Thalidomide in the Management of Recurrent Aphthous Ulcerations in Patients Who fire HIV-Positive: A Review and Case Reporst

Recurrent Aphthous Ulceration (RAU) is an inflammatory ulcerative disease of unknown etiology. Although RAU are common in the general population, people with HIV disease may have ulcers that are large and painful and take a long time to heal. Local and systemic steroid therapy has been the traditional method of treatment for recurrent lesions. Recent studies have shown that systemic thalidomide therapy has the best efficacy in the treatment of major RAU in HIV‐seropositive patients. Two case histories of complete resolution of the RAU are presented. We have included recommended guidelines for prescribing thalidomide according to the System for Thalidomide Education and Prescribing Safety (STEPS) Program.     

Oral mucosal leishmaniasis as a presenting feature of HIV infection and its management

Leishmaniasis is a chronic parasitic protozoal disease transmitted by sandfly vectors and is endemic in some regions of South America, Asia, Africa and Mediterranean countries. This case report describes a British patient who presented with oral mucosal leishmaniasis and in whom it was also the first sign of HIV disease. We believe it is the first reported case of isolated oral mucosal leishmaniasis as a presenting feature of otherwise unknown HIV infection.     

Innate immunity including epithelial and nonspecific host factors: workshop 1B

The majority of HIV infections are initiated at mucosal sites. The oral mucosal tissue has been shown to be a potential route of entry in humans and primates. Whereas HIV RNA, proviral DNA, and infected cells are detected in the oral mucosa and saliva of infected individuals, it appears that the oral mucosa is not permissive for efficient HIV replication and therefore may differ in susceptibility to infection when compared to other mucosal sites. Since there is no definitive information regarding the fate of the HIV virion in mucosal epithelium, there is a pressing need to understand what occurs when the virus is in contact with this tissue, what mechanisms are in play to determine the outcome, and to what degree the mechanisms and outcomes differ between mucosal sites. Workshop 1B tackled 5 important questions to define current knowledge about epithelial cell-derived innate immune agents, commensal and endogenous pathogens, and epithelial cells and cells of the adaptive immune system and how they contribute to dissemination or resistance to HIV infection. Discovering factors that explain the differential susceptibility and resistance to HIV infection in mucosal sites will allow for the identification and development of novel protective strategies.     

Salivary and mucosal immune responses to HIV and its co-pathogens

The profound effects that HIV induces in systemic immunity have been well characterised, but the situation with regard to mucosal immune responses is less clear. Oral cavity fluids have been used as a marker of the mucosal immune system. Whole and parotid saliva IgA, IgA1 and IgA2 concentrations have been found to be lower in both HIV infection and AIDS subjects, whereas serum IgA and IgA subclasses are markedly raised, suggesting a dichotomy between systemic and secretory immunity. Salivary antibodies to HIV can be readily detected and secretory IgA antibody can be neutralising to some strains of HIV. HIV vaccines can also induce antibody responses in saliva, but vaccination routes other than parenteral immunisation are needed. Antibody responses to oral microbes have also been studied and it has been shown that IgA, IgA1 and IgA2 subclass antibody titres to Candida albicans and to Streptococcus mut-ans are increased in whole or parotid saliva from HIV patients, but reduced in AIDS patients, suggesting a compensatory response which is overcome with progressive immunodeficiency. The avidity of salivary IgA antibodies to Candida in HIV seems unimpaired, whereas relative avidities of serum antibodies in HIV patients with candidiasis are lowered. Non-specific factors which may inhibit Candida and other opportunist pathogens are also found in saliva. The candidacidal, myelomonocytic protein calprotectin is present in saliva at levels which are biologically active, although levels are lowered in HIV infection. Overall, HIV infection appears to be associated with disregulation of a number of immune factors at the mucosal surface, but the ability of patients with HIV infection to mount specific antibody secretory responses seems to be relatively intact until late in infection.     

原发灶不明的颈部转移癌的放射治疗：选择性黏膜腔照射是否临床获益？

目的： 探讨对原发灶不明的颈部转移癌患者行黏膜腔预防性照射是否有临床获益。方法： 收集2009年1月—2016年4月接受放疗的所有原发灶不明的颈部转移癌患者的临床资料，采用SPSS 20.0软件包中的Kaplan-Meier法进行生存分析和Log-rank法检验。结果： 62例患者纳入研究，中位随访时间为63个月（5 ~126个月）。选择性黏膜腔照射组和单纯颈部处理组5年黏膜控制率分别为100%和72.0%（P=0.003），5年颈部控制率分别为92.9%和57.7%（P=0.002）。单纯颈部处理组有7例（26.9%）出现原发肿瘤，2组之间在晚期毒性方面无显著差异。结论： 选择性黏膜腔照射有助于在原发灶不明的颈部转移癌患者中寻找一种疗效和毒性之间可能的平衡，但仍需要长期随访的前瞻性研究给出更好的答案。     

口腔艾滋病的临床及研究进展

目的 被誉为世纪恶魔的艾滋病正在全球肆虐。根据国家最新资料,我国于1985年首次发现艾滋病病人。截止今年6月底,全国累计报告艾滋病病毒感染者26085例,其中艾滋病病人1111例,死亡584例。据专家估计,至2000年底,全国实际艾滋病病毒感染者已超过60万人,这不能不引起广大医务工作者,包括口腔医务工作者的高度警惕和重视。本文介绍了与艾滋病毒感染有关的主要口腔粘膜损害、交叉感染途径及治疗原则,旨在帮助口腔医务工作者对艾滋病的临床及研究进展有一个正确的认识。     

沙利度胺在口腔黏膜病临床治疗实践中的安全性分析

沙利度胺诞生至今已经超过60年,目前广泛应用于炎症性疾病和自身免疫性疾病的治疗,包括多种口腔黏膜疾病的治疗。由于沙利度胺曾造成严重的致畸不良事件,所以较多医生对其在临床具体应用过程中的安全性尚存在一些疑问和顾虑。本文通过回顾分析有关沙利度胺的药物代谢动力学、药物作用机制以及临床治疗试验研究的文献,着重探讨沙利度胺的药物安全性、对育龄期患者的影响以及对儿童患者的影响等问题,以期为口腔黏膜病科医生提供更为全面的信息,确保其安全有效的应用。     

Thalidomide for the treatment of recalcitrant oral Crohn's disease and orofacial granulomatosis

It has been suggested that thalidomide may be effective in the management of Crohn's disease, including the associated oral lesions. We detail the clinical response to low-dose thalidomide of 5 patients with clinical features of orofacial granulomatosis or oral Crohn's disease recalcitrant to recognized immunosuppressant therapy. All patients had clinical resolution of their symptoms and signs. Transient somnolence was the only reported adverse effect. Remission was maintained by extending the period between thalidomide doses. Thalidomide should be considered an effective therapy for the short-term treatment of severe orofacial granulomatosis in appropriately counseled patients.     

HIV infection and specific mucosal immunity: workshop 4B

Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues-namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.     

Changes in the prevalence of HIV-associated mucosal disease at a dedicated clinic over 7 years

OBJECTIVE: To investigate changes in the prevalence of mucosal disease in patients with HIV/AIDS. DESIGN: Retrospective analysis of clinic database. SETTING: An open-access dental clinic dedicated to the dental treatment of patients infected with HIV in London, UK. SUBJECTS: Dental patients attending for routine assessment (check-up). MAIN OUTCOME MEASURES: Prevalence of HIV associated oral lesions, diagnosed in accordance with EC classification criteria, in patients taking and not taking antiretroviral therapies (ARTs). RESULTS: Data were collected at 2789 dental examinations for 1590 patients between 1992 and 1998. More patients taking ART had one or more oral manifestations in the years up to 1996, after which the prevalence fell to a similar level to those not taking medications. The prevalence of mucosal disease in patients not taking ART was relatively constant over time. These trends were observed for oral hairy leukoplakia, pseudomembranous and erythematous candidiasis and Kaposi's sarcoma but not for oral papillomata. CONCLUSIONS: These data provide evidence that decreases in the prevalence of oral disease in people with HIV infection can be attributed to the effectiveness of ART.     

A topical imiquimod-induced oral mucosal lichenoid reaction: A case report

Background.Imiquimod (IMI) is a topical immune response modifier used in the treatment of actinic keratosis and cheilitis. Actinic cheilitis is a potentially premalignant condition that requires therapeutic intervention. IMI therapy is noted for producing cutaneous and mucosal adverse effects. The authors report the case of an 88-year-old woman who was treated for actinic cheilitis of the upper lip with IMI and who consequently experienced an oral mucosal lichenoid reaction of the lower lip and right buccal mucosa.Results.The patient was treated successfully with high-dose steroid therapy, and the oral lesions resolved in 17 days.Conclusions.To our knowledge, this is the first case report regarding an IMI-induced oral mucosal lichenoid reaction. Clinicians should be aware of the potential of IMI to cause lichenoid reactions.Practical Implications.IMI is an efficacious therapeutic agent when used in the treatment of actinic cheilitis, but it is prone to cause oral mucosal side effects such as lichenoid reactions. Therefore, it is important for dentists to be knowledgeable concerning potential mucosal IMI side effects.     

Oral mucosal Langerhans'' cells as target, effector and vector in HIV infection

The mechanism underlying a transition of the oral cavity mucosal epithelium towards susceptibility to opportunistic infections in HIV-seropositive patients was investigated. Phenotypic markers CD1a, HLA-DR, and CD86 of oral mucosal Langerhans' cells (LCs), p17 core protein of human immunodeficiency virus (HIV), and CD45RO of memory T cells were labeled on oral hairy leukoplakia lesional biopsies and clinically normal autologous tissue of HIV-infected patients. HIV p17 protein was detected in association with mucosal LCs, mainly within the lesional epithelium. There were significant correlations between the detection of HIV p17 and the depletion of LCs, and between the depletion of LCs and the presence of hairy leukoplakia lesions. Conjugates of activated LCs and memory T cells were also evident in the submucosal area of lesional biopsies. The findings from this study support the hypothesis that oral mucosal LCs are also the target of HIV infection. Cytopathic changes of LCs caused by productive HIV infection may contribute to selective depletion of LCs, which may impair the mucosal immunologic protection against colonization by microorganisms causing HIV-associated oral mucosal lesions.     

The effects of HIV infection on oral mucosal immunity

Oral mucosal infections, especially candidiasis, are a feature of HIV disease, suggesting that compromised mucosal immunity within the oral cavity is a consequence of the viral infection. However, how this mucosal immunity is compromised and at what stage of HIV infection this occurs are unclear. Better understanding of the protection of the oral cavity against infection has allowed us to gain some insight into the local consequences of HIV infection. From a humoral perpective, IgA2 subclasses are reduced in HIV infection in saliva, and total secretory IgA levels are reduced in later disease. Similarly, mucosal antibody responses appear near normal in early HIV infection but reduced in AIDS. There is now convincing evidence that salivary IgA can be neutralizing to HIV 1 and HIV 2, as well as block epithelial transmigration. Oral cellular immunity is also affected by HIV infection. Transmission of HIV from one oral cell type to another appears to be confirmed by work showing that HIV can bind to or infect epithelial cells, Langerhans cells, and other mucosal cells. CXCR4 tropic (via GalCer and CXCR4) and dual tropic HIV strains have been shown to be able to infect normal human oral keratinocytes (NHOKs), and infectious HIV virions can also be conveyed from NHOKs to activated peripheral blood lymphocytes, suggesting a potential role of oral epithelial cells in the transmission of HIV infection. There is evidence of up-regulation of various receptors, including HIV receptors, on the surface of oral epithelium, and the epithelium may become more permeable. HIV may exploit this antigen uptake mechanism to cross epithelial barriers during co-infection with damage-inducing pathogens such as Candida. Immune responsiveness to many of the co-pathogens associated with HIV has been demonstrated to depend on a family of innate recognition molecules, known as Toll-like receptors (TLR), and recognition of a single pathogen can involve activation of multiple TLRs. Consequently, TLR-pathogen interactions could play an indirect but major role in regulating HIV-associated disease in the oral cavity. Thus, HIV infection appears to have both direct and indirect effects on oral mucosal immunity, affecting both cellular and humoral immunity as well as both specific and innate immunity.     

72例HIV/AIDS口腔病损的临床观察

目的：分析HIV感染者和AIDS患者常见口腔病损,以期提高临床医师对AIDS早期临床表现的认识,提高早期诊断准确性。方法：回顾分析72例HIV／AIDS患者临床症状、体征和实验室检查,分析口腔病损在AIDS早期诊断中的意义及与病程进展的关系。结果：常见口腔病变有：口腔白色念珠菌病、疱疹性口炎、非特异性口腔溃疡,其它病损如颌面部淋巴结炎、毛状白斑、卡波济肉瘤、带状疱疹、涎腺肿大,牙周病等,可单发或同时伴发。全身系统性疾病主要包括：肺炎、慢性腹泻、结核等。结论：AIDS患者发病前已开始出现明显口腔表现,其中以口腔白色念珠菌感染最为常见,对非法采供血、输血、静脉吸毒或不安全性行为等特殊人群,如出现难以治愈的”霉菌性口炎”或反复发作、原因不明的疱疹性口炎,或出现毛状白斑、卡波济肉瘤等口腔病变,应及时进行HIV检测。     

New approaches to Candida and oral mycotic infections: Workshop 2A

This workshop reviewed aspects of the following: oral fungal disease in HIV-infected patients and the predictive value of oral mucosal disease in HIV progression; the role of the oral biofilms in mucosal disease; microbial virulence factors and the pseudomembranous oral mucosal disease process; the role that oral mucosal disease may have in HIV transmission; and the available topical antifungal treatment. This article summarizes the ensuing discussions and raises pertinent problems and potential research directions associated with oral fungal disease in HIV-infected patients, including the frequency of oral candidosis, the role of the intraoral biofilm in the development of oral mucosal disease, and host-pathogen interactions, as well as the development of the fetal oral mucosa, neonatal nutrition, and the role of oral candidosis in this setting. Finally, discussions are summarized on the use of inexpensive effective antifungal mouthwashes in resource-poor countries, the potential stigmata that may be associated with their use, as well as novel topical medications that may have clinical applicability in managing oral candidal infections in HIV-infected patients.     

Gender differences in characteristics, infection control practices, knowledge and attitudes related to HIV among Ontario dentists

Abstract We surveyed 5,997 dentists in Ontario to investigate gender differences in the characteristics, infection control practices, knowledge and attitudes regarding the treatment of HIV-infected patients. The response rate was 70.3%. Reports indicated that female dentists are younger and more likely to work in larger urban centres (P<0.00001), and in general practice (P<0.0001) than their male counterparts. Multiple logistic regression analyses indicated that many significant gender differences in the univariate analyses could be explained by the confounding influence of age, practice location, and specialty; however, some differences remain significant: Women were more likely than men to report attending continuing education dealing with HIV/AIDS in the past two years (P<0.001), and to use masks and eye protection (P<0.00001). Men reported more economic concerns than women: they were more concerned about the financial burden of infection control costs (P<0.00001), and losing patients from their practice if it is known that they treat patients with HIV (P<0.05). However, there were no significant differences in willingness to provide treatment for patients with HIV. We conclude that there is little evidence to show that access to oral care for patients with HIV is affected by gender differences.     

Prevalence of oral mucosal lesions in adults undergoing highly active antiretroviral therapy in Hong Kong

Aim:  Highly active antiretroviral therapy (HAART) has altered the prevalence and incidence of oral mucosal lesions of HIV infection. Recent reports show a variation in the prevalence of oral mucosal lesions in different population groups. Understanding the prevalence of these lesions is of paramount importance in the efficient delivery of dental care to such cohorts. The aim of the present study was to investigate the prevalence of oral mucosal lesions and salivary parameters during HAART in an ethnic Chinese cohort in Hong Kong. Methods: A cross‐sectional estimation of the prevalence of oral mucosal lesions was carried out in 101 HIV‐infected ethnic Chinese in Hong Kong using the European Community–Clearinghouse classification. Results: The prevalence of oral mucosal lesions was more common in patients who were classified at baseline as Centers for Disease Control (CDC) C3 category than CDC A2, A3, B2, and B3 (P < 0.05). An overall prevalence of 1.98% was observed for oral Kaposi’s sarcoma. Additionally, the HIV group on HAART (0.37 ± 0.23 mL/min) had significantly lower salivary flow rates (P < 0.01) compared with the healthy group (0.49 ± 0.15 mL/min). Conclusions: Although HAART appears to markedly reduce the prevalence of oral mucosal lesions during the course of HIV disease, regular systematic oral screening is still warranted for such populations for the early diagnosis and management of pathologies, such as Kaposi’s sarcoma.     

Necrotising ulcerative gingivitis/periodontitis as indicators of HIV-infection.

Necrotising ulcerative gingivitis/periodontitis (NUG/NUP) are well-documented oral manifestations of HIV infection/AIDS. However, no information is available regarding the predictive value of NUG in the diagnosis of HIV-infection in South Africa. OBJECTIVES: The purpose of this study was to determine a possible correlation between NUG/NUP and HIV infection in the as yet undiagnosed patients. METHODS: Eighty-six systemically asymptomatic patients were diagnosed with NUG/NUP. All patients were treated with 400 mg of metronidazole and 500 mg paracetamol, three times a day for five days. Mechanical debridement under local anesthesia was performed five days after the initial consultation. The possible involvement of HIV-infection was explained and patients were advised to have a blood test taken. RESULTS: Fifty-six patients consented and received pre- and post-test counselling. Of the fifty-six patients, thirty-nine were found to be HIV positive with CD+ T cell counts ranging between 9 and 1,205 cells/mm3. There was a statistically significant correlation between CD4+ T cells below 500 cells/mm3 (p = 0.000) as well as with CD4+ T cells below 200 cells/mm3 (p = 0.001) and NUP/NUG. CONCLUSION: From these results it is concluded that in the GaRankuwa and surrounding areas, NUG/NUP in otherwise systemically healthy individuals is strongly correlated with HIV infection, with a predictive value of 69.6 per cent (p = 0.01). It is recommended that patients presenting with these conditions be encouraged to undergo testing to establish their HIV status for appropriate referrals and management.     

Salivary calprotectin levels are raised in patients with oral candidiasis or Sjögren's syndrome but decreased by HIV infection

Calprotectin levels were determined in whole saliva from patients predisposed to oral candidiasis due to HIV infection or Sj?gren's syndrome and from patients with candidiasis associated with various oral disorders (e.g. lichen planus, oral ulceration). Mean calprotectin levels were higher in whole saliva (2 microgram/ml) than in parotid saliva (0.3 microgram/ml). Oral candidiasis was associated with raised whole saliva calprotectin levels in all groups studied. HIV infection was associated with lower levels of salivary calprotectin, in the presence of high or low salivary Candida counts, although CD4+ lymphocyte counts did not significantly correlate with calprotectin concentrations. Calprotectin levels were elevated in saliva from Sj?gren's syndrome patients with oral candidiasis, consistent with mucosal transudation of calprotectin from inflamed mucosa and limited dilution due to decreased salivary flow rates. This study indicates that oral candidiasis is associated with raised calprotectin levels secondary to mucosal inflammation, but that diminution of this candidacidal factor due to HIV infection may be a predisposing factor in the aetiology of oral candidiasis.