Atopic Eczema-From Epidemiology to Therapeutic Approach

Atopic dermatitis is one of the epidemically expanding non-infectious diseases in the 21 century. It poses immense challenges to both patients and physicians. With a steady growth in its incidence and prevalence, the disease carries a heavy social and economical burden. Herein we discuss the therapeutic algorithm for atopic dermatitis in accordance with the disease severity. We emphasize on the personalized approach in selecting the proper treatment method and regimen for each patient. Review Article Atopic Eczema From Epidemiology to Therapeutic Approach Denitza Zheleva*and Razvigor Darlenski Department of Dermatology and Venereology, Tokuda Hospital Sofi a, Bulgaria Dates: Received: 10 February, 2017; Accepted: 23 February, 2017; Published: 24 February, 2017 *Corresponding author: Denitza Zheleva, Department of Dermatology and Venereology, Tokuda Hospital Sofi a, 51B, Nikola Vaptzarov blvd, 1407 Sofi a, Bulgaria, Tel: 00359 895 788551; E-mail: https://www.peertechz.com


Introduction
Atopic dermatitis (AD, syn. 'atopic eczema') is the commonest infl ammatory skin disorder in children and represents a serious problem for the providers of health care all over the world [1][2][3][4] with an impressive effect on patients' quality of life [1,[5][6][7][8][9]. In 40-60% of paediatric patients with AD persist having symptoms later on in life [10,11]. Although AD often starts in early infancy, there are adult onset forms which start in adolescence or adulthood [11]. Most of the patients with AD can control their skin disease with topical therapy and emollient skin care. There is a considerable group of patients with severe AD who do not respond to the prescribed treatment with moisturizers, topical corticosteroids (TCS), and/or topical calcineurin inhibitors (TCI) or experience immediate fl are-ups after tapering topical anti-infl ammatory therapy.

The European Academy of Allergology and Clinical
Immunology (EAACI) [12] suggested defi nition of the term atopy -'a personal or familial tendency to produce IgE antibodies in response to low doses of allergens, usually proteins, and to develop typical symptoms of asthma, rhinoconjunctivitis or eczema/dermatitis'. As an alternative term the authors also suggested 'atopic eczema/dermatitis syndrome' [12]. In 2003, the Nomenclature Review Committee of the World Allergy Organization (WAO) updated the EAACI 2001 position statement [13] and suggested that the term 'eczema' should replace the provisional term 'atopic eczema/dermatitis syndrome'. The update further suggested that 'eczema' could be subclassifi ed as 'atopic eczema' and 'nonatopic eczema' according to the presence or absence of IgE antibodies.
The pathophysiology and clinical phenotype of AD are very heterogeneous and change from patient to patient as well as within the history of a given patient. The disease has great impact over patients' quality of life and beyond, a socioeconomic burden. Moderate to severe AD causes over two billion euro in lost productivity in the European Union (EU) every year [14,15]. Lapidus et al., estimated that the annual amount spent on ambulatory care, emergency department care, inpatient care, and outpatient prescriptions for American children with AD is US$364 [16]. The cost of medical services and prescription drugs was estimated to be between US$0.9 and US$3.8 billion in the United States between 1997 and 1998.

Epidemiology
For the last 30 years there is a dramatic increase in the prevalence of AD. It has increased from 9% to 12% for 10 year period between 1960 and 1970 [17], and nowadays the prevalence is approximately between 15-20% [10,18]. In developed countries it is currently estimated between 10-20% for children and 1-3% for adults. Last studies re veal that the prevalence range in various borders according to the goegraphic regions and the environmental factors. It varies for different countries: less than 1-2% in Iran and Albania, approximately 11 % for the United States, up to 16-17% in Japan and Nigeria.
The Australasia and Northern Europe shows higher prevalences of the condition, while the prevalences reported in Eastern and Central Europe and Asia is lower [19]. AD often starts in early infancy; approximately 45% of all cases begin within the fi rst 6 months of life, 60% during the fi rst year, and 85% before 5 years of age. Up to 70% of these children outgrow the disorder before adolescence [20]. The prevalence of AD continues to increase, particularly in young children from low-income countries, such as in Africa and East Asia, where there is also often an urban-rural gradient of disease.

Therapeuthic approach
There is a wide variety of treatment strategies that has been established for AD. For most of the patients a combination of emollient and anti-infl ammatory therapy is regarded as an optimal choice [21,22] (Table 1). A step-wise approach to AD treatment with regard to the disease severity is presented at When dealing with infants and children it is important to involve actively the parents so they are partners in a reasonable overall treatment scheme. It is helpful to give them a written list of recommendations and to give them enough information.
The parents are the most important member of the team, as they will settle on choices consistently with a major impact on their child's current and future health. We have to make their problems together and to convince the parents that we are working together and as a team we will go through it.

Topical anti-infl amatory therapy
The approach to AD varies with the age of the patient and the type of manifestations. The classical approach is targeting acute fl ares with short-term treatment regimens, i.e. reactive management. On the other hand, a novel strategy is the so called proactive therapy. This is an alternative treatment that includes intensive topical anti-infl ammatory therapy until all lesions have mostly cleared. After that the application of the anti-infl amatory agents is only twice weekly (on the affected areas) in combination with daily applications of emollients Table1: Therapeuthic approach in atopic dermatitis

Topical anti-infl amatory therapy
Topical corticosteroids Topical calcineurin inhibitors Topical phosphodiesterse inhibitors

Phototherapy
UVA1, UVA combined with UVB and NB-UVB

Climate therapy
Textile materials Complementary medicine (TCM) Homeopathy  to unaffected ones ( Figure 2). This modality is based on the recent insights into the underlying skin barrier defect and its relationship to subclinical infl ammation in the clinically health skin of atopic patients [23].

Therpeutic patient education
In the last 10 years proactive therapy was a major breakthrough for the topical anti infl amatory treatment of AD. It is evidence-based, immunologically founded treatment approach, based on the fact that normal-looking, nonlesional skin of patients with AD is not normal. Nonlesional AD skin looks normal to the naked eye, but harbours subclinical infl ammation. Proactive therapy is defi ned as long-term, usually twice weekly, low-dose administration of antiinfl ammatory therapy to previously affected skin, together with daily application of emollients to unaffected areas. In TCI are reasonable option and there are two products that are approved for the treatment of AD -tacrolimus 0.03% and 0.1% ointment (for moderate to severe disease) and pimercolimus 1% cream (for mild to moderate disease).
Both are approved for application in children older than 2 years although many clinicians prescribe these drug offlabel in younger age groups. The major adverse effect of both medications is the burning at the site of application; they are not associated with cutaneous atrophy. TCIs are particularly suitable for AD affecting the face and intertriginous areas, and at sites where corticosteroid-induced skin atrophy is present.
TCIs are also benefi cial in patients with frequently fl aring to persistent AD that would otherwise require almost continual use if topical corticosteroids.
A serios and frequent problem among parents of atopic children is the so called "topical cortico phobia". More than 50% of the parents requested non-steroidal prescriptions due to concerns regarding skin atrophy and growth retardation [24]. Corticosteroid phobia frequently leads to the worsening Another important concern is about the association between TCI use and lymphoma risk in clinical practice, and the incidences of malignancy and lymphoma in clinical databases.
To date, this risk remains theoretical and is based mainly on the drug's mechanism of action, data from animal studies and a few single case reports of lymphoma and skin cancer in patients treated with TCIs (26). No defi nitive human clinical trial data has demonstrated an increased risk of malignancy with TCI exposure and that makes the validity of the boxed warning in large part questionable [27]. Even though the right therapeutical approch requires prescribing TCIs appropriately as corticosteroid-sparing agents and proactively.
Some new non-steroidal topical treatment has been approved for the treatment of patients with mild to moderate AD, recently [28]. Introducing topical phosphodiesterase inhibitors (crisaborole) in treatment of AD promises new horizons for patients with AD. According to the latest studies it is an alternative medication with favorable safety profi le [29]. Crisaborole leads to reduction of the pruritus and showed signifi cant improvement of the symptoms of the disease.
Future studies will investigate potential risks in long term usage and patients younger than 2 years of age [30,31]. In randomized controlled trials Cyclosporine (150-300 mg/ daily; 3-6 mg/kg/daily paediatric) was approved as an effective and recommended as a treatment option for patients with AD refractory to conventional topical treatment. There are some serious side effects including nephrotoxicity (after 3-6 months of therapy) and increased blood pressure, which seem to be dose-dependent. Moreover cyclosporine is often not suffi cient as mono-therapy, requiring combination with TCS to reach an almost complete remission.
Azathioprine (1-3 mg/kg/daily; 1-4 mg/kg/daily paediatric) is recommended as a systemic agent for the treatment of refractory AD. Once clearance or near-clearance is achieved and maintained, azathioprine should be tapered or discontinued, with maintenance of remission via emollients and topical agents. months has been reported in 80% of patients [34,35]. In general mycophenolate mofetil is safe to use, nevertheless some side effects like nausea, vomiting, and abdominal cramping. Rarely, hematologic (anemia,leukopenia, thrombocytopenia) and genitourinary (urgency, frequency, dysuria) symptoms have been reported [36].
Several studies has shown reduction in both sypmtoms and signs of AD with Interferon gamma, which is is a dimerised, soluble cytokine whose action in AD is poorly understood. It has varying results but still only a limited role in the treatment of severe AD [36].

Targeted molecular therapy («Biologics»)
Recently it has been reported that there are   [46]. Patients and physicians are quite intrested in this alternative method due to the lack of adverse effects and the good perspective for long term therapy.
Diagnosis and prescriptions are made only by certifi ed medical doctors with engough knowledge in this terapeuti approach.
Several publicated studies confi rm the effectiveness of the homeopathic intervention with signifi cant improvement in the dermatological status [47]. Moreover the homeopathic intervention has led to modest reductionsin the use of medications commonly prescribed for AD [48].

Therpeutic patient education
Education is undoubtedly one of the most important factor for the adherence of the patients and their parents to the prescribed therapy. The question now is how to best deliver it, considering outcomes and cost. We can improve treatment adherence and lessen fears and misconsception by some educational methods .They might vary greatly in scope, intensity, frequency, setting, and personnel used. Diseasedirected teaching can be on an individual or group basis. The so called eczema school has been established in some countries in formal, structured multidisciplinary educational programs [49]. An adjunction to the conventional therapy are hand outs with written instructions, video interventions, eczema workshops and nurse-led programs.

Conclusive Remarks
AD is a multi-factor disease that requests personalized approach. The step-wise model with regard to the disease severity provides a practical algorithm to the disease management. Patient and parent therapeutic education represent an important element of the treatment plan. The future of AD treatment belongs to novel biological therapeutic agents coming in the recent years.