ETIOLOGY AND PATHOGENESIS The precise cause of atopic dermatitis is not known.

A complex interaction of genetic and environmental factors are believed to induce immunological and biochemical changes that produce the pruritic, inflammatory dermatosis. Genetic Factors: Atopic dermatitis runs in families. The prevalence of AD in children is about 50% when on parent has AD, while it may be as high as about 80% when both parents have the disease The precise mode of inheritance in not known, it is probably polygenic. Genetic factors may produce disease through abnormality in IgE synthesis, expression of IgE receptors on cells, or through cytokine production by leukocytes. Immunologic abnormalities: Functionally, there are two subsets of helper T lymphocytes: (a) TH1 cells which mainly produce interferon gamma, interleukin-2 and mediate cell-mediated immune response and (b) TH2 cells, that produce IL-4, IL-5, IL-6, and Il-10 and promotes antibody-mediated immune response. IL-4 induces IgE production and inhibits gamma interferon production and prevents differentiation of TH1 cells. In atopic dermatitis, there is a TH2 cell predominance which leads to increased IgE production by B lymphocytes and by its suppressive action of TH1 cells, diminishes cellular immune response. In response to various allergens, AD patients are genetically prone to produce high levels of IgE. IgE-mediated allergic reaction causes mediator release from mast cells, this reaction is biphasic, the immediate reaction producing redness and itching and the delayed reaction may cause chronic inflammation. Langerhans cells of AD patients express high levels of IgE receptors, they capture specific allergens more avidly and present them to TH2 cells more efficiently. Tissue specificity of the TH2 cell response is explained by high CLA (cutaneous lymphocyte antigen) expression on circulating T cells that specifically home to the skin. Increased prostaglandin E2 (PGE2) secretion by monocytes of atopic dermatitis patients inhibits interferon gamma production, this inhibits TH1 cells. Monocytes of AD patients have increased Cyclic AMP-phosphodiesterase enzyme activity this leads to increased IgE synthesis by B lymphocytes and release of histamine from basophils. Keratinocytes, injured by scratching may also secrete cytokines that helps migration of TH2 cells to the skin, thus modulation the immunological phenomenon. Allergens: Food: a subset of patients, particularly infants and children, may have hypersensitivity to foods, particularly to milk, peanuts, fruits , fish and soybeans. Aeroallergens: house dust mites, pollens, and animal danders may exacerbate or perpetuate disease in a number of patients. Microbial products: staphylococcal toxins may act as superantigens and stimulates the allergic reaction. Other infections like dermatophytes of pityrosporum may also act as allergens. Dryness of skin: Dry skin is a prominent feature in many atopic dermatitis patients. Abnormalities in lipid

metabolism with reduced synthesis of ceramide may lead to decreased water-binding capacity of skin. Dryness causes microfissures on the skin surface that promotes entry of irritants, allergens and microbes. Climatic factors: A dry and cool environment increases xerosis of skin. Sweating in hot , humid climates may cause irritation, while sunlight tend to improve the symptoms. Psychological factors: The psychological impact of the disease on the patients leading to depression, anxiety, and frustration may cause reduced itch threshold and increase the inherent irritability of the skin, thus contributing to the pathogenesis of the disease.

TREATMENT
GENERAL MEASURES Provide psychological support. Avoidance of factors that promotes dryness, itching or inflammation. Avoidance of contact with local irritants like woolen garments, use soft cotton garments. Clothing and linens should be washed in mild detergents and rinsed well. Fingernails should be kept short. Avoidance of contact with animals, dust, sprays and perfumes. Avoidance of excessive bathing. Soaps should be bland and non-irritant Foods that are suspected to aggravate symptoms in individual patients should be avoided. Avoidance of extremes of temperature and humidity. In severe cases, hospitalization for a short period may promote rapid reduction of symptoms mainly by providing a changed environment. SPECIFIC TREATMENTS: Specific measures are aimed at modifying the following pathogenetic factors: dryness, inflammation, infection and itching. A. Corticosteroids Topical steroids: These are the cornerstones of therapy of atopic dermatitis. The following principles should be adhered to while instituting topical steroid therapy: High potency steroids are used for a short period to rapidly reduce inflammation. Maintenance therapy, if needed is best done with mild steroids like hydrocortisone. On face and intertriginous areas, mild steroids should be used, mid-potency formulations are used for trunk and limbs. Topical steroids are applied initially twice or thrice a day After the symptoms are lessened, frequency of application should be reduced. Intermittent use if topical steroid may be alternated with application of emollients. Ointments are superior to creams or lotions. The potential side-effects of topical steroids should always be kept in mind.

Systemic steroids: a short course of systemic steroids (prednisolone, triamcinolone) may occasionally be needed to suppress acute flare-ups. Intralesional steroids (triamcinolone acetonide) may help resolve thickened plaques of eczema not responding to topical agents Emollients: Atopic dermatitis patients frequently have dry skin which aggravates during winter months. Xerosis breaks the barrier function of the skin and promotes infection and inflammation. Ointments are preferred over lotions or creams. Emollients should be applied immediately after a soaking bath to retain the moisture. Emollients containing urea or alpha-hydroxy acids often cause stinging or burning sensations. Adding emulsifying oils to bath water is also helpful. Antihistamines: Antihistamines give variable results in controlling pruritus of atopic dermatitis since histamine is not the only mediator of itching in atopic patients. Any of the non-sedating antihistamines like cetirizine, loratadine or fexofenadine may be used. The conventional antihistamines like diphenhydramine or hydroxyzine may give better results for their additional actions as sedative or anxiolytic. Topical antihistamines should be avoided for their sensitizing potential. Antimicrobials Infections and colonization with Staphylococcus aureus may aggravate or complicate AD. Antibiotics like erythromycin, cephalosporins, or cloxacillin are usually prescribed. Dermatophytosis or Pityrosporum infections are treated with antifungals. Acyclovir or other appropriate antiviral agents should be promptly advised for treatment of herpes simplex infections. Tar compounds: Liquor carbonis detergens in ointment or other vehicles are useful adjuncts to topical steroids in pats with chronic dermatitis by their antipruritic and antiinflammatory actions. They may be used alternately with topical steroids. Phototherapy: Ultraviolet B (UVB) alone, or in combinations with UVA may be beneficial in selected patients. Narrow-band UVB (311nm) is also used. In adult patients, psoralens in association with UVA (PUVA) are often beneficial. Cyclosporine: By virtue of its immunomodulating action, cyclosporine has a limited role in controlling atopic dermatitis in recalcitrant adult cases. The potential side effects should always be kept in mind. Azathioprine: this immunosuppressive agent has also been used in severe adult cases. Again, potential side effects limit its role in selected cases. Tacrolimus: Topical tacrolimus, an immunomodulator, is a very promising new topical agent for the

treatment of atopic dermatitis. Controlled trials have shown impressive results in controlling symptoms of AD. Topical ascomycin and phosphodiesterase inhibitors: Topical application of these agents has given beneficial results in AD. Other immunomodulating agents like interferon gamma and thymopentin have not shown much benefit. Essential fatty acids: Evening primrose oil had its advocates, but controlled trial has not shown any beneficial effect. http://dermind.tripod.com/atopicderm.htm

CHARACTERISTICS OF ATOPIC SKIN

The discovery of the high-affinity IgE receptor (FcepsilonR) on LCs of patients with AD provides a mechanism for LCs to accept and then present IgE allergens to receptive sensitized T cells [6] and mast cells. T-helper lymphocytes with Th2 characteristics predominate in the skin lesions of AD. [4] [7] Recently, Thepen et al [28] have demonstrated a biphasic response to aeroallergens in AD. [28] They found that an early predominance of Th2 cells in AD, with their cytokine profile of interleukin IL-4 and IL-5, helps initiate an IgE/mast cell-eosinophil allergentriggered reaction. Although IL-5 induces a tissue eosinophilia (the source of eosinophilic major basic protein [EMBP] found in the dermis of subacute and chronic AD lesions), [16] IL-4 contributes to mast cell activation and the release of mediators (especially histamine), which may play a role in AD. In addition, Th2 cells require an exogenous pulse of IL-4 to initiate their differentiation and the subsequent synthesis of specific cytokines. Mast cells also release more IL-4 upon activation, [11] and it may act as that essential activator. It is also likely that histamine, the predominant mediator released by IgE-induced mast cell degranulation, can cause a pruritus, which when scratched can produce the eczematous lesions, a phenomenon recognized as "Koebnerization." In the later or chronic phase of AD, the usual allergic contact IFNgammaproducing Th1 cells appear and eventually predominate over Th2 cells. [28] Because the mediators released from both types of activated T cells are able to produce an eczematous (spongiotic) reaction, a concomitant type of contact- (allergic or irritant) triggered cause for AD is very conceivable http://www.allergyasthmatherapy.com/Articles/MitesAtopicDermatitis.pdf
Major features (3 of 4 present) pruritus typical morphology and distribution of skin lesions chronic or chronically relapsing dermatitis personal or family history of atopy Minor features (3 of 23 present) xerosis ichthyosis/palmar hyperlinearity/keratosis pilaris

immediate (type I) skin test reactivity elevated serum IgE early age of onset tendency towards cutaneous infections/impaired cell-mediated immunity tendency towards non-specific hand or foot dermatitis nipple eczema cheilitis recurrent conjunctivitis Dennie-Morgan infraorbital fold keratoconus anterior subcapsular cataracts orbital darkening facial pallor/erythema pityriasis alba anterior neck folds itch when sweating intolerance to wool and lipid solvents perifollicular accentuation food intolerance course influenced by environmental/emotional factors white dermographism/delayed blanch

133 Mieloid dendritik dan plasmasitoid dendritik buat yg nomer 1