Summary
Background
Guidelines discourage the use of systemic corticosteroids for atopic dermatitis (AD), but their use remains widespread.
Objectives
To reach consensus among an international group ...of AD experts on the use of systemic corticosteroids for AD.
Methods
A survey consisting of statements accompanied by visual analogue scales ranging from ‘strongly disagree’ to ‘neutral’ to ‘strongly agree’ was distributed to the International Eczema Council (IEC). Consensus was reached in agreement on a statement if < 30% of respondents marked to the left of ‘neutral’ towards ‘strongly disagree’.
Results
Sixty of 77 (78%) IEC members participated. Consensus was reached on 12 statements, including that systemic corticosteroids should generally be avoided but can be used rarely for severe AD under certain circumstances, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event or in the most severe cases. If used, treatment should be limited to the short term. Most respondents agreed that systemic corticosteroids should never be used in children, but consensus was not reached on that statement. The conclusions of our expert group are limited by a dearth of high‐quality published evidence. If more stringent consensus criteria were applied (e.g. requiring < 20% of respondents marking towards ‘strongly disagree’), consensus would have been reached on fewer statements.
Conclusions
Based on expert opinion from the IEC, routine use of systemic corticosteroids for AD is generally discouraged and should be reserved for special circumstances.
What's already known about this topic?
Despite recommendations against their use in practice guidelines, systemic corticosteroids are commonly used for atopic dermatitis (AD).
What does this study add?
The International Eczema Council reached consensus on circumstances in which systemic corticosteroids can be used for AD, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event, or in the most severe cases.
Clinicians should limit the use of systemic corticosteroids for severe AD to those circumstances.
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Adaptive radiation of a lineage into a range of organisms with different niches underpins the evolution of life’s diversity. Although the role of the environment in shaping adaptive radiation is well ...established, theory predicts that the evolvability and niche of the founding ancestor are also of importance. Direct demonstration of a causal link requires resolving the independent effects of these additional factors. Here, we accomplish this using experimental bacterial populations and demonstrate how the dynamics of adaptive radiation are constrained by the niche of the founder. We manipulated the propensity of the founder to undergo adaptive radiation and resolved the underlying causal changes in both its evolvability and niche. Evolvability did not change, but the propensity for adaptive radiation was altered by changes in the position and breadth of the niche of the founder. These observations provide direct empirical evidence for a link between the niche of organisms and their propensity for adaptive radiation. This general mechanism may have rendered the evolutionary dynamics of extant adaptive radiations dependent on chance events that determined their founding ancestors.
Summary
Allergic diseases are rare in areas with high helminth parasite exposure and common where helminth exposure is lacking or significantly reduced, such as urban areas of developing countries ...and industrialized nations. Studies suggest that helminths induce a systemic immuno‐modulatory network, including regulatory T cells and anti‐inflammatory IL‐10, which might play a key role in the protection against the allergic phenotype. Here, we review the current cross‐sectional, birth cohort, and intervention study evidence for a protective effect of helminth infection on allergy. There is increasing evidence for a causal relationship between helminth infection and reduced skin prick test responsiveness to allergens. Cross‐sectional studies have shown a consistent negative relationship, and these results have been confirmed in several, although not all, intervention studies. The immunological basis for this protective effect is less clear. Recent studies do not support the mast‐cell IgE saturation hypothesis, but suggest that protection is associated with IL‐10 production. As for allergic disease, cross‐sectional studies support a negative relationship between clinical asthma and infection with some helminth species, particularly hookworm, but more studies are required to draw conclusions for eczema and rhinitis. In addition, none of the few intervention studies to date have demonstrated an increase in clinical allergy after helminth treatment, and further studies are needed. Furthermore, we are only beginning to understand the host genetic factors that are potentially involved. A genetically predetermined T‐helper type 2 cell‐dominated cytokine milieu reduces parasite burden and may enhance host survival in an environment where helminth parasites are prevalent. Lack of parasite exposure in such hosts might lead to hypersensitivity to seemingly minor environmental allergen stimuli. Large birth cohort studies in helminth‐endemic areas that use epidemiological, genetic, and immunological tools are required to further examine how helminth parasites affect the development of atopy and allergic disease. Intervention studies with hookworm in parasite‐naïve allergic individuals are currently ongoing in the United Kingdom to test the above hypotheses further.
Abstract The International Study of Asthma and Allergies in Childhood (ISAAC) is the largest epidemiological study ever performed and the only truly global allergy study. This review summarises the ...childhood eczema-related findings from ISAAC and discusses how these fit into our current understanding of eczema aetiology, with particular emphasis on worldwide time trends in eczema prevalence, climatic and dietary risk factors, breastfeeding, the role of skin barrier impairment and allergic sensitisation.
Summary
Background
There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient ...management.
Objectives
The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey was established to collect data on current prescribing practice, to identify factors influencing the use of specific systemic agents, and to inform the design of a clinically relevant intervention study.
Methods
Consultant physician members of the paediatric dermatology societies and interest groups of eight European countries were invited to participate in a web‐based survey. The multiple‐response format questionnaire collated data on clinical practice in general, as well as detailed information on the use of systemic agents in refractory paediatric atopic eczema.
Results
In total, 343/765 members (44·8%) responded to the invitational emails; 89·2% were dermatologists and 71% initiate systemic immunosuppression for children with severe atopic eczema. The first‐line drugs of choice were ciclosporin (43·0%), oral corticosteroids (30·7%) and azathioprine (21·7%). Ciclosporin was also the most commonly used second‐line medication (33·6%), with methotrexate ranked as most popular third choice (26·2%). Around half of the respondents (53·7%) replied that they routinely test and treat reservoirs of cutaneous infection prior to starting systemic treatment. Across the eight countries, penicillins were the first‐line antibiotic of choice (78·3%).
Conclusions
In the absence of a clear evidence base, the European TREAT survey confirms the wide variation in prescribing practice of systemic immunosuppression in refractory paediatric atopic eczema. The results will be used to inform the design of a randomized controlled trial relevant to patient management across Europe.
What's already known about this topic?
There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management.
What does this study add?
The TREAT survey is the first European venture investigating current practice in the use of systemic agents in severe childhood atopic eczema.
The survey confirms significant variability in therapeutic approaches, although there are strong trends favouring a small number of agents, namely ciclosporin, oral corticosteroids and azathioprine.
There are numerous systemic medications in use for psoriasis, with additional investigational agents being studied. However, head-to-head, randomized clinical trials are rare and cannot feasibly ...compare all treatments. A network meta-analysis (NMA) synthesizes the available evidence to provide estimates for all pairwise comparisons. Here, we summarize and appraise two recent NMAs that assessed systemic therapies for moderate-to-severe psoriasis.
Two systematic reviews searched databases and the grey literature to identify relevant randomized clinical trials.
The reviews mostly included trials that involved adults with moderate-to-severe psoriasis. One of the reviews also included two trials involving children.
Interventions common to both reviews include adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, secukinumab and methotrexate. One of the reviews included additional interventions, primarily other biological agents along with new small-molecule treatments and systemic conventional treatments.
One review focused on 'clear/nearly clear' and withdrawals from adverse events as study outcomes, while the second review focused on improvement of ≥ 90% measured on the Psoriasis Area and Severity Index (PASI 90) and serious adverse events.
Additional outcomes included quality of life, PASI 75, Physician's Global Assessment of 0/1 and any adverse event.
Overall, both NMAs are of high quality and provide a comprehensive summary of the evidence base and treatment effects. Results, in terms of both estimates and rankings, suggest that newer biologics targeting the interleukin (IL)-12/23 and IL-17 axes appear to be more effective than older biologics and oral agents.
Patients, clinicians and policy makers can use the relative efficacy assessments of NMAs to inform decision making regarding the clearance of psoriasis skin lesions at relevant time points and improvement in quality of life.
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