Update on Challenging Disorders of Pigmentation in Skin of Color

Transcription

1 Update on Challenging Disorders of Pigmentation in Skin of Color Heather Woolery-Lloyd, M.D. Director of Ethnic Skin Care Voluntary Assistant Professor Miller/University of Miami School of Medicine Department of Dermatology and Cutaneous Surgery

2 What Determines Skin Color?

3 What Determines Skin Color? No significant difference in the number of melanocytes between the races 2000 epidermal melanocytes/mm 2 on head and forearm 1000 epidermal melanocytes/mm 2 on the rest of the body differences present at birth Jimbow K, Quevedo WC, Prota G, Fitzpatrick TB (1999) Biology of melanocytes. In I. M. Freedberg, A.Z. Eisen, K. Wolff,K.F. Austen, L.A. Goldsmith, S. I. Katz, T. B. Fitzpatrick (Eds.), Dermatology in General Medicine 5th ed., pp , New York, NY: McGraw Hill

4 Szabo G, Gerald AB, Pathak MA, Fitzpatrick TB. Nature1969;222: Jimbow K, Quevedo WC, Prota G, Fitzpatrick TB (1999) Biology of melanocytes. In I. M. Freedberg, A.Z. Eisen, K. Wolff, K.F. Austen, L.A. Goldsmith, S. I. Katz, T. B. Fitzpatrick (Eds.), Dermatology in General Medicine 5th ed., pp , New York, NY: McGraw Hill Melanosomes in Black and White Skin Black White

5 Role of Melanin-Advantages Melanin absorbs and scatters energy from UV and visible light to protect epidermal cells from UV damage

6 Disadvantages Inflammation or injury to the skin is almost immediately accompanied by alteration in pigmentation Hyperpigmentation Hypopigmentation

7 Dyschromias Post-Inflammatory hyperpigmentation Acne Melasma Lichen Planus Pigmentosus Progressive Macular Hypomelanosis Vitiligo

8 Post Inflammatory Hyperpigmentation: Acne

9 PIH from Acne Acne hyperpigmented macule Patients are most concerned with pigmentation Not the acne!!!

10 Pigment and Acne in Skin of Color Common Questions Does benzoyl peroxide bleach the skin? No Rarely can cause post-inflammatory hypopigmentation Post inflammatory hyperpigmentation more common

11 Pigment and Acne in Skin of Color Common Questions Does benzoyl peroxide cause hyperpigmentation in SOC? Yes if patient develops irritation Approximately 5% of the population is sensitive to BP Many can tolerate lower concentrations (less than 5%)

12 Pigment and Acne in Skin of Color Common Questions Does minocycline cause hyperpigmentaion in SOC? Yes Clinically can see overall darkening of face Also reported darkening of lips, scars, legs Use other antibiotics as first line therapy in SOC

13 Pigment and Acne in Skin of Color Common Questions Do retinoids cause hyperpigmentation in SOC? Yes if patient develops irritation More common with tretinoin and tazarotene Less common with adapalene but still possible Usually occurs within a month of use Resolves once agent is discontinued

14 Pigment and Acne in Skin of Color Common Questions Do retinoids also treat hyperpigmentation? Yes Tretinoin Tazarotene Adapalene

15 Tretinoin Influences melanosome transfer Tretinoin 0.1% has been demonstrated to be effective for melasma in a vehiclecontrolled trial Slow results Griffiths CE. Finkel LJ. Ditre et al.british Journal of Dermatology 1993; 129(4):415-21

16 Tretinoin for dyschromia Blinded vehicle controlled trial 68 AA subjects with hyperpigmentation due to acne, folliculitis, eczema, shaving irritation 40 weeks Topical tretinoin 0.1% cream or vehicle applied to face and arms Investigator assessments and colorimetry La Voo EJ. New Eng J Med Nov 1993

17 Tretinoin for dyschromia Evaluated hyperpigmented and normal skin Hyperpigmented skin Improvement in affected skin seen clinically at 4 weeks with tretinoin vs 24 weeks with vehicle Normal skin No significant lightening observed clinically but mild skin lightening was observed via colorimetry in the tretinoin group La Voo EJ. New Eng J Med Nov 1993

18 Tretinoin for dyschromia Tretinoin 0.1% cream achieved more rapid clearance of hyperpigmented lesions compared to vehicle 4 weeks vs 24 weeks La Voo EJ. New Eng J Med Nov 1993

19 Patient with acne and hyperpigmentation treated with Tretinoin 0.1% cream La Voo EJ. New Eng J Med Nov 1993

20 Tazarotene for PIH Blinded vehicle controlled trial 74 patients from darker racial ethnic groups who had acne Once-daily application of tazarotene cream was shown to be effective against PIH Reductions in overall PIH severity and in the intensity and area of hyperpigmentation was observed when compared to vehicle within 18 weeks (P< or =.05). Grimes P. Callender V. Cutis. 77(1):45-50, 2006 Jan.

21 Adapalene in Black Africans for PIH Open label trial of patents with acne N=44 Identified 5 lesions on each patient and observed color change over 4 weeks 66% of patients experienced reductions in both number of hyperpigmented macules and density of the hyperpigmentation Jacyk WK J Eur Acad Vener Dermatol Vol15 Suppl3 2001

22 Tazarotene vs Adapalene for PIH Blinded controlled trial n=180 Evaluated in improvement in acne and PIH Demographics (Total nonwhite subjects=62%) Black 29% Asian 12% Hispanic 15% Other 6% Tanghetti E et al J Drugs Dermatol May;9(5):549-58

23 Tazarotene vs Adapalene Both tazarotene 0.1% cream and adapalene 0.3% gel were effective for acne The percentage of non-white patients with compete resolution of their PIH at week % (5/25) in the tazarotene 0.1% cream group 7% (2/29) in the adapalene 0.3% gel group Tazarotene 0.1% cream was more effective than adapalene 0.3% gel in reducing PIH Subjects experienced more erythema, peeling, dryness and burning with tazarotene compared to adapalene Tanghetti E et al J Drugs Dermatol May;9(5):549-58

24 Isotretinoin reduces hyperpigmentation in acne Ten black patients, ranging in age from 17 to 34 years, were treated for nodulocystic acne with 1 mg/kg/d of isotretinoin for 20 weeks The authors concluded isotretinoin is as safe and effective in the black patient with acne as it is in the white patient with acne An additional benefit in black patients was the prevention of new, and repression of old, postinflammatory hyperpigmentation. Kelly, A. Paul, and Darlene D. Sampson. "Recalcitrant nodulocystic acne in black Americans: treatment with isotretinoin." Journal of the National Medical Association (1987): 1266.

25 Before and after 20 weeks Isotretinoin 1mg/kg Kelly, A. Paul, and Darlene D. Sampson. "Recalcitrant nodulocystic acne in black Americans: treatment with isotretinoin." Journal of the National Medical Association (1987): 1266.

26 Retinoids work for PIH in acne Don t hesitate to use them in skin of color Choose the one that best suits your patients needs!

27 Acne and Post-Inflammatory Hyperpigmentation - Treatment Acne and dyschromia (<16yo) Retinoids not only improve acne but also pigmentation Azelaic acid 20% cream or 15% gel Works on hyperpigmentation and acne Moisturizer with sunscreen Consider natural therapies (soy, licorice or emblica)

28 Acne and Post-Inflammatory Hyperpigmentation Acne and dyschromia (>16yo) Add hydroquinone 2% available OTC 4% available with a prescription 6-8% can be compounded Apply only to the affected area as needed Avoid continued long term use Less than 2 months Maintain with alternate therapies

29 Hydroquinone Sensitivity A subset of patients are sensitive to and irritated by HQ Irritation from HQ is frequently due to HQ sodium metabisulfite (a common preservative in HQ preparations) Continuing HQ despite irritation can lead to postinflammatory hyperpigmentation Pei-Ying Huang, Chia-Yu Chu (2007) Allergic contact dermatitis due to sodium metabisulfite in a bleaching cream Contact Dermatitis 56 (2),

30 Before treatment After 8 weeks of HQ8%/Tret0.025%/Dex0.1%

31 Hydroquinone Halo Occurs when hydroquinone is applied with the fingertips To avoid the hydroquinone halo Advise patient not to rub HQ in with fingertips Utilize cotton tipped applicator to spot treat Apply HQ to dark spots first and then apply retinoid to full face

32 Post-Inflammatory Hyperpigmentation- Summary Prevention is the best therapy Remember post inflammatory hyperpigmentation can take an average of 4 months to clear

33 Melasma

34 Clinical Pearls in Hyperpigmentation -Focus on Melasma Melasma Dialogue Treatment Plan Maintenance Plan

35 Melasma Dialogue Just as important as the treatment plan Patient must understand the natural course of melasma Take time with new patients Ask about meds (specificallyhormones)

36 Melasma- Manage Expectations *What I tell every patient* Melasma is a chronic condition Disease of women in their 30 s, 40 s, and 50 s Tends to resolve in later decades. You won t have this forever There is no one simple cream or peel that you use once to make it go away BUT There are many great treatments to keep your melasma under control

37 *Our Goal* Decrease Pigment Size and Intensity and Prevent Flares NO TREATMENT WITH TREATMENT/MANAGEMENT

38 Treatment Plan Sun avoidance and sun protection Treatment Phase Maintenance Phase

39 Sun Avoidance and Sun Protection

40 Sun Avoidance and Sun Protection Spend time to emphasize the importance of sun block and sun avoidance In some ways this is more important than the treatment itself 10 minutes of unprotected sun exposure and the melasma will come right back

41 Sun Avoidance and Sun Protection Broad Spectrum UVA/UVB Blocker Add Visible light coverage if possible Look for sunscreens that contain Iron Oxide Iron oxide is a pigment so color matching different skin types can be challenging Add an oral agent

42 UV-Visible Light Sunscreen vs UV only Sunscreen in Melasma 68 patients with melasma were randomized in two groups to receive HQ 4 % plus either UV-VL sunscreen SPF 50 UV-only sunscreen SPF 50 8 weeks Assessed by Melasma Activity and Severity Index Colorimetry (L*) Histological analysis of melanin Castanedo Cazares, Juan Pablo, et al. "Near visible light and UV photoprotection in the treatment of melasma: a double blind randomized trial." Photodermatology, photoimmunology & photomedicine 30.1 (2014):

43 UV-Visible Light Sunscreen vs UV only Sunscreen in Melasma Improvement in UV-Visible light group showed 15% greater improvement over UV only sunscreen for MASI 28% greater improvement over UV only sunscreen for colorimetry (L*) 4% greater improvement over UV only sunscreen for melanin Castanedo Cazares, Juan Pablo, et al. "Near visible light and UV photoprotection in the treatment of melasma: a double blind randomized trial." Photodermatology, photoimmunology & photomedicine 30.1 (2014):

44 Tropical fern plant Antioxidant Provides systemic photoprotection Significant decrease in erythema sunburn cells cyclobutane pyrimidine dimers Polypodium Leucotomos Oral Photoprotection Middelkamp-Hup MA, Pathak MA, Parrado C et al. J Am Acad Dermatol Dec;51(6): Woolery-Lloyd, Martin, Caperton, Poster AAD 2012

45 Polypodium Leucotomos Investigator Initiated, double blinded, placebo controlled 21 subjects, 12 weeks PL 240 mg BID vs placebo pill BID Both groups used sunscreen SPF 45 Patient Assessment Mild and Moderate Improvement PL subjects- Mild Imp 50%, Moderate Imp 13% Placebo subjects- Mild Imp 17%, Moderate Imp 0% MELASQOL Improvement 59% of PL subjects 27% of placebo (p<0.05) Woolery-Lloyd, Martin, Caperton, Poster AAD 2012

46 Woolery-Lloyd, Martin, Caperton, Poster AAD 2012

47 Photos Polypodium leucotomos Baseline Week 12 Woolery-Lloyd, Martin, Caperton, Poster AAD 2012

48 Treatment Phase

49 Treatment Phase Start with HQ for 1-2 months Modified Kligman from compounding pharmacy Hydroquinone 8%/Tretinoin 0.025%/ Dexamethasone 0.1% Emphasize the importance of hydroquinone holidays Why? Because the effect of HQ plateaus over time The longer the time periods between HQ the better Goal 2-3 courses per year at the most

50 Treatment Phase - Clinical Pearl Add Hydrocortisone 2.5% cream at night for the first month and then as needed after excessive sun exposure Why add a steroid? Multiple studies to support the use of fluorinated steroids in melasma Hydrocortisone 2.5% may offer some benefit without unwanted side effects Most importantly - may reduce any irritation caused by the modified Kligman formula Tell patient to stop HQ if any redness or irritation

51 Maintenance Phase: The Hydroquinone Holiday

52 Maintenance Phase This is actually the most challenging aspect of treating melasma Maintain with a hydroquinone free skin brightener May need to rotate products Only use HQ as needed 4-6 weeks a few times a year Use hydrocortisone 2.5% cream at night as needed after any excessive sun exposure Keep emphasizing sun block and sun avoidance Patients who practice strict sun avoidance are the most successful

53 Hydroquinone Alternatives Open label & Animal Studies Arbutin/Deoxyarbutin Aloesin Kojic Acid Linoleic acid/alpha linoleic acid/oleic acid Ellagic acid Acerola fruit extract Methimazole Dioic Acid Tranexamic acid Blinded Controlled Trials Soy Flutamide Licorice Extract Vitamin C Niacinamide Azelaic Acid Lignin Peroxidase Phenylethyl resorcinol transaminic acid, tetrapeptides, niacinamide, plankton extracts, marine extracts, polysaccharides Hydroxyphenoxyproprionic acid, ellagic acid, yeast, salicylic acid combination N-acetylglucosamine-split face Decapeptide -12 Kojic Acid/Emblica

54 Sample regimen-treatment Phase AM Cleanse Antioxidant with Skin brightener Broad Spectrum UVA/UVB/VL PLUS Oral Antioxidant PM Cleanse HQ 8%/ Tretinoin 0.025%/ Dexamethasone 0.1% ( 4-8 weeks) Hydrocortisone 2.5% (4 weeks) Moisturizer if needed

55 Sample regimen-maintenance Phase AM Cleanse Antioxidant with skin brightener Broad Spectrum UVA/UVB/VL PLUS Oral Antioxidant PM Cleanse HQ free skin brightener (ex: azelaic acid) Hydrocortisone 2.5% (as needed if excessive sun exposure) Moisturizer if needed

56 Clinical Pearls for Challenging Cases Add oral photoprotection Add Hydrocortisone 2.5% cream for 1 month while using a high concentration HQ and after any excessive sun exposure Add visible light photoprotection if possible Consider adding monthly chemical peels and microneedling Set expectations so that the patient understands the natural course of melasma

57 Lichen Planus Pigmentosus

58 Lichen planus pigmentosus Starts in the third or fourth decade of life Slight female predilection Lesions initially appear as small, ill-defined oval to round macules, which later become confluent to form large areas of pigmentation Pigmentation in different patients varies from slate grey to brownish-black

59 Lichen planus pigmentosus

60 Lichen planus pigmentosus Common diagnosis in India Constituted 4.1% ( ) of patients referred to the pigmentary clinic In earlier reported series, pruritus was present in 50% to 62% May also have associated LP or FFA Kanwar, A. J., et al. "A study of 124 Indian patients with lichen planus pigmentosus." Clinical and experimental dermatology28.5 (2003):

61 New onset dermal pigmentation on the neck present for 4 months

62 Lichen planus pigmentosus LPP probably represents a lichenoid reaction to an unknown agent or stimuli Treatment is challenging Prednisone Topical steroids Tacrolimus / Pimecrolimus Glycolic acid Azelaic acid Kanwar, A. J., et al. "A study of 124 Indian patients with lichen planus pigmentosus." Clinical and experimental dermatology28.5 (2003):

63 Drug Induced Hyperpigmentation

64 Drug Induced facial hyperpigmentation Common in African American population Clinically dark brown hyperpigmentation on the face (not slate grey) Most common cause is HCTZ

65 Drug Induced facial hyperpigmentation Consider switching to BP med that is not photosensitizing Start HC 2.5% cream and a HQ free skin brightener

66 Drug Induced facial hyperpigmentation BP drugs that don t cause photosenitivity Atenolol Labetalol Angiotensin receptor blocker except losartan Clonidine Amlodipine Verapamil BP drugs associated with photosensitivity Metoprolol All ace inhibitors Thiazide Bumetanide Lasix Diltiazem Losartan

67 Stopped HCTZ and used Moisturizer/Sunscreen with Soy Daily June 2007 June 2008

68

69 Progressive Macular Hypomelanosis First described in 1988 by Guillet in Martinique Observed asymptomatic hypopigmented macules on the trunk of young women of mixed racial background Progressive slow course Guillet G. Helenon R. Gauthier Y. Surleve-Bazeille JE. Plantin P. Sassolas B. Progressive macular hypomelanosis of the trunk: primary acquired hypopigmentation. Journal of Cutaneous Pathology. 15(5):286-9, 1988 Oct Relyveld GN. Menke HE. Westerhof W. Progressive macular hypomelanosis: an overview. American Journal of Clinical Dermatology. 8(1):13-9, 2007 Perman M. Sheth P. Lucky AW. Progressive macular hypomelanosis in a 16-year old. Pediatric Dermatology. 25(1):63-5, 2008 Jan-Feb

70 Progressive Macular Hypomelanosis Differential diagnosis includes extensive pityriasis alba and tinea versicolor Differs histologically and clinically Relyveld GN. Menke HE. Westerhof W. Progressive macular hypomelanosis: an overview. American Journal of Clinical Dermatology. 8(1):13-9, 2007

71 Progressive Macular Hypomelanosis Etiology Propionibacterium acnes bacteria in hair follicles are the cause of PMH as a result of production of a hypothetical depigmenting factor Red follicular fluorescence in the hypopigmented spots and the absence of this phenomenon in normal skin when examined under a Wood's light in a dark room Cultivation of P. acnes from the follicles in the hypopigmented spots but not from follicles in normal-looking skin Improvement with topical antimicrobial treatment in combination with UVA light Relyveld GN. Menke HE. Westerhof W. Progressive macular hypomelanosis: an overview. American Journal of Clinical Dermatology. 8(1):13-9, 2007 Westerhof W. Relyveld GN. Kingswijk MM. de Man P. Menke HE. Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis. Archives of Dermatology. 140(2):210-4, 2004 Feb

72 Progressive Macular Hypomelanosis Etiology Biopsy from lesional skin of 8 women demonstrated gram-positive bacteria in the pilosebaceous duct, and a mild perifollicular lymphocytic infiltrate was seen 7/8 cultured biopsy specimens grew P. acnes in affected skin No bacteria identified in normal skin histology and culture negative Proposed that these strains of P acnes may produce a factor that interferes with melanogenesis Westerhof W. Relyveld GN. Kingswijk MM. de Man P. Menke HE. Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis. Archives of Dermatology. 140(2):210-4, 2004 Feb

73 Progressive Macular Hypomelanosis- Wood s Lamp

74 P Acnes strains (PMH 5 and PMH7)

75 Combination therapy with clindamycin and benzoyl peroxide UVA three times a week for a period of 12 weeks NBUVB Progressive Macular Hypomelanosis Treatment Oral doxycycline Chung YL. Goo B. Chung WS. Lee GS. Hann SK. A case of progressive macular hypomelanosis treated with narrowband UVB. Journal of the European Academy of Dermatology & Venereology. 21(7):1007-9, 2007 Aug.

76 Progressive Macular Hypomelanosis Treatment UVA plus benzoyl peroxide 5% gel QAM and clindamycin 1% lotion QHS vs UVA plus fluticasone 45 patients 26 week randomized within-patient left-right comparison study Repigmentation rate 62% benzoyl peroxide/clindamycin/uva side 22% fluticasone/uva side p < Relyveld GN. Menke HE. Westerhof W. Progressive macular hypomelanosis: an overview. American Journal of Clinical Dermatology. 8(1):13-9, 2007

77 Before After 3 months of Benzoyl Peroxide 4% wash and Clindamycin lotion

78 Vitiligo

79 Vitiligo 1-2 percent of the world's population Over 40 million people are affected Affects all races More noticeable in people of color

80 Vitiligo-Work Up Ask about family history of autoimmune disease Do autoimmune work up ANA/Thyroid antibodies NALP1 is the gene associated with vitiligo and autoimmune thyroid disease N Engl J Med Mar 22;356(12):

81 Vitiligo-Treatment Topical steroids Intermittent treatment with Class I steroid for 1-2 weeks can be very effective Topical Immunomodulators Tacrolimus and Pimecrolimus Oral antioxidants/vitamins NB-UVB Age dependent Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol 1997;77:460 Schallreuter KU, Wood JM, Lemke KR, Levenig C. Treatment of vitiligo with a topical application of pseudocatalase and calcium in combination with short-term UVB exposure: a case study on 33 patients. Dermatology 1995;190:223

82 Vitiligo Topical tacrolimus is effective Works best on the face Combine with 10 minutes of sunlight/day Twice daily application is most effective Radakovic S. Breier-Maly J. Response of vitiligo to once- vs. twice-daily topical tacrolimus: a controlled prospective, randomized, observer-blinded trial. Journal of the European Academy of Dermatology & Venereology. 23(8):951-3, 2009 Aug. Grimes PE. Soriano T. Dytoc MT. Topical tacrolimus for repigmentation of vitiligo. Journal of the American Academy of Dermatology. 47(5):789-91, 2002 Nov.

83 Vitiligo-Coverage Coverage makeup Dermablend/Covermark Waterproof/smudge resistant Dyoderm or VitaDye Stain Mineral Makeup Contains zinc oxides, titanium dioxide, iron oxides Offers sun protection SPF Cover FX

84 Coverage Make Up

85 Vitiligo Support Groups National Vitiligo Foundation

86 Thank You!