BACKGROUND:Mucous membrane pemphigoid (MMP) has a broad range of clinical manifestations, from relatively benign self-limiting oral lesions to significant scarring (cicatrizing) of the oral, nasal and ocular tissues with severe functional impairment and morbidity. European Guidelines recommend rituximab as only second- or third-line therapy, based on the extent/severity of the disease; however, there are no established clinical or serological markers that are predictive of severe disease warranting the use of agents such as rituximab. METHODS:Retrospective cross-sectional cohort study of patients who met the following criteria: (1) biopsy confirmed MMP; (2) required a steroid-sparing immunosuppressant therapy, that is, mycophenolate and/or rituximab and (3) at least 6 months of clinical monitoring. The primary end point was complete or partial remission. RESULTS:Of the 45 patients who met the criteria, 12 (27%) had sustained remission with mycophenolate. Thirty-three (73%) patients had either relapsed or were refractory to mycophenolate and, therefore, were treated with rituximab. Of those who received rituximab, 97% achieved a complete remission after a single course (1 g given intravenously on Days 1 and 14), but 24% needed repeat treatment. The detection rates of key circulating antibodies, namely skin basement membrane antibodies (SBMA), BP180/230, collagen VII and laminin 332, were low and did not identify those patients refractory to mycophenolate. Adverse reactions, including infectious complications, were minimal in both patient groups. CONCLUSION:In our study of mostly localised mucosal MMP patients, there was an excellent response to a single course of treatment with rituximab, with durable remission and no major adverse complications.

BACKGROUND:Monitoring delivery of cancer care is critical to improve outcomes in increasingly resource-constrained settings. The aim of this study was to develop a priority set of multidisciplinary quality indicators (QIs) for benchmarking and monitoring the quality of care for head and neck cancer (HNC) in Australia. METHODS:Following a systematic literature review, a modified Delphi consensus process was undertaken with Australian health professionals and people with lived experience of HNC. Consensus was sought over three rounds. In Rounds 2 and 3, participants rated the importance of QIs on a scale of 1 (not at all important) to 7 (highly important). QIs reached consensus if they had a mean importance score ≥ 6 (out of 7) and ≥ 75% of participants rated them 6 or 7. RESULTS:The systematic review identified 317 unique QIs, and 81 were chosen for presentation in Rounds 2 of the Delphi. In Round 2, 66 health professionals and 12 people with lived experience of HNC reached consensus on 48 QIs, with three reworded and one new QI added. Fifty-two QIs were presented in Round 3; 42 health professionals and 10 people with lived experience participated, reaching consensus on 24 QIs. Most of the QIs fell under the treatment domain, with commencement of curative treatment and documentation of surgical margins attaining the highest consensus. CONCLUSION:We developed a priority set of 24 clinically relevant QIs for HNC, which will be tested in a clinical quality registry to benchmark optimal management of HNC and outcomes.

Introduction: Mucous membrane pemphigoid (MMP) is characterised by autoantibodies against various target antigens in the basement membrane zone of the epithelia. Patients can have broad disease manifestations from relatively benign self-limiting oral lesions to significant scarring of mucosal surfaces with functional impairment. Rituximab has been recommended in European guidelines as second or third line therapies based on the extent of disease involvement. Despite this there are no established biochemical or serological markers established that predict patients whom may have more extensive or refractory disease requiring biologic agents such as rituximab.

Objectives This prospective cohort study aimed to assess the association between dental disease burden and postoperative infective complications (POICs) in patients undergoing major surgical procedures under general anaesthesia. Methods Pre-surgical dental assessment was undertaken on patients planned for major surgery. Demographic and surgical variables including putative risk factors for POICs and POIC status were documented. The univariable association between POIC status and each factor was examined. Those variables associated at P value ≤ 0.2 were candidates for inclusion in multiple logistic regression models. Backward stepwise variable selection was used to identify the independent predictors for POIC in the best fitting logistic regression model. The area under the receiver operating curve (AUC) was used to quantify the model’s global classification performance. Results Among the 285 patients, 49 patients (17.2%) had POICs. The independent predictors for POIC were expected length of hospital stay (4–6 days; odds ratio [OR] = 4.80, 95% confidence internal [CI]: 1.30–17.70, P = 0.018, 7–9 days; OR = 5.42, 95% CI: 1.51–19.41, P = 0.009, ≥ 10 days; OR = 28.80, 95% CI: 4.12–201.18, P < 0.001), four or more decayed teeth (OR = 6.03, 95% CI: 2.28–15.94, P < 0.001) and visible tongue plaque (OR = 3.21, 95% CI: 1.54–6.70, P = 0.002). The AUC was 0.78 (95% CI: 0.71–0.85) indicating good discrimination. A simple screening tool for POIC was developed. Conclusions/Clinical relevance In addition to systemic/surgical factors, this study identified clinically detected decayed teeth and visible tongue plaque as independent predictors for POICs. Preoperative dental assessment/care might be beneficial to assess risk for POICs and improve postoperative outcomes.

Oral epithelial dysplasia (OED) represents a spectrum of histologic changes in the oral cavity mucosa that has the potential to transform into oral squamous cell carcinoma. Predicting the risk of malignant transformation is predominantly based on clinicopathologic correlation, histologic examination and grading. OED often poses a diagnostic challenge, primarily due to its histologic mimics and a large number of terminologies used in the literature. The grading system for OED is also fraught with significant interobserver variability. This review summarizes the essential clinical and histopathologic features of OED and its mimics. Practical preanalytical, analytical, and postanalytical considerations for anatomic pathologists are discussed to improve the diagnostic accuracy and increase the reproducibility in the grading of OED.

Purpose Determine health professionals’ (HPs’) perceptions of oral mucositis (OM), including clinical presentation of chemotherapy (CT)-induced vs radiation therapy (RT)-induced OM, its assessment and management. Methods HPs involved in the care of head and neck cancer (HNC) patients receiving RT to the oral cavity/oropharynx and haematopoietic stem cell transplantation (HSCT) patients receiving mucositis-inducing CT regimens were invited to participate in a customised 20-question survey. Themes included OM presentation, assessment and management. Results Survey response rate was 81.4%. Most were nurses (33%) and specialist doctors/dentists (25%). Majority (45%) identified as part of the haematology service, followed by radiation oncology (32%). Most haematology and radiation oncology HPs (89% and 70%, respectively) agreed/strongly agreed that OM impacted patients’ ability to complete treatment. There was a significant association (p<0.01) between HPs’ specialty and their perceptions of OM manifestations. Most radiation oncology (85%) and all oral medicine HPs agreed/strongly agreed that clinical manifestations of CT-induced OM and RT-induced OM were different, whereas haematology HPs varied in their perceptions (11% disagreed, 41% were neutral and 48% agreed/strongly agreed). There was uncertainty regarding differences in management of CT vs RT-induced OM: 30% of haematology HPs and 45% of radiation oncology HPs agreed/strongly agreed but most (52% and 45%, respectively in each group) responded “neutral.” Conclusion OM was recognised to adversely impact HSCT and HNC RT patients’ ability to complete treatment. There were differences in HPs’ perceived understanding of OM manifestations and management. Interventions to address these may reduce unwanted variations in patient care and outcomes.

The most common endocrine disorders are: diabetes mellitus, obesity, thyroid disorders including hypothyroidism, hyperthyroidism, goiter, menstrual disorders and/or hirsutism, usually due to polycystic ovarian syndrome, hypogonadism, osteoporosis and metabolic bone disease, subfertility, and disorders of growth or puberty. Endocrine disorders are common, and are increasing in frequency. Endocrine disorders are complex and their diagnosis is complicated by four interacting components: hypothalamus, pituitary, major endocrine glands, and hormones. Endocrine diseases can be divided into two major disease states: hormone excess and hormone deficiency. The hypothalamic neurons secrete both pituitary hormone-releasing and pituitary-inhibitory factors via the portal system, which passes down the stalk into the pituitary. Antidiuretic hormone is synthesized in the hypothalamus and migrates in neurosecretory granules via axonal pathways to the posterior pituitary. Thyroid disease occurs frequently and is the most common endocrine disease. The gonads, like most other endocrine organs, are incorporated into an endocrine axis: the hypothalamic-pituitary-gonadal.

A 64-year-old man presented in April 2020 to the emergency department (ED) with severe and worsening odynophagia of 7-weeks’ duration, associated with a week of hemoptysis with 2 to 3 episodes a day of bright red sputum and intermittent night sweats.

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Background: Rituximab is an effective treatment for inducing remission in pemphigus vulgaris (PV) refractory to conventional immunosuppression. Re-treatment is required on relapse, but there are currently no reliable biomarkers in predicting clinical relapse. Method: We prospectively followed 18 PV patients previously treated with rituximab at Westmead Hospital over a 2-year period. Disease activity was assessed by pemphigus disease activity index (PDAI) along with desmoglein (dsg), intercellular cement substance (ICSA) antibody titres, total B-cell and memory B-cell (CD19+CD27+) counts. Results: 9/18 patients relapsed requiring further rituximab administration. Of these, relapse was preceded by dsg elevation in 5/9 and B-cell return in 2/9 patients. Chronic elevation in dsg antibodies and B-cells were seen in the remaining 2/9 patients with no relationship to PDAI. Of the 9 patients in clinical remission, 5 had normal dsg antibody levels. Review of their clinical data prior to the study suggests correlation of dsg titre elevation with disease relapse. The remaining 4 patients had chronic elevation of dsg antibodies and B-cells. There was no additional information gained from measuring memory B-cells and no correlation between PDAI and ICSA antibody levels. Discussion: Both dsg antibody levels and B-cell counts can predict relapse in subgroups of rituximab-treated refractory PV patients.

Rituximab has demonstrated efficacy in pemphigus vulgaris (PV) but a significant number of patients eventually relapse requiring further treatment. We present the case of a 39-year-old male who originally presented to us in 2013 with a 3-year history of severe generalised mucocutaneous PV, refractory to first line treatment with oral prednisolone and mycophenolate. Immunosuppression was escalated to rituximab (1 g weekly × 2) leading to disease remission and cessation of corticosteroids. Between 2013 and 2018, he experienced multiple relapses at regular intervals, requiring seven further rituximab infusions. Each of the first six infusions was able to induce remission without additional immunosuppression but relapse inevitably occurred after B-cell return in the peripheral blood. Interestingly, his desmoglein (dsg) antibody levels, which were initially significantly elevated, steadily declined with each rituximab infusion. After completing the 7th infusion in April 2018, he was able to remain in remission despite B-cell return. This corresponded to normalisation of his dsg antibodies. We hypothesise that repeated treatment with rituximab has eradicated the 'clone' of pathogenic autoantibody-producing B cells, leading to sustained remission.

BACKGROUND:Conflicting recommendations exist addressing the management of direct oral anticoagulants (DOACs) for invasive dental procedures.OBJECTIVES:To determine the safety of DOAC continuation compared to warfarin continuation for dental extractions with regards to bleeding outcomes.METHODS:A single-center, prospective, cohort study was performed to compare 7-day bleeding outcomes between patients who continued their DOAC, and patients on warfarin with an International Normalized Ratio (INR) between 2.0 and 4.0. Blood tests including oral anticoagulant drug levels were measured immediately prior to extraction. The gauze used to apply pressure to the socket was weighed before and after extraction to estimate blood loss. Patients were contacted by phone 2 and 7 days after extraction.RESULTS:Eighty-six patients on a DOAC had a total of 145 teeth extracted, and 21 patients on warfarin had 50 teeth extracted. There were no major bleeding events. The rate of minor plus clinically relevant nonmajor bleeding was comparable between the DOAC and warfarin cohorts (36% and 43%, respectively; odds ratio, 0.75; 95% confidence interval, 0.29-1.98). Preextraction apixaban and dabigatran levels were comparable between bleeders and nonbleeders, while rivaroxaban levels were higher in those who bled. The weight change of gauze used to tamponade the socket was similar between the 2 cohorts.CONCLUSION:Dental extractions on patients continuing DOACs led to bleeding rates similar to patients on warfarin with an INR between 2.0 and 4.0. There is no need to adjust DOAC dosing prior to dental extractions.

Objective. Complete excision of oral potentially malignant lesions (OPMLs) could result in improved and earlier detection of more severe grades of oral epithelial dysplasia and/or frank malignancy. Transoral microsurgical carbon dioxide laser techniques allow for resection of OPMLs, even those that are extensive. The advantages are improved diagnostic yield, improved viability of the specimen for pathologic evaluation, reduced postoperative morbidity, and easier postoperative clinical surveillance. Study Design. Retrospective review of the histopathology slide material and attendant clinical notes of 31 sequential patients with OPMLs demonstrated the following histopathologic diagnoses on conventional incisional biopsy (CIB): verrucous hyperplasia (2 patients); mild dysplasia (11 patients), moderate dysplasia (3 patients) or severe dysplasia (15 patients); and subsequently, these patients went on to have laser excision biopsy (LEB) of their OPMLs. Results. Histologic diagnosis was upgraded after LEB in 14 (45%) patients (P < .001), with unexpected findings of cancer in 9 cases (29%) and more severe dysplasia in 5 cases (16%). Conclusions. Use of LEB to supplement CIB appears superior in the detection of severe dysplasia and frank malignancy in OPMLs compared with use of CIB alone. Prospective trials are indicated to determine if the superior diagnostic utility of LEB improves patient outcomes with regard to earlier detection of oral squamous cell and/or verrucous carcinoma.

Background Pemphigus vulgaris (PV) is an autoimmune blistering disease driven by pathogenic antibodies to desmoglein-1 and -3, levels of which correlate with disease activity. Anti-desmoglein-3 IgG4 isotype antibodies are said to predominate in active disease and anti-desmoglein-3 IgG1 in remission; however, these observations arose from vertical studies, with limited assessments of clinical activity. The objective of this study was to examine the relationship between desmoglein autoantibodies, subdivided by isotype and disease activity using the validated PV activity tool "Pemphigus Disease Area Index (PDAI)." Methods Forty PV patients with predominantly mucosal disease were studied prospectively, 24 serially, and PDAI and anti-desmoglein antibodies recorded at each visit over a period of up to 15 months. Results At enrolment, only anti-desmoglein-3 IgG4 levels were significantly associated with disease activity but the correlation was weak. During follow-up, within-patient changes in disease activity correlated with changes in anti-desmoglein-3 IgG levels, but correlations were similar for both anti-desmoglein-3 IgG1 and IgG4. These trends were not observed in anti-desmoglein-1 IgG levels, although the majority of patients were negative at baseline. Conclusions Anti-desmoglein-3 IgG4 levels correlated only weakly with PDAI scores at a single time point. Reciprocity of IgG1 vs IgG4 anti-desmoglein-3 with changes in disease activity over time could not be confirmed, but rather, changes in levels of anti-desmoglein-3 IgG, irrespective of isotype, were useful in following individual patient responses.