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.

Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case-control diagnostic accuracy study (DIPSOC study).

BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed.

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.

Do patient characteristics matter when calculating sample size for eczema clinical trials?

Background: The Patient-Oriented Eczema Measure (POEM) is the core outcome instrument recommended for measuring patient-reported atopic eczema symptoms in clinical trials. To ensure that the statistical significance of clinical trial results is meaningful, trials are often designed by specifying the target difference in the primary outcome as part of the sample size calculation. One method used to specify the target difference is a score that corresponds to a standardized effect size. Objectives: to assess how the standardized effect size of POEM scores vary across age, gender, ethnicity and disease severity. Methods: This study combined data from five UK-based randomized clinical trials of eczema treatments in order to assess differences in self-reported eczema symptoms (POEM) corresponding to a standardized effect size (0.5 SD of baseline POEM scores) across age, gender, ethnicity and disease severity. Results: POEM scores corresponding to 0.5 SD(baseline) were remarkably consistent across participants of varying ages, gender, ethnicity and disease severity from datasets of five UK trials in children (range 2.99-3.45). Conclusions: This study provides information that can support those designing clinical trials to determine their sample size and can aid individuals interpreting trial results. Further exploration of differences in populations beyond the United Kingdom is needed.

Is urinary incontinence associated with lichen sclerosus in females? A systematic review and meta-analysis.

Background: Lichen sclerosus (LS) is a scarring chronic inflammatory disease with a predilection for genital skin in both sexes. The aetiology of LS is controversial, but evidence increasingly suggests that the occluded exposure of susceptible epithelium to urine is involved in the pathogenesis of genital LS in males. This theory has not yet been robustly investigated in females. Objectives: This review and meta-analysis examined whether there is an association between urinary incontinence (UI) and genital lichen LS in females. Methods: We performed a comprehensive search of MEDLINE, Embase and CINAHL to identify observational studies assessing the prevalence of UI in females with LS. DerSimonian and Laird random-effects models were used to estimate the overall pooled prevalence and risk ratio compared to controls. Heterogeneity was assessed. Results: In total, eight studies met the inclusion criteria and five studies were included in a meta-analysis. Three studies were graded as moderate quality and five were poor. The pooled prevalence for UI in LS was 0.35 (95% confidence interval [CI] 0.13-0.58, I 2 = 98.4%). The risk ratio of UI in LS was 0.97 (95% CI 0.53-1.75, I 2 = 87.5%). Conclusion: There appears to be no difference between patients with LS and those without LS in terms of UI. Studies are limited by clinical and methodological quality and heterogeneity is high. Well-designed prospective studies are needed.

Can atopic eczema and psoriasis coexist? A systematic review and meta-analysis.

Importance: Previous studies report both coexistence and mutual exclusivity of atopic eczema (AE) and psoriasis, but these have not been appraised systematically. Knowledge of such disease association throws light on disease mechanisms and may influence therapeutic choices. Objective: To summarise evidence for AE and psoriasis occurring in the same person at the same point in time. Planned primary outcome was the incidence, prevalence or risk of psoriasis or eczema. Methods: Ovid MEDLINE and Ovid Embase were searched from inception to 1st February 2020. The search strategy was built around the key terms 'atopic eczema', 'psoriasis' and 'co-existence'. Observational studies (cohort, case-control, cross-sectional and case-series) with a minimum of 10 consecutive patients were included. There were no restrictions on participants, geography or language. Studies were selected, data extracted and critically appraised by two independent reviewers. Data were extracted on the method of diagnosis: health professional (dermatologist, criteria, other), self-reported, not specified. Study quality was assessed using validated Joanna Brigg's Institute critical appraisal tools. A random-effects model was used to combine studies. The effect of study quality on the pooled estimate was investigated using stratification. Heterogeneity was explored by subgroup analysis. Results: This review included 31 studies and 20 523 individuals with psoriasis and 1 405 911 with AE. Eight studies reported the prevalence of AE in those with psoriasis and values ranged from 0.17% to 20%: the pooled prevalence was 2% (95% confidence interval [CI]: 1, 3). Seven studies reported the prevalence of psoriasis in those with AE and values ranged from 0.3% to 12.6%; the pooled prevalence was 2% (95% CI: 1, 3). Ten studies were assessed as low risk of bias. Geographical area, method of diagnosis, setting and whether the assessment of diagnosis was blinded, partly contributed to the heterogeneity. Conclusions: This review provides some evidence for the coexistence of AE and psoriasis. Clinicians should be aware of coexistence at diagnosis, when selecting therapies and when reviewing poor response to treatment.

A 10-year review of surgical management of dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer. Standard treatment in the UK is either wide local excision (WLE) or Mohs micrographic surgery (MMS). It is unclear which approach has the lower recurrence rate. OBJECTIVES: We undertook a retrospective comparative review of surgical management of DFSP in the UK National Health Service in order to define (i) current surgical practice for primary and recurrent DFSP, (ii) local recurrence rates for primary DFSP and (iii) survival outcomes for DFSP. METHODS: A retrospective clinical case-note review of patients with histologically confirmed DFSP (January 2004 to December 2013) who have undergone surgical treatment. RESULTS: The surgical management of 483 primary and 64 recurrent DFSP in 11 plastic surgery and 15 dermatology departments was analysed. Almost 75% of primary DFSP (n = 362) were treated with WLE and 20% (n = 97) with MMS. For recurrent DFSP, 69% (n = 44) and 23% (n = 15) of patients underwent WLE and MMS, respectively. Recurrent primary DFSP occurred in six patients after WLE and none after MMS. The median follow-up time was 25·5 months (interquartile range 6·8-45·1) for new and 19·8 (IQR 4·5-44·5) for recurrent DFSP [Correction added on 1 Feb 2021, after first online publication: 4.8 years (interquartile range 3.5-5.8) was incorrect], with eight reported deaths during the follow-up analysis period (one confirmed to be DFSP related). CONCLUSIONS: WLE was the most common surgical modality used to treat DFSP across the UK. The local recurrence rate was very low, occurring only after WLE. Although a prospective randomized controlled trial may provide more definitive outcomes, in the absence of a clearly superior surgical modality, treatment decisions should be based on patient preference, clinical expertise and cost.

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.

Development and initial testing of a new instrument to measure the experience of eczema control in adults and children: Recap of atopic eczema (RECAP).

BACKGROUND: Eczema control has been identified as an important outcome by key stakeholders in eczema research (including patients, carers, healthcare professionals and researchers) but no validated instruments for the domain have been identified. OBJECTIVES: To develop a measurement instrument to capture a patient's perspective of eczema control that is suitable for use in eczema clinical trials. METHODS: Best practice for the development of a patient-reported outcome was followed. A mixed-methods approach was used to develop and refine a conceptual framework, generate, refine and select items and to test the distribution and construct validity of the final scale. The mixed-methods approach involved expert panel meetings (including patient representatives, healthcare professionals and methodologists), and data collection using a focus group, cognitive interviews and an online survey with people with eczema and caregivers. Multivariable linear regression was used in the item selection process. RESULTS: Fourteen expert panel members co-produced the instrument, with input from people with eczema and caregivers via a focus group (n = 6), cognitive interviews (n = 13) and an online survey (n = 330). The resulting instrument, Recap of atopic eczema (RECAP), is a seven-item questionnaire that captures eczema control via self or caregiver report. The development process aimed to ensure good content validity and feasibility. Initial testing suggested no floor or ceiling effects and good construct validity. Hypothesized correlation with the Patient-Oriented Eczema Measure was confirmed [r(258) = 0·83, P < 0·001]. CONCLUSIONS: RECAP has the potential to improve reporting of eczema control in research and clinical practice. Further exploration of measurement properties is required. Linked Comment: Pattinson and Bundy. Br J Dermatol 2020; 183:418-419. What's already known about this topic? Eczema control has been identified as an important outcome by key stakeholders in eczema research (including patients, carers, healthcare professionals and researchers). Qualitative studies suggest eczema control is a multifaceted and individual experience and no instrument has been identified that captures eczema control in this way. What does this study add? We have developed Recap of atopic eczema (RECAP), a seven-item questionnaire to capture the experience of eczema control in all ages and eczema severities; there are two versions: a self-reported version for adults and older children with eczema, and a caregiver-reported version for younger children with eczema. Designed with input from people with eczema, caregivers and healthcare professionals to ensure good content validity. Initial testing of score distributions and construct validity suggests good measurement properties. What are the clinical implications of the work? The RECAP instrument is appropriate and feasible for measuring eczema control in clinical trials and may also be useful in routine practice.

Hepatitis B crónica / Chronic B hepatitis

Chronic hepatitis B is a major public health problem, causing 30% of cirrhosis worldwide and up to 50% of hepatocellular carcinoma. In high prevalence regions, virus transmission is mainly vertical, which is associated with a risk of chronic disease in 90% of cases. The development of chronic hepatitis in adults is less than 5%, but it could reach up to 30% in patients with immunosuppression. In the evaluation of subjects with HBV infection is recommended to investigate risk factors for progression to cirrhosis and hepatocellular carcinoma, test for sexually transmitted infections and control liver comorbidities that will affect patient's prognosis, such as chronic alcohol consumption, nonalcoholic fatty liver disease and coinfection with hepatitis C and HIV. Management of patients with chronic hepatitis B includes testing and prevention for contacts, control of comorbidities, and specific treatment with antivirals when indicated. Treatment with nucleotide/nucleoside analogues is considered of choice as they are safe, achieves adequate control of viral replication and reduces the risk of liver complications. The goal of the WHO is to achieve a significant decrease in the prevalence of hepatitis B by 2030 through preventive measures in regions with a high prevalence of the disease.

La infección por el virus de la hepatitis B (VHB) es un importante problema de salud pública, estimándose que causa 30% de los casos de cirrosis a nivel mundial y hasta 50% de los hepatocarcinomas. En las regiones de alta prevalencia, la transmisión del virus es principalmente vertical, la que se asocia a un riesgo de cronificación de hasta 90%. Por el contrario, el desarrollo de hepatitis crónica en adultos es menor de 5% y en inmunosupresión puede alcanzar hasta 30%. En la evaluación de sujetos con infección por VHB es necesaria pesquisar factores de riesgo de progresión a cirrosis y hepatocarcinoma, detectar otras infecciones de transmisión sexual y controlar comorbilidades hepáticas que afectarán el pronóstico del paciente, como el consumo crónico de alcohol, el hígado graso no alcohólico o la coinfección con hepatitis C y VIH. El manejo de los pacientes con hepatitis B crónica requiere preocuparse del testeo y medidas de prevención para los contactos, control de comorbilidades y tratamiento específico con antivirales cuando existe indicación. El tratamiento con análogos de nucleótidos/nucleósidos se considera de elección al ser seguro, lograr un adecuado control de la replicación viral y disminuir riesgo de complicaciones hepáticas. El objetivo de la OMS es lograr una disminución significativa de la prevalencia de la hepatitis B el año 2030 a través de medidas preventivas en regiones de alta prevalencia de la enfermedad.

Routine rhesus-D genotyping in amniotic fluid: analysis of exon 10 versus intron 4 by polymerase chain reaction.

Both the exon 10 and the intron between exons 4 and 5 of the Rh-D gene were analyzed in DNA from amniotic cells by polymerase chain reaction (PCR) in order to determine the fetal Rh-D status. Residual (0.3-2 ml) samples of amniotic fluid obtained by diagnostic amniocentesis in Rh-D-negative women were analyzed. It is important to standardize the sampling and preanalytical storage and to optimize DNA extraction procedures as well as the detection of PCR products for maximal sensitivity. Genotyping was successful in approximately 90% (229 of 256) of amniotic fluid samples tested. Consistent Rh-D results were obtained by both methods in all 229 typed samples with a single exception. Our experience demonstrates that routine genotyping of the Rh-D blood group in small volumes of amniotic fluid (0.5-2 ml) is feasible. Its validity is currently tested by comparison of the prenatal genotype with the serotype of the newborn.

Rhesus D genotyping in amniotic fluid.

Rhesus D genotyping by PCR of amniotic fluid offers a very valuable tool for prenatal care of Rhesus D-alloimmunized women. Misleading results have been reported for the method of Bennett et al. analysing the 3'-terminal end of the RhD gene. We have observed also problems with Rhesus D genotyping of DVI-variant samples in the assay of Simsek et al. utilizing size differences of intron 4 between the Rhesus D and the Rhesus CcEe gene. We, thus, prefer to amplify two different regions including the 3'-terminal region of the Rhesus D gene to further minimize the very low risk of false-negative results. This rapid Rhesus D genotyping usually does not require more than 2 ml of amniotic fluid.