**4. Acknowledgment**

ALK-Abello supported this study by providing immunotherapy extract. MM is ALK Abellò employee.

### **5. References**

304 Atopic Dermatitis – Disease Etiology and Clinical Management

treatment was very well tolerated. Treatment with SLIT, furthermore, has allowed a gradual and relevant reduction of concomitant therapies with corticosteroids and immunosuppressants. SLIT can modulate the immuno-system in patients with AD and HDM sensitivity. In conclusion the data available from different trials suggest that SIT (both SCIT and SLIT) could be a relevant therapeutic option in the management of AD.

Fig. 2. Modification of specific anti HDM IgE serum levels at baseline and after1 year of SLIT

Atopic Dermatitis (AD) is a common inflammatory itching skin disease affectings a large number of children and adults. Symptoms commonly could vary from person to person. The most common symptoms are dry, itchy skin and rashes on the face, inside the elbows and behind the knees, and on the hands and feet. Itching is the most relevant and common symptom of atopic dermatitis. Scratching and rubbing in response to itching irritates the skin, increases inflammation, and actually increases itchiness. The cause of atopic dermatitis is not known, but the disease seems to result from a combination of genetic and environmental factors. Children are more likely to develop this disorder if one or both parents have had it or have had other allergic conditions like asthma or allergic rhinitis. While some people outgrow skin symptoms, approximately three-fourths of children with atopic dermatitis go on to develop hay fever or asthma. AD frequently is associated with allergic respiratory disease and often is the first manifestation of allergic disease. Patients suffering from AD will develop allergic rhinitis and asthma. The inflammatory process in the skin of patients with AD initiates with the allergen uptake by epidermal dendritic cells which share in their surface the IgE-receptor. These cells, after the contact with the allergens, start the homing process of T cells. This process plays a

treatment (n = 96); p = 0.0001 paired t-test.

**3. Conclusion** 


Thinking Atopic Dermatitis Treatment Differently: Specific Immunotherapy as an Option 307

[26] Novak N, Kruse S, Potreck J, Weidinger S, Fimmers R, Bieber T. Single nucleotide

[27] Adinoff AD. Atopic dermatitis and aeroallergen contact sensitivity. *J Allergy Clin* 

[28] Novak N, Valenta R, Bohle B, Laffer S, Haberstok J, Kraft S et al. Fcepsilon RI

[29] Scalabrin DM, Bavbek S, Perzanowski MS,.Use of specific IgE in assessing the relevance

and non asthmatic control subjects. *J Allergy Clin Immunol* 1999;104: 1273-9. [30] Maintz L, Novak N. Getting more and more complex: the pathophysiology of atopic

[31] Werfel T, Kapp A. Environmental and other major provocation factors in atopic

[32] Tan BB, Weald D, Strickland I, et al. Double-blind controlled trial of effect of house dust

[33] Subramanyan K. Role of mild cleansing in the management of patient skin. *Dermatol* 

[34] Loden M. Role of topical emollients and moisturizers in the treatment of dry skin

[35] McHenry PM, Williams HC, Bingham EA. Management of atopic eczema: Joint

[36] Korting HC, Kerscher MJ, Schafer- Korting M. Topical glucocorticoids with improved

[37] Wahn U, Bos JD, Goodfield M, Caputo R, Papp K, Manjra A et al. Efficacy and safety of

[38] Mastrandrea F. The potential role of allergen-specific sublingual immunotherapy in

[40] Novak N, Simon Atopic dermatitis - from new pathophysiologic insights to individualized therapy. *Allergy*. 2011 Mar 3. doi: 10.1111/j.1398-9995.2011.02571.x [41] Bussmann C, Bockenhoff A, Henke H, et al. Does allergen-specific immunotherapy

[42] Werfel T, Breuer K, Rueff F, Przybilla B, Worm M, Grewe M et al. Usefulness of specific

Workshop of the British Association of Dermatologists and the Research Unit of the

pimecrolimus cream in the longterm management of atopic dermatitis in children*.* 

represent a therapeutic option for patients with atopic dermatitis? *J Allergy Clin* 

immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multicentre, randomized, dose–response study. *Allergy*

mite allergen avoidance on atopic dermatitis. *Lancet* 1996;347:15–8.

phenotypes in vitro. *J Allergy Clin Immunol* 2004;113:949–57.

eczema. Eur J Dermatol 2007; 17:267–283.

barrier disorders. *Am J Clin Dermatol* 2003;4:771–88

atopic dermatitis*. Am J Clin Dermatol* 2004;5:281–94. [39] Bousquet J. Sublingual immunotherapy: validated. *Allergy* 2006;61:5-6

Royal College of Physicians of London. BMJ 1995;310:843–7.

benefit/risk ratio: do they exist? *J Am Acad Dermatol* 1992;27:87–92.

dermatitis. *Allergy* 1998;53:731-9.

*Ther* 2004;17:26–34.

*Pediatrics* 2002;110:e2.

*Immunol* 2006; 118:1292–1298

2006;61:202–5.

*Immunol* 2005;115:828–33.

*Immunol* 1988;81:736-42

polymorphisms of the IL18 gene are associated with atopic eczema. *J Allergy Clin* 

engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell

of fungal and dust mite allergens to atopic dermatitis: a comparison with asthmatic


[7] Boguniewicz M, Leung DYM. Atopic dermatitis. *J Allergy Clin Immunol* 2006;

[8] Leung DYM, Bhan AK, Schneeberger EE, Geha RS. Characterization of the mononuclear

[9] Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic

[11] Novak N, Valenta R, Bohle B, et al. Fcepsilon RI engagement of Langerhans cell-like

[13] Proksch E, Folster-Holst R, Jensen JM. Skin barrier function, epidermal proliferation

[15] Cork MJ, Robinson DA, Vasilopoulos Y, et al. New perspectives on epidermal barrier

[16] Williams H, Flohr C. How epidemiology has challenged 3 prevailing concepts about

[17] Anonymous. Worldwide variation in prevalence of symptoms of asthma, allergic

[18] Hoffjan S, Epplen JT. The genetics of atopic dermatitis: recent findings and future

[19] Bradley M, Soderhall C, Luthman H, Wahlgren CF, Kockum I, Nordenskjold M.

[20] Williams HC, Strachan DP. The natural history of childhood eczema: observations from

[21] Gustafsson D, Sjoberg O, Foucard T. Development of allergies and asthma in infants

[22] Novak N, Bieber T, Leung DY. Immune mechanisms leading to atopic dermatitis. *J* 

[24] Purvis DJ, Thompson JM, Clark PM, Robinson E, Black PN, Wild CJ et al. Risk factors

[10] Novak N, Kraft S, Bieber T. IgE receptors. *Curr Opin Immunol* 2001;13:721–6.

and differentiation in eczema. *J Dermatol Sci* 2006;43:159-69. [14] Hudson TJ. Skin barrier function and allergic risk. *Nat Genet* 2006;38:399-400.

atopic dermatitis. J Allergy Clin Immunol 2006;118:209-13.

Swedish population. HumMol Genet 2002;11:1539–48.

*Allergy Clin Immunol* 2003;112(suppl):S128–39.

the British 1958 birth cohort study. *Br J Dermatol* 1998;139:834–9.

[23] Strachan DP. Hay fever, hygiene, and household size. *BMJ* 1989;299:1259-60.

[25] Ozkaya E. Adult-onset atopic dermatitis. *J Am Acad Dermatol* 2005;52:579–82.

cell infiltrate in atopic dermatitis using monoclonal antibodies. *J Allergy Clin* 

dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro. *J Allergy Clin* 

dysfunction in atopic dermatitis: gene-environment interactions. *J Allergy Clin* 

rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. *Lancet*

Susceptibility loci for atopic dermatitis on chromosomes 3, 13, 15, 17 and 18 in a

and young children with atopic dermatitis—a prospective follow-up to 7 years of

for atopic dermatitis in New Zealand children at 3.5 years of age. *Br J Dermatol*

117(suppl):S475-80.

*Immunol* 1983;71:47–56

*Immunol* 2004;113:949–57.

*Immunol* 2006;118:3-21

1998;351:1225–32.

options. *J Mol Med* 2005;83:682–92.

age. *Allergy* 2000;55:240–5.

2005;152:742–9.

dermatitis. *J Clin Invest* 2004;113:651–7.

[12] Leung DY, Bieber T. Atopic dermatitis. *Lancet* 2003;361:151-60.


**19** 

*Japan* 

**Improvement of Atopic Dermatitis** 

 **by Human Sebaceous Fatty Acids** 

Hiroyuki Araki, Yoshiya Sugai and Hirofumi Takigawa

Our bodies are protected against a variety of external factors such as transient pathogens and can preserve homeostasis. This defense mechanism consists of many components, including antimicrobial lipids such as *cis*-6-hexadecenoic acid (C16:1Δ6) (Wille & Kydonieus, 2003) and sphingosine (Arikawa et al., 2002), as well as antimicrobial peptides such as β-defensins and cathelicidin (Harder et al., 2010; Hsu et al., 2009; Tay et al., 2011). The levels of these antimicrobial components in the skin of atopic dermatitis (AD) patients are lower than those of healthy subjects (Arikawa et al., 2002; Harder et al., 2010; Takigawa et al., 2005). It has been reported that the uncommon lipid C16:1Δ6 is present as a major component of sebaceous lipids in human skin and hair but that it is not generally included in plant or animal oils. We have focused on this very unique unsaturated fatty acid, and have been investigating the relationship between this fatty acid and the resident flora of human skin as well as transient pathogens. In the course of that research, we found a correlation between C16:1Δ6 and AD, and have developed a method for the production of C16:1Δ6 on an industrial-scale (Araki et al., 2007; Koike et al., 2000a, 2000b; Takeuchi et al., 1990). In addition, we have made further progress in antimicrobial research involving C16:1Δ6 (Araki et al., 2005) and have selected fatty acid derivatives (oxa-fatty acids) with higher activity by means of analyses of structure-activity

In this chapter, we introduce our research into fatty acids, and we also review approaches to

Human skin lipids, including sphingosine and C16:1Δ6, provide a defense against external factors and function to maintain homeostasis. It is well established that human skin lipids contribute to the defense mechanism termed "self-sterilization" (Wille & Kydonieus, 2003) and the antimicrobial activities of each lipid component have been evaluated (Arikawa et al., 2002; Harder et al., 2010). A significant difference was found in the fatty acid composition of sebum lipids between AD patients and healthy controls (Takigawa et al.,

**1. Introduction** 

relationships (Sugai et al., in preparation).

normalizing AD from a microbiological point of view.

**2. Function of human sebaceous fatty acid "C16:1∆6"** 

2005). We describe the results of our investigation in the section below.

 **and Related Lipids** 

*Tochigi Research Laboratories, Kao Corporation* 

