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.

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. TOOLS
2 Olsen,E et al. 2004

3. SEVERITY OF ALOPECIA AREATA
3
S1 (0-24%) S2 (25-49%) S3 (50-74%) S4 (75-99%) S5 (100%)

4. DERMOSCOPY
4

5. OUTLINE
All treatment and management should be tailored
• Treatment:
Medications- Focus on systemic
Blood work/Labs
• Management:
Nutrition
Stigma/Education

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. MEDICAL MANAGEMENT OF ALOPECIA
AREATA IS USUALLY THE FIRST STOP

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. 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. 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
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. 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. 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. 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. 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. 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. 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. 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. 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

21. 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

22. 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.

23. 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

24. 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

26. WHY NOT TREAT EVERYONE WITH JAK
INHIBITORS?

27. 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

28. 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)

29. Are we using them in kids? Yes Off-label

30. EXPERIENCE IN ADOLESCENT PATIENTS
Castelo-Soccio, 2017 JAAD

31. 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%

32. 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

33. Castelo-Soccio, 2017 JAAD
Stopped medication

34. 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

35. 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.

36. 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

37. Do I use it?
• Yes in some patients
• Cost associated with use
• Sometimes just for eyebrows

38. 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

39. 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

40. Clinical trial ongoing
• Emma Gutman at Mount Sinai in collaboration with Rockefeller
University
• Still enrolling
• Clinicaltrials.gov

41. 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

42. Microbiome in Pediatric Alopecia Areata
42

43. Infant Gut Development: De novo assembly
of Complex Microbial Community

45. 45

47. • 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

48. 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

49. Can probiotics change this?
• Maybe but not clear which ones yet
• Safety is a concern with probiotics
• Probiotics make things worse?

50. 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)

51. DDo I recommend
PProbiotics?
• Not yet
• Need better guidelines for use
• Need more consistent probiotics
• Consider food as alternative

52. FFood Alternatives
• Kombucha, Yogurt, Kefir, Sauerkraut, tempeh, kimchi, miso, pickles,
traditional buttermilk, nato, some cheeses (cheddar, mozzarella,
gouda)

53. EMOTIONAL HEALTH/ STIGMA /EDUCATION

54. 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

55. 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

56. 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

57. 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

58. 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

59. RESOURCES
• NAAF has wonderful resources, books, guides for schools,
parents
• American Academy of Dermatology Kids Corner
• Local and national support groups
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60. BOOKS

61. 61