FRONTAL FIBROSING ALOPECIA

South Eastern Consortium

Durham, North Carolina

JERRY SHAPIRO, MD, FAAD

PROFESSOR

DIRECTOR

DISORDERS OF HAIR

AND SCALP

The Ronald O. Perelman Department of Dermatology

Disclosures

• Consultant/Investigator for:

• Aclaris

• Samumed

• Incyte

• Applied Biology

• Biologics MD

• Replicel Life Sciences Inc.

• RegenLab

• Bioniz

• Cassiopea

• Non approved uses of Naltrexone and Pioglitazone2

MY MEDICAL PRACTICE

• Unique in that my practice is restricted to only disorders of the

scalp and hair

• 1 hour per patient

• Patient ends the consultation, not I

• 35% alopecia areata

• 30% cicatricial alopecia

• 35% pattern hair loss and telogen effluvium

My clinic epidemiology on alopecia types

4

Androgenetic alopecia 33% (66)Frontal fibrosing alopecia 23% (46)Alopecia areata 16.5% (33)Acute telogen effluvium 9.5% (19)Lichen planopilaris 10% (20)

Central centrifugal cicatricial alopecia 4.5% (9)Lichen simplex chronicus 1.5% (3)Chronic telogen effluvium 1.5% (3)Folliculitis decalvans 0.5% (1)

Bolduc C. Sperling,

L.

Shapiro J

Clinical Indications for treatment

Activity

• Hyperkeratosis

• Erythema

• Pull test positive

• Symptomatic (itch, burn and pain)

6

Fotofinder: quantification and quality assessment

7

Fotofinder: quantification and quality assessment

8

Frontal Fibrosing Alopecia (FFA): overview

• Typically occurs on the frontotemporal region of the scalp, but

upper periauricular and occipital localization are not uncommon

• The band of alopecia is often readily distinguishable from the sun

damaged skin of the forehead

• Most common in postmenopausal women, but 15% of cases

occur in younger; may occur in men

• Usually presents in patients who are between 55 and 65 years of

age

9

Frontal Fibrosing Alopecia (FFA): clinical manifestations

• Loss of the eyebrows

• Facial papules reflect vellus hair

involvement

• Frontal recession can be

measured by the distance

between the glabella and frontal

hairline

10

FACIAL PAPULES OF FFA

Scarring Alopecias

16

• Lichen Planopilaris and FFA

17

Frontal Fibrosing Alopecia (FFA)

19

Patient Demographics

20

Total: 92

Women: 90

Men: 2

Eyebrow involvement: 96%

Symptoms: 14%

Autoimmune disease: 11%

21

Photos for FFA

22

How do I measure?

FFAGlabella to hair line

Right and left outer canthi to

hair line

Sides to hair line

23

24

Glabella to

hairlineRight outer

canthus to

hairline

Left outer

canthus to

hairline

SideburnsSideburns

25

Frontal Fibrosing Alopecia (FFA)

• TOPICAL/INTRALESIONAL

Treament:

• Corticosteroids: reduce pruritus

• Calcineurin inhibitors:

• Minoxidil

• Intralesional Corticosteroid:

Kenalog 2.5mg/cc, 3cc

26

CT M

Frontal Fibrosing AlopeciaIntralesional triamcinolone acetonide2.5 mgs/cc X 3cc ear to ear

27

Lichen Planopilaris (LPP)

28

JDD

November 2017 1140 VOLUME 16 • ISSUE 11

Copyright © 2017ORIGINAL ARTICLE

Journal of Drugs in Dermatology

Novel Treatment Using Low-Dose Naltrexone for

Lichen Planopilaris

Lauren C. Strazzulla BA, Lorena Avila MD, Kristen Lo Sicco MD, Jerry

Shapiro MD

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York,

NY

ABSTRACT

Lichen planopilaris (LPP) is a variant of lichen planus that affects the scalp causing scarring hair loss.

Patients also frequently experience symptoms of scalp itch, pain, and burning. To date, there are no long-

term remittive nor curative therapies available. Low-dose naltrexone has anti-inflammatory properties and

has recently been described in the context of treating autoimmune conditions. This retrospective medical

record review describes four LPP patients treated with low-dose (3 milligrams per day) naltrexone. This

medication provided benefit in these four patients including reduction in symptoms of pruritus, clinical

evidence of inflammation of the scalp, and disease progression. All patients tolerated naltrexone without

adverse effects. This is the first case series demonstrating the beneficial effects of low-dose naltrexone for

patients with LPP. This medication was well-tolerated by the patients and is cost-effective.

J Drugs Dermatol. 2017;16(11):1140-1142.

INTRODUCTION

Lichen planopilaris (LPP), a variant of lichen planus, causes an inflammatory, cicatricial alopecia; the

hallmarks of this disease include irregular patchy hair loss, destruction of follicular ostia, perifollicular

erythema, and scaling. LPP includes three distinct clinical variants: classic LPP, frontal - brosing alopecia

(FFA) and Graham-Little syndrome. Patients may experience intensely symptomatic affected areas with

severe pruritus, scalp pain and tenderness as well as burning sensations.1

The goals of therapeutic

treatment regimens for LPP patients are to minimize symptoms, and prevent progression of scarring hair

loss. Conventional treatment consists of high potency topical corticosteroids and immunosuppressants,

intralesional corticosteroids, topical minoxidil, and systemic anti-inflammatory agents such as doxycycline and

hydroxychloroquine.2 Responses to available treatments can be unpredictable and are often inadequate.

Currently, there are no consistently effective treatment options. The cause of LPP is unknown, but the

histologic findings including dense lymphocytic in filtrate have led some to postulate this condition may be

autoimmune.1 Recently, naltrexone an opioid antagonist with the greatest affinity for mu receptors, approved

by the Food and Drug Administration for substance addiction treatment, has been suggested to be beneficial

in treating autoimmune diseases. At low doses of less than 5mg daily, naltrexone acts paradoxically leading

to an increase in endogenous opioids, among them β-endorphins which possess broad anti-inflammatory

properties and orchestrate activity of T and B cells.3-5

In mice, administration of naltrexone following

lipopolysaccharide-induced septic shock has been shown to block tumor necrosis factor-alpha production

lending support to the assumption that this medication blocks inflammatory mediators.6

In addition,

naltrexone alters the activity of macrophages causing a switch to the M1 type resulting in increased

phagocytosis and processing of a greater number of antigens. Naltrexone has also been shown to produce

an antagonistic effect on non-opioid receptors involved in the immune system including Toll-like receptor-4

found on cells such as macrophages and microglia, which may mediate both inflammation and neuropathic

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• New treatments:

• Pioglitazone (PPAR gamma agonist): 15-30mg/day;

• Naltrexone (anti-opioid): 3mg daily, reduction of the symptoms

• Excimer laser (308 nm ultraviolet B light)

PPAR gamma is essential for

healthy pilosebaceous units and it

is significantly decreased in LPP

patients

29

What is new?

30

Twice as many women in the FFA group regularly used a sunscreen

compared with controls, a difference that was highly significant.

What is new?

31

• The time course of sunscreen use by the population does seem to parallel

the apparent increase in the incidence of FFA.

• To some extent the predominant distribution of FFA corresponds with the

usual sites of moisturiser and sunscreen application.

FFA and Sunscreens

• Studies with men and women support the conclusion that there is an

association between FFA and the use of facial moisturisers and

sunscreens.

• Ingredients possibly to avoid: Oxybenzone and Avobenzone introduced

by FDA in 1988. First cases of FFA reported in 1994

• Better sunscreens: mineral types

• Zinc oxide

• Titanium dioxide

32

FFA x Sunscreen

35

FFA and Sunscreens

• Studies with men and women support the conclusion that there is an

association between FFA and the use of facial moisturisers and

sunscreens.

• Ingredients possibly to avoid: Oxybenzone and Avobenzone introduced

by FDA in 1988. First cases of FFA reported in 1994.

• Better sunscreens: mineral types

• Zinc oxide

• Titanium dioxide

36

F FRONTALF FIBROSING

ALOPECIA

43

44

Scarring Alopecias

45

Take home

message

• Trichologic emergency

• Early intervention can potentially avert scarring and secondary complications

• Ensure diagnosis with biopsy

• Trichoscopy helps in following up progress

• Disease-directed medical therapy is only indicated in those with active disease

• Adjunctive agents that can improve cosmeticis

• Topical minoxidil

• Hair transplantation

PRP and micro-needling

JERRY SHAPIRO, MD, FAAD

PROFESSOR

The Ronald O. Perelman Department of

Dermatology

South Eastern Consortium

Durham, North Carolina

Platelet Rich Plasma (PRP)

Cell-based therapy

Concentrated suspension of autologous platelets

1980’s: Orthopedic use for bone

2000’s: Skin rejuvenation

• “Vampire Facial”: PRP with microneedling

2010’s: Hair restoration

47

Division Name or Footer48

Division Name or Footer49

POSITION IMAGE QUANTIFY

PRP responses in androgenetic alopecia50

PLATELET-RICH PLASMA (PRP) TREATMENT PROTOCOL

3/4/5/6 Month

Repeat assessment

PRP Treatment

Month 2

AssessmentMonth 1

Assessment

PRP Treatment

Month 0

Assessment

PRP Treatment

No further PRP

Continue other

treatments

/ / >/ / / /

>

NYU retrospective study on PRP

51

PRP responses in androgenetic alopecia52

PATIENT COHORT DEMOGRAPHICS

71%

17%

12%

Caucasian

Hispanic

Asian

Total: 24

Women: 19

Men: 5

24

17

6

10

5

10

15

20

25

30

Num

ber

of P

atients

Concurrent Therapies

PRP responses in androgenetic alopecia53

COMBINATION THERAPY ACHIEVES QUANTITATIVE INCREASES IN HAIR DENSITY

All patients

(N=24)

Responders

(N=17)

Non-Responders

(N=7)

Start count: 155 hair/cm2

End count: 179 hairs/cm2

Mean D: +24 hairs/cm2

(P=0.022)

Responders:

Start count: 163 hair/cm2

End count: 198 hairs/cm2

Mean D: +35 hairs/cm2 (P<0.0001)

Average Age: 44

Non-Responders

Start count: 135 hair/cm2

End count: 133 hairs/cm2

Mean D: -2 hairs/cm2 (Not significant)

Average Age: 37

No significant change in hair diameter

Month 0 Month 6

Trichologic Responses are Time-Dependent

PRP responses in androgenetic alopecia54

Month 1 Month 2 Month 3Month 0 Month 4

+20

+40

+60

+80

0+

100

Responders

(N=17)

Ch

an

ge

in

Ha

ir D

en

sity (

ha

irs/c

m2)

Time

+10 hairs/cm2

Threshold

Non-Responders

(N=7)

• Segregation of responders vs

non-responders after 2 months

• Most benefit achieved within 2

to 4 months

• No shock loss

PRP: Take Home Points

Can I use PRP with other treatments?

• No apparent downside to use PRP as combination therapy

What are the chances of it working?

• Nearly 3 out of 4 recipients of combination therapy show increased hair density

How much benefit can I expect?

• Average increase: +35 hairs/cm2. No change in hair diameter.

Which people do worse with therapy?

• Patients with earlier-onset disease and lower baseline hair counts don’t respond as well

When will I see benefit?

• Usual response at 2-4 months, but may increase or decrease

55

Our PRP Protocol:

56

2 PRP

sessions at 1

month intervals

Assessment with

hair count and

diameter

Successful

response(hair density increase

greater than 10

hairs/cm2)

Stop PRP

Continue monthly

PRP for more 4

months and

reevaluate

N

O

YES

PRP clinical trial NYU

Clinicaltrials.gov

• Randomized, double blinded, placebo controlled study

• 50 men and women screened between 18-65 years old with

androgenetic hair loss

• Blood tests to rule out diseases related to hair loss

• Platelets > 150 000/ul

• Split scalp: PRP injection vs Saline injection

• Injected area is tattooed

• Funded by Regenlab

Dynamic Quantitative Trichoscopy Tracks Response

Handheld Dynamic Quantitative Trichoscopy58

Ba

se

line

6 m

on

ths

Time (months)

Ha

ir D

en

sity (

ha

irs/c

m2)

120

130

140

150

160

170

180

190

6 months w/o PRP

Current

6 months w/o PRP

= PRP

0 1 2 3 4 5 || 12 13 || 19 20

Standard Photography

Summary:

Cervantes et al. Effectiveness of Platelet-Rich Plasma for Androgenetic Alopecia: A Review of the Literature

Skin Appendage Disord 2018;4:1–11 59

For a better understanding, we need:

• large-scale double-blind, randomized controlled studies

• men and women included

• standardized PRP preparation methods and administration protocol

• repeated treatments

• standardized objective data documentation and evaluation

• physician and subject assessment

• analysis of effects of PRP in different grades of AGA

• long-term follow-up

When NOT to use PRP: presence of skin cancer on the head

60

Nodular BCC

on the scalp

Microneedling Clinical Trial at NYU

•Split scalp; one side MN

•Both sides receive Minoxidil 5% foam bid

•Single blinded study

•Hair counts and diameters

•Treatment q 2 weeks for 20 weeks

MICRONEEDLING (MN) Intra-dermabrasion

Length: 25 to 3000 microns

Transient epidermal and/or papillary dermal pores with disruption of dermal microcirculation

Mechanisms of action:

Neo-angiogenesis, growth factor production

Breach of stratum corneum allows for more effective drug delivery

Bellus Medical SkinPen®

Microneedling (MN)

Mechanisms of action:

• Neo-angiogenesis, growth factor production

• Breach of stratum corneum allows for more effective

drug delivery

Skin Pen II

Automated vibrating cartridge, stamp-like and fractionated

Variable length needles, set for 1.5 mm in our study

FDA registered as medical device

Bellus Medical SkinPen®

Our Study:

66

Evaluating the

efficacy of dermal

microneedling in the

treatment of

androgenetic

alopecia: a dual-

center, randomized,

controled, single-

blinded pilot trial

Microneedling half head study

67

68

• Subjects were randomly allocated into 3 groups

• Topical 5% minoxidil (group 1, n = 20),

• Electrodynamic microneedle treatment (group 2, n

= 20),

• Electrodynamic microneedle treatment with

topical 5% minoxidil (group 3, n = 20).

• Patients received microneedle treatments every 2 weeks,

for a total of 12 times.

• The best therapeutic effect was observed in group 3: non-

vellus and the total hair counts, the hair thickness,

investigator assessment, and patient self-assessment

• 80% of these patients showed greater than 50%

improvement of hair growth

Full Terms & Conditions of access and use can be found at

http:/ /www.tandfonline.com/action/journalInformation?journalCode=ijcl20

Download by: [University of Tasmania] Date: 16 October 2017, At: 04:02

Journal of Cosmet ic and Laser Therapy

ISSN: 1476-4172 (Pr int ) 1476-4180 (Online) Journal homepage: ht tp:/ /www.tandfonline.com/ loi/ ijcl20

Randomized t r ial of elect rodynamic m icroneedlecombined with 5% minoxidil topical solut ion forthe t reatment of Chinese male Androgenet icalopecia

Linlin Bao, Lin Gong, Menger Guo, Taoming Liu, Anyu Shi, Haifeng Zong,Xuegang Xu, Hongduo Chen, Xinghua Gao & Yuanhong Li

To cite this ar t icle: Linlin Bao, Lin Gong, Menger Guo, Taoming Liu, Anyu Shi, Haifeng

Zong, Xuegang Xu, Hongduo Chen, Xinghua Gao & Yuanhong Li (2017): Randomized trial

of electrodynamic microneedle combined with 5% minoxidil topical solution for the treatment

of Chinese male Androgenetic alopecia, Journal of Cosmetic and Laser Therapy, DOI:

10.1080/14764172.2017.1376094

To link to this ar t icle: http://dx.doi.org/10.1080/14764172.2017.1376094

Accepted author version posted online: 13Oct 2017.

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J Cosmet Laser Ther. 2017 Oct 13.

Microneedling

Alopecia Areata (AA):PRP

70

• PRP may have the ability to induce a longer disease remission.

• Patients treated with PRP appeared to regrow pigmented hairs from the

beginning of hair regrowth compared with 25% of those treated with

TAC

• Non- standardized treatment protocols and methods for assessing

response make it challenging to adequately assess the potential benefit

of the treatments.

Alopecia Areata (AA):PRP

71

PRP 1st

treatment

PRP 2nd

treatment

PRP 3rd

treatment

Baseline

NYU Hair Research Group

Dr. Jerry Shapiro

Dr. Kristen Lo Sicco

Dr. Loren Krueger

Dr. Nooshin Brinster

Paul Curtiss

Sarah Leventhal

Garrett Yoon

Anthony Ho, MS3

Dr. Maura Bourroul (Brazil)

Dr. Lorena Avila (Brazil)

Lauren Strazzulla

Katerina Svigos

Catherine Motosko

Prag Batra

72

ACKNOWLEDGEMENTS

73

Thank you from NYU School of Medicine