frontal fibrosing alopecialipopolysaccharide-induced septic shock has been shown to block tumor...
TRANSCRIPT
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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
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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
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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
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My clinic epidemiology on alopecia types
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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)
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Bolduc C. Sperling,
L.
Shapiro J
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Clinical Indications for treatment
Activity
• Hyperkeratosis
• Erythema
• Pull test positive
• Symptomatic (itch, burn and pain)
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Fotofinder: quantification and quality assessment
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Fotofinder: quantification and quality assessment
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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
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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
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FACIAL PAPULES OF FFA
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Scarring Alopecias
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• Lichen Planopilaris and FFA
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Frontal Fibrosing Alopecia (FFA)
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Patient Demographics
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Total: 92
Women: 90
Men: 2
Eyebrow involvement: 96%
Symptoms: 14%
Autoimmune disease: 11%
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Photos for FFA
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How do I measure?
FFAGlabella to hair line
Right and left outer canthi to
hair line
Sides to hair line
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Glabella to
hairlineRight outer
canthus to
hairline
Left outer
canthus to
hairline
SideburnsSideburns
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Frontal Fibrosing Alopecia (FFA)
• TOPICAL/INTRALESIONAL
Treament:
• Corticosteroids: reduce pruritus
• Calcineurin inhibitors:
• Minoxidil
• Intralesional Corticosteroid:
Kenalog 2.5mg/cc, 3cc
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CT M
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Frontal Fibrosing AlopeciaIntralesional triamcinolone acetonide2.5 mgs/cc X 3cc ear to ear
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Lichen Planopilaris (LPP)
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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
To order reprints or e-prints of JDD articles please contact [email protected]
Journal of Drugs in Dermatology. All Rights Reserved. No reproduction or use of any portion of the contents ofthese materials may be made without the express written consent of JDD. If you feel you have obtained this
copy illegally, please contact JDD immediately. Licensed to [email protected].
• 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
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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.
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What is new?
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• 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.
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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
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FFA x Sunscreen
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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
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F FRONTALF FIBROSING
ALOPECIA
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Scarring Alopecias
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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
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PRP and micro-needling
JERRY SHAPIRO, MD, FAAD
PROFESSOR
The Ronald O. Perelman Department of
Dermatology
South Eastern Consortium
Durham, North Carolina
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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
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Division Name or Footer48
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Division Name or Footer49
POSITION IMAGE QUANTIFY
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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
/ / >/ / / /
>
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NYU retrospective study on PRP
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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
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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
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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
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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
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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
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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
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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
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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
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When NOT to use PRP: presence of skin cancer on the head
60
Nodular BCC
on the scalp
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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
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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®
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Microneedling (MN)
Mechanisms of action:
• Neo-angiogenesis, growth factor production
• Breach of stratum corneum allows for more effective
drug delivery
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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®
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Our Study:
66
Evaluating the
efficacy of dermal
microneedling in the
treatment of
androgenetic
alopecia: a dual-
center, randomized,
controled, single-
blinded pilot trial
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Microneedling half head study
67
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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.
Submit your article to this journal
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J Cosmet Laser Ther. 2017 Oct 13.
Microneedling
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Alopecia Areata (AA):PRP
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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
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71
PRP 1st
treatment
PRP 2nd
treatment
PRP 3rd
treatment
Baseline
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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
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73
Thank you from NYU School of Medicine