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Atopic dermatitis (AD), also known as atopic eczema, is a common, itchy and unpleasant condition. AD has significant, well-established comorbidities, including food allergy, asthma and allergic rhinitis. In addition, newly-recognised comorbidities include those related to chronic loss of sleep and mental health issues. There are also early signals of increased cardiovascular comorbidities.
Cumulatively, AD and its comorbidities create a very significant impact on the quality of life for people living with the condition. Systemic biomarkers (proteins), which are present in the blood of people with moderate and severe AD, also demonstrate that the entire body is affected by the condition and that a systemic therapy (ie, ‘entire-body’ treatments in the form of existing oral or newly-developed injectable biologic treatments) may be appropriate for treatments.
The therapeutic mainstay for so many people with AD is topical treatments with steroid creams/ointments or topical immunomodulators such as tacrolimus.
Often, these treatment approaches are inadequate, too involved to administer and for these or other reasons are entirely unsatisfactory for patients.
Methotrexate for Severe Childhood Atopic Dermatitis: Clinical Experience in a Tertiary Centre
(Paediatric Dermatology, 21 July 2017.
Dvorakova V, O’Regan GM, Irvine AD)
Atopic dermatitis (AD) affects up to 20 per cent of children. Although the majority of patients are adequately controlled using emollients, topical corticosteroids, topical calcineurin inhibitors, or phototherapy, children with moderate-to-severe AD may require systemic treatment for control. The objective of the current study was to evaluate the efficacy and safety of methotrexate in children with severe AD attending a tertiary referral centre.
A retrospective chart review was undertaken of all children who received methotrexate for severe AD at our tertiary referral centre from November 2010 to August 2015.
Forty-seven children were started on methotrexate for AD during this period. The mean Investigator Global Assessment (IGA) at the three-to-five month follow-up improved from 4.25 to 2.8, with further improvement to 1.9 in the patients that continued therapy beyond 10 months.
Changes in the Children’s Dermatology Life Quality Index (CDLQI) mirrored changes in the IGA, with improvement in the mean CDLQI from 14.4 at the start of the treatment to 7.5 at the three-to-five month follow-up.
Further improvement in the CDLQI to 6.6 in patients who continued methotrexate beyond 10 months confirmed continued improvement in disease control beyond medium-term therapy. The treatment was well tolerated.
Methotrexate appears to be an effective, safe treatment for severe paediatric AD. Its therapeutic effects continue beyond the medium-term treatment period, as reflected by further improvement in IGA and CDLQI scores in patients who continued methotrexate therapy beyond 10 months.
When should patients with atopic dermatitis (AD) be offered systemic therapy?
The decision on when to offer systemic therapy is a complex one, dependent on patient and physician preferences and familiarity with systemic medicines, a decision further complicated by the fact that many established therapies are used off-license.
Patients may be offered very different therapies, depending on their location and the healthcare provider they attend. In the last number of years, there have been exciting new developments in AD therapy heralding a new range of systemic therapeutic options coming on-stream.
The International Eczema Council (www.eczemacouncil.org) has just published a consensus framework (see Figure 1) to provide a structure to better inform patients and care-givers contemplating this complex decision-making.
It concludes that the decision to start systemic medication should include assessment of severity and quality of life, while considering the individual’s general health status, psychological needs and personal attitudes toward systemic therapies.
When parents are making decisions regarding systemic therapy for children, they often have very pertinent questions regarding how effective the therapy will be, how safe it will be and for how long the effects will last.
The best way to answer these questions is through a randomised, placebo-controlled clinical trial, many of which are underway for new agents. For older agents such as methotrexate and ciclosporin, we are working with Dr Carsten Flohr, Consultant Paediatric Dermatologist at St John’s Institute of Dermatology, Guy’s and St Thomas NHS Foundation Trust, UK, to get better insights through the TREAT trial (TREatment of Severe Atopic Eczema Trial, http://treat-trial.org.uk). The trial aims to recruit 102 patients aged two-to-16 years who require systemic treatment. Participants will be allocated at random to receive either methotrexate or ciclosporin for nine months and then followed-up for another six months to assess short- and long-term effectiveness and the safety profile of both drugs.
TREAT will also address how the two medicines reduce skin inflammation and itch, which is an important gap in current knowledge.
To provide better information for parents, the International Eczema Council recently published data from the last 47 consecutive patients we treated with methotrexate (see panel).
Disclosure: Prof Irvine consults for many of the companies developing these drugs.
The Irish Skin Foundation will host a free Eczema Expert Event on 16 September 2017 in the Red Cow Moran Hotel, Naas Road, Dublin 24, to coincide with National Eczema Awareness Week (11-17 September). The informative meeting will provide people with, or caring for those with eczema the knowledge and practical tips they require to manage the often-misunderstood condition.
This year’s meeting will cover topics such as: ‘What is eczema?’; ‘Latest on current and emerging therapies’; ‘Eczema myths vs facts’; ‘Managing your child’s eczema’; and practical tips, advice for life and an insight into one man’s experience of living with eczema as an adult.
There will also be an opportunity to speak with exhibitors who will be showcasing both current and new products available on the market.
You can register for the meeting at www.irishskin.ie