Oral Mucositis in Children with Leukemia Undergoing Chemotherapy: A Case Series

ABSTRACT Objective: To report nine cases of pediatric patients with Acute Lymphoid Leukemia (ALL) or Acute Myeloid Leukemia who developed severe oral mucositis (SOM) at the first week of chemotherapy. Material and Methods: The cases were selected from a sample of 105 children followed for 10 consecutive weeks. Hematological and personal data were obtained from the patient's medical records. The oral cavity was examined weekly using the modified Oral Assessment Guide. Results: More of the patients were male (55.6%), had black/brown skin (55.6%), with ALL (66.7%), and the mean age was 5.55. Two patients had values below normal for leukocytes, platelets, and creatinine over the follow-up. However, all patients showed changes in the normality of hematological data in most weeks. The most used chemotherapeutic agents were aracytin, etoposide, and methotrexate, known for their high stomatotoxic potential. Patients had 2 to 6 (mean of 4) episodes of SOM and 4 to 7 (mean of 5.5) episodes of OM. One patient at week 7, one patient at week 5, and one patient at weeks 2 and 10 did not have OM. Saliva (84 times) and lips (44 times) were the most affected items. Conclusion: The patients showed oscillations in the severity of oral mucositis and hematological parameters over the follow-up. All patients were exposed to stomatotoxic drugs during the initial phase of cancer treatment.

Curcuma longa extract protects against 5-fluorouracil-induced oral mucositis in hamsters

Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1ß and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (p˂0.05), and decreased IL-1ß (p˂0.05) and TNF-α (p˂0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.

Estudo comparativo do uso do gel de própolis e da geleia real no tratamento da mucosite oral induzida quimicamente? Estudo experimental in vivo / Comparative study of the use of propolis gel and royal jelly in the treatment of chemically induced oral mucositis? In vivo experimental study

Objetivo: Avaliar os efeitos da própolis(P) e da geleia real(GR) em comparação a terapia de fotobiomodulação (FBM) com laser de baixa intensidadeem um modelo animal de mucosite oral (MO) quimioinduzida por 5-fluorouracil (5-FU). Adicionalmente, verificar por meio de uma revisão sistemática da literatura o efeito da fitoterapia no tratamento da MO quimioinduzida 5-FU em modelo animal. Material e Métodos: Trata-se de um estudo in vivo, experimental, controlado e cego. Setenta e dois ratos Wistar foram distribuídos aleatoriamente em quatro grupos (n = 18): controle (C) (sem tratamento), terapia de fotobiomodulação (FBM) (laser intraoral 6 J/cm2 ), gel de própolis (P) e geleia real (GR). Nos dias 0 e 2, os animais receberam uma injeção intraperitoneal de 5-FU. Nos dias 3 e 4, a mucosa bucal foi escarificada. As terapias foram iniciadas no dia 5. Seis animais por grupo foram eutanasiados nos dias 8, 10 e 14. A análise fitoquímica da própolis e da geleia real foi realizada por Cromatografia em Camada Delgada (CCD). As análises clínica e histopatológica (baseada nos escores de reepitelização e inflamação) foram realizadas por fotografias e lâminas coradas em Hematoxilina e Eosina, respectivamente. Os estudos imuno-histoquímicos (pAKT, p-S6 e NFκB) e do estresse oxidativo (Superóxido Dismutase-SOD, Glutationa reduzida-GSH e Malonaldeído-MDA) foram realizados.Em seguida, uma busca sistemática da literatura foi realizada por meio da pesquisa nas bases de dados PubMed/Medline, CENTRAL (The Cochrane Library), EMBASE e Web of Science, a partir dos registros iniciais até janeiro de 2020. Resultados: A análise da CCD revelou à presença de compostos como terpenos, saponinas, óleos essenciais e flavonoides no P e de alta quantidade de sacarose (Rf 0,34) na RG. Nos dias 8 e 10, os animais dos grupos FBM, P e GR apresentaram melhora clínica da MO e cicatrização acelerada com menores escores morfológicos, aumento da imunoexpressão das proteínas pS6 (exceto no dia 10), pAKT (ANOVA e teste de Tukey; p <0,05) e fator de transcrição NF-kB (teste de Mann Whitney; p <0,05) quando comparados ao grupo controle. No dia 14, o grupo P aumentou os níveis do antioxidante GSH quando comparado ao grupo controle (ANOVA e teste de Tukey; p <0,05). Treze artigos foram incluídos na revisão sistemática da literatura (todos utilizando o 5-FU para indução de MO em animais), de um total de 503 artigos. A formulação dos tratamentos variou de aplicação tópica de pomada, gel e extrato, até a ingestão de fitoterápicos. Todas as pesquisas investigadas exibiram resultados promissores no uso de fitoterápicos no manejo da MO. Conclusões: Nossos resultados evidenciaram que a P e a GR, assim como a FBM, são terapias eficazes no tratamento da MO. A presença de açúcares na GR e de flavonoides, terpenos e óleos essenciais na P justifica a excelente ação cicatrizante de feridas e seus efeitos antiinflamatórios. Adicionalmente, o grupo P, exibiu redução do estresse oxidativo tecidual, em comparação aos grupos FBM, GR e controle.Nas 13 pesquisas avaliadas, pôde-se observar excelentes resultados na cicatrização tecidual, ação antiinflamatória, antimicrobiana e antioxidante, com o uso de fitoterápicos no tratamento da MO. Diante disso, pode-se sugerir que o uso de fitoterápicos é uma alternativa promissora no tratamento da MO quimioinduzida (AU).

Objective: To evaluate the effects of propolis (P) and royal jelly (RJ) compared to photobiomodulation therapy (PBMT) with low intensity laser in an animal model of oral mucositis (OM) chemically induced by 5-fluorouracil (5-FU). Additionally, to verify by means of a systematic review of the literature the effect of phytotherapy in the treatment of chemoinduced OM 5-FU in an animal model. Material and Methods: This is an in vivo, experimental, controlled and blind study. Seventy-two male and female Wistar rats were randomly assigned to four groups (n = 18): control (C) (without treatment), photobiomodulation therapy (PBMT) (6 J / cm2 intraoral laser), propolis gel (P) and royal jelly (RJ). On days 0 and 2, the animals received an intraperitoneal injection of 5-FU. On days 3 and 4, the oral mucosa was scarified. Therapies were started on day 5. Six animals per group were euthanized on days 8, 10 and 14. Phytochemical analysis of P and RJ were performed by Thin Layer Chromatography (TLC). The clinical analysis was performed using photographs and the histopathological evaluation (hematoxylin / eosin) was based on the reepithelization and inflammation scores. Immunohistochemical studies (pAKT, p-S6 and NFκB) and oxidative stress (Superoxide Dismutase-SOD, Glutathione reduced-GSH and Malonaldehyde-MDA) were performed. Then, a systematic search of the literature was performed, by searching the PubMed / Medline, CENTRAL (The Cochrane Library), EMBASE and Web of Science databases, from the initial records until January 2020). Results: The TLC analysis revealed the presence of compounds such as terpenes, saponins, essential oils and flavonoids in P and a high amount of sucrose (Rf 0.34) in RJ. On days 8 and 10, animals in the PBMT, P and RJ groups showed clinical improvement of OM and accelerated healing with lower morphological scores, increased immunoexpression of pS6 proteins (except on day 10), pAKT (p <0.05, ANOVA and Tukey test) and NF-kB transcription factor (Mann Whitney test; p <0.05) when compared to the control group. On day 14, the P group increased the levels of the antioxidant GSH when compared to the control group (p <0.05, ANOVA and Tukey's test). Thirteen articles were included in the systematic literature review (all using the 5-FU to induce OM in animals), out of a total of 503 articles. The formulation of treatments ranged from topical application of ointment, gel and extract, to the intake of herbal medicines. All investigations showed promising results in the use of herbal medicines in the management of OM. Conclusions: Our results showed that P and RJ, as well as PBMT, are effective therapies in the treatment of OM. The presence of sugars in RJ and flavonoids, terpenes and essential oils in P justifies the excellent wound healing action and its anti-inflammatory effects. In addition, the P group exhibited a reduction in tissue oxidative stress compared to the PBMT, RJ and control groups. In the 13 studies evaluated, it was possible to observe excellent results in tissue healing, antiinflammatory, antimicrobial and antioxidant action with the use of herbal medicines in the treatment of OM. Therefore, it can be suggested that the use of herbal medicines is a promising alternative in the treatment of chemically induced OM (AU).

Efeitos anti-inflamatório e antioxidante do extrato da folha de Spondias mombin em modelo experimental de mucosite oral / Anti-inflammatory and antioxidant effects of Spondias mombin leaf extract in an experimental model of oral mucositis

A Mucosite Oral (MO) caracteriza-se como uma condição inflamatória que se apresenta clinicamente como áreas eritematosas e ulceradas. É a complicação oral mais frequente nos pacientes sob quimioterapia e/ou radioterapia de cabeça e pescoço, e seu tratamento visa aliviar a sintomatologia dolorosa e induzir o processo de reparo da lesão. Spondias mombin é uma planta bastante utilizada no nordeste do Brasil e suas folhas são usadas na medicina popular para o tratamento de infecções orais e faríngeas. Objetivo: Avaliar os potenciais antioxidante e anti-inflamatório do extrato hidroetanólico da folha de Spondias mombin (HESM) em modelo experimental de mucosite oral. Metodologia: Foi realizado um ensaio pré-clínico, in vivo, cego, randomizado e controlado. A amostra foi composta por 42 hamsters machos, distribuídos em 6 grupos: Salina (S), Trauma mecânico (TM), 5-fluorouracil/Trauma mecânico (5-FU/TM) e experimentais do HESM nas doses de 50, 100 e 200 mg/kg, administrados diariamente, por dez dias. Os animais foram submetidos a análises bioquímicas e as amostras de bolsas da mucosa jugal foram submetidas a análises macroscópicas, histopatológicas e imuno-histoquímicas, com os marcadores Cox-2, iNOS, NF-kB p50 NLS e MMP-2. Os níveis de IL-1ß e TNF-α foram analisados por imunorreação ELISA e os níveis de estimativa de superóxido dismutase (SOD), glutationa (GSH) e malondialdeído (MDA) foram submetidos à análise espectroscópica. Resultados: O grupo tratado com HESM na dose de 200 mg/kg apresentou o melhor efeito cicatrizante, não mostrando evidência de ulceração na análise macroscópica (p <0,05). A análise histopatológica desse grupo mostrou reepitelização, infiltrado inflamatório mononuclear discreto e ausência de escore de hemorragia e edema de 1 (1-1) (p <0,05), além de uma grande quantidade de fibras colágenas. Imunoexpressão reduzida de Cox-2, iNOS , NF-kB p50 NLS e MMP-2; diminuição nos níveis de SOD (p <0,05), MDA (p <0,001), IL-1ß (p <0,05) e TNF-α (p <0,001); e aumento nos níveis de GSH (p <0,01) também foram observados nesse mesmo grupo. Conclusão: O HESM (200 mg / kg) reduziu o estresse oxidativo e a inflamação na mucosite oral induzida por 5-fluorouracil em hamsters (AU).

Oral mucositis (MO) is characterized as an inflammatory condition for clinically presenting erythematous and ulcerated areas. It is the most common oral complication in patients undergoing chemotherapy and / or head and neck radiation therapy, and its treatment aims to relieve painful symptoms and induce the injury repair process. Spondias mombin is a plant widely used in northeastern Brazil and its leaves are used in folk medicine to for the treatment of oral and pharyngeal infections. Aim: To evaluate the antioxidant and antiinflammatory potentials of the hydroethanolic extract of the leaf of Spondias mombin (HESM) in an experimental model of oral mucositis. Methods: A pre-clinical, in vivo, blind, randomized and controlled trial was performed. The sample consisted of 42 male hamsters, divided into 6 groups: Saline (S), Mechanical trauma (TM), 5 fluorouracil / Mechanical trauma (5-FU / TM) and experimental HESM doses of 50, 100 and 200 mg / kg, administered daily, for ten days. The animals were submitted to biochemical analyzes and the samples of pouches of the cheek mucosa were subjected to macroscopic, histopathological and immunohistochemical analyzes, with Cox-2, iNOS, NF-kB p50 NLS and MMP-2 markers. The levels of IL-1ß and TNF-α were analyzed by ELISA immunoreaction and the levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were submitted to spectroscopic analysis. Results: The HESM-treated group at a dose of 200 mg / kg showed the best healing effect, showing no evidence of ulceration in macroscopic analysis (p <0.05). Histopathological analysis of this group showed reepithelialization, a mild mononuclear inflammatory infiltrate and absence of a bleeding and edema score of 1 (1-1) (p <0.05), in addition to a large amount of collagen fibers. Reduced immunoexpression of Cox-2, iNOS, NF-kB p50 NLS and MMP-2; decreased levels of SOD (p <0.05), MDA (p <0.001), IL-1ß (p <0.05) and TNF-α (p <0.001); and an increase in GSH levels (p <0.01) were also observed in this same group. Conclusion: HESM (200 mg / kg) reduced oxidative stress and inflammation in oral mucositis induced by 5-fluorouracil in hamsters (AU).

Geographic stomatitis with palate involvement

Abstract: Benign migratory glossitis or geographic tongue is a benign condition that usually manifests as asymptomatic erythematous and migratory circinate patches, involving the lateral and dorsal aspects of the tongue. Extra-lingual lesions uncommonly occur and are mainly located on labial and buccal mucosae, lips and floor of the mouth. The present report describes one patient with a geographic lesion on the hard palate associated with lingual lesions and another patient who had multiple geographic lesions both in the hard and soft palate without lingual lesions. We found 64 cases in the English literature of ectopic locations with 22 palate involvement. No case of simultaneous involvement of the hard and the soft palate was found.

Avaliação das atividades anti-inflamatórias e antioxidantes da gliclazida em modelo experimental de mucosite oral induzida por 5-fluorouracil / Evaluation of the anti-inflammatory and antioxidant activities of gliclazide in an experimental model of oral mucositis induced by 5-fluorouracil

A mucosite oral (MO) é uma inflamação aguda da mucosa oral, sequela mais importante dos tratamentos de radioterapia ou/e quimioterapia. As lesões na cavidade oral são graves, dolorosas e podem levar a sepse e morte. Não existe um protocolo único de prevenção e cura para MO. Na perspectiva de encontrar terapias farmacológicas para prevenir MO, propomos a investigação do efeito pleiotrópico do medicamento comercial gliclazida, um anti-diabético de ação secundária anti-inflamatória e antioxidante nunca estudada na MO. Este estudo teve como objetivo avaliar o efeito da gliclazida em um modelo MO experimental induzido por 5-fluorouracil. Hamsters machos foram pré-tratados com gliclazida oral (1, 5 ou 10mg/kg) por 10 dias. As amostras das mucosas dos animais foram submetidas à análise macroscópica, histopatológica e imuno-histoquímica (COX2, iNOS, MMP-2, NFκB P65, GPx) e imunofluorescência (P-selectina). Os níveis de IL-1ß e TNF-α, a atividade de mieloperoxidase (MPO) e os níveis de malondialdeído (MDA) foram investigados por análise espectroscópica ultravioleta-visível. A expressão protéica de NFκB NLS P50 foram analisados por western blotting. O grupo tratado com gliclazida na dose de 10 mg / kg apresentou melhores resultados como ; presença de eritema, ausência de erosão e de ulceração da mucosa com escore de 1 (1-2) (p <0,01) nos achados clínicos. Os dados histopatológicos do grupo tratado com gliclazida 10 mg / kg mostraram reepitelização, discreto infiltrado inflamatório mononuclear, úlceras com escore de 1 (1-1) (p <0,01). O tratamento com gliclazida 10 mg/kg reduziram os níveis de atividade de MPO (p <0,001), MDA (p <0,001) e NFκB NLS P50 (p <0,05), resultando em baixa imunocoloração para Cox-2, iNOS (p <0,05) , NFκB P65 (p <0,05) e imunorreacção negativa para MMP-2 (p <0,001).Para Gpx, a coloração foi menos intensa no grupo GLI 10-FUT em comparação com 5FUT/solução salina (p <0,05). A Imunofluorescência revelou diminuição dos níveis de P-selectina (p <0,001) após o tratamento com gliclazida 10 mg/kg (p <0,05). A gliclazida na dose de 10mg/kg atenuou a severidade da MO e reduziu o estresse oxidativo e a inflamação na MO induzida pelo 5-FU em hamsters (AU).

Oral mucositis (OM) is acute inflammation of the oral mucosa, the most important sequelae from radiotherapy and/or chemotherapy treatments. The lesions in the oral cavity are severe and painful, and can lead to sepsis and death. There is no single protocol for preventing or curing OM. From the perspective of finding pharmacological therapies to prevent OM, we propose an investigation of the pleiotropic effect of commercial drugs, among them gliclazide, an anti-diabetic with anti-inflammatory and anti-oxidant side action which has never studied regarding OM. This study aimed to evaluate the effect of gliclazide on an experimental OM model induced by 5-fluorouracil. Male hamsters were pretreated with oral gliclazide (1, 5 or 10 mg/kg) for 10 days. The mucosal samples of the animals were submitted to histopathological and immunohistochemical analysis (COX2, iNOS, MMP-2, NFκB P65, GPx) and immunofluorescence (P-selectin). Levels of IL-1ß and TNF-α, myeloperoxidase activity (MPO) and malondialdehyde levels (MDA) were investigated by ultraviolet-visible spectroscopic analysis. Protein expression of NFkB NLS P50 was analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg presented erythema, absence of erosion and mucosal ulceration with a score of 1 (1-2) (p <0.01) in the clinical findings. The histopathological data of the gliclazide 10 mg/kg group showed reepithelialization, a discrete mononuclear inflammatory infiltrate, and ulcers with a score of 1 (1-1) (p <0.01). Treatment with 10 mg/kg gliclazide reduced the activity levels of MPO (p <0.001), MDA (p <0.001) and NFκB NLS P50 (p <0.05), resulting in low immunostaining for Cox-2, iNOS (p <0.05), NFκB P65 (p <0.05) and negative immunoreaction for MMP-2. For Gpx, staining was restored in the GLI 10-FUT group compared to 5FUT/saline (p <0.05). Immunofluorescence showed a decrease in P-selectin levels (p <0.001) after treatment with 10 mg/kg gliclazide (p <0.05). Furthermore, 10 mg/kg gliclazide attenuated OM severity and reduced oxidative stress, and 5-FU induced OM in hamsters (AU).

Amifostine reduces inflammation and protects against 5-fluorouracil-induced oral mucositis and hyposalivation

Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.

Periodontal disease, peri-implant disease and levels of salivary biomarkers IL-1ß, IL-10, RANK, OPG, MMP-2, TGF-ß and TNF-α: follow-up over 5 years

Abstract Objective The aim of this study was to evaluate the levels of salivary biomarkers IL-1β, IL-10, RANK, OPG, MMP-2, TG-β and TNF-α in individuals with diagnosis of peri-implant mucositis in the absence or presence of periodontal and peri-implant maintenance therapy (TMPP) over 5 years. Material and Methods Eighty individuals diagnosed with peri-implant mucositis were divided into two groups: one group that underwent periodontal and peri-implant regularly maintenance therapy, called GTP (n=39), and a second group that received no regular maintenance GNTP (n=41). Each participant underwent a complete periodontal and peri-implant clinical examination. Collection of saliva samples and radiographic examination to evaluate peri-implant bone levels were conducted at two times: initial examination (T1) and after 5 years (T2). The salivary samples were evaluated through ELISA for the following markers: IL-1β, IL-10, RANK, OPG, MMP-2, TGF and TNF-α. Results A higher incidence of peri-implantitis was observed in the GNTP group (43.9%) than in the GTP group (18%) (p=0.000). All individuals (n=12) who presented peri-implant mucositis and had resolution at T2 were in the GTP group. After 5 years, there was an increase in the incidence of periodontitis in the GNTP group compared to the GTP group (p=0.001). The results of the study revealed an increase in the salivary concentration of TNF-α in the GNTP group compared to the GTP group. The other salivary biomarkers that were evaluated did not show statistically significant differences between the two groups. Conclusions The salivary concentration of TNF-α was increased in individuals with worse periodontal and peri-implant clinical condition and in those with a higher incidence of peri-implantitis, especially in the GNTP group. Longitudinal studies in larger populations are needed to confirm these findings and elucidate the role of this biomarker in peri-implant disease.

Measurement of oral health quality of life among patients who underwent haematopoietic stem-cell transplantation

Abstract Oral mucositis is a painful condition that occurs in patients who have undergone haematopoietic stem-cell transplantation (HSCT) and has a huge impact on their quality of life. The objective of this study was to examine the extent to which interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) are associated with oral health quality of life among patients who underwent HSCT. A. C. Camargo Cancer Center patients were evaluated over 20 months at 4 different time-points: a) at patient admission (M1); b) on the day of infusion of HSC (M2); c) 12 and 20 days after the first day of the conditioning regimen for autologous and allogeneic transplantation, respectively (M3); and d) 30 days after the first day of the conditioning regimen (M4). Mucositis clinical evaluations were performed using World Health Organization (WHO) criteria. Oral health quality of life was measured using the Oral Health Impact Profile short form (OHIP-14), Oral Mucositis Quality of Life (OMQoL) and Patient-Reported Oral Mucositis Symptom (PROMS) scales. Correlations between clinical data and quality of life scores were examined. STATA 11.0 was used to perform the statistical analyses (5% level of significance). Eighty-two patients participated in the study; 62.2% were male, 28.05% had multiple myeloma, and the mean age was 48.49 years (SD 13.76). Higher scores (worse quality of life) were observed as mucositis scores increased, but the results were not significant. The OMQoL had a high correlation with OHIP-14 (0.8377), but the correlation between the PROMS scale and the OHIP-14 was lower (0.6643). Higher concentrations of IL-6 and TNF-α were associated with worse quality of life, according to all indices (p < 0.05). Oral mucositis was associated with quality of life scores (p < 0.01).

Motor Alterations Favor the Occurrence of Oral Mucositis in Pediatric Oncology Patients

Objective: To identify the predictive factors for the appearance of oral mucositis (OM) in pediatric oncology patients based on their motor alterations. Material and Methods: This study was an observational, cross-sectional study with 2-19-year-old patients undergoing treatment at the pediatric oncology outpatient service of the Napoleão Laureano Hospital in João Pessoa, Brazil. The convenience sample consisted of 42 patients aged 2 to 19 years with a first diagnosis of cancer and under treatment. The instruments used were a questionnaire with sociodemographic questions - the modified Oral Assessment Guide (OAG) - and some categories of the International Classification of Functioning Disability and Health (CIF), applied by a calibrated examiner (Kappa>0.65). The data were organized in Excel spreadsheet and analyzed descriptively and inferentially using logistic regression (α=5%). Results: Most patients were female (52.4%, n=22), mean age of 11.6 years, median 12.0 years, self-declared as non-white (61.9%, n=26), non-white (66.7%, n=28), family monthly income of up to 2 Brazilian minimum wages (88.1%, n = 37). Most patients presented hematologic neoplasia (54.8%, n=23) with acute lymphoid leukemia (36.6%; n=15) and most of them were subjected to chemotherapy (45.2%; n = 19). OAG identified oral mucositis in a few cases (23.8%, n=10). Logistic regression and odds ratio showed that individuals with moderate and mild difficulty in changing basic body position had, respectively, 19.7 and 30.8 times more chances of developing oral mucositis. In patients with severe motor impairment, this risk is 17.3 times greater and those with mild difficulty in taking care of the bodily parts had an increase of 33.4 times the risk for oral mucositis. Conclusion: The deficit in motor activities increased the chances of developing oral mucositis.

Probiotic therapy reduces inflammation and improves intestinal morphology in rats with induced oral mucositis

Abstract The aim of the present study was to evaluate the effect of systemic administration of probiotics (PROB) on the progression of experimentally induced oral and intestinal mucositis in rats immunosuppressed by chemotherapy (5-fluorouracil: 5-FU). Twenty-four rats were divided into the following groups (n=6): GC (control), GPROB, G5FU and G5-FU/PROB. Groups GPROB and G5-FU/PROB received 1 g of probiotic incorporated into each 100 g of feed (Bacillus subtilis, Bifidobacterium bifidum, Enterococcus faecium and Lactobacilllus acidophilus), beginning 30 days before oral mucositis induction. Groups G5FU and G5-FU/PROB received 60 mg/kg of 5-FU on days 0 and 2. The left oral mucosa of each animal was irritated by mechanical trauma (days 1 and 2). On days 3 and 7, three animals from each group were sacrificed, and their oral mucosa and small intestine were biopsied and processed for histopathological analysis. Groups G5-FU and G5-FU/PROB showed ulcerated oral lesions at day 3, with progression in group G5-FU and regression in group G5-FU/PROB at day 7. Histologically, less severe signs of inflammation in the oral mucosa were observed in group G5-FU/PROB than in group G5-FU. Regarding the intestine, villus-related defects of lesser magnitude were observed in group G5-FU/PROB, compared with group G5-FU. Group GPROB showed greater villus height than group GC. It can be concluded that probiotic supplementation reduced oral and intestinal inflammation in immunosuppressed rats with experimentally induced mucositis, and may protect the intestine from changes induced by chemotherapy, thus contributing to overall health.

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate

ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.

Serious stomatitis and esophagitis: a peculiar mucous reaction induced by pegylated liposomal doxorubicin

Pegylated liposomal doxorubicin is an important antineoplastic agent with activity in a variety of solid tumors. It has a totally different profile of pharmacokinetics and toxicity compared with doxorubicin. It rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in many kinds of mucocutaneous reactions, including palmar-plantar erythrodysesthesia, diffuse follicular rash, intertrigo-like eruption, new formation of melanotic macules, stomatitis and radiation recall dermatitis. We present a rare case of multiple myeloma who immediately developed serious stomatitis and esophatitis associated with minor palmar-plantar erythrodysesthesia after a single course of pegylated liposomal doxorubicin.

New drugs, new challenges for dermatologists: mucocutaneous ulcers secondary to everolimus

Everolimus, a mammalian target of rapamycin inhibitor, is an emerging drug, which is being increasingly applied in oncology and solid organ transplantation. Oral ulcers are a frequent side effect associated with this immunosupressor. We report the case of a renal transplant recipient who developed disfiguring oral and perianal ulcers secondary to everolimus's toxicity. This is probably the first report of perianal involvement. Dermatologists need to be aware of the potential mucocutaneous adverse effects related to these new drugs that are becoming evermore common in our clinical practice.

Effect of laser phototherapy in the prevention and treatment of chemo-induced mucositis in hamsters

The aim of this study was to investigate the effect of laser phototherapy (LPT) in the prevention and/or treatment of oral mucositis induced by 5-fluorouracil (5-FU; Eurofarma, São Paulo, Brazil) in hamsters. Ninety-six hamsters were divided into four groups (n = 24): Control (no treatment); Preventive [LPT from day (D) D-5 to D+5]; Therapeutic (LPT from D+5 to D+15); and Combined (preventive plus therapeutic LPT from D-5 to D+15). The animals received an intraperitoneal injection of 5-FU on Days 0 and 2. The pouch mucosa was scratched on Days 3 and 4. The irradiation parameters were: indium-gallium-aluminum-phosphide (InGaAlP) diode laser (MM Optics, São Carlos, Brazil) (660 nm), beam area of 0.036 cm2, 40 mW, 1.11 W/cm2, 6.6 J/cm2, power density applied daily of 39.6 J/cm2, in punctual mode (six points and six seconds per point) and contact mode, one application per day. The animals were sacrificed on Days 0, 5, 10 and 15 (n = 6) and weighed, and the pouch mucosa was removed for histopathological analysis. Clinical and corresponding histological scores were compared using ANOVA and Tukey's test (p ≤0.05). Similar weight losses ranging from 5% to 10% occurred in all groups. The therapeutic group had significantly lower clinical and histological scores than the other groups at Day 10. This study showed that positive effects on oral mucositis management were obtained only when LPT was applied in the therapeutic protocol (from D+5 to D+15 after chemotherapy).

Case for diagnosis / Caso para diagnóstico

Pyodermatitis-pyostomatitis vegetans is a rare mucocutaneous dermatosis characterized by pustular and vegetating lesions of the skin and oral mucosa. It is considered a highly specific marker for inflammatory bowel diseases. The authors describe a case of pyodermatitis-pyostomatitis vegetans in a pediatric patient who presented marked clinical improvement after beginning treatment with oral corticosteroids, azathioprine, and dapsone. Bowel surveillance is mandatory, since the dermatosis is associated with inflammatory bowel diseases in more than 70% of patients, especially ulcerative colitis.

A piodermatite-pioestomatite vegetante é uma dermatose mucocutânea rara, caracterizada por lesões pustulosas e vegetantes na pele e mucosa oral. É considerada um marcador altamente específico para doenças intestinais inflamatórias. Os autores descrevem um caso de piodermatite-pioestomatite vegetante em paciente pediátrico, o qual apresentou boa resposta a corticoterapia oral associada à azatioprina e à dapsona. A vigilância intestinal é mandatória, uma vez que a dermatose está associada a doenças intestinais inflamatórias em mais de 70% dos casos, especialmente a colite ulcerativa.

Oral lichenoid lesions: Clinico-pathological mimicry and its diagnostic implications.

Oral cavity is commonly affected by number of lichenoid lesions, whose clinical and histopathologic features overlap due to the presence of inflammatory cells in connective tissue. Segregation of these lichenoid lesions is mandatory as each may embody a distinct disease entity in terms of cause, diagnosis and prognosis. The literature discussed in the article is an attempt to segregate individual lichenoid lesions by defining clinical and histopathologic variations among each other, which avoids the diagnostic problem.

Piodermatite-pioestomatite vegetante: relato de caso e revisão de literatura / Pyodermatitis-pyostomatitis vegetans: case report and review of medical literarture

A piodermatite-pioestomatite vegetante é uma rara dermatose inflamatória de etiologia desconhecida, com típico comprometimento mucocutâneo. Relatamos caso de paciente feminina com lesões pustulosas e vesiculosas em axilas, evoluindo com placas vegetantes e pústulas com agrupamento anular. Houve progressão com comprometimento vulvar, inguinal e mucosas oral, nasal e ocular. Proposto o diagnóstico, optou-se por iniciar prednisona 40mg ao dia, com remissão das lesões após um mês de uso da medicação. A associação com doença inflamatória intestinal ocorre em 70 por cento dos casos. A imunofluorescência é um fator que ajuda a caracterizar a doença, sendo tipicamente negativa. A rápida resposta à terapêutica com corticosteroides sistêmicos é esperada.

Pyodermatitis-pyostomatitis vegetans is a rare inflammatory dermatosis of unknown etiology, with a typical mucocutaneous involvement. We report the case of a woman with pustular and vesicular lesions in the axillae, evolving with vegetating plaques and pustules with annular grouping. The disease progressed with vulvar and inguinal involvement as well as involvement of the oral, nasal and ocular mucous membranes. She started the treatment with prednisone (40 mg/day), with remission of the lesions after one month of use of such medication. Association with inflammatory bowel disease occurs in 70 percent of the cases. Immunofluorescence, which is typically negative, helps to characterize the disease. A rapid response to systemic steroids is expected.

Mucosite oral: perspectivas atuais na prevenção e tratamento / Oral mucositis: recent perspectives on prevention and treatment

A mucosite oral é resultante de toxicidade e um dos efeitos colaterais mais comuns da radioterapia e da quimioterapia, no tratamento oncológico e para o transplante de células tronco hematopoiéticas. Clinicamente estas alterações se caracterizam por atrofia epitelial, edema, eritema e pelo aparecimento de ulcerações, que podem acometer toda a mucosa bucal, gerando dor e desconforto, prejudicando a fala, a deglutição e a alimentação. Além da importante sintomatologia, as ulcerações aumentam o risco de infecção local e sistêmica, comprometem a função oral e interferem no tratamento antineoplásico, podendo levar à sua interrupção. O diagnóstico, prevenção e estratégias terapêuticas de suporte à mucosite oral são de competência do cirurgião-dentista. Através de análise crítica da literatura, o presente trabalho busca apresentar a mucosite oral, sua etiopatogenia, características clínicas e tratamentos propostos nos dias atuais para a sua resolução ou controle, destacando a importância da atuação do cirurgião-dentista no manejo desta entidade.

Oral mucositis is a result of toxicity and one of the most common side effects of radiotherapy and chemotherapy in cancer treatment and in hematopoietic stem cell transplantation. Clinically these changes are characterized by epithelial atrophy, edema, erythema and the appearance of ulcerations that can affect the entire oral mucosa, causing pain and discomfort, impairing speech, and swallowing food. In addition to the major symptoms, the ulcers increase the risk of local and systemic infection, compromising function and interfering with oral antineoplastic treatment and may lead to it being discontinued. The diagnosis, prevention and therapeutic strategies in providing support in cases of oral mucositis are the dentist's responsibility. Through critical analysis of literature, the aim of this article is to present oral mucositis, its pathogenesis, clinical features and treatments offered today to address or control the condition, highlighting the importance of dentist's role in its management.