What is in? What is out? Updating the British Society for Cutaneous Allergy facial series.

BACKGROUND: Allergic contact dermatitis (ACD) to cosmetics is widely reported. To ensure we are accurately diagnosing ACD, patch test series should be continually reviewed to identify relevant and emerging allergens and highlight those that are outdated. The current British Society for Cutaneous Allergy (BSCA) facial series recommends 26 allergens and was last modified in 2012. OBJECTIVES: To review and update the BSCA facial series. METHODS: We retrospectively reviewed the results from 12 UK and Ireland patch test centres' facial series from January 2016 to December 2017. We recorded the number of allergens tested in each centre and the detection rate for each allergen. Using a 0·3% positive rate as the inclusion threshold, we established which allergens in the BSCA facial series had positive patch test rates < 0·3% and > 0·3%. Allergens not in the BSCA facial series that had a positive patch test rate > 0·3% were identified. RESULTS: Overall, 4224 patients were patch tested to the facial series. The number of allergens included in individual centres' facial series ranged from 24 to 66, with a total of 103 allergens tested across all centres. Twelve of the 26 allergens in the BSCA facial series had a positive patch test rate < 0·3% and 14 had a rate > 0·3%. Twenty-five allergens not recommended in the BSCA facial series had a positive patch test rate > 0·3%. CONCLUSIONS: This audit has highlighted the significant variation in practice that exists among patch test centres, despite a recommended facial series. The BSCA facial series has been updated and now contains 24 allergens. Fifteen allergens remain, 11 allergens have been dropped and nine new allergens have been added.

Recommendation to include hydroxyethyl (meth)acrylate in the British baseline patch test series.

BACKGROUND: (Meth)acrylates are potent sensitizers and a common cause of allergic contact dermatitis (ACD). The frequency of (meth)acrylate ACD has increased with soaring demand for acrylic nails. A preliminary audit has suggested a significant rate of positive patch tests to (meth)acrylates using aimed testing in patients providing a clear history of exposure. To date, (meth)acrylates have not been routinely tested in the baseline patch test series in the U.K. and Europe. OBJECTIVES: To determine whether inclusion of 2-hydroxyethyl methacrylate (2-HEMA) 2% in petrolatum (pet.) in the baseline series detects cases of treatable (meth)acrylate ACD. METHODS: During 2016-2017, 15 U.K. dermatology centres included 2-HEMA in the extended baseline patch test series. Patients with a history of (meth)acrylate exposure, or who tested positive to 2-HEMA, were selectively tested with a short series of eight (meth)acrylate allergens. RESULTS: In total 5920 patients were consecutively patch tested with the baseline series, of whom 669 were also tested with the (meth)acrylate series. Overall, 102 of 5920 (1·7%) tested positive to 2-HEMA and 140 (2·4%) to at least one (meth)acrylate. Had 2-HEMA been excluded from the baseline series, (meth)acrylate allergy would have been missed in 36 of 5920 (0·6% of all patients). The top (meth)acrylates eliciting a positive reaction were 2-HEMA (n = 102, 1·7%), 2-hydroxypropyl methacrylate (n = 61, 1·0%) and 2-hydroxyethyl acrylate (n = 57, 1·0%). CONCLUSIONS: We recommend that 2-HEMA 2% pet. be added to the British baseline patch test series. We also suggest a standardized short (meth)acrylate series, which is likely to detect most cases of (meth)acrylate allergy.

Long-term results of acetabular reconstruction using irradiated allograft bone.

AIMS: The management of acetabular defects at the time of revision hip arthroplasty surgery is a challenge. This study presents the results of a long-term follow-up study of the use of irradiated allograft bone in acetabular reconstruction. PATIENTS AND METHODS: Between 1990 and 2000, 123 hips in 110 patients underwent acetabular reconstruction for aseptic loosening, using impaction bone grafting with frozen, irradiated, and morsellized femoral heads and a cemented acetabular component. A total of 55 men and 55 women with a mean age of 64.3 years (26 to 97) at the time of revision surgery are included in this study. RESULTS: At a mean follow-up of 16.9 years, there had been 23 revisions (18.7%), including ten for infection, eight for aseptic loosening, and three for dislocation. Of the 66 surviving hips (58 patients) that could be reassessed, 50 hips (42 patients; 75.6%) were still functioning satisfactorily. Union of the graft had occurred in all hips with a surviving implant. Survival analysis for all indications was 80.6% at 15 years (55 patients at risk, 95% confidence interval (CI) 71.1 to 87.2) and 73.7% at 20 years (eight patients at risk, 95% CI 61.6 to 82.5). CONCLUSION: Acetabular reconstruction using frozen, irradiated, and morsellized allograft bone and a cemented acetabular component is an effective method of treatment. It gives satisfactory long-term results and is comparable to other types of reconstruction. Cite this article: Bone Joint J 2018;100-B:1449-54.

Treatment of severe, chronic hand eczema: results from a UK-wide survey.

Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain information about their usual treatment pathways to inform the choice of the comparator in a trial of alitretinoin in severe HE (ALPHA trial); the results indicated that the treatment approaches favoured by UK dermatologists differ. Psoralen combined with ultraviolet A (PUVA) and alitretinoin were identified as the most frequent first-line treatment options for hyperkeratotic HE, whereas oral corticosteroids were identified as the most frequent first-line treatment for vesicular HE, followed by PUVA and alitretinoin. In terms of potential adverse effects of long-term or repeated use, oral steroids and ciclosporin A were reported to cause most concern. There is uncertainty about which treatment gives the best short and long-term outcomes, because of a lack of definitive randomised controlled trials evaluating the effectiveness of different treatment pathways in severe HE.

Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival.

Correction to: Oncogene (2015) 34, 4482­4490; doi:10.1038/onc.2014.378; published online 24 November 2014. Following the online publication of this article, the authors have noticed a misspelt surname: S Hider should read S Haider. There is also an addition to the acknowledgements to read 'This study makes use of data generated by the Molecular Taxonomy of Breast Cancer International Consortium, which was funded by Cancer Research UK and the British Columbia Cancer Agency Branch'. The corrected article appears in this issue. The authors would like to apologise for any inconvenience this may cause.

Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival.

Activation of cellular transcriptional responses, mediated by hypoxia-inducible factor (HIF), is common in many types of cancer, and generally confers a poor prognosis. Known to induce many hundreds of protein-coding genes, HIF has also recently been shown to be a key regulator of the non-coding transcriptional response. Here, we show that NEAT1 long non-coding RNA (lncRNA) is a direct transcriptional target of HIF in many breast cancer cell lines and in solid tumors. Unlike previously described lncRNAs, NEAT1 is regulated principally by HIF-2 rather than by HIF-1. NEAT1 is a nuclear lncRNA that is an essential structural component of paraspeckles and the hypoxic induction of NEAT1 induces paraspeckle formation in a manner that is dependent upon both NEAT1 and on HIF-2. Paraspeckles are multifunction nuclear structures that sequester transcriptionally active proteins as well as RNA transcripts that have been subjected to adenosine-to-inosine (A-to-I) editing. We show that the nuclear retention of one such transcript, F11R (also known as junctional adhesion molecule 1, JAM1), in hypoxia is dependent upon the hypoxic increase in NEAT1, thereby conferring a novel mechanism of HIF-dependent gene regulation. Induction of NEAT1 in hypoxia also leads to accelerated cellular proliferation, improved clonogenic survival and reduced apoptosis, all of which are hallmarks of increased tumorigenesis. Furthermore, in patients with breast cancer, high tumor NEAT1 expression correlates with poor survival. Taken together, these results indicate a new role for HIF transcriptional pathways in the regulation of nuclear structure and that this contributes to the pro-tumorigenic hypoxia-phenotype in breast cancer.

The management of myxofibrosarcoma - a ten-year experience in a single specialist centre.

The aim of this study was to assess the management of myxofibrosarcoma in a single specialist centre, and examine factors contributing to local recurrence, metastasis and patient survival. Retrospective analysis of the referral, diagnosis, and management were obtained. Outcome measures including local recurrence, metastasis and death were recorded. 30 patients (mean age of 65.8 years) were treated for myxofibrosarcoma with limb salvage surgery between January 2003 and July 2012. 25 patients were treated for primary disease. Mean follow-up was 49 months (range 10-122). Larger tumours were most likely to metastasise (p = 0.041). Tumour size, resection margin and grade did not predict local recurrence or death. Local recurrence developed in eight patients (26.7%) with six subsequently requiring amputation, and four patients (16.7%) developed metastasis. Our results regarding local control and patient survival compare with that of the literature regarding limb salvage for primary disease, but amputation may be required for recurrent disease.

Real-life experience of managing vulval erosive lichen planus: a case-based review and U.K. multicentre case note audit.

BACKGROUND: There is a lack of published evidence for treatment and outcome measures for vulval erosive lichen planus (ELPV). OBJECTIVES: To conduct a multicentre case note review to examine real-life management of ELPV comparing current U.K. practice against an agreed audit standard. METHODS: Criteria for standards of care for which to evaluate current service provision were set following communication with experts from the British Society for the Study of Vulval Disease. Participants from 10 U.K. centres included nine dermatologists and one gynaecologist who run specialist vulval clinics. Standards examined the documentation of disease severity/impact measures, the use of diagnostic biopsies, treatments used and assessment of treatment response. RESULTS: Audit data were collected from 172 patients. Documentation of symptoms/clinical findings was excellent (99%, 170/172). A schematic diagram was present in the notes of 87% (150/172). Patient-related disease impact measures including Dermatology Life Quality Index (3%, 6/172) or visual analogue scales (1%, 2/172) were less well documented. Biopsies were performed in 78% (135/172); 71% (96/135) showed histological features consistent with erosive lichen planus. Squamous cell carcinoma developed in four patients (two vulval, two oral) and vulval intraepithelial neoplasia in two further patients. Recommended first-line treatment with a very potent topical steroid was used in 75% (129/172) with improvement in 66% (85/129). Significant variation in second-line therapy was seen. CONCLUSIONS: Wide variation in U.K. practice demonstrates the absence of standardized guidance for treating ELPV and the need for vulval-specific outcomes. This audit should act as a framework towards improving ELPV management and to plan future research in this area.

Solar capillaritis as a cause of solar purpura.

Appearance of purpura acutely after sun exposure is rare. We report a 51-year-old woman who repeatedly developed an asymptomatic petechial eruption on her legs after strong sun exposure. Investigation found an action spectrum within the ultraviolet A waveband, and histological examination of an evoked lesion found features of capillaritis. We briefly review the literature on solar purpura, and suggest that it is a feature of several distinct conditions, rather than a single condition.

Injuries among judokas during competition.

AIMS: To investigate the type and severity of injury sustained during judo competitions, and to investigate any possible correlation between injury rate and gender, grade, weight category and rapid weight loss. METHOD: Three hundred and ninety-two judokas (284 males, 108 females) competed in three consecutive competitions. A judoka was "injured" if they requested medical treatment or could not continue. Following injury, a questionnaire was completed. Uninjured judokas were asked to complete a questionnaire at one competition to assess risk factors of injury. Follow-up was conducted 6 weeks after each competition. RESULTS: Fifty-three out of 392 judokas (13.5%) (40 males, 13 females) sustained an injury. No difference was found between injury rates among males (41.3/1000 anthlete-exposures (A-E's)) and females (40.9/1000 A-E's), or between judokas of different weight groups or grades. Rapid weight loss of 5% or more of a judoka's body weight placed the athlete at a higher risk of injury (P=0.022). Most injuries affected the upper extremities. Injuries most often resulted from grip fighting, being thrown, or attempting to throw. CONCLUSIONS: Judokas are advised not to lose weight before a competition as this increases the risk of injury. Neither grade, nor gender, or weight category are associated with an increase in injury rate.

Lack of association of p53 polymorphisms and haplotypes in high and normal tension open angle glaucoma.

BACKGROUND: The final common pathway for open angle glaucoma (OAG) is retinal ganglion cell apoptosis. Polymorphisms in p53, a major regulator of apoptosis, affect the efficiency of cell death induction. Association studies of p53 haplotypes and OAG have had conflicting results. OBJECTIVE: To examine the association between p53 haplotypes and OAG in a larger white population than in previous reports, and extend the analysis to normal tension glaucoma. METHODS: 345 unrelated people with OAG were recruited (283 subjects with high tension glaucoma and 62 with normal tension glaucoma) and compared with 178 age matched controls. Genomic DNA was analysed for the p53 codon 72 Arg/Pro polymorphism as well as for the presence or absence of a 16 bp intron 3 insertion. RESULTS: In this white cohort no association was found between glaucoma (high or normal tension) and either sequence variant or haplotype. CONCLUSIONS: The p53 codon 72 Arg/Pro polymorphism is not associated with age of onset or severity of glaucoma.

Investigative methods for natural rubber latex allergy in the UK.

Allergy to natural rubber latex (NRL) has become an important health issue in recent years, but little is known about how this condition is investigated by physicians in the UK. This postal questionnaire of British dermatology and allergy specialists shows substantial variation in diagnostic practice, most notably with regard to the utilization and choice of starting dose of commercial latex prick test dilutions, reliance on allergen-specific immunoglobulin E measurement, investigation of associated fruit allergy and provision of resuscitation equipment/method of consent when challenge testing. 17% of responding physicians who investigate for NRL allergy do not perform prick test or glove challenge because of the potential risk of anaphylaxis or lack of resuscitation facilities. 87% of allergy clinic specialists report no reduction in the number of patients presenting as new referrals with suspected NRL allergy. These findings suggest a need for robust guidance to achieve more consistent investigative practice by those dealing with this condition.

Budding yeast Rad9 is an ATP-dependent Rad53 activating machine.

We find budding yeast Rad9 in two distinct, large, and soluble complexes in cell extracts. The larger (> or =850 kDa) complex, found in nondamaged cells, contains hypophosphorylated Rad9, whereas the smaller (560 kDa) complex, which forms after DNA damage, contains hyperphosphorylated Rad9 and Rad53. This smaller Rad9 complex is capable of catalyzing phosphorylation and release of active Rad53 kinase, a process requiring the kinase activity of Rad53. However, Mec1 and Tel1 are no longer required once the 560 kDa complex has been formed. We propose a model whereby Mec1/Tel1-dependent hyperphosphorylation of Rad9 results in formation of the smaller Rad9 complex and recruitment of Rad53. This complex then catalyzes activation of Rad53 by acting as a scaffold that brings Rad53 molecules into close proximity, facilitating Rad53 in trans autophosphorylation and subsequent release of activated Rad53.

Susac syndrome: microangiopathy of the retina, cochlea and brain.

BACKGROUND: Susac syndrome is characterized by the triad of branch retinal arterial occlusions, encephalopathy and cochlear microangiopathy. The underlying process is believed to be a small vessel vasculitis causing microinfarcts in the retina, brain and cochlea. METHODS: Analysis of two male and two female cases of Susac syndrome recognized in Australia. RESULTS: In this series the epidemiology, mode of presentation, ophthalmologic features, neurologic and cochleo-vestibular features, radiologic characteristics, cerebrospinal fluid findings, therapeutic interventions, clinical course and outcome of Susac syndrome is examined. Key ophthalmologic differential diagnoses include systemic lupus erythematosis (SLE), Behçet's syndrome and other vasculitides such as sarcoidosis, tuberculosis, syphilis and lymphoma. Neuro-otologic features are most frequently misdiagnosed as multiple sclerosis. CONCLUSION: Susac syndrome, first described in 1979, is becoming an increasingly recognized condition. Early recognition of the syndrome is important because treatment with systemic immunosuppression may minimize permanent cognitive, audiologic and visual sequelae.

Accuracy and implications of a reported family history of glaucoma: experience from the Glaucoma Inheritance Study in Tasmania.

OBJECTIVES: To ascertain the prevalence of previously undiagnosed primary open-angle glaucoma (POAG) within 5 large POAG pedigrees and to evaluate the reliability of a reported family history of glaucoma within these pedigrees. METHODS: The Glaucoma Inheritance Study in Tasmania (GIST) identified several large adult POAG pedigrees. Intraocular pressure (IOP), optic disc stereophotography, and automated perimetry were performed on all adult pedigree members. Participants were classified as normal (IOP <22 mm Hg and normal optic disc and field); glaucoma suspect (normal field, but an IOP >/=22 mm Hg and/or suspicious optic disc); or POAG (field defect and glaucomatous optic disc). Some individuals with POAG had been previously diagnosed by their local ophthalmologist; others were diagnosed as a result of the GIST project. Family members with a prior diagnosis of POAG were asked to report if they were aware of any relatives with POAG. This reported family history was then directly compared with the actual pedigree (before the diagnosis of new cases) to calculate agreement. MAIN OUTCOME MEASURE: The rate of glaucoma in pedigrees and percentage of previously diagnosed glaucoma cases who were aware of the positive family history of POAG. RESULTS: Four hundred forty-two subjects (mean age, 54 years [range, 13-97 years]) from 5 pedigrees were examined: 316 subjects (71%) were normal, 47 (11%) were previously diagnosed with POAG, and 8 (2%) were previously diagnosed glaucoma suspects; 30 cases (7%) of POAG and 41 suspects (9%) were newly diagnosed as a direct result of the GIST examination. Of the 47 previously diagnosed POAG cases, 41 were questioned about their prior knowledge of any family history and 11 (27%) were unaware of their family history of POAG. CONCLUSIONS: Examination of all adult subjects from POAG families yields new cases. Even in large POAG pedigrees, 27% of previously diagnosed POAG patients were unaware of their positive family history. These findings suggest that a higher percentage of adult POAG may be inherited than hitherto reported. Arch Ophthalmol. 2000;118:900-904