Oral disease profiles in chronic graft versus host disease.

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials.

Malnutrition in patients with chronic GVHD.

Malnutrition is a known complication of chronic GVHD (cGVHD), but has not been well described in the context of organ-specific manifestations and the recent National Institutes of Health (NIH) criteria. Here, 210 cGVHD patients were analyzed, in a cross-sectional study design, for demographics, transplant-related history, clinical assessments, symptoms, function, quality-of-life, laboratory values and survival in order to determine their associations with nutritional status. Most patients had long-standing, moderate or severe cGVHD and had failed many lines of therapy. Twenty-nine percent (60/210) of subjects were malnourished, using the subjective Patient-Generated Subjective Global Assessment (PG-SGA) questionnaire and evaluation. No demographic or transplant characteristics were associated with malnutrition; cGVHD of the lungs, gastrointestinal (GI) tract and mouth, NIH global score, cGVHD symptoms, worse functioning, low albumin, poorer survival and low BMI were associated with malnutrition. A predictive model was developed from all variables of significance: cGVHD of the lungs, GI tract, mouth and BMI accurately predicted 84.2% of malnourished patients as well as 87.2% of well-nourished patients. The PG-SGA questionnaire may be a useful tool in diagnosing nutritional deficits in cGVHD patients undergoing one-time evaluations. Longitudinal prospective studies should assess the utility of nutritional support interventions in cGVHD.

Validation of the National Institutes of Health chronic GVHD Oral Mucosal Score using component-specific measures.

Oral chronic GVHD (cGVHD) is a common, late complication of alloSCT that is associated with significant patient morbidity. The NIH Oral Mucosal Score (NIH OMS) was developed to assess oral cGVHD therapeutic response, but has not been fully validated. This study's purpose was to conduct a rigorous construct validity and internal consistency analysis of this score and its components (erythema, lichenoid, ulcers, mucoceles) using established measures of oral pain, oral function, oral-related quality-of-life, nutrition and laboratory parameters in 198 patients with cGVHD. The construct validity of the NIH OMS was supported: a moderate correlation was observed between NIH OMS and mouth pain (rho=0.43), while a weaker correlation was observed with low albumin (rho=-0.26). Total NIH OMS, erythema and lichenoid components were associated with malnutrition, oral pain and impaired oral QOL, while ulcers were only associated with oral pain. No associations were found between mucoceles and any indicator evaluated, including salivary function or xerostomia. Kappa determined between scale components was low overall (all 0.35), supporting a conclusion that each component measures a distinct manifestation of oral cGVHD. This study supports the use of the NIH OMS and its components (erythema, lichenoid and ulcerations) to measure clinician-reported severity of oral cGVHD.

Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research.

Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. In this review, we discuss the presentation, prevalence, diagnosis, and treatment of oral manifestations in chronic graft-versus-host disease (cGVHD), which is a major late complication in patients treated by allogeneic hematopoietic stem cell transplantation. We assess current general knowledge of systemic and oral cGVHD and present general treatment recommendations based on literature review and our clinical experience. Additionally, we review areas where the understanding of oral cGVHD could be improved by further research and address tools with which to accomplish the long-term goal of providing better health and quality of life to patients with cGVHD.

Oral chronic graft-vs.-host disease characterization using the NIH scale.

Chronic graft-vs.-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Oral cGVHD is manifested by mucosal, salivary, and/or sclerotic changes that have been linked to pain and poor quality of life. Our aim was to describe the demographic, clinical, and laboratory markers of oral cGVHD in alloHSCT patients (N = 187) enrolled in a cGVHD cross-sectional study at the NIH (#NCT00331968). We propose a meaningful and reproducible measure of disease defined by a cut-off point reflecting clinical minimally detectable change (0-2 = no oral cGVHD, 3-15 = oral cGVHD) on the 15-point NIH cGVHD clinician assessment scale. Forty-four patients had oral cGVHD. Oral cGVHD was associated with a quiescent or de novo type of cGVHD onset (p = 0.05), higher cGVHD severity (p = 0.033), lower albumin (p = 0.0008), higher total complement (p = 0.012), greater bother from foods or oral ulcers and greater mouth pain, and sensitivity (p < 0.0001). Multivariable logistic regression modeling with albumin, mouth pain, and total complement was 74.3% predictive of oral cGVHD and 80.2% predictive of non-oral cGVHD. We propose the use of >2 points on the NIH scale as a reproducible definition of clinically significant oral cGVHD, which may be useful in clinical settings or as eligibility criterion or as an endpoint in clinical trials.

Craniofacial and dental findings in cystinosis.

OBJECTIVES: Cystinosis is a rare autosomal recessive lysosomal storage disorder with developmental and mineralization anomalies as part of its clinical presentation. The objective of this study was to provide the first systematic assessment of the craniofacial and dental characteristics associated with cystinosis. STUDY DESIGN: Oral and radiographic evaluations were performed on 73 patients with cystinosis. Analyses of cephalometry (n = 20), taurodontism (n = 47), caries (n = 47), enamel defects (n = 48), soft tissue anomalies (n = 48), and dental age (n = 41) were performed on the cystinosis group, and compared with age- and sex-comparable controls or standards. RESULTS: Cystinosis patients manifested relative mandibular deficiency, an increased facial height, and a reduced airway space. Taurodontism and enamel defects were significantly more prevalent in cystinosis patients compared with controls (P < 0.0001 and P = 0.027, respectively). Children (aged <15 years) with cystinosis also demonstrated a significant delay, of almost 9 months, of their dental development (P < 0.001). CONCLUSION: Novel craniofacial and dental features are associated with cystinosis. Craniofacial deficiencies may influence the swallowing and respiratory complications seen in cystinosis. Renal pathology and associated mineral imbalance may explain the dental root and enamel anomalies found in cystinosis patients; the developmental delays in cystinosis include delayed dental formation.

Enamel defects and salivary methylmalonate in methylmalonic acidemia.

INTRODUCTION AND OBJECTIVE: To characterize enamel defects in patients with methylmalonic acidemia (MMA) and cobalamin (cbl) metabolic disorders and to examine salivary methylmalonate levels in MMA. SUBJECTS AND METHODS: Teeth from patients (n = 32) were evaluated for enamel defects and compared with age- and gender-matched controls (n = 55). Complementation class (mut, cblA, cblB and cblC) and serum methylmalonate levels were examined. Primary teeth from two patients were examined by light and scanning electron microscopy and salivary methylmalonate levels from two patients were analyzed. RESULTS: Enamel defects were significantly more prevalent per tooth in the affected group than the control group, across complementation types (P < 0.0001). The mut MMA subgroup had a significantly higher prevalence per individual of severe enamel defects than controls (P = 0.021), and those with enamel defects exhibited higher serum methylmalonate levels than those without (P = 0.017). Salivary methylmalonate levels were extremely elevated and were significantly higher than controls (P = 0.002). Primary teeth were free of enamel defects except for two cblC patients who exhibited severe enamel hypoplasia. One primary tooth from a cblC patient manifested markedly altered crystal microstructure. CONCLUSION: Enamel anomalies represent a phenotypic manifestation of MMA and cbl metabolic disorders. These findings suggest an association between enamel developmental pathology and disordered metabolism.

Salivary procalcitonin and periodontitis in diabetes.

Periodontitis and type 2 diabetes are co-morbid conditions, both characterized by infectious susceptibility. We investigated procalcitonin (ProCT) levels in the serum and saliva of persons with periodontitis and type 2 diabetes (n = 20), to determine if these levels are altered by periodontitis activity or by hyperglycemia. Persons with severe periodontitis showed higher levels of salivary-ProCT than did those with moderate periodontitis (241 +/- 71 vs. 77 +/- 516 pg/mL, p = 0.02) and higher levels than did healthy control individuals (118 +/- 26 pg/mL, p = 0.05). Salivary-ProCT levels were correlated with bleeding-on-probing (r = 0.45, p = 0.05), as well as with HgbA(1c) (r = 0.49, p = 0.03). Salivary levels of ProCT were higher than serum levels for the periodontitis/diabetes group (152 +/- 37 vs. 78 +/- 17 pg/mL, p = 0.02) and the control group (118 +/- 146 vs. 48 +/- 17 pg/mL, p = 0.01). Persons with periodontitis and type 2 diabetes have salivary-ProCT levels that reflect their degree of periodontitis activity and hyperglycemia. This study demonstrates, for the first time, the presence of procalcitonin (ProCT), an established serum marker of infection, in saliva.