The effectiveness of fire needle therapy in the treatment of recurrent aphthous stomatitis: A systematic review and meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is common in clinical practice and imposes both physical and psychological distress on patients. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of fire needle therapy for the treatment of RAS, providing a basis for clinical decision-making. METHODS: Eight databases, in both Chinese and English, were searched from their inception until December 2022. All randomized controlled trials (RCTs) that utilized fire needle therapy, either alone or combined with other treatments for RAS, were considered. Data evaluation and extraction were conducted independently by 2 authors. RESULTS: The revised Cochrane Risk of Bias Version 2 tool was employed to assess the risk of bias in the included RCTs. A meta-analysis was conducted using Review Manager 5.4 and Stata 15.0. Nine RCTs involving 1469 patients were selected for inclusion. The meta-analysis revealed that, compared to a non-fire-needle control group (primarily utilizing vitamin and transfer factor treatments), fire needle therapy for RAS significantly improved the total effective rate (relative risk = 1.25, 95% confidence interval [CI] [1.14, 1.36], P < .00001), reduced the visual analogue scale score (mean difference = -1.68, 95% CI [-1.82, -1.53], P < .0001), diminished the Traditional Chinese Medicine symptom score (standardized mean difference = -1.20, 95% CI [-1.76, -0.65], P < .0001), and shortened the healing time (mean difference = -1.66, 95% CI [-2.73, -0.59], P = .002). Notably, there was no significant difference in the recurrence rate between the groups (relative risk = -0.18, 95% CI [-0.36, 0.01], P = .06). Further subgroup analysis on total efficacy rate was performed based on variables such as experimental group intervention, control group intervention, and duration of therapy to explore potential sources of heterogeneity. CONCLUSION: Fire needle therapy appears to be a clinically effective treatment for RAS, offering benefits such as pain alleviation, symptom improvement based on the Traditional Chinese Medicine parameters, and faster recovery. Nonetheless, the overall quality of the RCTs available raises concerns. Future research, involving high-quality RCTs, is essential to confirm the clinical efficacy and safety of this treatment. Registration number: PROSPERO (CRD42023387973).

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis recurrence temporally associated with allergen-specific immunotherapy in a female adolescent: a case report.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in pediatric patients. It is clinically characterized by fever flares lasting 3-7 days, reappearing every 2-8 weeks with a distinctive clockwork regularity. PFAPA generally begins before 5 years of age and usually ceases 3-5 years after onset. Recurrences may be observed in adolescence and adulthood in up to 20% of cases. The authors aim to describe a case of PFAPA recurrence in adolescence temporally associated with allergen-specific immunotherapy (ASIT). A 16-year-old female patient was referred to the rheumatology unit due to recurrent episodes of fever one month after initiating ASIT for allergic rhinitis. These episodes occurred every 4 weeks and lasted 3 days. During these episodes, she also presented with a sore throat, tonsillar exudates, and cervical lymphadenopathy. Abortive treatment with oral prednisolone was attempted in these episodes, with complete resolution of fever after a single dose. After reviewing her medical background, she had previously experienced febrile episodes accompanied by aphthous ulcers and tonsillar exudates occurring every 7-8 weeks from age 2-7. The etiopathogenesis of PFAPA remains uncertain. Environmental triggers, particularly those with immunomodulator effects, may interfere with the immune responses responsible for PFAPA occurrence, but the mechanisms are still unclear. The authors describe the first report of the reappearance of PFAPA flares, possibly due to ASIT. Further studies are needed to fully clarify if ASIT constitutes a true environmental trigger of PFAPA.

Dental implants for patients with oral mucosal diseases: A narrative review and clinical guidance.

Oral mucosal diseases are a group of conditions that affect the oral mucosa with variable severity and include recurrent aphthous stomatitis (RAS), oral lichen planus (OLP), pemphigus vulgaris (PV), mucous membrane pemphigoid (MMP), and systemic lupus erythematosus (SLE). These may manifest clinically as painful oral ulcerations, reticulations and/or erosions, with differences between each. Management protocols often include initial topical and/or systemic corticosteroid (CS) therapy to control the patient's acute symptoms, followed by CS-sparing agents for long-term maintenance therapy. Patients with oral mucosal diseases often require dental implants to replace missing teeth. However, data on potential complications and success rates for these cases is still lacking. Considering the steady increase in the incidence of immune-related systemic conditions in the general population globally, dentists are expected to have the needed knowledge and ability to safely place dental implants in this group of patients. Therefore, this review aims to discuss the underlying pathogeneses of common oral mucosal diseases, clinical presentations, best practice approaches, and recommendations for the placement of dental implants in patients with similar conditions.

PFAPA syndrome in children.

ABSTRACT: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is, as the name implies, characterized by an extremely regular cycle of fevers that is accompanied by one or more other symptoms such as oral ulcers, pharyngitis, adenitis, tonsillitis, sore throat, cervical adenopathy, and headache. Originally known as Marshall syndrome, PFAPA is most commonly identified in children younger than age 5 years; however, adults may also present with the disease, though they may report additional symptoms. PFAPA is now understood to be a diagnosis of exclusion. Laboratory studies are typically unremarkable except for increases in acute phase reactants such as C-reactive protein. Treatment is primarily supportive and most frequently uses systemic steroids to suppress the inflammatory response. Acute flares are self-limited, and the syndrome typically resolves on its own as the child reaches age 7 or 8 years.

Estomatitis aftosa recurrente / Recurrent aphthous stomatitis

La estomatitis aftosa recurrente (EAR) es la enfermedad clínica más frecuente de la mucosa oral. Su prevalencia en la población general varía entre el 5 y el 25%, siendo su pico de aparición en la segunda década de la vida. Hasta el momento, la etiopatogenia no está aclarada. En pacientes genéticamente predispuestos, el efecto de ciertos factores desencadenantes iniciaría la cascada de citocinas proinflamatorias dirigidas contra determinadas regiones de la mucosa oral. Las úlceras son redondas u ovaladas con márgenes eritematosos bien definidos y centro poco profundo ulcerado cubierto con una seudomembrana fibrinosa de color gris o amarillento. Pueden reaparecer a intervalos de pocos días y meses. Ante la aparición de aftas periódicas en la mucosa bucal, lo primero será realizar con correcto diagnóstico diferencial, descartar enfermedades sistémicas asociadas y valorar causas tratables antes de llegar al diagnóstico de EAR. En el momento actual no existe tratamiento curativo (AU)

Recurrent aphthous stomatitis (RAS) is the most common clinical disease of the oral mucosa. Its prevalence in the general population varies between 5 and 25%, with its peak appearance in the second decade of life. So far, the etiopathogenesis is not clear. In genetically predisposed patients, the effect of certain triggering factors would initiate the proinflammatory cytokine cascade directed against certain regions of the oral mucosa. Ulcers are round or oval with well-defined erythematous margins and a shallow ulcerated center covered with a gray or yellowish fibrinous pseudomembrane. The ulcers may reappear at intervals of a few days and months. Given the appearance of periodic thrush in the oral mucosa, the first thing to do is to make a correct differential diagnosis, rule out associated systemic diseases and assess treatable causes before reaching the diagnosis of RAS. At present, there is no curative treatment (AU)

[Recurrent aphthous stomatitis]. / Estomatitis aftosa recurrente.

Recurrent aphthous stomatitis (RAS) is the most common clinical disease of the oral mucosa. Its prevalence in the general population varies between 5 and 25%, with its peak appearance in the second decade of life. So far, the etiopathogenesis is not clear. In genetically predisposed patients, the effect of certain triggering factors would initiate the proinflammatory cytokine cascade directed against certain regions of the oral mucosa. Ulcers are round or oval with well-defined erythematous margins and a shallow ulcerated center covered with a gray or yellowish fibrinous pseudomembrane. The ulcers may reappear at intervals of a few days and months. Given the appearance of periodic thrush in the oral mucosa, the first thing to do is to make a correct differential diagnosis, rule out associated systemic diseases and assess treatable causes before reaching the diagnosis of RAS. At present, there is no curative treatment.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome and Syndrome of Unexplained Recurrent Fevers in Children and Adults.

Children and adults with autoinflammatory disorders, who often experience recurrent fevers, rashes, cold-induced symptoms, conjunctivitis, lymphadenopathy, recurrent infections, aphthous stomatitis, and abnormal blood cell counts, may present to the allergist/immunologist because the symptoms mimic allergies and disorders of immunity. In recent years, there has been increased recognition of non-monogenic autoinflammatory disorders, including periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and syndrome of undifferentiated recurrent fevers. For many clinical practitioners, the natural history, diagnostic criteria, differential diagnoses, and preferred therapies remain challenging because of the presumed rarity of patients and the evolving field of autoinflammation. Here, we aim to provide a practical framework for the clinical allergist/immunologist to evaluate and treat this patient population.

Characterization of immune landscape and development of a novel N7-methylguanine-related gene signature to aid therapy in recurrent aphthous stomatitis.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is the most common inflammatory disease of the oral mucosa resulting in an impaired life quality and even leading to tumors in susceptible populations. N7-Methylguanine (m7G) plays a vital role in various cellular activities but has not yet been investigated in RAS. We aimed at picturing the immune landscape and constructing an m7G-related gene signature, and investigating candidate drugs and gene-disease association to aid therapy for RAS. METHODS: For our study, m7G-related differentially expressed genes (DEGs) were screened. We outlined the immune microenvironment and studied the correlations between the m7G-related DEGs and immune cells/pathways. We performed functional enrichment analyses and constructed the protein-protein interaction (PPI) and multifactor regulatory network in RAS. The m7G-related hub genes were extracted to formulate the corresponding m7G predictive signature. RESULTS: We obtained 11 m7G-related DEGs and studied a comprehensive immune infiltration landscape, which indicated several immune markers as possible immunotherapeutic targets. The PPI and multifactor regulatory network was constructed and 4 hub genes (DDX58, IFI27, IFIT5, and PML) were identified, followed by validation of the corresponding m7G predictive signature for RAS. GO and KEGG analyses revealed the participation of JAK-STAT and several immune-related pathways. Finally, we suggested candidate drugs and gene-disease associations for potential RAS medical interventions. CONCLUSIONS: The present study pictured a comprehensive immune infiltration landscape and suggested that m7G played a vital role in RAS through immune-related pathways. This study provided new insight for the future investigation of the mechanisms and therapeutic strategies for RAS.

[Marshall syndrome]. / Syndrome de Marshall.

MARSHALL SYNDROME. Marshall syndrome also known as PFAPA syndrome belongs to the group of autoinflammatory diseases. The acronym reflects the main clinical features of the disease: periodic fever, aphthous stomatitis, pharyngitis, and adenitis. It is the most common autoinflammatory disease, beginning between 1 and 5 years of age. There is little or no impact on growth, but the recurrence of febrile seizures can compromise the quality of life of patients. Clinical diagnosis meets positive and exclusion criteria. Putting it correctly allows a reassuring framework of care and avoids many unnecessary antibiotic treatments. Corticosteroid therapy is the reference treatment for the crisis. Tonsillectomy associated with adenoidectomy can be discussed but is not systematically recommended in this pathology, which is generally benign and most often heals spontaneously with age.

SYNDROME DE MARSHALL. Le syndrome de Marshall, aussi connu sous le nom de syndrome PFAPA, appartient au groupe des maladies auto-inflammatoires. L'acronyme reflète les principales caractéristiques cliniques de la maladie : fièvre périodique, aphtes, pharyngite, adénite. Il s'agit de la maladie auto-inflammatoire la plus fréquente, débutant entre 1 et 5 ans. Il n'y a pas ou peu de retentissement sur la croissance, mais la récurrence des accès fébriles peut obérer la qualité de vie des patients. Le diagnostic clinique répond à des critères positifs et d'exclusion. Bien poser celui-ci permet de poser un cadre de prise en charge rassurant pour l'entourage et d'éviter de nombreux traitements antibiotiques inutiles. La corticothérapie est le traitement de référence de la crise. L'amygdalectomie associée à l'adénoïdectomie peut être discutée mais n'est pas recommandée de façon systématique dans cette pathologie en général bénigne et guérissant le plus souvent spontanément avec l'âge.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome: Clinical characteristics and treatment outcomes - a single center study in Japan.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease occurring in children. Although PFAPA is the most common periodic fever syndrome found in children, there are only a few studies defining the clinical characteristics and the efficacy of treatment strategies among Japanese children. This study aimed to clarify the demographic characteristics and clinical features of patients with PFAPA syndrome and to evaluate treatment efficacy. METHODS: We retrospectively reviewed the clinical features of children with PFAPA who visited Saitama Children's Medical Center between January and December 2019. We also evaluated treatment strategies and their efficacy; abortive treatment with corticosteroids, prophylaxis with cimetidine or colchicine, and surgical management with tonsillectomy. RESULTS: A total of 100 Japanese children (61% male) with PFAPA were included. Median age of onset was 3 years, median duration of fever episodes was 5 days, and median interval between episodes was 4 weeks. The symptoms (frequencies) were pharyngitis (89%), exudate on tonsils (71%), cervical adenitis (50%), and aphthous stomatitis (49%). Approximately 37% of patients took prednisolone for aborting fever attacks, showing a 100% response; 93% were treated with cimetidine, showing an 79.6% response, and 18% were treated with colchicine, showing a 66.7% response. Only one patient underwent tonsillectomy. CONCLUSIONS: Among Japanese children with PFAPA, 28% of them were ≥5 years with a male predominance. Pharyngitis is the most frequent symptom associated with fever. Cimetidine is suitable for initial therapy because of its safety and efficacy.

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome in children: a brief literature review.

OBJECTIVE: To describe clinical, diagnostic and therapeutic characteristics of the periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. DATA SOURCE: Literature review in the PubMed database by using specific descriptors to identify all articles published in the English language in the last three years; 38 articles were found. After performing selection of titles and abstract analysis, 13 out of the 38 articles were fully read. Relevant studies found in the references of the reviewed articles were also included. DATA SYNTHESIS: The PFAPA syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis and cervical Adenitis) is a medical condition grouped among the periodic fever syndromes. The etiology is uncertain, but possibly multifactorial, and its symptoms are accompanied by recurrent febrile episodes although weight and height development are preserved. It is a self-limiting disease of benign course with remission of two to three years without significant interference in the patient's overall development. Treatment consists of three pillars: interruption of febrile episodes, increase in the interval between episodes, and remission. CONCLUSIONS: Despite several attempts to establish more sensitive and specific criteria, the diagnosis of PFAPA syndrome is still clinical and reached by exclusion, based on the modified Marshall's criteria. The most common pharmacological options for treatment include prednisolone and betamethasone; colchicine may be used as prophylaxis, and surgical treatment with tonsillectomy can be considered in selected cases.

Tratamiento de la estomatitis aftosa recurrente en pacientes inmunocomprometidos. Revisión sistemática / Treatment of recurrent aphthous stomatitis in immunocompromised patients. Systematic review

RESUMEN Fundamento: Aunque la estomatitis aftosa recurrente no tiene una etiología bien definida porque es una enfermedad multicausal, se ha reconocido que las interacciones o el debilitamiento del sistema inmunitario, contribuyen principalmente a la magnitud del proceso patológico. Las propuestas de tratamiento en pacientes inmunocomprometidos son diversas y por lo general se centran en alteraciones inmunológicas específicas. Objetivo: Evaluar el efecto clínico de los tratamientos propuestos para la estomatitis aftosa recurrente en pacientes inmunocomprometidos. Metodología: La búsqueda se realizó en las bases de datos PubMed/Medline y Cochrane. Se incluyeron ensayos clínicos que tuviesen entre sus variables de respuesta principales: Cicatrización de la úlcera aftosa, tiempo de cicatrización, de recurrencia e intensidad del dolor y entre las variables secundarias: Los efectos adversos y los síntomas. La extracción de datos se realizó de manera independiente por los autores. Se aplicó la metodología por la colaboración Cochrane para evaluar el riesgo de sesgo en cada uno de los estudios. Resultados: Se incluyeron 11 ensayos clínicos (8 controlados) publicados entre 1995 y 2020 y que aportan resultados de la eficacia de varias intervenciones terapéuticas: talidomida (4), irsogladine (2), rebamipida (1), láser de diodo (1), cápsulas de Omega-3 (1), vitamina B 12 (1), Complejo B (1). Seis de estos estudios incluyeron pacientes con la forma menor de estomatitis aftosa recurrente. El periodo de seguimiento estuvo entre los 14 y 360 días. Conclusiones: La talidomida puede ser eficaz en el alivio de los síntomas, la cicatrización y remisión de las lesiones, el diodo de láser y vitamina B12 en la disminución de la intensidad del dolor.

ABSTRACT Background: Although recurrent aphthous stomatitis does not have a well-defined etiology due to it is a multicausal disease, it has been recognized that the interactions or the weakening of the immune system, contribute mainly to the magnitude of the process pathological. Treatment proposals in immune compromised patients are diverse and they usually focus on specific immunological alterations. Objective: To evaluate the clinical effect of the proposed treatments for recurrent aphthous stomatitis in immunocompromised patients. Methodology: The search was performed in the PubMed/Medline and Cochrane databases. Clinical trials were included that could have among their main response variables: Aphthous ulcer healing, healing time, recurrence and pain intensity and among the secondary variables: Adverse effects and symptoms. data extraction was done independently by the authors. The methodology was applied by Cochrane collaboration to assess the risk of bias in each of the studies. Results: 11 clinical trials (8 controlled) published between 1995 and 2020 and that provided the results of the efficacy of various therapeutic interventions: thalidomide (4), irsogladine (2), rebamipide (1), diode laser (1), Omega-3 capsules (1), vitamin B 12 (1), Complex B (1). Six of these studies included patients with the minor form of stomatitis recurrent aphthous. The follow-up period was between 14 and 360 days. Conclusions: Thalidomide may be effective in relieving symptoms, healing and remission of the lesions, the laser diode and vitamin B12 in the decrease of the intensity of the pain.

The role of inflammatory mediators in the pathogenesis of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.

INTRODUCTION: As a recurrent disease, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is characterized by episodes of febrile attacks and is often prominent in children under five years of age. However, the etiology of this condition has not been fully understood yet. MATERIALS AND METHODS: The search in the extensive literature of peer-reviewed articles published from the inception to December 2021 was conducted to identify the relevant studies, using the electronic databases of MEDLINE/PubMed, Embase, Scopus, the Cochrane Library, and the Web of Science. RESULTS: The analysis of complex relationships indicates that inflammatory factors, such as various cytokines and acute-phase proteins (APPs), play leading roles in the pathogenesis of this disease. Accordingly, this article summarizes the current state of knowledge to explain the mechanisms involved in inflammatory responses among patients with PFAPA syndrome and investigate its role in the pathogenesis of this disease. Moreover, the possibilities for further implementation of new therapeutic strategies are pointed out. CONCLUSION: It is concluded that some pathophysiological processes are associated with immune dysregulation, which itself may be secondary to environmental factors, genetic background, and underlying diseases, including latent infections that multiply inflammatory mediators. elevated inflammatory markers similarly play a significant part in the clinical outcomes of this condition, whose pyrogenic nature is the reason for the development of episodes of febrile attacks in the population of patients suffering from PFAPA syndrome.

Fire needle for recurrent aphthous stomatitis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS), are common inflammatory lesions of the oral mucous, usually round or ovoid, circumscribed by erythematous haloes with a yellow-grey floor and mostly painful. The purpose of this study was to evaluate the efficacy and safety of fire needle in the treatment of RAS. METHODS: PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database were searched by 2 reviewers from the inception until December 2021. The original study that randomized control trials of fire needle for RAS will be selected and is not limited by country or language. In addition, researches in progress, the reference lists and the citation lists of identified publications will be retrieved similarly. Study selection, data extraction, and assessment of the quality will be performed independently by 2 reviewers who have been trained prior to data extraction. A meta-analysis will be conducted if the quantity and quality of the original studies included are satisfactory; otherwise, a descriptive analysis will be conducted. Review Manager V5.4 software will be using for data synthesis and assessment of the risk of bias according to Cochrane Handbook. RESULTS: This study will provide a comprehensive review of current evidence for the treatment of fire needle on RAS. CONCLUSION: The conclusion of this study will provide a judging basis that whether the treatment of RAS with fire needle is effective. INPLASY REGISTRATION NUMBER: INPLASY2021120118.

Recent advances in the aetiology of recurrent aphthous stomatitis (RAS).

Recurrent aphthous stomatitis (RAS) is the most common disease of oral mucosa, which almost attacks each individual once in their lifespan. Although plenty of factors have been suggested to play a role in the pathogenesis of RAS, the aetiology of RAS is still controversial, which might lead to limited clinical therapies in accordance with each RAS patient. This review mainly illustrates recent advances in potential causes associated with RAS in detail. Deeper comprehension of the aetiology of RAS will support doctors and researchers to make a better management of RAS patients and to discover new treatments. The aetiology of RAS is complicated, hence we should take a comprehensive view into its aetiology, with multiple potential factors being considered. Sample collection of RAS patients have greatly limited the progress in the aetiology of RAS. A research model of multiagency cooperation can help achieve perfect sample collection of year-round and multiposition.

Tratamiento de la estomatitis aftosa recurrente en pacientes inmunocomprometidos. Revisiónsistemática / Treatment of recurrent aphthous stomatitis in immunocompromised patients. Systematic review

Fundamento: Aunque la estomatitis aftosa recurrente no tiene una etiología bien definida porque es una enfermedadmulticausal, se ha reconocido que las interacciones o el debilitamiento del sistema inmunitario, contribuyen principalmente ala magnitud del proceso patológico. Las propuestas de tratamiento en pacientes inmunocomprometidos son diversas y por logeneral se centran en alteraciones inmunológicas específicas.Objetivo: Evaluar el efecto clínico de los tratamientos propuestos para la estomatitis aftosa recurrente en pacientesinmunocomprometidos.Metodología: La búsqueda se realizó en las bases de datos PubMed/Medline y Cochrane. Se incluyeron ensayos clínicosque tuviesen entre sus variables de respuesta principales: Cicatrización de la úlcera aftosa, tiempo de cicatrización, derecurrencia e intensidad del dolor y entre las variables secundarias: Los efectos adversos y los síntomas. La extracción dedatos se realizó de manera independiente por los autores. Se aplicó la metodología por la colaboración Cochrane para evaluarel riesgo de sesgo en cada uno de los estudios.Resultados: Se incluyeron 11 ensayos clínicos (8 controlados) publicados entre 1995 y 2020 y que aportan resultados de laeficacia de varias intervenciones terapéuticas: talidomida (4), irsogladine (2), rebamipida (1), láser de diodo (1), cápsulas deOmega-3 (1), vitamina B 12 (1), Complejo B (1). Seis de estos estudios incluyeron pacientes con la forma menor de estomatitisaftosa recurrente. El periodo de seguimiento estuvo entre los 14 y 360 días.Conclusiones: La talidomida puede ser eficaz en el alivio de los síntomas, la cicatrización y remisión de las lesiones, el diodo de láser y vitamina B12 en la disminución de la intensidad del dolor [AU]

Mannose-binding lectin serum levels and (Gly54asp) gene polymorphism in recurrent aphthous stomatitis: A case-control study.

Objectives: Dysregulation of the immune response appears to play a significant role in recurrent aphthous stomatitis (RAS) development. The main objective of this case-control study is to investigate the blood levels of mannose-binding lectin (MBL) and the frequency of the MBL2 gene (gly54asp) polymorphism in RAS patients, including 40 RAS patients and 40 healthy controls. Methods: Serum MBL levels were determined by ELISA, while the PCR-restriction fragment length polymorphism was used in MBL2 genotyping. Results: The median serum MBL level was significantly lower in the RAS group than in the control group (975 ng/mL (545-1320) vs. 1760 ng/mL (1254-2134); p≤ 0.001). The MBL levels were significantly lower in the BB genotype, whereas they were significantly higher in the wild type AA with a median of 525 and 1340 ng/mL, respectively (p =0.005). The B allele was expressed in significantly higher percentages of RAS patients than in controls. There was no significant association between MBL serum levels (p=0.685) or MBL2 codon 54 genotypes (p=0.382) with the type of ulcers. Conclusion: There was an association between low MBL serum levels and the variant allele B of the MBL2 (gly54asp) gene, and the susceptibility to RAS. As a result, potential novel therapeutic options for RAS patients with MBL deficiency should be investigated.