Q:

2/1/2019
Can delayed reaction to foods present as aphthous ulcers 2-3 days after ingesting the culprit food? If yes what is the mechanism?
 

A:

The pathogensis of simple aphthous ulcers is unknown although there are theories that the ulcers are related to immune dysregulation (1). There are genetic or environmental predispositions with a greater prevalence in the Mediterranean region, Middle East and Asia. One study suggests genetic polymorphisms of the IL-10 gene, again supporting an immunologic mechanism (2). There is an increased occurrence of aphthous ulcers in certain families, further supporting a genetic contribution. Oral trauma (3) and emotional stress (4) are also associated with the condition. Infectious etiology is not supported with evidence.

There is no evidence that food allergy contributes to this disorder. Some patients report certain foods aggravate the symptoms of existing ulcers, likely from irritation, and some report that foods provoke the lesions. However, there is no evidence that immunologic food reactions are responsible. Vitamin or mineral deficiencies have also been linked with aphthous ulcers, but evidence does not support causality (5).

In summary, recurrent, simple aphthous ulceration is an idiopathic disorder with some suggestions of an immunologic mechanism but the pathogenesis is unknown. There is no evidence of food allergy being related to this condition.

1. Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review.
Slebioda Z, Szponar E, Kowalska A
Arch Immunol Ther Exp (Warsz). 2014;62(3):205. Epub 2013 Nov 12.
Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers; canker sores) belongs to the group of chronic, inflammatory, ulcerative diseases of the oral mucosa. Up to now, the etiopathogenesis of this condition remains unclear; it is, however, considered to be multifactorial. The results of currently performed studies indicate that genetically mediated disturbances of the innate and acquired immunity play an important role in the disease development. Factors that modify the immunologic response in RAS include: food allergies, vitamin and microelement deficiencies, hormonal and gastrointestinal disorders (e.g., celiac disease, Crohn's disease, ulcerative colitis), some viral and bacterial infections, mechanical injuries and stress. In this paper, we presented the main etiopathogenetic factors of RAS with a special emphasis on the mechanisms of the immune response modification. Moreover, we discussed the crucial clinical symptoms and types of RAS together with epidemiologic data based on the current medical literature reports and our own observations.

2. Interleukin-10 gene polymorphisms in recurrent aphthous stomatitis.
Najafi S, Firooze Moqadam I, Mohammadzadeh M, Bidoki AZ, Yousefi H, Farhadi E, Tonekaboni A, Meighani G, Amirzargar AA, Rezaei N
Immunol Invest. 2014;43(4):405. Epub 2014 Feb 24.
Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease with unknown etiology in which the immune system seems to have a role in oral tolerance. Interleukin (IL)-10 is a cytokine synthesis inhibitory factor. Single nucleotide polymorphisms (SNPs) of IL10 gene could alter this cytokine production. The aim of this study was to investigate frequencies of IL10 alleles and genotypes in a group of individuals with RAS. Genomic DNA of 60 Iranian patients with RAS were typed for IL10 gene (C/A -1082, C/T -819, and C/A -592), using PCR-SSP method. Frequency of each allele and genotype was compared to control group. A significantly higher frequencies of the T allele at position -819 (p=0.006) and the A allele at position of -592 (p<0.001) were found in the patients with RAS group, when compared to the controls. IL10 GA genotype at position -1082 (p=0.007), CA genotype at position -592 (p=0.001), and CT genotype at position -819 (p=0.001) were significantly higher in the RAS patients. The results of this study suggest that certain SNPs of IL10 gene have association with predisposition of individuals to RAS. However, further multicenter studies should be conducted to confirm the results of this study.

3. Role of mucosal injury in initiating recurrent aphthous stomatitis.
Wray D, Graykowski EA, Notkins AL
Br Med J (Clin Res Ed). 1981;283(6306):1569.
The buccal mucosa of 30 patients with recurrent aphthous stomatitis and 15 healthy controls was injured by suture and penetration with a tenaculum and a hypodermic needle and each of the six puncture wounds produced monitored for up to seven days for the development of ulcers. Altogether 26 lesions were induced in 13 patients, whereas none occurred in the controls (p less than 0.001). Sutures caused most of the lesions (15), and those so induced had a mean maximum diameter of 2.3 mm and lasted for an average of four days. Ulcers induced mechanically were clinically indistinguishable from those usually seen in the patients, except that they were generally smaller and healed more quickly. These findings confirm that mechanically induced injury of the oral mucosa may cause ulceration in people susceptible to aphthous stomatitis. Such a procedure may therefore be helpful in identifying subsets of patients

4. Stress associated with onset of recurrent aphthous stomatitis.
Keenan AV, Spivakovksy S
Evid Based Dent. 2013;14(1):25.
DESIGN Randomised controlled trial (RCT).
INTERVENTION One hundred and sixty patients participating in a RCT in which they were randomised to multivitamins (n=81) or placebo (n=79) completed ulcer diaries and a weekly telephone survey by calling an automated interactive voice response (IVR) system. Stressful events were quantified using the validated Recent Life Changes Questionnaire (RLCQ) and were classified as mental or physical stressors.
OUTCOME MEASURE Onset and duration of RAS episodes
RESULTS Stressful life events were significantly associated with the onset of RAS episodes (P<0.001), but not with the duration of the RAS episodes. Experiencing a stressful life event increased the odds of an RAS episode by almost three times (OR = 2.72; 95% CI = 2.04-3.62). When controlled for each other, mental stressors had a larger effect (OR = 3.46, 95% CI = 2.54- 4.72) than physical stressors (OR = 1.44; 95% CI = 1.04- 1.99) on the occurrence of RAS episodes. RAS episodes did not occur more frequently or last longer with increasing stress severity.
CONCLUSIONS In patients with a history of RAS, stressful events may mediate changes involved in the initiation of new RAS episodes. Mental stressors are more strongly associated with RAS episodes than physical stressors

5. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial.
Lalla RV, Choquette LE, Feinn RS, Zawistowski H, Latortue MC, Kelly ET, Baccaglini L
J Am Dent Assoc. 2012;143(4):370.
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.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI
 

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