Todd A. Meyer, DO, FAOCO, FAAOA

Transcription

1 Todd A. Meyer, DO, FAOCO, FAAOA

2 None vivianpaige.com

3 Atopic Dermatitis Epidemiology Pathophysiology Diagnosis Management

4

5 2 year old female New widespread rash on her face, arms, abdomen, and behind both knees. Rash has been present for the last two weeks and seems to be getting worse. Patient is scratching uncontrollably while sitting on her mothers lap. Mother states that this scratching is negatively affecting her sleep. Previous to this rash the child has been healthy, up to date with immunizations and at the 50th percentile for height ht and weight. She has a good appetite and has no gastrointestinal complaints. There have been no sick contacts or recent travel.

6 Additional pertinent history: Mother has asthma and allergic rhinitis (Major diagnostic criteria) No sun exposure, new soaps, detergents, lotions, clothing, bedding, etc. Patient has several potential infant triggers: PMH: Unremarkable PSH: None Allergies: NKDA

7 Family History: Mother with asthma and allergic rhinitis 1. Foods such as eggs, milk, and soy in the diet. 2. The family has a dog 3. No smoke exposure Physical exam: The rash is particularly severe in the popliteal fossa. The rash generally has a fine papular p appearance with some slight scaling and prominent erythema on the face, arms abdomen, there is sparing of the diaper area. There are no crusts, pustules or exudates HEENT: Positive for Dennie Morgan lines, periorbital darkening Otherwise unremarkable exam with normal vitals

8 Is made through history and appearance Di t ib ti f ki Distribution of skin lesions!

9 In 1980, Hanifin and Rajka developed criteria for the diagnosis of AD. They developed main criteria and numerous minor criteria. Many articles have questioned the validity of the minor criteria, and the original criteria have been modified on numerous occasions. Following are the criteria for Essential features: These features must be present and, if complete, are sufficient for diagnosis. Pruritus Eczematous changes Typical and age-specific changes: Patterns include facial, neck, and extensor involvement in infants and children, current or prior flexural lesions in adults or persons of any age, and sparing of the groin and axillary regions. Chronic and relapsing course Important features (seen in most cases): These features are seen in most cases and add support to the diagnosis Early age of onset Atopy (IgE reactivity) Xerosis Associated features (clinical associations): These changes help in suggesting the diagnosis of AD but are too nonspecific to be used for defining or detecting AD for research and epidemiologic studies. Keratosis pilaris/ichthyosis/palmar hyperlinearity Atypical vascular responses Perifollicular l changes Ocular/periorbital changes Perioral/periauricular lesions Exclusions: Note that a firm diagnosis of AD depends on excluding conditions such as scabies, allergic contact dermatitis, seborrheic dermatitis (SD), cutaneous lymphoma, ichthyosis, psoriasis, and other primary disease entities. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol (Stockh). 1980;92 (suppl):44-7.

10 According to the criteria of Williams et al, proposed diagnostic guidelines include the following: Patients must have an itchy skin condition (or parental report of scratching or rubbing in children). Patients also must have 3 or more of the following: History of involvement of the skin creases, such as folds of the elbows, behind the knees, fronts of the ankles, or neck Personal history of asthma or hay fever or a history of atopic disease in a first-degree relative in patients younger than 4 years History of generally dry skin in the last year Visible flexural dermatitis or dermatitis involving the cheeks or forehead and outer limbs in children younger than 4 years Onset younger than age 2 years (not used if child is <4 y)

11 Essential Features (3 of 4 Required) Pruritus Facial and extensor eczema in infants and young children/flexural eczema in older children and adults Chronic or relapsing dermatitis Personal or family history of atopic disease

12 allergyasthma.wordpress.com skin-disease.org travinka.ru

13 Xerosis Cutaneous infections Cheilitis Non-specific dermatitis of hands and feet Elevated serum IgE Positive allergy skin tests Early age at onset Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol (Stockh). 1980;92 (suppl):44-7.

14 Ichthyosis jaskin.com Palmar Hyperlinearity y medicaljournals.se Keratosis Pilaris emedicine.medscape.com

15 Pityriasis alba vitiligoarab.net t White dermatographism and delayed blanch response kmle.co.kr Anterior subcapsular cataracts, Keratoconus

16 Dennie-Morgan infra-orbital folds Orbital Darkening University of Iowa Dermatology 1997 Facial erythema or pallor medicine-article.com

17 Prevalence 10-20% Children, hld 1-3% Adults Higher in industrialized nations Higher in urban vs. rural regions More common in higher social class Up to 85% develop symptoms before age 5 Symptoms frequently present in early infancy 45% before 6 months, 60% before age 1 year 30% develop asthma 35% develop allergic rhinitis Horii KA, Simon SD, Liu DY, Sharma V. Atopic dermatitis in children in the United States, : visit trends, patient and provider characteristics, and prescribing patterns. Pediatrics. Sep 2007;120(3):e [Medline]. Schultz-Larsen, Immunol Allergy Clin North Am 2002; 22: 1-24 Taylor, Lancet 1984; 2: Williams, Atopic Dermatitis, 2000: Luoma, Allergy 1983; 38:

18 Aberg (1995) Questionnaire study of Swedish School Children ( year-olds) in 1979 and 1991 Prevalence of AD more than doubled (7% to 18%) Sugiura(1998) 7000 Japanese school children examined Prevalence of AD in 9-12 year-olds doubled d compared to 20 years earlier 18 year-olds had a 5-fold increase in prevalence over 20 years Aberg, Clin Exp Allergy 1995; 25: Sugiura, Acta Derm Venereol 1998;

19 Atopic Dermatitis seems to be the Entry Point for the development of allergic disease Bustos, Clin Exp Allergy 1995; 25:

20 Should AD children be targeted for asthma prevention? YES! Children with AD, age 1-36 months, treated with daily antihistamine (randomized, placebo controlled) 25% fewer diagnoses of asthma in the anti-histamine group ETAC Study 817 infants, age 1-2, treated with placebo or cetirizine 50% developed asthma, but 25% less in cetirizine treated patients who had specific sensitizations to dust or grass Bustos, Clin Exp Allergy 1995; 25: Warner, ETAC Study Group, J Allergy Clin Immunol 2001; 108:

21 60% of AD children are symptom free by early adolescence 50% may recur in adulthood Predictors of persistent disease course: Early onset, severe early disease, asthma and hay fever, and family history Evidence of food and inhalant allergy by age 2 also predicts severe disease Lammintausta, Int J Dermatol 1991; 30: Illi, J Allergy Clin Immunol 2004; 113:

22 Two types of atopic dermatitis Extrinsic i Associated with IgE-mediated sensitization 70-80% of patients Intrinsic Absence of IgE-mediated sensitization 20-30% of patients Types of AD are identical clinically

23 Infantile Phase exudative, erythematous papules and vesicles Face, trunk, extensor surfaces Childhood Phase lichenified papules and plaques Hands, feet, wrists, ankles, antecubital, popliteal Adult Phase dry, scaling, erythematous papules and plaques with large lichenified ed plaques Flexural folds, face, neck, upper arms, back, dorsa of hands, feet, fingers, and toes

24 Most have peripheral blood eosinophilia and increased serum IgE Increased allergen-specific Th2-cells IL-4 and-13 Isotype switching to IgE Induce expression of VCAM-1 (eosinophil infiltration) Downregulate Th1 cytokines IL-5 Development, activation, and survival of eosinophils Hamid, J Clin Invest 1994; 94:

25 Food allergy induces skin rash in 40% of children with AD Can be diagnosed with IPDFT, elim/challenge or mrast Most commonly egg, milk, wheat, soy, and peanut T-cells specific for foods have been cloned from skin lesions Sampson, J Allergy Clin Immunol 1999; 103: Van Reijsen, J Allergy Clin Immunol 1998; 101:

26 Double-Blind, Placebo Controlled Oral Food Challenges Food allergens caused increased symptoms Symptoms resolved when food was eliminated Sicherer, J Allergy Clin Immunol 1999; 104

27 Sensitization to aeroallergens correlates with severity of AD Inhalation challenge in sensitized individuals can exacerbate pruritus and skin lesions Proper avoidance measures in dust sensitive patients has led to improvement in AD Immunotherapy is not universally helpful Recent study showed improved AD when dust allergy is treated with immunotherapy Capristo, Allergy 2004; 59(suppl 78):53-60 Schafer, J Allergy Clin Immunol 1999; 104: Scalabrin, J Allergy Clin Immunol 1999; 104: Holm, Allergy 2001; 56: Werfel, Allergy 2006; 61:

28 Atopy Patch Testing Mostly used for research Occlusive patch testing with aeroallergens elicits eczematoid reactions in 30-50% of AD patients Allergic patients without AD have no reaction to this patch test Wheatley in Leung, Allergic Skin Disease: A Multidisciplinary Approach 2000; 423

29 Multipronged Approach Skin Care Identification and Elimination of Triggers Anti-pruritus Treatment Anti-inflammatory inflammatory Treatment

30 Clinical Recommendation Evidence Rating References Emollients are the mainstay of maintenance therapy for 3, 4, 10 atopic dermatitis. B Topical corticosteroids should be first-line treatments for patients with atopic dermatitis flare-ups. Sedating antihistamines are indicated for the treatment of atopic dermatitis when patients have sleep disturbances and concomitant allergic conditions. A A Antibiotics should be reserved for the treatment of acutely 4 infected lesions associated with atopic dermatitis. A Topical calcineurin inhibitors should be second-line treatments for atopic dermatitis flare-ups and maintenance. A A =consistent, good-quality patient-oriented evidence; B =inconsistent or limited-quality patient-oriented evidence; C =consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 453 or / f

31 Liberal amounts of a lubricant or emollient cream should be applied to the skin immediately after bathing. Emollients should be applied once or twice daily to prevent skin dryness and irritation. Patients generally prefer emollient creams over ointments for daytime use because emollients have a non greasy, cosmetic appearance. Lubricating ointments may be preferred for nighttime use because of their superior hydrating properties. Wearing cotton gloves or socks at night may enhance these properties.

32 Numerous studies have evaluated a variety of dietary, environmental, and alternative approaches to the prevention of atopic dermatitis flareups. [3] [4] [11] Scratch-itch-scratch behavior Begins with habitual scratching Perpetuates dry, irritated skin Can be effectively modified with psychological treatment. [12 TABLE 2 -- Unproven Prevention and Treatment Strategies for Atopic Dermatitis Information from reference 4. Chinese herbal therapy Delayed introduction of solid foods in infants Dietary restrictions Homeopathy Massage therapy Prolonged breastfeeding Reduction of house mite dust Salt baths Use of different diaper materials

33 Use soft Clothing next to the skin. Cotton is comfortable Can be layered in the winter. Wool products should be avoided. Clothes should be washed in a mild detergent with no bleach or fabric softener. Cool temperatures, particularly l at night, are helpful Sweating causes irritation and itch. A humidifier (cool mist) prevents excess drying Used in both winter, when the heating dries the atmosphere, and in the summer, when air conditioning absorbs the moisture from the air. Food avoidance

34 Want to maintain moist skin at all times Soak in clean, warm water (bath, not shower) Avoid soap at every bath Use gentle non-drying soaps (Aveeno, Dove, Basis, Neutrogena) minimal defatting and neutral ph Avoid bath oils Avoid scrub brushes and washcloths

35 Pat dry after the bath While skin is still moist, apply an emollient (Aquaphor, Eucerin, Cetaphil, Neutrogena) Petroleum jelly, mineral oil, or Crisco can be used if xerosis is severe realsimple.com

36 When rash leads to open, oozing sores: Frequent baths (4 per day) in clean, warm water Add colloidal oatmeal to the bath water (3 tbsp) Avoid irritants! omurtlak.bloguez.com

37 Soaps and detergents Want minimal i defatting activity i and neutral ph Wash clothes in gentle, liquid detergent and add extra rinse cycle Heat and perspiration Occlusive clothing Loose fitting cotton, silk, and cotton blends are best Sunburn

38 Identify potential allergens through history and skin testing or mrast Foods are very important and proper elimination / rotation diets should be used Immunotherapy for AD has not been proven to be beneficial Reserve for patients with clear seasonal exacerbations or other symptoms of allergic disease

39 Proper bathing and emollients may be enough Add antihistamine if needed Cetirizine, loratadine, desloratadine, fexofenadine, diphenhydramine, hydroxyzine Try non-sedating in morning and sedating at night to help with sleep Topical Doxepin works well, but is sedating

40 Increased colonies of S aureus in 90% of AD skin lesions Improved response to therapy when anti-staph antibiotics are included Superantigen production is the likely mechanism Leyden, Br J Dermatol 1977; 96: Breuer, Allergy 2000; 55:

41 Scratching enhances binding Exposes extracellular l matrix adhesins Th2 inflammatory responses promote binding IL-4 induces fibronectin expression AD skin is deficient in antimicrobial peptides (βdefensins) Cho, J Invest Dermatol 2001; 116: Ong, N Engl J Med 2002; 347: Cho, J Allergy Clin Immunol 2001; 108:

42 Topical mupirocin (Bactroban) works well when Staph colonization i is present (almost always) Treat the nose, too! Watch for super-imposed HSV infection

43 Reduce inflammation and pruritus in acute and chronic AD Goal is to use the lowest strength possible to control o symptoms s Ointments are generally preferred over cream / gel More occlusive and fewer additives

44 Thinning skin Telangiectasias Bruising Hypopigmentation Acne Striae Face and intertriginous areas are more susceptible to these events Low Potency formulations only! Elidel and Protopic for the Treatment of Eczema, Black Box Warning on Elidel and Protopic by Daniel More, MD, About.com Guide Updated September 08, 2011 Acta Derm Venereol Suppl (Stockh). 1989;151:26-30; discussion Adverse effects of topical corticosteroids. Piérard GE, Piérard-Franchimont C, Ben Mosbah T, Arrese Estrada J. Department of Dermatopathology, University of Liège, Belgium

45 Least Potent to Most Potent Group 7 Hydrocortisone (Hytone) 1 and 2.5% oint/cream Group 6 Desonide (DesOwen).05% oint/cream/lotion Alclometasone (Aclovate).05% oint/cream Group 5 Fluocinolone (Synalar).025% cream Hydrocortisone valerate (Westcort).2% oint Group 4 Mometasone (Elocon).1% cream Fluocinolone (Synalar).025% oint Triamcinolone (Kenalog).1% oint/cream Group 3 Fluticasone (Cutivate).005% oint Halcinonide id (Halog).1% oint Betamethasone (Valisone).1% oint Group 2 Mometasone (Elocon).1% oint Halcinonide (Halog).1% cream Fluocinonide (Lidex).05% oint/cream Desoximetasone (Topicort).25% oint/cream Group 1 Betamethasone (Diprolene).05% (ointment, gel) Clobetasol (Temovate).05% oint/cream Hengge, U, Ruzicka, T, Schwartz, R, and Cork, M. ÒAdverse Effects of Topical Glucocorticosteroids, Journal of the American Academy of Dermatology January Vol. 54, No. 1, P 4

46 BID dosing for most, QD for Fluticasone and Mometasone 30g is needed to cover the entire body of an average age adult Instruct patients in the FTU (Finger Tip Unit) Medication extends from tip to the first joint of the index finger 1 FTU = Hand or groin, 2 FTU s = face or foot, 3 FTU s = arm, 6 FTU s = leg, 14 FTU s = trunk

47 Start with a higher potency steroid for moderate to severe AD When improved after 2 weeks or so step down to a lower potency before stopping If not tapered, AD flares can develop Steroid therapy may be discontinued when inflammation has resolved Continue hydration and emollients Consider twice weekly steroid maintenance Van Der Meer, Br J Dermatol 1999; 140:

48 Tacrolimus (Protopic) and Pimecrolimus (Elidel) Bind to intracellular immunophilins in T-cells Inhibits calcineurin a calcium-ion-calmodulin dependent protein phosphatase necessary for signal transduction Cytokine gene transcription cannot occur Boguniewicz, J Allergy Clin Immunol 2003; 112: S140-50

49 Tacrolimus.03% BID -- Moderate to severe AD, over the age of 2, unresponsive to, or intolerant of, steroids Tacrolimus.1% BID -- As above, over the age of 16 Pimecrolimus 1% BID -- Mild to Moderate AD, over the age of 2, unresponsive to steroids

50 A 2006 black box warning has been issued in the United States based on research that has shown an increase in malignancy in association with the calcineurin inhibitors. While these claims are being investigated further, the medication should likely only be used as indicated (ie, for atopic dermatitis in persons older than 2 y and only when first-line therapy has failed). Primate study with oral pimecrolimus demonstrated development of lymphoma 30x the maximum recommended human dose 2005 ACAAI and AAAAI Calcineurin Inhibitor Task Force Recommend no change in current usage patterns Black Box Warning, Safety of Allergy and Asthma Medicines by Daniel More, MD, About.com Guide Updated July 27, 2007 Elidel and Protopic for the Treatment of Eczema, Black Box Warning on Elidel and Protopic by Daniel More, MD, About.com Guide Updated September 08, 2011 FDA Approves Updated Labeling with Boxed Warning and Medication Guide for Two Eczema Drugs, Elidel and Protopic, January 19, 2006 Fonacier, J Allergy Clin Immunol 2005; 115(6):

51 Phototherapy sunlight in small doses, UV-A, UV- B, a combination of both, psoralen plus UV-A (PUVA), or UV-B1 (narrow-band UV-B) therapy may be used. Long-term adverse effects of skin malignancies in fair-skinned individuals should be weighed against the benefits. Systemic steroids Avoid as much as possible (discontinuing i i usually associated with flares) Interferon Gamma Downregulate Th2 function Cyclosporin systemic calcineurin inhibitor can improve symptoms, but side effects (renal impairment and HTN) limit its use

52 Antimetabolites Mycophenolate, Methotrexate, Azathioprine Psychological Treatment Emotional stressors exacerbate disease Probiotics The rationale for their use is that bacterial products may induce an immune response of the T h 1 series instead of T h 2 and could therefore inhibit the development of allergic IgE antibody production. Some report limited benefit in preventive/therapeutic p roles. This research has yet to be proven. 56 infants with mod-severe AD, randomized to lactobacillus or placebo significant improvemnet in probiotic group after 8 weeks Tar Preparations coal tar is anti-pruritic and antiinflammatory, may induce folliculitis and photosensitivity, use restricted to chronic lesions Michail S. The role of Probiotics in allergic diseases. Allergy Asthma Clin Immunol. Oct ;5(1):5.7 Weston, Arch Dis Child 2005; 90:

53 Omalizumab IgG humanized antibody to binding site on IgE Approved in mod-severe asthma 2 small case series in AD one shows benefit, one shows none Efalizumab Humanized monoclonal antibody to CD11a Blocks T-cells ability to bind to ICAM-1 on antigen presenting cells Approved in mod-severe chronic plaque psoriasis TNF-α Inhibitors (etanercept, infliximab, adalimumab) Blocks migration of T-cells, blocks attraction of TH-2 cells, blocks eosinophil and basophil recruitment Approved in psoriasis and rheumatoid arthritis Lane, J Am Acad Dermatol 2006; 54: Krathen,, J Am Acad Dermatol 2005; 53: Connor, Curr All Asthma Rep 2006; 6: