Pediatric Pearls: Part 2

Transcription

1 7/25/17 Pediatric Pearls: Part AAD Summer Mee7ng Karen A. Chernoff, M.D. Assistant Professor of Dermatology and Pediatrics Weill Cornell Medical College Objec7ves Apply current guidelines regarding treatment of pediatric atopic derma99s and acne to prac9ce Develop strategies for trea9ng severe and recalcitrant cases of eczema and acne Review safety and efficacy data regarding topical steroids, with emphasis on how to address parental concerns regarding their use Atopic Derma77s Case Scenario: You re seeing a 2- year- old boy with atopic derma99s as a new pa9ent Has had intermigent flares since infancy Parents tell you they ve seen 3 other doctors and they ve tried everything but nothing works Pearl #1: Define Everything Which potency of steroid used (if any)? Quan9ty of medica9on used? What does not working mean Fail to clear vs. recurrent disease Topical Steroid Potency Children oven given low potency topical cor9costeroids (TCs) due to concerns of skin atrophy and systemic absorp9on However, safety data for stronger TCs is reassuring with low rates of adverse events when used appropriately Supports more potent TC use for severe disease 1

2 2002 study assessing safety of medium- potency TC 32 pa9ents (3 months to 6 years old) Treated BID un9l clear up to 4 weeks Analyzed serum cor9sol levels, skin changes, adverse events No change in cor9sol levels Low post- s9mula9on cor9sol (CST) values aver treatment in 2/43 No clinical signs Reversible aver treatment Large amounts of flu9casone used (561g, 209g) 2 pa9ents with reversible facial telangiectasias 2006 RTC - safety of flu9casone lo9on 438 pa9ents with moderate to severe AD 50% <17 years; 6% <1 year of age Daily dosing up to 4 weeks No reports of skin changes Lab markers not reported Topical Steroid Dosing Even when topical steroids are used in children they are s9ll oven underdosed Important to prescribe an appropriate quan9ty of medica9on Educate parents regarding proper dosing and dura9on of treatment Finger7p Unit Dosing Maintenance Phase Important to discuss transi9oning from trea9ng flares to maintenance regimen Emollients alone not always sufficient Can add intermigent topical steroid or topical calcineurin inhibitor if eczema frequently recurs Dermatology 3 rd Edi9on

3 7/25/17 Evaluated safety of intermigent maintenance dosing 348 pa9ents (247 children) with eczema enrolled aver clearance with flu9casone cream Followed by 4x weekly dosing x 4 weeks à 2x weekly dosing x 20 weeks Evaluated for skin atrophy, drug- related adverse event No reports of skin thinning or atrophy One case of acne in an adolescent boy 2 cases of abnormal CSTs (one borderline) Improved control in treatment group Scenario 2: Control group relapsed in ~4.7 weeks Majority of treatment group had not yet relapsed at 20 week study end- point Pearl #2: Consider Allergies You ve done all of the above but the pa9ent s9ll has frequent flares requiring medica9on most days Contact Derma77s Most Common Allergens Allergen % Up to 40% of children with atopic derma99s will develop contact allergy Common allergens in AD: metals, fragrance, an9bio9cs, emollients Nickel 22 Fragrance 11 Cobalt 9 Balsam of Peru 8 Neomycin 7 Propylene glycol 7 Suspect if eczema refractory to treatment or unusual distribu9on Cocamidopropyl betaine Bacitracin Formaldehyde Gold Topical steroid allergy occurs less commonly Giordano- Labadie et al. Contact Derma,,s 1999 Goldenberg et al. Derma,,s 201 3

4 What About Food Allergies? Approximately 40% of infants and young children with moderate to severe AD will have a posi9ve food- specific IgE on tes9ng Most common: nuts, cow s milk, egg whites However, food- specific IgE measurements do not reliably predict clinical allergy When Should We Test for Food Allergy? Clinical signs of immediate allergic reac9on Ur9caria, anaphylaxis Young child with severe, recalcitrant eczema Final Pearl on Food Allergy Overavoidance of all poten,al allergens is not the answer Can lead to malnutri9on and unnecessary restric9ons Data suggests early exposure may induce tolerance Study showed early peanut exposure decreases risk of clinical allergy by 70-85% Recommends introduc9on at 4-11 months Highest risk infants (severe AD, egg allergy) should be evaluated by allergist first Du Toit G et al. N Engl J Med 2015 Pearl #3: Consider Infec7on Bacterial coloniza9on is extremely common in pa9ents with atopic derma99s Staph aureus carriage in 70-90% of lesional skin samples Toxin- producing strains in 30-70% AD pa9ents up to 20x more likely to have S. aureus coloniza9on than controls ToGe JEE et al. Br J Dermatol 2016 Williams MR et al. Curr Allergy Asthma Rep 2015 Randomized placebo- controlled study of children 6 months to 17 years of age with moderate to severe eczema and signs of bacterial infec9on All given cephalexin Interven9on group treated with bleach baths and intranasal mupirocin Control group given water baths, petrolatum Interven9on group had greater eczema improvement Huang JT et al. Pediatrics

5 Scenario 3: You ve done all of the above but the pa9ent s9ll has poorly controlled eczema AAD AD Treatment Guidelines Guidelines for systemic agents Phototherapy is a 2 nd line treatment Systemic immunomodulatory agents are indicated for pa9ents who fail to respond to op9mized topical regimens and/or phototherapy Cyclosporine, azathioprine, and methotrexate are recommended agents SYSTEMIC STEROIDS SHOULD BE AVOIDED IF POSSIBLE. THEIR USE SHOULD BE EXCLUSIVELY RESERVED FOR ACUTE, SEVERE EXACERBATIONS AND AS A SHORT- TERM BRIDGE THERAPY TO OTHER SYSTEMIC, STEROID- SPARING THERAPY. Adapted from: Eichenfield et al. J Am Acad Dermatol 2014 New Advances in Biologics: Dupilumab Human monoclonal IL- 4Rα an9body Blocks signaling of IL- 4 and IL- 13 (key Th2 cytokines) Currently FDA approved for adults only Study with children 6-17 years underway Early studies also show improvement in asthma, chronic sinusi9s Dupilumab Two randomized, placebo- controlled phase 3 trials 1,379 total pa9ents Dupilumab 300mg SQ weekly, every other week, placebo Significant improvement vs. placebo Most common adverse events were nasopharyngi9s, AD flare, injec9on site reac9on Serious treatment- related adverse events were rare and similar to placebo Simpson et al. N Eng J Med 2016 Acne Vulgaris Scenario 1 You re seeing a 6- year- old girl for new onset of acne Should you simply treat the child or evaluate for underlying abnormali9es? 5

6 Acne Considera7ons in Younger Kids Acne onset between 1-7 years may be marker of precocious puberty or hyperandrogen state PCOS, CAH, gonadal/adrenal tumor Malignant adrenocor9cal tumors rare % of pediatric neoplasms Associated signs: accelerated growth curve, body odor, pubic hair, enlarged genitalia Mid- Childhood Acne 2014 review of 24 pa9ents with pre- adolescent acne 12 mid- childhood onset 4 girls with premature adrenarche Acne onset 2-6 years All had other signs (breast development, height) No endocrinopathies but 1 with advanced bone age Caveat: premature adrenarche can be early sign of PCOS, metabolic syndrome Bree et al. Pediatr Dermatol 2014 Pearl #1: When to Worry about Acne History: Age of onset Body odor Menarche Abnormal History or PE: Refer to Peds Endo Adapted from Bree et al. Pediatr Dermatol 2014 Physical Exam: Axillary/pubic hair Breast development Escutcheon Normal History, PE, Growth Curve: Follow clinically >2 SD above norm: Refer to Peds Endo Growth Curve: Height Weight BMI Abnormal Growth Curve: check bone age Normal: Follow clinically Scenario 2 You have a 15- year- old girl with moderate inflammatory acne who has required mul9ple courses of doxycycline to remain under control, totaling > 1 year of use Pa9ent is happy with results and would like to remain on the medica9on indefinitely Systemic An7bio7cs in Acne Doxycycline = 1 st line Alterna9ves: minocycline, azithromycin, trimethoprim- sulfamethoxazole, cephalosporins Limit dura9on to reduce risk of bacterial resistance Re- evaluate pa9ents within 3-4 months to determine whether ongoing use is required 2016 ID guidelines: 3 months ideally and never as monotherapy Goal to transi9on to topical therapy or alterna9ve med Walsh et al. Lancet Infect Dis 2016 Transi7oning from Systemic An7bio7cs RCT showed topical tazarotene as effec9ve as minocycline for maintenance Pa9ents included aver successful treatment with minocycline and/or tazarotene Results at week 24: ~80% maintained >50% improvement ~50% maintained >75% improvement Leyden et al. Arch Dermatol

7 Hormonal Therapies: OCPs 4 combo estrogen + proges9n pills approved for acne Improve acne via an9androgenic proper9es Decrease ovarian androgen produc9on é sex hormone- binding globulin à ê free testosterone Consider pa9ent s risk factors in determining use Blood clots, hypertension, migraine with aura, tobacco use Endo eval prior if concern for underlying disorder Check BP, pregnancy test prior In teens, typically wait 2+ years aver menarche Hormonal Therapy: Spironolactone Aldosterone receptor antagonist Potent an9androgen ac9vity Decreases testosterone produc9on Compe99vely binds to androgen receptors in skin Use in acne not FDA- approved although numerous studies show efficacy and safety Dose range: mg (typically ~50-100mg daily) Hyperkalemia is a rare side effect in young women OVen used as combina9on therapy with OCPs Black box warning: tumorigenic effects in rats References Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology Third Edi,on. Elsevier Bree AF, Siegfried EC. Acne Vulgaris in Preadolescent Children: Recommenda9ons for Evalua9on. Pediatr Dermatol 2014;31: Du Toit G, Roberts G, Sayre PH et al. Randomized Trial of Peanut Consump9on in Infants at Risk for Peanut Allergy. N Engl J Med 2015;272: Eichenfield LF, Krakowski AC, PiggoG C et al. Evidence- Based Recommenda9ons for the Diagnosis and Treatment of Pediatric Acne. Pediatr 2013;131:S Eichenfield, LF, Miller BH. Two randomized, double- blind, placebo- controlled studies of flu9casone propionate lo9on 0.05% for the treatment of atopic derma99s from 3 months of age. J Am Acad Dermatol 2006;54: Friedlander SF, Hebert AA, Allen DB. Safety of flu9casone propionate cream 0.05% for the treatment of severe and extensive atopic derma99s in children as young as 3 months. J Am Acad Dermatol 2002;46: Giordano- Labadie F, Rance F, Pellegrin F, et al. Frequency of contact allergy in children with atopic derma99s: results of a prospec9ve study of 137 cases. Contact Derma,,s 1999;40: References Goldenberg A, Mousdicas N, Silverberg N, et al. Pediatric Contact Derma99s Registry Inaugural Case Data. Derma,,s 2016;27: Hanifin J, Gupta AK, Rajagopalan R. IntermiGent dosing of flu9casone propionate cream for reducing the risk of relapse in atopic derma99s pa9ents. Br J Dermatol 2002;147: Horimukai K, Morita K, Narita M et al. Applica9on of moisturizer to neonates prevents development of atopic derma99s. J Allergy Clin Immunol 2014;134: Huang JT, Abrams M, Tlougan B, Rademaker A, Paller AS. Treatment of Staphylococcus aureus Coloniza9on in Atopic Derma99s Decreases Disease Severity. Pediatrics 2009;123:e Simpson el, Bieber T, GuGman- Yassky E et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Derma99s. N Eng J Med 2016;375: ToGe JEE, van der Feltz WT, Hennekam M et al. Prevalence and odds of Staphylococcus aureus coloniza9on in atopic derma99s: a systemic review and meta- analysis. Br J Dermatol 2016;175: Vieira BL, Lim NR, Lohman ME, Lio PA. Complementary and Alterna9ve Medicine for Atopic Derma99s: An Evidence- Based Review. Am J Clin Dermatol 2016;17: Williams MR, Gallo RL. The Role of the Skin Microbiome in Atopic Derma99s. Curr Allergy Asthma Rep 2015;15:1-10. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2016;74: