Managing and Minimizing Flare-ups in Atopic Dermatitis

Transcription

1 Managing and Minimizing Flare-ups in Atopic Dermatitis Importance of the skin barrier & how commonly used drugs are impacting it Dr. Benjamin Barankin, MD FRCPC Medical Director & Founder of Toronto Dermatology Centre

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

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4 Objectives Review atopic dermatitis (AD) epidemiology Describe the role of immune abnormalities and skinbarrier dysfunction in the pathogenesis of AD Differentiate the role of corticosteroids and pimecrolimus in skin regeneration Optimize AD treatment for improved patients outcomes 4

5 Epidemiology and Co-morbidity

6 6 Dermatitis is Multi-factorial Allergic contact dermatitis Irritant contact dermatitis Chronic dermatitis Atopic dermatitis Vesicular and hyperkeratotic dermatitis Exogenous extrinsic factors Endogenous intrinsic factors Adapted from Halioua et al. Ann Dermatol Venereol 2010;137(4):

7 Atopic Dermatitis Dermatitis- term used to describe inflammation of the skin Synonymous with eczema Chronic inflammatory cutaneous disease with pruritic symptoms and frequent recurrence Guidelines of care for the management of atopic dermatitis J Am Acad Dermatol 2014;70:338-51

8 Diagnosis 1 ESSENTIAL FEATURES: Pruritus Eczema (acute, subacute, chronic) Typical morphology and age-specific patterns* Chronic or relapsing history *Patterns include: 1. Facial, neck, and extensor involvement in infants and children 2. Current or previous flexural lesions in any age group 3. Sparing of the groin and axillary regions IMPORTANT FEATURES: Early age of onset Atopy Personal and/or family history Immunoglobulin E reactivity Xerosis Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis; 8

9 Disease Prevalence AD is the most common chronic skin disease in young children 1 Onset in 1 st year in 60%; by 5 years in 85% 1 Persists into adulthood in 10% to 30% of cases 2 Affects 2% to 3% of adults 3 Up to 17% of Canadians suffer from AD at some point in their lives 4 Affects all races (being of Black race appears to increase risk) 5 Increased prevalence, esp. in industrialized countries; parallels increase in asthma 6 1. Bieber T. N Engl J Med. 2008;358: Ellis CN et al. Semin CutanMed Surg. 2012;31(3 Suppl):S18-S Eichenfield LF et al. J Am Acad Dermatol. 2014;70(2): CDA official website; 5. Shaw TE et al. J Invest Dermatol. 2011;131: Spergel JM. Immunol Allergy Clin North Am. 2010;30(3):

10 Atopic Dermatitis Location By Age

11 Triggers Environmental: Detergent, hard water, microbial organism Colonization with Staphylococcus aureus 1 74% in acute lesional skin of AD patients 38% in chronic lesional skin of AD patients 3% in control skin Increased susceptibility to secondary bacterial infection, including S aureus 1 Extremes of heat or cold, sweating Others: Strong family history Stress Sweating 1. Park HY et al. Ann Dermatol. 2013;25(4):

12 Sleep Disturbance Sleep disturbances seen in 60% of children with AD Increases to 83% during exacerbations Even in clinical remission, children with AD demonstrate more sleep disturbance than healthy children Camffermann D et al. Sleep Med Rev. 2010;14(6):

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14 Optimizing Treatment

15 Management Goals of AD Early treatment to reduce flaring frequency and intensity Key Goals 1. Improving and maintaining skin hydration 2. Controlling pruritus and breaking the itch-scratch cycle 3. Treating flares 4. Reducing incidence of flares and the progression of flares Additional Goals 1. Controlling active skin inflammation and infections 2. Restoring the normal appearance of skin 3. Reducing trigger factors 4. Addressing emotional stress 5. Educating the patient and the caregiver 15

16 Symptom Severity Management Goals of AD Before Treatment Managed During Treatment Improving and Maintaining Skin Hydration Controlling Pruritus Treating Flares Reducing Incidence of Flares and The Progression of Flares

17 17 European Academy of Allergology: Consensus Report Treatment steps adapted to disease severity in AD 3 Recalcitrant - Severe Step IV: Systemic therapy or UV Moderate - Severe Step III: Mid-high potency TCS Mild - Moderate Step II: Low-mid potency TCS and/or topical immunomodulators Dry skin no flare up Step I: Moisturizer +/- topical immunomodulators twice weekly to prevent flares 3. Akdis, et al: Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. J Allergy Clin Immunol 2006;118:

18 Classification 18

19 Potency of Topical Corticosteroids 4 potencies: Class1 (Ultra-High) Class2 (High) Class3 (High) Class4 (Mid) Class5 (Mid) Class6 (Low) Class7 (very low) High Potency Low Potency Factors affecting potency Concentration Vehicle Occlusion/hydration Halogenation

20 Potency Chart: Ultra-High Molecule Product Name Vehicle Cream Ointment Foam Spray Gel Ultra High Potency BETAMETHASONE dipropionate DIPROLENE 0.05% CLOBETASOL DERMOVATE 0.05% CLOBETASOL CLOBEX SPRAY 0.05%* CLOBETASOL OLUX-E FOAM 0.05%* HALOBETASOL ULTRAVATE 0.05%* *No generic available Lotion 20

21 Potency Chart: High Molecule Product Vehicle High Potency AMCINONIDE BETAMETHASONE dipropionate BETAMETHASONE valerate Cream Ointment Gel Lotion CYCLOCORT 0.1% DIPROSONE 0.05% BETADERM 0.1% BETAMETHASONE valerate LIDEX, LYDERM 0.05% DESOXIMETASONE TOPICORT 0.25% * DESOXIMETASONE MOMETASONE TRIAMCINOLONE ACETONIDE *No generic available TOPICORT Gel 0.05% * ELOCOM 0.1% ARISTOCORT C 0.5% * 21

22 Potency Chart: Medium MOLECULE PRODUCT VEHICLE Cream Ointment Lotion Medium Potency BECLOMETHASONE dipropionate PROPADERM 0.025% * DESOXIMETASONE TOPICORT Mild * PREDNICARBATE DERMATOP 0.1% * BETAMETHASONE valerate PREVEX B 0.1% BETAMETHASONE valerate BETADERM 0.05% BETAMETHASONE valerate BETADERM 0.1% DIFLUCORTOLONE valerate NERISONE OILY 0.1% * MOMETASONE ELOCOM CREAM 0.1% FLUOCINOLONE acetonide SYNALAR 0.025% TRIAMCINOLONE acetonide ARISTOCORT R *No generic available 22

23 Potency Chart: Low & TCI MOLECULE PRODUCT Vehicle Cream Ointment Lotion Foam Low Potency DESONIDE DESOCORT 0.05% DESONIDE VERDESO FOAM 0.05% * HYDROCORTISONE EMO-CORT 2.5% * HYDROCORTISONE EMO-CORT 1% TCI Pimecrolimus Elidel 1% * Tacrolimus Protopic 0.03% & 0.1% * *No generic available 23

24 Vehicle Variability Vehicle is the key to treatment success or failure Vehicle affects: penetration, permeation, absorption, reservoir and compartmentalization drug stability and shelf life. Characteristics of vehicle can profoundly modulate the local and systemic safety as well as potency of corticosteroids Vehicle choice can impact patient acceptance and adherence to treatment. Kircik L., Understanding Generics. JDD 13 (7): s75-76

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26 How much to apply, what, where? 26

27 Preferred Use based on Potency Low: Use in children Use on face, genitals, armpits, skinfolds Mid: Trunk, arms, legs High: Localized areas, thick lesions, palms, soles and scalp Very High: Resistant conditions Thicker skin (palms, soles of feet) For short periods of time to reduce acute inflammation

28 Steroid Side Effects:

29 How is it different from TCS? 29

30 What can they do for my patient? 1) Suppresses inflammatory T Cell Inhibit calcineurin responsible for signal transduction leading to the production of inflammatory interleukins by T-cells They suppress release of T cells by binding to calcium dependent phosphatase (white blood cells) and therefore the release of inflammatory cytokines. T 2) Anti-inflammatory, without being anti-proliferative Steroids disrupt skin barrier function and increase trans epidermal water loss. 3) Increase skin barrier function Intact skin barrier will prevent future flares.

31 Skin barrier function TCIs (Tacrolimus/Pimecrolimus) and TCS differ not only in their effect on inflammation but also in their influence on the skin barrier structure. TCS are effective in AD treatment, but their long-term use is limited by local and systemic adverse events and increasing evidence that they do not address the disturbed epidermal barrier. Tacrolimus/Pimecrolimus are able to restore disrupted epidermal differentiation in AD. Tacrolimus/Pimecrolimus seems superior in repairing skin barrier architecture compared with corticosteroids of medium or strong potency, which may prevent allergen penetration and relapse of AD.

32 Optimizing AD Therapy with TCIs Patients with AD inevitably require long-term treatment. Chronic intermittent and proactive use of TCIs may spare the need for as much topical corticosteroid. In sensitive skin areas such as the face, neck, or genitals, corticosteroid use may not be suitable due to a greater risk of thinning of the skin, glaucoma, and periorificial dermatitis To avoid possible stinging or burning, put the TCI in the fridge the first week until tolerance is assured Draelos ZD. Use of topical corticosteroids and topical calcineurin inhibitors for the treatment of atopic dermatitis in thin and sensitive skin areas. Curr Med Res Opin. 2008;24(4): Hengge UR, Ruzicka T, Schwartz RA, et al. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006;54(1):1 15. (quiz 16 18). 32

33 Difference between Protopic and Elidel Elidel Pimecrolimus Mild to Moderate Cream Indication: 2 years up As a second-line therapy for short-term and intermittent long-term therapy Protopic Tacrolimus Moderate to Severe Ointment Indication: 0.03%: 2 years up 0.1%: 15 years up Indicated as a second-line therapy for short and long-term intermittent treatment Maintenance therapy

34 Canadian Dermatologist Association: Position Statement on Topical Calcineurin Inhibitors 1 There is no evidence of an increased rate of lymphoma when compared to the general population. The clinical and histological patterns of the observed lymphomas are not consistent with typical immunosuppression- related lymphomas. There is minimal absorption of topical calcineurin inhibitors, with nondetectable or negligible blood levels, making long-term intense immunosuppression unlikely. There is no evidence of interference with effectiveness of immunization, delayed hypersensitivity skin responses, or rates of systemic infections. 1.

35 Cost of medication Elidel- 30 grams Protopic- 30 grams 1% Cream- $ %- $ %- $66.30

36 Off-Label Uses of Tacrolimus/Pimecrolimus Allergic & irritant contact dermatitis Hand dermatitis irritant, allergic Lichen planus (glans, oral) Lichen sclerosus Lichen simplex chronicus / notalgia paresthetica Lupus erythematosus Morphea Necrobiosis lipoidica Paronychia Perioral dermatitis (when weaning off steroid use) Pityriasis alba Psoriasis (especially intertriginous, face) Red scrotum syndrome or Itchy vulva or perianal dermatitis Seborrheic dermatitis Steroid phobic patients with inflammatory skin disease Vitiligo

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40 Adherence and Persistence in Atopic Dermatitis

41 Atopic Dermatitis Non-Adherence Factors Complex treatment Fear of side effects - corticophobia Prevalence is estimated to be 80.7% 2. The greater the fear, the poorer the compliance Vehicle of topical drug, Greasy creams and ointments are not preferred by patients Selection based on features and location of lesions Patient preference for specific galenic properties 1. Tan X, et al., Expert Opin. Drug Deliv. 2012, 9(10): Aubert-Wastiaux H., et al., Br. J. of Dermatol 2011;165(4):808-14

42 Techniques for Improving Adherence in AD Factors that promote therapeutic adherence include: Education by the physician and staff Selection of optimal vehicle/dosage Patient preference Recommendation of appropriate, supportive skin care Choosing less irritating lower doses and/or formulations optimized for tolerability (such as with a moisturizing base) Providing written instructions 1. Chen DM, Feldman SR. How patients experience and manage dryness and irritation from acne treatment. Journal of Drugs in Dermatology In press.

43 Adherence & Persistence - Conclusion Topical therapies work much better when patients use them Adherence is key to optimize patient outcomes Factors that hinder patient adherence include Tolerability, vehicle formulation, time constraints, fear of side effects, etc. Better adherence and persistence can be promoted by Having strong relationships with patients and their parents Educating patients and providing clear, written instructions Simplifying treatment Dealing with anticipated side effects and patient concerns Scheduling a return visit 1. Baldwin H, Tricks for improving compliance with acne therapy, Dermatologic Therapy, 19, 2006, Accessed on Dec

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45 Summary Up to 17% of Canadians suffer from atopic dermatitis (AD) at some point in their lives 1. Patients with AD have an epidermal barrier dysfunction, which allows invasion of allergens to occur [1]. Factors affecting potency of TCS include concentration, occlusion, formulation, and halogenation. Important differences exist between and among generics and the reference brand. Bioequivalence allows for a wide margin (45%) of variability among substitute generic products. In addition to the steroid-sparing effect, tacrolimus/pimecrolimus reduces the number of flares and improves overall disease control of adult AD. Reserving steroids for rescue therapy will reduce the need for their long-term use. Patient preference and educating patients are key for patients adherence 45

46 Thank You!