Significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia in oral precancer patients.

BACKGROUND/PURPOSE: Our previous studies found relatively higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia in patients with different types of oral mucosal diseases. This study evaluated whether patients with oral precancerous lesions (oral precancer patients) had significantly higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects. METHODS: The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects were measured and compared. RESULTS: We found significantly lower mean serum iron (for women only), vitamin B12, and folic acid levels and a significantly higher mean serum homocysteine level in oral precancer patients than in healthy control subjects (all P-values < 0.05). Moreover, 131 oral precancer patients had significantly higher frequencies of blood hemoglobin (3.1%), vitamin B12 (43.5%), and folic acid (46.6%) deficiencies and hyperhomocysteinemia (22.1%) than 131 healthy control subjects (all P-values < 0.05). Of 131 oral precancer patients, lower mean serum folic acid levels were found in 87 cigarette smokers than in 44 non-smokers (P = 0.002), in 26 smokers consuming > 20 cigarettes per day than in 61 smokers consuming ≤ 20 cigarettes per day (P = 0.024), and in 52 betel quid chewers than in 79 non-chewers (P = 0.051). CONCLUSION: There are significantly higher frequencies of anemia, serum vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in oral precancer patients than in healthy control subjects.

Increased oral inflammation, leukocytes, and leptin, and lower adiponectin in overweight or obesity.

OBJECTIVES: The association between body mass index (BMI) and oral diseases was investigated, and levels of obesity-related inflammatory mediators were evaluated. SUBJECTS AND METHODS: Participants (n = 160) were clinically and radiographically examined for oral diseases. Blood profiles were recorded. Levels of adiponectin, leptin, and C-reactive protein (CRP) were measured. RESULTS: One hundred and thirteen (70.6%) participants had overweight or obese status (BMI ≥ 23.0 kg/m2 ). Sum of dental diseases and severe periodontitis were higher in overweight or obese individuals than in normal-weight participants (p = .037 and p = .002, respectively). A significant difference in oral mucosal disorders between normal weight and overweight or obesity was not found. Plasma leukocyte counts, liver enzymes, leptin, and CRP levels were increased while adiponectin levels were decreased in individuals with BMI≥23.0 kg/m2 compared with normal-weight participants. After adjusting for age, sex, fasting plasma glucose level, smoking, and exercise, obesity was associated with sum of dental diseases (ß = 0.239, p = .013), severe periodontitis (OR=4.52; 95% CI 1.37, 14.95, p = .013), adiponectin (ß = -0.359, p < .001), leptin (ß = 0.630, p < .001), and CRP levels (OR=12.66; 95% CI 3.07, 52.21, p < .001). CONCLUSION: Overweight or obese Thai people were related to an increase in inflammatory dental and periodontal diseases with an altered health profile and plasma inflammatory mediators.

Anemia and hematinic deficiencies in oral mucosal disease patients with microcytosis.

BACKGROUND/PURPOSE: Patients with microcytosis (defined as mean corpuscular volume < 80 fL) are not uncommonly found in oral mucosal disease clinics. This study assessed the anemia statuses and hematinic deficiencies in 240 oral mucosal disease patients with microcytosis. METHODS: The mean red blood cell (RBC) count, mean corpuscular volume, and RBC distribution width, as well as blood concentrations of hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine in 240 microcytosis patients and in 240 age- and sex-matched healthy control individuals were measured and compared. RESULTS: Microcytosis patients had significantly lower mean Hb, iron, and folic acid levels as well as significantly higher mean RBC count and RBC distribution width than healthy control individuals. Microcytosis patients also had significantly greater frequencies of Hb, iron, vitamin B12, and folic acid deficiencies as well as of RBC number > 5 × 1012/L, and abnormally high homocysteine levels than healthy control individuals. Moreover, 162 (67.5%) of the 240 microcytosis patients had anemia. Of 162 anemic microcytosis patients, 87 (53.7%) had iron deficiency anemia, 61 (37.7%) had thalassemia trait (TT)-induced anemia, and 14 (8.6%) had other microcytic anemia. CONCLUSION: We conclude that approximately 45%, 4%, and 5% of microcytosis patients have iron, vitamin B12, and folic acid deficiencies, respectively, and approximately 10% of microcytosis patients have abnormally high homocysteine levels. Moreover, 67.5% of 240 microcytosis patients and 50.8% of 120 TT patients had anemia. Iron deficiency anemia is the most common type of anemia in microcytosis patients, followed by TT-induced anemia and other microcytic anemia.

Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and -negative oral mucosal disease patients with microcytosis.

BACKGROUND/PURPOSE: Microcytosis is defined as mean corpuscular volume (MCV) < 80 fL. This study assessed the anemia statuses and hematinic deficiencies in 30 patients with gastric parietal cell antibody-positive microcytosis (GPCA+/microcytosis) and 210 patients with GPCA-negative microcytosis (GPCA-/microcytosis). METHODS: We measured and compared the mean red blood cell (RBC) count, MCV, and RBC distribution width (RDW), as well as blood levels of hemoglobin, iron, vitamin B12, folic acid, and homocysteine among the aforementioned patient groups and 240 healthy controls. RESULTS: Compared with GPCA-/microcytosis, the positive counterparts presented with a lower mean serum vitamin B12 level (marginal significance), significantly higher mean RDW and serum homocysteine level, and significantly greater frequencies of vitamin B12 deficiency and high homocysteine level. GPCA-/microcytosis patients had significantly greater frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of RBC count > 5 × 1012/L than healthy controls. Moreover, 19 of 30 GPCA+/microcytosis patients and 143 of 210 GPCA-/microcytosis patients had anemia, with iron deficiency anemia being the most common type, followed by thalassemia trait-induced anemia and microcytic anemia due to other causes. CONCLUSION: We conclude that GPCA in microcytosis patients' sera may have caused significantly lower mean vitamin B12 level as well as significantly higher mean RDW and serum homocysteine level in our GPCA+/microcytosis patients than in GPCA-/microcytosis patients. Herein, iron deficiency anemia was the most common type of anemia in anemic GPCA+/microcytosis and GPCA-/microcytosis patients.

Association of serum cytokines with oral HPV clearance.

BACKGROUND: Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. METHODS: From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1ß, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. RESULTS: Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4<500 cells/µl) among HIV-infected participants. No other cytokines were associated with clearance. CONCLUSION: High serum TNF-α is associated with reduced clearance of oral HPV infection.

Serum and salivary IgG and IgA antibodies to desmoglein 3 in mucosal pemphigus vulgaris.

BACKGROUND: The use of saliva for the diagnosis of pemphigus vulgaris (PV) by enzyme-linked immunosorbent assay (ELISA) using desmoglein (Dsg)3 antigen has not been extensively documented, nor has the detection of serum IgA antibodies to Dsg3. OBJECTIVES: (i) To establish whether whole saliva might provide a suitable alternative to serum for diagnosing and monitoring PV; (ii) to investigate whether anti-Dsg3 IgA antibodies can be detected in serum and saliva and (iii) to establish whether there is an association between serum or saliva anti-Dsg3 antibodies and disease severity. METHODS: Precoated Dsg3 ELISA plates were used to test serum and/or saliva for IgG and IgA antibodies. Matched serum and whole saliva samples were collected from 23 patients with PV, 17 healthy subjects and 19 disease controls. All patients with PV, disease controls and six healthy controls provided matched parotid saliva. RESULTS: Whole saliva IgG antibodies to Dsg3 were detected in 14 of 23 patients (61%) and serum IgG antibodies were detected in 17 of 23 (74%) with a strong positive correlation. Serum IgA antibodies were detected in 14 of 23 patients with PV (61%) with a combined positivity (IgG and/or IgA antibodies to Dsg3) of 78% (18 of 23). We were unable to show IgA anti-Dsg3 antibodies in either whole or parotid saliva of patients with PV. Sequential samples showed that changes in IgG antibody titres in whole saliva were associated with a change in disease severity scores. CONCLUSIONS: Assay of salivary IgG antibodies to Dsg3 offers a diagnostic alternative to serum in the diagnosis and monitoring of PV. The role of anti-Dsg3 IgA antibodies requires further elucidation in the pathogenesis of PV.

Correlation of serum ANA and direct immunofluorescence studies in elderly Thai patients with red and white oral lesions.

OBJECTIVES: This study investigated the presence of serum antinuclear antibodies (ANA) profile and direct immunofluorescence (DIF) evaluation in elderly Thai patients with red and white oral lesions. MATERIALS AND METHODS: Thirty-two patients with red and white oral lesions were divided into two groups: group I consisted of 10 cases not taking medications, while group II consisted of 12 cases taking medications, and 30 healthy subjects as a control group. Blood samples were used to determine the ANA profile. DIF was investigated in the lesion containing groups. RESULTS: Serum ANA was found in six cases (60%) in group I, eight cases (66.7%) in group II, and 19 cases (63.3%) in the control group. There were no significant differences between group I and group II and the control group (P > 0.05). Serum ANA was most commonly found in patients taking hypolipidemics (80%), followed by antihypertensives (71.4%), NSAIDs (50%), hypoglycemics (50%), and others (66.7%). The anticytoplasmic staining frequency in group II was higher compared with group I and the control group. Anti-dsDNA antibodies were not found in any group. CONCLUSIONS: Elderly patients with red and white oral lesions who were taking medications had a higher serum ANA frequency than group I and the control group.

Blood profile of oral mucosal disease patients with both vitamin B12 and iron deficiencies.

BACKGROUND/PURPOSE: Vitamin B12 and iron deficiencies lead to macrocytosis [mean corpuscular volume (MCV) ≥ 100 fL] and microcytosis (MCV < 80 fL), respectively. This study evaluated anemic status, MCV, serum homocysteine level, and serum gastric parietal cell antibody (GPCA) level in oral mucosal disease patients with both vitamin B12 and iron deficiencies. METHODS: The blood hemoglobin (Hb), iron, vitamin B12, folic acid and homocysteine concentrations, MCV, and serum GPCA in 149 patients with both vitamin B12 and iron deficiencies were measured and compared with the corresponding data in 149 age- and sex-matched healthy control subjects. RESULTS: We found that 54 (36.2%), 16 (10.7%), 44 (29.5%), and 36 (24.2%) patients with both vitamin B12 and iron deficiencies had Hb deficiency (men <13 g/dL, women <12 g/dL), folic acid deficiency (≤ 6 mg/mL), abnormally high blood homocysteine level (>12.6 µM), and serum GPCA positivity, respectively. Patients with both vitamin B12 and iron deficiencies had a significantly higher frequency of Hb deficiency, abnormally elevated blood homocysteine level, and serum GPCA positivity than healthy control subjects (all p values < 0.001). Of 149 patients with both vitamin B12 and iron deficiencies, 10 (6.7%) had high MCV (≥ 100 fL), 108 (72.5%) had normal MCV (between 80 fL and 99 fL), and 31 (20.8%) had low MCV (<80 fL). CONCLUSION: Approximately 73%, 30%, and 24% of patients with both vitamin B12 and iron deficiencies are found to have normal MCV, abnormally high blood homocysteine level, and serum GPCA positivity, respectively.

Hematinic deficiencies and pernicious anemia in oral mucosal disease patients with macrocytosis.

BACKGROUND/PURPOSE: Macrocytosis is defined as having the mean corpuscular volume (MCV) ≥ 100 fL. This study assessed hematinic deficiencies and pernicious anemia (PA) in oral mucosal disease patients with macrocytosis. METHODS: The blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine concentrations and MCV in 60 oral mucosal disease patients with macrocytosis were measured and compared with the corresponding data in 120 age- and sex-matched healthy control participants. PA was defined by the World Health Organization (WHO) as having an Hb concentration < 13 g/dL for men and < 12 g/dL for women, an MCV ≥ 100 fL, a serum vitamin B12 level < 200 pg/mL, and serum gastric parietal cell antibody (GPCA) positivity. RESULTS: We found that 30 (50.0%), 7 (11.7%), 24 (40.0%), and three (5.0%) oral mucosal disease patients with macrocytosis had deficiencies of Hb (men < 13 g/dL, women < 12 g/dL), iron (< 60 µg/dL), vitamin B12 (< 200 pg/mL), and folic acid (< 4 mg/mL), respectively. Moreover, 38 (63.3%) and 16 (26.7%) macrocytosis patients had abnormally high blood homocysteine level (> 12.3 µM) and serum GPCA positivity, respectively. Macrocytosis patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency, of abnormally elevated blood homocysteine level, and of GPCA positivity than healthy control participants (p < 0.001). However, only 16.7% of 60 macrocytosis patients were diagnosed as having PA by the WHO definition. CONCLUSION: Only 16.7% of oral mucosal disease patients with macrocytosis are discovered to have PA by the WHO definition.

Interrelationship of clinical, histomorphometric and immunohistochemical features of oral lesions in chronic paracoccidioidomycosis.

BACKGROUND: This study aimed to analyze the oral lesions of chronic paracoccidioidomycosis concerning their histomorphometric, immunohistochemical, and clinical features in a standardized sample. METHODS: Fifty biopsy specimens of oral lesions of chronic paracoccidioidomycosis were submitted to hematoxylin and eosin (H&E), Grocott-Gomori and immunohistochemical staining. Data regarding disease duration and size and number of oral lesions, as well as erythrocytes, leukocytes, lymphocytes, hematocrit, hemoglobin, and erythrocyte sedimentation rate, were collected from medical charts. Granuloma density and number and diameter of buds and fungal cells, and IL-2, TNF-alpha and IFN-gamma expression, as well as clinical and hematological features, were quantified and correlated. RESULTS: Bud diameter was significantly greater in intermediate density granulomas compared to higher density granulomas. The other variables (number of buds, number and diameter of fungi, expression of IL-2, TNF-alpha and IFN-gamma, and clinical and hematological features) did not significantly change with the density of granulomas. There was a positive correlation between bud number and fungal cell number (r = 0.834), bud diameter and fungal cell diameter (r = 0.496), erythrocytes and number of fungi (r = 0.420), erythrocytes and bud number (r = 0.408), and leukocytes and bud number (r = 0.396). Negative correlation occurred between number and diameter of fungi (r = -0.419), bud diameter and granuloma density (r = -0.367), TNF-alpha expression and number of fungi (r = -0.372), and TNF-alpha expression and bud number (r = -0.300). CONCLUSION: The histological, immunological, and clinical features of oral lesions evaluated did not differ significantly between patients in our sample of chronic paracoccidioidomycosis. TNF-alpha levels were inversely correlated with intensity of infection.

Resistant oral mucosal lesions in pemphigus vulgaris responsive to double filtration plasmapheresis: First case report from Turkey.

BACKGROUND: Adjuvant therapeutic methods are employed when pemphigus vulgaris (PV) fails to be controlled by conventional corticosteroid treatment. OBJECTIVE: The efficacy of double filtration plasmapheresis (DFPP) was investigated in a PV patient with severe, refractory mucosal disease. METHODS: A total of 3 DFPP cycles, each cycle consisting of 5 double filtration sessions conducted on alternate days was completed. RESULTS: DFPP provided immediate clinical relief of symptoms as well as a significant decrease in anti-desmoglein antibody levels and allowed for a much lower corticosteroid dose. CONCLUSION: DFPP was an effective and safe adjuvant therapy in our patient with PV and it offers a valid treatment option in PV patients with recalcitrant disease.

Correlation between viral load, plasma levels of CD4 - CD8 T lymphocytes and AIDS-related oral diseases: a multicentre study on 30 HIV+ children in the HAART era.

This experimental retrospective multicenter study carried out on 30 seropositive children treated with Highly Active Antiretroviral Therapy (HAART), between the ages of 18 months and 14 years, in the clinical categories Centers for Disease Control (CDC) classification 1993 A (mildly symptomatic), B (moderately symptomatic) and C (severely symptomatic) aims to: 1) clinically and immunologically demonstrate the therapeutic benefits of HAART; 2) monitor the frequency of AIDS-related oral diseases in seropositive children with HAART therapy; 3) monitor the plasma levels of total CD4, CD4 percent, CD8 percent, CD4-CD8 lymphocytes and viral load from 1997 to 30 April, 2011. The statistic methods used are the analysis of covariance and the Bonferroni Test. More than 100 AIDS-related oral diseases were found in the study samples, the most frequent being: oral candidiasis, oropharyngeal candidiasis, HSV-1 herpetic esophagyitis, herpetic gingivolstomatitis (RHOG), recurrent aphthous stomatitis (RAS), parotid swelling, oral hairy leukoplakia (OHL), Herpes simplex 1 (HSV-1), linear gingival erythema (LGE), necrotizing gingivitis (NUG), facial lipodistrophy, facial-cervical lymphadenopathy (FCL), xerostomia, dysgeusia, hyposmia, oral mucosa hyperpigmentation (OMP). The Bonferroni test showed a significant difference between the mean plasma values (mpVTL) of total CD4, CD4 percentage, CD4-CD8 T lymphocytes and Viral Load (VL) of the various oral diseases found in the study samples. The therapeutic benefits of HAART are: immune reconstitution; reduction of the HIV/AIDS-related stomatology diseases; prevention and cure of the AIDS correlated neoplasias; reduction in maternal-fetal transmission of the HIV virus. The negative effects of HAART in relation to odontostomatolgy are: increase in oral lesions from HPV; xerostomia; dysgeusia/ageusia, hyposmia, perioral paresthesia; hyperpigmentation of oral mucosa; facial lipodystrophy, recurrent aphthous stomatitis (RAS). No case of immune reconstitution inflammatory syndrome or human papillomavirus (HPV)-related oral diseases were found in this study.

The Predictive Value of Interleukin-6 and Neutrophil-Lymphocyte Ratio in Patients with Severe and Extremely Severe Oral and Maxillofacial Space Infections.

OBJECTIVE: To investigate the correlation between clinical manifestation and neutrophil-lymphocyte ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) in the patients with severe and extremely severe oral and maxillofacial space infection (OMSI). METHODS: In this retrospective study, we included 18 patients with severe and extremely severe OMSI from November 2012 to October 2018. Pearson or Spearman correlation coefficients were calculated to measure the association between the number of complications and locations and the number and percentage of lymphocyte, leukocyte, neutrophil, eosinophil, basophil, monocyte, CRP, and IL-6. A multivariable regression model was used to predict the number of complications and locations from these measures. RESULTS: IL-6 was positively correlated with neutrophil-lymphocyte ratio (r s = 0.773, P = 0.005), percentage of neutrophil (r s = 0.927, P = 0.001), and the number of neutrophil (r s = 0.627, P = 0.039). It was negatively correlated with percentage of monocyte (r s = -0.773, P = 0.005). CRP was positively correlated with neutrophil-lymphocyte ratio (r s = 0.556, P = 0.020) and percentage of neutrophil (r s = 0.515, P = 0.035). It was negatively correlated with the number of lymphocyte (r s = -0.517, P = 0.017), percentage of lymphocyte (r s = -0.578, P = 0.015), number of eosinophil (r s = -0.560, P = 0.020), percentage of eosinophil (r s = -0.504, P = 0.039), number of basophil (r s = -0.504, P = 0.039), and percentage of basophil (r s = -0.548, P = 0.023). The number of the involved organs was positively correlated with neutrophil-lymphocyte ratio (r s = 0.511, P = 0.030). The number of complications was positively correlated with the percentage of neutrophils (r = 0.738, P = 0.001), the neutrophil-lymphocyte ratio (r = 0.576, P = 0.012), IL-6 (r s = 0.907, P = 0.001), and CRP (r s = 0.599, P = 0.011). Multivariable regression analysis showed that the neutrophil-lymphocyte ratio (ß = 0.080) was a significant predictor of the number of the involved organs and the neutrophil-lymphocyte ratio (ß = 0.099). In addition, IL-6 (ß = 0.002) was a significant predictor of the number of complications. CONCLUSIONS: The neutrophil-lymphocyte ratio and IL-6 contributed to the assessment of general condition in severe and profound OMSI patients. These parameters can be used as predictors to evaluate the severity of OMSI.

[Immunological aspects of a case of extragenital endometriosis localized in the mouth]. / Aspects immunologiques d'un cas d'endométriose extra-génitale à localisation buccale à Abidjan.

To appreciate the role of the immune system in transportation and development of endometer cells in mouth, authors reported the results of immunological parameters analysis in one patient suffering to a mouth localisation healed endometriosis out of hormonal therapy in experimental and analytic study. Immunoglobulin A, G, M and C3, C4 complement fractions were measured by Mancini radial immunodiffusion. The count of CD4+, CD8+and B Cell was performed by BD FASCalibur flow cytometer. Autoimmune diseases were searched after by measuring autoantibodies using agglutination and immunofluoresence methods. The results showed any antibodies detected and the count of CD4, CD8 and B cells was normal. However, IgG and IgA increased. But C3, C4 factions and IgM decreased. This seems an immunological disorder which could be more explored in NK cells and cytokines study.

What can we learn about functional importance of human antimicrobial peptide LL-37 in the oral environment from severe congenital neutropenia (Kostmann disease)?

The human antimicrobial peptide LL-37 is produced by neutrophils and epithelial cells, and the peptide can be detected in plasma as well as saliva. LL-37 is active against both gram-positive and gram-negative bacteria including oral pathogens such as Porphyromonas gingivalis and Streptococcus mutans. Besides its antimicrobial properties, LL-37 modulates the innate immune system, and furthermore, it also affects host cell viability. Although, both structural and functional properties of LL-37 have been extensively investigated, its physiological/pathophysiological importance in-vivo is not completely understood. In this review, Kostmann disease (morbus Kostmann) is highlighted since it may represent a LL-37 knockdown model which can provide new important information and insights about the functional role of LL-37 in the human in-vivo setting. Patients with Kostmann disease suffer from neutropenia, and although they are treated with recombinant granulocyte colony-stimulating factor (G-CSF) to normalize their levels of neutrophils, they lack or have very low levels of LL-37 in plasma, saliva and neutrophils. Interestingly, these patients suffer from severe periodontal disease, linking LL-37-deficiency to oral infections. Thus, LL-37 seems to play an important pathophysiological role in the oral environment antagonizing oral pathogens and thereby prevents oral infections.