Risk factors for recurrent aphthous stomatitis: a systematic review / Factores de riesgo para la estomatitis aftosa recurrente: revisión sistemática

SUMMARY: The cause and prevention of recurrent aphthous stomatitis (also called aphthous ulcers or canker sores) are still unknown. This may be due in part to ignorance of the risk factors present in susceptible people. In this systematic review (PROSPERO record #CRD42019122214), we show that most of the risk factors for the disease are single nucleotide genetic polymorphisms in genes related to the functioning of immune system (TLR4, MMP9, E-selectin, IL-1 beta and TNF-alpha). Single nucleotide genetic polymorphisms do not constitute a modifiable risk. This indicates that, at least in part, susceptibility to recurrent aphthous stomatitis is hereditary, and that these factors cannot be modified.

RESUMEN: Aún se desconoce la causa y cómo prevenir la estomatitis aftosa recurrente (más conocida como aftas). En esta revisión sistemática (registro PROSPERO #CRD42019122214) mostramos que la mayoría de los factores de riesgo para la enfermedad son polimorfismos genéticos de un solo nucleótido en genes relacionados con el funcionamiento del sistema inmune (TLR4, MMP9, E- selectin, IL-1 beta y TNF-alfa). Los polimorfismos genéticos de un solo nucleótido no constituyen un riesgo modificable.Ello indica que, al menos en parte, la susceptibilidad para las aftas es hereditaria y que esos factores no pueden ser modificados.

Clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: an analysis of 13 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis.@*METHODS@#A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome.@*RESULTS@#All 13 children had disease onset within the age of 3 years, with a mean age of onset of (14±10) months. They all had periodic fever, with 8-18 attacks each year. The mean interictal period of fever was (30±5) days. Pharyngitis, cervical adenitis, and aphthous stomatitis were the three cardinal symptoms, with incidence rates of 100% (13/13), 85% (11/13), and 38% (5/13) respectively. There were increases in white blood cells, C-reactive protein, and erythrocyte sedimentation rate during fever. Of all the 13 children, 6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease, and the results showed single heterozygous mutations in the @*CONCLUSIONS@#For children with unexplained periodic fever with early onset accompanied by pharyngitis, cervical adenitis, aphthous stomatitis, elevated inflammatory indices, and good response to glucocorticoids, PFAPA syndrome should be considered. This disorder has good prognosis, and early diagnosis can avoid the long-term repeated use of antibiotics.

Immune system and zinc are associated with recurrent aphthous stomatitis: an assessment using a network-based approach

OBJECTIVE: The aim of this research was to identify genes, proteins and processes from the biomedical information published on recurrent aphthous stomatitis (RAS) using network-based foci. METHODS: The clinical context was defined using MeSH terms for RAS and biomarkers, combined with words associated with risk. A set of protein coding genes was prioritized using the Génie web server and classified with PANTHER. For defining biologically relevant proteins, protein-protein interaction networks were constructed using Reactome database and Cytoscape. Top 20 proteins were then subjected to functional enrichment using STRING. RESULTS: From 1,075,576 gene-abstract links, 1,491 genes were prioritized. Proteins were related to signaling molecule proteins (n=221), receptor proteins (n=221) and nucleic acid binding proteins (n=169). The network constructed with these proteins included 3,963 nodes and functional analysis showed that main processes involved immune system and zinc ion binding function. CONCLUSIONS: For the first time, bioinformatics tools were used for integrating pathways and networks associated with RAS. Molecules and processes associated with immune system recur robustly in all analyzed information. The molecular zinc ion binding function could be an area for exploring more specific and effective therapeutic interventions

Utility of dermatoglyphics as a non-invasive diagnostic tool inrecurrent aphthous stomatitis / Utilidade da dermatoglifia como ferramenta diagnóstica não invasivapara estomatite aftosa recorrente

Introduction: Dermatoglyphics is an advancing branch of medical science in which the dermal ridge patterns are studied and used in prediction of genetic disorders. Objective: To assess the usefulness of dermatoglyphics, as a non-invasive early predicator in RAS, since genetics plays a role in both. Materials and methods: This case control study comprised of 40 patients with recurrent aphthous stomatitis compared to 30 control subjects of similar age and sex. All subjects were investigated for their dermatoglyphic patterns of both hands, which were obtained by smearing the ink uniformly over the palm and fingers and pressing the hands firmly against the good quality paper. Qualitative analysis of prints was done for arches, loops and whorls and quantitative analysis included Total Finger Ridge Count (TFRC) and atd angle. Fisher’s Exact Tests were used to evaluate the significance between recurrent aphthous stomatitis and the dermatoglyphic features. Results: Among various dermatoglyphic parameters analyzed, recurrent aphthous stomatitis patients showed 9% arches, 62% loops and 29% whorls as the finger ridge configuration. In comparing the results between the two groups, the frequency of arches was observed more in study group while composite whorl and the nar pattern were more frequent in control group, the results were statistically significant (p < 0.05). In addition to this, study group patients demonstrated higher frequency of total finger ridge count, and control group showed higher frequency for atd angle on both hands, statistically significant difference is observed (p < 0.05). Conclusion: The study found significant correlation between palmar dermatoglyphics and recurrent aphthous stomatitis, suggesting that genetics is one of the host risk factor associated with the latter, and could aid in early detection of the disease.

Introdução: Dermatoglifia é um avançado ramo da ciência médica em que os padrões de cristas dérmicas são estudados e utilizados para predizer distúrbios genéticos. Objetivo: Avaliar a utilidade da dermatoglifia, como método de diagnóstico não invasivo para a estomatite aftosa recorrente, uma vez que a genética desempenha um papel em ambos. Materiais e métodos: Estudo caso-controle composto por 40 pacientes com estomatite aftosa recorrente comparados a 30 controles de mesma idade e sexo. Todos os sujeitos foram avaliados quanto a seus padrões dermatóglifos de ambas as mãos. Os padrões dermatóglifos foram obtidos espalhando uniformemente uma tinta sobre a palma da mão e os dedos e pressionada firmemente contra um papel de boa qualidade. A análise qualitativa das impressões foi feita por arcos, laços e espirais e a análise quantitativa pela contagem total da polpa do dedo (TFRC) e ângulo atd. Teste de Fischer foi utilizado para avaliar a significância entre estomatites recorrentes e características dermatoglíficas. Resultados: Entre os vários parâmetros dermatoglíficos analisados, os pacientes com estomatite aftosa recorrente mostraram 9% de arcos, 62% de laços e 29% de espirais na configuração da polpa digital. Ao comparar os resultados entre os dois grupos, a frequência de arcos foi mais observada no grupo de estudo, enquanto verticilos e padrão tênar foram mais frequentes no grupo controle, com resultados estatisticamente significativos (p < 0,05). Além disso, os pacientes do grupo de estudo demonstraram maior frequência de contagem total da polpa digital e o grupo controle apresentou maior frequência para o ângulo atd em ambas as mãos, com diferenças estatisticamente significativas (p < 0,05). Conclusão: O estudo encontrou correlação significativa entre a dermatoglifia palmar e estomatites recorrentes, sugerindo que a genética é um dos fatores de risco de hospedeiro associado com estomatite aftosa recorrente, e poderia ajudar na detecção precoce da doença.

Correlation between histocompatibility antigens and recurrent aphthous stomatitis in the brazilian population / Estudo da associação entre antígenos de histocompatibilidade e estomatite aftoide recorrente em população brasileira

Recurrent aphthous stomatitis is a common oral mucosa disorder that affects 20 percent of the world's population, characterized by recurring painful ulcers in the mouth. The diagnosis is primarily based on the patient's clinical history. Inheritance may pose as a risk factor for the disease; however, the studies available are inconclusive as to the results attained, and they vary according to the population studied. AIM: to typify class I and class II HLA molecules and to assess how frequent these molecules are present in the Brazilian population with Recurrent Aphthous Stomatitis, compared to healthy controls. MATERIALS AND METHODS: In this prospective, cross-sectional and investigative study, thirty one patients with diagnostic hypothesis of recurrent aphthous stomatitis were seen from February of 2004 to May of 2006. We obtained the DNA from those patients who matched the inclusion criteria and typified their HLA by PCR. RESULTS: In those patients with Recurrent Minor Aphthous Stomatitis we found statistically significant occurrences of HLA-A33 and HLA-B35. CONCLUSION: HLA-A33 and HLA-B35 may be associated with recurrent minor aphthous stomatitis in the Brazilian's population.

A Estomatite Aftoide Recorrente é uma doença oral com incidência em 20 por cento da população mundial, caracterizada por úlceras mucosas de caráter recidivante. O diagnóstico baseiase principalmente na história clínica do paciente. Hereditariedade pode ser um fator de risco para doença, entretanto, os estudos disponíveis não são conclusivos quanto aos resultados obtidos, variando segundo a população estudada. OBJETIVO: Tipificar moléculas HLA de classe I e de classe II e avaliar a frequência destas moléculas em pacientes brasileiros, portadores de Estomatite Aftoide Recorrente, comparando com grupo controle. MATERIAL E MÉTODO: Este trabalho possui um desenho prospectivo, transverso e investigativo. Foram estudados 31 pacientes com suspeita diagnóstica de Estomatite Aftoide Recorrente no período de fevereiro de 2004 a maio de 2006. Os pacientes foram submetidos a protocolo de exames e, daqueles que obedeceram aos critérios de inclusão, foi extraído o DNA e realizada a tipificação HLA por Reação de Polimerização em Cadeia. RESULTADO: Nos pacientes portadores de Estomatite Aftoide Recorrente do tipo minor encontramos as frequências HLA A33 e B35 estatisticamente significantes. CONCLUSÃO: As frequências HLA-A33 e HLA-B35 podem estar associadas à Estomatite Aftoide Recorrente minor na população brasileira.

Estudio clínico epidemiológico en aftas recidivantes bucales / A clinical and epidemiological study of recurrent oral aphthae

Se realizó un estudio epidemiológico en 119 pacientes que concurrieron al Servicio de Estomatología del CEMIC, con historia y diagnóstico de aftas recidivantes. Se evaluó el aspecto clínico, tamaño, localización, inicio, tiempo de evolución, historia familiar, factores generales (alt. hemáticas, hormonales, gastrointestinales), factores locales (sepsis y trauma). Si bien el factor local se hallaba presente en un 85 por ciento de los casos, los factores de orden general se presentaban concomitantemente con los mismos. La detección temprana de alteraciones orgánicas a través de esta patología resulta beneficiosa no sólo por el control de la misma, sino también por e diagnóstico precoz de las afecciones generales en ocasiones desconocidas por el paciente