Validation of an Oral Disease Severity Score (ODSS) tool for use in oral mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease predominantly affecting the oral mucosa. Optimal management relies upon thorough clinical assessment and documentation at each visit. OBJECTIVES: The primary aim of this study was to validate the Oral Disease Severity Score (ODSS) for the assessment of oral involvement in MMP. We also compared its inter- and intraobserver reliability with those of the oral parts of the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Physician's Global Assessment (PGA). METHODS: Fifteen patients with mild-to-moderately severe oral MMP were scored for disease severity by 10 oral medicine clinicians from four U.K. centres using the ODSS, the oral sections of MMPDAI and ABSIS, and PGA. Two clinicians rescored all patients after 2 h. RESULTS: In terms of reliability, the interobserver ODSS total score intraclass correlation coefficient (ICC) was 0·97, MMPDAI activity 0·59 and damage 0·15, ABSIS total 0·84, and PGA 0·72. The intraobserver ICCs (two observers) for ODSS total were 0·97 and 0·93; for MMPDAI activity 0·93 and 0·70 and damage 0·93 and 0·79; for ABSIS total 0·99 and 0·94; and for PGA 0·92 and 0·94. Convergent validity between ODSS and MMPDAI was good (correlation coefficient 0·88). The mean ± SD time for completion of ODSS was 93 ± 31 s, with MMPDAI 102 ± 24 s and ABSIS involvement 71 ± 18 s. The PGA took < 5 s. CONCLUSIONS: This study has validated the ODSS for the assessment of oral MMP. It has shown superior interobserver agreement over MMPDAI, ABSIS and PGA, and superior intraobserver reliability to MMPDAI. It is quick and easy to perform. What's already known about this topic? There are no validated scoring methodologies for oral mucous membrane pemphigoid (MMP). Proposed disease activity scoring tools for MMP include the Mucous Membrane Disease Area Index (MMPDAI) and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). The Oral Disease Severity Score (ODSS) has been validated for use in oral pemphigus vulgaris (PV). It has been shown to be reliable and sensitive in both lichen planus (LP) and MMP. What does this study add? The ODSS has been shown to be a thorough, sensitive and reproducible, yet quick scoring tool for the assessment of oral involvement in MMP. Its versatility for use in oral PV, MMP and LP is an added advantage over other scoring methodologies. What are the clinical implications of this work? We propose that the ODSS be used as a clinical scoring tool for monitoring activity in oral MMP in clinical practice as well as for use in multicentre studies.

An Oral Disease Severity Score validated for use in oral pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a rare autoimmune bullous disease, which can present with recalcitrant oral mucosal lesions. Optimal management of PV relies upon careful clinical assessment and documentation. OBJECTIVES: The primary aim of this study was to validate the Oral Disease Severity Score (ODSS) for the assessment of oral involvement in PV. A secondary aim was to compare its inter- and intraobserver variability and ease of use with the Physician's Global Assessment (PGA) and the oral scoring methods used in the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI). METHODS: Fifteen patients with mild-to-moderately severe oral PV were scored for disease severity by 10 oral medicine clinicians using the ODSS, the PGA and the oral sections of ABSIS and PDAI. Two clinicians rescored all patients after a minimum 2-h interval. RESULTS: Interobserver reliability was assessed using an intraclass correlation coefficient (ICC). For the ODSS total score the ICC was 0·83, for PDAI (oral total activity) 0·79, ABSIS (oral total) 0·71 and PGA 0·7. Intraobserver agreement between initial scoring and rescoring of the same patient by two clinicians demonstrated an ICC for each of 0·97 and 0·96 for ODSS total score; 0·99 and 0·82 for PDAI oral activity; 0·86 and 0·45 for ABSIS total; and 0·99 and 0·64 for PGA. Convergent validity was good, with a correlation coefficient > 0·5 (P < 0·001). The mean ± SD times taken to complete each scoring method were ODSS 76 ± 37 s, PDAI 117 ± 16 s and ABSIS 75 ± 19 s. CONCLUSIONS: This study has validated the ODSS for the assessment of oral PV. It has shown superior inter- and intraobserver reliability to PDAI, ABSIS and PGA and is quick to perform.

Oral dryness and Sjögren's: an update.

Oral dryness is a very common condition presenting to a general dental practitioner or hospital specialist. The most common cause of oral dryness is drug related, however, patients with Sjögren's syndrome, a multisystem autoimmune condition, may present to their dentist rather than their GP complaining of dry mouth and dry eyes. This update article explores the causes of oral dryness and how to manage it. The update on Sjögren's syndrome explains the latest relevant diagnostic criteria, presenting signs, symptoms, investigations and management principles.

Efficacy of mycophenolate mofetil in severe mucocutaneous lichen planus: a retrospective review of 10 patients.

BACKGROUND: Ulcerative lichen planus is an uncommon and severe subtype of lichen planus primarily affecting the oral mucosal surfaces. It may be associated with significant morbidity and often requires immunosuppressive therapy to achieve disease control. There have been no previous reports in which objective outcome measures have been used to assess the efficacy of mycophenolate mofetil (MMF) in severe ulcerative lichen planus. OBJECTIVE: To evaluate the clinical responses of patients with severe ulcerative oral lichen planus who were treated with MMF at a tertiary oral medicine/dermatology centre. METHODS: This was a retrospective review of oral disease severity scores performed in 10 patients with recalcitrant ulcerative oral lichen planus (vulvovaginal-gingival, n = 8; penogingival, n = 1; oral, n = 1) before and after treatment with MMF therapy. The results were analysed using the Wilcoxon matched pairs signed-rank test. RESULTS: The mean duration of MMF treatment was 3·7 (SD ± 2·4) years with a mean follow-up of 4·2 (SD ± 2·7) years. The mean baseline oral disease severity scores (39·1 ± 11·9) improved by 40% after 12-15 months (24·3 ± 11·9, n = 8, P = 0·01) and by 43% after 21-24 months of MMF treatment (22·2 ± 10·4, n = 9, P = 0·01). Of the 10 patients, six achieved remission, one had well-controlled disease and three had partially controlled disease. Two patients who achieved remission successfully discontinued treatment. MMF was well tolerated in all patients. CONCLUSION: Our case series demonstrates the efficacy and favourable side-effect profile of MMF in the treatment of severe ulcerative lichen planus.

DNA ploidy in proliferative verrucous leukoplakia.

Proliferative verrucous leukoplakia (PVL) is a clinicopathologically distinctive form of oral leukoplakia presenting with multifocal flat, nodular and verrucous lesions that progress inexorably to squamous carcinoma. The aims of this investigation were to describe the clinical and histopathological features of six cases of PVL and to determine whether lesional epithelium demonstrates DNA ploidy anomalies prior to malignant transformation. The clinical and pathological features of six patients were reviewed and all biopsy specimens were subjected to image-based DNA ploidy analysis. The female:male ratio was 5:1 and the average age on first biopsy was 66 years. Only one patient reported both tobacco smoking and alcohol intake. The most frequently affected sites were alveolar ridge and/or gingiva (6/6), buccal mucosa (3/6), palate (3/6), tongue (2/6), buccal sulcus (2/6), and lip (1/6). Three patients developed multiple primary carcinomas, either invasive or verrucous. A ploidy anomaly at any oral site would have predicted malignant transformation in four cases and probably in a fifth for whom DNA ploidy failed to meet diagnostic criteria but was suspicious of aneuploidy. The site of transformation was predicted by ploidy and histopathology for three carcinomas and a further carcinoma showed severe dysplasia and a suspicious ploidy result in adjacent tissue. Both conventional histopathology and DNA ploidy proved effective in predicting the site of transformation in this limited series.

Impact of wearing an intra-oral lubricating device on oral health in dry mouth patients.

OBJECTIVE: To establish whether an intra-oral lubricating device for dry mouth alters the oral environment. DESIGN: A single-blind randomized cross-over study. METHOD: Twenty-nine dentate subjects from the Sjogren's syndrome clinic attended on five occasions at 4-week intervals. They were randomized, having the device fitted on either the second or the fourth visit for the experimental period, whilst using their preferred method of lubrication throughout the rest of the study. The preferred methods of lubrication were either water (group 1, n = 10) or saliva substitute (group 2, n = 9) or sugar-free chewing gum (group 3, n = 10). At each visit microbiological, unstimulated and stimulated saliva samples were collected. Dry mouth score, speech test and periodontal indices were recorded. RESULTS: The water lubrication group (1) had a resting salivary flow greater than lubrication groups (2 and 3) by post-ANOVA contrasts (P < 0.001). The postdevice data also demonstrated a salivary flow greater than lubrication group (3) by post-ANOVA contrasts (P < 0.05). The epithelial cell count using the Spearman correlation was high, possibly reflecting increased viscosity of the saliva (P = 0.044). The speech test indicated that the experimental subjects had difficulty in speaking (P = 0.001). This was slightly easier postdevice wear. Streptococcus mutans (P = 0.009) and Lactobacillus (P = 0.058) increased in the saliva after wearing the device. Salivary flow rate, Candida albicans, oral dryness, speaking and periodontal indices were unchanged. CONCLUSIONS: The oral environment was altered by wearing a lubricating device with an increase in the numbers of Strep. mutans and Lactobacillus. Clinical dryness and speech test correlated with the mean whole salivary flow suggesting a screening method for xerostomia.

Serum and salivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease.

Orofacial granulomatosis (OFG) is a condition of unknown aetiology with histological and, in some cases, clinical association with Crohn's disease (CD). However, the exact relationship between OFG and CD remains uncertain. The aim of this study was to determine whether OFG could be distinguished immunologically from CD by comparing non-specific and specific aspects of humoral immunity in serum, whole saliva and parotid saliva in three groups of patients: (a) OFG only (n = 14), (b) those with both oral and gut CD (OFG + CD) (n = 12) and (c) CD without oral involvement (n = 22) and in healthy controls (n = 29). Non-specific immunoglobulin (IgA, SigA, IgA subclasses and IgG) levels and antibodies to whole cells of Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans were assayed by enzyme-linked immunosorbent assay (ELISA) in serum, whole saliva and parotid saliva. Serum IgA and IgA1 and IgA2 subclasses were raised in all patient groups (P < 0.01). Salivary IgA (and IgG) levels were raised in OFG and OFG + CD (P < 0.01) but not in the CD group. Parotid IgA was also raised in OFG and OFG + CD but not in CD. The findings suggest that serum IgA changes reflect mucosal inflammation anywhere in the GI tract but that salivary IgA changes reflect involvement of the oral cavity. Furthermore, the elevated levels of IgA in parotid saliva suggest involvement of the salivary glands in OFG. Serum IgA antibodies to S. cerevisiae were raised markedly in the two groups with gut disease while serum IgA (or IgG) antibodies to C. albicans were elevated significantly in all three patient groups (P < 0.02). No differences were found with antibodies to S. mutans. Whole saliva IgA antibodies to S. cerevisiae (and C. albicans) were raised in the groups with oral involvement. These findings suggest that raised serum IgA antibodies to S. cerevisiae may reflect gut inflammation while raised SIgA antibodies to S. cerevisiae or raised IgA or IgA2 levels in saliva reflect oral but not gut disease. Analysis of salivary IgA and IgA antibodies to S. cerevisiae as well as serum antibodies in patients presenting with OFG may allow prediction of gut involvement.

Patient preferences in a preliminary study comparing an intra-oral lubricating device with the usual dry mouth lubricating methods.

OBJECTIVE: To compare an intra-oral device to relieve oral dryness with the other methods of lubricating the mouth at night. DESIGN: Multidisciplinary single blind randomised cross over study. SETTING: The subjects were drawn from patients attending a dry mouth clinic. MATERIALS AND METHODS: Thirty-four dentate subjects attended on five occasions at intervals of 4 weeks. At the first visit the teeth were scaled and impressions were recorded. The device was fitted either on the second or the fourth visit. At all visits samples were taken of the resting and stimulated saliva for volumetric analysis and the dry mouth score recorded. Data were collected from the lubrication timings and the questionnaire. RESULTS: Ten water, nine saliva substitute and ten sugar-free chewing gum lubricators completed the study. There were 27 female and two male subjects with an average age of 62 years. Nine out of 10 of those lubricating with chewing gum preferred wearing the device (P = 0.037). After the device wearing period the subjects' self assessment of mouth dryness (P = 0.056), speech (P = 0.009) and swallowing (P = 0.031) were more favourable when compared with the alternative lubrication with 66% preferring the intra-oral device to their alternative method of lubrication. CONCLUSIONS: The majority of the subjects preferred wearing the device at night compared with their normal method of lubrication. Subjects' perception of dryness, speech and swallowing became closer to the clinician's assessment after wearing the device.

Oral and dental care and treatment protocols for the management of HIV-infected patients.

This paper describes the workings of the workshop dedicated to oral and dental care and treatment protocols for the management of HIV-infected patients. The questions addressed were: 1) What are the current ethical issues in dental care of HIV patients, do they need to be addressed? 2) Do we need to modify the dental care we give HIV-positive patients? 3) When is it necessary to give antibiotic prophylaxis to HIV-positive patients? 4) What is the evidence for the effective treatment of oral lesions associated with HIV? 5) What is the most successful palliative treatment for KS? 6) Can we provide clinical treatment that has a scientific basis rather being trial based? 7) Is ddI + hydroxy-urea an effective African alternative to HAART? 8) What is the influence of protease inhibitors and HAART on the excretion of HIV in saliva? 9) What is the effect of anti-HIV therapy on the oral mucosa and oral health? This workshop did not fully cover the issue of ddI and hydroxy-urea as an alternative HIV therapy as this was considered to be the remit of general physicians caring for patients with HIV and AIDS rather than that of oral health care workers.

The transition of pemphigus vulgaris into pemphigus foliaceus: a reflection of changing desmoglein 1 and 3 autoantibody levels in pemphigus vulgaris.

The transition of pemphigus vulgaris (PV) into pemphigus foliaceus (PF) is rare and the immunological changes underlying this event are not well understood. We report a 44-year-old woman who presented with oral and cutaneous erosions typical of PV. Over a 9-year period, the clinical features evolved into those of PF. To examine whether quantitative changes in desmoglein (Dsg) antibodies were associated with this transition, Dsg1 and Dsg3 antibody levels were measured by enzyme-linked immunosorbent assay in 82 sequential serum samples collected over this period. At presentation, when the phenotype was PV with oral and cutaneous erosions, antibodies to both Dsg1 and Dsg3 were detected. The disappearance of oral involvement was associated with a decline in Dsg3 antibodies, which are now undetectable, while the development of more severe skin involvement was associated with rising Dsg1 antibody levels. These data strongly suggest that the change in clinical features is a reflection of qualitative and quantitative changes in antibody profile. It is not known whether the transition to PF is permanent or whether disease relapses in the future may be associated with the re-emergence of Dsg3 antibodies, oral ulceration and a PV phenotype.

Pyoderma gangrenosum associated with severe oropharyngeal involvement and IgA paraproteinaemia.

We report a patient with combined cutaneous and oropharyngeal pyoderma gangrenosum in association with an IgA lambda paraproteinaemia. The differential diagnosis of oral pyoderma gangrenosum is discussed.

Cowden's syndrome (multiple hamartoma and neoplasia syndrome): diagnostic dilemmas in three cases.

Cowden's syndrome is a multisystem disease inherited as an autosomal dominant trait with incomplete penetrance and variable expression. The disease has typical oral manifestations which often precede more systemic involvement, and the dental professional is therefore well placed to institute a regime of regular checks to ensure early treatment of any neoplasms which may occur. However, since not all of the classical signs are present in all patients, diagnosis may be difficult. The case report of a patient with most of the features of Cowden's syndrome is presented and features compared with two other possible cases.

Paraneoplastic cicatricial pemphigoid.

We report a 39-year-old woman with antiepiligrin cicatricial pemphigoid (CP) in association with non-small cell carcinoma of the lung. At presentation, mucosal lesions showed minimal response to combined systemic immunosuppressive agents. Following the diagnosis of non-small cell lung carcinoma and subsequent treatment with gemcitabine (a second-line chemotherapeutic agent), a significant reduction in both tumour mass and mucosal blistering was observed. Metastatic disease was subsequently associated with recurrent oral erosions. We believe this patient represents the first reported case of paraneoplastic CP.

Cicatricial pemphigoid: serial titres of circulating IgG and IgA antibasement membrane antibodies correlate with disease activity.

We have recently shown in a cohort of patients (n = 67) with mucous membrane pemphigoid, 63 of whom had cicatricial pemphigoid (CP), that the presence of both IgG and IgA circulating antibasement membrane zone antibodies was associated with a more severe and persistent disease. In this study we sought to ascertain whether in CP, serial titres of IgG and IgA might provide a reliable marker of disease activity. Serum titres for IgG and IgA antibodies were assayed at 6- to 12-monthly intervals in 56 patients over 32.2 +/- 20.3 (mean +/- SD) months. Antibody titres were correlated with the clinical score recorded at each follow-up visit. Sequential titres for both IgG (P < 0.001) and IgA (P = 0.015) were significantly associated with variations in disease activity. Greatest improvement was seen in patients with the greatest change in either IgG or IgA antibody titre. We suggest that serial antibody titres may therefore be useful in the assessment and management of CP.

Pyostomatitis vegetans associated with asymptomatic ulcerative colitis: a case report.

Pyostomatitis vegetans, a rare pustular disorder of the oral mucosa, is a highly specific marker for inflammatory bowel disease and may be difficult to treat. A case of pyostomatitis vegetans in a patient with long-standing asymptomatic ulcerative colitis is presented. Complete remission was achieved with topical steroids; no systemic treatment was required.

Gene expression of differentiation-specific keratins (4/13 and 1/10) in normal human buccal mucosa.

The aim of the present study was to compare gene expression of the major differentiation-specific keratins in oral epithelium: keratins 4, 13, 1, and 10. Previous studies have shown that the dominant keratins in normal buccal epithelium are K4 and K13, with minor populations of cells showing K1 and K10 expression; herein, we have further examined expression of these keratins at the mRNA level. Six biopsies from normal buccal mucosa were immunohistochemically stained for keratin proteins by means of monoclonal antibodies to K4, K13, K1, and K10. Adjacent sections were processed for mRNA by nonisotopic in situ hybridization, using specific riboprobes labeled with digoxigenin. Proteins for K4 and K13 were expressed suprabasally throughout buccal epithelium, with columns of cells staining additionally for K1 and K10. In situ hybridization revealed a comparable pattern of mRNA distribution for K4 and K13, with expression restricted to parabasal and lower prickle cells. Transcripts for K1 and K10 were present in basal, parabasal, and lower prickle layers, showing a much wider expression than that of their proteins. This study has shown that in buccal epithelium, there is extensive mRNA expression of the "inappropriate" differentiation-specific keratins, despite minimal protein expression. This suggests that K1 and K10 are regulated at the post-transcriptional level, so that they may be expressed adaptively as proteins. The findings will form a useful baseline for the study of these keratins in pathologically altered oral epithelia as well as in nonkeratinized epithelia from extra-oral sites.

Minor salivary gland hyalinisation and amyloidosis in low-grade lymphoma of MALT.

Two patients with low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) arising in primary Sjögren's syndrome developed solitary nodules in their lips. Histologically both lesions showed enlargement and hyalinisation of single minor salivary glands with acinar atrophy, loss of most ducts and conversion into almost acellular sclerotic eosinophilic masses. In one case the lesion was shown to contain an amyloid component. No amyloid was detected in the second case but deposition of collagen and basement membrane and sclerotic neoplasm were excluded.