湖南地区口腔黏膜下纤维性变流行趋势变化(附278例回顾性研究)

目的 :观察湖南地区口腔黏膜下纤维性变 (OSF)流行趋势。方法 :对 2 78例OSF患者的年龄、性别、职业、地区来源、咀嚼槟榔时间、频率、主要症状、病变部位、张口度等临床资料进行分析。结果 :OSF患者平均年龄3 4.5岁 ,男女性别比为 94.6∶5 .4,OSF发病以司机、公务员、商人、警察等职业为多 ,湖南各地区都发现OSF患者。OSF患者典型临床表现为黏膜刺激痛、黏膜苍白、张口受限、纤维条索。其它症状有舌功能障碍 ,黏膜水疱、溃疡、烧灼痛等 ,病变部位以口腔后份为主 ,病变部位越靠前 ,范围越广 ,张口度越小 ,病变程度越严重 ( p <0 .0 0 5 ) .结论 :湖南地区OSF流行趋于年轻化 ,以男性为主 ,OSF发病覆盖全省各地区 ,OSF在某些职业中发病率较高 ,OSF患者到医院就诊大多为中晚期 ,临床症状、体征明显 ,病变部位与疾病严重程度 (即张口度 )有明显关系     

An immunohistochemical study of oral submucous fibrosis

Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity characterized by inflammation and progressive mucosal fibrosis. These reactions may be the result of either direct stimulation from exogenous antigens like areca alkaloids or by changes in tissue antigenicity that may lead to an autoimmune response. This study investigated the presence and distribution of inflammatory cells and MHC class II antigen expression by epithelial and immunocompetent cells using a three-stage immunoperoxidase method on frozen sections. Thirty OSF tissue specimens and ten normal buccal mucosae were studied and compared. All tissues were investigated using antibodies to T cells (CD3), T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8), B cells (CD20), naive T cells and monocytes (CD45RA), macrophages. Langerhans' cells (CD68) and HLA-DR-positive cells (HLA-DR alpha). The predominant cell populations detected in normal tissues were CD3, CD4 and HLA-DR-positive cells. The distribution of CD4-positive cells was similar to that of CD3-positive cells, which were scattered, often uniformly distributed, both in the epithelium and connective tissue. CD8-positive cells were occasionally seen in the normal epithelium and lamina propria. Few scattered B cells (CD20) and macrophages (CD681) were observed in normal mucosa. Naive T cells (CD45RA) were seen in all normal tissues focally concentrated around the connective tissue papillae with a similar distribution to that of CD3-positive cells. All normal sections showed HLA-DR-positive cells scattered both in the epithelium and in the lamina propria. Epithelial cells did not show any positive reaction to this antibody and many intraepithelial positive cells showed a dendritic morphology. The cell populations detected in OSF showed higher numbers of CD3 and HLA-DR-positive cells compared with those of the normal tissues. The pattern of staining for CD4-positive cells in OSF tissues was similar to that of CD3-positive cells both in the epithelium and connective tissue and was higher than that in normal tissues. A few scattered CD8-positive cells and only occasional CD20- and CD68-positive cells were seen in OSF sections. Few CD45RA-positive cells were found in the epithelium and lamina propria of OSF sections. However, OSF specimens showed high numbers of HLA-DR-positive cells in the basal layer of the epithelium, juxtaepithelium and in the lamina propria in a similar distribution to that of CD3 cells compared with the normal tissues. Most HLA-DR-positive cells in the epithelium showed dendrites directed vertically towards the surface. The increased evidence of CD4 and HLA-DR-positive cells in OSF tissues suggests that most lymphocytes were activated and shows an increased presence of Langerhans' cells. The presence of these immunocompetent cells and high ratio of CD4 to CD8 in OSF tissues suggest an ongoing cellular immune response leading to a possible imbalance of immunoregulation and alteration in local tissue architecture.     

口腔黏膜下纤维性变的药物治疗进展

由于口腔黏膜下纤维性变(OSF)发病机制复杂,目前尚缺乏特效治疗手段,主要治疗方式仍为药物治疗.本文回顾介绍了近年来国内外临床上治疗OSF的药物种类,并主张根据疾病的病程选择不同的药物治疗.     

Treatment of oral submucous fibrosis by collagenase: effects on oral opening and eating function

OBJECTIVE: Patients with oral submucous fibrosis (OSF) suffer from the limitation of the oral opening. The aim of this study was to develop a simple and rapid method to improve the opening of the oral cavity and determine its effect on the incidence of developing oral carcinoma. METHODS: We first induced an OSF-like lesion in rabbits which histopathologically resembles OSF in betel nut chewers and evaluated the effects of exogenous collagenase on these lesions. We then applied the collagenase treatment regimen to patients with OSF. RESULTS: Endogenous collagenase activities in normal oral mucosa of patients exhibited 3- to 5-fold higher levels than that of OSF tissues. The collagenase treatment not only resulted in a significant improvement of oral opening, but patients also experienced a striking reduction in hypersensitivity to spices, sour, cold, and heat which helped restore eating function. Sub-mucosal fibrous proliferation, persistently good vascularization, and a mild increase in thickness of the sub-mucosal fibrous tissues were noticed 10 months after collagenase treatment. Within the 2-year follow-up period none of the treated patients developed an oral squamous cell carcinoma. CONCLUSION: A reduced content of functional collagenase observed in OSF mucosa of patients might be one mechanism responsible for collagen accumulation. Intervention of OSF by collagenase treatment at the early stage may reduce the incidence of developing oral carcinoma.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性、具有癌变倾向的炎性疾病.患者进食刺激性食物时口内疼痛,口腔黏膜苍白僵硬,触摸有条索感,舌运动、张口受限,以致咀嚼、吞咽困难,有的甚至发生癌变,严重影响患者的生存质量和身心健康.复杂的发病机制导致该病至今尚无满意的治疗方法.本文介绍了目前主要的治疗方法,包括药物治疗、物理治疗和手术治疗等,主张根据病变发展的阶段,采用多种方法联合治疗.     

Current protocols in the management of oral submucous fibrosis: An update

Oral submucous fibrosis (OSMF) is a debilitating condition of oral cavity which has significant potential for malignant transformation. In spite of over 20 years of research, the pathogenesis of the condition is still obscure and no single management modality is effective. Many OSMF treatment protocols have been proposed to alleviate the signs and symptoms of the disorder and there is overwhelming evidence that as areca nut is primary cause, stopping its use may have a considerable effect on symptoms rather than reversing pre‐existing fibrosis. We present a review of the current protocols for managing OSMF.     

Auto-fluorescence spectra of oral submucous fibrosis

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic oral mucosal disease characterized by progressive deposition of collagen in the subepithelial connective tissue and epithelial atrophy. Previous studies have shown that at 330-nm excitation, the 380- and 460-nm emission peaks of the auto-fluorescence spectra for oral mucosal tissues reflect the collagen content in the subepithelial connective tissue and the nicotinamide adenine dinucleotide phosphate (NADH) content in the epithelial cells, respectively. Therefore, at 330-nm excitation OSF mucosa may have a higher 380-nm emission peak and a lower 460-nm emission peak than the normal oral mucosa (NOM). METHODS: To test the above hypothesis, we measured the in vivo auto-fluorescence spectra of 59 OSF mucosal sites and compared the measured spectra with auto-fluorescence spectra obtained from 15 NOM samples from 15 healthy volunteers, five samples of friction hyperkeratosis (histologic diagnosis, hyperkeratosis and acanthosis) on OSF buccal mucosa (FHOSF), and 29 samples of oral leukoplakia (histologic diagnosis, hyperkeratosis and acanthosis) on OSF buccal mucosa (OLOSF). RESULTS: We found that the spectrum of the OSF mucosa had a significantly higher 380-nm emission peak and a significantly lower 460-nm emission peak than the spectra of NOM, FHOSF, and OLOSF samples. When the mean (+/-SD) fluorescence intensities at 380 +/- 15 nm (I380 +/- 15 nm) and 460 +/- 15 nm (I460 +/- 15 nm) emission peaks and the mean ratio of I460 +/- 15 nm/I380 +/- 15 nm were compared between groups, we found that OSF group had a significantly higher mean value of I380 +/- 15 nm, a significantly lower mean value of I460 +/- 15 nm, and a significantly lower mean ratio of I460 +/- 15 nm/I380 +/- 15 nm than the NOM, FHOSF, and OLOSF groups (P < 0.001). However, no significant differences in the mean values of I380 +/- 15 nm, I460 +/- 15 nm, and ratio of I460 +/- 15 nm/I380 +/- 15 nm were found between NOM and FHOSF or OLOSF samples as well as between FHOSF and OLOSF samples (P > 0.05). CONCLUSION: Because OSF mucosa has a very unique pattern of auto-fluorescence spectrum, we conclude that auto-fluorescence spectroscopy is a good method for real-time diagnosis of OSF.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性、具有癌变倾向的口腔黏膜病。本文对OSF的病名来由、病因、发病机制和病变的性质进行了系统的描述。     

HLA-antigens in oral submucous fibrosis

HLA–typing was carried out on 122 areca nut chewers who attended hospitals for complaints unrelated to the habit. The subjects were South Africans of Indian extraction. The study did not include haplotypes. Palpable fibrous bands in the mouth indicated oral submucous fibrosis. The subjects were divided into 4 groups based on specific oral symptoms and signs. Groups A and B were without fibrous bands. Group A (47 subjects) included those with one or no symptoms while group B (28 subjects) suffered from 2 to 7 oral symptoms. Group C (17 subjects) had oral symptoms and represented early or mild oral submucous fibrosis and exhibited at least one discrete palpable fibrous hand. Group D (30 subjects) were classic oral submucous fibrosis cases with multiple bands. The high occurrence of oral submucous fibrosis in this study group (39%) is similar to the occurrence in comparable age groups reported earlier–n South Africa and is conceivably due to the higher age range of the subjects and their relatively long exposure to the area nut. We were unable to demonstrate a specific pattern of HLA–antigen frequencies in chewers with or without the disease. Furthermore, there were no differences between the study population and the controls. It is concluded that there is not necessarily a HLA–associated susceptibility in oral submucous fibrosis.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性且具有癌变倾向的疾病,主要发生于印度、巴基斯坦等东南亚国家以及我国湖南、台湾两省。OSF病因不明,咀嚼槟榔是其最主要的致病因素,且咀嚼槟榔的频率越高、年限越长,越易患OSF。所有OSF患者都有咀嚼槟榔史,咀嚼槟榔还与口腔白斑、口腔癌发病高度相关。此外,OSF的发生还与遗传因素、免疫反应、胶原相关性基因,营养缺乏等有关。本文就OSF致病因素做一简单介绍。     

The fibroblast population in oral submucous fibrosis

The purpose of the investigation was to compare the morphology of fibroblasts cultured from healthy oral mucosa and mucosa of patients with oral submucous fibrosis (OSF) and to collate the occurrence of cell types of similar morphology. Cells cultured from biopsy specimens from the buccal mucosa of six subjects who did not chew the areca nut and six patients with OSF who chewed areca nut were grown according to standard techniques. Ninety cells per cell line were recorded daily for 8 days, classified into types F1, F2 and F3 according to their morphology, and the results statistically analyzed. We found that there was a relative increase of F3 cells in relation to Fl cells in OSF resulting in the ratio of F3 to F1 cells being significantly larger in OSF than the ratio in the controls. As it has been reported that F3 cells m rat connective tissues produce significantly more collagen types I and III than F1 cells, we concluded that a change of fibroblast population has occurred in OSF and that this relative increase of F3 cells in humans, which could be committed to the production of large quantities of collagen, can be an explanation for the excessive collagen formation in OSF.     

口腔黏膜下纤维性变组织中Smad2/3蛋白的表达研究

目的：检测Smad2／3蛋白在13腔黏膜下纤维性变（OSF）组织中的表达及分布,探讨其在OSF发病机制中的作用。方法：采用免疫组化SABC法,用Smad2／3兔抗人多克隆抗体检测20例OSF病变组织及10例正常13腔黏膜组织中的Smad2／3蛋白的表达及分布。结果：Smad2／3在OSF病变组织中为中等强度表达,在正常口腔黏膜组织中为强阳性表达,具有显著性差异（P〈0．05）。结论：Smad2／3蛋白在OSF病变组织中中等强度表达,在OSF发病机制中有重要作用。     

HLA typing in Taiwanese patients with oral submucous fibrosis

BACKGROUND: A significant association of certain human leukocyte antigens (HLA) and haplotypic pairs with oral submucous fibrosis (OSF) has been reported. However, controversial result of no HLA association with OSF has also been reported. In this study, the phenotype and haplotype frequencies of HLA-A, -B, -C, -DRB1, and -DQB1 in 135 Taiwanese OSF patients were calculated and compared with those in 540 healthy control Taiwanese. METHODS: The analysis of HLA-A, -B, and -C antigens, and of HLA-DRB1 and -DQB1 alleles in OSF patients and healthy control subjects, was performed by serologic typing and DNA typing using polymerase chain reaction with sequence-specific primers (PCR-SSP), respectively. RESULTS: We found that the phenotype frequency of HLA-B76 (3.0%) in OSF patients was significantly greater than that (0%) in healthy control subjects (corrected P (Pc) = 0.000). In addition, the haplotype frequencies of HLA-B48/Cw7 (3.0%), -B51/Cw7 (6.7%), and -B62/Cw7 (8.2%) in OSF patients were significantly greater than the corresponding haplotype frequencies (0, 0.7, and 1.9%, respectively) in healthy control subjects (Pc = 0.000). The relative risk (RR) values of haplotypes B51/Cw7 (9.57) and B62/Cw7 (4.7) were greater than the RR values of phenotypes B51 (1.81), B62 (2.31), and Cw7 (1.91) in OSF patients. In addition, the etiologic fraction (EF) value of haplotype B51/Cw7 (0.63) was higher than the EF values of phenotypes B51 (0.2) and Cw7 (0.59). CONCLUSIONS: We conclude that some Taiwanese areca quid (AQ) chewers with particular HLA phenotypes and haplotypes are prone to have OSF. In addition, some particular HLA haplotypes may play more important roles than the individual HLA phenotypes for the genetic susceptibility to OSF. However, the significantly increased HLA phenotype B76 and three of the common HLA haplotypes detected are present in only about 20% of incident cases of OSF.     

High incidence of autoantibodies in Taiwanese patients with oral submucous fibrosis.

BACKGROUND: Previous study has shown a high incidence of autoantibodies including antinuclear (ANA), antismooth muscle (SMA), antigastric parietal cell (GPCA), antithyroid microsomal (TMA), and antireticulin antibodies in a small group of 26 patients with oral submucous fibrosis (OSF). The reasons why some of the OSF patients have high titers of autoantibodies in serum have not been completely explained and no further study on autoantibodies in OSF patients has been done in a large group of patients. METHODS: In this study, we determined the serum levels of ANA, SMA, GPCA, and TMA in a large group of 109 male Taiwanese patients with OSF by an indirect immunofluorescence technique (for ANA, SMA, and GPCA), and by a semiquantitative microtiter particle agglutination test (for TMA). The presence of serum autoantibodies in OSF patients was further correlated with patients' oral habits and the severity of OSF measured by maximum mouth opening (MMO) and sites of involvement. RESULTS: We found that the frequencies of presence of serum ANA (23.9%), SMA (23.9%), and GPCA (14.7%) in OSF patients were significantly higher than those (9.2, 7.3, and 5.5%, respectively) in healthy control subjects (P < 0.01, P < 0.005, and P < 0.05, respectively). Although the frequency of presence of TMA (5.5%) in OSF patients was also greater than that (2.8%) in healthy control subjects, the difference was not significant (P > 0.05). The presence of serum GPCA in OSF patients was significantly associated with daily areca quid (AQ) consumption (P < 0.05). The presence of serum ANA in OSF patients associated with daily AQ consumption was of borderline statistical significance (P = 0.066). However, no significant correlations were demonstrated between the presence of serum autoantibodies in OSF patients and other variables of oral habits, MMO, and sites of involvement. CONCLUSION: In this study, all the 109 OSF patients had AQ chewing habit and 73.4% of the OSF patients swallowed the 'juice' of AQ during the chewing process. The presence of serum GPCA and ANA in OSF patients was associated with daily consumption of AQs. AQ chewing caused mucosal microtrauma, and ulcerations facilitated the diffusion of genotoxic and cytotoxic AQ ingredients into the oral and gastric tissues. Altered autoantigens released from AQ ingredients-damaged cells may induce autoantibody production. Higher frequencies of specific HLA-DR antigens in OSF patients may also help autoantibody production. Therefore, we conclude that the high incidence of autoantibodies in OSF patients may be due to AQ chewing habit, toxic AQ ingredients, and genetic susceptibility of the OSF patients.     

A case-control study of oral submucous fibrosis with special reference to the etiologic role of areca nut

A case-control study to elucidate the etiology of oral submucous fibrosis was conducted in Bhavnagar, Gujarat. Sixty consecutively arriving oral submucous fibrosis patients at a dental clinic were selected as cases. An equal number of controls matched for age, sex, religion and socioeconomic status were selected from individuals who did not exhibit any oral mucosal lesion or condition. Among cases, 98% chewed areca nut regularly in one form or the other whereas among controls 35% chewed areca nut, giving an overall relative risk of 109.6. Areca nut chewing was practiced most commonly in the form of mawa: a mixture containing mainly areca nut (over 90% by weight), some tobacco, and a few drops of lime. Mawa chewers and those who chewed mawa along with other chewing habits showed very high relative risks. The relative risks increased with increase in the frequency as well as the duration of chewing habits. In a bivariate analysis the effect of frequency and duration of chewing appeared to be multiplicative. The present findings confirm areca nut as the most important etiologic factor in oral submucous fibrosis.     

Focal vascular dilatations and petechiae in oral submucous fibrosis

Abstract – The occurrence in oral submucous fibrosis of small raised blue spots has not been reported. This feature was observed in nine (22%) of 40 submucous fibrosis cases diagnosed in the Ernakulam district, Kerala, India. None of the patients complained of bleeding from the spots or from elsewhere, nor was there any history of systemic disorders. Histologically, the lesions could be explained by juxtaepithelial, endorthelial-lined luminae containing erythrocytes and the presence of juxta- and intraepithclial petechial homorrhages.     

Association between lysyl oxidase polymorphisms and oral submucous fibrosis in older male areca chewers

Objective:  Areca use is the major cause for oral squamous cell carcinoma and oral submucous fibrosis (OSF) in South Asians. Lysyl oxidase (LOX) is a copper-activated enzyme critical for collagen cross-linking and organization of extracellular matrix. The presence of a G to A polymorphism at nucleotide 473 caused a non-conservative Arg158Gln change in the LOX amino acid sequence. OSF is a precancerous lesions characterized by the accumulation of collagen in oral submocousa. The aim of this study was to investigate the relationship between LOX Arg158Gln polymorphism and the risk of OSF.
Method:  PCR-restriction fragment length polymorphisms and direct sequencing was utilized to compare LOX polymorphic allelotype in male areca-chewing controls ( n  = 216) and OSF ( n  = 83) patients.
Results:  There was a borderline of statistically significant difference in Arg158Gln genotype lying between control and OSF patients. However, the G/A+A/A of LOX Arg158Gln in OSF patients older than 50 year was statistically significantly higher than controls older than 50 year (odd's ratio: 4.48; 95% CI = 1.58–12.67).
Conclusion:  The elder OSF patients were increased in LOX Arg158Gln. Our findings may suggest a potential application in risk population selection using LOX polymorphism for preventive intervention of OSF genesis in a subset of areca chewers.     

Role of areca nut in the causation of oral submucous fibrosis: a case-control study in Pakistan

A case-control study on chewing and smoking habits and oral submucous fibrosis (OSF) was undertaken in Karachi in 1989/90. Cases were patients detected with fibrous bands and leathery mucosa and hospital-based controls were matched by age and sex. Information on habits was collected by personal interview of 157 cases and 157 controls. Despite overall female preponderance, a substantial number of young men were enlisted. The male/female risks were found to be similar. Immigrants from India to Pakistan (Mohajir) had a similar risk status to local Punjabis. No differences between risks were found when comparing the three age categories. 21.21-40, 41-60 yr. Among the cases, an increased risk was observed for areca nut chewing. This habit when practised alone appeared to have the highest risk (RR 154), followed by pan with or without tobacco (RR 64. 32 respectively). Logistic regression and discriminant analysis showed that daily consumption rates appeared to be more important with respect to risk than lifetime duration of habit. Tobacco habits were more prevalent amongst those 15 cases who presented with concurrent carcinoma and OSF: We conclude that areca nut chewing has a causal relationship with OSF: additional tobacco insult may be necessary for subsequent carcinoma development.