Orofacial diseases in solid organ and hematopoietic stem cell transplant recipients

Oral Diseases (2012) 19 , 18–36 Objective: Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at risk of several diseases, principally attributable to immunosuppression. This global overview of SOT/HSCT‐associated orofacial diseases is aimed at providing a practical instrument for the oral healthcare management of SOT/HSCT recipients. Methods: Literature search was made through MEDLINE. The associations between orofacial diseases and SOT/HSCT were assessed using observational studies and case series and were classified into ‘association’, ‘no association’, and ‘unclear association’. Results: Lip/oral cancers, drug‐induced gingival overgrowth (DIGO), infections, including hairy leukoplakia and, less frequently, post‐transplantation lymphoproliferative disorders (PTLDs) and oral lichenoid lesions of graft‐versus‐host disease (GVHD), were associated with SOT. Lip/oral cancers, GVHD, mucositis, DIGO, infections and, less frequently, PTLDs were associated with HSCT. Associations of orofacial granulomatosis‐like lesions and oral mucosa‐associated lymphoid tissue‐type lymphoma with SOT, and of pyogenic granuloma and hairy leukoplakia with HSCT were unclear. Periodontal disease and dental caries were not associated with SOT/HSCT. For none of the local treatments was there a strong evidence of effectiveness. Conclusions: Solid organ transplant/HSCT recipients are at risk of orofacial diseases. Adequate management of these patients alleviates local symptoms responsible for impaired eating, helps prevent systemic and lethal complications, and helps where dental healthcare has been neglected.     

Prevalence of gingival overgrowth in transplant patients immunosuppressed with tacrolimus

AIMS: The study aims to determine the prevalence and severity of gingival overgrowth in a group of adult organ transplant recipients immunosuppressed with tacrolimus in comparison with ciclosporin, and to examine various risk factors for the development of gingival overgrowth. METHODS: Forty patients taking tacrolimus were compared with 197 ciclosporin patients. Demographic, pharmacological and periodontal data were recorded for all patients. Comparison between the groups was made using independent sample t-tests, chi2 statistic or Mann-Whitney test. The effects of risk variables on overgrowth severity were examined using forward and backward stepwise regression analysis. RESULTS: Those taking tacrolimus had a significantly lower mean gingival overgrowth score (14.1%) compared with ciclosporin (22.4%). Fifteen percent of the tacrolimus group had clinically significant gingival overgrowth compared with 30% in the ciclosporin group (p=0.053). CONCLUSIONS: The prevalence and severity of gingival overgrowth is less in adult transplant patients taking tacrolimus compared with ciclosporin. Concomitant use of calcium channel blockers and previous medication with ciclosporin are significant risk factors for the presence and severity of gingival overgrowth. Patients who have alteration of their immunosuppressant from ciclosporin to tacrolimus may persist in demonstrating gingival overgrowth attributable to their ongoing therapy with calcium channel blockers.     

Oral Candida infection and colonization in solid organ transplant recipients

Introduction:  Oral Candida carriage and infection have been reported to be associated with a greater risk for systemic infection in transplant recipients; however, a systematic analysis of the oral Candida titers and species has not been previously conducted. The objectives of this study were to determine the prevalence of oropharyngeal candidiasis, the oral carrier status, Candida titers and species in this population.
Methods:  Ninety kidney and heart transplant subjects and 72 age-matched healthy controls were included. Swabs from the oral mucosa and a standardized amount of unstimulated saliva were plated on Chromagar™ Candida , and colony-forming units per millilitre were calculated. Initial speciation was based on colony color and was confirmed by standard germ tube, biotyping, or polymerase chain reaction assays.
Results:  Infection with C. albicans was detected in seven transplant subjects and none of the controls. The transplant group had significantly higher oral Candida titers than the control group. There were no statistically significant relationships between the dose or type of immunosuppressants and oral Candida titers or infection. A significantly higher percentage of transplant subjects were colonized by more than one species, compared with control subjects. The most frequent species combination in transplant subjects was C. albicans and C. glabrata . C. glabrata was isolated from 13.5% of transplant carriers and none of the controls.
Conclusions:  Increased oral Candida infection and carriage titers were found in the transplant population. Although the majority of transplant patients were colonized by C. albicans , C. glabrata appears to emerge as the second most prevalent species.     

The prevalence of dysplasia and malignant lip lesions in transplant patients

J Oral Pathol Med (2012) 41 : 113–118 Background: Solid organ transplant patients are at an increased risk of developing lip malignancies. The role of HLA mismatch as a risk factor for such changes has only been described in skin. Methods: Lip lesions were evaluated in 403 solid organ transplant patients (immunosuppressed for at least 3 months) and findings compared to age and sex matched, otherwise healthy patients who acted as controls. HLA typing was provided for the transplant patients. All patients provided details of smoking history, alcohol consumption, skin type, as assessed by ease of burning to sunlight, and exposure to sunlight or other forms of ultraviolet radiation. Results: Lip lesions were identified in 36 transplant patients and 29 were biopsied. Fourteen of the biopsies confirmed dysplastic or malignant changes. For the control patients, one lesion was identified as dysplastic. The prevalence of dysplastic and malignant lip lesions was significantly higher (P = 0.006) in the transplant patients when compared to controls. Risk factors for dysplastic/malignant changes in the transplant group included age (P = 0.01), smoking (P = 0.033) and HLA‐B mismatch (P = 0.001). Lip covering provided a significant reduction (P = 0.045) in the development of lip changes. Conclusion: All transplant patients should be regularly screened for lip malignancies and consulted on smoking and sunlight exposure. HLA‐B mismatch does appear to make these patients more susceptible to dysplastic/malignant changes.     

心脏移植患者3种牙周可疑致病菌的检测

目的：应用聚合酶链反应法对心脏移植患者龈上菌斑中牙龈卟啉单胞菌、福赛坦氏菌和齿垢密螺旋体进行检测,分析其存在状况与牙周临床指标的关系。方法：55例心脏移植患者为实验组,36例正常成人为对照组。以16、26为受检牙位,分别采集龈上菌斑,应用PCR技术检测菌斑中的Pg,Tf,Td。同时记录受检牙位的菌斑指数、龈沟出血指数,龈沟探诊深度及附着丧失。结果：心脏移植组PLI、SBI、PD均高于对照组（P〈0.05）,心脏移植组龈上菌斑中Pg、Tf、Td检出率分别为为81.8%、69.1%、76.4%,对照组中3种细菌检出率分别为58.3%、41.7%、41.7%。检出率均高于对照组（P〈0.05）。心脏移植组3种致病菌同时检测出率为53.6%（59/110）,对照组3种致病菌同时检出率为29.2%（21/72）,两组差异有统计学意义（P〈0.05）。心脏移植组中3种致病菌均为阳性患者的PLI、SBI、PD均高于对照组（P〈0.05）。结论：心脏移植患者口腔卫生状况较差,为防止牙周疾病的发生,应及早进行口腔卫生干预治疗。     

The comparative effects of azathioprine and cyclosporin on some gingival health parameters of renal transplant patients

The periodontal health of 24 adult renal transplant patients was investigated in a longitudinal study. Post-transplant patients were receiving either azathioprine or cyclosporin to prevent graft rejection. No significant difference (P greater than 0.05) was observed for plaque scores on gingival inflammation, either between treatment groups or throughout the investigation period. However, patients on cyclosporin therapy had significantly more gingival hyperplasia and probing sites greater than 3 mm than those on azathioprine (P less than 0.05). In the cyclosporin group, a significant increase in hyperplasia and probing sites greater than 3 mm was observed at 3 and 6 months post-transplant. A significant correlation (rs = 0.55, P less than 0.05) was observed between mean plasma concentrations of cyclosporin throughout the 6-month investigation period and the increase in gingival hyperplasia. The finding from this study would suggest that azathioprine has no unwanted effects on the periodontal health of post-renal transplant patients. Cyclosporin therapy caused an increase in gingival hyperplasia, which may be related to plasma concentrations of the drug.     

The prevalence and severity of cyclosporin and nifedipine-induced gingival overgrowth

Abstract The gingival health of 32 renal transplant patients who were medicated with cyclosporin was compared with a similar cohort of 23 renal transplant patients medicated with both cyclosporin and nifedipine. Both groups of patients had been taking the above medication for at least 3 months. Plaque scores, gingival inflammation and probing depths were similar for both groups. Patients medicated with the combination of nifedipine and cyclosporin had a significantly higher gingival overgrowth score (p= <0.046) when compared with the group receiving cyclosporin alone. The incidence of clinically significant overgrowth (i.e., overgrowth >30% which would require surgical intervention) was similar in both groups. Gingival overgrowth was not related to cyclosporin dosage. It is concluded that patients taking cyclosporin or cyclosporin and nifedipine experience gingival overgrowth and that the severity of the overgrowth is greater in patients taking the combined therapy. The levels of plaque and gingival inflammation appear to be associated with this phenomenon.     

Dental Pulp Autotransplantation: A New Modality of Endodontic Regenerative Therapy—Follow-Up of 3 Clinical Cases

The aim of this study was to develop a novel method of endodontic therapy, which we refer to as dental pulp autotransplantation. Three patients (2 males and 1 female) were selected for endodontic treatment of a uniradicular premolar and extraction of a third molar (without odontosection). Electric assessment of pulp vitality and computed tomographic imaging were undertaken followed by endodontic access and instrumentation using triantibiotic solution for irrigation in the host tooth. A few minutes before the transplant procedure, the third molar was extracted, the tooth was sectioned with a diamond blade in a low-speed handpiece, and the pulp was carefully removed. After premolar instrumentation, the harvested and preserved pulp tissue was reinserted into the root canal followed by direct pulp capping performed using Biodentine (Septodont, Saint-Maur-des-Fossés, France), a liner of resin-modified glass ionomer cement and composite resin restoration. The teeth were followed up for at least 12 months after the procedures and were analyzed using computed tomographic imaging, electric pulp vitality testing, and Doppler ultrasound examination. At the 3- and 6-month follow-ups, positive pulp vitality and regression of periapical lesions were verified. After 9–12 months, all teeth were revascularized as determined by Doppler imaging, and the tooth vitality was reestablished with no signs of endodontic/periodontal radiolucency or complications. Within the limitations of the study, considering that it was a case series with only 3 patients, we described a highly innovative procedure of pulp autotransplantation, which appears to be feasible, highlighting the potential for clinical application of pulp regeneration using this new modality of endodontic therapy.     

Development and terminal differentiation of pulp and periodontal nerve elements in subcutaneous transplants of molar tooth germs and incisors of the rat

Ectopic tooth transplants are known to receive rich innervation of local neurons, but the precise location and structural features of neurites in the pulp and periodontal ligament (PDL) of such transplants are unclear. In this experiment, the molar tooth germs of rat embryos and incisors of young rats were subcutaneously transplanted into the dorsal regions of rats and processed, at various time intervals, for immunohistochemical demonstration of neural elements. Teeth with periodontal tissue elements developed in most of the molar transplants in 6 or 8 wk and received rich innervation, including some autonomic fibres, in the pulp. Nerve elements were also confirmed to be present in the PDL of these transplants, including specialized nerve ending-like structures reminiscent of the periodontal Ruffini endings. Mechanoreceptor-like structures were also induced in the regenerated PDL of similarly transplanted incisors, although the success rate was low. We conclude that rich and highly ordered innervation of the pulp, and occasional development of mechanoreceptors in the regenerated PDL of ectopic dental transplants, imply a high probability of successful induction of teeth with both nociceptive and mechanical sensations in the ectopic tooth and/or tooth germ transplant systems, although differentiation of mechanoreceptor-like nerve endings occured in only a few rare cases.     

Cyclosporin-a-induced gingival overgrowth in heart transplant patients

Abstract The incidence of gingival overgrowth secondary to the administration of cyclosporine A (CsA) is widely reported in renal transplant recipients, while there is no information about periodontal conditions in heart transplant patients. In the present cross-sectional investigation the relationship between clinical periodontal conditions and pharmacological profiles of CsA was determined in 39 patients (31 male and 8 female, aged 18–63 years, mean 45.6±15.2 years) who possessed their 6 upper and 6 lower anterior teeth. All patients had been on a CsA-based immunosoppression regimen for at least 6 months (6–101. mean 39.3±30.1). 2 periodontal parameters (recorded on the 12 anterior teeth only) relating to gingival overgrowth were considered: hyperplastic index and % of sites with probing depth >3 mm. These parameters were always recorded by the same observer at first appointment and 2 months after an oral hygiene programme. Both non parametric statistical analysis (Kruskal-Wallis one-way analysis by rank. Wilcoxon signed rank-test and Mann Whitney U-test) and parametric analysis (stepwise multiple regression analysis, one-sample and two-sample t-test) were used to investigate the relationship between the periodontal parameters (dependent variables) and a series of independent variables: age. sex. plaque index (PI), gingival index (GI), CsA dose, CsA blood level, duration of therapy (months since allograft). Results failed to demonstrate any significant correlation between gingival overgrowth and age, sex, CsA dose or CsA blood level, PI. A positive significant correlation was found between periodontal conditions and GI and a significant inverse correlation between periodontal conditions and duration of therapy, suggesting that the relation between CsA therapy and gingival overgrowth in heart-transplant patients could be time-related and the negative influence of the drug on the periodontal status could spontaneously decrease over time.     

Determinants of gingival overgrowth severity in organ transplant patients

Abstract The role of HLA phenotype as a risk factor for drug-induced gingival overgrowth was investigated in a cohort of 172 transplant recipients. Clinically significant overgrowth warranting surgical correction was observed in 72 patients (42%). Using stepwise regression modelling. 6 clinical parameters were identified as significant risk factors for the severity of gingival overgrowth. These were; age. sex. creatinine plasma level, duration of therapy, papilla bleeding index and concomitant medication with a calcium channel blocking drug. 3 HLA alleles were also identified as risk factors when adjusted for other clinically significant risk factors (HLA -DR2, A24, B37). However, when the p-values for the HLA variables were corrected to compensate for the use of multiple significance testing, only HLA-B37 remained statistically significant at the 5% level. Organ transplant patients are at risk of developing gingival overgrowth, with approximately 25% medicated with cyclosporin alone requiring corrective gingival surgery. This figure more than doubles in patients concomitantly medicated with a calcium blocking drug. The data at present available would suggest that the severity of gingival overgrowth is also significantly associated with the HLA-B37 phenotype.     

Oral health in renal transplant recipients administered cyclosporin A or tacrolimus

OBJECTIVE: The aim of this study was to determine the oral status of renal transplant recipients receiving cyclosporin A (CsA) or tacrolimus (FK-506) as immunosuppressant. SUBJECTS AND METHODS: A total of 88 renal transplant recipients receiving CsA (63 men and 25 women, mean age 51.4 years) and 67 receiving FK-506 (57 men and 10 women, mean age 33.5 years) were included in the study. Donor type, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Demographics and pharmacological data were recorded for all subjects. RESULTS: The results demonstrated that CsA caused a greater number of oral diseases. A greater number of gingival overgrowth was present in patients treated with CsA. However, the combined use with calcium channel blockers increased the gingival overgrowth number. The occurrence of candida in saliva was observed in 80 renal recipients treated with CsA and 20 treated with FK-506. The presence of squamous oral carcinoma (n = 3) and herpes simplex (n = 10) was observed in patients treated with CsA. These alterations were not observed in renal recipients treated with FK-506. CONCLUSIONS: Renal recipients constitute a high-risk group for oral diseases, as they are immunocompromised. However, the FK-506 regime appears to ameliorate this effect, compared with CsA. Adequate pre- and post-transplant oral health care is recommended for these subjects, irrespective of the time interval for which the drug is administered.     

Nifedipine pharmacological variables as risk factors for gingival overgrowth in organ-transplant patients

The prevalence and severity of gingival overgrowth in organ-transplant patients medicated with cyclosporin are greater in patients concomitantly medicated with nifedipine; however, no relationship between the gingival overgrowth and any of the nifedipine pharmacological variables has been demonstrated. The study examined the effect of five nifedipine pharmacological variables (nifedipine dosage, plasma concentration and gingival crevicular fluid concentration, M1 metabolite plasma concentration and the nifedipine:M1 ratio). The effect of the nifedipine variables on the gingival overgrowth score were examined using univariate and multivariate regression analysis. Adjustment for the effect of other risk factors was made by adding the distribution of each of the nifedipine variables in turn to a stepwise regression model containing previously identified risk factors for this condition. Despite the high levels of nifedipine sequestered in the GCF, only the plasma concentration of nifedipine was identified as a risk factor for the severity of gingival overgrowth in these patients (P = 0.01) once adjusted for other known risk factors (r ² for the model = 55%).     

Cyclosporin-A-induced gingival overgrowth in renal transplant children

Gingival overgrowth was assessed in renal transplant children, 19 boys and 13 girls, aged 2.5–18 yr, who had been on a cyclosporin-A (CsA)-based immunosuppressive regimen for at least 12 months. Data collected included number of posttransplant months, total CsA dose administered during the first 6 posttransplant months, oral dose and blood trough level of CsA on the day of examination, plaque accumulation (VPI%), gingival inflammation (GBI%), loss of attachment, and gingival overgrowth. Thirteen percent of the children exhibited gingival overgrowth characterized by one or more units with increased sulcus probing depth (≥4 mm), i.e. pseudopockets. The total amount of CsA administered during the first 6 posttransplant months was significantly higher in the children with gingival overgrowth than in those without. The study indicates that the development of CsA-induced gingival overgrowth is positively related to the total dose of the drug administered to the children during the first 6 posttransplant months.     

Tooth pigmentation caused by bilirubin: a case report and histological evaluation

Systemic disorders in pediatric patients, such as congenital biliary atresia, acute liver failure, and biliary hypoplasia, may be the indications for a need of liver transplantation. One of the manifestations of these disorders is the elevated serum levels of bilirubin (hyperbiliru‐binemia), a product of hemoglobin degradation, which is deposited in different tissues, including mineralized and soft tissues. When hyperbilirubinemia occurs during the period of dental development, these teeth can develop a green coloration, which remains permanently, because, after maturation, these tissues loose their metabolic activity. This case report describes a 9‐year‐old girl who required a liver transplant due to biliary atresia when she was three years old. Some of her pigmented teeth needed extraction and afterwards were submitted for histological analysis and compared with sound teeth.     

Intraoral features and considerations in face transplantation

Face transplantation (FT) is a unique and novel addition to the field of reconstructive surgery, which offers new hope to facially disfigured individuals. This review provides an overview of FT, including clinical indications, immunological principles, and functional outcomes, as well as an in‐depth characterization of the intraoral hard and soft tissue findings in the six patients transplanted to date at Brigham and Women's Hospital in Boston, MA, USA. Six FT recipients underwent comprehensive clinical and radiographic evaluation to assess their intraoral status, function, and overall health. The extra‐ and intraoral soft tissue was assessed via quantitative sensory testing. The vitality of the transplanted dental hard tissue was evaluated with clinically available testing methods. Native teeth and prostheses were also assessed. Sensation of transplanted oral mucosa varied based on time elapsed from FT, ranging from minimal at 3 months post‐FT, to nearly complete recovery by approximately 24 months. There was mixed success with the integration of donor teeth (Patients 1, 4 and 6), including associated occlusal discrepancies. Mucosal complications included constriction at the donor/recipient interface (Patients 2 and 5) and solitary episodes of mucosal rejection presenting as lichenoid inflammation (Patients 2 and 4). Face transplantation represents a pivotal moment in the history of reconstructive surgery and transplant medicine, providing new optimism to patients with gross facial deformities. This report highlights the successes of FT, but also the challenges of transplanting hard and soft tissues to restore complex stomatognathic function. Further attention directed toward comprehensive oral rehabilitation in FT will contribute to improved outcomes, with the ultimate goal of restoring and optimizing patient quality of life.     

Pyogenic granuloma in a renal transplant patient: case report

This case report describes a 14-year-old female referred to Pediatric Dentistry for evaluation and treatment of cyclosporine-induced gingival hyperplasia. Examination of the anterior maxillary area showed a red, vascular, exophytic, soft-tissue mass which had been excised a few months earlier without a histopathologic examination being done. The mass did not appear consistent with gingival overgrowth induced by long-term use of medication, and thus an excisional biopsy was performed, which diagnosed the lesion as a pyogenic granuloma. A review of the literature and management recommendations are discussed.