Causes and Treatment of Atopic Dermatitis 14 September 2010 Causes and Treatment of Atopic Dermatitis Dong Seok Cha, Ph.D. Department of Oriental Pharmacy College of Pharmacy Woosuk University http://www.dermatitisfacts.com/atopic-dermatitis-eczema/

Contents Characteristic of Atopic Dermatitis (AD) Causes of AD Treatment of AD Prevention of AD Definition Symptom Genetic factor Environmental factor Immune system imbalance Dysfunction of skin barrier Avoiding allergens Drug treatment Phototherapy Alternative Treatment

Characteristic of Atopic Dermatitis

What is Atopic Dermatitis? Atopy or atopic syndrome = allergic hypersensitivity Dermatitis = inflammation of the skin Atopic Dermatitis (AD) A type of eczema Non-contagious Often begins in childhood and may persist into adulthood. Occurs together with other atopic diseases

Prevalence Rate of Atopic Dermatitis

Symptoms of Atopic Dermatitis

Causes of Atopic Dermatitis http://www.dermatitisfacts.com/atopic-dermatitis-eczema/

Causes of Atopic Dermatitis Genetic factor Environmental factor Immune system imbalance Dysfunction of skin barrier

Causes of AD – Genetic Factor Family history is very important The inheritance pattern is complex AD genetics involve several genes, each with a different function - IgE response related gene - skin barrier function related gene - skin inflammation related gene Genetic mutation of the epidermal barrier protein, filaggrin is one predisposing factor for atopic dermatitis Effect of genetics Numerous studies have confirmed the role of genetic factors in the development of atopic dermatitis. They have shown that atopic dermatitis is a genetic disorder based on the interactions of unknown number of genes and environmental factors. In a family with a child affected by atopic dermatitis, there is generally a family history of eczema or any of the other atopic diseases; asthma and rhinitis. The inheritance pattern is more complex and does not follow the Mendelian pattern. Parental atopy (parents with allergies) carries the highest risk factor. An atopic mother is a higher risk factor than an atopic father. This can be explained by stronger maternal genetic heritability, shared physical environment of mother and child, or environmental events that affect the fetus in utero. In one study of all atopic diseases, a stronger correlation was found between siblings than between siblings and parents, indicating that environmental factors, especially during childhood, may be responsible for increased incidence of atopic dermatitis. The identification of parental genes may be of great help in studying the pathogenesis of atopic dermatitis. Atopic dermatitis is often accompanied by asthma and hay fever. A multifactorial cause for atopic dermatitis has been suggested, with genetic and environmental factors influencing disease development. However, genetic studies on atopic dermatitis show, interestingly, that the suspected gene regions of high risk identified show little overlap with the suspected gene regions of asthma suggesting a strong possibility that different sets of genes may be responsible for these two atopic diseases. Instead, some of the identified regions overlap with suspected regions for psoriasis, another chronic skin disease. The implication being, those genes in the skin involved in psoriasis might be playing an important role in atopic dermatitis pathogenesis. Genetic mutation of the epidermal barrier protein, called, filaaggrin is one predisposing factor for atopic dermatitis, but there are many more unkown genes involved. One important suspected region is on a chromosome, whose genes are involved in the regulation of epidermal differentiation. Recent genetic studies have identified a cluster of genes on the outermost layer of the skin which may be as important as those which modify atopic dermatitis. Identification of the responsible genes would be of enormous help in diagnosis and treatment of the disease. To summarize, atopic dermatitis genetics are complex and appear to involve several genes, each with a different function. Some relate to immunoglobin E response, some to the skin barrier function and some to skin inflammation. However, there are still gaps in our knowledge about gene–environment interactions, better studies of the natural history of atopic dermatitis

Causes of AD – Genetic Factor Effect of genetics Numerous studies have confirmed the role of genetic factors in the development of atopic dermatitis. They have shown that atopic dermatitis is a genetic disorder based on the interactions of unknown number of genes and environmental factors. In a family with a child affected by atopic dermatitis, there is generally a family history of eczema or any of the other atopic diseases; asthma and rhinitis. The inheritance pattern is more complex and does not follow the Mendelian pattern. Parental atopy (parents with allergies) carries the highest risk factor. An atopic mother is a higher risk factor than an atopic father. This can be explained by stronger maternal genetic heritability, shared physical environment of mother and child, or environmental events that affect the fetus in utero. In one study of all atopic diseases, a stronger correlation was found between siblings than between siblings and parents, indicating that environmental factors, especially during childhood, may be responsible for increased incidence of atopic dermatitis. The identification of parental genes may be of great help in studying the pathogenesis of atopic dermatitis. Atopic dermatitis is often accompanied by asthma and hay fever. A multifactorial cause for atopic dermatitis has been suggested, with genetic and environmental factors influencing disease development. However, genetic studies on atopic dermatitis show, interestingly, that the suspected gene regions of high risk identified show little overlap with the suspected gene regions of asthma suggesting a strong possibility that different sets of genes may be responsible for these two atopic diseases. Instead, some of the identified regions overlap with suspected regions for psoriasis, another chronic skin disease. The implication being, those genes in the skin involved in psoriasis might be playing an important role in atopic dermatitis pathogenesis. Genetic mutation of the epidermal barrier protein, called, filaaggrin is one predisposing factor for atopic dermatitis, but there are many more unkown genes involved. One important suspected region is on a chromosome, whose genes are involved in the regulation of epidermal differentiation. Recent genetic studies have identified a cluster of genes on the outermost layer of the skin which may be as important as those which modify atopic dermatitis. Identification of the responsible genes would be of enormous help in diagnosis and treatment of the disease. To summarize, atopic dermatitis genetics are complex and appear to involve several genes, each with a different function. Some relate to immunoglobin E response, some to the skin barrier function and some to skin inflammation. However, there are still gaps in our knowledge about gene–environment interactions, better studies of the natural history of atopic dermatitis

Causes of AD – Environmental Factor Industrialization Hygiene hypothesis Dietary life Food allergy Trans fat Residential Environment Aeroallergens eg. dust mites, pollens, animal danders VOCs eg. formaldehyde, benzene 산업화가 잘 이루어진 나라에서 아토피 발병률 높음 -> 아프리카 난민 아토피?? Sick building syndrome

Causes of AD - Immune System Imbalance Th1 Th2 [Homeostatic state] Th2 Th1 hygiene hypothesis 위생가설 Th1 Th2 [Cell-mediated Immunity] [Allergy / Atopy]

Causes of AD - Immune System Imbalance

Causes of AD – Dysfunction of Skin Barrier TEWL Allergen Irritant Chronic Stage of AD Skin Barrier Function Ceramide The skin of people with atopic dermatitis loses its moisture holding capacity and becomes dry. A dry skin is a poor barrier to germs. The condition becomes difficult to control when certain factors make the skin still drier. These include winters (cold, dry air), frequent washing with very hot water, soaps and antiseptics, low humidity, and high temperatures. Regular use of emollients may help in reducing the dryness. 피부위에서 수분이 증발되는 양을 TEWL(TRANS-EPIDERMAL WATER LOSS)

Treatment of Atopic Dermatitis http://www.dermatitisfacts.com/atopic-dermatitis-eczema/

Treatment of Atopic Dermatitis Treatment for Atopic Dermatitis has multidimensional aims Improving the skin barrier function Reducing the inflammation Identifying the responsible triggers Preventing any secondary infection Common treatment options for AD - Avoiding allergens Drug treatment Phototherapy Alternative therapy The skin of people with atopic dermatitis loses its moisture holding capacity and becomes dry. A dry skin is a poor barrier to germs. The condition becomes difficult to control when certain factors make the skin still drier. These include winters (cold, dry air), frequent washing with very hot water, soaps and antiseptics, low humidity, and high temperatures. Regular use of emollients may help in reducing the dryness. 피부위에서 수분이 증발되는 양을 TEWL(TRANS-EPIDERMAL WATER LOSS)

Treatment of AD – Avoiding Allergens Discovering the triggers of allergic reactions Learning to avoid them. 아토피 치료법이 없으므로 일차적 치료방법은 알러겐 제거가 우선이다 (예방개념)

Treatment of AD – Drug Treatment Topical Treatment - Emollient (moisturizer) - Topical corticosteroids - Topical calcineurin inhibitors eg. Pimecrolimus and Tacrolimus - Topical antimicrobial therapy - Coal tar Systemic Treatment - Antihistamines - Corticoteroids - Immunomodulators eg. Azathioprine - Antimicrobials Topical treatments focus on reducing both the dryness and inflammation of the skin.

Treatment of AD – Recent Drugs Being Tested for AD Corticosteroids, immunosuppressants have serious side effects AD imposes tremendous social and financial costs on patients Improved drugs are necessary Leukotriene antagonist Monoclonal antibodies Topical treatments focus on reducing both the dryness and inflammation of the skin. Leflunomide Recombinant interferon-gamma

Treatment of AD – Phototherapy Ultraviolet (UV) light therapy Works as an anti-inflammatory agent Various type of UV - Psoralen plus UVA (PUVA) - A combination of broadband UVB/UVA light treatment - Broadband UVA exposure - Broad-band UVB exposure - Narrowband UVB (280-320 nm) - UVA-1 (340-400 nm) Side effects - stinging, burning, ageing of the skin, pigmentation - risk of squamous cell carcinoma and melanoma. Topical treatments focus on reducing both the dryness and inflammation of the skin.

Treatment of AD – Alternative Therapy Currently, the level of interest in alternative treatments continues to increase Traditional herbal medicine formulation External application Combined internal and external treatment Merit Demerit Reducing corticosteroid usage Prescribed differently for each patient Less side effect Unique flavor Regulation of immune responses Herbal allergens Synergic effect Expensive 소풍산, 보중익기탕, 계지복령환, 황련해독탕, 가미소요산, 오령산, 당귀작약산, In Traditional Chinese Medicine, AD is called “wet sore” and belongs to the syndrome type of Dampness – Heat infusion. The therapeutic principles include removing dampness, strengthening the spleen and dispelling pathogenic wind and dampness. The herbs used in the TCHM have functions of clearing heat, removing dampness and strengthening the spleen.

Prevention of Atopic Dermatitis http://www.dermatitisfacts.com/atopic-dermatitis-eczema/

Prevention of Atopic Dermatitis Diet Mental health care Skin care Lifestyle 소풍산, 보중익기탕, 계지복령환, 황련해독탕, 가미소요산, 오령산, 당귀작약산, In Traditional Chinese Medicine, AD is called “wet sore” and belongs to the syndrome type of Dampness – Heat infusion. The therapeutic principles include removing dampness, strengthening the spleen and dispelling pathogenic wind and dampness. The herbs used in the TCHM have functions of clearing heat, removing dampness and strengthening the spleen.

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