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Pediatric Alopecia Areata: What's New in Management, Treatment and Education

Dr. Leslie Castelo-Soccio presented an overview of what parents need to know about alopecia areata in children and adolescents, including the differences between pediatric and adult patients, and the risks and benefits of current and evolving off-label treatment options. Dr. Castelo-Soccio is Assistant Professor of Pediatrics and Dermatology at the University of Pennsylvania School of Medicine and head of the Pediatric Hair Clinic and Director of Research in Pediatric Dermatology at the Children’s Hospital of Philadelphia. Her clinical and academic research focus is on pediatric hair disorders.

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Pediatric Alopecia Areata: What's New in Management, Treatment and Education

  1. 1. PEDIATRIC ALOPECIA AREATA: WHAT IS NEW IN MANAGEMENT, TREATMENT AND EDUCATION Leslie Castelo-Soccio, MD, PhD Assistant Professor of Pediatrics and Dermatology University of Pennsylvania School of Medicine
  2. 2. TOOLS 2 Olsen,E et al. 2004
  3. 3. SEVERITY OF ALOPECIA AREATA 3 S1 (0-24%) S2 (25-49%) S3 (50-74%) S4 (75-99%) S5 (100%)
  4. 4. DERMOSCOPY 4
  5. 5. OUTLINE All treatment and management should be tailored • Treatment: Medications- Focus on systemic Blood work/Labs • Management: Nutrition Stigma/Education
  6. 6. THERE IS NO ONE SIZE FITS ALL • Age of the patient • Duration of hair loss • “Activity” of the alopecia • Impact of alopecia on child and family • Characteristics of the child (what they can tolerate, length of hair, texture of hair, whether they wear a wig or not etc…..) 6
  7. 7. MEDICAL MANAGEMENT OF ALOPECIA AREATA IS USUALLY THE FIRST STOP
  8. 8. OUTLINE Managing alopecia with topical and systemic therapy • Steroids (topical, oral and intralesional) • Other non steroidal modalities • Newer/off label therapies: JAK inhibitors- Systemic and Topical Tofacitinib in children 8
  9. 9. TOPICAL STEROIDS ARE FIRST LINE IN KIDS • Goal: block the immune system attack • Painless • Simple to apply • Few side effects • Most children need mid to strong topicals to be effective • Come in liquids, foams, creams, ointments • Best if you have <50% hair loss • Can be used on and off with new flares 9 Tosti, JAAD 2003; Lenane JAMA Derm 2014
  10. 10. INTRALESIONAL STEROIDS/KENALOG • Evidence for efficacy • For younger children can be traumatic (<12 yrs) • For those that can tolerate: EMLA, Cooling sprays, Ice, Buzzy, squeeze balls, other distractors • Kids more likely to get atrophy of skin • Not worth doing if you cannot get ideal number of injections done
  11. 11. 11 SYSTEMIC CORTICOSTEROIDS- CONTROVERSIAL 1. Smith et al. 2015: Methylpred 2. Jahn-Bassler, K, 2017: High dose low dose 3. Yoshimasu, 2016: Methyl pred 4. Castelo-Soccio et al. Unpublished CHOP: Oral taper high to low
  12. 12. HIGH RELAPSE RATES DESPITE EARLY INTERVENTION WITH INTRAVENOUS METHYLPREDNISOLONE PULSE THERAPY-SEVERE CHILDHOOD ALOPECIA AREATA Pediatric Dermatology Volume 32, Issue 4, pages 481-487, 15 APR 2015 DOI: 10.1111/pde.12578 http://onlinelibrary.wiley.com/doi/10.1111/pde.12578/full#pde12578-fig-0002
  13. 13. JAHN-BASSLER, K, 2017- HIGH DOSE LOW DOSE • 13 children • SALT >60 • 2mg/kg po initial pulse then tapered by 9 weeks to lower dose • Maintained steroids at sub-cushingoid threshold and followed 1-3 years • 62% complete growth by 6.6 weeks • >50% maintained for f/u period
  14. 14. SEQUENTIAL HIGH AND LOW DOSE SYSTEMIC CORTICOSTEROID THERAPY FOR SEVERE CHILDHOOD ALOPECIA AREATA JDDG: Journal der Deutschen Dermatologischen Gesellschaft Volume 15, Issue 1, pages 42-47, 31 JAN 2017 DOI: 10.1111/ddg.12875 http://onlinelibrary.wiley.com/doi/10.1111/ddg.12875/full#ddg12875-fig-0002
  15. 15. YOSHIMASU, 2016- METHYLPRED • 55 pts (mix of children and adults) • methylprednisone 500mg/day for 3 days • followed for 6 months from last pulse • SALT <50 100% response rate • Those with good response with half relapsing after 6 months
  16. 16. CHOP EXPERIENCE- UNPUBLISHED • 120 pts AA, AT or AU • 3 weeks of oral prednisone/prednisolone 1mg/kg/day week 1 tapered to 0.5mg/kg/day week 2 and then 0.25mg/kg/day week 3 • Average number of courses 2, spaced 8-12 weeks apart • 63% showed improvement • 59% relapsed after 12 months (Higher relapse with more severe alopecia) • No serious adverse effects including weight gain noted 16
  17. 17. TTake Home 1.Systemic Steroids can lead to remission for 8 months to sometimes longer 2.Relapse does occur for most after cessation of therapy especially for most severe
  18. 18. OFF LABEL USE OF MEDICATIONS IN CHILDREN: METHOTREXATE • Methotrexate is an immunosuppressant • Small studies looking at efficacy in Alopecia • Some suggest modest response and durable response for few • Used for many years in children for other diseases • Side effects well known 18
  19. 19. EEfficacy and Safety of MMethotrexate iin Combination wwith Mini Pulse Doses of Methylprednisolone in Severe Alopecia Areata. The Vietnamese Experience • 38 patients (16-64) • severity of AA (SALT >50%) • methylprednisolone 24mg/day for 3 days of a week in combination with oral methotrexate 7.5mg weekly for 12 weeks then followed for 12 weeks Open Access Maced J Med Sci. 2019 7(2):200-203
  20. 20. MMethotrexate ffor the treatment of ppediatric alopecia areata. • 14 patients • 8/14 (57%) good regrowth • No long term follow-up J Dermatolog Treat. 2018 Mar;29(2):145-148
  21. 21. MMethotrexate in Severe Childhood Alopecia Areata: LLong-term Follow-up • 13 evaluable children with >50% hair loss • 5/13 MTX was associated with hair regrowth • Followed children after treatment • In 2 of these patients no relapse occurred after stopping MTX; follow- up after last MTX dose was conducted at 6 and 4.3 years, respectively. • In the 3 remaining patients, no sustained hair regrowth was observed, even though 2 of them were successfully treated again with MTX Acta Derm Venereol. 2016 Jan;96(1):102-3.
  22. 22. Do I use? • Yes • CHOP experience has been good. About to publish study looking about our patients • Average time on methotrexate 12-18 months • Is response durable? No but sometimes improvement for 9-12 months after therapy
  23. 23. Off label Use of Medications in Children: JAK inhibitors • Tofacitinib, ruxolitinib and baricitinib • 30 studies and 289 cases, there were 72.4% responders, good responders 45.7% and partial responders 21.4% • All 37 recurrences occurred 2.7 months after stopping • Oral route better than topical therapy. • No difference between pediatric and adult cases in proportion of responses. 24J Eur Acad Dermatol Venereol. 2019 May;33(5):850-856
  24. 24. WHY NOT TREAT EVERYONE WITH JAK INHIBITORS?
  25. 25. Risks of JAK inhibitors • 1.5- to 2-fold higher risk of infection requiring hospitalization or serious infection than the general population • Increase risk for Herpes Virus • Increase risk for tuberculosis • Increase risk for Malignancy including Non-melanoma skin cancer • Increase risk for lymphoma • Increase risk for DVTs/PE
  26. 26. Recent FDA warning • FDA warns that treatment with the Janus kinase inhibitor tofacitinib at a dose of 10 mg twice daily is associated with an increased risk for pulmonary embolism and death in patients with rheumatoid arthritis (RA)
  27. 27. Are we using them in kids? Yes Off-label
  28. 28. EXPERIENCE IN ADOLESCENT PATIENTS Castelo-Soccio, 2017 JAAD
  29. 29. EXPERIENCE IN 13 ADOLESCENTS Craiglow et. al, 2017 JAAD 0 months 2 months 5 months • 10/13 regrowth • 1 responder regrowth then patchy Increased dose and regrowth again • Mean change in SALT score 61%
  30. 30. RELAPSE AFTER CESSATION • Within 3 months of discontinuation of oral JAKs loss • Need long-term safety data Kennedy Crispin M, Ko JM, Craiglow BG, et al. 2016 Mackay-Wiggan J, Jabbari A, Nguyen N, et al. 2016 Liu LY et al. J Investig Dermatol Symp Proc. 2018
  31. 31. Castelo-Soccio, 2017 JAAD Stopped medication
  32. 32. TAKE HOME • Off label use of medication • We do not know long term safety risks • Labs monitoring cbc, cmp, lipid, quantiferon gold at baseline, 6 weeks and then every 4-6 months afterward • Hard to get due to insurance and costs Should we be considering them in kids during first 10 years of alopecia? • Adults with hair loss >10 years less likely to respond • ?Merit to pursuing treatment, even if only intermittently, in adolescents or even younger patients with stable, severe alopecia areata
  33. 33. TOPICAL THERAPY • Tofacitinib 2% compounded cream • Daily or twice daily • Out of pocket, off-label • ~$330 for 30gram • Ruxolitinib 0.6% to 1% • Daily or twice daily • 30 gram tube for $1,500 Craiglow BG, Tavares D, King BA. Topical Ruxolitinib for the Treatment of Alopecia Universalis. JAMA Dermatol. Published online December 09, 2015. doi:10.1001/jamadermatol.2015.4445.
  34. 34. TOPICAL THERAPY Bayart et. Al., 2017 JAAD 6 patients Ages 3,4,5, 13,15,17 4 with AU 1 AT 1 AA 2% tofacitinib 2% Ruxolitinib 1% Ruxolitinib Better in liposomal base Clinical trials underway
  35. 35. Do I use it? • Yes in some patients • Cost associated with use • Sometimes just for eyebrows
  36. 36. Take Home • Corticosteroids still first line in most children • Systemic steroids consider for some during acute flares • Systemic steroids not a long term solution • Topical JAK inhibitors for some but risks and we need long term use data
  37. 37. OOFF Label Use of Medications: Dupilimab • Monoclonal antibody • Approved in 2017 as the first biologic for atopic dermatitis • Approval for children >12 March 2019 • Positive effects on alopecia areata reported in patients who had before start of treatment • Some reports of new AA with therapy 39
  38. 38. Clinical trial ongoing • Emma Gutman at Mount Sinai in collaboration with Rockefeller University • Still enrolling • Clinicaltrials.gov
  39. 39. Am I using? • Yes since approval for atopic dermatitis in children >12 years of age in March • An get this covered if child also has severe eczema • Most common side effect is conjunctivitis • Injection every 2 weeks
  40. 40. Microbiome in Pediatric Alopecia Areata 42
  41. 41. Infant Gut Development: De novo assembly of Complex Microbial Community
  42. 42. 45
  43. 43. • AA subjects were 40.3 ± 14.7 years old, female (72%) and identified as Caucasian (60%) • Differences in scalp and gut microbiome noted with decreased Bacteroides and increased Firmicutes in Adults
  44. 44. Microbiome in Pediatric Alopecia Areata • Changes in gut bacteria (dysbiosis) and inflammation of the gut may be a trigger for AA 1) Need to approach this systematically by looking at the differences in gut flora between children with AA and those without AA 2) Second need to integrate metabolomics data with metagenomics data derived from gut microbiota to understand microbial functions 100 pairs of siblings one with AA and one without to compare microbiome coming very soon 48
  45. 45. Can probiotics change this? • Maybe but not clear which ones yet • Safety is a concern with probiotics • Probiotics make things worse?
  46. 46. What has been reported recently • INCREASED MORTALITY Probiotics in Pancreatitis Trial (PROPATRIA)- prophylactic clinical trial for acute pancreatitis showed large number of deaths in probiotic (multi-strain) group 16% versus 6% (154 subjects) • INCREASED ASTHMA AD New Zealand: Increased risk of asthma like symptoms in relation to supplementation with L. acidophilus at age 6–12 months but slight protective effect on asthma symptoms at 4 years and 6 years • POOR RESPONSE TO IMMUNOTHERAPY Melanoma patients using over-the-counter probiotic supplements associated with a 70 percent lower chance of response to cancer immunotherapy treatment with anti-PD-1 checkpoint inhibitors (AACR 2019 meeting)
  47. 47. DDo I recommend PProbiotics? • Not yet • Need better guidelines for use • Need more consistent probiotics • Consider food as alternative
  48. 48. FFood Alternatives • Kombucha, Yogurt, Kefir, Sauerkraut, tempeh, kimchi, miso, pickles, traditional buttermilk, nato, some cheeses (cheddar, mozzarella, gouda)
  49. 49. EMOTIONAL HEALTH/ STIGMA /EDUCATION
  50. 50. ALL THERAPY MUST INCLUDE EMOTIONAL HEALTH • Even if medical therapy is stopped/not initiated, children should still have check ups for their emotional well being • Emotional Health is fluid (Someone who is adjusting well at one point may need more support at another time) 54
  51. 51. KEYS TO EMOTIONAL HEALTH • Realistic hope and honesty • Recognizing when therapy has failed and when to move on or stop therapy • Providing a safe forum to discuss the anxieties, uncertainties and fears, losses and sadness • Some kids feel guilty when they had been praised for adjusting so well and then they do not feel great about their hair loss 55
  52. 52. FAMILY CENTERED CARE • Continue to plan for what is ahead- new schools, new clubs, new friends and sports. This diagnosis can’t stop this process • Help kids contribute to someone or something outside of themselves • Be positive and realistic at the same time. Allow expressions of frustration for yourself and the child
  53. 53. STIGMA OF PEDIATRIC SKIN DISEASE Stigma, Anxiety and Depression in Children and Adolescents with Skin Disorders – The “Big Study” • Assesses anxiety, depression, and social functional issues in addition to stigma in children with skin diseases. • 1000 pairs of children and parents 57
  54. 54. TEACHING MEDICAL DIFFERENCES IN DIVERSITY, INCLUSION AND EQUITY EDUCATION • Schools must prioritize efforts to promote medical diversity within their school culture and within the classroom. • Pilot project: Lesson Plan for pre-K-1st graders to teach about skin differences including AA • Plan to expand to a curriculum for older children with access for teachers across the country • Read along with book “Henry wears a hat” • Measure differences using a doll study before and after lesson 58
  55. 55. RESOURCES • NAAF has wonderful resources, books, guides for schools, parents • American Academy of Dermatology Kids Corner • Local and national support groups 59
  56. 56. BOOKS
  57. 57. 61
  • PujaRaj11

    Dec. 5, 2020
  • KavitaGajria

    Jan. 2, 2020
  • CkGo1

    Nov. 13, 2019
  • NURATIKAHADAM

    Oct. 4, 2019

Dr. Leslie Castelo-Soccio presented an overview of what parents need to know about alopecia areata in children and adolescents, including the differences between pediatric and adult patients, and the risks and benefits of current and evolving off-label treatment options. Dr. Castelo-Soccio is Assistant Professor of Pediatrics and Dermatology at the University of Pennsylvania School of Medicine and head of the Pediatric Hair Clinic and Director of Research in Pediatric Dermatology at the Children’s Hospital of Philadelphia. Her clinical and academic research focus is on pediatric hair disorders.

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