The effect of vitamin D supplementation on attacks in PFAPA syndrome patients with low vitamin D levels.

BACKGROUND-AIM: To evaluate the effect of vitamin D supplementation on the frequency and duration of attacks in patients of PFAPA syndrome with low vitamin D levels. METHODS: This retrospective study comprised PFAPA patients with vitamin D deficiency/insufficiency between 2018 and 2023. The frequency and duration of PFAPA attacks before and after vitamin D supplementation were noted. RESULTS: Seventy-one patients were included. Of the 71 patients, 24 (33.8%) had vitamin D insufficiency, and 47 (66.2%) had vitamin D deficiency. In patients with vitamin D insufficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 4.3 ± 1.9/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.5 ± 2.7/year per year and 1.3 ± 0.9 days respectively (p = 0.2, p = 0.2, respectively). In patients with vitamin D deficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 7.4 ± 2.1/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.3 ± 2.4/year and 1.3 ± 0.9 days respectively (p < 0.01, p = 0.04, respectively). When the vitamin D level and the frequency of attacks were compared, the cut-off value of vitamin D was found to be 29.7 nmol/L. CONCLUSIONS: In PFAPA patients with low vitamin D levels, the frequency and duration of PFAPA attacks were reduced with vitamin D supplementation. Especially at vitamin D level cut-off > 29.7 nmol/L, the frequency of attacks reduced significantly.

Elevated serum fibrinogen levels in Chinese patients with minor recurrent aphthous stomatitis: An observational study.

Fibrinogen is a protein that reflects systemic inflammation and regulates the immune response to disease. However, there is a scarcity of data on fibrinogen in recurrent aphthous stomatitis (RAS). We aimed to test the hypothesis that fibrinogen is involved in the aetiology of RAS. Between November 2016 and November 2018, we included 109 minor RAS patients and 29 age- and sex-matched controls in a single-center, observational study. Their clinical history and ulcer manifestations led to the diagnosis of minor RAS. The ulcer severity score (USS) was used to assess disease severity, and fibrinogen was also collected. We conducted three analyses: Analysis 1 (comparison of fibrinogen levels between patients and controls), Analysis 2 (comparison of fibrinogen levels between high and low USS patients) and Analysis 3 (comparison of fibrinogen levels between before and after anti-inflammatory treatment in patients). The fibrinogen levels in the 109 minor RAS patients were statistically higher than in the 29 controls (mean [SD], 2.6 [0.5] vs. 2.3 [0.3]; Student's t-test, p < 0.001). However, there were no significant differences in fibrinogen levels among the 43 patients with high USS and the 39 patients with low USS (mean [SD], 2.7 [0.5] vs. 2.6 [0.4]; Student's t-test, p = 0.278). Furthermore, fibrinogen levels were significantly higher before anti-inflammatory treatment in comparison to those after anti-inflammatory treatment in the 35 paired patients (mean [SD], 2.6 [0.4] vs. 2.5 [0.4]; Student's t-test, p = 0.026). Interestingly, fibrinogen levels were significantly higher in the 35 paired patients after anti-inflammatory treatment compared to the 29 control subjects (mean [SD], 2.5 [0.4] vs. 2.3 [0.3]; Student's t-test, p = 0.026]. Fibrinogen may play a role in the aetiology of RAS and may be a drug target for RAS treatment. Clinicians should be alert that high serum fibrinogen levels might be associated with the risk of RAS.

Determinants and inequality of recurrent aphthous stomatitis in an Indonesian population: a cross sectional study.

INTRODUCTION: Recurrent Aphthous Stomatitis (RAS) is the most common type of ulceration in the oral cavity which can occur due to several factors. AIMS: To determine the factors related to the incidence of RAS and examine the social class inequality in RAS among the Indonesian population using data from the fifth wave of the Indonesian Family Life Survey (IFLS5) in 2014. METHODS: This study is a descriptive study with a cross-sectional design using secondary data from IFLS5 data in 2014 (n = 28,410). Socio-economic position (SEP) was calculated by Adult Equivalent Scale and categorized into 4 classes. Outcome is RAS. Mediating factors were psychosocial (stress), eating behavioral (food consumption), and systemic diseases. Descriptive analysis, chi-square and a series of logistic regressions were performed to analyze the data. Odds ratio (OR) and 95% confidence interval (CI) were used to report the results. RESULTS: Only 18.39% of IFLS5 respondents experienced the incidence of recurrent aphthous stomatitis in 2014. The bivariate (chi-square) results showed that there was a relationship between the incidence of RAS and the related independent variables. Logistic regression showed the highest possibility of RAS in respondents aged 18-34 years, female, unmarried, high school education level, living in the city, having frequent stress levels, having food habits that frequently drinking soda, sweet foods, chili sauce, fried food and has systemic diseases such as, asthma, cancer, rheumatism, and digestion. The lowest SEP group had the highest probability of occurrence of RAS over the other groups among the different models. CONCLUSIONS: There are several factors that determine the incidence of RAS. There was a monotonic gradient of inequality in RAS according to SEP group. This study might be useful to provide information regarding the relationship of determinants factors with the incidence of RAS to prevent it and promote oral health in the future.

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.

The relationship between Helicobacter pylori infection and recurrent aphthous stomatitis: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was designed to provide new insights into the relationship between Helicobacter pylori (H. pylori) infection and recurrent aphthous stomatitis (RAS). MATERIALS AND METHODS: We included and evaluated studies on H. pylori infection and RAS from PubMed, EMBASE, Cochrane Library, and Web of Science databases published up to January 31, 2023. The characteristics of these studies were collected, and the quality was evaluated by Newcastle-Ottawa Scale (NOS). The random effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI). To further explore the sources of heterogeneity, meta-regression analysis and subgroup analyses were performed. Funnel plot, Egger's test, and Begg's test were used to assess publication bias. RESULTS: In total, fifteen case-control studies with 1137 individuals (601 cases and 536 controls) were included. The H. pylori was found to be significantly associated with RAS (OR: 1.83 95% CI: 1.41-2.37, P = 0.001). In the subgroup analyses, studies that used PCR (OR: 2.03 95% CI: 1.31-3.15) or UBT (OR: 1.83 95% CI: 1.13-2.96) yielded a significant positive association, while a non-significant association (OR: 1.12 95% CI: 0.61-2.08) was found from studies that used ELISA method. Sensitivity analyses showed that the results were robust. No significant publication bias was found. CONCLUSIONS: The current evidence does not rule out an association between H. pylori and RAS. The effect of H. pylori on RAS varies in detection methods and sources of sample. Large samples, multiple clinical studies, and improved methods are still needed to determine the exact effect of H. pylori on RAS. CLINICAL SIGNIFICANCE: H. pylori infection may be a risk factor for the pathogenesis of RAS.

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler. RESULTS: A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis. CONCLUSIONS: The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively. TRIAL REGISTRATION: The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).

Vulvar Aphthous Ulcers in Perimenarchal Adolescents after COVID-19 Vaccination: A Multicenter Case Series.

This case series from 3 academic hospital-based pediatric and adolescent gynecology services outlines the temporal association between vulvar ulcers in female adolescents and COVID-19 vaccination. We identified 8 cases and describe each patient's presentation, differential diagnosis, diagnostic workup, complications, treatment modalities, and overall course of illness. All cases seek to illustrate the clinical experiences of patients and providers interfacing with vulvar aphthous ulcers and contribute to the emerging literature exploring the novel association between vulvar aphthous ulcers and COVID-19 vaccination. To date, this is the largest described case series of this association in the literature. Key Words: COVID-19, Vaccine, Aphthous ulcers, Vulva, Adolescent.

Long-term efficacy of tonsillectomy/adenotonsillectomy in patients with periodic fever aphthous stomatitis pharyngitis adenitis syndrome with special emphasis on co-existence of familial Mediterranean fever.

Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome is one of the most common autoinflammatory fever disorders in the childhood which may co-exists with familial Mediterranean fever (FMF) causing treatment complexity. As the role of surgery in PFAPA syndrome is still controversial, in this paper, our aim is to present our results of tonsillectomy/adenotonsillectomy in the treatment of PFAPA syndrome. Archives of a tertiary care hospital were investigated for patients who underwent tonsillectomy or adenotonsillectomy due to PFAPA Syndrome between 2010 and 2020. 344 patients were found but only 281 of them were accessible. Through phone call interview and chart review methods, preoperative and postoperative the number and severity of the attacks and general satisfaction after the operation were recorded and analyzed. Also, patients with concomitant FMF were analyzed separately. A total of 281 patients were included in the study. There was no improvement in 10 (3.55%) patients. Eight (2.84%) patients showed mild improvement, 29 (10.32%) patients had moderate improvement and 234 (83.27%) patients had full recovery after tonsillectomy. There were 266 PFAPA patients without FMF. No improvement, mild improvement, moderate improvement, and full recovery in this patient group were 5 (1.9%), 6 (2.3%), 25 (9.4%) and 230 (86.5%), respectively. FMF was present in 5.33% (15/281) of the patients. In PFAPA + FMF group 5 patients had no improvement (33.3%), 2 had mild improvement (13.3%), 4 had moderate improvement (26.7%) and 4 had full recovery (26.7%). Benefit of tonsillectomy was significantly lower in the patients with concomitant FMF when compared to the patients who did not have FMF (p < 0.001). Age of diagnosis, age of operation, severity of the disease, type of operation, and gender were found to have no significant relationship with the benefit from surgery (p < 0.05). According to the findings of this study, tonsillectomy is an effective long-term treatment for PFAPA syndrome with success rate of 83.27%. Also, preoperatively FMF should be considered in these patients, which dramatically reduces surgical efficacy.

Oral manifestations associated with inflammatory bowel disease and early endoscopic findings in patients with spondyloarthritis.

BACKGROUND AND AIMS: Spondyloarthritis (SpA) is a group of autoinflammatory disorders, of which the primary extra-articular manifestation is inflammatory bowel disease (IBD). The oral cavity being a part of gastrointestinal tract, is significantly compromised in IBD, and in many cases, it is the first site of clinical manifestations of IBD. This study aimed to identify changes in the oral mucosa associated with the onset of IBD and their association with endoscopic/histological findings. MATERIALS AND METHODS: The study assessed 80 patients with SpA and 52 healthy controls. Oral, rheumatological, and gastroenterological assessments were performed. The ileocolonoscopy was performed via digital magnification chromoendoscopy. The statistical analysis consisted of Chi-square, Fisher's exact, and multiple correspondence discriminant analysis tests. RESULTS: From the disease cohort, 63.0% patients showed oral lesions (p = 0.050). These manifestations ranged from gingivitis (55.0%, p = 0.001), aphthous stomatitis (3.8%, p = 0.091), angular cheilitis (2.6%, p = 0.200), and perioral erythema with scaling (1.3%, p = 0.300). All patients who presented with alterations in colonic mucosa also had oral lesions associated with IBD (p = 0.039), specifically gingivitis/aphthous stomatitis (p = 0.029). CONCLUSION: The patients with SpA without IBD present significant oral signs and symptoms. Gingivitis seems to be the most relevant because of its associations with early endoscopic and histological findings. CLINICAL RELEVANCE: An integral approach to the diagnostic tests that includes evaluations of oral, rheumatological and gastroenterological tissues may favor timely attention and improve patients' quality of life.

[Sweet syndrome of childhood with acquired cutis laxa (Marshall syndrome) as primary manifestation of Takayasu arteritis]. / Sweet-Syndrom des Kindesalters mit erworbener Cutis laxa (Marshall-Syndrom) als Erstmanifestation einer Takayasu-Arteriitis.

A special form of the rare infantile Sweet syndrome (acute febrile neutrophilic dermatosis) is facultative healing in the form of postinflammatory elastolysis with acquired cutis laxa, named "Marshall" syndrome after the authors who first described it. We report the case of a 3-year-old child in whom the cutaneous manifestation led to diagnosis of Takayasu arteritis. Postinflammatory elastolysis with acquired cutis laxa is a clinically relevant cutaneous indicator of life-threatening cardiovascular complications such as aortitis, aortic aneurysm, coronary stenosis and heart failure in children with Sweet's syndrome. Cutis laxa usually precedes cardiac complications or, as in our case, occurs simultaneously; thus, immediate cardiac and rheumatologic examinations are important to initiate systemic therapy with anti-inflammatory and immunomodulatory agents early to prevent complications.

Vulvar Aphthous Ulcers in an Adolescent After Coronavirus Disease 2019 (COVID-19) Vaccination.

BACKGROUND: Nonsexually acquired genital ulcers have been described among girls who are prepubertal after various viral illnesses due to mucosal inflammation from an immunologic response. Until recently, nonsexually acquired genital ulcers have only been associated with viral infections. CASE: We present a case of an adolescent girl developing nonsexually acquired genital ulcers after both her first and second coronavirus disease 2019 (COVID-19) vaccine doses. Her course followed an expected timeline for severity and resolution of ulcers. CONCLUSIONS: Aphthous ulcers may arise from inflammatory effects of COVID-19 vaccination. Clinical monitoring after COVID-19 vaccination from all formulations should include assessment for nonsexually acquired genital ulcers if vaginal pain is reported.

The rs13075270 and rs13092160 polymorphisms of CCR1 and CCR3 genes on oral aphthous-like lesions in PFAPA syndrome.

Fever is a common symptom of infection in children. Periodic fever syndromes are less common but more complex. One of these Periodic fever syndromes is PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome which is known as the most benign syndromes. The cause of this disease is unknown. Various factors, including environmental and genetic factors, are involved in the development of this disease. In this study, the association of rs13075270 and rs13092160 polymorphisms were investigated in CCR1 and CCR3 genes with susceptibility to this syndrome in the Chinese population. In this regard, 38 patients with PFAPA syndrome and 100 healthy individuals were selected. After DNA sampling and extraction, polymorphisms of CCR1 and CCR3 receptor genes were examined by the PCR-RFLP method. Findings were analyzed using SPSS software version 22 with a significant level of P <0.05. The frequency of T/T genotype rs13092160 polymorphism in the patient and control groups was 78.95% and 83%, respectively, C/T genotype was 21.05% and 17% (P = 0.421). The frequency of the C/C genotype was 0 in both groups. Regarding rs13075270 polymorphism, the frequency of T/T genotype in patient and control groups was 15.79% and 81%, C/T genotype was 78.95% and 18% and C/C genotype was 5.26% and 1%, respectively (P<0.05). Thus, in rs13075270 polymorphism, the C/T genotype was associated with the risk of PFAPA syndrome (P<0.05), but rs13092160 polymorphism did not show a significant difference between individuals with PFAPA syndrome and controls.

Recurrent reactive non-sexually related acute genital ulcers: a risk factor for Behcet's disease?

BACKGROUND AND AIM: Lipschutz ulcers (LU) are idiopathic genital lesions characterized by the sudden appearance of painful, usually symmetric vulvar ulcers, typically occurring in sexually inactive adolescents. LU is a diagnosis of exclusion. As these lesions heal spontaneously, in the absence of tissue scarring, the therapy is mainly symptomatic and focuses on pain relief. Recurrence of LU associated with oral ulcers describes the clinical picture of complex aphthosis, which belongs to Behçet's disease (BD) pathological spectrum. Our work aims to analyze the correct diagnostic approach to recurrent aphthous, focusing on the importance of a multidisciplinary assessment and immunogenetic investigation to identify the subjects at risk of progression towards BD.   Methods: We present the case of a 12-year-old non sexually active Italian girl who was diagnosed with LU. After 15 months, she presented recurrent reactive non sexually related acute genital ulcer associated with a history of oral aphthous. According to clinical features and anamnesis, complex aphthosis was diagnosed. For diagnostic purposes, she underwent an immunogenetic analysis that showed HLA-B51 positivity. RESULTS: In the absence of clinical and laboratory criteria to define the risk of progression of complex aphtosis towards BD, we think that besides a strict follow-up, in pediatric patients with a suggestive clinical history, it is crucial to adopt a multidisciplinary approach, comprehensive of HLA investigation, in order to guarantee an early diagnosis and a prompt therapeutic intervention. CONCLUSIONS: In children and adolescents with genital ulcers, it is essential to consider all the possible differential diagnoses to undertake a timely and correct course of treatment.

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.

Evaluation of cinnamaldehyde mucoadhesive patches on minor recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND & OBJECTIVE: The use of herbal medicines to treat common oral diseases increases rapidly. Recurrent aphthous stomatitis is one of the most common oral mucosal diseases, which has an unclear etiology and could lead to severe pain and dysfunction. Cinnamaldehyde is a major component of cinnamon bark oil. Biological properties of cinnamaldehyde, such as antioxidant, antitumor, antifungal, cytotoxic, and anti-mutational characteristics, have been identified. Considering the prevalence of recurrent aphthous stomatitis and the importance of using herbal resources for treatment, the present study aimed to evaluate the effect of mucosal adhesive patches containing Cinnamaldehyde on minor recurrent aphthous stomatitis lesions. MATERIAL & METHODS: In this randomized, double-blind clinical trial, patients were divided into two groups. The intervention group received three daily mucosal adhesive patches to be used in the morning, afternoon, and night. The control group also did the same with a placebo. To evaluate the healing and determine the diameter of the lesions, patients were clinically examined on days zero, 3, 5, and 7. The VAS scale evaluated pain at baseline and after each meal for seven days. The Fisher's exact test, t-test, Shapiro Wilk test, Friedman test, and the Mann-Whitney test were used to analyze the data using the SPSS 20 software. RESULTS: There was no statistically significant difference in the mean diameter of the inflammatory lesion and pain intensity in the two groups in the baseline (p > 0.05). However, the ulcer size was significantly reduced in the cinnamaldehyde group on the third, fifth, and seventh days of the study. Except for baseline, the mean pain intensity significantly decreased in the cinnamaldehyde group compared to the placebo group (p < 0.05). CONCLUSION: Cinnamaldehyde mucoadhesive patches effectively reduced and improved aphthous lesions and pain intensity in patients and can be considered a treatment for RAS. REGISTRATION NUMBER: IRCT20180312039060N2-First registration date: 20/07/2018. The present study was registered as a retrospective study.

Clinical characterization, long-term follow-up, and response to treatment of patients with syndrome of undifferentiated recurrent fever (SURF).

OBJECTIVES: To describe a homogeneous group of patients with undifferentiated recurrent fevers followed-up in a tertiary referral center for systemic autoinflammatory diseases (SAIDs). METHODS: Patients with undifferentiated recurrent fevers seen at our Center from 2008 to 2021 and followed-up for at least one year were included in a retrospective study. Monogenic recurrent fevers, patients carrying variants of unknown origin and PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis) syndrome were excluded. RESULTS: Fifty patients (34 male, 16 female) were included in the study. The median age at onset was 3 years, and the median follow-up was 3.3 years. At baseline, arthralgia (70%) and abdominal pain (65%) were the most frequent manifestations. NSAIDs or steroids on demand had a variable and transient effect. Tonsillectomy was ineffective in the 10 patients (20%) that underwent surgery. Forty-eight patients (96%) were treated with colchicine. A complete response (absence of fever) was achieved in 31 patients (64.6%). Nine patients (18%) showed a partial response, with a median reduction of fever episodes per year of 72%. Nine patients (16.7%) were considered resistant to colchicine. The presence of generalized lymphadenopathy and, to a lesser extent, exudative tonsillitis was associated with a lack of response to colchicine. CONCLUSIONS: We describe the largest series of patients with syndrome of undifferentiated recurrent fever (SURF) reported in the literature so far. SURF should be considered as a distinct clinical entity in the context of multifactorial autoinflammatory diseases.

Common Oral Lesions.

Familiarity with common oral conditions allows clinicians to observe and treat patients in the primary care setting or refer to a dentist, oral surgeon, otolaryngologist, or other specialist. Recurrent aphthous stomatitis (canker sores) is the most common ulcerative condition of the oral cavity. Recurrent herpes simplex labialis and stomatitis also commonly cause oral ulcers. Corticosteroids, immunocompromise, antibiotics, and dentures can predispose patients to oral candidiasis. Benign migratory glossitis (geographic tongue) occurs in up to 3% of the population but generally lacks symptoms, although some people experience food sensitivity or a burning sensation. Hairy tongue is associated with a low fiber diet, tobacco and alcohol use, and poor oral hygiene in older male patients. Generally, hairy tongue is asymptomatic except for an unattractive appearance or halitosis. Tobacco and alcohol use can cause mucosal changes resulting in leukoplakia and erythroplakia. These can represent precancerous changes and increase the risk of squamous cell carcinoma. Mandibular and maxillary tori are common bony cortical outgrowths that require no treatment in the absence of repeat trauma from chewing or interference with dentures. Oral lichen planus occurs in up to 2% of individuals and can present as lacy reticulations or oral erosions and ulcerations. Traumatic buccal mucosal fibromas and labial mucoceles from biting can be excised.

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.

Adamantiades-Behçet disease: from clinical heterogeneity to diagnosis during the COVID-19 pandemic.

Adamantiades-Behçet disease (ABD) is a systemic disease with vasculitis, characterized by recurrent oral aphthosis and ocular, cutaneous, articular, vascular, cardiopulmonary manifestations and it is mainly found in the territories of the antique "silk road". ABD pathogenesis remains unknown although genetic, infectious and environmental factors seem to be implicated in the development of the disease, which is considered an auto-inflammatory condition. COVID-19 infection can present some symptoms, in particular at the level of oral and pulmonary mucosa, which require a differential diagnosis with ABD. Furthermore, the immunological alterations of this disease, and the drugs used for its treatment could influence the infection by COVID-19, and its clinical evolution. Nevertheless, vaccination anti-COVID-19 is recommended in ABD patients. The most commonly used diagnostic criteria for ABD are those established in 2014 by the International Team for the Revision of the International Criteria for BD (ITR-ICBD). Furthermore, criteria for disease severity according to the Overall Damage Index of Behçet's Syndrome (BODI) have recently been proposed in order to quantify the severity of the disease as well as the evolution during follow-up. In ABD patients it is mandatory to investigate on the presence of active/latent tuberculosis, because of the common organ involvement, such as eyes and bowel. ABD has a high morbidity and low mortality, sometimes linked to the rupture of an arterial aneurysm and/or neurological complications. This article is based on a general review on ABD ranging from the history of ABD to possible causes and clinical manifestations. A specific section has been dedicated to the COVID-19 pandemic.

Probiotic use in the prophylaxis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a retrospective cohort study.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is an autoinflammatory recurrent fever syndrome that mainly affects children. Probiotics are currently used to prevent upper respiratory tract infections and flares of diseases associated with immune dysregulation. We aimed to evaluate the response to probiotic treatment in PFAPA patients. Patients with PFAPA syndrome who received probiotics and were followed between July 2019 and July 2021 were included in this retrospective study. Demographic and clinical features and response to probiotics were assessed. Twenty out of 111 children with PFAPA syndrome (F/M:1) were included. The median (min-max) ages at symptoms onset and diagnosis were 24 (3-72) and 51.5 (11-120) months, respectively. All 20 patients received probiotics during the disease course. The probiotic preparation they received included a combination of two lactobacilli as Lactobacillus plantarum HEAL9 (Lp HEAL9) and Lactobacillus paracasei 8700:2 (Lpa 8700:2). The median age at probiotic onset was 60 (33-192) months, while the duration of probiotic use was 4.5 (3-19) months. All patients except one experienced a decrease in attack frequency with probiotic use. After probiotic treatment, the median number of episodes during 3 months decreased from 3 to 1 (p < 0.001). Eight (40%) patients had no attacks during the 3 months after probiotic initiation. And, 5 (45%) of 11 patients who had ≥ 1 attacks on probiotics mentioned that the attack severity decreased significantly after probiotic initiation. Our results suggest that probiotic strains Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2 could be beneficial in PFAPA patients by decreasing the attack frequency.