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ATOPIC DERMATITIS

Clinical Course and Therapeutic Options
Bindi M. Nikhar, M.D., FAAP Division of Dermatologic and Dental Drug Products, ODE V
Pediatric Subcommittee of the AIDAC October 29-30, 2003 29-

Introduction
‡ Atopic dermatitis is a chronic inflammatory disease of the skin primarily seen in the pediatric age group ‡ Characterized by dry skin, pruritus, erythema, edema, scaling, excoriations, oozing, lichenification ‡ Increasing prevalence, rising costs ‡ Together with asthma and allergic rhinitis forms part of the µatopic triad¶
Pediatric Subcommittee of the AIDAC October 29-30, 2003 292

Epidemiology
‡ 10-20% of children in industrialized countries develop atopic dermatitis ‡ Rising incidence, commoner in higher socioeconomic groups ‡ Overall clearance 50-60%. 80% of children with severe disease continue to have lifelong exacerbations.
Pediatric Subcommittee of the AIDAC October 29-30, 2003 293

lack of concentration at school or work ‡ Repeated treatments.Morbidity Impact on quality of life occurs at all ages. ‡ Psychological problems from visible skin lesions due to stigmatization ‡ Itch-scratch cycle ‡ Sleeplessness. 2003 29- 4 . time involved. financial costs Pediatric Subcommittee of the AIDAC October 29-30.

Pediatric Subcommittee of the AIDAC October 29-30. 2003 295 . we recognize that cost is an important factor in drug availability. highest in first few years ‡ While FDA does not consider pharmacoeconomic issues in drug approvals.Cost ‡ Drain on financial resources of patients and health services ‡ Costs increase with disease severity.

concomitant or family history of asthma/allergic rhinitis. age of onset is 6 months or younger ‡ Clearance rate of 60% expected by age 16.Clinical Manifestations ‡ Seen in early infancy. biparental history of atopy Pediatric Subcommittee of the AIDAC October 29-30. early onset.75% of cases. relapses occur in adulthood ‡ Worse prognosis ± severe childhood disease. 2003 296 . in 50 .

2003 29- 7 .Clinical Features ‡ Three main age-related stages. Skin barrier function decreased. may lead to increased absorption of topically applied treatments. Usually improves with adequate treatment Pediatric Subcommittee of the AIDAC October 29-30. Dry skin and pruritus associated with all stages.

Clinical Phases ‡ Infantile Phase ( 0-2 years ) Onset around 3 months of age. the face and scalp commonly involved. crusted weeping patches with excoriations seen on both cheeks and extensor surfaces of extremities Course chronically relapsing and remitting Pediatric Subcommittee of the AIDAC October 29-30. at an older age. 2003 298 . Under 6 months. limb folds and hands involved Red. scaly.

2003 299 . shoulders. Persistent rubbing and scratching leads to lichenified plaques and excoriations ‡ Adult Phase (puberty onwards) Flexural lichenified eczema with facial involvement in periorbital regions seen. Upper trunk.Clinical Phases (cont¶d) ‡ Childhood Phase ( 2-12 years ) Papular areas in flexural regions common. scalp affected with chronic remissions and exacerbations Pediatric Subcommittee of the AIDAC October 29-30.

2003 2910 . PGE2 and IL-10 ‡ Expansion of IL-4 and IL-5 secreting Th 2-like cells ‡ Decreased numbers of IFN-gamma-secreting Th 1-like cells Pediatric Subcommittee of the AIDAC October 29-30.Reported Immunological Features of Atopic Dermatitis ‡ Increased IgE production ‡ Specific IgE to multiple antigens ‡ Increased basophil spontaneous histamine release ‡ Decreased CD8 suppressor/cytotoxic number and function ‡ Increased expression of CD 23 on mononuclear cells ‡ Chronic macrophage activation with increased secretion of GM-CSF.

Chronic or chronically relapsing course 4.Diagnosis of Atopic Dermatitis This requires the presence of three or more major and three or more minor criteria as defined by Hanifin and Rajka ‡ Major criteria 1. Lichenification 3. Personal or family history of atopy Minor criteria There are 23 minor criteria ‡ Pediatric Subcommittee of the AIDAC October 29-30. 2003 2911 . Pruritus 2.

2003 29- 12 . dietary manipulation controversial ‡ Family education important ‡ Reduce exposure to allergens Pediatric Subcommittee of the AIDAC October 29-30. ideal treatment available ‡ Each patient should have a flexible plan tailored for their need ‡ Dietary history important.Management of Atopic Dermatitis ‡ No single.

ointments or lotions can be used depending on individual needs ‡ Avoidance of drying bathing products ‡ Itch control ± Distressing symptom. use oral antihistamines.General Treatment Guidelines ‡ Moisturizers ± are the cornerstone of therapy in AD. Creams. Frequent use important because AD is often accompanied by dry skin. 2003 2913 . try to break the itchscratch cycle Pediatric Subcommittee of the AIDAC October 29-30.

A course of oral antibiotics ± topical antibiotics needed for lichenified. warts. Viral infections. aureus. eg. eczema herpeticum are seen in these patients Pediatric Subcommittee of the AIDAC October 29-30. 2003 2914 .General Treatment Guidelines (cont¶d.) ‡ Control of infection ± Patients with extensive AD are often colonized with Staph. excoriated lesions not responding to treatment.

2003 2915 .Selection of treatment This depends on ‡ Disease severity ‡ Age ‡ Compliance ‡ Efficacy ‡ Safety data ‡ Treatment costs Pediatric Subcommittee of the AIDAC October 29-30.

Photochemotherapy 2.Rx Treatment Options 1.therapy 6. Systemic corticosteroids Off-Label and other treatment options 1. Topical immunosuppressants 3. Traditional Chinese medicine 7. Thymopentin 5. Azathioprine 4. -linoleic acid Pediatric Subcommittee of the AIDAC October 29-30. 2003 2916 . Cyclosporin 3. Interferon. Topical corticosteroids 2.

generally 2-3 weeks Pediatric Subcommittee of the AIDAC October 29-30.Topical corticosteroids (TCS) ‡ First introduced in the 1950s and are currently the mainstay of prescription therapy for atopic dermatitis ‡ Safe and effective when used as recommended ‡ Weakest steroid that will keep the eczema under control should be used ‡ Potent steroids should be used in short pulses. 2003 2917 .

emulsion. Site to be treated 5. 2003 2918 . Extent of eczema 6. gel or lotion Potency classified from group I (most potent) to VII (least potent) 2. Acute or chronic eczema 3. Method of application Pediatric Subcommittee of the AIDAC October 29-30. cream. Age of child 4.Factors to consider when prescribing topical corticosteroids 1. Type of preparation (base and potency) ± Base can be ointment.

leading to flattening of the basal cell layer and thinning of the stratum corneum and stratum granulosum Pediatric Subcommittee of the AIDAC October 29-30. Antiinflammatory effects TCS affect inflammatory cells. chemical mediators and tissue responses which are all responsible for cutaneous inflammation 2. Antiproliferative effects TCS may reduce mitotic activity in the epidermis. 2003 2919 .Mechanism of action of TCS 1.

Atrophogenic Effects TCS can promote atrophy of the dermis through inhibition of fibroblast proliferation.Mechanism of action of TCS (cont¶d) 3. 2003 29- 20 . chemotaxis and protein synthesis Pediatric Subcommittee of the AIDAC October 29-30. migration.

Systemic Effects of TCS ‡ If a TCS is absorbed percutaneously in significant quantities. Discussed under adverse effects Pediatric Subcommittee of the AIDAC October 29-30. it can cause systemic adverse side effects similar to systemically administered corticosteroids. 2003 29- 21 .

Adverse effects of TCS Can result from ‡ the drug substance. 2003 29- 22 . or ‡ the vehicle which can potentiate problems Pediatric Subcommittee of the AIDAC October 29-30.

2003 2923 .Systemic adverse effects of TCS ‡ Suppression of hypothalamicpituitary-adrenal axis ‡ Iatrogenic Cushing¶s syndrome ‡ Growth retardation in infants and children These effects are usually associated with the large body surface area use of potent TCS. Pediatric Subcommittee of the AIDAC October 29-30.

Risk factors for systemic adverse effects ‡ Young age (infants and children) ‡ Liver and renal disease ‡ Amount of TCS applied ‡ Extent of skin disease treated ‡ Frequency of application ‡ Length of treatment ‡ Potency of drug ‡ Use of occlusion It is not established whether catch up growth in children will occur when TCS are discontinued. Pediatric Subcommittee of the AIDAC October 29-30. 2003 2924 .

2003 29- 25 . fungal and viral infections Pediatric Subcommittee of the AIDAC October 29-30.Local side effects of TCS ‡ Epidermal Atrophy .wrinkled skin with prominent vasculature. striae or purpura ‡ Steroid dependence/rebound ‡ Glaucoma/cataracts ‡ Increased susceptibility to bacterial. pseudoscars.

Topical Immunosuppressants ‡ Newest pharmacological class for AD ‡ Introduced in this decade ‡ Direct immunosuppressive action in diseases with immunologic basis ‡ 2 FDA approved products ‡ Tacrolimus (FK506) (trade name Protopic) ‡ Pimecrolimus (SDZ ASM 981) (trade name Elidel) Pediatric Subcommittee of the AIDAC October 29-30. 2003 29- 26 .

‡ Systemic tacrolimus (Prograf) first introduced for prevention of allograft rejection.1% ointment approved for adults. 2003 2927 . liver and heart transplantation Pediatric Subcommittee of the AIDAC October 29-30. now used in kidney. 0. ‡ Indication in both age groups is short and intermittent long term therapy of patients with moderate to severe AD. 0.Background ‡ Protopic (tacrolimus) ointment approved on 12/08/2000.03% ointment approved for children 2 to 15 years.

Background (cont¶d) ‡ Elidel (pimecrolimus) cream 1% approved on 12/13/2001 ‡ Indicated for patients 2 years of age and older for short and intermittent long term therapy in the treatment of mild to moderate atopic dermatitis ‡ Both drugs not approved for use in children less than 2 years of age ‡ Systemic absorption can take place in both adult and pediatric age groups from topical application of both drugs Pediatric Subcommittee of the AIDAC October 29-30. 2003 2928 .

2003 29- 29 .) ‡ Pediatric patients enrolled in clinical studies of tacrolimus and pimecrolimus had an increased incidence of certain adverse events eg. the effects of topical immunosuppressants on the developing immune system are unknown Pediatric Subcommittee of the AIDAC October 29-30. viral infections compared to vehicle. ‡ Currently.Background (cont¶d.

conventional therapies are deemed inadvisable because of potential risks. 2003 2930 . or in the treatment of patients who are not adequately responsive to or are intolerant of alternative.Indications for use (Second-line) (Second‡ Both Protopic and Elidel are indicated for patients in whom the use of alternative. conventional therapies Pediatric Subcommittee of the AIDAC October 29-30.