Atopic Dermatitis

1. Atopic Dermatitis by Leow Atomic Chuan Tse (Group1) B.Agri.Sc(Hons); Dip.Ed., PhD (Toxicology); Grad.Dip.CS (1st Class Hons); MDiv (1st Class Hons)

2. Eczema/Atopic DermatitisEczema is a nonspecific term for many types of skin inflammation (dermatitis). Atopic Dermatitis is a type of eczema, and it is a long term skin disease. “Atopic” refers to a tendency to develop allergy conditions. “Dermatitis” means swelling of the skin or inflammation of the skin. • The most common inflammatory skin condition • Most confusing skin ailment for both patients and their nondermatologic health care providers

3. Atopic dermatitis is the most common type of eczema. It is a chronic, inflammatory, itchy skin condition with unpredictable course of flares and remissions. It affects 5% to 10% of the United States population. Most cases begin in childhood (often in infancy); however may start any age. The disease frequently remits spontaneously-reportedly in 40% to 50% of children- but it may return in adolescence or adulthood and possibly persist for a lifetime. Typically families are advised that children “will grow out of eczema” (About 2 in 3 children with atopic eczema grow out of it by their mid teens)

4. Atopic dermatitis is an inherited Type I hypersensitivity disorder of the skin. It is usually associated with personal or family history of hay fever, asthma, allergic rhinitis or sinusitis. M Grandfather M. Grandmother P. Grandfather P. Grandmother MOM DAD BABY

5. Type 1 Hypersensitivity • In type 1 hypersensitivity, an antigen is presented to CD4+ Th2 cells specific to the antigen that stimulate B-cell production of IgE antibodies also specific to the antigen. The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1 hypersensitivity the antibody is IgE instead of IgA, IgG, or IgM. During sensitisation, the IgE antibodies bind to Fcε receptors on the surface of tissue mast cells and blood basophils.Mast cells and basophils coated by IgE antibodies are "sensitised." Later exposure to the same allergen cross-links the bound IgE on sensitised cells, resulting in degranulation and the secretion of pharmacologically active mediators such as histamine, leukotriene (LTC4 and LTD4), and prostaglandin that act on the surrounding tissues. The principal effects of these products are vasodilation and smooth-muscle contraction. • Type 1 hypersensitivity can be further classified into an immediate and late-phase reaction. The immediate hypersensitivity reaction occurs minutes after exposure and includes release of vasoactive amines and lipid mediators, whereas the late-phase reaction occurs 2–4 hours after exposure and includes the release of cytokines.

6. Normal Skin

7. Skin of Acute Eczema Eczematous epidermis contains intercellular and intracellular fluid that appears in a sponge-like formation (spongiosis); Vasodilatation of the dermis occurs, resulting in the clinical manifestation of ACUTE eczema.

8. Classification of atopic dermatitis(AD)/eczema Non-allergic AD (Intrinsic） AD Allergic AD(Extrinsic） AD Coexiatence Transition IgE mediated AD （Classical AD） Non IgE AD ●Impaired barrier function ●Abnormal sweating ●Altered innate immunity (Defensin, Toll like receptor, NALP proteins (linked to autoimmune disease)) ●Emotional stress T cells Eosinophils IgG（Autoantibody） Etc. Eczema Itch Xerosis Allergy 2001:56:813-824

9. Pathphysiology of atopic dermatitis Chemicals Allergens Bacteria Barrier dysfunction Horny layer IgE FceR1 Cytokine Epidermis Dendritic cell Mast cells Chemokines IgE Inflammatory cells FceR1 Dermis Th2 Lymphocytes Th2 Allergic Inflammation

10. Damage of barrier function and keratinocytes SCRATCH Stratum corneum FceR1 Dendritic cell Elongation of peripheral nerve release of substance P epidermis dermis chemical mediators

11. Immunology of Atopic Dermatitis

12. Mechanism of PruritusN ENGL J MED 2008; 358:1483-1494April 3, 2008 The most important symptom in atopic dermatitis is persistent pruritus, which impairs the patient's quality of life. The lack of effect of antihistamines argues against a role of histamine in causing atopic dermatitis–related pruritus. Neuropeptides, proteases, kinins, and cytokines induce itching. Interleukin-31 is a cytokine produced by T cells that increases the survival of hematopoietic cells and stimulates the production of inflammatory cytokines by epithelial cells. It is strongly pruritogenic, and both interleukin-31 and its receptor are overexpressed in lesional skin. Moreover, interleukin-31 is up-regulated by exposure to staphylococcal exotoxins in vitro. These findings implicate interleukin-31 as a major factor in the genesis of pruritus in atopic dermatitis.

13. Intense Itching and Unceasing Scratching

14. Clincal features of atopic dermatitis Itch is an unpleasant sensation to evoke scratching Rothman S1941(Samuel Hafenreffer 1660) Scratching aggravates atopic dermatitis

15. Acute Eczema Appears as “itchy” erythematous patches, plaques, or papules that may develop into vesicular lesions, or may continue as a less nonvesicular, erythematous eruption.

16. Chronic Eczema Later, the epidermis will thicken (acanthosis) and retain parakeratosis (abnormal keratinization of the squamous epithelium), resulting in an overabundance of cellular infiltrate in the dermis. These changes account for the scale and lichenification of CHRONIC eczema. The epidermis shows hyperkeratosis, acanthosis, and a prominent granular layer. There is liquefaction degeneration at the dermal-epidermal interface.

17. Lichens on a tree • The word “Lichen” has a Greek origin and denotes the superficial growth of an algae and fungus on the bark of a tree

18. Chronic Eczema(aka: Chronic eczematous dermatitis) • Has a hallmark lichenification (plaque with an exaggeration or hypertrophy of the normal skin markings). • Scale and hemorrhagic crusts can result from scratched or drying vesicles. • Older lesions exhibit hypo or hyper pigmentation. Hypo-pigmentation Lichenification

19. Severity Atopic dermatitis can present with a wide spectrum of severity. • mild, recurrent, localized itchy rash on “dry” skin or • more severe, extensive eruption that can be accompanied by unremitting pruritus, sleepless nights, secondary cutaneous bacterial infections, and/or embarrassing lichenification.

20. Psychosocial Effects Psychosocial problems, such as poor self-image, anger, and frustration may lead to depression and social isolation.

21. Different Phases of Atopic Dermatitis The character and distribution of the skin rash tends to vary according to the patient’s age. Any or all manifestations of atopic dermatitis may exist in a single patient. The different phases of atopic dermatitis are not always clearly distinct. Infantile Phase Childhood Phase Adolescent and Adult Phase

22. Infantile Phase Eruption may become generalized, in most cases it first manifests with severe “cradle cap” or severe intertriginous (inflammatory) rashes (groin, neck, axillae). As the patient approaches age 2 years, the flexor creases become involved. Lesions consist of scaly, red, and occasionally oozing plaques that tend to be symmetric. Occurs on the • scalp • face, particularly cheeks • neck • chest • extensor extremities

23. Childhood Phase(patients aged 2 years to 12 years of age) These patients tend to be less acute and lesions less exudative than those seen in infancy. Inflamed lesions become lichenified (especially in Asian and African-American patients) secondary to chronic rubbing symmetrically, with characteristic distribution in the flexural folds and scratching. Lesions tend to occur. • Occurs on the: • Antecubital and popliteal fossae • Neck, wrists, and ankles • May occur on the eyelids, lips, scalp, and postauricular areas

24. Adolescent and Adult Phase(patients 12 years and older) Post inflammatory hyper or hypo pigmented changes tend to be seen. The appearance of atopic dermatitis may change to a more poorly defined, itchy, erythematous rash, possibly with papules and/or plaques. Lichenified plaques of atopic dermatitis are typically less well demarcated than are the plaques seen in psoriasis. These plaques tend to blend into surrounding normal skin.

25. Possible Complications Pruritus (itching) may interfere with sleep. Pruritis is increased by repeated scratching and rubbing, which leads to lichenification, oozing, and secondary bacterial infection. Secondary infection with Staphylococcus aureus may trigger relapse of atopic dermatitis.

26. Clinical AspectsClues to diagnosing Atopic Dermatitis: • Persistent Xerosis (abnormal dry, “sensitive” skin) • “Allergic Shiners” (darkened or tanned coloring in the periorbital areas) • Hyperlinear palmar creases (exaggerated skin creases or lines in the palms of the hand. • Follicular eczema (Lesions accentuated around hair follicles) • Ichthyosis vulgaris (an inherited skin disorder in which dead skin cells accumulate in thick, dry scales) • Keratosis Pilaris (skin condition that looks like small goose bumps)

27. Differential DiagnosisDiagnosis of atopic dermatitis is generally not difficult, especially in patients with atopic history. The following should be considered or excluded: Determine whether the patient was exposed to a substance that could cause contact dermatitis. The location of the lesions may suggest an external cause. Contact Dermatitis

28. Differential Diagnosis Psoriasis • Lesions are generally in extensor locations (elbows, knees, and other large joints) rather than the flexor creases. May be palmar or plantar as seen in this image. • Patients typically have a positive family history of psoriasis. Psoriasis is less pruritic than eczema, lesions tend to be clearly demarcated from normal surrounding skin, and the scale of psoriasis tends to be thicker in appearance. However, psoriasis may at times be clinically indistinguishable from atopic dermatitis

29. Differential Diagnosis A positive KOH test or fungal culture result will confirm (remember, an unresolved eczematous-like rash, worsening with topical corticosteroids could be tinea) Tinea

30. Japanese guide line for atopic dermatitis Katayama et al.(JSA) Allergology International 2011 Diagnosis Assessment of dermatitis Skin care Rectification of aberrant skin barrier functions Evaluation of Aggravation factors Drug therapy Emolients Tacrolims(Face) Steroid ointment Anti-hisitamine Imunosuppresants Appropriate guidance for patients in daily life Clean of the skinBathing・Showering・Emolient

31. Narrow Band UVB Phototherapy • Eczema light therapy refers to the use of ultraviolet (UV) light to treat the skin rash and itching of eczema. Exposing the skin to UV light suppresses overactive skin immune system cells that cause inflammation

32. Management In children, NICE ( National Institute for Health and Clinical Excellence) suggest a treatment schema based on severity: • mild atopic eczema • emollients • mild potency topical corticosteroids • moderate atopic eczema • emollients • moderate potency topical corticosteroids • topical calcineurin inhibitors e.g. pimecrolimus • bandages • severe atopic eczema • emollients • potent topical corticosteroids • topical calcineurin inhibitors • bandages • phototherapy • systemic immunosuppressive therapy (cyclosporine, azathioprine, interferon-gamma)

33. Aggravating factors in atopic dermatitis Katayama et al.(JSA) Allergology International 2011 Infants～2 y 2 y～13 y 13 y～Adult 1.Foods (Egg,milk,wheat,etc) 2.Sweat,dryness,scratching 3.Slaver,soap,shampoo, cloth 4.Environmental factors 5.Bacteria, fungus etc. 1.Sweat,dryness,scratching 2.Slaver,soap,shampoo, cloth 3.Bacteria, fungus,etc. 4.Environmental factors 5.Stress 6.Foods *Aggravation factors are different in each patient. Start to eliminate responsible factors after sufficient evaluation.

34. Avoidance Irritants: • Recommend non-irritant fabric, such as cotton. Wool may induce itching • Overheating and sweating: Excess dryness or humidity should be avoided. An air conditioner or humidifier in a child’s bedroom may help to avoid the dramatic changes in climate that may trigger outbreaks.

35. Avoidance • Allergens: • Environmental elimination of airborne substances may bring lasting relief.

36. Thank You