Bisphosphonate-related osteonecrosis of the jaws (Bronj)

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an extremely therapy resistant osteomyelitis-like disease exclusively involving the jaw bones of patients in treatment with bisphosphonates (BPs) OBJECTIVES: The aim of this study was to evaluate the radiological and clinical findings and management of 51 patients with BRONJ diagnosed from 2004 to 2009 in our Reference Center. STUDY DESIGN:A prospective study was performed. The patients were examined every 2-6 months, depending on their clinical conditions. Positive outcome variables were the resolution of symptoms, persistence of bone exposure and /or fistula and the status of the lesional mucosa. RESULTS: The higher prevalence of the disease was noted in 2006 and 2007 and at the time of diagnosis 90% of patients had been treated with iv BPs. The main precipitating event leading to BRONJ was an invasive dental procedure in 61% of patients while no traumatic event could be identified in 16% of patients. The median time of follow-up was 19 months (range: 2-57), during which 31% of patients healed and 39% succumbed. In 78% of patients the therapy was medical, in 16% it consisted in surgical deep curettage and only in 6% it was necessary to perform an osteotomy to avoid a mandibular pathological fracture. All the patients in treatment with oral BPs healed from BRONJ with a median time of conservative treatment of 19 months. CONCLUSIONS: Prevention has lead to a progressive reduction in the prevalence of BRONJ. In our experience medical treatment is often sufficient to keep the disease under control and to lead to the healing of the lesions by spontaneous loss of the sequestrum. This approach seems to be very effective in patients who were in treatment with oral Bps preparations; BRONJ seems to have a more benign clinical behaviour in these patients (AU)

Bisphosphonate-related osteonecrosis of the jaws (Bronj).

UNLABELLED: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an extremely therapy resistant osteomyelitis-like disease exclusively involving the jaw bones of patients in treatment with bisphosphonates (BPs). OBJECTIVES: The aim of this study was to evaluate the radiological and clinical findings and management of 51 patients with BRONJ diagnosed from 2004 to 2009 in our Reference Center. STUDY DESIGN: A prospective study was performed. The patients were examined every 2-6 months, depending on their clinical conditions. Positive outcome variables were the resolution of symptoms, persistence of bone exposure and /or fistula and the status of the lesional mucosa. RESULTS: The higher prevalence of the disease was noted in 2006 and 2007 and at the time of diagnosis 90% of patients had been treated with iv BPs. The main precipitating event leading to BRONJ was an invasive dental procedure in 61% of patients while no traumatic event could be identified in 16% of patients. The median time of follow-up was 19 months (range: 2-57), during which 31% of patients healed and 39% succumbed. In 78% of patients the therapy was medical, in 16% it consisted in surgical deep curettage and only in 6% it was necessary to perform an osteotomy to avoid a mandibular pathological fracture. All the patients in treatment with oral BPs healed from BRONJ with a median time of conservative treatment of 19 months. CONCLUSIONS: Prevention has lead to a progressive reduction in the prevalence of BRONJ. In our experience medical treatment is often sufficient to keep the disease under control and to lead to the healing of the lesions by spontaneous loss of the sequestrum. This approach seems to be very effective in patients who were in treatment with oral Bps preparations; BRONJ seems to have a more benign clinical behaviour in these patients.

Oral linear epidermal nevus: a review of the literature and report of two new cases.

Linear epidermal nevus (LEN) is a sporadic hamartomatous lesion of the skin due to the proliferation of clones of embryonic ectodermal cells, which are arranged according to a typical linear configuration known as Blaschko's lines. Oral involvement of LEN is very rare and few cases have been reported in the medical literature. We report two new cases of LEN with exclusive oral involvement, which presented with the typical unilateral or midline distribution. Oral LEN presents as an exophytic lesion with well defined borders and a verrucous or papillary surface which correspond, histologically, to epithelial papillomatosis with a moderate degree of hyperkeratosis and acanthosis. Oral LEN appears mainly at birth, grows slowly during childhood and stabilize by adolescence. Localized lesions do not show any recurrence after surgical removal but widespread lesions seem to have more risk of recurrence and are more difficult to manage. Functional problems and malignant transformation have not been reported.

Metastatic renal cell carcinoma to the oral cavity and clear cell mucoepidermoid carcinoma: comparative clinicopathologic and immunohistochemical study.

BACKGROUND: Metastatic clear cell renal cell carcinoma (CCRCC) should be considered in differential diagnosis of intraoral clear cell tumors, including mucoepidermoid carcinoma (MEC). OBJECTIVE AND STUDY DESIGN: We compared the clinical, histologic, histochemical, and immunohistochemical characteristics of 9 oral metastatic CCRCCs and 8 intraoral clear cell MECs. RESULTS: Oral metastatic CCRCC affected salivary-gland containing tissues in 7 cases (78%). Microscopically, oral metastasis revealed a proliferation of neoplastic clear cells arranged in an alveolar pattern with central blood vessels, features that were not seen in any intraoral clear cell MEC. Mucicarmine staining was positive only in clear cell MEC. Immunohistochemistry showed similarities in cytokeratin expression; vimentin and CD10 were expressed in all oral metastatic CCRCCs but in only 1 clear cell MEC each. CONCLUSIONS: Besides clinical history, the alveolar pattern, vessel distribution, absence of mucicarmine staining, and vimentin and CD10 immunoexpression are useful in histologic differential diagnosis of CCRCC and clear cell MEC.

Pyostomatitis vegetans: cellular immune profile and expression of IL-6, IL-8 and TNF-alpha.

The aim of this study was to investigate the cellular immune profile and the expression of IL-6, IL-8 and TNF-alpha in tissue biopsies of pyostomatitis vegetans (PV). Working hypothesis was that knowledge of the cellular immune profile and role of mediators such as IL-6, IL-8 AND TNF-alpha may contribute to a better understanding of the pathogenesis of this rare entity. Archival tissues from three patients with clinically and histologically confirmed PV were studied. Analysis of the immune profile of the cellular infiltrate and expression of IL-6 and IL-8 were evaluated by immunohistochemistry. ISH was performed to evaluate the expression of TNF-alpha. Biopsy tissues from erythema multiforme, recurrent aphthous stomatitis, lichen planus and normal buccal mucosa were analyzed as controls. All patients were affected by multiple mucosal ulcerations and yellow pustules mainly located in the vestibular, gingival and palatal mucosa. Histopathologically, all specimens showed ulcerated epithelium with characteristic intraepithelial and/or subepithelial microabscesses containing abundant eosinophils plus a mixed infiltrate composed of lymphocytes and neutrophils. Cellular immune profile of the inflammatory infiltrate revealed a predominance of T-lymphocytes, mainly of cytotoxic (CD3+/CD8+) phenotype, over B-cells. CD20+ B-lymphocytes were also identified to a lesser degree among the lymphoid cells present in the lamina propria. Overexpression of IL-6 and TNF-alpha was found in both epithelial and inflammatory mononuclear cells. IL-8 expression was shown in the mononuclear cells scattered among the inflammatory infiltrate. Similar findings of overexpression of IL-6, IL-8 and TNF-alpha were, however, found in control tissues. In PV lesions, the inflammatory infiltrate shows a predominance of cytotoxic lymphocytes. Expression of IL-6, IL-8 and TNF-alpha, although not specific to PV, appears up-regulated thus these cytokines would represent a suitable therapeutic target. However, the complexity of the cytokine network and their numerous functions require further studies in order to confirm our findings.

Oral pulse granuloma: histological findings by confocal laser scanning microscopy.

Pulse granuloma is a rare benign entity considered to be a foreign-body reaction to vegetables particles. It occurs most frequently in the oral cavity of edentulous patients wearing a complete mobile denture, associated with impacted lower third molar or in postextractive alveolar sockets. The authors analyzed 2 cases by both optical and confocal laser scanning microscopy, a research technique based on laser light microscopic analysis of biological samples stained for fluorescence observation. CLSM allowed improved tissue imaging, bidimensional pictures with better resolution at cellular level, and, in particular, the possibility of a three-dimensional image reconstruction. In conclusion, this study reports the fine definition of pulse granuloma at microscopic level by CLSM and the results warrant the use of this technique for further analyses.

Oral herpes simplex virus infection in pregnancy: what are the concerns?

Although epidemiologic data and the potentially serious effects of transmission of genital herpes from mother to infant during birth have been widely reported, published reports on oral herpes disease in pregnancy remain scarce and no clear management guidelines exist. Thus, questions remain about acquisition, transmission and outcome of infection, especially with respect to acute gingivostomatitis in pregnancy. In response to these questions, we summarize previous reports on herpes simplex virus 1 (HSV-1) oral disease in pregnancy and, briefly, present 2 cases of primary gingivostomatitis in the first trimester of pregnancy, resulting in a favourable outcome for both mother and infant. We also point out the most recent data on rare, potentially severe in outcome, but treatable, primary central nervous system HSV-1 infection in later stages of pregnancy. Finally, we emphasize a multidisciplinary approach to oral HSV disease in pregnancy, with dentist participation in the diagnosis and treatment.

Syphilis: the renaissance of an old disease with oral implications.

Syphilis is caused by Treponema pallidum an anaerobic filamentous spirochete. In recent years, striking outbreaks have occurred in USA, Canada, Russia, China and some areas of Central and Eastern Europe. Main epidemiology changes reflect sex industry, sexual promiscuity, decreasing use of barrier protection (i.e. condoms) due to false sense of security that nowadays sexually transmitted diseases are curable and lack of pertinent knowledge. Considering that the initial presentation of syphilis may be the oral cavity, it is of great relevance to include this disease in the differential diagnosis of unusual oral ulcerations and white patches. Primary syphilis is a highly infectious disease in which inappropriate treatment may be apparently curative while the patient remains highly infectious. It is then of pivotal importance that clinicians maintain a high clinical index of suspicion. At the present time, clinical-pathologic correlation together with serologic studies remain essential in establishing the diagnosis of syphilis.

Management of oral lesions in HIV-positive patients.

HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop. We found the largest body of evidence for treatment of OPC in HIV patients. Future trials will be needed to test drugs currently in development for treatment of Candida strains that are resistant to existing therapies. There were no double blind, placebo-controlled randomized clinical trials (RCT) for topical treatment of OHL, and only one RCT for systemic treatment of the lesion with desciclovir. Systemic thalidomide was the only drug tested in RCT for treatment or prevention of RAU. Only 1 double-blind RCT comparing vinblastine and sodium tetradecyl sulfate was identified for localized treatment of OKS. Three drugs (famciclovir, acyclovir, and valaciclovir) were shown to be effective in randomized, double-blind trials for treatment or suppression of mucocutaneous HSV lesions in HIV patients. In all 3 trials, the effects of these medications on orolabial HSV lesions were not reported separately. There were no double-blind, placebo-controlled RCT testing topical treatments for orolabial HSV lesions in HIV patients. No trials testing treatments of oral VZV were identified. There were no double-blind, placebo-controlled RCT for treatment of HIV-associated intraoral or perioral warts or periodontal diseases. In conclusion, there is a need for well-designed RCTs to assess the safety and efficacy of topical and systemic treatments of most oral mucosal and perioral lesions in HIV patients. There is also a need to develop newer drugs for treatment of resistant fungal and viral microorganisms. Finally, standardized outcome measures should be developed for future clinical trials to allow comparisons of studies using different populations.

Bisphosphonate - related osteonecrosis of the jaws: the point of view of the oral pathologist.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is mainly reported in patients with bone metastasis from a variety of solid tumors and disseminated multiple myeloma receiving iv bisphosphonates therapy. These patients represent 95% of reported cases. The reported incidence of BRONJ is significantly higher with the iv preparations zoledronic acid and pamidronate while the risk appears to be minimal for patients receiving oral bisphosphonates. Currently, available published incidence data for BRONJ are based on retrospective studies and estimates of cumulative incidence range from 0.8% to 12%. The mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. The signs and symptoms that may occur before the appearance of clinical evident osteonecrosis include changes in the health of periodontal tissues, non-healing mucosal ulcers, loose teeth and unexplained soft-tissue infection. Although the definitive role of bisphosphonates remains to be elucidated, the alteration in bone metabolism together with surgical insult or prosthetic trauma appear to be key factors in the development of BRONJ. Tooth extraction as a precipitating event is a common observation in the reported literature. The significant benefits that bisphosphonates offer to patients clearly outbalance the risk of potential side effects; however, any patient for whom prolonged bisphosphonate therapy is indicated, should be provided with preventive dental care in order to minimize the risk of developing this severe condition. This article provides a review of current developments about the pathogenetic, clinical, management and preventive aspects of BRONJ.

Bisphosphonate-related osteonecrosis of the jaws: an update on clinical, pathological and management aspects.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is mainly observed in patients with multiple myeloma and bone metastasis from solid tumors receiving iv bisphosphonate therapy. The reported incidence of BRONJ is significantly higher with the iv preparations zoledronic acid and pamidronate while the risk appears to be minimal for patients receiving oral bisphosphonates. Currently available published incidence data for BRONJ are based on retrospective studies and estimates of cumulative incidence range from 0.8 to 12%. The mandible is more commonly affected than the maxilla (2:1 ratio), and 60-70% of cases are preceded by a dental surgical procedure. The signs and symptoms that may occur before the appearance of clinical evident osteonecrosis include changes in the health of periodontal tissues, non-healing mucosal ulcers, loose teeth and unexplained soft-tissue infection. Although the definitive role of bisphosphonates remains to be elucidated, the inhibition of physiologic bone remodeling and angiogenesis by these potent drugs impairs the regenerative capacity of the bone causing the development of BRONJ. Tooth extraction as a precipitating event is a common observation. The significant benefits that bisphosphonates offer to patients clearly surpass the risk of potential side effects; however, any patient for whom prolonged bisphosphonate therapy is indicated, should be provided with preventive dental care in order to minimize the risk of developing this severe condition. This article provides an update review of current knowledge about clinical, pathological and management aspects of BRONJ.

The diagnosis and management of oral herpes simplex infection.

Acute herpetic gingivostomatitis and recurrent herpes labialis are the most common manifestations of infection with herpes simplex virus type 1 (HSV-1). In primary and recrudescent HSV-associated disease, the symptoms may range from subclinical to debilitating and life-threatening, depending on the host's immune responses or competence level. In this paper, the typical and atypical manifestations, and the current diagnostic and treatment options for localized, non-complicated oro-labial HSV infection are reviewed, with attention to cumulative evidence for the efficacy and safety of systemic antiviral agents. Some recent data on HSV-1 seroprevalence, viremia, and viral shedding are discussed in relation to disease transmission and global importance of herpesvirus disease.

IL-4, IL-5, TGF-beta1 and IFN-gamma mRNAs detected by a new in situ amplification system in cicatricial pemphigoid.

The process that induces chronic progressive scarring in cicatricial pemphigoid (CP), a rare group of autoimmune mucocutaneous blistering diseases, is still under investigation. The tendency to heal with scar formation observed in CP could be due to the specific localization of the antigen in the basement membrane zone or could depend on the frequent recurrence of the disease in a localized area. The release of soluble fibrogenic factors by inflammatory infiltrating cells has also been considered as pathogenetically relevant. The aim of this study is to evaluate the expression of mRNA for IL-4, IL-5, TGF-beta1, IFN-gamma in patients with CP, and investigate the role of the cytokine profile as a possible cause of the clinical features and course of the disease. Fourteen patients (3 male, 11 female; age range 40-72 years) with oral (n = 10), preputial (n = 3) and cutaneous (n = 1) CP were studied. The formalin-fixed and paraffin-embedded biopsies were examined by in situ hybridization performing a new amplification system based on biotinyl-tyramide. As a control, 4 patients (2 male, 2 female; age range 58-73 years) affected by bullous pemphigoid (BP), the most common autoimmune subepidermal blistering disease, were also examined. In CP, IL-4 mRNA expression was present in 4 out of the 14 cases analysed. IL-5 was detected in 12 CP biopsies. TGF-beta1 and IFN-gamma mRNAs were identified in 9 and 11 CP cases, respectively. In BP, an IL-4 hybridization signal could not be observed in any of the cases. By contrast IL-5, TGF-beta1 and IFN-gamma mRNA analyses were positive in all four BP cases. Our results suggest the presence of a T-cell population with a mixed cytokine pattern in the cellular infiltrate of both blistering diseases, with a corresponding increase of Th2-like activity in fully developed lesions, irrespective of the different sites involved. In addition, on the basis of the constant presence of TGF-beta1 mRNA in the different lesional phases of CP, and its overlapping expression in BP, we hypothesize that the involvement of additional factors is responsible for the scarring course typical of CP.

Silicone granuloma of the facial tissues: a report of seven cases.

The liquid form of silicone, called dimethicone (dimethylpolysiloxane), has been used extensively in some countries during the past 4 decades for soft tissue augmentation. Although considered biologically inert, this material has been reported as potentially inducing, after tissue injection, a granulomatous inflammatory response of variable severity. Interestingly, a remarkable paucity of reports exists about the development of complications after injections of liquid silicone into the facial tissues, especially considering its high frequency of use. The purpose of this article is to describe the clinical and microscopic features of 7 cases of silicone-induced granulomas that developed after injection of the facial tissues for cosmetic purposes and to discuss the differential diagnosis and management of this condition.

A rare lesion of the periodontium: the gingival cyst of the adult--a report of three cases.

This article describes the clinical aspects and the histologic features of three cases of gingival cyst of the adult. The diagnostic problems of this rare entity are discussed. Radiographic examination to determine the presence of bone loss must be undertaken to differentiate the gingival cyst of the adult from the more frequent lateral periodontal cyst.