Propolis Use in Dentistry: A Narrative Review of Its Preventive and Therapeutic Applications.

Propolis is a resinous substance produced naturally by bees, and it consists of the exudates of plants mixed with enzymes, wax, and pollen. Propolis continues to gain considerable scientific interest due to its potential health benefits. The modern-day use of propolis in pharmaceutical preparations, such as toothpastes, mouthwashes, chewable tablets, mucoadhesive gels, and sprays, is increasing. However, the effectiveness of using propolis-containing pharmaceuticals in dentistry is not clear. The present paper aims to review the literature on the dental applications of propolis in preventive dentistry, periodontics, oral medicine, and restorative dentistry and discuss its clinical effectiveness. A literature search was conducted using Scopus, PubMed, and Web of Science databases. In total, 104 studies were included, of which 46 were laboratory studies, 5 animal studies, and 53 human clinical studies. Overall, the laboratory studies revealed a range of antimicrobial effects of propolis on oral pathogens. Clinical investigations of propolis in biofilm and dental caries control as well as adjuvant periodontal therapies reported positive outcomes in terms of plaque control, pathogenic microbial count reduction, and periodontal tissue inflammation control. Additional investigations included the use of propolis for the management of recurrent aphthous stomatitis, oral mucositis, and cavity disinfection after caries removal as well as the development of a range of restorative dental materials. Based on the reported outcomes of the studies, the clinical usage of propolis has potential. However, the majority of the evidence is derived from studies with flaws in their methodological design, making their results and conclusions questionable. As a consequence, properly designed and well-reported clinical studies are required to affirm the effectiveness of propolis for dental applications. Additionally, the safety of propolis and the optimal concentrations and extraction methods for its clinical use warrant further investigation. Utilisation of standardised propolis extracts will help in quality control of propolis-based products and lead to the achievement of reproducible outcomes in research studies.

Adult-onset Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis Syndrome Responsive to Colchicine.

We herein report a rare case of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome that occurred in an 18-year-old man. He visited our hospital with recurrent episodes of a fever, pharyngitis and adenitis without suggestive findings of infection. These episodes resolved within 5 days and recurred quite regularly, with an interval of about 30 days. As the febrile episodes significantly impaired his quality of life, he was treated with colchicine (0.5 mg) as prophylaxis. This completely prevented the episodes during six months of follow-up. Colchicine may therefore be effective in cases of adult-onset PFAPA syndrome.

Colchicine versus cimetidine: the better choice for Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome prophylaxis, and the role of MEFV gene mutations.

BACKGROUND: During childhood, the most common periodic fever is periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. The effective treatment and prevention of febrile attacks improve these patients' and their families' quality of life. However, there is no single strategy or evidence-based guideline to manage this syndrome, and most of them are based on consensus treatment plans. METHODS: This randomized controlled trial was carried out on 67 PFAPA patients referred to three tertiary centers of pediatric rheumatology. The patients were divided into two groups, including group 1 (n = 36) receiving prednisolone plus colchicine and group 2 (n = 31) receiving prednisolone plus cimetidine. Demographic characteristics and the number of febrile episodes were compared between the two groups before and after the intervention. RESULTS: In both groups, the number of febrile episodes after the treatment decreased (P ≤ 0.001). Statistical Analysis showed no significant difference between the two groups (P = 0.88). Moreover, 44 patients from both groups were checked for the MEFV gene. There were no statistical differences between MEFV positive and negative subgroups in response to colchicine (P = 1). CONCLUSION: This study showed that both drug regimens are significantly effective in preventing febrile attacks in PFAPA syndrome, and the presence of a MEFV gene mutation might not be the only significant risk factor for a response to colchicine. TRIAL REGISTRATION: IRCT, IRCT20191222045847N1. Registered 23 October 2019, https://fa.irct.ir/search/result?query=IRCT20191222045847N1.

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.

Zinc supplementation for prevention and management of recurrent aphthous stomatitis: a systematic review.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a very common oral ulcerative disease with no definitive cure. Growing evidence suggests a significant association between zinc deficiency and RAS. OBJECTIVES: To assess the efficacy of systemic zinc supplementations in the prevention and management of RAS. METHODS: Five databases were searched for all English and Chinese studies published up to November 2020. All clinical trials that assessed the efficacy of zinc supplementations in the management and/or prevention of RAS were included. RESULTS: Seven clinical trials comprising 482 RAS patients (250 in zinc group) fulfilled the inclusion criteria. The follow-up period ranged from three months to one year. Five studies showed significantly better efficacy of zinc in reducing the recurrence rates of RAS, whereas two studies did not report any significant differences compared to the controls. Four studies reported on signs/symptoms of RAS, three of which showed superior outcomes in favour of zinc, while one study reported comparable results. CONCLUSION: Zinc supplementation seems to be efficacious in the management and prevention of RAS. However, further clinical trials with standardized methodologies and adequate follow-up periods are required to confirm the efficacy of zinc supplementations.

Lactic acid 5% mouth wash vs Kenalog in Orabase 0.1% for treatment and prophylaxis of recurrent aphthous ulcer.

BACKGROUND: The outcomes of most therapeutic modalities for recurrent aphthous ulcer (RAU) are still unsatisfactory. AIM: To evaluate lactic acid 5% mouth wash vs Kenalog in Orabase for treatment and prophylaxis of RAU. PATIENTS/METHODS: Forty cases with early-onset idiopathic RAU were enrolled in this study. Patients were divided into two equal groups; group A patients had used Kenalog in Orabase twice daily, and group B patients had used lactic acid 5% mouth wash 3 times daily. All patients had used the therapy for 1-2 weeks according to patients' clinical response that was evaluated according to oral clinical manifestations index (OCMI); before therapy, during course of treatments and in follow-up visits. RESULTS: At the ends of both first and second weeks, from beginning of therapy, OCMI was reduced more in group B patients than in group A with statistically significant results. These results revealed that group B achieved more reduction in the size, pain, and healing time of RAU. During the follow-up period, group A showed 40% recurrence rate while group B showed 5% only. CONCLUSIONS: Lactic acid 5% mouth wash is natural, safe, and effective so it is better alternative to corticosteroids for treatment and prophylaxis of RAU without any side effects.

Assessment of the oral microbiome in the development of recurrent oral aphthae in patients with gastrointestinal pathology

Chronic recurrent oral aphthae in residents living in an ecologically unfavourable region are characterized by a permanent course and prolonged recovery processes of regeneration of pathological elements of the oral mucosa. Using the microbiological method and modern test systems, it has been found that on the surface of aphthae an extremely diverse state of the oral microbiota is determined and its types are diverse. Trigger mechanisms have been determined. The role of representatives of various types of microorganisms - enterococci, staphylococci, streptococci, yeast-like fungi of the genus Candida (C. albicans) and obligate-anaerobes in the development of recurrent oral aphthae has been established. The data obtained can serve as an indication for the development of modern treatment and preventive measures regarding this category of patients.

Extraintestinal Manifestations in Vedolizumab and Anti-TNF-Treated Patients With Inflammatory Bowel Disease.

BACKGROUND: Extra-intestinal manifestations (EIMs) can impact morbidity in patients with inflammatory bowel diseases (IBD; Crohn's disease [CD] and ulcerative colitis [UC]). This study compared incidence rates of EIMs in patients with moderate to severe IBD receiving gut-selective vedolizumab (VDZ) vs those receiving systemic anti-tumor necrosis factor (anti-TNF) therapies. METHODS: Adult IBD patients receiving VDZ or anti-TNFs were identified from the MarketScan claims database from September 28, 2012, through September 30, 2016. Incidence rates of EIMs were compared between the 2 cohorts. Descriptive analyses were performed for all courses of treatment. Generalized linear models estimated the impact of treatment on the likelihood of developing EIMs. RESULTS: Compared with patients receiving anti-TNF therapy, VDZ-treated CD patients were 28% more likely to develop "any EIMs" (adjusted incident rate ratio [IRR], 1.28; 95% confidence interval [CI], 1.02-1.62). Specifically, CD patients treated with VDZ were more likely to develop erythema nodosum (IRR, 4.29; 95% CI, 1.73-10.64), aphthous stomatitis (IRR, 3.73; 95% CI, 1.51-9.23), episcleritis/scleritis (IRR, 2.51; 95% CI, 1.02-6.14), arthropathy (IRR, 1.45; 95% CI, 1.15-1.84), primary sclerosing cholangitis (PSC) (IRR, 7.79; 95% CI, 3.32-18.27), and uveitis/iritis (IRR, 2.89; 95% CI, 1.35-6.18). UC patients receiving VDZ did not have a statistically significant increase in "any EIMs" vs patients receiving anti-TNFs, but were more likely to develop specific EIMs (aphthous stomatitis: IRR, 3.67; 95% CI, 1.30-10.34; pyoderma gangrenosum: IRR, 4.42; 95% CI, 1.00-19.45; and PSC: IRR, 3.44; 95% CI, 1.23-9.68). CONCLUSIONS: IBD patients receiving VDZ may be more likely to develop EIMs vs patients receiving anti-TNF therapies. The gut-selective inflammatory control of VDZ may potentially limit its clinical effect on EIM prevention.

The association between minor recurrent aphthous stomatitis (RAS), children's poor oral condition, and underlying negative psychosocial habits and attitudes towards oral hygiene.

BACKGROUND: Minor Recurrent Aphthous Stomatitis (RAS) represents a disease which is very difficult to prevent. This case-control study focused on possible associations between minor Recurrent Aphthous Stomatitis in children, their oral health, and underlying behavioral indexes of children's attitudes and habits pertaining to (home) oral hygiene, with the further goal of enabling the dentist to prevent these specific kind of lesions, both from a clinical and a broader psychosocial perspective. METHODS: Four hundred one school-children (5-10 years old) in Milan (Italy) were submitted to an intra-oral examination, and interviewed with the aid of a brief psychosocial questionnaire. RESULTS: At the clinical level, statistically significant associations were observed between the presence of decayed teeth and minor Recurrent Aphthous Stomatitis (Odds Ratio: 3.15; 95% CI: lower limit 1.06; upper limit: 9.36; Z-test: 2.07, p = 0.039; Chi-square = 4.71, p = 0.030), and between the Decayed Missing or Filled Teeth (DMFT) index and minor aphthous stomatitis (Odds Ratio: 3.30; 95% CI: lower limit 1.13; upper limit: 9.67; Z-test = 2.18, p = 0.029; Chi-square = 5.27; p = 0.022), both results pointing to a significant increase-by circa 3 times-in the risk of developing minor Recurrent Aphthous Stomatitis in children exposed to the two above-identified factors (i.e., the presence of decayed teeth and a clearly compromised oral condition, as signaled by the DMFT index), if compared with the risk run by their non-exposed counterparts. At the psychosocial level of analysis, statistically significant associations were observed (1) between children's practice of spontaneously brushing teeth when not at home and a comparatively lower (i.e. better) Decayed Missing or Filled Teeth index (Chi-square: 8.95; p = 0.011), and (2) between receiving parental aid (e.g., proper brushing instructions) while practicing home oral hygiene and a significantly reduced presence of decayed teeth (Chi-square = 5.40; p = .067; Spearman's Rho, p = .038). Further, significant associations were also observed between children's reported severity of dental pain and both (a) the presence of decayed teeth (Chi-square = 10.80; p = 0.011), and (b) children's (poor) oral health condition as expressed by the Decayed Missing or Filled Teeth index (Chi-square = 6.29; p = 0.043). Interestingly, specific lifestyles and social status, showed no systematic association to other clinical or psychological/psychosocial indices. CONCLUSIONS: These systematic relations suggest that, in the presence of Recurrent Aphthous Stomatitis in pediatric patients, the dentist should carefully monitor children for potential carious lesions, implement protocols of prevention to control Recurrent Aphthous Stomatitis disease in children affected by caries, and also be particularly aware of the right or wrong habits children may acquire in the course of continued social exchange with their caregivers and peers.

Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants?

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most frequent repetitive fever syndrome in childhood. It is characterized by fever episodes lasting for approximately 3-6 days, once every 3-8 weeks. METHODS: Clinical and laboratory data for PFAPA syndrome patients between January 2010 and December 2014 followed up at a tertiary pediatric care hospital were reviewed. RESULTS: Four hundred children (256 male, 144 female; mean age at diagnosis, 4.2 ± 2.2 years), were enrolled in the study. During the episodes, mean leukocyte number was high (12 725/mm3 ) with predominant neutrophils. The mean number of monocytes was 1256/mm3 , and 90.2% had monocytosis. Serum amyloid A and C-reactive protein were high in 84.6% and in 77.8% of the patients, respectively. Mediterranean fever (MEFV) gene heterozygous mutation was identified in 57 of the 231 patients (24.7%) in whom genetic analysis had been performed. The most frequent mutation was heterozygous M694V (10%, n = 23). Extension of between-episode interval following prophylaxis was noted in 85% of those on regular colchicine treatment (n = 303). In the colchicine group, between-episode interval was prolonged from 18.8 ± 7.9 days (before colchicine treatment) to 49.5 ± 17.6 days on prophylactic colchicine therapy; also, prophylactic treatment was more effective in reducing episode frequency in patients with MEFV gene variant (n = 54, 96%) than in those without (n = 122, 80%; P = 0.003). CONCLUSIONS: This study has involved the largest number of PFAPA syndrome patients in the literature. It is particularly important to assess and to demonstrate the high rate of response to colchicine prophylaxis in PFAPA syndrome patients, especially those with MEFV variant. On blood screening, neutrophilia associated with monocytosis and low procalcitonin could contribute to diagnosis.

Copper/zinc and copper/selenium ratios, and oxidative stress as biochemical markers in recurrent aphthous stomatitis.

PROJECT: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disorder characterized by recurrent, painful oral aphthae, and oxidative stress presumably contributes to its pathogenesis. The aim of this study is to scrutinize the relationship between oxidative stress and serum trace elements (copper, Cu; zinc, Zn; selenium, Se), and to evaluate the ratios of Cu/Zn and Cu/Se in this disorder. PROCEDURE: Patients with RAS (n = 33) and age- and sex-matched healthy control subjects (n = 30) were enrolled in this study. Malondialdehyde (MDA) concentrations in plasma and the activities of superoxide dismutase (SOD1; CuZnSOD), glutathione peroxidase (GPx) and catalase (CAT) in erythrocyte were determined as spectrophotometric. Also, the levels of Se, Zn and Cu in serum were determined on flame and furnace atomic absorption spectrophotometer using Zeeman background correction. RESULTS AND CONCLUSIONS: Oxidative stress was confirmed by the significant elevation in plasma MDA, and by the significant decrease in CAT, SOD1, and GPx (p < 0.05). When compared to controls, Zn and Se levels were significantly lower in patients, whereas Cu levels was higher in RAS patients than those in controls (p < 0.05). In addition, the correlation results of this study were firstly shown that there were significant and positive correlations between Se-CAT, Se-GPx, and Cu-MDA parameters, but negative correlations between Se-Cu, Se-MDA, Cu-CAT, Cu-SOD1 and Cu-GPx parameters in RAS patients. Furthermore, the ratios of Cu/Zn and Cu/Se were significantly higher in the patients than the control subjects (p < 0.05). Our results indicated that lipid peroxidation associated with the imbalance of the trace elements seems to play a crucial role in the pathogenesis of RAS. Furthermore, the serum Cu/Zn and Cu/Se ratios may be used as biochemical markers in these patients.

Management of nonsexually acquired genital ulceration using oral and topical corticosteroids followed by doxycycline prophylaxis.

BACKGROUND: Data regarding the treatment of nonsexually acquired genital ulceration (NSAGU) are limited. OBJECTIVE: We sought to provide evidence for the safety and efficacy of topical and systemic corticosteroids followed by doxycycline prophylaxis for acute and recurrent NSAGU. METHODS: A retrospective chart review was conducted of patients with NSAGU treated in a private dermogynecology practice. RESULTS: A total of 26 girls and women with NSAGU were identified and divided into 2 groups: group A = 17 patients with moderate to severe ulceration treated in the acute stage with oral corticosteroid; and group B = 9 patients with mild ulceration treated in the acute stage with topical corticosteroid. Patients in group A, with a mean age of 27.9 years (range, 11-62 years), were treated with oral prednisolone commencing with 15 to 50 mg per day depending on severity. Sixteen (94%) achieved rapid pain relief and complete healing of ulcers within 16 days. Eight (47%) commenced doxycycline prophylaxis. Women in group B, with a mean age of 42.5 years (range, 26-67 years) were treated with topical corticosteroids. Eight (89%) had a history of recurrent ulcers and 6 (66%) commenced doxycycline prophylaxis. Of all 14 patients on doxycycline prophylaxis, none reported any recurrences during a mean follow-up of 18.3 months. There were no adverse effects caused by prednisolone. One patient experienced mild photosensitivity from doxycycline but continued to take it. LIMITATIONS: This was a retrospective case series from a single private practice-based population. CONCLUSION: Topical or oral corticosteroids followed by prophylactic doxycycline can be effective in rapidly resolving acute flareups and preventing recurrences of NSAGU. All patients responded to therapy without treatment-limiting side effects.

[Clinical aspects and treatment of recurrent aphthous ulcers]. / Klinik und Therapie chronisch rezidivierender Aphthen.

Recurrent aphthous ulcers are the most common inflammatory lesions of the oral mucosa, occurring in up to 10% of the population and even more common in children. The history, morphological characteristics, predilection sides and typical stages of aphthae help to distinguish them from other diseases that may exhibit aphthous-like lesions. Underlying diseases should be excluded. The main goals of therapy are to minimize pain and functional disabilities as well as decrease frequency and severity of recurrences. Topical symptomatic relief is the standard of care for simple cases of recurrent aphthosis. In cases of major aphthosis or systemic involvement, topical therapies are still useful but should be combined with systemic therapy, such as colchicine, pentoxifylline or prednisolone. In case of Adamantiades-Behçet disease, systemic immunomodulatory drugs can inhibit the development of new lesions. This overview summarizes morphological and presentation forms of aphthae, differential diagnoses and evidence-based therapeutic possibilities.

Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a painful condition of unknown etiology, affecting more than 2.5 billion people worldwide. Vitamin deficiencies have been implicated as a possible cause. METHODS: The authors conducted a single-center, randomized, parallel-arm, double-masked, placebo-controlled study to examine the effect of daily multivitamin supplementation on the number and duration of RAS episodes. The authors randomly assigned 160 adults who had a validated history of at least three episodes of idiopathic minor RAS within the previous 12 months to one of two groups: the first group (n = 83) received a once-daily multivitamin containing 100 percent of the U.S. reference daily intake (RDI) of essential vitamins, and the second group (n = 77) received once-daily placebo for up to 365 days. RESULTS: The results showed no significant difference in the mean number of new RAS episodes between the multivitamin (4.19 episodes) and placebo (4.60 episodes) arms during the study period (P = .69). The mean duration of new RAS episodes also was similar for the multivitamin (8.66 days) and placebo (8.99 days) arms (P = .60). Furthermore, the authors found no differences between the two arms with regard to mouth pain, normalcy of diet or compliance with the study medication regimen. CONCLUSION: Daily multivitamin supplementation, with the RDI of essential vitamins, did not result in a reduction in the number or duration of RAS episodes. CLINICAL IMPLICATIONS: Clinicians should not recommend multi-vitamin supplementation routinely as prophylaxis for RAS.

From aphthous ulcer to full-blown Crohn's disease.

At onset, Crohn's disease (CD) is characterized by transmural inflammation with mucosal ulcerations. In its earliest phase the lesions are mainly aphthous ulcers. The ulcers then become larger, a nodular pattern develops and penetration of the deep ulcers leads to fistulas and collagen deposition to fibrotic strictures. The best model to study the earliest lesions in CD is the postoperative recurrence situation where these early lesions recur within weeks to months after surgery. CD recurrence is triggered by the fecal contents of the gut since temporary diversion prevents the recurrence of bowel inflammation. With the development of newer techniques, such as microarray analysis of total mucosal gene expression and molecular analysis of gut content and mucosal microbiome, this model will allow to shed light on the earliest pathogenic features of CD.

Clinical evaluation of low-level laser treatment for recurring aphthous stomatitis.

OBJECTIVE: The aim of the present study was to assess the effect of low-level laser on the control of pain and the repair of recurring aphthous stomatitis (RAS). BACKGROUND: One of the most frequent pathologic conditions in the oral cavity is RAS. This multifactor immunologic inflammatory lesion causes patient discomfort, and treatment is controversial because of its unknown etiology. A number of treatment modalities have been proposed, but none is definitive. Low-level laser treatment (LLLT) has been used for lesions of an inflammatory nature, not as an inhibitor of the process, but for its modulating action and reparative effect on tissues. MATERIALS AND METHODS: Twenty patients with RAS were divided into one group treated with a topical corticoid agent (n = 5) and another group treated with laser (n = 15). Group I received conventional treatment with triamcinolone acetonide 4 times per day. The patients in Group II received laser treatment with an InGaA1P diode laser with wavelength of 670 nm, 50 mW, 3 J/cm(2) per point in daily sessions (once per day) on consecutive days. Both treatments were applied until the disappearance of the lesions. All patients were evaluated on a daily basis, and the following clinical parameters were determined during each session: pain intensity before and after treatment and clinical measurement of lesion size. RESULTS: The results revealed that 75% of the patients reported a reduction in pain in the same session after laser treatment, and total regression of the lesion occurred after 4 days. Total regression in the corticoid group was from 5 to 7 days. CONCLUSION: The use of LLLT under the conditions administered in the present study demonstrated analgesic and healing effects with regard to RAS.

Haematological deficiencies in patients with recurrent aphthosis.

BACKGROUND: Recurrent aphthosis is a common oral ulcerative condition consisting also of a subset of similar ulcers, properly named 'aphthous-like' ulcers (ALU), linked to systemic diseases and among these, to iron, folic acid and vitamin B(12) deficiencies. OBJECTIVES: The main objectives of this study were: (i) to evaluate the association between recurrent aphthosis and the most common predisposing factors; (ii) to assess the frequency of ALU in recurrent aphthosis; (iii) to verify the efficacy of a replacement therapy in all ALU patients. METHODS: Thirty-two adults with recurrent aphthosis and 29 otherwise healthy controls were consecutively recruited, interviewed and subjected to haematological investigations. RESULTS: Family history of recurrent aphthosis was significantly associated (P < 0.01). The overall frequency of haematinic deficiencies was 56.2% in recurrent aphthosis patients vs. 7% in controls (P < 0.0001). All ALU patients with a negative family history showed a complete remission of the ulcerative episodes after replacement therapy, while those with a positive family history only had a reduction in frequency and severity. In the logistic regression model, only family history was associated with recurrent aphthosis (P = 0.0137). CONCLUSION: The strong association with familiarity, the unexpected higher frequency of ALU (compared with the idiopathic variant) and the good response to replacement therapy means that familiarity should always be investigated. Furthermore, routine haematological screening and tests for serum iron, folic acid and vitamin B(12) deficiencies should be assessed in all patients with recurrent aphthosis to treat any nutritional deficiency and to prevent more important related systemic manifestations.