Association between serum zinc levels and recurrent aphthous stomatitis: a meta-analysis with trial sequential analysis

Al‐Maweri, Sadeq Ali; Halboub, Esam; Al-Sharani, Hesham Mohammed; Shamala, Anas; Al-Kamel, Ahlam; Al-Wesabi, Mohammed; Albashari, Abdullkhaleg Ali; Al-Sharani, Amani Abdulhakeem; Abdulrab, Saleem

doi:10.1007/s00784-020-03704-8

Cited by 12 publications

(11 citation statements)

References 26 publications

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“…52,57 A variety of contributing factors, such as genetic, immunological, nutritional, allergic, and systemic disease, have been proposed as potential triggers for the development of aphthous stomatitis. 51,52,[57][58][59][60][61][62][63][64][65] A microbial origin of recurrent aphthous stomatitis has also been explored, but an infectious causation has not been proven. 58,59 Genetic factors contributing to recurrent aphthous stomatitis have been investigated due to the possible hereditary nature of the condition.…”

Section: Pathophysiologymentioning

confidence: 99%

Common Oral Conditions

Stoopler,

Villa,

Bindakhil

et al. 2024

JAMA

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ImportanceDry mouth, oral candidiasis, and recurrent aphthous ulcers are 3 of the most common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity.ObservationsIn a meta-analysis of 26 population-based cohort and cross-sectional studies, the global prevalence of dry mouth symptoms was 23% (95% CI, 18% to 28%), placing individuals at risk of oral candidiasis, dental caries, dysgeusia, masticatory/speech impairment, and oropharyngeal dysphagia. Dry mouth is associated with using more than 3 oral medications per day (odds ratio [OR], 2.9 [95% CI, 1.4 to 6.2]), head and neck radiation, and Sjögren disease. Symptoms may include difficulty swallowing and speaking, thirst, and halitosis. Dry mouth is associated with an 11.5% (95% CI, 3.6% to 27%) higher risk of oral candidiasis, based on a meta-analysis of 6 observational cohorts. Management of dry mouth includes mechanical salivary stimulants, oral moisturizers, and/or systemic sialagogues. Oral candidiasis is an opportunistic fungal infection caused by overgrowth of the Candida genus with C albicans, which accounts for 76.8% of infections. The prevalence of oral candidiasis is higher in patients who are immunosuppressed, for example, those with HIV (35% [95% CI, 28% to 42%]) and those with salivary gland hypofunction (OR, 3.02 [95% CI, 1.73 to 5.28]). Common risk factors associated with oral candidiasis include use of antibiotics (P = .04) and oral mucosal disorders such as lichen planus. Oral burning and dysgeusia are common symptoms of oral candidiasis. Treatment includes addressing risk factors and use of topical and/or systemic antifungal medications. Recurrent aphthous stomatitis is characterized by symptomatic round or oval oral ulcers, which are covered by a gray-white fibrin layer and encircled by an erythematous ring. A meta-analysis of 10 case-controlled studies revealed an increased risk of recurrent aphthous stomatitis associated with polymorphism of IL-1β (+3954C/T) (OR, 1.52 [95% CI, 1.07 to 2.17]) and IL-1β (−511C/T) (OR, 1.35 [95% CI, 1.09 to 1.67]). Another meta-analysis of 9 case-control studies reported that patients with recurrent aphthous stomatitis had a higher frequency of nutritional deficiencies, including vitamin B12 (OR, 3.75 [95% CI, 2.38 to 5.94]), folic acid (OR, 7.55 [95% CI, 3.91 to 14.60]), and ferritin (OR, 2.62 [95% CI, 1.69 to 4.06]). Recurrent aphthous stomatitis can be associated with systemic diseases. A meta-analysis of 21 case-control studies revealed that celiac disease is associated with a higher incidence of recurrent aphthous stomatitis (25% vs 11%; OR, 3.79 [95% CI, 2.67 to 5.39]; P &lt;.001). Topical corticosteroids are first-line agents to manage recurrent aphthous stomatitis; however, systemic medications may be necessary in more severe cases.Conclusions and RelevanceDry mouth, oral candidiasis, and recurrent aphthous ulcers are common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. First-line treatment includes over-the-counter sialagogues for dry mouth, topical antifungals for oral candidiasis, and topical corticosteroids for aphthous ulcers. Oral conditions that do not improve with first-line treatment may require treatment with systemic medications.

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Section: Pathophysiologymentioning

confidence: 99%

Common Oral Conditions

Stoopler,

Villa,

Bindakhil

et al. 2024

JAMA

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“…Despite the extensive research on the topic, the exact etiopathogenesis of RAS is still unclear, 3 yet the existing evidence suggests an immunological background 3 . Reported predisposing factors include, but are not limited to, psychological stress, trauma, genetic factors, immunological dysfunction, and nutritional and hematological deficiencies 4 …”

Section: Introductionmentioning

confidence: 99%

“…3 Reported predisposing factors include, but are not limited to, psychological stress, trauma, genetic factors, immunological dysfunction, and nutritional and hematological deficiencies. 4 Currently, there is no specific therapy for RAS; the main aim of RAS management is basically to control the symptoms (pain and discomfort) and reduce the healing time. 5,6 Various topical preparations have been used for the management of RAS; these include corticosteroids, antibiotics (such as tetracycline mouth rinse and doxycycline gel), local anesthetics (such as lidocaine), herbal agents (such as aloe vera and curcumin), and hyaluronic acid, among others.…”

Section: Introductionmentioning

confidence: 99%

Topical medications for the treatment of recurrent aphthous stomatitis: A network meta‐analysis

Mashrah,

Fang,

Song

et al. 2023

J Oral Pathology Medicine

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BackgroundThe present network meta‐analysis aims to answer the question “what is the best topical intervention for the treatment of recurrent aphthous stomatitis that can provide an acceptable pain relief and promote wound healing?”MethodsFrom inception to October 2022, PubMed, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure were searched to identify all potentially eligible randomized controlled trials. The primary outcomes were pain scores and/or healing time, while the secondary outcomes were the associated side effects. The Bayesian network meta‐analysis accompanied by a random effect model and 95% credible intervals were calculated.ResultsForty‐three randomized controlled trials with a total of 3067 participants, comparing 20 different topical medications, were included. Concerning pain reduction, the network meta‐analysis failed to show any statistically significant differences when different topical treatments were compared together or even with a placebo at different time intervals. Except for doxycycline, which showed a statistically significant difference in terms of accelerating healing time, other topical interventions showed no statistically significant differences when compared with placebo or with each other.ConclusionWithin the limitations of the current network meta‐analysis, it seems that: A low to moderate quality of evidence showed no superiority of any topical treatment over others concerning pain reduction, although rank probability tests revealed sucralfate, doxycycline, hyaluronic acid, and chamomile as the most efficacious treatment options at different evaluation times. Hence, further well‐designed clinical trials with larger sample sizes are warranted. Topical doxycycline was shown to be the most efficacious intervention in promoting healing of recurrent aphthous stomatitis.

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“…Some traditional treatments such as freezing [19] and cautery [20] have a positive effect on cell metabolism and tissue regeneration which are still heavily used in some areas. Low serum zinc levels have also been shown to be a risk factor for RAS in numerous studies [21]; hence, topical zinc supplementation is also recommended. In addition, some natural extracts such as curcumin [22], glycyrrhiza [23], honey [24], quercetin [25], chitosan [26], aloe [27], berberine gelatin [28], diosmectite [29], allicin [30] and other extracts have been shown in some studies to be promising topical interventions for ulcers.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Topical Intervention for Recurrent Aphthous Stomatitis: A Network Meta-Analysis

Líu

Tan

et al. 2022

Medicina

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Background and objectives: To compare the efficacy and safety of topical interventions used for recurrent aphthous stomatitis. Materials and Methods: This network meta-analysis was conducted in accordance with the PRISMA statement. We searched four electronic databases, PubMed, Web of Science (WOS), Cochrane Central Register of Controlled Trials and Embase, for randomized controlled trials reporting efficacy and safety data on topical interventions for recurrent aphthous stomatitis. We performed a quality evaluation using a methodology based on the Cochrane Handbook. Two authors independently extracted data on healing effect, size reduction effect, symptom reduction effect, recurrence and safety assessment. Network meta-analysis was then performed using ADDIS and RevMan. Results: A total of 72 trials (5272 subjects) involving 29 topical interventions were included. Honey, lnsulin liposome gel, laser, amlexanox, glycyrrhiza and triamcinolone had better efficacy performance. Probiotics and chlorhexidine helped to prolong ulcer intervals and reduce recurrence. Doxycycline and penicillin had a high risk of adverse events. Hematologic evaluation showed no preference. The rank possibility of size-reducing effect and symptom-reducing effect supported the short-term effect of laser and the long-term effect of probiotics. Conclusions: We recommend the use of laser as a short-term intervention during the exacerbation phase of RAS and probiotics as a long-term intervention during the exacerbation and remission phases of RAS.

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Association between serum zinc levels and recurrent aphthous stomatitis: a meta-analysis with trial sequential analysis

Cited by 12 publications

References 26 publications

Common Oral Conditions

Common Oral Conditions

Topical medications for the treatment of recurrent aphthous stomatitis: A network meta‐analysis

Efficacy of Topical Intervention for Recurrent Aphthous Stomatitis: A Network Meta-Analysis

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