MULTIDICLIPLINARY MANAGEMENT OF VITILIGO

Transcription

1 MULTIDICLIPLINARY MANAGEMENT OF VITILIGO Richard H. Huggins, MD Department of Dermatology Henry Ford Hospital, Detroit, MI 1

2 DISCLOSURE I have no conflicts of interest to disclose. 2

3 This presentation contains many off-label applications of medications 3

4 PHOTOGRAPHY & VIDEOTAPING ARE STRICTLY PROHIBITED IN ALL EDUCATIONAL SESSIONS CELL 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. FOTOGRAFIA E FILMANDO SÃO ESTRITAMENTE PROIBIDOS EM TODAS AS SESSÕES EDUCACIONAIS TELEFONES CELULARES DEVEM SER COLOCADOS EM VIBRAR OU DESLIGADOS Violações desta política resultará na remoção de sessão e possível revogação do registo da reunião. Diretores de sessão irão acompanhar de perto tais ocorrências.

5 OUTLINE Background Vitiligo Subtypes Vitiligo Management Conclusion 5

6 OUTLINE Background Vitiligo Subtypes Vitiligo Management Conclusion 6

7 VITILIGO Acquired white macules/patches on the body 0.5 2% of the world s population affected No racial or gender predominance Alkhateeb et al. Pigment Cell Res. 2003;16:208 7

8 VITILIGO ETIOLOGY Absence of melanocytes in the epidermis of affected areas Likely multifactorial etiology Genetic predisposition 1 in 6 pts have a 1 st degree relative with the disease Autoimmunity T-cells attacking melanocytes Oxidative Stress ROS involved in melanocyte destruction Alkhateeb et al. Pigment Cell Res. 2003;16:208 8

9 OUTLINE Introduction Vitiligo Subtypes Vitiligo Management Conclusion 9

10 FOCAL VITILIGO Confined to a limited area (non-dermatomal) Most responsive to medical management 10

11 SEGMENTAL VITILIGO Quasidermatomal distribution Usually unilateral Decreased progression after 2 years Usually more resistant to medical treatment Most responsive to surgical treatment Park JH et al. Ann Dermatol. 2014;26:6, Mulekar SV. Int J Dermatol. 2003;42:132 11

12 GENERALIZED VITILIGO Widespread involvement Often symmetric 12

13 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 14

15 SIGNS OF ACTIVE VITILIGO Patient subjective report of rapid spread Koebner phenomenon Trichrome lesions Inflammatory lesions Confetti-like depigmentation Rodrigues et al. JAAD. 2017;77:1 15

16 Confetti Vitiligo Inflammatory Vitiligo Trichrome Vitiligo Rodrigues et al. JAAD. 2017;77:1 16

17 OUTLINE Introduction Vitiligo Subtypes Vitiligo Management Conclusion 17

18 VITILIGO MANAGEMENT Medical Management Surgical Management Psychosocial Management 18

19 VITILIGO MANAGEMENT Medical Management Surgical Management Psychosocial Management 19

20 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 Vrijman 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 20

21 TOPICALS 21

22 COVER-UP Camouflage cosmetically sensitive areas 22

23 COVER-UP BRANDS Dermablend (Macy s), CoverFx (Sephora), CoverBlend (Ulta), Iman Cosmetics (Target), Kat Von D (tattoo coverup, 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 Hossain C et al. J Drugs Dermatol. 2016;15:4 23

24 DIHYDROXYACETONE Self-tanning products Clarins Concentrations range from % Darker skin, higher concentration Safe, inexpensive Water resistant, last up to a week Hossain C et al. J Drugs Dermatol. 2016;15:384 24

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

26 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 Kwon HB et al. J Drugs Dermatol. 2013;12:e

27 SYSTEMICS 27

28 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) Dell'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 28

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

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

31 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 corticosteroids 31

32 25-YEAR OLD FEMALE WITH WIDESPREAD Baseline VITILIGO 6 months of NB-UVB, oral corticosteroids and thyroid replacement Courtesy of Dr. Iltefat Hamzavi 32

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

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

35 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 Lim HW et al. JAMA Dermatol. 2015;151:42 35

36 AFAMELANOTIDE Combination therapy yielded significantly superior (48.64% vs 33.26%) and faster (41-46 days vs 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 Lim HW et al. JAMA Dermatol. 2015;151:42 36

37 AFAMELANOTIDE Combination Therapy Group NB-UVB Only Group Lim HW et al. JAMA Dermatol. 2015;151:42 37

38 AFAMELANOTIDE Combination Therapy Group NB-UVB Only Group Lim HW et al. JAMA Dermatol. 2015;151:42 38

39 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

40 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% Craiglow, King. JAMA Dermatol. 2015;Jun 24:E1 40

41 41

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

43 -centr 43

44 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, nonmelanoma skin cancer) HTN, transaminitis, increased creatinine and lipids Tofacitinib Monitoring BP, CBC, CMP, lipids Similar for ruxolitinib 44

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

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

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

48 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 % repigmentation of her chest and arms, including her hands SB. Case Rep Dermatol Med. 2017;20174:

49 PHOTOTHERAPY 49

50 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 Leone G et al. J Eur Acad Dermatol Venereol. 2003;17:531 50

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

52 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 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 52

53 NB-UVB PHOTOTHERAPY CONSENSUS RECOMMENDATIONS Full Global Vitiligo Foundation recommendations available on 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 treatments to determine lack of response 53

54 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) Hexsel et al. JAAD. 2009;60:929, Mohammad et al In press, Paradisi et al. JAAD.2014;71:1110, Teulings et al. BJD. 2013;168:162 54

55 DEPIGMENTATION 55

56 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 paratertiary butyl phenol Rubber sandal /black shoes minimize use without socks Black socks - minimize use due to components of black dye Eyeliner minimize use Ghosh S et al. Br J Dermatol. 2009;160:

57 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 net/new/causes-andtreatment-of-vitiligo-byexpert/ Freedberg IM et al. In Fitzpatrick s Dermatology in General Medicine, 5 th edn:945 57

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

59 VITILIGO MANAGEMENT Medical Management Surgical Management Psychosocial Management 59

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

61 SURGICAL VITILIGO TREATMENTS Tissue Grafting: intact pieces of uninvolved epidermis are transplanted Punch Grafting Split-Thickness Grafting Suction Blister Roof Grafting 61 61

62 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

63 GRAFT HARVESTING Split-thickness graft Ideally 200 microns Courtesy of Iltefat Hamzavi, MD 63 63

64 CELL SEPARATION Epidermis chemically and physically separated from dermis Courtesy of Iltefat Hamzavi, MD 64 64

65 TRANSPLANTATION OF CELLULAR SUSPENSION Recipient site epidermis is removed with either motorized dermabrasion or CO2 laser Courtesy of Iltefat Hamzavi, MD 65 65

66 TRANSPLANTATION OF CELLULAR SUSPENSION Epidermal cell suspension evenly seeded on dermabraded lesions Collagen dressing applied Courtesy of Iltefat Hamzavi, MD 66 66

67 HENRY FORD MKTP RESULTS Long-term (1-6 yr) follow-up study of all MKTP patients treated through April of pts with segmental and nonsegmental vitiligo SV : 75.6% improvement in VASI NSV: 59.2% improvement of VASI Silpa-Archa N et al. JAAD.77:

68 Baseline 3 months 10 months 4.5 years 4 years Silpa-Archa N et al. JAAD.77:

69 VITILIGO MANAGEMENT Medical Management Surgical Management Psychosocial Management 69

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

71 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 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 71

72 PSYCHOSOCIAL MORBIDITY Low self-esteem/embarrassment Increased marital difficulties and higher divorce rates Sexual difficulties (~ 20% ) 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 72

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

74 PATIENT RESOURCES List of US Vitiligo Support Groups/Facebook Groups Books and camps for children with vitiligo Other resources Vitiligo Research Foundation (vrfoundation.org) Global Vitiligo Support Community ( Vitiligo Support International (vitiligosupport.org) 74

75 OUTLINE Background Vitiligo Subtypes Vitiligo Management Conclusion 75

76 CONCLUSION Key clinical subtypes of vitiligo Summarized medical and surgical vitiligo management modalities Importance of psychosocial management of vitiligo 76

77 Acknowledgements James Griffith, MD Iltefat Hamzavi, MD Tasneem Mohammed, MD Cynthia Nicholson, MD E. Nikki Pritchett, MD, MPH Henry W. Lim, MD 77