Disclosures. Managing Dyschromias. Objectives. Epidemiology in Skin of Color. Epidemiology in Skin of Color. Categorization

Transcription

1 Managing Dyschromias Fall Clinical Dermatology Conference Las Vegas, NV October 21, 2016 Disclosures No pertinent conflicts of interest in relation to this presentation Seemal R. Desai, MD, FAAD Clinical Assistant Professor Department of Dermatology University of Texas Southwestern Medical Center Founder & Medical Director Innovative Dermatology, PA Dallas, Texas Galderma (C) (H) Symbio (R) Allergan (C) (H) Valeant Pharmaceuticals (C) (H) Abbott (C) (H) (R) Objectives Epidemiology in Skin of Color Better formulate treatment plans and paradigms for patients with skin of color Utilize newer therapies used globally for pigmentary anomalies, psoriasis and acne Review literature on combination treatment modalities for Epidemiology in Blacks Acne vulgaris 27.7% Eczema 20.3% Pigmentary Disorders 9% Includes PIH and Melasma Seborrheic Dermatitis 6.5% Alopecia 5.3% Halder R et al Cutis 1983;32: Alexis A et al Cutis 2007;80: % 9.1% 20% Epidemiology in Skin of Color Prevalence in Latinos Eczematous Dermatitis 20% Condyloma/Warts 17.5% Acne vulgaris 12.3% Dermatophyte 9.3% Pyoderma 8.8% Dyschromia 7.5% Seborrheic Dermatitis 7.2% Psoriasis 5 5% Sanchez M. Derm Clin 2003; 21(4): Categorization IMPORTANT TO DETERMINE FIRST WHETHER THE DISORDER IS ASSOCIATED WITH AN INCREASE OR DECREASE IN MELANIN Hypopigmented Disorders Tinea Versicolor, Sarcoidosis, Mycosis Fungoides, Pityriasis Alba Depigmented Disorder Protypical disorder is Vitiligo Hyperpigmented Disorders Melasma and PIH (commonly due to acne) 1

2 Hypopigmentation These conditions have a DECREASE in melanin Tinea Versicolor Sarcoidosis Hansen s disease Mycosis Fungoides Idiopathic Guttate Hypomelanosis Progressive Macular Hypomelanosis Pityriasis Alba TREATMENT OPTIONS Vitiligo Topicals including steroids, vit D analogues, calcineurin inhibitors Depigmentation Systemic tx Phototherapy Surgical Treatment Psychological Therapy IF TREATMENTS FAIL ANALYZE PATIENTS DESIRES Let s try to define! Active/Unstable Vitiligo Depigmentation spreading more than 2% BSA in one month Chronic Vitiligo Depigmentation present for at least 1 year with no h/o spontaneous repigmentation Refractory Vitiligo Disease that is poorly responding to therapy <25% repigmentation Systemic Steroids Stabilizing Vitiligo Oral Mini-Pulse Therapy (OMP) Dexamethasone 4mg daily on 2 consecutive days per week i.e Saturday and Sunday Half the dose in children less than 16 years of age Must counsel patients on side effects Parsad D, De D. Corticosteroid minipulses. In: Vitiligo. 1st ed. New York: Springer, 2010.p Pandya et al. DermQuest. What I do Stabilizing Vitiligo IM Triamcinolone Acetonide 60mg qmonth for 3 months Transition to Oral Mini-Pulse Therapy (OMP), if still spreading Dexamethasone 4mg daily on 2 consecutive days per week Have the patient on a traditional therapy Antioxidants in Vitiligo Number of studies support the use anti-oxidants Especially in combination with phototherapy (NBUVB) Alpha Lipoic Acid, Vit E, Vit C Start patient on Calcium/Vitamin D supplement Dell Anna ML et al. Clin Exp Dermatol Nov;32(6):

3 Antioxidants in Vitiligo 28 Pts with non-segmental vitiligo 2 months before and for 6 months during the NB-UVB treatment 47% of pts > 75% repigmentation vs.18% in placebo group Improvements in catalase activity, decrease in overall ROS production Oral antioxidants containing alpha-lipoic acid combined with NB-UVB enhanced repigmentation by reducing oxidative stress Picardo M et al. Clin Exp Dermatol, 2007 Nov;32(6):631-6 Antioxidants in Vitiligo Polypodium Leucotomas NBUVB 2x weekly Treated with PLE 250mg TID vs placebo for 26 weeks Higher repigmentation of head and neck region in test (44%) vs placebo group (27%) [P = 0.06] Other sites with limited repigmentation Middlekamp-Hup MA et al. JEADV. 2007;21: Antioxidants in Vitiligo Afamelanotide 57 patients with generalized vitiligo Polypodium 480mg daily + NB-UVB vs. NB-UVB alone Response rate of the combined group significantly higher than the NB-UVB only group 40% vs. 22%, p< In responders, repigmentation was observed within the first month as compared to a mean of 3 mo in the group of phototherapy only patients Analogue of α melanocyte-stimulating hormone Binds with the melanocortin-1 receptor (MC1R) MC1R is not expressed by melanocyte stem cells Afamelanotide can stimulate pigmentation and increase proliferation of melanocytes Phototherapy needed to induce melanoblast proliferation Pacifico, et al. Poster Paper presented at: Amer Acad of Dermatology; March 2009; San Francisco, CA. Lim, H, JAMA Dermatol, 2015;151(1):42-50 Afamelanotide and Narrowband UV-B Phototherapy for the Treatment of Vitiligo JAMA Dermatol. Published online September 17, doi: /jamadermatol Janus Kinase Inhibitors for Vitiligo Tofacitinib 5 mg QOD 5 mg QD Half the RA dose of 5mg BID 2 months: partial repigmentation 5 months: white patches nearly all gone Craiglow BG et al. JAMA Dermatol, 2015;151(10):

4 van Geel N, Depaepe L, Speeckaert R. Laser (755 nm) and cryotherapy as depigmentation treatments for vitiligo: a comparative study. J Eur Acad Dermatol Venereol Jun; 29(6): van Geel N, Depaepe L, Speeckaert R. Laser (755 nm) and cryotherapy as depigmentation treatments for vitiligo: a comparative study. J Eur Acad Dermatol Venereol Jun; 29(6): Depigmentation in Vitiligo Depigmentation in Vitiligo 20% Monobenzone topically I start with a small zone i.e. one arm treated for 3-4 months Stinging is usually NOT an allergic reaction Have the patient apply the cream BID for 3-4 days Female patients more likely to desire depigmentation Do NOT apply at night 20% Monobenzone topically I start with a small zone i.e. one arm treated for 3-4 months Stinging is usually NOT an allergic reaction Have the patient apply the cream BID for 3-4 days Female patients more likely to desire depigmentation Do NOT apply at night Tacrolimus in Vitiligo 20% Monobenzone topically BID for 3 wks I start with a small zone i.e. one arm treated for 3-4 months Stinging is usually NOT an allergic reaction Have the patient apply the cream BID for 3-4 days Female patients more likely to desire depigmentation Do NOT apply at night 4

5 Tacrolimus in Vitiligo Depigmentation in Vitiligo 20% Monobenzone topically I start with a small zone i.e. one arm treated for 3-4 months Stinging is usually NOT an allergic reaction Have the patient apply the cream BID for 3-4 days Female patients more likely to desire depigmentation Do NOT apply at night Hair may or may not depigment, but eyes WILL NOT Recheck zone in person & via photos in 2-3 months Pt usually pleased Can then treat other arm, face, neck ACD the most common side effect Some small guttate areas of repigmentation T t ith 20% 40% LN2 d b i Hyperpigmentation LOCALIZED Post inflammatory Hyperpigmentation Melasma Hyperpigmentation DIFFUSE Metabolic Causes Vitamin Deficiencies like B12, Folate Check Cortisol, TSH and Iron Medications Discontinue the offending agent Malignant Hx of Melanoma Autoimmune and Infectious Systemic Sclerosis, POEMS, PCT, HIV etc PIH Pathogenesis Post inflammatory Hyperpigmentation & Acne Thought to be due to inflammatory mediators Prostaglandins including PGE2 Leukotrienes including LTC4 and LTD4 All of which have been shown to stimulate epidermal melanocytes In turn, a disruption is noted in the skin s basal layer dermal deposition of melanin and subsequent macrophage Taylor activation S et al. J Cutan Med Surg

6 PIH Treatment Options FIRST AND FOREMOST Treat any underlying underlying dermatoses and stress the important of sun protection Topical Retinoids Azelaic Acid Hydroquinone Chemical Peels Case 1 Acne PIH Tazarotene vs Adapalene for Post inflammatory Controlled Blinded Trial of 180 patients Investigators evaluated improvement of PIH and acne Subjects included African Americans, Asians, and Hispanics 20% of patients in the tazoretene 0.1% cream group had complete resolution at week 16 7% of patients in the adapalene 0.3% gel group Tazoretene 0.1% Tanghetti cream E was et al. JDD more May effective 2012 than Adapalene CHEMICAL PEELS Superficial Peels Glycolic Acid 20-70% Salicylic Acid 20-30% TCA 10-25% Jessner s solution Acne PIH Have the patient use Hydroquinone 4% topically (if available) Discontinue topical retinoids 7 days prior to peel Acne PIH CHEMICAL PEELS Salicylic Acid Peels Case 2 25 patients in an open label trial 5 salicylic acid peels from 20-30% concentration 2 weeks intervals between each treatment Combined with HQ 4% pre treatment x 2 weeks 4/5 patients with Fitzpatrick type V or VI had >75% improvement Grimes P. Dermatol Surg

7 Risk Factors Melasma Melasma Triple Combination Fixed Therapy Sunlight Pregnancy Genetic predisposition Hormonal contraceptives Cosmetics Endocrine issues Thyroid dysfunction AND NEVER FORGET MEDICATIONS!! Multicenter RCT of Southeast and East Asian patients 260 patients 129 in Triple combo group 260 patients 131 in Hydroquinone only group 8 weeks treatment Assessed by Melasma GSS, MASI, patient satisfaction Triple combo had superior efficacy to monotherapy in GSS and other variables but more adverse effects Chan R et al, BJD 2008 Hydroquinone Safety The supervised use of prescription topical hydroquinone had no more than a theoretical risk of malignancy, developing ochronosis or other long term safety side effects Melasma Second Line Topical Agents Azelaic Acid No substantial evidence to prove its carcinogenicity TAKE THE TIME TO DISCUSS LONG TERM USE WITH EACH OF YOUR PATIENTS!! Nordlund JJ, Grimes PE, Ortonne Jp JEADV 2006; Kojic Acid Zinc Azelaic Acid Melasma Kojic Acid Melasma Prospective, single blinded, right left comparison study 40 Indian patients with melasma BID application of 20% AZA cream to one half of face for 24 weeks Second half had application of Clobetasol 0.05% for 1 st 8 weeks followed by 20% AZA cream for next 16 weeks Sequential therapy had more significant improvement than monotherapy side (p<0.01) Sarkar R, Dermatology 2002; 205: Produced by Aspergillus oryzae Tyrosinase inhibitor and photo protective effect More clinically stable molecule but with weaker lightening properties Comparative study showed that Glycolic Acid with kojic acid and Glycolic acid with hydroquinone were effective in treatment of melasma Garcia A et al Dermatol Surg 1996; 22:

8 Melasma Zinc Formulation of Zinc Sulfate topical used N=28 BID for 4 weeks 49.78% MASI improvement (p<0.005) maintained up to 3 months Mild burning sensation in few patients Zinc itself has a desquamative and epidermal exfoliative property, and has been shown to decrease melanin Sharquie KE et al. Dermatol Surg What are some newer global therapies? Ingredient Strength Function Octinoxate 7.5% UVB filter Kojic Acid Dipalmitate 2% Tyrosinase inhibitor Arbutin 1.5% Tyrosinase inhibitor, interferes with melanosome maturation by inhibiting DHICA polymerase and silver protein Mulberry Extract 1% Tyrosinase inhibitor, anti-oxidant Tocopheryl Acetate 1% Anti-oxidant, photoprotectant Tetrahydrocurcumin (Sabi Tyrosinase inhibitor, anti-oxidant, 0.2% White) anti-inflammatory Licorice Extract 40% 0.05% Tyrosinase inhibitor, anti-oxidant, anti-inflammatory, melanin dispersion and removal Artocarpus Extract (Oxyresveratrol 95%) 0.02% Tyrosinase inhibitor, anti-oxidant Kojic Acid Dipalmitate Antibiotic produced by many species of aspergillus and penicillium Kojic Acid + di-palmitic Acid Unlike kojic acid, kojic dipalmitate is more stable to light, heat, ph and oxidation, and also compatible with most organic sunscreens. MOA: inhibits tyrosinase More efficacious than kojic acid. Aspergillus oryzae (koji) growing on rice Oral Antioxidants A number of different options available Green tea extracts, Procyanidin, oral zinc supplementation Polypodium leucotomas, orally administered 240mg taken 3 times daily for 12 weeks Though it is a potent anti-oxidant from a fern Glutathione Potent antioxidant indirect inactivation of tyrosinase Assists in converting eumelanin to phaeomelanin Typically used orally Also being given IV in Asia. Still controversial due to bioavailability, but some promising results in studies Ahmed AR et al, JAMA Dermatology 2013; 149: Allen J et all. J Altern Complement Med 2011; 17:

9 Kojic Acid Dipalmitate KA 0.75% showed significant improvement in melasma area and severity index (MASI) score as early as 8 weeks, which was maintained till 12 weeks of treatment. Side effects reported are erythema, sensitization and irritant contact dermatitis 1. Monteiro et al. Indian J Dermatol. 2013;58(2): Topical Methimazole Melasma A potent peroxidase inhibitor leading to morphologic change in melanocytes Kasraee et al showed 20 patients with no TSH, free thyroxine or free iodothyronine levels Prepared by dissolving MMI in distilled water and placing in a cream base to make a final concentration of 5% qhs for 8 weeks Abbas et al. Dermatol Ther 2013 Jan;26(1):69-72 Abbas et al. Dermatol Ther 2013 Jan;26(1):69-72 Abbas et al. Dermatol Ther 2013 Jan;26(1):69-72 Study #4: Assessment of a Superficial CAssessment of a Superficial Chemical Peel Combined With a Multimodal, Hydroquinone-Free Skin Brightener Using In Vivo Reflectance Confocal Microscopy Goberdhan et al., 2013 mbined With a Multimodal, Hydroquinone-Free Skin Brightener Using In Vivo Reflectance Confocal Microscopy Goberdhan et al., 2013 Baseline Standard View 1 Peel + 6 Weeks Tx 9

10 Brown Channel Chemical Peels & Melasma Baseline 1 Peel + 6 Weeks Tx Peels in Melasma Peels in Melasma CHEMICAL PEELS Superficial Peels Glycolic Acid 20-70% Salicylic Acid 20-30% TCA 10-25% Jessner s solution Have the patient use Hydroquinone 4% topically (if available) Discontinue topical retinoids 7 days prior to peel Glycolic Acid 30-50% 5-6 peels q2-3 weeks Salicylic Acid Peels 15-30% 5-6 peels q2-3 weeks Trichloracetic Acid Peels 10-15% Can prime skin with Glycolic and then follow with TCA Although, commonly use 10-15% in Types IV-VI Laser Therapy 27 female subjects, phototypes II V Mixed-type melasma refractory to previous therapies Do Lasers work in the treatment of melasma? Low-fluence QS Nd:YAG laser treatment of J/cm 2 with 5 or 6 mm spot was administered immediately following microdermabrasion. Daily application of a broad-spectrum sunscreen began immediately Subjects used a topical skin care regimen of hydroquinone with Kauvar et al. Lasers in Surg and Med. 44: (2012) 10

11 Melasma Pigmentary Disorders Academy First line therapy Topicals with Triple Combination Should patients develop irritation/allergy to triple combination therapy Dual Combinations can be used Kauvar et al. Lasers in Surg and Med. 44: (2012) Second line therapy J Am Acad Dermatol 2006;54: S Chemical Peels in combination ith topicals Epidemiology 2009 National Health and Nutrition Examination Survey Total prevalence of psoriasis is US adults was 3.2 percent Psoriasis in Skin of Color Of those patients: Caucasians most common at 3.6% African Americans at 1.9% Hispanics at 1.6% Differing opinions Rachakonda nowet al. from JAAD previous 2014; 70: studies in the past African population alone Epidemiology Eastern Africa HIGHER PREVALENCE 2.6%-3.3% Western Africa much lower at 0.05%-0.4% Wide variation of prevalence globally Environmental factors and triggers Seen more as Farber you et increase al. Dermatol distance Clin. 1994; from 12: equator Climate and genetics Namazi MRseem Int J Dermatol play2004; a role 43: Psoriasis in Skin of Color Clinical Features Scaling may be less prominent, but with more violaceous discoloration and areas of hyperpigmentation Dyschromia on other parts of the body can be more common 11

12 Clinical Cases Heath, David, Taylor et al. JAAD. Jan Vol Psoriasis in Skin of Color Clinical Features Differential diagnosis includes Lichen Planus Cutaneous Lupus Severe Fungal Infections Sarcoidosis Infectious causes Heath, David, Taylor et al. JAAD. Jan Vol Psoriasis in Skin of Color Treatments Considerations: Topical Steroids, Vit D analogues and calcineurin inhibitors Immunomodulators Biologics However, your patient may be resistant to Psoriasis in Skin of Color Treatments Considerations: Phototherapy can be very successful The Psoriasis itself can lead to PIH So can the phototherapy In addition, if the patient already has PIH, could 12

13 Scalp Disease Can be very common in patients with Skin of Color Hair care practices in different ethnicities Shampoo and washing of the scalp often at a much less frequency Indian Dermatol Online J Jan-Mar; 5(1): doi: / Varying degrees of seborrheic dermatitis can be seen Scalp Disease Scalp washing ideal once weekly up to twice weekly especially for African American hair Topical corticosteroids and vitamin D analogues can be used up to twice daily, but vehicle matters! Oil emulsions tend to be preferred as do foams Some patients with ethnic hair, may actually prefer ointments Treatment Is one treatment better than the other in Skin of Color? We really do NOT know Need more cohort and population specific trials for psoriasis in Skin of Color One study evaluated Etanercept was evaluated for potential safety and efficacy in different sub-populations 12 week data on BSA Shah et al. J Drugs Dermatol. 2011; 10: N i ifi t diff Af i A i ti t L ti Case 4 Case 5 13

14 Case 6 What I do Detailed History Detailed medication history & +/- Family History Previous treatments Cosmetics/Fragrance Based Products I do patch test when suspicious Take Serial Photographs Pre-treatment and during with a dark Background Patients tend to often think its not working Empathize Will increase your credibility and rapport dramatically Biopsy Do not be scared to if needed 2mm punch to elucidate dermal vs epidermal vs other processes (!) Treatment What I do Take Home Messages Topical triple combination therapy My own compound containing HQ, Kojic Acid, Triamcinolone and Tretinoin in special base Add on chemical peels Start with Salicylic Acid can help concomitant acne Otherwise, studies favoring glycolic acid I do increase the percentage strength of hydroquinone if needed Dermabrasion for special cases Pigmentary Disorders continue to be a large part of a busy medical dermatology practice More randomized controlled trials are needed to evaluate the efficacy of up and coming treatments in the diagnosis, management and treatment of conditions such as melasma and vitiligo Always take a step back and try to establish the underlying pathology ALWAYS EMPHASIZE UV PROTECTION EVEN IN SOC Questions / Comments Seemal R. Desai, MD Clinical Assistant Professor Department of Dermatology University of Texas Southwestern Medical Center Dallas, Texas Innovative Dermatology, PA seemald@yahoo.com 14