Atopic dermatitis activation

The topical immunomodulators tacrolimus (Protopic) and pimecrolimus (Elidel) inhibit calcineurin, which normally initiatives T-cell activation. These agents can be used on all parts of the body for prolonged periods without producing corticosteroid-induced adverse effects. Tacrolimus ointment 0.03% and 0.1% is applied twice daily the lower strength is preferred in children with moderate to severe atopic dermatitis. The most common adverse effect is transient itching and burning at the site of application. Pimecrolimus cream 1% is applied twice daily for mild to moderate atopic dermatitis in adults and children older than age 2. 

Atopic dermatitis has been proposed to be the cutaneous manifestation of IgE-mediated hypersensitive reaction to allergenic substances [29]. Conceptually, antagonizing IgE emerges as a logical therapeutic option. Systemic treatment with omalizumab, however, appears to be less efficacious in the skin than in the airway mucosa [23]. It is possible that small molecule Syk inhibitors may offer a more suitable mode to reach and prevent activation of sensitized dermal mast cells and dendritic cells. 

Akdis M, Akdis CA, Weig IL, Disch R, Blaser K Skin homing, CLA-F memory T cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern. IgG4 counter-regulation byCLA+ memory T cells. J Immunol 1997 159 4611-4619. 

Microorganism Activate T Lymphocytes and Bystander Cells in the Skin in Atopic Dermatitis An important strategy by which S. aureus exacerbates atopic dermatitis is by secreting exotoxins. Some of them function as superantigens, which stimulate activation of T cells and major histocompatibility (MHC) class II + APC or keratinocytes, which express MHC class II upon activation. Many effects on T lymphocytes and other cells are elicited by superantigens (table 1). 

IL-23 has recently been shown to be produced by dendritic cells and by human cultured keratinocytes in healthy skin and in psoriasis - its role in atopic dermatitis has to be defined [22]. Interaction of keratinocytes with activated T cells via CD40-CD40L may enhance IL-23 production and subsequently the IFN-y production by memory T cells [23]. 

It has been shown that IFN-y induces Fas on keratinocytes which renders them susceptible to apoptosis induction by infiltrating FasL+ T cells. This has been interpreted as an important event in eczema, mainly in atopic dermatitis. There is further evidence that cleavage of E-cadherin and sustained desmosomal cadherin contacts between keratinocytes that are undergoing apoptosis result in spon-gioform morphology in the epidermis as a hallmark of eczematous lesions. Suppression of keratinocyte activation and apoptosis thus remains a potential target for the treatment of atopic dermatitis [2]. 

T regulatory cells in atopic dermatitis and subversion of their activity by superantigens. J Allergy Clin Immunol 2004 113 756-763. 

Pimecrolimus (58 Elidel ) Ascomycin Macrolactum antibiotic Semi-synthetic NP Microbial Inflammatory skin diseases and atopic dermatitis Blocks T-cell activation 505-517... 

Pharmacology Tacrolimus is a macrolide immunosuppressant produced by Streptomyces tsukubaensis. The mechanism of action of tacrolimus in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. Pharmacokinetics ... 

It is a cromolyn analogue. It is an antihistaminic (H antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate. It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria. It is absorbed orally and well tolerated. Bioavailability is 50% due to first pass metabolism and is primarily metabolized. The common side effects include dry mouth, sedation, dizziness and nausea. 

It is an immunosuppressant macrolide antibiotic produced by Streptomyces tsukubaensis. Like cyclosporine, tacrolimus binds to a cytoplasmic immunophylin and the complex inhibits the activity of the calcium dependent phosphatase known as calcineurin. This in turn, inhibits the translocation of the transcription factor NF-AT into the cell nucleus, blocking the initiation of NF-AT dependent T-cell responses. It is indicated in atopic dermatitis. 

Topical doxepin hydrochloride 5% cream (Zonalon) may provide significant antipruritic activity when utilized in the treatment of pruritus associated with atopic dermatitis or lichen simplex chronicus. The precise mechanism of action is... 

N.A. Butylphthalide, cadinene, carvacrol, n-dodecanol, isosafrole, linoleic acid, palmitic acid, safrole, sesquiterpene, sesquiterpenic alcohol, n-tetradecanol.100 Immunosuppressive activity, treat hay fever, asthma, and atopic dermatitis. Analgesic, deobstruent, emmenagogue, sedative. 

Nowicki and Bara ska-Rybak (2007) studied the protective effect of shark liver oil. They observed a significant protection against bacterial and fungal infections by shark liver oil treatment which contains mostly squalene and alkylglycerol. Further, this treatment showed improved effects on xerosis and skin lesion-induced atopic dermatitis. This antibacterial and antifungal effect could be accounted for the high-squalene-including composition of the shark liver oil however, detailed studies are needed to be carried out for reputed activity of squalene as an anti-infectant. 

Wuthrich B, Joller-Jemelka H, Kagj MK Levels of soluble ICAM-1 in atopic dermatitis. A new marker for monitoring the clinical activity Allergy 1995 50 88-89. 

Yamashita N, Kaneko S, Kouro O, Furue M, Yamamoto S, Sakane T Soluble E-selectin as a marker of disease activity in atopic dermatitis. J Allergy Clin Immunol 1997 99 410 U6. 

Czech W, Schopf E, Kapp A Soluble E-selectin in sera of patients with atopic dermatitis and psoriasis - Correlation with disease activity. Br J Dermatol 1996 134 17-21. 

Topical doxepin hydrochloride 5% cream (Zonalon) may provide significant antipruritic activity when utilized in the treatment of pruritus associated with atopic dermatitis or lichen simplex chronicus. The precise mechanism of action is unknown but may relate to the potent Hi and H2-receptor antagonist properties of dibenzoxepin tricyclic compounds. Percutaneous absorption is variable and may result in significant drowsiness in some patients. In view of the anticholinergic effect of doxepin, topical use is contraindicated in patients with untreated narrow-angle glaucoma or a tendency to urinary retention. 

Jensen, J.M., Folster-Holst, R., Baranowsky, A., Schunck, M., Winoto-Morbach, S., Neumann, C., Schutze, S., and Proksch, E., Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis, J. Invest. Dermatol., 122, 1423-1431, 2004. 

Chamlin, S.I., Kao, J., Frieden, I.J., Sheu, M.Y., Fowler, A.J., Fluhr, J.W., Williams, M.L., and Elias, P.M., Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis changes in barrier function provide a sensitive indicator of disease activity. J. Am. Acad. Dermatol., 47, 198— 208, 2002. 

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