Dr. Maria Hordinsky provides an informative, straightforward presentation of everything you need to know about alopecia areata, including risks and benefits of current and evolving off-label treatment options. Dr. Hordinsky is Professor and Chair of the Department of Dermatology at the University of Minnesota and is recognized for her clinical expertise in alopecia areata.

1. Everything You Need to Know About
Alopecia Areata
Maria Hordinsky, MD
Professor and Chair
Department of Dermatology
University of Minnesota
Minneapolis, Minnesota

2. Alopecia Areata:
Pediatric
Alopecia
Areata
Affecting
the Scalp

3. Adult
Alopecia
Areata
Affecting
the Scalp

4. Focal Patchy Alopecia Areata

5. Brittle, Fragile Nails

7. Inheritance of Alopecia Areata
• A multifactorial condition
Source: Greenwood Genetics Center

8. EPIDEMIOLOGY OF ALOPECIA AREATA
• Affects 1.7-2.1% of the population
• 50-80% of cases are sporadic
• Disease associations may vary around the world
and include vitiligo, thyroid disease, atopy
(allergic rhinitis, asthma, atopic dermatitis)
• Both males and females of all ages and races can
be affected

9. NORMAL HAIR CYCLE
• Anagen –90% of follicles -lasts 2-7 years
• Catagen – 1-2% of follicles – lasts 2-3 weeks
• Telogen – Up to 10% of follicles – lasts 2-3 months

10. Normal
Scalp:
Vertical
Section

11. IMMUNOLOGY
A hallmark of
alopecia areata:
–peribulbar
lymphocytes
around anagen
follicles

12. Histopathology:
Normal Human Scalp: Horizontal Section

13. A17 02-0573 L

14. Alopecia
Areata
Anagen
Attack
↓
Anagen
Arrest !

15. DERMOSCOPY OF ALOPECIA AREATA
Yellow Dots, Typical of Alopecia Areata, with
exclamation mark hairs

17. Pathophysiology of Alopecia Areata
• AA is associated with the loss of immune
privilege.
• Recent work in mouse model systems shows that
cytotoxic CD8+NKG2D+ T cells are both necessary
and sufficient for the induction of AA.
• Multiple lines of evidence suggest that there are
shared genetic risk factors between AA and other
autoimmune diseases such as rheumatoid
arthritis and type I diabetes.

18. History:
Questions That May be Asked
– Hair care habits
– Medications
– Symptoms – pain, itch, burning, other
– Body hair – is there too much or too little?
– Nail abnormalities
– Menstrual cycle/Pregnancies
– Diet/Supplements
– Family History
– Questions about androgen excess,
autoimmune/endocrine diseases

19. Clinical Examination
SCALP
• Presence and extent of vellus, indeterminate and
terminal fibers may be assessed.
• Presence or absence of scale, erythema
(redness) follicultis, atrophy.
BODY
• Extent of eyebrow, eyelash or body hair loss may
be documented.
NAILS
• Findings such as dystrophy, pitting, etc.

20. Laboratory Tests
• Thyroid Function Studies
• Heme and Iron Profiles including serum
ferritin and hemoglobin
• If indicated,
– Non cycle dependent hormones such as DHEA-S
and total/free testosterone
– ANA or other autoantibodies
– “Nutrition Labs” including Vitamin D, Thiamine,
Zinc, total protein, other

21. CURRENT TREATMENTS OF
ALOPECIA AREATA (AA)
• Patient/family goals
• Clinical Examination

22. In the absence of an approved
treatment by the Federal Drug Administration,
choosing a treatment for AA in children and adults
takes into consideration several factors including:
• age of the patient
• location of the loss
• disease extent
• disease activity
• presence of other medical problems
• scalp biopsy report on the hair cycle, inflammation
• patient/parent choice after a review of proposed
treatment risks, benefits and expectations.

23. What Treatment?

24. What Treatment?

25. What
Treatment
Now?

26. Alopecia Areata:
an Autoimmune Disease
Patients and family members need to be
educated and reminded that this autoimmune
disease may recur and if this happens, disease
extent is unpredictable and our most used tool
to halt disease activity at this time is the use of
topical, intralesional, oral or even intravenous
corticosteroids.

27. The Clinic Visit in 2017 - the
Treatment Discussion
A number of treatments can induce hair growth
in AA but few have been tested in randomized
controlled trials and there are few published
data on long-term outcomes; most focus on hair
regrowth.

28. The Clinic Visit in 2017 - the
Treatment Discussion
• Patients and families have heard the “buzz” about
potential new treatment for alopecia areata and the
discussion needs to include a conversation about
ongoing and future clinical research opportunities
as well as off label use of Janus kinase inhibitors
and in particular oral tofacitinib.
• Patients and some physicians are eager to try this
off label therapy with the support of industry
patient assistance programs or in some cases,
insurance coverage.

29. The Clinic Visit in 2017 - the
Treatment Discussion
• In contrast, there are patients with long
standing recalcitrant extensive AA who have
tried and failed treatments or have elected
not to treat their AA who view the emerging
treatments and opportunities for clinical trial
participation with interest and hope.
• Such patients frequently make clinic visits to
catch up on the latest information and many
but not all are eager to join in clinical research
activities.

30. Randomized Controlled Trials in
Alopecia Areata
We analyzed in PubMed
“randomized controlled trials”
“alopecia areata”
and assessed the quality of the studies.
Hordinsky M, Donati A. Alopecia areata: an
evidence-based treatment update. Am J Clin
Dermatol. 15:231-245, 2014.

31. Randomized Controlled Trials in AA
We found 29 trials that examined the efficacy of the
following:
• Anthralin
• Antidepressants
• Biologics
• Calcineurin inhibitors,
• Corticosteroids (topical and systemic)
• Minoxidil
• Prostaglandin analogs
• Sensitizers
• Miscellaneous: topical and oral drugs including aromatherapy,
photodynamic therapy, azelaic acid, garlic gel, bexarotene,
triiodothyronine, inosiplex, and total glucosides of paeony.

32. Results and Conclusions
• Using the American College of Physicians Guideline
grading system, our assessment was that the majority
of these studies were only of moderate quality.
• At the same time, a number of treatments were
found to be effective, for example, topical and oral
corticosteroids and the sensitizing agents
diphenylcyclopropenone and dinitrochlorobenzene.
• Most studies though had major limitations that
hindered the interpretation of study results.

33. Alopecia Areata:
Patchy Alopecia Areata

34. PATCHY ALOPECIA AREATA:
TREATMENTS
• Topical or Intralesional
Corticosteroids
• Minoxidil Solution- 2% or 5%
• Anthralin
• Combination Therapy
• Steroids in Shampoo Formulations
• Topical Immunotherapy

35. Intralesional Kenalog
• Local injection of corticosteroids such as
triamcinolone acetonide (Kenalog) into lesions of
patchy AA has been a preferred treatment since
the late 1950s and is considered standard of care.
• Side effects tend to be local with a potential for
adrenal suppression.

37. Topical Immunotherapy
• Topical immunotherapy has long been another
accepted therapy for alopecia areata and
application in particular of diphenylcyclopropenone
(DPCP) is recommended throughout the world.

38. Topical Immunotherapy
• Until recently physicians/health care providers in the
United States were able to buy compounds like DPCP from
a chemical store house in order to prepare the desired
dilutions for sensitization purposes; this is not always the
case currently.
• Even though DPCP is not specifically banned by the Food
and Drug Administration, due to other aspects of increasing
regulatory oversight, this approach may now be more
difficult to implement in some large health care systems.

39. Extensive
Alopecia
Areata

40. • Corticosteroids:
– Topical
– Intralesional
– Pulsed methlypredisolone
– Oral
• Topical minoxidil
• Topical immunotherapy
– DPCP
– SADBE
• Dithranol
• Phototherapy
– PDT
– PUVA
– NBUVB
• Laser therapy - Excimer laser/Fractional
Photothermolysis Laser
• Immunosuppresive agents
– Methotrexate
– Cyclosporine
• Prostaglandin analogues
• Biologics
Treatments

41. • Corticosteroids:
– Topical
– Intralesional
– Pulsed high dose systemic
– Daily oral systemic
• Topical minoxidil
• Topical immunotherapy
– DPCP
– SADBE
• Dithranol
• Phototherapy
– PUVA
– NBUVB
• Laser therapy
• Immunosuppresive agents (steroid sparing)
– Methotrexate
– Cyclosporine
• Prostaglandin analogues
• Biologics
Treatments: Literature Review

42. – Lenane et al. recently demonstrated that higher
potency topical steroids might be most beneficial for
pediatric AA patients.
– Comparing clobetasol propionate 0.05% cream and
hydrocortisone 1% cream in 42 patients, the
investigators found the clobetasol group had a
statistically significant greater amount of regrowth
after 24 weeks.
– A 2004 case series also showed better responses to
high potency steroids. Of 4 patients, 2 were treated
with clobetasol and both had complete resolution
after about 9 months.
Evidence for children

43. • Often first line for limited, patchy AA
• Used in addition to other treatments for
extensive AA
• Despite widespread use, there isn’t much data in
kids
Lenane P, Macarthur C, Parkin PC, Krafchik B, Degroot J, Khambalia A, Pope E.
Clobetasol Propionate, 0.05%, vs Hydrocortisone, 1%, for Alopecia Areata in
Children: A Randomized Clinical Trial. JAMA Dermatol. 2014 Jan 1;150(1):47-50.
doi: 10.1001/jamadermatol.2013.5764.
• Tan E, Tay YK, Giam YC. A clinical study of childhood alopecia areata in
Singapore. Pediatr Dermatol. 2002 Jul-Aug;19(4):298-301.
Key points

44. • Use is more limited in children because
of fear of injections and pain
• To decrease pain, topical anesthetics can
be used
Intralesional corticosteroids

45. • Limited use in kids because of side effects
• No good studies in kids
• Reserved by many for rapid onset or rapidly
progressive, extensive AA
Oral Corticosteroids: Key points

46. • May be useful in acute crises of hair loss
• High relapse rate
• Must monitor carefully
Hubiche T, Léauté-Labrèze C, Taïeb A, Boralevi F. Poor long term outcome of
severe alopecia areata in children treated with high dose pulse corticosteroid
therapy. Br J Dermatol. 2008 May;158(5):1136-7. doi: 10.1111/j.1365-
2133.2008.08458.x.
Sharma VK, Muralidhar S. Treatment of widespread alopecia areata in young
patients with monthly oral corticosteroid pulse. Pediatr Dermatol. 1998 Jul-
Aug;15(4):313-7.
Kiesch N, Stene JJ, Goens J, Vanhooteghem O, Song M. Pulse steroid therapy for
children's severe alopecia areata? Dermatology. 1997;194(4):395-7.
Key points

47. • 2012 chart review of DPCP:
– 41/108 (38%) showed improvement after 6 months
– Response down to 32% responders after 12 months
– Only 11% had complete regrowth
• 2002 chart review of SADBE:
– 40/54 (74%) patients had >50% regrowth after 6 months
• 1996 trial of DPCP (started treatment on half of scalp; if
response, then treated whole scalp)
– 8/25 (32%) patients had cosmetically acceptable growth after 12
months
– No follow up data
• 1996 trial of 33 children treated with SADBE:
– 10/33 (30%) responded after 12 months
– At follow up (mean 5.9 years), 7/10 responders now had
relapses not responsive to further treatment
– Only 9% had persistent benefit
Topical immunotherapy
DPCP, SADBE: Evidence for children

48. • Used in chronic and extensive AA
• Effective in short term but high relapse rate
• May be more difficult for children to tolerate
• Requires frequent visits
• Problem with allergic contact dermatitis
Key points

49. • Last but not least, the treatment of the
patient with AA should also include:
– an awareness and discussion of the psychosocial
impact of this disease on the patient, family
members and significant others. .

50. • Crucial to assess child’s psychosocial well-
being; issues like self-confidence, self-image,
and acceptance by peers
• Parental anxiety, frustration, guilt and
expectations must also be proactively
managed
• No treatment may be an option in some cases
Holistic management of pediatric
AA patients

51. At the present time…
• Most physicians generally prefer topical therapy for
AA.
• However, following the recently published studies
in which the systemic Janus kinase family protein
tyrosine kinase inhibitors were shown to reverse
the AA process for patients treated with Tofacitinib
or Ruxolitinib, there has been a surge of
enthusiasm for using more aggressive systemic
therapies including not only Tofacitinib and
Ruxolitinib but also methotrexate and interleukin-
2.

52. November 14-15, 2016, Alopecia Areata Summit, New York City
Building and Crossing the Translational Bridge
Angela Christiano: Update on Genetics and Immunology
• GWAS studies have provided at least 14 genes involved
in AA.
• Immunological studies have focused on the role of CD8+
T cells in mediating disease, and the use of JAK inhibitors
to prevent and treat AA in the C3H/H3J mouse model.
• These preclinical studies paved the way for early clinical
investigation in patients, which has been done in several
centers to date.
• Gene expression studies have uncovered biomarker
signatures that can be used to follow response to
treatment. 52

53. Success Stories:
Lessons from Clinical Studies with JAK Inhibitors
532016 AA Research Summit
Dr. Julian Mackay-Wiggan: Update on Clinical Research in AA,
Columbia University
Ruxolitinib study – 12 patients, 20mg BID. Regrowth as early as 4 weeks. 9 of 12 had
50% regrowth.8 of 9 achieved their endpoint by week 12 (75% response rate).
Tofacitinib study – 12 patients 5mg BID up to 10mg BID. Followed for 6 months. 7 of 12
had 50% regrowth. 6 of 7 responders needed dose escalation (approx. 65% response
rate). Relapse 4-8 weeks after stopping.
Dr. Wilma Bergfeld, MD: Cleveland Clinic AA Tofacitinib Results
Open retrospective study. Moderate to severe, recalcitrant patients, some with RA
and AA. Thirteen patients, all recalcitrant to other therapies. Average regrowth at 4
months, some as late as 9 months. Some on drug for 18 months. One AU patient was
African American, regrew his eyebrows and lashes but not scalp and not body hair.
Three patients had total regrowth. One was duration of 30 yrs. Response rate =
approx. 54%.

54. Dr. Justin Ko: Oral Tofacitinib in Severe AA – Stanford/Yale
Study
All patients on 5mg BID and for 3 months duration only. Enrolled 70 patients – 66
finished study. Long durations 1-43 years; average 5 years duration. ¾ were AU/AT
patients. Biomarker analysis using gene expression studies. Outside the study –
treating approx. 80 patients. About 2/3 of patients grow clinically acceptable patients
at 6 months or longer. Roughly 66% overall response rate.
Dr. Brett King: Yale Study of Tofacitinib in AA in Adults and
Adolescents
Approx. 90 adult patients treated and 13 adolescents with tofacitinb alone or
tofacitinb with pulse steroid. Overall response rate approx. 60% in adults, 75% in
teenagers. Patients with disease duration less than 11 years have better responses.
Relapses seen while on treatment, and after drug stopped. Topical studies treating
one patient with compounded ruxolitinib, regrew brows. Three compounded
tofacitinib formulations, no positive results.

55. • Multiple treatments available but most
studies have been completed in adults.
• More research needs to be done for pediatric
AA (both on novel new treatments and
established adult treatments) with detailed
outcome measurements along with follow up
data.
CONCLUSIONS

56. CONCLUSIONS
• Until clinical research studies are completed, there
will be ongoing debate regarding the risks and
benefits, cost, and sustainability of the new
approach with Jak kinase inhibitors or other new
approaches as with IL-2 in the treatment of AA.
• This is particularly true in the case of children with
alopecia areata.