers cause epithelial damage, leading to increased mucosal permeability and exposure of underlying tissues to irritants and immune cells [42].
4.2 Role of the Immune System
The immune system plays a central role in the pathogenesis of mouth ulcers. Studies indicate that T-cell mediated immune response is the primary mechanism [43]. Activated CD8+ cytotoxic T-lymphocytes infiltrate the oral mucosa, releasing pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and interferon-gamma (IFN-γ) [44]. These cytokines induce apoptosis of epithelial cells, leading to ulcer formation. Additionally, reduced levels of anti-inflammatory cytokines such as IL-10 have been reported in patients with recurrent aphthous stomatitis, further tipping the balance towards mucosal damage [45].
4.3 Inflammatory Mediators
The inflammatory cascade involves the release of reactive oxygen species (ROS), prostaglandins, and matrix metalloproteinases (MMPs) that degrade connective tissue and delay healing [46]. Neutrophil infiltration around the ulcer margins further amplifies tissue destruction through oxidative stress and proteolytic activity [47].
4.4 Role of Microbial Agents
Although mouth ulcers are not directly infectious, microorganisms may play a contributory role. Streptococcus sanguinis has been implicated as a potential trigger, while Helicobacter pylori infection has shown association in some studies [48]. Viral infections, including herpes simplex virus (HSV) and Epstein-Barr virus (EBV), may act as cofactors in susceptible individuals [49]. Dysbiosis of the oral microbiome may also alter immune responses, thereby increasing the risk of ulcer recurrence [50].
4.5 Genetic and Molecular Factors
Genetic predisposition is supported by the clustering of cases within families. Specific HLA genotypes (HLA-B12, HLA-B51, HLA-Cw7) have been associated with increased susceptibility to recurrent aphthous stomatitis [51]. At the molecular level, polymorphisms in cytokine genes such as TNF-α and IL-1β have also been linked to heightened inflammatory responses in affected individuals [52].
4.6 Healing Phase
The natural healing of mouth ulcers involves re-epithelialization, fibroblast proliferation, and angiogenesis. Growth factors such as vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are upregulated during this process, promoting tissue repair [53]. However, frequent recurrence is attributed to incomplete resolution of the inflammatory response and persistence of underlying triggers [54].
4.7 Summary of Pathogenesis
In summary, mouth ulcers develop due to a combination of epithelial barrier disruption, T-cell mediated immune attack, pro-inflammatory cytokine release, microbial interactions, and genetic predisposition. The chronic, recurrent nature of the disease highlights the importance of both environmental and host-related factors in its pathogenesis [55].
5. Classification of Mouth Ulcer
Mouth ulcers can be broadly classified based on clinical features, size, number of lesions, duration, and etiology. Among these, the most widely accepted classification is that of recurrent aphthous stomatitis (RAS), which is categorized into three main clinical types: minor, major, and herpetiform ulcers [56].
5.1 Minor Aphthous Ulcer (Mikulicz Ulcer)
These are the most common type, accounting for nearly 80–90% of all aphthous ulcers [57]. Lesions are small, measuring less than 1 cm in diameter, and usually appear on non-keratinized mucosa such as the inner lips, cheeks, and floor of the mouth [58]. They are shallow, round or oval, with a yellowish-white pseudomembrane and a red erythematous halo [59]. Healing occurs spontaneously within 7–14 days, and scarring is uncommon [60].
5.2 Major Aphthous Ulcer (Sutton’s Ulcer or Periadenitis Mucosa Necrotica Recurrens) Represent about 10–15% of cases [61].
Lesions are larger than 1 cm in diameter, deeper, and often more painful compared to minor ulcers [62]. They commonly occur on the lips, soft palate, and oropharynx, and may persist for 2–6 weeks [63]. Healing is usually associated with scarring, which may cause long-term functional or cosmetic problems [64]. They are more frequently seen in immunocompromised individuals and in association with systemic diseases such as Behçet’s syndrome and HIV [65].
5.3 Herpetiform Ulcer
A less common type, accounting for about 5–10% of aphthous stomatitis cases [66]. Characterized by multiple small ulcers (1–3 mm in size) that may occur in clusters of 10–100 lesions, resembling herpes simplex infection, although HSV is not the causative agent [67]. Lesions may coalesce to form larger irregular ulcers, often causing severe pain [68]. Healing usually takes 10–14 days, but recurrence is frequent [69].
5.4 Other Classifications Based on Etiology
Apart from the clinical subtypes, ulcers can also be classified according to their underlying causes:
6. Clinical Features and Diagnosis of Mouth Ulcer
Mouth ulcers, particularly recurrent aphthous stomatitis (RAS), are recognized by their distinctive clinical appearance, recurrent nature, and associated symptoms. Accurate diagnosis is crucial to differentiate them from other oral lesions, including malignant and infectious conditions [74].
6.1 Clinical Features
6.1.1 General Characteristics
Appearance: Ulcers typically present as round or oval lesions with a central necrotic area covered by a yellowish-white pseudomembrane surrounded by an erythematous halo [75].
Pain: They are painful, especially when eating spicy, acidic, or salty foods, and during speaking or swallowing [76].
Location: Most commonly affect non-keratinized mucosa such as the inside of the lips, buccal mucosa, ventral tongue, and floor of the mouth [77].
6.1.2 Specific Clinical Types
Minor ulcers: Small (<1 cm), shallow, heal within 7–14 days, and rarely scar [78].
Major ulcers: Large (>1 cm), deep, persist for weeks, and often heal with scarring [79].
Herpetiform ulcers: Multiple pinpoint ulcers (10–100), which may coalesce into larger irregular lesions [80].
6.1.3 Associated Symptoms
Burning or tingling sensation before ulcer eruption (prodromal stage) [81]. Difficulty in eating, drinking, or speaking [82]. In severe cases, systemic symptoms like fever, malaise, or lymphadenopathy may occur [83].
6.2 Diagnosis
The diagnosis of mouth ulcers is usually clinical, based on history and physical examination. However, additional investigations may be required in chronic or recurrent cases to rule out systemic diseases [84].
6.2.1 Clinical History
Onset, frequency, and duration of ulcers. Family history of recurrent aphthous stomatitis. Dietary habits, stress levels, trauma, and drug intake [85].
6.2.2 Physical Examination
Inspection of ulcer size, number, shape, and location. Palpation for tenderness and induration to rule out malignancy [86].
6.2.3 Laboratory Investigations
Hematological tests: Complete blood count (CBC) to detect anemia, iron, folate, or vitamin B12 deficiency [87].
Microbiological tests: Swabs to rule out infectious causes such as candidiasis or herpes simplex [88].
Serological tests: For systemic conditions like HIV, celiac disease, or autoimmune disorders [89].
Biopsy: Indicated in persistent, non-healing ulcers (>3 weeks) to rule out oral squamous cell carcinoma [90].
6.2.4 Differential Diagnosis
Mouth ulcers should be distinguished from:
Oral cancer (persistent, indurated, non-healing lesion) [91]. Oral lichen planus (white lacy striations with ulceration) [92]. Herpes simplex infection (vesicles that rupture into ulcers) [93]. Candidiasis (white plaques that scrape off, leaving erythematous base) [94].
6.3 Diagnostic Challenges
Diagnosis may be challenging due to the similarity of mouth ulcers to other mucosal lesions. Hence, a multidisciplinary approach involving dentists, physicians, and pathologists is often required for accurate identification [95].
7. Current Treatment Approaches for Mouth Ulcer
Management of mouth ulcers primarily focuses on symptomatic relief, reduction of inflammation, acceleration of healing, and prevention of recurrence. The choice of treatment depends on the type, severity, frequency, and underlying cause of the ulcer [96].
7.1 Symptomatic Relief
7.2 Topical Corticosteroids
7.3 Topical Antiseptics and Anti-inflammatory Agents
7.4 Systemic Therapy
7.5 Other Pharmacological Agents
7.6 Non-pharmacological Measures
7.7 Limitations of Current Treatments
8. Novel & Advanced Therapeutic Approaches for Mouth Ulcer
While conventional treatments primarily focus on symptom relief, recent research has explored innovative strategies to enhance healing, reduce recurrence, and target underlying pathophysiological mechanisms of mouth ulcers [113].
8.1 Nanotechnology-Based Drug Delivery
Nanoparticles, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been used to deliver anti-inflammatory and antimicrobial agents directly to the ulcer site [114]. Advantages include enhanced bioavailability, sustained release, and targeted delivery, resulting in faster healing and reduced systemic side effects [115]. Studies show that nanoparticle-based gels containing corticosteroids or curcumin accelerate mucosal repair in recurrent aphthous stomatitis [116].
8.2 Mucoadhesive Films and Gels
Mucoadhesive systems adhere to the oral mucosa, providing prolonged drug retention at the ulcer site [117]. These formulations can deliver analgesics, corticosteroids, or antimicrobial agents for extended periods, reducing the frequency of application [118]. Examples include chitosan-based films loaded with triamcinolone or herbal extracts [119].
8.3 Photobiomodulation Therapy (Low-Level Laser Therapy)
Low-level lasers have been shown to stimulate tissue regeneration, reduce inflammation, and relieve pain in oral ulcers [120]. Mechanisms involve enhanced cellular proliferation, increased collagen synthesis, and improved local circulation [121]. Clinical trials report faster healing and reduced recurrence compared to conventional therapy [122].
8.4 Biologic and Immunomodulatory Approaches
Biologic agents, such as TNF-α inhibitors and interleukin modulators, have been investigated for severe or refractory cases of RAS [123]. These agents target specific cytokines involved in mucosal inflammation, providing precision therapy in patients unresponsive to conventional treatment [124]. Early studies demonstrate promising results in reducing ulcer frequency and severity [125].
8.5 Advanced Topical Formulations
Novel gels, pastes, and patches with combined anti-inflammatory, antioxidant, and woundhealing properties are under development [126]. For instance, curcumin-based mucoadhesive gels exhibit anti-inflammatory, antimicrobial, and antioxidant effects, supporting mucosal repair [127].
8.6 Gene Therapy and Future Prospects
Experimental approaches explore gene modulation to enhance local immunity and epithelial repair [128]. Delivery of growth factor genes or anti-inflammatory cytokine genes to the oral mucosa shows potential in preclinical models [129]. While still experimental, these strategies may redefine personalized treatment for chronic and recurrent ulcers in the future [130].
SUMMARY
Novel and advanced therapeutic approaches aim not only to relieve symptoms but also to target the underlying mechanisms of mouth ulcer formation. Integration of nanotechnology, mucoadhesive systems, photobiomodulation, biologics, and gene therapy represents a promising direction in the management of recurrent aphthous stomatitis [131].
9. Herbal and Natural Remedies for Mouth Ulcer
Herbal and natural remedies have gained significant attention for the management of mouth ulcers due to their anti-inflammatory, antimicrobial, and wound-healing properties. These remedies are often used as adjuncts or alternatives to conventional therapies, especially in patients seeking natural treatments or experiencing side effects from pharmacological agents [132].
9.1 Aloe Vera
Aloe vera gel is widely used for oral ulcers due to its anti-inflammatory, antioxidant, and wound-healing properties [133]. Studies show that topical application of aloe vera gel reduces pain, erythema, and ulcer size, and accelerates healing [134]. Active components such as acemannan and glycoproteins promote collagen synthesis and epithelial regeneration [135].
9.2 Honey
Honey has natural antibacterial, anti-inflammatory, and tissue-repairing effects [136]. Clinical studies report that applying honey to mouth ulcers significantly reduces pain and healing time compared to placebo [137]. Its high osmolarity prevents microbial growth and supports mucosal repair [138].
9.3 Turmeric (Curcuma longa)
Curcumin, the active ingredient in turmeric, exhibits potent anti-inflammatory, antioxidant, and antimicrobial properties [139]. Topical curcumin gels or pastes help reduce ulcer size, pain, and recurrence [140]. Curcumin modulates pro-inflammatory cytokines like TNF-α and IL-1β, contributing to faster healing [141].
9.4 Licorice (Glycyrrhiza glabra)
Licorice extract contains glycyrrhizin, which possesses anti-inflammatory, antiviral, and wound-healing effects [142]. Application in mouth ulcers can soothe pain, reduce inflammation, and prevent secondary infection [143].
9.5 Neem (Azadirachta indica)
Neem exhibits antimicrobial, anti-inflammatory, and antioxidant activities, making it suitable for oral ulcer management [144]. Neem-based mouth rinses or gels have been shown to reduce ulcer size and prevent microbial colonization [145].
9.6 Other Herbal Remedies
Chamomile: Anti-inflammatory and antimicrobial, useful in ulcer healing [146].
Tulsi (Ocimum sanctum): Reduces inflammation and promotes mucosal repair [147].
Tea tree oil: Antimicrobial effect prevents secondary infection [148].
9.7 Mechanism of Action
Herbal remedies generally act via:
Reducing inflammatory mediators (TNF-α, IL-1β) [149]. Enhancing collagen synthesis and epithelial regeneration [150]. Preventing microbial colonization and secondary infection [151]. Providing analgesic effect through natural bioactive compounds [152].
9.8 Advantages of Herbal Remedies
Minimal side effects compared to long-term corticosteroid or systemic therapy. Cost-effective and easily available. Can be used as adjunct therapy alongside conventional treatment [153].
10. Recent Research and Clinical Trials on Mouth Ulcer
Recent research in the field of mouth ulcers (recurrent aphthous stomatitis) has focused on understanding the pathogenesis, innovative therapies, and clinical outcomes of existing and novel treatments. Clinical trials provide evidence for efficacy, safety, and patient quality of life improvements [154].
10.1 Novel Pharmacological Interventions
Recent trials have evaluated topical corticosteroid combinations with antioxidants or mucoadhesive carriers, showing faster healing and pain relief compared to standard gels [155]. Systemic immunomodulators, such as low-dose thalidomide or colchicine, have been investigated in patients with severe or refractory RAS, demonstrating reduced ulcer frequency and severity [156]. Sucralfate-based oral gels have shown effectiveness in protecting ulcer sites and accelerating epithelial repair [157].
10.2 Nanotechnology-Based Approaches
Studies using nanoparticle-based drug delivery systems report enhanced drug bioavailability, sustained release, and reduced local irritation [158].
For example, curcumin-loaded nanoparticles applied topically on aphthous ulcers significantly reduced lesion size and pain within a shorter duration compared to conventional gels [159].
10.3 Photobiomodulation and Laser Therapy
Clinical trials on low-level laser therapy (LLLT) demonstrate rapid pain relief, decreased ulcer size, and faster healing [160]. Comparative studies indicate that LLLT may be superior to topical corticosteroids in reducing recurrence rates and improving patient comfort [161].
10.4 Herbal and Natural Product Trials
Clinical evaluation of aloe vera gel and curcumin-based mucoadhesive gels confirms significant reduction in pain and faster healing [162]. Honey-based therapy has been shown to reduce ulcer size and inflammation, providing a natural, safe alternative to synthetic agents [163]. Neem and tulsi extracts have demonstrated antimicrobial and anti-inflammatory effects, contributing to mucosal repair [164].
10.5 Dietary and Nutritional Interventions
Trials assessing vitamin B12, folic acid, and iron supplementation in patients with deficiencyrelated ulcers show reduced recurrence and improved healing rates [165]. Omega-3 fatty acid supplementation has been reported to modulate inflammatory pathways and reduce frequency of ulcer episodes [166].
10.6 Quality of Life Studies
Recurrent aphthous stomatitis significantly impacts oral health-related quality of life (OHRQoL) [167]. Clinical trials incorporating patient-reported outcome measures show that effective therapy improves eating, speaking, and psychological comfort [168].
10.7 Summary of Recent Findings
Recent research emphasizes multimodal approaches, integrating pharmacological, herbal, nanotechnology-based, and photobiomodulation therapies [169]. Clinical trials consistently highlight the importance of addressing underlying deficiencies, immune dysregulation, and local trauma for effective management [170].
11. Complications and Prognosis of Mouth Ulcer
While most mouth ulcers are self-limiting and benign, certain cases, especially major aphthous ulcers or recurrent aphthous stomatitis (RAS), may lead to complications that affect oral function, nutrition, and quality of life [171].
11.1 Common Complications
11.1.1 Pain and Functional Impairment
Pain from ulcers can cause difficulty in eating, swallowing, and speaking, impacting daily activities [172]. Chronic pain may lead to avoidance of certain foods, resulting in poor nutrition [173].
11.1.2 Secondary Infections
Ulcers can act as entry points for bacterial or fungal infections, particularly in immunocompromised individuals [174]. Secondary infections may prolong healing time and increase discomfort [175].
11.1.3 Scarring and Tissue Damage
Major aphthous ulcers often heal with scarring, which can affect oral mucosal flexibility and aesthetics [176]. Recurrent ulcers may lead to chronic mucosal changes, including fibrosis in severe cases [177].
11.1.4 Systemic Associations
Frequent or severe mouth ulcers may indicate underlying systemic conditions, such as Crohn’s disease, Behçet’s syndrome, celiac disease, or hematological disorders [178]. Failure to recognize these associations can delay diagnosis and treatment of systemic diseases [179].
11.2 Prognosis
Minor ulcers: Excellent prognosis; self-limiting, heal within 1–2 weeks without scarring [180]. Major ulcers: Healing may take several weeks, sometimes with residual scarring or persistent discomfort [181].
Herpetiform ulcers: Heal within 10–14 days but often recur frequently, requiring ongoing management [182].
11.3 Factors Affecting Prognosis
Frequency of recurrence: Higher recurrence may indicate underlying nutritional deficiencies, immune dysregulation, or systemic disease [183].
Treatment compliance: Early intervention with topical or systemic therapy improves outcomes [184].
Underlying health status: Patients with immunosuppression, chronic illness, or deficiencies may experience delayed healing and frequent relapses [185].
11.4 Long-Term Management
Regular monitoring and preventive strategies, including nutritional supplementation, oral hygiene, and stress management, can reduce recurrence [186]. Education on trigger avoidance, such as specific foods or trauma, improves quality of life and overall prognosis [187].
11.5 Summary
Mouth ulcers are generally benign, but complications such as pain, secondary infection, scarring, and systemic associations may arise, particularly in major or recurrent ulcers. Prognosis is generally favorable with appropriate management and preventive measures [188].
12. Future Perspectives and Challenges in Mouth Ulcer Management
Although current treatments for mouth ulcers focus primarily on symptom relief, recent advancements and ongoing research suggest promising directions for improved prevention, targeted therapy, and personalized care [189].
12.1 Personalized Medicin
Future management may incorporate genetic profiling to identify individuals at higher risk for recurrent aphthous stomatitis (RAS) [190]. Understanding HLA genotypes and cytokine polymorphisms can help develop tailored therapies for faster healing and reduced recurrence [191].
12.2 Advanced Drug Delivery Systems
Nanotechnology-based formulations, including nanoparticles, liposomes, and mucoadhesive patches, are expected to improve drug efficacy and reduce systemic side effects [192]. Sustained-release and targeted delivery approaches could enhance patient compliance and minimize the need for frequent application [193].
12.3 Biologics and Immunomodulation
Development of biologic agents targeting TNF-α, IL-1β, or other inflammatory mediators may offer precision therapy for severe or refractory ulcers [194]. Challenges include high cost, potential immunosuppression, and long-term safety, which require careful evaluation [195].
12.4 Integration of Herbal and Natural Remedies
Combining traditional herbal therapies with modern drug delivery may enhance therapeutic outcomes [196]. Clinical trials on curcumin, aloe vera, honey, and neem-based formulations are expected to validate their efficacy and safety in standardized doses [197].
12.5 Photobiomodulation and Non-Pharmacological Approaches
Low-level laser therapy (LLLT) and other light-based therapies have shown promise in reducing pain, inflammation, and recurrence [198].
Wider adoption requires standardized protocols and accessibility in clinical practice [199].
12.6 Addressing Systemic Associations
Recognition of underlying systemic diseases (Crohn’s disease, Behçet’s syndrome, celiac disease) is essential for holistic management [200]. Future research may focus on early diagnostic markers and integrated care models for patients with recurrent ulcers [201].
12.7 Challenges
High recurrence rates remain a major challenge despite symptomatic treatment [202]. Variability in individual response to therapy complicates management strategies [203]. Limited large-scale clinical trials on novel and herbal therapies restrict their routine clinical adoption [204].
12.8 Future Directions
Emphasis on multimodal therapy, combining pharmacological, herbal, nanotechnology-based, and photobiomodulation strategies [205]. Development of personalized and preventive approaches, focusing on patient-specific risk factors, dietary supplementation, and lifestyle modifications [206]. Expansion of evidence-based clinical trials to evaluate safety, efficacy, and quality-of-life outcomes [207].
CONCLUSION
Mouth ulcers, particularly recurrent aphthous stomatitis (RAS), are among the most common oral mucosal disorders, affecting individuals worldwide. Although generally benign and selflimiting, these lesions can cause significant pain, functional impairment, and psychological discomfort. The etiology of mouth ulcers is multifactorial, involving local trauma, nutritional deficiencies, stress, hormonal changes, genetic predisposition, microbial factors, systemic diseases, and drug-induced causes. Understanding these factors is essential for accurate diagnosis and effective management. Pathophysiologically, mouth ulcers are characterized by epithelial damage, immune dysregulation, cytokine-mediated inflammation, and delayed healing, leading to recurrent lesions in susceptible individuals. Clinical classification into minor, major, and herpetiform ulcers guides treatment decisions and prognostic evaluation. Management strategies have evolved from symptomatic relief with topical anesthetics and corticosteroids to advanced approaches including nanotechnology-based delivery systems, mucoadhesive films, photobiomodulation therapy, biologics, and herbal remedies. Recent clinical trials highlight the efficacy of these novel therapies in reducing pain, accelerating healing, and improving quality of life. Despite significant progress, challenges remain, including high recurrence rates, variability in individual response, and limited large-scale clinical evidence for novel and herbal therapies. Future directions involve personalized medicine, integrated multimodal approaches, and preventive strategies tailored to individual risk factors. In conclusion, a comprehensive understanding of the etiology, pathophysiology, clinical features, and emerging therapies is essential for the effective management of mouth ulcers. Continued research, innovation, and clinical trials will further enhance therapeutic outcomes and patient quality of life.
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Nikam Sunil*, Ragini Kadvekar, A Comprehensive Review Article on Mouth Ulcer, Int. J. Sci. R. Tech., 2025, 2 (10), 275-290. https://doi.org/10.5281/zenodo.17342417
10.5281/zenodo.17342417
