Neuropathic Pain in the Eyes, Body, and Mouth: Insights from the Sjögren's International Collaborative Clinical Alliance.

OBJECTIVE: To evaluate how ocular, oral, and bodily neuropathic pain symptoms, which characterize small fiber neuropathies, are associated with Sjögren's syndrome (SS) classification based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. METHODS: Participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry had ocular, rheumatologic, oral, and labial salivary gland (LSG) biopsy examinations, blood and saliva samples collected, and completed questionnaires at baseline. We used mixed effects modeling with age, country, gender, and depression being fixed effects and study site, a random effect, to determine if neuropathic pain indicators (assessed via questionnaires) were associated with being classified as SS. RESULTS: A total of 3,514 participants were enrolled into SICCA, with 1,541 (52.9%) meeting the 2016 ACR/EULAR classification criteria for SS. There was a negative association between being classified as SS and experiencing bodily neuropathic pain features of needle-like pain, prickling/tingling sensation, ocular neuropathic pain of constant burning, and constant light sensitivity, and having a presumptive diagnosis of neuropathic oral pain. CONCLUSIONS: We found that those classified as SS had lower scores/reports of painful neuropathies compared with those classified as non-SS. Non-SS patients with dry eye disease or symptoms could benefit from pain assessment as they may experience painful small-fiber neuropathies (SFNs). Pain questionnaires may help identify pain associated with SFNs in patients with SS and non-SS dry eye. Future studies would be helpful to correlate self-reports of pain to objective measures of SFNs in those with SS, non-SS dry eye, and healthy controls.

Biomarkers of oral inflammation in perinatally HIV-infected and perinatally HIV-exposed, uninfected youth.

AIM: To examine oral biomarkers that have been associated with periodontal disease progression in HIV-infected adults in perinatally HIV-infected and HIV-exposed but uninfected youth. MATERIAL AND METHODS: This was a cross-sectional, multicentre substudy of youth participating in the Oral Health Pediatric HIV/AIDS Cohort study. Gingival crevicular fluid repository samples from participants with and without periodontal disease (using Gingival Index [GI] and Bleeding on Probing [BOP] parameters on dental examination) were tested for concentration levels of inflammatory biomarkers. Associations were assessed using Wilcoxon test and Spearman correlation. RESULTS: For perinatal HIV youth (n = 129), the markers consistently elevated (p < .05) in sites with GI ≥2 and in sites with BOP were interleukin-1ß, 6 and 13, macrophage inflammatory protein-1α and metalloproteinase-9. Serum tumour necrosis factor-α and soluble CD14 were positively correlated with a summary count of elevated cytokines. No associations were seen among HIV-uninfected subjects (n = 71). CONCLUSIONS: The association of oral biomarkers of inflammation with clinical indicators of periodontal inflammation and systemic immune activation suggests that perinatal HIV-infected youth may be at higher risk for developing significant periodontal disease, associated with tooth loss and HIV progression. More frequent dental care of this group is needed to prevent potential periodontal progression.

2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts.

OBJECTIVES: To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS. METHODS: We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgement. We then validated the performance of the classification criteria in a separate cohort of patients. RESULTS: The final classification criteria are based on the weighted sum of five items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2, each scoring 3; an abnormal Ocular Staining Score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 min and an unstimulated salivary flow rate of ≤0.1 mL/min, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, that is, 96% (95% CI92% to 98%) and 95% (95% CI 92% to 97%), respectively. CONCLUSION: Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well suited as criteria for enrolment in clinical trials.

Prevalence of periodontal diseases in a multicenter cohort of perinatally HIV-infected and HIV-exposed and uninfected youth.

AIMS: To compare the prevalence and severity of periodontal diseases between 180 perinatally HIV-infected (PHIV) and 118 perinatally HIV-exposed and uninfected (PHEU) youth in a cross-sectional study conducted at 11 clinical sites in the United States and Puerto Rico from the Adolescent Master Protocol study of the Pediatric HIV/AIDS cohort study (PHACS) network. METHODS: Several analyses were conducted, employing the current CDC/AAP classification for periodontitis and incorporating a definition of gingivitis based on a bleeding on probing (BOP) threshold, and analyses based on more detailed whole-mouth, intra-oral regionally, site-based and tooth-based criteria of BOP, plaque levels, pockets depths and clinical attachment levels. RESULTS: After adjusting for plaque control habits and behavioural and sociodemographic factors, there were no significant differences in periodontal diseases between the PHIV and PHEU youth using any of these criteria. For PHIV youth, there was no significant association between parameters of periodontal disease and current HIV status. CONCLUSIONS: Although no significant differences in periodontal parameters were noted between the PHIV and PHEU youth, the influence of antiretroviral therapy merits further exploration in this cohort in a longitudinal study.

Oral Human Papillomavirus in Youth From the Pediatric HIV/AIDS Cohort Study.

In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.

The SSB-positive/SSA-negative antibody profile is not associated with key phenotypic features of Sjögren's syndrome.

OBJECTIVE: To determine whether the Sjögren's syndrome B (SSB)-positive/Sjögren's syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS. METHODS: Among registrants in the Sjögren's International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders. RESULTS: Among 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria. CONCLUSIONS: The presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.

Assessing the knowledge and awareness of US oncologists regarding the specialty of oral medicine.

OBJECTIVES: This cross-sectional study aimed to assess the awareness among United States (US) oncologists about oral medicine (OM) as a specialty of dentistry, and their collaboration with OM providers. METHODS: An online survey was conducted, inviting 1350 US oncologists, with data collected on demographics, practice background, comfort level with diagnosing and treating oral conditions, referral practices for oral conditions, and more. RESULTS: Of the invited 1350 oncologists, 192 responded (14% response rate). Among respondents, 46% were familiar with the OM specialty. Of these, 73% had previously sought consultation from OM specialists. The primary reasons for referral included dental clearance before initiating chemotherapy (38.5%), dental clearance before initiating radiotherapy (37%), and managing oral ulcers and oral potentially malignant disorders equally (32.2%). Regarding referrals to providers outside of OM, oncologists primarily referred patients with oral lesions to otolaryngologists (64.6%), followed by oral and maxillofacial surgeons (55.2%) and general dentists (45.3%). CONCLUSION: Our study showed that over half of US oncologists were unfamiliar with the OM specialty. However, the referral rate to OM providers was high among oncologists who had prior OM knowledge. It is advisable to enhance the collaboration between OM and oncology specialists to ensure optimal care for patients with cancer.

Sjögren's Versus Non-Sjögren's Ocular Features: Similar Symptoms, But Significantly Worse Signs.

Purpose: To examine the ocular signs and symptoms in participants of the Sjögren's International Collaborative Clinical Alliance cohort, and to compare them across Sjögren's disease (SjD) status. Methods: Our study population comprised 3380 Sjögren's International Collaborative Clinical Alliance participants who had no missing data relevant to this study. Participants' SjD status was assessed using the updated 2016 American College of Rheumatism/European League Against Rheumatism SjD classification criteria. Participants completed baseline questionnaires of ocular symptoms and underwent ocular examinations. Differences in the ocular signs and symptoms between SjD and non-SjD groups were assessed. We used multivariable linear and linear mixed-effects models to investigate the impact of SjD on Ocular Surface Disease Index-6 and OSS. Results: Among 1532 participants classified as SjD, their Ocular Surface Disease Index-6 did not clinically differ from those classified as non-SjD (adjusted difference, -0.97; 95% confidence interval, -1.52 to -0.41). However, SjD participants exhibited an elevated ocular staining score (adjusted difference, 3.47; 95% confidence interval, 3.36-3.57; P < 0.001) compared with non-SjD participants. In addition, SjD was associated with increased odds of ocular signs, such as reduced tear break-up time, abnormal Schirmer I test, and corneal abnormalities, and was strongly related to more intense corneal and conjunctival staining, as well as additional corneal staining points. Conclusions: SjD is associated with a higher risk of ocular signs and pathology compared with non-SjD, whereas ocular symptoms remain similar. In addition, corneal abnormalities and corneal staining patterns could serve as a potential biomarker in identifying SjD-related dry eye.

The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation.

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.

World Workshop on Oral Medicine VIII: Barriers to research in oral medicine: results from a global survey.

OBJECTIVES: To explore factors influencing research interest and productivity and perceived barriers to conducting research in Oral Medicine (OM). METHODS: Invitations to participate in an online survey were e-mailed to a network of international OM practitioners and related professional organizations. Questions captured respondents' demographic/professional variables and gauged research interest, productivity, and perceived barriers to conducting research specifically in OM. Statistical analysis was conducted via descriptive, logistic regression, and multivariate modeling. RESULTS: Five hundred and ninety-three OM practitioners from 55 countries completed the survey, with 54%, 25%, and 21% practicing in high, upper-middle, and lower-middle-income countries, respectively. Eighty-six percent of respondents were interested in conducting research. Age (less interest with an increase in age), working in academia, and practicing in a lower-middle vs high-income country were significant predictors of research interest. Self-reported research productivity was significantly greater among males, those working in academia, and those who graduated from programs that mandated research presentation/publication. Obtaining research funding was a significant barrier among respondents from lower and upper-middle-income countries, whereas finding time for research was a reported barrier by respondents from high-income countries. CONCLUSION: The results of this survey identified perceived barriers to conducting research in OM and highlighted solutions to address such barriers.

Calibration and reliability testing of a novel asynchronous photographic plaque scoring system in young children.

OBJECTIVES: The Simplified Oral Hygiene Index for Maxillary Incisors (OHI-MIS) is a novel plaque scoring system adapted for young children. This study describes calibration training and testing used to establish the inter- and intra-rater reliability for OHI-MIS measured from clinical photographs. METHODS: Two raters from the Coordinated Oral Health Promotion Chicago (CO-OP) and one from the Behavioral EConomics for Oral health iNnovation (BEECON) randomized controlled trials (RCTs) underwent calibration with gold standard raters, followed by annual re-calibration. Raters from CO-OP also completed inter-rater reliability testing; all three raters completed intra-rater reliability testing rounds. Photographs were obtained from children aged 9-39 months. RESULTS: All three raters achieved greater than 0.77 Lin's Concordance Correlation (LCC) versus gold standard consensus during calibration. All three raters had LCC ≥0.83 at recalibration 1 year later. CO-OP trial raters scored 604 photos (151 sets of 4 photographs); mostly both raters were somewhat/very confident in their scoring (≥89%), describing the most photos as "clear" (90% and 81%). The CO-OP inter-rater LCC for total OHI-MIS score was 0.86, changing little when low quality or confidence photos were removed. All three raters demonstrated high intra-rater reliability (≥0.83). CONCLUSIONS: The OHI-MIS plaque scoring system on photos had good reliability within and between trials following protocol training and calibration. OHI-MIS provides a novel asynchronous plaque scoring system for use in young children. Non-clinicians in field or clinical settings can obtain photographs, offering new opportunities for research and clinical care.

Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjögren's syndrome among 1,726 registry participants.

OBJECTIVE: To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sjögren's syndrome (SS). METHODS: The database of the Sjögren's International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features. RESULTS: LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of ≥1 per 4 mm²) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of ≥1 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of ≥1 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of ≥1 than were those with a higher flow rate, after controlling for other phenotypic features of SS. CONCLUSION: Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of ≥1 per 4 mm², as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.

Associations Between Smoking and Primary Sjögren Syndrome Classification Using the Sjögren's International Collaborative Clinical Alliance Cohort.

OBJECTIVE: The objective of this study was to examine the association of smoking with Primary Sjögren syndrome (pSS) classification and pSS diagnostic test results. We hypothesized that past and current smokers would have lower odds of being classified as having Sjögren syndrome (SS) and lower odds of having abnormal individual SS diagnostic test results compared with nonsmokers. METHODS: Participants with suspected or established pSS were enrolled into the Sjögren's International Collaborative Clinical Alliance (SICCA) registry and had oral, ocular, and rheumatologic examinations performed; blood and saliva samples collected; and labial salivary gland biopsy examinations performed; they also completed questionnaires at baseline. Logistic regression was used to determine whether smoking status was associated with pSS classification and individual pSS diagnostic test results. RESULTS: A total of 3514 participants were enrolled in SICCA. A total of 1541 (52.9%) met classification criteria for pSS. Compared with never smokers, current smokers had reduced odds of being classified as having pSS, reduced odds of having a focus score ≥ 1 and serologic positivity for anti-SSA/anti-SSB antibodies, and lower odds of having abnormal signs or test results of dry eye disease. Compared with never smokers, past smokers did not have a statistically significant reduction in odds of being classified as having pSS and of having abnormal individual pSS diagnostic test results. CONCLUSION: Compared with never smokers, current smokers in the SICCA cohort had lower odds of being classified as having pSS, lower odds of exhibiting abnormal signs and test results for dry eye disease, and lower odds of having a labial salivary gland biopsy supportive of pSS classification. Such negative associations, however, do not suggest that current smoking is of any benefit with respect to pSS.

Substantial regional differences in human herpesvirus 8 seroprevalence in sub-Saharan Africa: insights on the origin of the "Kaposi's sarcoma belt".

Equatorial Africa has among the highest incidences of Kaposi's sarcoma (KS) in the world, thus earning the name "KS Belt." This was the case even before the HIV epidemic. To date, there is no clear evidence that HHV-8 seroprevalence is higher in this region but interpretation of the available literature is tempered by differences in serologic assays used across studies. We examined representatively sampled ambulatory adults in Uganda, which is in the "KS Belt," and in Zimbabwe and South Africa which are outside the Belt, for HHV-8 antibodies. All serologic assays were uniformly performed in the same reference laboratory by the same personnel. In the base-case serologic algorithm, seropositivity was defined by reactivity in an immunofluorescence assay or in 2 enzyme immunoassays. A total of 2,375 participants were examined. In Uganda, HHV-8 seroprevalence was high early in adulthood (35.5% by age 21) without significant change thereafter. In contrast, HHV-8 seroprevalence early in adulthood was lower in Zimbabwe and South Africa (13.7 and 10.8%, respectively) but increased with age. After age adjustment, Ugandans had 3.24-fold greater odds of being HHV-8 infected than South Africans (p < 0.001) and 2.22-fold greater odds than Zimbabweans (p < 0.001). Inferences were unchanged using all other serologic algorithms evaluated. In conclusion, HHV-8 infection is substantially more common in Uganda than in Zimbabwe and South Africa. These findings help to explain the high KS incidence in the "KS Belt" and underscore the importance of a uniform approach to HHV-8 antibody testing.

Ocular Clinical Signs and Diagnostic Tests Most Compatible With Keratoconjunctivitis Sicca: A Latent Class Approach.

PURPOSE: To evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard. METHODS: Cross-sectional study of participants from the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based "gold standard" classification formed the basis for estimated sensitivity and specificity associated with these predictors. RESULTS: A total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard-positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard-negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard-positive group, whereas these signs in the gold standard-negative group had a specificity of 88.8% and 73.0%, respectively. CONCLUSIONS: OSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.

Oral disease burden and utilization of dental care patterns among pediatric solid organ transplant recipients.

OBJECTIVES: We conducted a study among pediatric renal (RTRs) and liver transplant recipients (LTRs) to determine: a) the overall burden of oral disease; and b) the frequency with which this population utilizes dental care services in relation to sociodemographic factors and oral disease burden. METHODS: In this cross-sectional survey, study procedures included the completion of a standardized questionnaire (by parents/guardians), oral mucosal examination, assessment of caries, gingival enlargement, and plaque index. RESULTS: The 142 children (82 RTRs and 60 LTRs) enrolled from April 2002 to November 2005 were predominantly Latino (41 percent) and Caucasian (34 percent). Forty-three percent had at least one carious surface (in either a deciduous or permanent tooth), 19 percent had five or more carious surfaces, and 25 percent had gingival enlargement. We found only one case of oral candidiasis. Even though 72 percent of parents/guardians reported their child had a regular source of dental care, only 49 percent had a dental cleaning and 44 percent had dental radiographs in the past year, reflecting a low prevalence of preventive dental care. Among children with no regular source of dental care, there were statistically significantly higher proportions of Latinos, younger children, and families with an annual household income <$35,000. CONCLUSION: While the prevalence of oral mucosal disease and gingival enlargement was low, the prevalence of children with caries was high, and there was low use of preventive dental care. Strategies to improve this population's utilization of preventive dental care are needed.

Gingival enlargement in pediatric organ transplant recipients in relation to tacrolimus-based immunosuppressive regimens.

PURPOSE: Tacrolimus, in contrast to cyclosporine, has not been found to be associated with gingival enlargement (GE) among adult transplant recipients. The purpose of this study was to explore the prevalence of GE in relation to tacrolimus and cyclosporine-based immunosuppressive regimens among pediatric solid-organ transplant recipients, controlling for the use of calcium channel blockers (CCB) and the presence of supragingival plaque. METHODS: A standardized questionnaire was administered and a comprehensive oral examination was performed among pediatric renal and liver transplant recipients who were at least 6 months post-transplant. RESULTS: The prevalence of GE among 133 participants was 26%, with the highest incidence among subjects receiving cyclosporine and CCB (60%) and the lowest among those receiving tacrolimus without CCB (13%). A multivariate model showed that the odds of having GE were 5 times higher among children receiving cyclosporine than in those not receiving this medication, and 4 times higher among boys than girls. Supragingival plaque and the use of CCB, however, were not found to be associated with GE. CONCLUSION: This study revealed that tacrolimus was not associated with gingival enlargement while cyclosporine remains a risk factor for the development of this condition in pediatric renal and liver transplant recipients.

Gingival enlargement among renal transplant recipients in the era of new-generation immunosuppressants.

BACKGROUND: Tacrolimus is a new-generation immunosuppressant as successful as cyclosporin in suppressing organ transplant rejection. Although cyclosporin is known to cause gingival enlargement (GE), tacrolimus has not been associated with this condition. We sought to explore the prevalence of GE among renal transplant recipients (RTRs) in relation to cyclosporin and tacrolimus while controlling for the effect of calcium channel blockers (CCBs) and supragingival plaque. METHODS: RTRs were recruited from our institution's Kidney Transplant Unit. Participants completed a standardized questionnaire and received a complete oral examination, including a soft tissue examination and a periodontal examination measuring probing depth, recession, bleeding on probing, plaque index (PI), and GE. RESULTS: Among 115 RTRs, 39 (34%) presented with GE, with the highest prevalence among those taking cyclosporin and CCBs (76%) and the lowest among tacrolimus users not on a CCB (15%). Tacrolimus was not found to be associated with GE. Cyclosporin was found to be associated with GE in a univariate analysis stratified by the use of CCBs, but multivariate analysis revealed that the only significant risk factors for GE were the use of CCBs and the widespread presence of abundant supragingival plaque (PI > or =2 on >40% of tooth surfaces). CONCLUSIONS: This study confirmed that tacrolimus is not associated with GE. Cyclosporin taken at the currently recommended low dosage and not in combination with a CCB may not be associated with a significant risk for GE in individuals with good oral hygiene. CCBs should be avoided among patients taking cyclosporin and those with poor oral hygiene.