Oral mucosal lesions in older people: relation to salivary secretion, systemic diseases and medications.

OBJECTIVES: To determine the prevalence of oral mucosal lesions in a sample of older Danish people and to investigate their associations with age, gender, systemic diseases, medications, xerostomia and salivary secretion. METHODS: A total of 668 community-dwelling individuals aged 65-95 years underwent a clinical examination, measurements of unstimulated and stimulated whole and labial salivary flow rates and an interview regarding xerostomia, general health, medication, tobacco and alcohol habits. RESULTS: Seventy-five per cent of all participants and 70% of the non-medicated ones had one or more oral mucosal lesions. The most prevalent lesions were lingual varicosities (28.3%), denture stomatitis (12.7%), candidiasis (11.8%), fissured tongue (9.1%) and frictional keratosis (8.4%). Lesions were generally associated with smoking and xerostomia. Varicosities were more common in participants with systemic diseases and medication intake, particularly with cardiovascular diseases and agents. Fissured tongue and atrophic tongue were associated with female gender, xerostomia and low unstimulated whole and labial salivary secretion. Oral candidiasis was associated with older age; being male; current smoker; having >3 diseases, intake of medications and low salivary flow rates; and identified in relation to denture stomatitis, fissured tongue and atrophic tongue and median rhomboid glossitis. CONCLUSIONS: Oral mucosal lesions are prevalent in older Danish people and generally associated with changes in both local and systemic factors. Tongue lesions in particular appeared as indicators that may identify patients with specific need of oral intervention.

Subgrouping of patients with oral lichen planus according to cytochrome P450 enzyme phenotype and genotype.

OBJECTIVE: This study aimed to determine if the activity of the environmentally influenced cytochrome P450 enzyme CYP1A2, alone or in combination with CYP2D6*4 genotype, discriminates subgroups of oral lichen planus (OLP) according to lifestyle factors and clinical manifestations. STUDY DESIGN: A total of 111 patients with OLP were categorized according to normal, low, or high CYP1A2 activity and CYP2D6 4 genotype. Lifestyle parameters influencing the CYP1A2 activity and symptoms and manifestations of OLP were recorded. RESULTS: Of the 111 patients, 21% had low, 65% normal, and 14% high CYP1A2 activity. The high-CYP1A2-activity group was more exposed to CYP1A2 inducers than the low-CYP1A2-activity group. In the normal-CYP1A2-activity group, more patients had a CYP2D6 4 genotype (58%) (P = .02), and they presented more symptoms (P = .003) and gingival lesions (P = .03). More patients in the low-CYP1A2-activity group and without CYP2D6 4 genotype presented red lesions (P = .04). CONCLUSIONS: We suggest CYP2D6 4 genotype as a disease-susceptible genotype and low or high CYP1A2 activity levels as indicators of environmental influence in OLP subgroups.

Associations between oral and ocular dryness, labial and whole salivary flow rates, systemic diseases and medications in a sample of older people.

OBJECTIVE: To investigate the associations between age, gender, systemic diseases, medications, labial and whole salivary flow rates and oral and ocular dryness in older people. METHODS: Symptoms of oral and ocular dryness, systemic diseases, medications (coded according to the Anatomical therapeutic chemical (ATC) classification system), tobacco and alcohol consumption were registered, and unstimulated labial (LS) and unstimulated (UWS) and chewing-stimulated (SWS) whole salivary flow rates were measured in 668 randomly selected community-dwelling elderly aged 65-95. RESULTS: Presence of oral (12%) and ocular (11%) dryness was positively correlated. Oral dryness was associated with low UWS, SWS and LS, and ocular dryness with low UWS and SWS. Oral and ocular dryness was related to female gender, but not to age. Only four persons in the healthy and nonmedicated subgroups reported oral and ocular dryness. The numbers of diseases and medications were higher in the older age groups and associated with oral and ocular dryness, low UWS, SWS and LS. On average, women were slightly older, reported more oral and ocular dryness and had lower UWS, SWS, LS and higher numbers of diseases and medications. High prevalence and odds ratios for oral dryness were associated with metabolic, respiratory and neurological diseases and intake of thyroid hormones, respiratory agents (primarily glucocorticoids), psycholeptics and/or psychoanaleptics, antineoplastics, proton pump inhibitors, antidiabetics, loop diuretics, antispasmodics, quinine and bisphosphonates. Ocular dryness was especially associated with neurological diseases and intake of psycholeptics and/or psychoanaleptics. Intake of magnesium hydroxide, antithrombotics, cardiac agents, thiazides, beta-blockers, calcium channel blockers, ACE inhibitors/angiotensin II antagonists, statins, glucosamine, paracetamol/opioids, ophthalmologicals and certain combination therapies was related to oral and ocular dryness. CONCLUSIONS: In older people, oral and ocular dryness are associated with low salivary flow rates, specific as well as high number of diseases and medications, but neither with age and gender per se nor with tobacco and alcohol consumption. New detailed information concerning associations between medications and oral and ocular dryness has been obtained using the ATC classification system.

Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?

BACKGROUND: Lichenoid drug eruptions (LDE) in the oral cavity are adverse drug reactions (ADR) that are impossible to differentiate from oral lichen planus (OLP) as no phenotypic criteria exist. Impaired function of polymorphic cytochrome 450-enzymes (CYPs) may cause increased plasma concentration of some drugs resulting in ADR/LDE. In an earlier study we did not find more patients with OLP (OLPs) with impaired CYP-genotype. OBJECTIVES: To test if more OLPs have an impaired CYP-phenotype than to be expected from the CYP-genotype and to find clinical criteria characterising oral LDE. METHODS: One hundred and twenty OLPs were genotyped for the most common polymorphisms of CYP2D6 and CYP2C19 that result in impaired function. One hundred and ten did a phenotype test of both enzymes. The exposure to drugs and polypharmacy and the CYP metabolism of the drugs were evaluated. The OLP manifestations were registered. RESULTS: The only difference in OLP manifestations was that patients with a CYP2D6 genotype with less than two fully functional alleles presented more asymmetrical OLP distribution in particular in non-medicated patients (P < 0.05). No more OLPs than expected from the genotype had a phenotype with reduced function. However, the established phenotypic categories could not differentiate between the genotypes with two or one fully functional allele. Nevertheless, among the patients with a phenotype with normal function the patients with only one functional allele had a statistically significant higher metabolic ratio compared to patients with two fully functional alleles (P < 0.05). CONCLUSION: It was not possible to identify LDE by impaired function of polymorphic CYPs.

Polymorphic drug metabolizing CYP-enzymes--a pathogenic factor in oral lichen planus?

BACKGROUND: Oral lichen planus (OLP) is a chronic mucosal disease with a characteristic clinical phenotype. Environmental exposures, e.g. drugs have been associated with the pathogenesis. OBJECTIVES: To test the hypothesis that some OLP lesions have a pharmacological pathogenesis related to polymorphisms of the cytochrome P450 enzymes (CYPs) resulting in poor or intermediate CYP metabolism. METHODS: One hundred and twenty patients with OLP and 180 gender-matched controls without OLP were genotyped for CYP2C9, CYP2C19, and CYP2D6 alleles with absent or reduced function. RESULTS: The prevalence of poor or intermediate metabolizers was not higher among the OLPs as compared with the controls; however, there were higher numbers of variant CYP2D6 genotypes among the OLP females (P < 0.05). There were no differences between the groups with regard to intake of drugs metabolized by polymorphic CYPs or drug or herbal products inhibiting CYPs. The prevalence of CYP2D6*4 alleles among the OLPs was higher [28%; 95% confidence interval (CI) 20-36%] than previously reported among Danes (19%; 95% CI 17-22%). Fifty per cent of the OLPs had a CYP2D6*4 genotype as compared with 30% in the background population (P = 0.0001). The CYP2D6*4 protein has sequence homology with human herpes simplex virus type 1 (HSV1) and Candida albicans, which may result in molecular mimicry. CONCLUSION: It was not possible to substantiate a pharmacological pathogenesis of OLP based on poor or intermediate CYP metabolism. However, molecular mimicry between CYP2D6, in particular CYP2D6*4, and common oral pathogens may be involved in the pathogenesis of OLP.

Expression of two drug-metabolizing cytochrome P450-enzymes in human salivary glands.

OBJECTIVE: The oral cavity is constantly lubricated by saliva and even small amounts of xenobiotics and / or their metabolites in the saliva may affect the oral mucosa. Our aim was therefore to clarify if xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 are expressed in salivary glands. METHODS: Formalin-fixed paraffin-embedded specimens from parotid (10), submandibular (7) and labial (10) salivary glands were examined immunohistochemically and by in situ hybridization for expression of CYP1A2 and CYP3A4 protein and mRNA. RESULTS: CYP1A2 and CYP3A4 protein and mRNA were detected in ductal and seromucous / serous acinar cells in all gland types although to a varying degree and intensity. Mucous acinar cells were positive to a lesser extent. CONCLUSION: The results indicate a xenobiotic metabolizing capability of salivary glands. This may have implications for development of oral mucosal disease as a result of mucosal exposure to metabolites originating from internal sources (blood) as well as from saliva.

Oral lichen planus and intake of drugs metabolized by polymorphic cytochrome P450 enzymes.

OBJECTIVE: To study if patients with oral lichen planus (OLP) had a medication profile different from that of a control group without oral mucosal lesions. It was hypothesized that OLP lesions might result from poor drug metabolism (PM) because of genetic variation of the major cytochrome P450-enzymes (CYPs with a PM-risk). SUBJECTS AND METHODS: Dental records of 172 OLP patients were reviewed in this cross-sectional study and 152 sex- and age-matched subjects served as controls. The measures for the drug profiles were medicine type (ATC-code), mono- and polypharmacy, CYP-enzyme metabolism pattern, and medicine with a potential to induce lichenoid drug eruptions. RESULTS: Fifty per cent of the OLP patients consumed daily medications as compared with 59% of the controls. The OLP patients more frequently consumed medicines metabolized by CYPs with a PM-risk (P = 0.03). Furthermore, they consumed more medicine with an inhibitory effect on one or more CYPs than the controls (P = 0.01). CONCLUSION: Confounders like sex, age, systemic diseases, drug distribution into the therapeutic classes, and polypharmacy were similar in the two groups; but the OLP patients consumed more drugs metabolized by CYPs with a PM-risk. The results argue for further investigation of associations between OLP, medication intake and the CYP-enzyme metabolic pathways.