The global incidence of bullous pemphigoid: a systematic review and meta-analysis.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disorder that mainly affects older people. Although the disease is associated with considerable morbidity and mortality, the burden of disease worldwide is unclear. OBJECTIVES: The study aim is to pool the global incidence of BP and determine whether this varies according to geographic area, age group, setting and study quality. METHODS: Ovid MEDLINE, Ovid Embase and grey literature were systematically searched on 7 April 2020. Two reviewers independently screened, extracted data and appraised each study's quality using the Joanna Briggs Institute critical appraisal tool. Two domains, indicative of selection and survey bias, were used to identify high-quality studies. The cumulative incidence was standardized to 1 year and pooled in a random-effects meta-analysis. Subgroup and sensitivity analyses were conducted. RESULTS: Twenty-seven studies were identified, of which 23 provided cumulative incidence and four provided incidence rates. The cumulative incidence of BP was 8·2 [95% confidence interval (CI) 4·8-13.7] per million people whereas the incidence rate was 34·2 (95% CI 19·2-60·7) per million person-years. Of the continents that contributed more than one study, the cumulative incidence was 10·3 (95% CI 5·8-18·2) and 5·6 (95% CI 3·5-9·0) per million people in Europe and Asia, respectively. The incidence was highest in studies including adults only (n = 2), in population-based studies (n = 9) and in more recent years. The cumulative incidence was higher (13·3 per million people, 95% CI 6·0-29·5) when restricting the analysis to higher-quality studies (n = 11). High heterogeneity (I2 > 82%) was observed across all pooled estimates. CONCLUSIONS: The incidence of BP varies globally, is generally low but appears to be increasing over time. The burden of disease is likely to be underestimated.

Toxic epidermal necrolysis-like lupus.

Toxic epidermal necrosis (TEN)-like lupus is a rare condition characterized by epidermal loss and mucosal ulceration occurring in patients with acute severe flares of systemic lupus erythematosus. The clinical picture may mimic drug-induced Stevens-Johnson syndrome/TEN; however, the absence of a suitable culprit drug, and the context of acute lupus point to the correct diagnosis. In a case series of three patients, further discriminating features included a slower onset of epidermal loss, more limited mucosal ulceration and a lack of ocular involvement when compared with drug-induced TEN. Histology may show similar features, including basal layer vacuolation, apoptosis and full-thickness epidermal necrosis. Patients with TEN-like lupus may have additional features of lupus, and a lupus band on direct immunofluorescence. It is important to identify this condition correctly, so that these patients can be appropriately managed with early input from Rheumatologists and prompt treatment with high-dose combined immunosuppressant therapy.

Using electronic health records to inform trial feasibility in a rare autoimmune blistering skin disease in England.

BACKGROUND: Trials of novel agents are required to improve the care of patients with rare diseases, but trial feasibility may be uncertain due to concerns over insufficient patient numbers. We aimed to determine the size of the pool of potential participants in England 2015-2017 for trials in the autoimmune blistering skin disease bullous pemphigoid. METHODS: The size of the pool of potential participants was estimated using routinely collected healthcare data from linked primary care (Clinical Practice Research Datalink; CPRD) and secondary care (Hospital Episode Statistics; HES) databases. Thirteen consultant dermatologists were surveyed to determine the likelihood that a patient would be eligible for a trial based on the presence of cautions or contra-indications to prednisolone use. These criteria were applied to determine how they influenced the potential pool of participants. RESULTS: Extrapolated to the population of England, we would expect approximately 10,800 (point estimate 10,747; 95% CI 7191 to 17,239) new cases of bullous pemphigoid to be identified in a three-year period. For a future trial involving oral prednisolone (standard care), the application of cautions to its use as exclusion criteria would result in approximately 365 potential participants unlikely to be recruited, a further 5332 could be recruited with caution, and 5104 in whom recruitment is still possible. 11-17% of potential participants may have pre-existing dementia and require an alternative consent process. CONCLUSIONS: Routinely collected electronic health records can be used to inform the feasibility of clinical trials in rare diseases, such as whether recruitment is feasible nationally and how long recruitment might take to meet recruitment targets. Future trials of bullous pemphigoid in England may use the data presented to inform trial design, including eligibility criteria and consent processes for enrolling people with dementia.

Incidence, prevalence and mortality of bullous pemphigoid in England 1998-2017: a population-based cohort study.

BACKGROUND: A rising incidence and high mortality were found for bullous pemphigoid (BP) over a decade ago in the UK. Updated estimates of its epidemiology are required to understand the healthcare needs of an ageing population. OBJECTIVES: To determine the incidence, prevalence and mortality rates of BP in England from 1998 to 2017. METHODS: We conducted a cohort study of longitudinal electronic health records using the Clinical Practice Research Datalink and linked Hospital Episode Statistics. Incidence was calculated per 100 000 person-years and annual point prevalence per 100 000 people. Multivariate analysis was used to determine incidence rate ratios by sociodemographic factors. Mortality was examined in an age-, sex- and practice-matched cohort, using linked Office of National Statistics death records. Hazard ratios (HRs) were stratified by matched set. RESULTS: The incidence was 7·63 [95% confidence interval (CI) 7·35-7·93] per 100 000 person-years and rose with increasing age, particularly for elderly men. The annual increase in incidence was 0·9% (95% CI 0·2-1·7). The prevalence almost doubled over the observation period, reaching 47·99 (95% CI 43·09-53·46) per 100 000 people and 141·24 (95% CI 125·55-158·87) per 100 000 people over the age of 60 years. The risk of all-cause mortality was highest in the 2 years after diagnosis (HR 2·96; 95% CI 2·68-3·26) and remained raised thereafter (HR 1·54; 95% CI 1·36-1·74). CONCLUSIONS: We report a modest increase in the incidence rate of BP, but show that the burden of disease in the elderly population is considerable. Mortality is high, particularly in the first 2 years after diagnosis.

What's new in atopic eczema? An analysis of systematic reviews published in 2018. Part 1: prevention and topical therapies.

This review is part of a series of annual updates that summarize the evidence base for atopic eczema (AE). The aim is to provide a succinct guide for clinicians on the key findings from 14 systematic reviews on the prevention and topical treatment of AE published or indexed in 2018. Various supplements, including long-chain polyunsaturated fatty acids, vitamin D and the probiotic Lactobacillus rhamnosus GG, given prenatally and postnatally, have not been shown to prevent AE in infants, although mixed strains of probiotics may decrease the risk of AE if given to the mother during pregnancy and to the infant for the first 6 months of life. In the postnatal period, there is no evidence that hydrolysed formula, compared with cow's milk formula (CMF), reduces the risk of AE in partially breastfed infants. However, weak evidence suggests that a specific partially hydrolysed whey formula decreases the risk of AE compared with CMF. No specific skin practices can be recommended to reduce the eczema risk in healthy term babies. There is weak evidence of a low risk of reversible hypothalamic-pituitary-adrenal axis suppression following 2-4 weeks of treatment with low-potency topical steroids, and conflicting evidence as to whether bleach bathing affects skin flora or AE severity. A single study demonstrated that the topical Janus kinase inhibitor tofacitinib at 2% significantly reduces the Eczema Area and Severity Index compared with vehicle. Topical naltrexone cream 1% improves pruritus (measured using a visual analogue scale) by 30% more than placebo. There is weak evidence that topical alternative therapies, including antioxidants, micronutrients and some herbal medicines, may improve AE.

What's new in atopic eczema? An analysis of systematic reviews published in 2018. Part 2: systemic therapies.

This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent research findings. The focus of this article is systemic therapies used in AE, while a review on prevention and topical therapies is provided in Part 1. In total, 17 SRs on various systemic treatments used in AE were first published or indexed in 2018. There is a lack of evidence to support vitamin D supplementation, montelukast and naltrexone in AE treatment. The adverse effects of systemic corticosteroids are the main barrier to their use, and there is also a lack of data to determine the optimal delivery and duration of treatment with them. Of other immunosuppressants, ciclosporin has the most robust evidence of efficacy. Biologic therapies in AE treatment are being increasingly investigated, and to date, the greatest quantity of data and evidence of efficacy relates to dupilumab. The most commonly reported adverse effects are injection-site reactions and conjunctivitis. Other biologics showing some evidence of efficacy include nemolizumab, lebrikizumab and tralokinumab, although further data are needed. There are currently insufficient data on oral small molecules, including Janus kinase inhibitors, in the treatment of AE. A Cochrane review on probiotics showed no significant benefit, and SRs and meta-analyses on complementary and alternative medicines, including probiotics, in paediatric AE demonstrated significant heterogeneity, thereby limiting their interpretation. This summary of recent SRs provides up-to-date evidence for clinicians on systemic therapies in AE.

What's new in atopic eczema? An analysis of systematic reviews published in 2017. Part 2: epidemiology, aetiology and risk factors.

This article forms part of a series of annual updates that summarizes the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2017, and focuses on the epidemiology, aetiology and risk factors of AE. AE is the largest single contributor to morbidity associated with skin disease worldwide, once mortality has been excluded. There is a high prevalence of sleep disturbance in individuals with AE and they take more sick leave than controls. While there is a lack of skin bacterial diversity in patients with AE, there is a relative abundance of Staphylococcus aureus and Staphylococcus epidermidis. Compared with controls, affected individuals more often show an IgE response to S. aureus antigens and have higher serum interleukin-31 levels. Early antibiotic exposure, environmental pollutants, maternal atopy and food allergy are associated with an increased risk of AE, and very preterm birth is associated with decreased risk. Patients with AE have a reduced risk of meningioma, but are more likely to develop attention-deficit hyperactivity disorder compared with controls. Patients with eosinophilic oesophagitis are significantly more likely than unaffected individuals to have AE. There is no significant overall association between AE and allergic contact dermatitis (ACD), and in children referred for patch testing, ACD was more common in those without AE. Hand eczema is more prevalent in patients with AE. There is no association between AE and Type 2 diabetes, hypertension, stroke or myocardial infarction.

What's new in atopic eczema? An analysis of systematic reviews published in 2017. Part 1: treatment and prevention.

This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE). It provides a summary of key findings from 25 systematic reviews that were published or indexed during 2017, and focuses on the treatment and prevention of AE. There is high-quality evidence to demonstrate that dupilumab is better than placebo for the treatment of AE, is not associated with a higher incidence of adverse effects and does not increase the risk of infection compared with placebo; however, comparison studies with other systemic treatments are necessary. Topical tofacitinib is a promising treatment for mild-moderate AE, but currently lacks sufficient evidence from well-designed randomized controlled trials (RCTs) comparing with other active treatments. Topical doxepin may be effective for pruritus in AE, but available studies have short follow-up periods and longer-term outcomes are needed. Bleach baths were no more effective than water baths alone at reducing AE severity. Topical antibiotics cannot be recommended for infected AE, owing to insufficient evidence of benefit. There is little comparison of different emollients in RCTs, but overall evidence indicates that they reduce AE severity, are steroid-sparing and lead to better outcomes in combination with topical corticosteroids (TCS) than TCS alone. No clear benefit was demonstrated for vitamin D/C/E supplementation in pregnancy for eczema prevention.

Pemphigus vulgaris and pemphigus foliaceus: an overview of the clinical presentation, investigations and management.

Pemphigus diseases are cutaneous and mucous membrane blistering diseases, related to the key antigens of desmoglein 1 and 3. This article reviews the topic, including diagnosis, and provides the physician with guidance on the treatment of these difficult to control disorders.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 2: Epidemiology, aetiology and risk factors.

This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE), providing a succinct guide for clinicians and patients. It presents the key findings from 14 systematic reviews published in 2016, focusing on AE epidemiology, aetiology and risk factors. For systematic reviews on the treatment and prevention of AE and for nomenclature and outcome assessments, see Parts 1 and 3 of this update, respectively. The annual self-reported prevalence of AE is a range of 11.4-24.2%, compared with a general practioner-diagnosed prevalence of 1.8-9.5%. The mean age of AE diagnosis is 1.6 years. Persistent AE is associated with more severe disease at the time of diagnosis, onset after the age of 2 years and female sex. There is a significant association between having AE and subsequent development of food allergy. Food allergy is also associated with more severe and persistent AE. No consistent association was found between the timing of allergenic food introduction and the risk of developing AE. Evidence from heterogeneous studies indicates that skin absorption is increased in patients with AE, and that there is increased colonization with Staphylococcus aureus in lesional and nonlesional skin and the nasal mucosa of patients with AE compared with controls. There is uncertain evidence indicating an association between AE and smoking exposure, antenatal infection and low maternal vitamin D levels during pregnancy. Weak evidence suggests an increased risk of basal cell carcinoma, but not of melanoma or squamous cell carcinoma, while the risk of glioma is reduced.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 3: nomenclature and outcome assessment.

This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE). It presents the key findings from 11 systematic reviews published in 2016 that focus on AE outcome assessment, disease impact and nomenclature. Systematic reviews on the treatment and prevention of AE are summarized in Part 1 of this update, and systematic reviews on the epidemiology of and risk factors for AE are summarized in Part 2. Six reviews summarized what outcome measurement instruments have been used in published AE trials, or summarized validation studies for the available instruments. These reviews were used to inform consensus decisions by the Harmonising Outcome Measures for Eczema initiative. Although validated instruments exist for clinical signs and patient-reported symptoms, there are currently no validated instruments for capturing quality of life or long-term control. Four reviews examined the impact of AE on children and their families, but few studies were included. One birth cohort study found no association between AE and educational attainment at 11 years. AE has a moderate impact on health-related quality of life and a substantial impact on family life. AE is a major risk factor for occupational hand dermatitis, and it is advised that young atopic individuals are informed about high-risk occupations. Further efforts are required to standardize the nomenclature for AE, which is also commonly known as 'atopic dermatitis' or 'eczema', and preferred terms vary around the world.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and prevention.

This review is part of a series of annual updates summarizing the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2016 with a focus on treatment and prevention of AE. There is reasonable evidence of benefit for topical corticosteroids, calcineurin inhibitors, a glycyrrhetinic acid-containing preparation (Atopiclair® ), oral ciclosporin, oral azathioprine, narrowband ultraviolet B radiation and education programmes. Overall, there is evidence that topical corticosteroids and calcineurin inhibitors have similar efficacy and that both can prevent AE flares when used twice weekly as maintenance therapy. However, topical calcineurin inhibitors are costlier and have more adverse reactions, thus topical corticosteroids should remain the standard of care for patients with AE. There is no evidence that multiple applications are better than once-daily application of topical corticosteroid. There is inconsistent evidence to support omalizumab and specific allergen immunotherapy use in AE. There is some evidence that vitamin D supplementation and synbiotics reduce AE severity, although the margin of improvement may not be clinically meaningful. There is little evidence to support the use of wet wraps or of complementary/alternative medicine (including Chinese herbal medicine). There is some evidence to suggest that a diet high in fish in infancy may be preventative for AE, but other dietary interventions for the prevention of AE show little promise. This review provides a succinct guide for clinicians and patients wishing to remain up to date with the latest evidence for the treatment and prevention of AE.

Generating new evidence, improving clinical practice and developing research capacity: the benefits of recruiting to the U.K. Dermatology Clinical Trials Network's STOP GAP and BLISTER trials.

Clinical trials may benefit clinical practice in three ways: firstly, clinicians may change their practice according to the new trial evidence; secondly, clinical processes can improve when working on a trial; and thirdly, research capacity is increased. We held a meeting to present and discuss the results of two large multicentre randomized controlled trials delivered through the U.K. Dermatology Clinical Trials Network. Investigators gave reflections on how the trials had changed their clinical practice. The STOP GAP trial showed that prednisolone and ciclosporin are equally effective as first-line systemic treatment for pyoderma gangrenosum. The final decision of which treatment to use should be based on the different adverse event profiles of the two drugs in relation to comorbidities, along with age, disease severity and patient preference. The BLISTER trial showed that starting people with pemphigoid on doxycycline produces acceptable short-term effectiveness and a superior safety profile to oral corticosteroids. Recruiting to these trials has led to the development of new specialist clinics with improved documentation. It has increased the profile of participating departments and embedded research in the department's activities. Helping to design and run these trials has also allowed trial staff to develop new skills in research design, which has been beneficial for career development. These and other benefits of recruiting to the trials are summarized here. We hope that these reflections will inspire wider involvement in clinical research.

Doxycycline-induced hypoglycaemia.

Tetracyclines, including doxycycline, are widely used drugs that form an integral part of daily prescribing, and serious adverse reactions (SARs) are rarely reported. The frequency of hypoglycaemia complicating tetracycline treatment remains unknown, and is not a recognized complication. We describe an 80-year-old man with a history of insulin-dependent diabetes who was recruited into a large research study, and subsequently experienced the unexpected SAR of hypoglycaemia following treatment with doxycycline.