NORTH CAROLINA DERMATOLOGY ASSOCIATION

2017 SUMMER MEETING

This continuing medical education activity is jointly provided by theNorth Carolina Dermatology Association and

Southern Regional Area Health Education Center FRIDAY HANDOUTS

JULY 7-9, 2017 | OMNI HOMESTEAD RESORT | HOT SPRINGS, VIRGINIA

1

Medical and DiagnosticPearls

Mark Lebwohl, MD

Sol and Clara Kest ProfessorAnd Chairman

Department of DermatologyThe Mount Sinai School of Medicine

Mount Sinai gets dollars from:

• Abbvie

• Amgen

• Boehringer Ingelheim

• Celgene

• Eli Lilly

• Janssen / Johnson & Johnson

• Kadmon

• Medimmune/Astra Zeneca

• Novartis

• Pfizer

• ViDac.

Consultant

• Allergan

• Dr. Reddy

• Pruritus in the elderly

• Lichen planus

• Ostomies

• Raynaud’s phenomenon

• Optimal phraseology for patients

• Actinic Keratoses

• Local anesthesia alternatives

• Tool tips

• Management of bleeding

2

• Patient with hyperverbia profundia

• Ocular rosacea

• Gingival hyperplasia

• Drug sampling

• Lyme disease

• Defibrillators

• Nickel allergy

• Atopic dermatitis

Chronic eczematous eruptions of the elderly are associated with chronic exposure to calcium channel blockers: results from a case-control study.Joly P, Benoit-Corven C, Baricault S, Lambert A, Hellot MF, Josset V, Barbaud A, Courville P, Delaporte E, Collet E, Carvalho P, Modeste-Duval AB, Lacour JP, L'Anthoën-Arditi MH, Thuillez C, Benichou J.J Invest Dermatol. 2007;127:2766-71.

[Lisinopril-induced erythroderma] Schmutz JL, Barbaud A, Tréchot P. Ann Dermatol Venereol. 2009;136:486. Epub 2009 Apr 3. French

3

ACE-I induced angioedema: a casereport and review of literature.Adebayo PB, Alebiosu OC.Cases J. 2009;2:7181.

Angiotensin-converting enzymeinhibitors as inducers of adversecutaneous reactions.Steckelings UM, Artuc M, Wollschläger T, Wiehstutz S, Henz BM.

Acta Derm Venereol. 2001;81:321-5.

Enalapril and vulvovaginal pruritus.Heckerling PS.Ann Intern Med. 1990;112:879-80.

4

Rash, eosinophilia, and hyperkalaemiaassociated with enalapril.Barnes JN et al.

Lancet. 1983;2:41-2.

[Captopril-induced eruptions: occurrence over a 3-year period] Daniel F, Foix C, Barbet M, Schwebig A, Plouin F, Ménard J, Baviera A.Ann Dermatol Venereol. 1983;110:441-6.French

LichenplanusGlsb

388

:k'l Udtm pllnus ll a prurtllc p.ipuloq.um1na dlJeuc 11bbdum:mts t lcb, lla,patbo ICand dlnlaJ rruum . Oal m>shT lldxn pbnu l iuJnlU m u" c mndbnuoous membuna, IJ r a , e d In a nu

lbJt an lfmctuptcr.

..,., T STRAJECY

AIOUJu#IUdlcn p..anm cm n:,oln sponunecw cmrmelll IHUJlly CkmJndcd b'f p1nmts, W CID be- l ' d f IJ'lllJ>

toJDJtlc. U n . 1 e dllcitts rutll .i1 hqutllls C or lllllOdmlla slloold be hL

In pnimt1 nil lilall!l!d dlJaW. s ,shoutd be 11pp!lal lW °a d.llly rtlr2-4 - IC tilt repoosr

lru i:, Mmtm. t l c .ll Into loc l-'11:e:l lelcru m be bm cnc:w.11 Jnt'lp:1'1111 1emu mn.u:lnl ll8""" ''"' '- a v." "'- I SV,l l l Y f l . cm be Uldll l . II

OTl t lupl , .m.J}ol l h nm.

m:I b<nellt In K\'a'.ely prurttlc JUllcnll,, 5eebtlll8 1111tlbl.sU

,em neu1e hdplll u bo:l1tne.

Tndtd .al p:zll.cnJ:I whh cnmthT l ld xn pa:nm tu,Tb t t n tl!IJ1ed wllh l}'IUIDX CIOOtm U n:tdJ. In r r a n q o,n,.:mnllit:cillu\ em u a nl1e:fltn'nle llUDulh ID

JJV,emlc CICJ1tlaictm> • 50 Ill.!! tW'a for 20-60 dJ}1hz p oh tn mimr p:.ntmrL In FJlr:m v.tlo do not tepood,t'l'JI J'ffi JD-OOmgwuy rtlT 2-wmu, or 111 equJ,·.ilent, Clpcn!dlbcensu'I 2-6 wcdi II o f t u dl t c . t h UnflmuJUt • C\TDtnp;axllls 11bo eJr wtlb qumm di, M U p 1e ttequrnt. It pllknll 111qulrr 11101'

thllll t1 IDUIXS bWi-4Clt 'Sl.mflc: CllllOOCl>IUJl'Dtdl rthe spm ar l few ma:nth!, JI tl'C5ltmma 1h Id be

to1'J1L::inln IIDM5or on lly twa d21ly Tl molllbs

hz been lqxxted lO dcu l l d l m i:t. irm In IC\Tnl FJl_m.,,,1 n:l 30 luJ :UJCJ ICIUl1al In IIUdc:ed lmp:rDl'mlt.n1or remlJ . In 1ell1 rya UVA (PUVA )nal1DVot:!imd UVll h dm>ol"lllDlf!d dnacy n the t1111unen1ortlchm pl111A I'll\' Im b t t n nlcularty bmd la l l tn lbellehm plJDus-llloe aupUon gft,O(jzed nb gn t.-\"mUJ-ltorldlxuc . Rlf x,-a:e and IEll1 n.un p..a uruapa:n-s"c to Cllber lbmp)e, lmmUDOISUfJptmh mo. llldud- ln& ctillrnff'1'11xi:1tt U..u.it11 , lie o:ten ctkll\'c.

SPECACI ST IJIIS

Six or panarts vnb Mxn plmla bad crmu u,-u ftul n ten. 1n:l On ot itx \ll weir tnmd tahJ\T cbmn 1ctni.! bepulia on ll\'a'. b

5

Topica.l corticosteroidslntralesional corticosteroids Antihistamines

C

D

C

MetronidazoleSystemic corticosteroids lsotretinoin, acitretin Narrowband or broad band UVB PUVA

C

B

A

C

C

Oral metronidazole treatment of lichen planus.Büyük AY, Kavala M.J Am Acad Dermatol. 2000;43(2 Pt 1):260-2.

• Metronidazole 500 mg bid x 20-60 d.

• 15/19 (79%) improved

• 13/15 → complete clearing

6

Efficacy of sulfasalazine in the treatment of generalized lichen planus: randomized double-blinded clinical trial on 52 patients.Omidian M, Ayoobi A, Mapar MA, Feily A,Cheraghian B.JEADV. 2010;24:1051-1054(4).

• sulfasalazine up to 2.5g/d vs. placebo x 6w• lesion improvement 82.6% vs. 9.6%• pruritus improvement 91.3% vs. 14.3%• side effects 30.7% - GI and HA

“Small fistula tracks … from which pus could be obtained on pressure.”

Brunsting LA, Goeckerman WH, O'Leary PAArch Dermatol Syph. 1930; 22:655

If you’re confident about a patient’s diagnosis and treatment, let them

know you see a lot of this condition and know exactly how to deal

with it.• Mycosis fungoides/CTCL

• Perioral dermatitis

7

Bilateral comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% 5-fluorouracil cream in the treatment of actinic keratoses of the face and scalp.Smith SR, Morhenn VB, Piacquadio DJ.

J Drugs Dermatol. 2006;5:156-9.

• Both work

• Diclofenac less irritating

Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.

Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, Lee JH, Fox TL.

J Am Acad Dermatol. 2004;50:714-21.

imiquimod cream biw x 16w.

Ingenol mebutate gel for actinic keratosis.

Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B.

N Engl J Med. 2012;366(11):1010-9.

8

Composite LSR Scoresa Through Day57:Safety Population

22

Mean composite LSR scores peaked at day 4and returned to baseline levels by day 15.

aThe composite LSR score represents the sum of the scores for the 6 specific types of LSRs graded from 0 to 4, with a maximum score of 24 at each study visit.

Pooled 016 and 025

Long-term follow-up of photodynamic therapy with a self-adhesive 5-aminolaevulinic acid patch: 12 months data.Szeimies RM, et al

Br J Dermatol. 2010;162:410-4.

• PDT – 1 rx: 63% and 79% efficacy at 1 yr

• Placebo PDT: 9% and 25%

• Cryosurgery: 63%

A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up

Krawtchenko N, Roewert-Huber J, UlrichM, Mann I, Sterry W, Stockfleth E.

British Journal of Dermatology.2007;157(s2):34-40.

9

• Cryo 20-40 sec per lesion x 1-2sessions

• 5FU bid x 4w.

• Imiquimod tiw x 4 w. x 1-2 courses

Clinical Evaluation:Comparison of All Treatment Groups

68%

96%85%

4%100%

80%

60%

40%

20%

0%

Imiquimod 5-FU Cryotherapy

Pat

ien

ts (

%)

Cleared Persistent

Krawtchenko et al. Br J Dermatol 2007;157(suppl. 2):34-40

p=.03 Imiquimod (n=26) 5-FU (n=24) Cryosurgery (n=25)

Histological Confirmation: Comparisonof All Treatment Groups

32%

67%73%

100%

80%

60%

40%

20%

0%

Pat

ien

ts (

%)

Cleared Persistent

Krawtchenko et al. Br J Dermatol 2007;157(suppl. 2):34-40

Biopsies are checked by 2 independent histopathologists

p=.03 for 5-FU and p=.008 for imiquimod

Imiquimod(n= 26)

5-FU(n= 24)

Cryotherapy(n= 25)

10

Sustained Clearance of Initially ClearedLesions in All Patients

Pat

ien

ts (

%)

Twelve months after end of treatment

80%

73%60%

40%

20%

0%Imiquimod (n=26) 5-FU (n=24) Cryotherapy (n=25)

Krawtchenko et al. Br J Dermatol 2007;157(suppl. 2):34-40

p<.01

Out of all treated patients (including in the denominator also those not cleared at end of therapy)

Severe refractory fingertip ulcerations in a patient with scleroderma: successful treatment with sildenafil.Colglazier CL, Sutej PG, O'Rourke KS.

J Rheumatol. 2005;32:2440-2.

Statins: Potentially useful in therapy of systemic sclerosis-related Raynaud’s Phenomenon and digital ulcers.Abou-Raya A et al.J Rheumatol 2008;35:1801-8.

• Atorvastatin 40/d vs placebo x 4 mos

• new ulcers: 1.6 vs 2.5

• RP, pain and severity of ulcers,

endothelial damage markers

11

Botox therapy for ischemic digits.Neumeister MW et al.Plast Reconstr Surg. 2009;124:191.

• 100 unit botulinum toxin vial dilutedin 2cc preservative-free saline

• 50-100 U of toxin injected into palm around neuromuscular bundles at MCP

Neumeister MW et al.Plast Reconstr Surg. 2009;124:191.

• pain relief was immediate• ulcers healed within 2 months• Doppler showed increased blood flow

within 30 minutes• pain relief persisted in 12/19 at 13-59

months

Management of vasospastic disorders withbotulinum toxin A.Van Beek AL et al.Plast Reconstr Surg. 2007;119:217-26.

• 11 patients, painful Raynaud’s, digital ulcerations.

• Failed vasodilators, anti-platelet agents,and IV prostacyclin.

12

Botox 100 U at 8-10 sites,perivascular digital and palmar.

• Temporary hand weakness in 3 patients.• All patients improved:• Less frequent and less severe vasospasm

and cyanosis within 48 hours.PreRx scores: 9-10PostRx: 0-2

Van Beek AL et al.Plast Reconstr Surg. 2007;119:217-26

Increased sensitivity to thermal painand reduced subcutaneous lidocaineefficacy in redheads.Liem EB et al.

Anesthesiology. 2005;102:509-14.

Tip # 8

Anesthetic requirement is increased in redheads.Liem EB et al.

Anesthesiology. 2004;101:279-83.

13

• Diphenhydramine– 50mg/mL (5%) Dilute 1:5 ( 1%)

– Lasts ~20 minutes

– Risk of necrosis and delayed sedation

• Bacteriostatic saline w/0.9% benzyl alcohol

– Sufficient volume and pressure

– Lasts ~2 minutes

Alternative Local Anesthetics

Tip # 9

Injectable sodium chloride as a local anesthetic for skin surgery.

Weiner SGCutis. 1979; :342-3.

“parallel scalpel technique, razor technique, orcurettage…punch biopsies and electrocauterytechniques”

Diphenhydramine versus lidocaine as alocal anesthetic.

Dire DJ, Hogan DE.Ann Emerg Med. 1993;22:1419-22.

• No significant differences btwn 1% lidocaineand 1% diphenhydramine injections for localanesthesia.

14

Lidocaine versus diphenhydramine for anesthesia in the repair of minor

lacerations.Ernst AA, et al.

J Trauma. 1993;34:354-7.

• 1% diphenhydramine more painful than 1% lidocaine, but anesthesia is equivalent

Reasons to Become a Registry Investigator

• Contribute to education/clinical knowledge of the psoriasiscommunity

• Opportunity to establish a database of your patient population

• Academic recognition and publication opportunities

• Supplement existing insurance fee schedules– Site compensation is $400 (including $20 for patient) per Enrollment

visit and $300 (including $20 for patient) per biannual Follow Up visit

41

If you are interested in participating in the Psoriasis Registry as a research investigator, please email

psoriasis@corrona.orgor visit www.corrona.org

or call 508.408.5432

Become a Registry Research Investigator

1

Breakthrough Drugs inDermatology

Mark Lebwohl, MDSol and Clara Kest Professor

And ChairmanKimberly and Eric J. Waldman Department of Dermatology

Icahn School of Medicine at Mount Sinai

LIFE CHANGING MEDICATIONS• New psoriasis therapies

•Dupilumab

•Omalizumab

•Vismodegib/Sonidegib

• Penetration enhancers that improve topicaltherapy

• JAKinhibitors

• New vitiligotherapies

Drugs for Psoriasis and Psoriatic Arthritis

• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB

• GOLIMUMAB

• USTEKINUMAB

• SECUKINUMAB

• IXEKIZUMAB

• APREMILAST

• METHOTREXATE

• CYCLOSPORINE

• ACITRETIN

• BRODALUMAB

• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

2

Drugs for Psoriasis and Psoriatic Arthritis-ORAL• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB

• GOLIMUMAB

• USTEKINUMAB

• SECUKINUMAB

• IXEKIZUMAB

• APREMILAST

• METHOTREXATE

• CYCLOSPORINE

• ACITRETIN

• BRODALUMAB

• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

Drugs for Psoriasis and Psoriatic Arthritis-FEW INJECTIONS

• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB

• GOLIMUMAB

• USTEKINUMAB• SECUKINUMAB

• IXEKIZUMAB

• APREMILAST

• METHOTREXATE

• CYCLOSPORINE

• ACITRETIN

• BRODALUMAB

• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

Drugs for Psoriasis and Psoriatic Arthritis –LONG Hx & ↓ CARDIAC DISEASE

• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB

• GOLIMUMAB• USTEKINUMAB

• SECUKINUMAB

• IXEKIZUMAB

• APREMILAST

• METHOTREXATE

• CYCLOSPORINE

• ACITRETIN

• BRODALUMAB

• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

3

Drugs for Psoriasis and Psoriatic Arthritis –OBESITY:ADJUST FOR WEIGHT

• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB• CERTOLIZUMAB

• GOLIMUMAB

• USTEKINUMAB• SECUKINUMAB

• IXEKIZUMAB

• APREMILAST

• METHOTREXATE

• CYCLOSPORINE

• ACITRETIN

• BRODALUMAB

• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

Drugs for Psoriasis and Psoriatic Arthritis –OBESITY:ADJUST FOR WEIGHT

• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB• GOLIMUMAB

• USTEKINUMAB

• SECUKINUMAB• IXEKIZUMAB

• APREMILAST

• METHOTREXATE

• CYCLOSPORINE

• BRODALUMAB

• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

Drugs for Psoriasis and Psoriatic Arthritis –OBESITY

• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB• GOLIMUMAB

• USTEKINUMAB

• SECUKINUMAB

• IXEKIZUMAB

• APREMILAST

• METHOTREXATE

• CYCLOSPORINE

• BRODALUMAB

• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

4

Drugs for Psoriasis and Psoriatic Arthritis-PSA• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB

• GOLIMUMAB• USTEKINUMAB• SECUKINUMAB

• IXEKIZUMAB

• APREMILAST

• METHOTREXATE• CYCLOSPORINE

• ACITRETIN

• BRODALUMAB

• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

Drugs for Psoriasis and Psoriatic Arthritis-PSA• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB

• GOLIMUMAB• USTEKINUMAB

• SECUKINUMAB

• IXEKIZUMAB• APREMILAST

• METHOTREXATE• CYCLOSPORINE

• BRODALUMAB• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

Drugs for Psoriasis and Psoriatic Arthritis- FAST• ETANERCEPT

• ADALIMUMAB

• INFLIXIMAB

• CERTOLIZUMAB

• GOLIMUMAB

• USTEKINUMAB

• SECUKINUMAB

• IXEKIZUMAB• APREMILAST

• METHOTREXATE

• CYCLOSPORINE• ACITRETIN

• BRODALUMAB• GUSELKUMAB

• TILDRAKIZUMAB

• RISANKIZUMAB

• LY3074828

SPEED

5

100

90

80

70

60

50

40

30

20

10

0

Dupilumab Phase 2b Study:Proportion of Patients Achieving ≥75% ImprovementFrom Baseline in EASI (EASI-75†) Over 16 Weeks

11.5

29.2

60.355.753.149.2

†Observed value with censoring after rescue medication; missing treated as non-responder. EASI: Eczema and Severity Index; q2w: every 2 weeks; q4w,:every 4 weeks.Adapted from Thaci D et al. Lancet. 2016;387(10013):4052.

0 4 8 12 16Week

P < 0.05 vs placebo, Weeks 23 and P ≤ 0.0001 vs placebo, Weeks 416

P < 0.05 vs placebo, Weeks 26 and P ≤ 0.0001 vs placebo, Weeks 816

P < 0.05 vs placebo, Week 2 and P ≤ 0.00001 vs placebo, Weeks 316

P < 0.05 vs placebo, Weeks 23 and Weeks 816; P ≤ 0.0001 vs placebo, Weeks 4 and 6; and P = 0.0147 vs placebo, Week 16

PlaceboDupilumab 100 mg q4wDupilumab 300 mg q4wDupilumab 200 mg q2wDupilumab 300 mg q2w Dupilumab 300 mg weekly

Pro

po

rtio

no

f p

ati

ents

a

ch

ievi

ng

EA

SI-

75(%

)

Dupilumab SOLO 1 & 2: Proportion (%) of Patients with IGA0 or 1 and ≥ 2-point Reduction From Baseline at week 16

10

0

10

20

30

40

50

Per

cen

to

f p

atie

nts

ach

ievi

ng

IGA

≤1

SOLO 1

Placebo Dupilumab 300 mg q2w Dupilumab 300 mg qw

8.5

0

10

20

30

40

50

Per

cen

to

f p

atie

nts

ach

ievi

ng

IGA

≤1

SOLO 2

Placebo Dupilumab 300 mg q2w Dupilumab 300 mg qw

38* 37* 36* 36*

* P<0.0001.IGA: investigator’s global assessment; qw: weekly; q2w: every 2 weeks.

15

0

10

20

30

40

50

60

Per

cen

tp

atie

nts

ach

ievi

ng

EA

SI-

75

SOLO 1

Placebo Dupilumab 300 mg q2w Dupilumab 300 mg qw

12

4448

0

10

20

30

40

50

60

Per

cen

tp

atie

nts

ach

ievi

ng

EA

SI-

75

SOLO 2

Placebo Dupilumab 300 mg q2w Dupilumab 300 mg qw

51* 52.5*

*

*

* P<0.0001.EASI: Eczema Area and Severity Index; EASI-75: 75% improvement in EASI; q2w: every 2weeks; qw: weekly.

Dupilumab SOLO 1 & 2: Proportion (%) of Patients Achieving EASI-75 at Week 16

6

Dupilumab SOLO 1 & 2: Percent (%) Change From Baseline to Week 16 in EASI Score

38

10

20

30

40

50

60

70

80

Pe

rce

nt

ch

an

ge

fro

m b

as

eli

ne

inE

AS

Is

co

re

SOLO 1

31

69

0

10

20

30

40

50

60

70

80

Pe

rce

nt

ch

an

ge

fro

mb

as

eli

ne

inE

AS

Is

co

re

SOLO 2

Placebo Dupilumab 300 mg q2w Dupilumab 300 mg qw

72* 72 *67*

*

0

Placebo Dupilumab 300 mg q2w Dupilumab 300 mg qw

* P<0.0001.EASI: Eczema Area and Severity Index; qw: weekly; q2w: every 2 weeks.

Dupilumab CHRONOS: Proportion (%) of Patients with IGA 0 or 1 and ≥ 2-point Reduction From Baseline at Week 52

36*40*

30

2012.5

10

0

40

50

Placebo + TCS Dupilumab 300 mg q2w + TCS

Dupilumab 300 mg qw +TCS

Pat

ient

sac

hiev

ing

IGA

1(%

)

* p<0.0001

IGA: investigator’s global assessment; q2w: every 2 weeks; qw: weekly; TCS: topical corticosteroid.

Source: Data on file

Dupilumab CHRONOS: Proportion (%) of Patients Achieving EASI-75 at Week 52

65* 64*60

40

2220

0

80

Placebo + TCS Dupilumab 300 mg q2w + TCS

Dupilumab 300 mg qw +TCS

Pat

ient

sac

hiev

ing

EA

SI-

75(%

)

* p<0.0001

EASI: eczema area and severity index; q2w: every 2 weeks; qw: weekly; TCS: topical corticosteroid.

Source: Data on file

7

Omalizumab treatment reduced mean weekly Itch Severity Scoreby Week 1

• Rapid-onset, dose-response, sustained efficacy at Wk 24 compared with Wk 12

Maurer M, et al. EADV 2013: FC09.1. Sponsored by Genentech, Inc. andNovartis

Mea

nch

ang

efr

om

b

asel

ine

0

–2

–4

–6

–8

–10

–120 4 8 12 16 36 40

Placebo Omalizumab 150 mg

Omalizumab 70 mg Omalizumab 300 mg

20 24 28 32Study week

4-weekly injections

All doses of omalizumab significantly reduced mean weekly ISS vsplacebo (primary endpoint)

–3.63

0-1-2-3-4-5-6-7-8-9

-10

PlaceboOmalizumab

75 mgOmalizumab

150 mgOmalizumab

300 mg

Mea

nch

ang

efr

om

bas

elin

ein

w

eekl

yIS

Sat

Wk

12

n=80 n=77 n=80 n=81

–6.46

p=0.0010

–6.66

p=0.0012

–9.40

p<0.0001

p values derived form t-test of least squares means of the differences between each of the omalizumab groups and placebo group using ANCOVA controlling for baseline weekly ISS (<13 vs ≥13) and baseline weight (<80 kg vs ≥80 kg). Baseline observation carried forward imputation was used for missing values

Maurer M, et al. EADV 2013: FC09.1. Sponsored by Genentech, Inc. andNovartis

Figur1e.Time to U1rt]car"a !Relapse·After 1Omallnz -1ab Tr1eatme1nt

U1, I - I

C :

' ! .;...._

12

10

8

a... 6

d;z 4

2

03

D Clh1ronic sl)Jo int a1neous 11J1rtlicaria

Cok 11J1rtlicaria

II Clholinergic urticaria

D So d ri-urtica·ri-ia

D Symptomati( de·rmog1ra1p!h'ism

4 s 6 1 7

onths· eeks

Tiim1e1Before eappearanc1e1of Symptoms

E.ch patment is n p resent ed by a square. wl hcolors nd icating the type of urtik:anl.adisease. Two oalors with n a s nglesquare ndk:ate comorb1d t.yaf2.urticana dis, ea5es..

8

Inhibition of the hedgehog pathway inadvanced basal-cell carcinoma.Von Hoff DD et al.N Engl J Med. 2009;361(12):1164-72.

• 33 patients – metastatic or advanced BCC• GDC – 044a 16 partial and 2

complete responses• fatigue, hyponatremia, muscle spasm, afib

Randomized, double-blind study of sonidegib (LDE225) in patients with locally advanced or metastatic basal-cell carcinoma

J Clin Oncol 32:5s, 2014 (suppl; abstr 9009a^) MR Migden, etal

SONIDEGIB

Absorption Azelaic acid

Azelaic acid is most commonly formulated as a 20% cream, as a15% gel and a 15% foam. There is some published data absorption.Percutaneous absorption of azelaic acid into human skin from the

20% cream formulation is 3.6% of the dermally applied dose.[1]

The 15% gel formulation probably delivers higher amounts of azelaic acid to the skin, as studies on mice showed an 8-fold higher delivery (25.3% versus 3.4%) into viable skin for the gel than the creamWith both formulations the majority of the applied azelaic acid

1. Täuber U, Weiss C, Matthes H. Percutaneious absorption of azelaic acid in humans. Exp Dermatol. (1992)2. Draelos ZD. Noxious sensory perceptions in patients with mild to moderate rosacea treated with azelaic acid 15% gel. Cutis. 2004; 74(4):257-60.3. bbLi N, Wu X, Jia W, Zhanq MC, TanF, Zhang J. Effect of inoization and vehicle on skin absorption and penetration of AzelaicAcid.

9

Topical corticosteroid compounding: effects on physicochemical stability and skin penetration rate.Krochmal L, Wang JC, Patel B, Rodgers J.J Am Acad Dermatol. 1989; 21:979-84.

Salicylic acid

Camphor,menthol, phenolLCD

Desoximetasone alone Urea

Salicylic acid

10

Dependence of corticosteroid penetrationon the vehicle.Polano MK, Ponec M.Arch Dermatol. 1976; 112:675-80.

Topical steroid formulation selected to balance skinpenetration and retention, while minimizing percutaneous

30

Kircik L, et al. Poster presented at Winter Clinical, Koloa, Hawaii, Jan 15–20, 2016

• Test formulation F-10 demonstrated optimal penetration – permeation balance:High epidermal and dermal concentrations of betamethasone dipropionate with minimal receptor fluid levels

• Sernivo selected for further clinical development

absorption

Penetration of steroid into various skin layers

F-C= oleyl alcoholPermeation of steroid into retention fluid

11

31

DFD-01 HAD HIGHEST PENETRATION OF TOTAL BETAMETHASONES INTO THE EPIDERMIS AFTER 24 HOURS VERSUS OTHER COMMERCIAL

FORMULATIONS

Kircik L, et al. Poster presented at Winter Clinical, Koloa, Hawaii, Jan 15–20, 2016

32

REDUCTION IN TSS WITH DFD-01 WAS SIGNIFICANTLY GREATER THANAUGBD AT DAY 4 AND VEHICLE AT ALL TIME POINTS

Stein Gold L, et al. Poster presented at Winter Clinical, Koloa, Hawaii, Jan 15–20, 2016Pooled analysis

Supersaturation of calcipotriene and betamethasone dipropionate in a novel aerosol foam formulation for topical treatment of psoriasis provides enhanced bioavailability of the active ingredients.Lind M et al.

Dermatol Ther. 2016;6:413-25.

●rapid evaporation of solvents leaves the calcipotriene and BD in a supersaturated state●crystals form with other formulations of Cal/BD (ointment, topical suspension) but do not form after dispensing of the foam

(both Cal and BD, fully dissolved in the DME and butane solvents, do not form crystals

12

In vitro skin penetration data for BDP

0

2

4

6

8

10

12

%of

appl

ied

dose

Penetration of BDP (in CBD ointment and LEO 90100) into skin at different time points

14

Receptor fluid Applied skin

CBD ointment, 2h CBD ointment, 6h CBD ointment, 21h LEO 90100, 2h LEO 90100, 6h LEO 90100, 21h

In vitro skin penetration data for calcipotriol

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

%of

appl

ied

dose

Penetration of calcipotriol (in CBD ointment and LEO 90100) into skin at different time points

Receptor fluid Applied skin

CBD ointment, 6h

CBD ointment, 2h

CBD ointment, 21h

LEO 90100, 2h LEO 90100, 6h LEO 90100, 21h

Primary Response CriterionSubjects (%) with Controlled Disease by the IGA at Week 4

16 June,2017

p. 036

Full analysis set (LOCF)

54.6%

P=0.025

43.0%

Note: Graph illustrates observed values at each visit

13

Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis.

Jarnagin K, Chanda S, Coronado D, Ciaravino V, Zane LT, Guttman-Yassky E, Lebwohl MG.

J Drugs Dermatol. 2016;15:390-6.

Primary Efficacy Endpoint: Percentage of Patients Achieving Success in ISGA (Clear [0] or Almost Clear [1] with ≥2-Grade Improvement From Baseline)

0

5

10

15

20

25

30

35

40

22 29*

%o

fP

atie

nts

Ach

ievi

ng

S

uc

ce

ss

(IS

GA

of

0o

r1

Wit

h≥

2-G

rad

eIm

pro

vem

ent)

15

Study Day

1 8

Crisaborole (AD-301; n = 503)

Crisaborole (AD-302; n = 513)

Vehicle (AD-301; n = 256)

Vehicle (AD-302; n = 250)

* Primary endpoints at Day 29: 301, p=0.038; 302, p<0.001

Crisaborole

Vehicle

Comparison of tofacitinib vs ETN or PBO in moderate to severe chronic plaquepsoriasis: Phase 3 RCT

Valenzuela F, et al. AAD 2014,

% patients achieving a PASI 75 responsethrough Week 12 (NRI)

PBO(N=107)Tofa 5 mg BID (N=329) Tofa 10 mg BID (N=330) ETN 50 mg BIW (N=335)

PA

SI7

5re

spo

nse

(%)

20

100

80

60

40

20

04 8 10 126

Week

5.6

63.6

58.8

39.5

% patients achieving a PGA response through Week 12 (NRI)

PG

A r

esp

on

se(S

E) 100

80

60

40

20

00 2 4 8 10 126

Week

15.0

68.266.347.1

% patients achieving a PASI 90 responsethrough Week 12 (NRI)

PA

SI9

0re

spo

nse

(%)

20

100

80

60

40

20

04 8 10 126

Week

36.132.221.0

0.9

14

Oral ruxolitinib induces hair regrowth in patients withmoderate-to-severe alopecia areata.Mackay-Wiggan J, et al. JCI Insight. 2016;1:e89790.

Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata Kennedy

Crispin M, et al.JCI Insight. 2016;1:e89776.

Reversal of Alopecia Areata Following Treatment With theJAK1/2 Inhibitor Baricitinib.Jabbari A, et al. EBioMedicine. 2015;2:351-5.

Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy.Craiglow BG, King BA.JAMA Dermatol. 2015;151:1110-2

Preliminary clinical activity of a topical JAK1/2inhibitor in the treatment of psoriasis.

Punwani N, et al.

J Am Acad Dermatol. 2012;67(4):658-64.

15

The efficacy of afamelanotide and narrowband UV-Bphototherapy for repigmentation of vitiligo.

Grimes PE, Hamzavi I, Lebwohl M, Ortonne JP, Lim HW.

JAMA Dermatol. 2013;149:68-73.

AAD Practice Management Center

Office of Access to Care and Treatment

Rachna Chaudhari

www.aad.org/priorauth

Prior Authorization Assistance Center

16

Prior Authorization Letter Tool

Prior Authorization Letter Tool

Prior Authorization Letter Tool

17

Prior Authorization Letter Tool

Prior Authorization Letter Tool

www.Parioar Adu.thoorrizgat/iopnrLieotterraTouotlh

1

Pediatric Dermatology PearlsCraig Burkhart, MD, MS

Pediatric Dermatology

The University of North Carolina at Chapel Hill

Male infant with coarse white hair and dark tips

Saggy, pudgy cheeks

Saggy, wrinkly skin

Pili torti

2

Menkes Disease

• X‐linked recessive neurodegenerative disorder

• Copper transporter mutation

• Copper depletion occurs after delivery

• Disease manifestations develop after 2‐3 months of age

• Hair reflects copper depletion over time

Hair that is distally darker

Blondeambitionblog.com

Saggy skin and floppy baby

http://escholarship.org/uc/item/85x9m8m1

3

Menkies Pearls

• Why the down face?

• History of copper dilution reflected in hair 

Annular erythema in an 8 day old

Spongiosis, perivascular inflammation, no interface component: annular erythema of infancy (AEI)

4

Annular Erythema of Infancy

Annular erythema of infancy

Scaly

• Neonatal lupus until proven otherwise• ENA• Cardiology evaluation

Not‐scaly

• Consider autoinflammatorydisease (NOMID)• Articular disease• Neurologic disease• Fever• ESR, CRP, CBC• Ophthalmology evaluation

• Immunology evaluation

Neonatal lupus

FaceTelangiectasiasAtrophy

LupusImages.com

5

NOMID/CINCA Syndrome

Autoinflammatory‐search.org

www.AutoInflammatory‐Search.org

6

Annular Erythema in Neonates Pearls

• Always consider neonatal lupus and autoinflammatory disease

• Refer to cardiology if you have any suspicion for neonatal lupus• Even if biopsy and serologies are negative

• www.autoinflammatory‐search.org

7

Pearly white lesion on the left nipple

Nipple Bump Differential

Children

• Milia

• Milia‐like Syringoma

• Trichoepithelioma

• Fibroma

• Milia‐like Idiopathic Calcinosis Cutis

• Neonatal Fibroadnexal Polyp

Neonate

• Milia

• Neonatal Fiboradnexal Polyp

Neonatal Nipple Pearl

• Isolated pearly bumps on neonates will self‐resolve within a year

8

Bloody discharge in a 9‐year‐old boy

Worisome signs:‐ Unilateral‐ Persists longer than 9 months‐ Spontaneous discharge

Reassuring signs:‐ Centered on the nipple‐ Preadolescent

Biopsied after 10 months persistence

Mammary duct ectasia‐ brown‐colored mass with bloodstained fluid

9

Work‐up of discharge in infants and young children• Gram‐stain and culture of discharge

• Serum prolactin, estradiol, and thyrotropin

• Ultrasound of the affected breast

• If the above is normal and ultrasound consistent with mammary duct ectasia, consider a biopsy if the lesion lasts longer than 9 months

Kelly et al. Bloody Nipple Discharge in an Infant and a Proposed Diagnostic Approach. Pediatrics April 2006, volume 117(4)

Pediatric Nipple Discharge Pearls

• Work‐up of masses that last longer than 9 months

• Culture

• Ultrasound

• Pituitary work‐up (prolactin, TSH, estrodiol)

• Biopsy males if really needed

10

18 month old with a slow growing plaque

Pathology c/w dermatofibroma

Plaque‐like myofibroblastic tumor of infancy

• Appear in infancy and early childhood

• Lower back and hip

• Large plaque

• Histology similar to dermatofibroma

• Positive for factor XIIIa and SMA, negative for S‐100 and CD34

2 of 3 initially diagnosed as dermatofibromas by a great dermatopathologist

11

12

Plaque‐like Myofibroblastic Tumor Pearls

• Pathologist may diagnose as a dermatofibroma if you don’t provide with enough information

• Does not recur after excision

• Reassess diagnosis if it recurs after excision

‐ 8 Patients

‐ 6 days to 18 months after initiation of sennosides

‐ All bowel movements occurred overnight

‐ Chemical burn noticed during diaper change

13

Laxative‐associated contact dermatitis

• Only in non‐toilet‐trained children

• Prevent by giving Senna products at a time of day the allows for bowel movements to occur during the day (and not overnight)• 6‐10 hours after injestion

Irritant diaper dermatitis pearls

• Can clean feces with Vaseline soaked gauze instead of wipes

• Quantity of barrier cream (one‐half golf ball per diaper change) is more important than type of barrier cream

• Add an antifungal for any diaper dermatitis that lasts longer than 72 hours

14

‐ 7 month old with this eruption 3 month

‐ Started upon tapering tacrolimus

‐ Biopsy of neck revealed EPF

‐ Cleared with triamcinolone 0.1% ointm

‐ 8 yo boy with pruritic macules and papules 2 months after transplantation

‐ Biopsy c/w EPF

‐ Cleared with 5 months of betamethasone dipropionate ointment

15

Eosinophilic pustular folliculitis

• Recurrent crops/clusters of erythematous papules and pustules with an eosinophilic infiltrate on the biopsy

• Four types• Classic EPF• Immunosuppression/HIV‐associated EPF

• Infantile EPF• HSCT EPF

EPF‐HSCT

• Pruritic, follicular, erythematous papules and pustules

• Head, upper extremities, and trunk

• 2‐3 months after HSCT

• Resolves in several months

Infantile EPF

Hyper‐IgE Syndrome?

16

Burkhart Pearl: Bad red rashes in the first month of life are either:1. Ichthyosis2. Immunodeficiency3. Infection (candida or syphilis)

Consider an immunology workup for eczematous rashes that start in the 1st month of life. Don’t worry about infantile EPF.

Pediatric Eosinophilic Pustular Folliculitis Pearls• Treat symptomatically with steroids

• HSCT EPF resolves within months

• Infantile EPF resolves within years

• Base hyper‐IgE workup on timing of eruption and health of infant rather than EPF

1

DERMOSCOPY FORTHE  NON‐DERMOSCOPIST

Kelly Nelson, MD FAAD  

Associate Professor  

Department of Dermatology  

The University ofTexas

MDAnderson Cancer Center

Start Slow

Phase 1: Dermatoscope as amagnifying glass

• Get a dermatoscope

• Keep it in your pocket

• Look at everything before you biopsyit

Phase 2: test tumoridentification accuracy

• Commit on your pathology form• BCC vsSCC

• Melanocytic vs non‐melanocytic

• Do the introduction to dermoscopy  course next year

Start Slow

Phase 3: Iterative learning

• Attend the advanced dermoscopy course

• Photographeverything

• Review your clinical impression, photographs and images

2

Data organization

• Organized folders• Year/Month/Clinic date

• Diagnosis spreadsheet

• Patient privacy/security

DermoscopyOverview

• Melanocytic: benign vsmalignant• Non‐melanocytic

• AK,SCC• BCC• SK

• Special sites• Facial• Acral

• Unknowns

Practical Use ofDermoscopy

• Ugly Duckling (clinical)

• Ugly Duckling (dermoscopic)

• Individual lesion (dermoscopic)• Pattern recognition

3

3 point check list

• Asymmetry

• AtypicalNetwork

• Blue‐white structures

Soyer et al. Three Point Checklist of Dermoscopy.  Dermatology2004;208:27‐31

3 point checklistAverage Range

SensitivityOverall3‐point checklist

69.796.3

61.5 – 76.893.3 –98.0

SpecificityOverall3‐point checklist

82.832.8

77.0 – 87.420.7 – 47.7

Sensitivity: true positive rate;if the test is highly sensitive and it is  negative, you can be nearly certain that  they don’t have the condition;Sn(out)

Specificity: true negative rate;if the test is highly specific and it is  positive, you can be nearly certain that  they do have the condition;Sp(in)

3 point checklistAverage Range

SensitivityOverall3‐point checklist

69.796.3

61.5 – 76.893.3 –98.0

SpecificityOverall3‐point checklist

82.832.8

77.0 – 87.420.7 – 47.7

The three point check list helps you rule outmelanoma

If the three point check list is positive,  it doesn’t mean that it certainly is  melanoma; your clinical intuition is  more reliable.

4

Pattern Recognition

•Reticular

• Globular

• Homogenous

•Organized

•Disorganized

Special Sites

• Facial• Asymmetrical pigmented  openings

• Slate grey structures

• Acral• Furrows are fine

• Ridges are wrong

Schiffner et al.  Improvement of early recognition of lentigo maligna using dermatoscopy.  JAAD 2000 42(1):25‐32

5

Braun et al. The Furrow Ink Test. JAMA Derm 2008; 144(12):1618‐20; PMID19075144

Ink test: furrows are fine, ridges arewrong

Acral structure

Christa

intermediaEccrine  

duct

Christa  

limitans

Christa  

intermedia

Stratum

corneum

epidermis

dermis

Fibrillar

Parallelfurrow

Lattice

J Am Acad Dermatol. 2005 Aug;53(2):230-6.

6

Acral algorithm

Koga H, Saida T.  Revised 3 step dermoscopic algorithm for the management of acral lesions. JAMA Derm2011;147(6):741