Summary
Background
Clinical practice guidelines (CPGs) play a critical role in standardizing and improving treatment outcomes based on the available evidence. It is unclear how many CPGs are ...available globally to assist clinicians in the management of patients with skin disease.
Objectives
To search for and identify CPGs for dermatological conditions with the highest burden globally.
Methods
We adapted a list of 12 dermatological conditions with the highest burden from the Global Burden of Disease (GBD) study 2019. A systematic literature search was done to identify CPGs published between October 2014 to October 2019. The scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) framework.
Results
A total of 226 CPGs were included. Melanoma had the greatest representation in the CPGs, followed by dermatitis and psoriasis. Skin cancers had a relatively high CPG representation but with lower GBD disease burden ranking. There was an uneven distribution by geographical region, with resource‐poor settings being under‐represented. The skin disease categories of the CPGs correlated weakly with the GBD disability‐adjusted life‐years metrics. Eighty‐nine CPGs did not have funding disclosures and 34 CPGs were behind a paywall.
Conclusions
The global production of dermatology CPGs showed wide variation in geographical representation, article accessibility and reporting of funding. The number of skin disease CPGs were not commensurate with its disease burden. Future work will critically appraise the methodology and quality of dermatology CPGs and lead to the production of an accessible online resource summarizing these findings.
What is already known about this topic?
Skin‐related diseases are leading causes of disability and disease burden globally.
Clinical practice guidelines (CPGs) are important to ensure appropriate standards of care for skin conditions.
The number, distribution, accessibility and quality of dermatological CPGs available globally is unknown.
What does this study add?
This is the first scoping review to describe the distribution of CPGs for common dermatological conditions of highest burden available internationally.
Inflammatory skin conditions and skin cancers represent a higher proportion of the number of CPGs produced, largely driven by high‐income countries.
Further studies to evaluate the quality of CPGs in dermatology, and the development of CPGs in skin diseases predominantly affecting resource‐poor countries, are needed.
Linked Comment: T.E. Sivesind and R.P. Dellavalle. Br J Dermatol 2021; 185:690–691.
Plain language summary available online
Summary
Background
Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for ...the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations–haemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe) syndrome and cessation of treatment.
Objectives
To provide unified guidelines for the treatment of IH with propranolol.
Methods
This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face‐to‐face multidisciplinary panel meeting and anonymous voting.
Results
The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment.
Conclusions
These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision‐making.
Linked Comment: Janmohamed. Br J Dermatol 2018; 179:553–554.
Plain language summary available online
Summary
Background
Little is known about U.K. dermatologists' treatment approaches towards adult patients with recalcitrant moderate‐to‐severe atopic eczema.
Objectives
We wanted to learn about (i) ...treatment approaches used for this disease in the U.K.; (ii) factors that influence treatment decisions and (iii) perceived gaps in evidence on treatment safety and efficacy, and priorities for future trials.
Methods
We conducted an online survey of consultant‐level dermatologists in the U.K.
Results
Sixty‐one respondents from over 30 centres reported on management of moderate‐to‐severe atopic eczema in adults, outwith the context of an acute flare. Phototherapy or psoralen–ultraviolet A was the most common therapeutic modality chosen first line (46%), and this was usually narrowband ultraviolet B. Systemic therapy was chosen as a first‐line approach by 36% of dermatologists. Azathioprine was the commonest drug reported being used as first line followed by oral corticosteroids, ciclosporin and methotrexate. Methotrexate was the most common second‐line treatment of respondents. The key factors that influenced decision making on the use of phototherapy and systemic agents were the respondent's clinical experience, results of baseline tests (systemic agents) and knowledge of both efficacy and acute and chronic side‐effect profiles. The most important evidence gaps identified were the relative effectiveness of treatments, the alternatives to current approaches and the safety of long‐term maintenance treatment. With regard to future trials, respondents suggested that priority should be given to studies involving methotrexate.
Conclusions
While survey study designs have limitations, we found that phototherapy, in particular narrowband ultraviolet B, was respondents' preferred first‐line treatment for adults with recalcitrant moderate‐to‐severe atopic eczema, perhaps reflecting access to, and clinical experience of, this approach. Azathioprine is widely used as a longer‐term maintenance treatment.
What's already known about this topic?
Clinical trials have shown that phototherapy is an effective treatment for moderate‐to‐severe atopic eczema in adults, but the extent to which it is used in clinical practice in the U.K. is unknown.
Ciclosporin is currently the only licensed systemic treatment for moderate‐to‐severe atopic eczema in adults.
It is known that other systemic drugs are widely prescribed off‐label, but the only reliable data on their use come from a systematic survey of dermatologists and paediatricians published in 2013 on the treatment of paediatric eczema across Europe.
What does this study add?
The majority of U.K. consultant‐level dermatologists use phototherapy and systemic drugs for treating adults with moderate‐to‐severe atopic eczema.
Key factors influencing the treatment decisions made by U.K. dermatologists were their own clinical experience, results of baseline tests, knowledge of treatment efficacy and knowledge of the acute and chronic side‐effect profiles of the various treatment options.
We report the clinical trials that dermatologists would like to see performed; a study involving methotrexate was identified as a priority.
Respond to this article
Linked Comment: Drucker. Br J Dermatol 2017; 176:1441–1442
Background
Observational studies suggest an increased risk of eczema in children living in hard versus soft water areas, and there is, therefore, an interest in knowing whether softening water may ...prevent eczema. We evaluated the feasibility of a parallel‐group assessor‐blinded pilot randomized controlled trial to test whether installing a domestic ion‐exchange water softener before birth in hard water areas reduces the risk of eczema in infants with a family history of atopy.
Methods
Pregnant women living in hard water areas (>250 mg/L calcium carbonate) in and around London UK, were randomized 1:1 antenatally to either have an ion‐exchange water softener installed in their home or not (ie to continue to receive usual domestic hard water). Infants were assessed at birth and followed up for 6 months. The main end‐points were around feasibility, the primary end‐point being the proportion of eligible families screened who were willing and able to be randomized. Clinical end‐points were evaluated including frequency of parent‐reported doctor‐diagnosed eczema and visible eczema on skin examination. Descriptive analyses were conducted, and no statistical testing was performed as this was a pilot study.
Results
One hundred and forty‐nine families screened were eligible antenatally and 28% (41/149) could not have a water softener installed due to technical reasons or lack of landlord approval. Eighty of 149 (54%) were randomized, the primary end‐point. Two participants withdrew immediately after randomization, leaving 39 participants in each arm (78 total). Attrition was 15% (12/78) by 6 months postpartum. All respondents (n = 69) to the study acceptability questionnaire reported that the study was acceptable. Fifty‐six of 708 (7.9%) water samples in the water softener arm were above the hard water threshold of 20 mg/L CaCO3. At 6 months of age 27/67 infants (40%) developed visible eczema, 12/36 (33%) vs. 15/31 (48%) in the water softener and control groups, respectively, difference −15% (95% CI −38, 8.3%), with most assessments (≥96%) remaining blinded. Similarly, a lower proportion of infants in the water softener arm had parent‐reported, doctor‐diagnosed eczema by 6 months compared to the control arm, 6/17 (35%) versus 9/19 (47%), difference −12% (95% CI −44, 20%).
Conclusion
A randomized controlled trial of water softeners for the prevention of atopic eczema in high‐risk infants is feasible and acceptable. Trial registration: NCT03270566 (clinicaltrials.gov)
In the SOFTER trial, approximately half of eligible families were willing and able to be randomized to a water softener. There were less infants that had visible or parent‐reported doctor‐diagnosed eczema in the water softener group in comparison with the control group, which had their usual hard domestic water supply. Lastly, this pilot trial showed that a trial of water softeners for preventing eczema in high‐risk infants is feasible and acceptable.
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Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co‐occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD ...disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta‐analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge‐proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/ and full‐text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7–53.2), 32.7% (28.8–36.6) and 40.7% (34.1–47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3–56.2), 45.3% (41.4–49.3) and 54.9% (47.0–62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4–55.1)) and FA (31.4% (26.9–36.1)) prevalences than adults with AD (28.6% (13.4–46.8) and 24.1% (12.1–38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients.
Background
Phototherapy is used to treat atopic dermatitis (AD). Evidence for its efficacy, impact on quality of life, cost‐effectiveness and short‐ and long‐term safety with real‐life usage is weak.
...Objectives
We established a taskforce to examine how phototherapy is currently being used as a treatment for AD across the United Kingdom and Europe to inform our understanding and guide future research into management of patients with AD using UV‐based phototherapies.
Methods
An anonymous electronic multiple‐response survey exploring phototherapy prescribing practices and experience of phototherapy modalities was developed by the study authors and sent to members of phototherapy networks from the United Kingdom and Europe. Responses were received between February and July 2021.
Results
About 144 respondents from 27 European countries completed the survey. NBUVB was the most widely used n = 138 (96%). Home‐based NBUVB was available in 8/27 countries (25/144 respondents, 17%). Oral psoralen‐UVA (PUVA) was more widely available than bath PUVA (n = 106, 74% vs. n = 60, 42%) and used mainly in adult patients. 49/144 (34%) of respondents had access to UVA1. Phototherapy would be considered instead of systemic treatment in 96% of adults and 82% of children for NBUVB, versus 40% of adults and 3% of children for PUVA. Starting doses, standard dosing increments, length of treatment courses, lifetime limits for treatments and thresholds for performing annual skin assessments varied between responders.
Conclusions
NBUVB was the most widely used phototherapy for AD in adult and paediatric patients, while PUVA and UVA1 were less used. Prescribing practices varied considerably, highlighting the lack of consensus practice in many different aspects of phototherapy for the treatment of AD in children and adults. This indicates that further studies are required to determine optimal phototherapeutic regimens for AD and informs our understanding of parameters that should be included in future high‐quality randomized controlled trials (RCT) of phototherapy.
Summary
Background
Several studies have identified an association between water hardness and atopic eczema (AE); however, there is a paucity of longitudinal data in early life.
Objectives
To examine ...whether water hardness is associated with an increased risk of AE and skin barrier dysfunction in infants and to assess effect modification by filaggrin (FLG) loss‐of‐function variants.
Methods
We performed a longitudinal analysis of data from infants in the Enquiring About Tolerance (EAT) study, who were enrolled at 3 months and followed up until 36 months of age.
Results
Of 1303 infants enrolled in the EAT study, 91·3% (n = 1189) attended the final clinic visit and 94·0% (n = 1225) of participants’ families completed the 36‐month questionnaire. In total, 761 (58·4%) developed AE by 36 months. There was no overall association between exposure to harder (> 257 mg L−1 CaCO3) vs. softer (≤ 257 mg L−1 CaCO3) water: adjusted hazard ratio (HR) 1·07, 95% confidence interval (CI) 0·92–1·24. However, there was an increased incidence of AE in infants with FLG mutations exposed to hard water (adjusted HR 2·72, 95% CI 2·03–3·66), and statistically significant interactions between hard water plus FLG and both risk of AE (HR 1·80, 95% CI 1·17–2·78) and transepidermal water loss (0·0081 g m−2 h−1 per mg L−1 CaCO3, 95% CI 0·00028–0·016).
Conclusions
There is evidence of an interaction between water hardness and FLG mutations in the development of infantile AE.
What's already known about this topic?
Several cross‐sectional studies have found an association between domestic water hardness exposure and atopic eczema (AE) risk.
Loss‐of‐function mutations in the skin barrier gene filaggrin (FLG) are the strongest genetic risk factor for AE.
What does this study add?
There was no overall association between AE risk and exposure to harder vs. softer domestic water in a large, well‐phenotyped cohort of infants living in England and Wales followed up at 3–36 months of age.
However, infants with at least one FLG loss‐of‐function mutation exposed to harder water have a threefold increased risk of developing AE up to age 36 months compared with infants with wild‐type FLG exposed to softer water.
Linked Comment: Arents and Leonardi-Bee. Br J Dermatol 2020; 183:203–204.
Plain language summary available online
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