Allergic contact dermatitis to para-phenylenediamine.

Exposure to hair dye is the most frequent route of sensitisation to para-phenylenediamine (PPD), a common contact allergen. International studies have examined the profile of PPD, but Australian-sourced information is lacking. Patients are often dissatisfied with advice to stop dyeing their hair. This study examines patients' characteristics, patch test results and outcomes of PPD allergy from a single Australian centre, through a retrospective analysis of patch test data from 2006 to 2013 at the Liverpool Hospital Dermatology Department. It reviews the science of hair dye allergy, examines alternative hair dyes and investigates strategies for hair dyeing. Of 584 patients, 11 were allergic to PPD. Our PPD allergy prevalence rate of 2% is at the lower end of international reported rates. About half these patients also react to para-toluenediamine (PTD). Affected patients experience a significant lifestyle disturbance. In all, 78% tried alternative hair dyes after the patch test diagnosis and more than half continued to dye their hair. Alternative non-PPD hair dyes are available but the marketplace can be confusing. Although some patients are able to tolerate alternative hair dyes, caution is needed as the risk of developing an allergy to other hair dye ingredients, especially PTD, is high.

Switching from Dose-Intensified intravenous to SubCutaneoUS infliximab in Inflammatory Bowel Disease (DISCUS-IBD): protocol for a multicentre randomised controlled trial.

INTRODUCTION: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring. METHODS AND ANALYSIS: The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants. ETHICS AND DISSEMINATION: Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment. TRIAL REGISTRATION NUMBER: ACTRN12622001458729.

Frequency of positive patch test reactions to preservatives: The Australian experience.

BACKGROUND/OBJECTIVES: Preservatives are important causes of allergic contact dermatitis. The frequency of allergy to preservatives in Australia has been unknown to date. Our objectives are to report the frequency of positive preservative patch test reactions in Australia, comparing them to the published international data, as well as exploring the current regulations in place for preservative use in Australia. METHODS: This was the first retrospective study of patch testing results, aggregated from four patch test clinics in three centres in Melbourne and Sydney. RESULTS: In all, 6845 patients were patch-tested during 1993-2006 and in this period the five most frequent preservative allergens were formaldehyde (4.6%), Euxyl K400 (containing methyldibromo glutaronitrile and phenoxyethanol) (3.3%), quaternium-15 (2.9%), diazolidinyl urea (2.4%), and methylchloroisothiazolinone/methylisothiazolinone (2.3%). These were followed by dimethylol dimethyl DMDM hydantoin (2.1%), chloroacetamide (2.1%) and imidazolidinyl urea (1.9%). The least frequent sensitisers were parabens (1.1%), 2-bromo-2-nitropropane-1, 3-diol (0.9%) and benzyl alcohol (0.4%). CONCLUSIONS: Formaldehyde was the most prevalent preservative allergen. Chloroacetamide allergy was more commonly seen in Australia. Parabens, 2-bromo-2-nitropropane-1,3-diol and benzyl alcohol were the least frequent sensitisers. Household products in Australia are not required to list all ingredients preventing sensitised individuals from properly assessing their exposure.

Interval fecal immunochemical testing in a colonoscopic surveillance program speeds detection of colorectal neoplasia.

BACKGROUND & AIMS: Rapidly progressing or missed lesions can reduce the effectiveness of colonoscopy-based colorectal cancer surveillance programs. We investigated whether giving fecal immunochemical tests (FITs) for hemoglobin between surveillance colonoscopies resulted in earlier detection of neoplasia. METHODS: The study included 1736 patients with a family history or past neoplasia; they received at least 2 colonoscopy examinations and were followed for a total of 8863 years. Patients were excluded from the study if they had genetic syndromes, colorectal surgery, or inflammatory bowel disease. An FIT was offered yearly, in the interval between colonoscopies; if results were positive, the colonoscopy was performed earlier than scheduled. RESULTS: Among the 1071 asymptomatic subjects (61%) who received at least 1 FIT, the test detected 12 of 14 cancers (86% sensitivity) and 60 of 96 (63%) advanced adenomas. In patients with positive results from the FIT, the diagnosis of cancer was made 25 months (median) earlier and diagnosis of advanced adenoma 24 months earlier. Patients who had repeated negative results from FIT had an almost 2-fold decrease in risk for cancer and advanced adenoma compared with patients who were not tested (5.5% vs 10.1%, respectively, P = .0004). The most advanced stages of neoplasia, observed across the continuum from nonadvanced adenoma to late-stage cancer, were associated with age (increased with age), sex (increased in males), and FIT result. The probability of most advanced neoplastic stage was lowest among those with a negative result from the FIT (odds ratio, 0.68; P < .001). CONCLUSIONS: Interval examinations using the FIT detected neoplasias sooner than scheduled surveillances. Subjects with negative results from the FIT had the lowest risk for the most advanced stage of neoplasia. Interval FIT analyses can be used to detect missed or rapidly developing lesions in surveillance programs.

Phenotypic diversity in patients with multiple serrated polyps: a genetics clinic study.

OBJECTIVE: Hyperplastic polyposis is a colonic polyposis condition of unknown aetiology. The purpose of this study was to examine the spectrum of phenotypic variation in patients with multiple serrated polyps as a basis for gene discovery. METHODS: One hundred and twenty-six patients with multiple (> or = 5) serrated polyps were recruited to the study. Polyp counts were extracted from histology and colonoscopy reports. Ethnicity was self-reported. Family history of cancer data were derived from pedigrees. Ascertainment status was classified as either index case or identified by screening. RESULTS: The average reported polyp count was 39. Patients with highest polyp numbers were more likely to be male (P = 0.02). Colorectal cancer (CRC) was identified in 49 of 119 patients (41%) and 28% of these patients had multiple CRC. Young onset patients had higher polyp numbers (P = 0.03) and were more likely to have their CRC in the distal colon (P = 0.02). CRC was significantly associated with the presence of adenomas (P = 0.03). Patients were divided into moderate polyposis (5-79 serrated polyps) and dense polyposis (80 or more) categories. The dense polyposis category was associated with a lack of family history for CRC (P = 0.034) and male gender (P = 0.014), independent of ascertainment status and recruitment site. CONCLUSION: Multiple serrated polyps were associated with an increased personal risk of CRC. A subset of patients with the highest polyp numbers was more likely to be male and to have no family history of CRC. This result suggests heterogeneous modes of inheritance and has implications for studies investigating the genetic basis of multiple serrated polyps.

Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study.

PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared the distribution of the mismatch repair mutations in our study population with that in a control group, including all pathogenic mismatch repair mutations of the International Society for Gastrointestinal Hereditary Tumours database (excluding those in our study population). In patients with MSH2 mutations, patients with HNPCC-associated SBCs had fewer mutations in the MutL homologue interaction domain (2.9% versus 19.9%, P = 0.019) but an increased frequency of mutations in codons 626 to 733, a domain that has not previously been associated with a known function, versus the control group (26.5% versus 2.8%, P < 0.001). CONCLUSIONS: In HNPCC patients, SBC can be the first and only cancer and may develop as soon as the early teens. The distribution of MSH2 mutations found in patients with HNPCC-associated SBCs significantly differed from that found in the control group (P < 0.001).

Correlates of Family Satisfaction with Hospice Care: General Inpatient Hospice Care versus Routine Home Hospice Care.

BACKGROUND: The quality of communication and support provided to families is associated with greater satisfaction with hospice care. Prior work has not explored whether the predictors of family satisfaction are different in different hospice care settings. OBJECTIVE: The study objective was to explore whether correlates of family satisfaction are different in general inpatient hospice care versus routine home hospice care. METHODS: Survey data from bereaved family members of approximately 1600 patients from a nonprofit, midsized hospice in western Pennsylvania were used. Data was obtained from Family Evaluation of Hospice Care (FEHC) survey responses from 2008-2013 and separated into two groups, general inpatient hospice care and routine home hospice care. The analysis was completed using a binomial logistic regression model. RESULTS: Three variables were associated with greater overall satisfaction in both care settings: being kept informed about the patient's condition (adjusted odds ratio [AOR]: 9.64, CI: 6.56-14.36); being provided with clear/consistent information (AOR: 2.34, CI: 1.47-3.72); and the perception that patients were provided with adequate treatment for anxiety (AOR: 2.64, CI: 1.19-5.81). Two variables, sufficient discussion with hospice team members concerning family members' religious or spiritual beliefs (AOR: 1.64, CI: 1.17-2.30) and being provided with the correct amount of emotional support after the patient's death (AOR: 2.01, CI: 1.10-3.66), were correlated with greater satisfaction in routine home hospice care only. CONCLUSIONS: Good communication is strongly associated with greater family satisfaction across hospice care settings. Hospices must ensure that they provide patients and families with consistent information and support.

A family with juvenile polyposis linked to the BMPR1A locus: cryptic mutation or closely linked gene?

BACKGROUND AND AIM: Familial juvenile polyposis syndrome (JPS) is a rare autosomal dominant condition in which patients develop hamartomatous gastrointestinal polyps with malignant potential. Pathogenic germline mutations in both the SMAD4 and BMPR1A genes involved in the transforming growth factor beta pathway account for 40% of cases of JPS. Genetic heterogeneity remains evident, as the balance of cases is not accounted for by mutations in these genes. The aim of this study was to determine the mutation responsible in a family with juvenile polyposis. METHODS: An Australian Caucasian family with juvenile polyposis have attended and followed surveillance plans through the Familial Bowel Cancer Clinic, The Royal Melbourne Hospital. A pedigree of the family was constructed with attention to the mixed phenotypic expression of polyps in affected members. Genetic testing for SMAD4 and BMPR1A mutations in germline DNA and linkage analysis to SMAD4, BMPR1A and 15q14 (CRAC1 locus) were performed. RESULTS: There were no pathogenic mutations in SMAD4 and BMPR1A. There was no linkage to SMAD4 or 15q14 (CRAC1 locus). Linkage analysis suggested a cryptic BMPR1A mutation or the presence of another gene in close proximity to the BMPR1A locus. Two additional candidate genes in the region of linkage (PTEN and MINPP1) were excluded. CONCLUSION: Most affected members of this Australian Caucasian family demonstrate a phenotype of mixed polyps: juvenile polyps, adenomas and/or hyperplastic polyps. Cloning of a potentially responsible gene closely linked to the BMPR1A locus or a cryptic mutation in BMPR1A may offer valuable insights into the pathogenesis of JPS.

Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH.

BACKGROUND & AIMS: Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. METHODS: Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. RESULTS: Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient. CONCLUSIONS: Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway.

A review of juvenile polyposis syndrome.

Juvenile Polyposis Syndrome is an uncommon hamartomatous disorder with significant gastrointestinal malignant potential. Mutations in SMAD4 and BMPR1A, implicated in the Transforming Growth Factor beta pathway, have recently been characterized, and hold significance in the management of patients and at risk family members. This article reviews our knowledge to date of the genetics and clinicopathological features of the Juvenile Polyposis Syndrome, and discusses the current expert recommendations for genetic testing, disease screening and management.

Survey of HNPCC Management Analysis of Responses from 18 International Cancer Centres.

Eighteen international cancer centres responded to a questionnaire designed to determine clinic practices regarding the management of Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Areas covered include definition, clinical intakes, pre-genetic testing for microsatellite instability (MSI) or expression of mismatch repair (MMR) genes by immunohistochemistry (IHC), mutational analysis, consent practices, counselling, surveillance planning, and surgical decision making. In the absence of a firm evidence base, some management practices were variable, with local access to funding and other resources being influential. More consistent responses were evident for management practices with a stronger evidence base from previous clinical research. This document provides important information to guide the management of HNPCC patients, allow comparisons to be made between the approaches of various clinics to HNPCC families, and define management issues that need to be addressed in clinical research.

Colorectal cancer and inherited mutations in base-excision repair.

Polyposis associated with mutations in the gene MUTYH is an autosomal recessive syndrome characterised by the development of multiple colorectal adenomas and cancer. It is the first cancer-predisposition disorder to be associated with defects in the pathway of base-excision repair. We review our knowledge to date of the disease, discuss base-excision repair in relation to cellular defence against oxidative damage, and give an overview of the molecular genetics and clinicopathological features of tumours associated with MUTYH mutations. No longer a research finding, genetic testing for MUTYH is now a necessary part of molecular diagnosis in familial cancer clinics throughout Australia and the UK. Current recommendations for the screening and management of the disease are also discussed.