Atopic Dermatitis. Marcia Hogeling, MD Pediatric Dermatologist Phoenix Children s Hospital

Transcription

1 Atopic Dermatitis Marcia Hogeling, MD Pediatric Dermatologist Phoenix Children s Hospital

2 Disclosure slide advisory board for Leo Pharma and Anacor we use some off label medications to treat atopic dermatitis

3 Objectives Review how to counsel patients and families on gentle skin care Improve knowledge of topical treatments in atopic dermatitis Recognize how quality of life and sleep is affected by atopic dermatitis

4 Atopic Dermatitis Most prevalent chronic inflammatory condition of childhood Affects 20% of kids at age 6 in western countries Can cause significant psychosocial impairment Leading cause of sleep loss in children About one third develop asthma or allergic rhinitis

5 Hanifin and Rajka: Criteria for Atopic Dermatitis Patients must have at least 3 basic features: Pruritus (Itch!!) Typical morphology and distribution Chronic or chronic relapsing course Personal or family history of atopy (asthma, allergic rhinitis, AD)

6 Concepts in AD Pathogenesis Abnormal inflammatory cells (langerhans cells and inflammatory epidermal dendritic cells) Skin barrier dysfunction Epidermis as immunologically important Neural mediators Microbial colonization/infection N Engl J Med Apr 3;358(14):

7 Filaggrin Mutations and AD Ichythyosis vulgaris is caused by mutations in the gene encoding filaggrin Filaggrin is the major protein of keratohyalin granules in the epidermal barrier It is cleaved into filaggrin peptides that bind to keratin fibers to form the cornified envelope of the skin barrier A large number of families with ichthyosis vulgaris also had AD The association between filaggrin mutations and AD was highly significant (p=3x10-17 ) Smith FJ et al. Nat Genet 2006;38:

8 Consequences of Barrier Impairment in AD Increased vulnerability to foreign irritants/allergens or pathogens Extreme dryness results in increased scratching and further barrier damage Increased antigen absorption and cutaneous hyper-reactivity

9 Case X

10 Differential Diagnosis: itchy red rash in a child Any thoughts?

11 Further Evaluation Culture obtained from skin on her cheeks Positive for Methicillin sensitive Staph aureus after 48 hours Diagnosis of Atopic Dermatitis made based on combination of clinical history and physical examination, skin biopsy was not necessary

12 Atopic Dermatitis (AD): Simply Defined Pruritic (itchy) skin condition Typical distribution Age <2: cheeks, forehead, scalp, & extensor surfaces Age >2: flexural areas of neck, elbows, knees, wrists, & ankles Chronic relapsing course Associated with other atopic conditions (asthma and allergic rhinitis)

13 Physical examination Cheeks and scalp in infants Lateral and extensor surfaces Later infancy, get flexural extremity involvement Diaper area spared

14 Atopic dermatitis on the extensor surface of an infant s arm Note follicular prominence on torso

15 Lichenification in a young child with atopic dermatitis Exaggerated skin markings are seen on the extensor surfaces of the arm.

16 Milder AD on the extensor surface

17 Differential diagnosis of infantile AD: COMMON disorders Seborrheic dermatitis Contact dermatitis (allergic and irritant) Scabies Psoriasis Ichthyosis vulgaris Keratosis pilaris

18 DDx of atopic dermatits: RARE disorders in infants Metabolic/nutritional/genetic disorders: acrodermatitis enteropathica nutritional deficiency (biotin, essential fatty acids) Netherton syndrome Phenylketonuria Omenn syndrome Prolidase deficiency Gluten-sensitive enteropathy Eosinophilic gastroenteritis Immune disorders: Hyper IgE syndrome Severe combined immunodeficiency syndrome Wiskott-Aldrich syndrome Agammaglobulinemia Ataxia-telangiectasia Neonatal lupus erythematosus

19 Approach to AD child

20 What the Parents Come Into the Office Knowing We did something wrong It must be something we re giving him/her, if we can only find the food she is allergic to Baths are bad for him Topical steroids scare us but that steroid-free one causes cancer and we don t want to hurt him There are so many lotions and potions - we can t remember what goes where We want a cure

21 What We Know It isn t really anyone s fault The cause is not an EVIL FOOD Baths are okay Topical steroids are safe, if used correctly This family isn t getting enough sleep There is no cure but there are effective treatments

22 Back to the Basics: Characteristics of Atopic Skin Drier than normal barrier defect Itchier than normal More sensitive to irritants ie soaps, detergents, wool, etc Lichenifies when rubbed: The itch that rashes Skin gets infected more easily (S. aureus, molluscum, HSV,warts, etc)

23 Atopic Dermatitis: Where to Start Multi-factorial disease Gentle skin care: basis of prevention, maintenance Treatment of dermatitis (topical Rx) Treat itch, treat infection (if present) Return for reevaluation and reinforcement!!

24 The Nitty-Gritty of Management: Good History is KEY How long? How bad (especially itch)? Previous medicines? What makes it worse/better? Role of diet, environment. Maintenance regimen: emollients and irritant avoidance Itching Nocturnal waking and/or scratching Where is the child sleeping (ie parents bed) Medicines: Still have them?

25 Management: 4 Key Factors Gentle skin care Control inflammation Treat infection, if present Antihistamines

26 Gentle Skin Care Addresses permeability barrier defect Mild soap, if any (dove, cetaphil) Daily or twice daily application of ointments & creams (better than lotions)

27 Why are Moisturizers used routinely in AD? Concept of Barrier dysfunction Dry Skin with increased transepidermal water loss Seem to help Recent evidence strongly supportive of this concept

28 Atopic Dermatitis: Bathing Wet school vs. Dry school Avoid baths, moisturize frequently Bathing is fine with soak and seal method

29 Too Wet or too Dry???? Skin bathing regimens are part of maintenance Marked variability in expert advice End-point is consistent: Hydrated skin!!! Regular bathing can hydrate the skin and debride crust. There is no evidence that bathing, when performed as outlined, adversely affects disease. Eichenfield LF et al. AAD Consensus Conference on Pediatric Atopic Dermatitis J Am Acad Dermatol

30 GENTLE SKIN CARE : Cornerstone of Treatment Baths are okay! IF: tepid water, followed by medicine then emollient (3 minutes rule) No soap or minimal soap: dirty areas only. (No bubble baths) Mild soap (e.g. dove, cetaphil cleanser) Emollient: petroleum jelly, vanicream

31 What about natural and organic products? virgin coconut oil effective in several studies olive oil WORSENS eczema sunflower seed oil helps (small study on olive oil vs sunflower seed)

32 Management: 4 Key Factors Gentle skin care Control inflammation Treat infection, if present Antihistamines

33 Topical corticosteroids: Mainstay of Rx Least strong corticosteroid which will do the job Ointments more effective for chronic eczema; most children don t mind lack of cosmetic elegance Creams have net drying effect, irritating, sensitizing, sting- but creams/gels sometimes okay for teens (adherence)

34 Topical Corticosteroid Phobia In a survey of patients with atopic dermatitis: 73% worried about use 24% admitted to noncompliance due to worry Patients key concerns: Skin thinning (35%) Nonspecific long-term effect (24%) Absorption/effect on growth (10%) Charman CR, et al. Br J Dermatol. 2000:142:

35 Atopic Dermatitis: Often Undertreated Corticosteroid phobia common in parents Changing formula and diet rather than use of topical medications Small quantity of topicals prescribed Difficult to adhere to treatment with chronic disease, education helps Important to treat; potentially prevent sequelae associated with severe disease

36 Issues re: topical corticosteroids Steroid Phobia and compliance Important to address fears! Side effects (uncommon if used correctly) Rosacea (careful of high potency on face) Atrophy and Striae (counsel on axilla/groin) Systemic absorption (rare- avoid ultrapotent) Iatrogenic Cushing s high potency diaper area - (rare reports)

37 Topical Steroid Ranking Class 1 Superpotent Clobetasol 0.05% Class 2 High Potency Fluocinonide 0.05% Class 3 High/Medium Potency Mometasone ointment Class 4 Medium Triamcinolone 0.1% Class 5 Medium/Low Triamcinolone % Class 6 Low Potency Desonide Class 7 Low Potency Hydrocortisone 1%

38 General Principles of Topical Steroid Use Vehicles include: ointments, creams, lotions, solutions, gels, and foams A steroid in an ointment base is more potent than the same steroid in a cream or lotion Ointments are better for dry lesions. Creams are elegant and rub in well. Use gels or foams for hairy areas. Avoid potent and superpotent steroids on the face and in body folds (can cause epidermal atrophy).

39 Topical steroids Triamcinolone 0.025% or 0.1% ointment Cheap!! i.e. 4 dollar generics, 80 grams triamcinolone 0.1% Apply twice daily to affected areas on body (except axilla, groin, diaper area)

40 Fluocinolone oil Oil formulation useful for scalp dermatitis diffuse dermatitis on torso, easy to spread Oil is moisturizing also Although derived from peanut oil, not contraindicated in peanut allergy

41 What about the face? Hydrocortisone 1% ointment bid Hydrocortisone 2.5% ointment bid Desonide ointment Long term use sometimes combine with TCIs (topical tacrolimus and pimecrolimus) Apply emollients on top

42 FDA Warnings Black Box Warning TCI s have been around for over 10 years Pimecrolimus and tacrolimus initially marketed to PCPs and overprescribed Concerns regarding? Photocarcinogenesis? Lymphoma risk

43 Update: Malignancy, AD & TCI s Longitudinal cohort study PEER Registry 7457 children used mean of 793 g of pimecrolimus when enrolled 5 malignancies (2 leukemia;1 osteosarcoma;2 lymphomas, no skin cancer) Compared to SEER data: no increased risk Margolis JAMA Derm 2015 Feb

44 When to Consider nonsteroidal TCI Rx Not currently 1st line Rx Not FDA approved under age 2 Face, periocular, intertriginous areas - as steroid sparing agent Recalcitrant disease for maintenance therapy - after flares cooled down with topical steroid

45 Infection Think of infection when eczema not improving with usual topical treatments Especially staph!

46 Treat Infection Commonly see Staph aureus and Group A Strep superinfections Act as trigger for a flare of the atopic dermatitis and stimulate inflammation Recommend systemic antibiotics for a 10 day course (cephalexin, clindamycin) Can also get viral infections such as Herpes Simplex, molluscum contagiosum, & warts

47 Superinfection with Staph aureus

48 Treating infection (Staph) Do swabs when flares occur Look for pustules, often scratched off Treat with keflex (and switch treatment if swab comes back CA-MRSA) Bleach baths: reduce the amount of systemic antibiotics needed ¼ cup of bleach in half an adult bath, 2-3 times per week Huang JT et al Treatment of staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics May;123 (5):e808-14

49 AAD Guidelines: Bleach Baths In patients with moderate to severe AD and clinical signs of secondary bacterial infection, bleach baths with intranasal mupirocin may be recommended toto reduce disease severity (strength of rec: B, level of evidence-2)

50 Infection: don t forget eczema herpeticum!

51 Sleep Disorders in Atopic Dermatitis Disorder initiating/maintaining sleep Due to pruritus initially Poor sleep habits become learned behavior 60-80% incidence in children with AD Sequellae include discipline problems, afternoon fatigue, parental sleep loss ~2.6 hours Dahl RE, et al. Arch Ped Adol Med 1995;149: Reuveni H, et al. Arch Ped Adol Med 1999;153:

52 Management: 4 Key Factors Gentle skin care Control inflammation Treat infection, if present Antihistamines

53 Antihistamines 2014 AAD Eczema guidelines: non sedating antihistamines are not recommended in treating atopic dermatitis rather, use sedating antihistamines

54 Antihistamine Therapy for Sleep Disorder Work primarily via sedation Is the child waking up scratching or scratching during sleep? Hydroxyzine 1mg/kg/d best initial Rx. Can give as single hs dose and increase prn to 2 mg/kg/d Doxepin (off label) 5-10mg for older children max dose 1 mg/kg :EKG Address co-sleeping

55 Atopic Dermatitis and Mental Health 2009 and 2010 population based studies in Germany Strong association between atopic dermatitis and ADHD in patients with sleep disturbance Systematic review of 6 subsequent studies confirmed the link Schmidt J et al JAMA 2009 Romanos M et al J Epidemiol Community Health 201 Schmitt J et al Allergy 2010

56 Atopic Dermatitis and Mental Health

57 Atopic Dermatitis and Mental Health Possible mechanism? Sleep disturbance Strengthens association between AD and ADHD Systemic inflammation Increased levels of pro-inflammatory cytokines in depression, anxiety, autism Chronic illness Children with chronic illness have increased risk of emotional and behavioural problems

58 Atopic Dermatitis and Mental Health Study limitations Cross sectional design Cannot determine causality Parental reporting of AD and mental illness diagnoses

59 Is My Child Allergic to Something? The answer is probably yes Is the allergy causing the skin rash: No Could the allergy be making the skin rash worse? Maybe, but probably not

60 AAD Eczema guidelines Elimination diets should not be initiated based on presence of AD or a suspicious history alone Sidbury et al JAAD 2014

61 What to say: We wish foods were the cause! It would be easier! But we re not that lucky If there is a food you are worried about, cut it, But: be systematic, thorough, and HONEST Let s try our regimen at the same time to heal the skin; then you can add food back and see

62 Allergy Evalution Not necessary/cost effective in mild, moderate disease unless co-morbidity May help liberalize food restrictions Overall, disappointing in finding a reversable, discrete trigger or triggers of atopic dermatitis. Worth doing in severe disease - specific correctable allergy is sometimes found Multi-disciplinary approach can be useful

63 Useful analogies and information There is a fire in the skin - we have to call the fire department I know you are concerned about your child s development. But your child s ability to develop normally can be affected by feeling itchy all the time and not sleeping well.

64 Useful analogies: Atopic Derm In treating, we are trying to re-set the thermostat Diaper area: Like a tropical rain forest Skin maintenance like regular oil changes for car: helps prevent problems BUT occasional breakdowns will happen anyway

65 Action plan Induction therapy (flare management, using topical steroids) Maintenance therapy Varies depending on disease severity and persistence May need stepped maintenance, decrease as tolerated

66 Flare Prevention Continued use of either topical corticosteroids (1-2x/week) or topical calcineurin inhibitors (2-3x/week) after disease stabilization to previously involved skin, is recommended to reduce subsequent flares or relapses Eichenfield et al. Atopic dermatitis consensus guidelines, American Academy of dermatology

67 Pearls for AD patients Ask about sleep disturbance and impact on individual/family Ask the last time the skin was totally clear and assess skin between visits Always ask about quantity of use of medications Tell amount of medicine to use in short-time frame Wet wraps

68 Wet wraps/wet dressings Apply corticosteroid (triamcinolone 0.1% ointment) to affected areas Apply moisturizer to rest of body Wet cotton pajamas (squeeze out excess water), apply overtop, then dry pair overtop

69 What about systemic therapy? Phototherapy NB UVB Cyclosporine Azathioprine Methotrexate Mycophenolate Biologic agents? Prednisone: Works well, BUT for too short a time; Rebound the rule even during taper

70 Systemic Corticosteroids 2014 AAD Guidelines: systemic steroids should generally be avoided in adults and children with AD because potential short and long term adverse effects..largely outweigh the benefits

71 Just to review some of the other items in our differential diagnosis

72 Seborrheic Dermatitis AKA cradle cap Common mild dermatitis Most common in first 4-6 weeks of life Likely caused by overproduction of sebum and the yeast Malassezia

73 Seborrheic Dermatitis Erythematous symmetric plaques with greasy scale Rarely pruritic Can treat with ketoconazole cream and hydrocortisone

74 More common on the scalp, face, neck folds and diaper area of infants Seen in adults/teens in a somewhat different distribution (eyebrows, nasolabial folds) Seborrheic Dermatitis

75 Psoriasis Chronic polygenic disease triggered by trauma, infection, medications More clearly demarcated than atopic dermatitis Pruritis is not as common a feature of psoriasis as it is of atopic dermatitis

76 Psoriasis Different distribution from atopic dermatitis Commonly affects elbows, knees, and scalp as well as the diaper area in infants affected with psoriasis

77 Urticaria AKA Hives Pruritic erythematous wheals that occur on the skin often in response to an allergic trigger No associated scale overlying lesions More transient, last hours

78 Contact Dermatitis Prurutic eczematous condition Can be caused by irritant (direct toxic effect on skin) or allergen (delayed type hypersensitivity) Nickel and poison ivy are the prototypes Usually welldemarcated and localized to site of contact with antigen

79 Summary Good history Basic plan: Hydrocortisone 2.5% ointment face bid, Triamcinolone 0.1% ointment body bid, petroleum jelly bid entire face/body overtop Review bathing and importance of ongoing bid moisturizer If not helping: consider infection: do swabs, antibiotics, bleach baths night time antihistamine Spend time counselling parents, give written instructions, reinforcement is key Suggest derm referral when not responding to standard tx

80 Thank You