MULTIDICLIPLINARY MANAGEMENT OF VITILIGOUlta), Iman Cosmetics (Target), Kat Von D (tattoo cover-up,...

MULTIDICLIPLINARY

MANAGEMENT OF VITILIGO

Richard H. Huggins, MD

Department of Dermatology

Henry Ford Hospital, Detroit, MI

1

DISCLOSURE

I have no conflicts of

interest to disclose.

2

This presentation contains many off-label

applications of medications

3

FOTOGRAFIA E FILMANDO SÃO ESTRITAMENTE PROIBIDOS EM TODAS AS SESSÕES EDUCACIONAIS

TELEFONES CELULARES DEVEM SER COLOCADOS EM VIBRAR OU DESLIGADOSViolações desta política resultará na remoção de sessão e possível revogação do registo da reunião.

Diretores de sessão irão acompanhar de perto tais ocorrências.

PHOTOGRAPHY & VIDEOTAPING ARE STRICTLY PROHIBITED

IN ALL EDUCATIONAL SESSIONSCELL PHONES MUST BE PLACED ON VIBRATE OR TURNED OFF

Violations of this policy will result in removal from the session and possible revocation of meeting registration.

Session directors will be closely monitoring such occurrences.

OUTLINE

• Background

• Vitiligo Subtypes

• Vitiligo Management

• Conclusion

5

OUTLINE

• Background



• Conclusion

6

VITILIGO

• Acquired white macules/patches on the body

• 0.5 – 2% of the world’s population affected

• No racial or gender predominance

7Alkhateeb et al. Pigment Cell Res. 2003;16:208

VITILIGO ETIOLOGY

• Absence of melanocytes in the epidermis of affected

areas

• Likely multifactorial etiology

• Genetic predisposition

– 1 in 6 pts have a 1st degree relative with the disease

• Autoimmunity

– T-cells attacking melanocytes

• Oxidative Stress

– ROS involved in melanocyte destruction8Alkhateeb et al. Pigment Cell Res. 2003;16:208

OUTLINE

• Introduction



• Conclusion

9

FOCAL VITILIGO

• Confined to a limited area (non-dermatomal)

• Most responsive to medical management

10

SEGMENTAL VITILIGO

• Quasidermatomal distribution

• Usually unilateral

• Decreased progression after 2 years

• Usually more resistant to medical

treatment

• Most responsive to surgical treatment

11Park JH et al. Ann Dermatol. 2014;26:6, Mulekar SV. Int J Dermatol. 2003;42:132

GENERALIZED VITILIGO

• Widespread involvement

• Often symmetric

12

ACROFACIAL VITILIGO

• Cases in which there is involvement of the

fingers/toes and perioral regions

• Lesions on ANY part of the body are less

responsive to all treatments

13

14

ACROFACIAL VITILIGO

SIGNS OF ACTIVE VITILIGO

• Patient subjective report of rapid spread

• Koebner phenomenon

• Trichrome lesions

• Inflammatory lesions

• Confetti-like depigmentation

15Rodrigues et al. JAAD. 2017;77:1

16Rodrigues et al. JAAD. 2017;77:1

Confetti Vitiligo Trichrome Vitiligo

Inflammatory Vitiligo

OUTLINE

• Introduction



• Conclusion

17

VITILIGO MANAGEMENT

• Medical Management

• Surgical Management

• Psychosocial Management

18

VITILIGO MANAGEMENT




19

ASSOCIATIONS

• Nearly 20% of vitiligo patients have at least 1 comorbid

autoimmune disease

• Autoimmune thyroid disease: ~15.1%– Check baseline TSH, annual recheck vs symptom screen at follow-up

• Less common associations: AA, IBD, pernicious anemia

• Newer associations: DLE, Guillain-Barre, linear

morphea, myasthenia gravis, Sjogren

20Vrijman C et al. Br J Dermatol. 2012;167:1224, Alkhateeb A et al. Pigment Cell Res. 2003;16:208, Gill et al. JAAD. 2016;74:295

TOPICALS

21

COVER-UP

• Camouflage cosmetically sensitive areas

22

COVER-UP BRANDS

• Dermablend (Macy’s), CoverFx (Sephora), CoverBlend

(Ulta), Iman Cosmetics (Target), Kat Von D (tattoo cover-

up, Sephora)

• Microskin

– Liquidized formulation

– Waterproof and resistant to frictional rubbing

– Lasts up to several days

– Computer color-matched (Pasadena, CA and NY, NY)

– Hundreds to thousands of dollars per year

23Hossain C et al. J Drugs Dermatol. 2016;15:4

DIHYDROXYACETONE

• Self-tanning products

– Clarins

• Concentrations range from 2.5-12%

– Darker skin, higher concentration

• Safe, inexpensive

• Water resistant, last up to a week

24Hossain C et al. J Drugs Dermatol. 2016;15:384

TOPICAL IMMUNOSUPPRESSANTS

• Focal > generalized vitiligo

• Class 3/4 topical corticosteroids (TCS) x 3-4 months → 75%

repigmentation in 55-56% of patients with localized vitiligo

• Calcineurin inhibitors and TCS have statistically equivalent

efficacy

• Face/neck - Calcineurin inhibitors preferred alternative

• Body - ? Increased efficacy of Class 1/2 TCS

– Non-statistically significant increased efficacy of topical corticosteroids on

the body

– Possible faster and increased efficacy observed clinically

25Njoo M.D et al. Arch Dermatol 1998;134:1532, Ho N et al. Br J Dermatol. 2011;165:626

TOPICAL RETINOIDS

• Placebo-controlled, paired-comparison, left-right study

• 50 patients diagnosed with generalized vitiligo received 6 months

of tretinoin plus topical corticosteroid and the vehicle plus the

same corticosteroid (vehicle plus)

• 55% showed a better response to tretinoin plus than to vehicle

plus

• The improved response was noted at an early stage of treatment,

during the first 3 months in 60% of patients

• Topical tretinoin is known to prevent skin atrophy induced by

long-term use of topical corticosteroids

26Kwon HB et al. J Drugs Dermatol. 2013;12:e63-7.

SYSTEMICS

27

ANTIOXIDANTS

• Oxidative stress involved in pathogenesis

• α-Lipoic Acid • 100 mg daily

• Best combined with NB-UVB

• Gingko Biloba• 60 mg twice per day

• Best at halting slowly spreading disease

• Foods (blueberries)

28Dell'Anna ML et al. Clin Exp Dermatol. 2007;32:631, Parsad D et al. Clin Exp Dermatol. 2003;28:285,

Szczurko O et al. BMC Complement Altern Med. 2011;11:21

MINOCYCLINE

• Antibiotic with anti-inflammatory, free-radical scavenging

properties

• Used in 32 patients with slowly spreading vitiligo at a dosage of

100 mg daily for 3 months

– Stopped spread in 29/32 (91%)

– Repigmentation in 7/32 (21%)

• RCT of 50 patients found that 6 months of minocycline was

comparable to oral mini-pulse steroids (2.5mg dexamethasone for

2 consecutive days/week x6 months) in stopping actively

spreading disease

29Parsad D et al. Dermatol Ther. 2010;23:305, Indian J Dermatol Venereol Leprol. 2014;80:29

ORAL STEROIDS AND VITILIGO

• Indicated for halting rapidly spreading vitiligo

– Confetti-like macules, koebnerization, new lesions

• Oral minipulse therapy

– Dexamethasone 2.5mg-10mg daily on the weekends

only x 3-6 months

– Minimizes adverse effects

30Kanwar A et al. J Cutan Med Surg. 2013;17:259, Majid I et al. Indian J Dermatol 2013;58:113

ORAL STEROID COMBINATION THERAPY

• Protocol developed by Dr. Hamzavi for patients with

recalcitrant widespread vitiligo

• NB-UVB TIW

• Oral corticosteroids

– Stepwise progression

– Minipulse dosing with dexamethasone 4mg daily on weekends

– Prednisone 20mg QOD

– Prednisone 20mg daily

• D/c after repigmentation plateaus or 6 months of

corticosteroids31

25-YEAR OLD FEMALE WITH WIDESPREAD

VITILIGO

Baseline

6 months of NB-UVB, oral

corticosteroids and thyroid

replacement

32Courtesy of Dr. Iltefat Hamzavi

REPIGMENTATION MAINTENANCE

THERAPY

• With successfully repigmented patients, 44% relapse

after treatment is discontinued

• Focal vitiligo – tacrolimus 0.1% ointment BIW

significantly reduces risk of local recurrence

• Generalized vitiligo

– gingko biloba and minocycline effective anecdotally

– Tapering of phototherapy may be necessary

33Cavalié et al. J Invest Dermatol. 2015;135:970, Nicolaidou et al. JAAD. 2007;56:274

AFAMELANOTIDE

• Afamelanotide is a synthetic analogue of

melanocyte-stimulating hormone (α-MSH)

• Rationale: defects in the melanocortin system in

vitiligo patients

– Decreased serum and lesional α-MSH

• α-MSH helps restore this deficiency and

stimulates melanocyte reproduction and growth

34Lim HW et al. JAMA Dermatol. 2015;151:42

AFAMELANOTIDE

• Randomized, controlled, multi-center clinical trial

(Including Henry Ford Hosp)

• Afamelanotide subcutaneous implants plus NB-

UVB (combination therapy) vs NB-UVB

monotherapy x 6 months

• 55 nonsegmental vitiligo patients with Skin

Phototypes III to VI


AFAMELANOTIDE

• Combination therapy yielded significantly superior

(48.64% vs 33.26%) and faster (41-46 days vs 61-69 days)

repigmentation of the face and upper extremities

• Hyperpigmentation of unaffected skin reported in 2

patients (7%) in the combination therapy group

– Other AE: nausea and abdominal pain


Combination

Therapy Group

NB-UVB Only

Group

AFAMELANOTIDE


JAK INHIBITORS

•Janus Kinase (JAK) enzyme inhibitors act

as immunosuppressors–JAK → ↑ IFN-γ → active CXCL10 → immune

system activation

•Tofacitinib – JAK 1/3 inhibitor

•Ruxolitinib – JAK 1/2 inhibitor

39

TOFACITINIB

• FDA approved: rheumatoid arthritis

• Off-label : alopecia areata, plaque psoriasis

• Case report of 1 woman in her 50s with generalized

vitiligo (~10% BSA)

• Treated with 5 months of PO tofacitinib - 5 mg QOD x 3

weeks, then daily

• Substantial repigmentation at 5 months

– Significant repigmentation of hands

– BSA decreased to 5%40Craiglow, King. JAMA Dermatol. 2015;Jun 24:E1

RUXOLITINIB

• FDA-approved for myelofibrosis and

polycythemia vera

• Case report of a 35-year-old man with widespread

vitiligo including > 99% facial depigmentation

• Improved to 51% repigmentation of his face with

ruxolitinib 20mg BID x 20 weeks

42Harris et al. JAAD. 2016;74:370

-centr

43

SIDE EFFECTS AND MONITORING

• Tofacitinib Side effects

– Immunosuppressive effects – Increased risk of

infection (upper respiratory tract infection, UTI) and

possible increased risk of cancer (lymphoma, non-

melanoma skin cancer)

– HTN, transaminitis, increased creatinine and lipids

• Tofacitinib Monitoring – BP, CBC, CMP, lipids

• Similar for ruxolitinib

44

TOPICAL JAK INHIBITORS

• If effective, should be safer and cheaper than the systemic agents

• Ruxolitinib 1.5% cream BID x 20 weeks in 12 patients

– Overall: 23% decrease in VASI

– Facial vitiligo (n=4): 76% improvement in facial VASI

– 3 of 8 responded on body surfaces, 1 of eight responded on acral surfaces

• Multi-center, phase III clinical trial using varying concentrations

and dosing regimens of ruxolitinib cream is ongoing (HF is one of

the sites)

45Rothstein B et al. JAAD. 2017;76:1054

CYCLOPHOSHPHAMIDE

• 50mg daily (normal dose is ≥ 80mg daily)

• repigmentation in 30/33 patients

• including some acral lesions

• many pts had failed PUVA

• side effects reported were nausea, transient hair

loss (4), and transient leukopenia (degree or

number of subjects not mentioned)

46Gokhale B. Int J Dermatol. 1979;18:92

METHOTREXATE

• MTX 12.5 -25mg weekly resulted in “clinically significant”

repigmentation in 3 pts

– response ≥ 6 weeks

– including 2/3 patients who previously failed TCIs and

phototherapy

– Including repigmentation of acral involvement

• MTX 10mg per wk and dexamethasone 5mg weekly

(OMP) x 6 mo equivalent in preventing new lesions

development in actively spreading vitiligo

47Garza-Mayers AC. J Drugs Dermatol. 2017;16:705, Singh H et al. Dermatology. 2015;231:286

APREMILAST

• Case report

• 52 yo f with chronic vitiligo who had previously failed

various topicals, PUVA, IM/PO steroids, and cyclosporine

• Apremilast 30mg BID x 11 months with IM triamcinolone

x 2

• 60-70% repigmentation of her chest and arms, including

her hands

48

SB. Case Rep Dermatol Med. 2017;20174:2386234

PHOTOTHERAPY

49

TARGETED PHOTOTHERAPY

• Localized vitiligo

• Excimer laser

• Rapid induction of repigmentation and fewer treatments

compared to conventional NB-UVB

– Treatment twice per week x 6 months

– >75% repigmentation in 49% of patients

50

Leone G et al. J Eur Acad Dermatol Venereol. 2003;17:531

WHOLE-BODY PHOTOTHERAPY

• Generalized vitiligo

• NB-UVB preferred modality

• >75% repigmentation by duration of tx– 3 mo – 13%

– 6 mo – 19.2%

– 12 mo – 35.7%

• 6-12 mo of NB-UVB by location

– Face/neck – 44.2%

– Trunk – 26.1%

– Extremities – 17.3%

51Bae J et al. JAMA Derm. 2017;153:666

COMBINATION PHOTOTHERAPY

• Synergistic effect with topicals

• Tacrolimus

– Enhances response

• Reduction in mean lesion size of 29% (NB-UVB alone) vs 42.1% (plus

Tac)

– Enhances repigmentation rates

• > 75% repigmentation in 19% (excimer laser alone) vs 50% (plus Tac)

• Pimecrolimus and topical steroids also potentiate effects of

phototherapy for facial vitiligo

52

Bae JM et al. 2016;74:907, Nordal EJ et al. J Eur Acad Dermatol Venereol 2011;25:1440, Esfandiarpour I et al. J

Dermatolog Treat 2009;20:14, Sassi F et al. Br J Dermatol. 2008;159:1186, Kawalek A et al. Dermatol Surg 2004;30:130

NB-UVB PHOTOTHERAPY CONSENSUS

RECOMMENDATIONS

• Full Global Vitiligo Foundation recommendations

available on www.vitiligoworkinggroup.com

• Goal is for vitiligo lesions to turn a light pink (carnation

color) following treatment

• Frequency of administration – TIW is optimal

• Dosing protocol – increase by 10-20% per treatment

• Max doses – 1500mj/cm2 for face, 3000mj/cm2 for body

• 48 - 72 treatments to determine lack of response

53

http://www.vitiligoworkinggroup.com/

PHOTOTHERAPY CONSENSUS

RECOMMENDATIONS

• Monthly tapering after complete repigmentation

• SPT I-III: Yearly follow-up for total body skin exam to

monitor for adverse effects of phototherapy, including

cutaneous malignancy

– Hexsel et al: nonsignificant increase in NMSCs

– Paradisi et al: decreased risk of NMSCs and melanoma

– Teulings et al: no increase in NMSC or melanoma with

phototherapy (questionnaire study)

– No long-term data (only 5-16 yrs)

54Hexsel et al. JAAD. 2009;60:929, Mohammad et al. 2017. In press, Paradisi et al. JAAD.2014;71:1110, Teulings et al. BJD.

2013;168:162

DEPIGMENTATION

55

CHEMICAL LEUKODERMA

• Some household and other commonly used items that can cause a leukoderma

mimicking vitiligo or can exacerbate pre-existing vitiligo

• Consider with confetti vitiligo or contact patterned vitiligo

• Hair dye – avoid hair dyes with para-phenylene diamine

• Deodorant ⁄perfume/detergent/cleansers - make sure they do not contain para-

tertiary butyl phenol

• Rubber sandal /black shoes – minimize use without socks

• Black socks - minimize use due to components of black dye

• Eyeliner – minimize use

56Ghosh S et al. Br J Dermatol. 2009;160:40-7

DEPIGMENTATION

• Removal of remaining skin color in patients with

vitiligo

• Used for patients with vitiligo involving either

>50% of their bodies or resistant involvement of

cosmetically sensitive areas

• The most effective vitiligo treatment (90-95%

complete depigmentation)

• Usually irreversible

• Cultural/psychological considerations

57

http://nationalmirroronline.

net/new/causes-and-

treatment-of-vitiligo-by-

expert/

Freedberg IM et al. In Fitzpatrick’s Dermatology in General Medicine, 5th edn:945

DEPIGMENTATION

• Monobenzyl ether of hydroquinone 20-40%

– Depigmentation usually starts within 1-4 months and complete

depigmentation may take 1-2 years

• Cryotherapy

• Laser

– The Q-switched ruby

– The Q-switched alexandrite

– The Q-switched 532nm Nd:YAG

58Taieb A et al. Br J Dermatol 2013;168:5

VITILIGO MANAGEMENT




59

SURGERY INDICATIONS

• Autologous skin transplantation

• Stable vitiligo for 6 - 24 months

• Vitiligo subtype: Segmental > Focal >

Generalized > Acrofacial

• 2013 European Dermatology Forum consensus

statement includes surgery in the treatment

algorithm for NSV and SV

60Taieb et al. Br J Dermatol. 2013;168(1)

SURGICAL VITILIGO TREATMENTS

Tissue Grafting: intact pieces of uninvolved epidermis

are transplanted

– Punch Grafting

– Split-Thickness Grafting

– Suction Blister Roof Grafting

6161

SURGICAL VITILIGO TREATMENTS

Cellular Grafting: epidermal cells transplanted as a

suspension

– Cultured melanocyte/epidermal sheet transplantation

– Non-cultured methods

• Melanocyte-Keratinocyte Transplantation Procedure

(MKTP)

• Best extent and quality of repigmentation

62

GRAFT HARVESTING

•Split-thickness

graft

• Ideally 200

microns

6363Courtesy of Iltefat Hamzavi, MD

CELL SEPARATION

• Epidermis chemically and physically separated from

dermis


TRANSPLANTATION OF

CELLULAR SUSPENSION

• Recipient site epidermis is removed with either motorized

dermabrasion or CO2 laser


TRANSPLANTATION OF

CELLULAR SUSPENSION

• Epidermal cell

suspension evenly

seeded on

dermabraded lesions

• Collagen dressing

applied


HENRY FORD MKTP RESULTS

• Long-term (1-6 yr) follow-up study of all MKTP

patients treated through April of 2014

• 52 pts with segmental and nonsegmental vitiligo

– SV : 75.6% improvement in VASI

– NSV: 59.2% improvement of VASI

67Silpa-Archa N et al. JAAD.77:318.

68

Baseline3 months

10 months4.5 years

4 years

Silpa-Archa N et al.

JAAD.77:318.

VITILIGO MANAGEMENT




69

VITILIGO PSYCHOSOCIAL

CHALLENGES

• QoL impairment similar to psoriasis and atopic dermatitis

• Can significantly alter appearance

• Unpredictable and progressive

• Most affected are: women, young, darker-complexioned, vitiligo on

exposed sites

• There are some patients for whom no treatment will be effective

• Effective treatments are slow

• Multidisciplinary approach is needed

70Amer, Gao. Int J Dermatol. 2016;55:729, Linthorst MW et al. JAAD. 2009;61:411

PSYCHOSOCIAL MORBIDITY

• Psychological Disorders in 30% of patients with

vitiligo

– Anxiety: 19% of vitiligo patients

– Depression

• 55% with some degree of depression

• 8% with full-blown depression

• Consider behavioral health referral

71

Porter J et al. Gen Hosp Psychiatry. 1979;1:73, Gieler U et al. Dermatol Psychosom 2000;1:6, Al-Harbi M. Skinmed

2013;11:327, Ajose FO et al. J Eur Acad Dermatol Venereol. 2014;28:925

PSYCHOSOCIAL MORBIDITY

• Low self-esteem/embarrassment

• Increased marital difficulties and higher divorce

rates

• Sexual difficulties (~ 20% )

72

Krüger C et al. Acta Derm Venereol 2011;91:152, Silverberg JI et al. JAMA Dermatol. 2013;149:159

Kim do Y et al. J Dermatol. 2013;40:1065 , Wang KY et al. J Eur Acad Dermatol Venereol. 2011;25:429

SUPPORT GROUPS

• Bring together groups of people with common

experiences

• Medical information (free and accessible)

• Provide behavioral role-modeling (day-to-day

management)

• Empowerment – active role in treatment, teaching

and otherwise helping others

73Dennis C.L. Int J Nurs Stud 2003;40:321, Glasgow RE et al. Patient Educ Couns 2001;44:119

PATIENT RESOURCES

• List of US Vitiligo Support Groups/Facebook Groups

– https://www.globalvitiligofoundation.org/support-groups

• Books and camps for children with vitiligo

– https://www.globalvitiligofoundation.org/global-vitiligo-support-community

• Other resources

– Vitiligo Research Foundation (vrfoundation.org)

– Global Vitiligo Support Community

(https://www.globalvitiligofoundation.org/global-vitiligo-support-

community)

– Vitiligo Support International (vitiligosupport.org)

74

https://www.globalvitiligofoundation.org/support-groups

OUTLINE

• Background



• Conclusion

75

CONCLUSION

• Key clinical subtypes of vitiligo

• Summarized medical and surgical vitiligo

management modalities

• Importance of psychosocial management of vitiligo

76

Acknowledgements

• James Griffith, MD

• Iltefat Hamzavi, MD

• Tasneem Mohammed, MD

• Cynthia Nicholson, MD

• E. Nikki Pritchett, MD, MPH

• Henry W. Lim, MD

77

MULTIDICLIPLINARY MANAGEMENT OF VITILIGOUlta), Iman Cosmetics (Target), Kat Von D (tattoo cover-up,...

Documents

Transcript of MULTIDICLIPLINARY MANAGEMENT OF VITILIGOUlta), Iman Cosmetics (Target), Kat Von D (tattoo cover-up,...