update on challenging disorders of pigmentation in skin of

Update on Challenging

Disorders of Pigmentation

in Skin of ColorHeather 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

What Determines Skin Color?

What Determines Skin Color?

No significant difference in the number of

melanocytes between the races

2000 epidermal melanocytes/mm2 on head and forearm

1000 epidermal melanocytes/mm2 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., pp192-220, New York, NY: McGraw Hill

Melanosomes in Black and White Skin

Black WhiteSzabo G, Gerald AB, Pathak MA, Fitzpatrick TB. Nature1969;222:1081-1082

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., pp192-

220, New York, NY: McGraw Hill

Role of Melanin-Advantages

Melanin absorbs and scatters energy from UV and visible

light to protect epidermal cells from UV damage

Disadvantages

Inflammation or injury to the skin

is almost immediately

accompanied by alteration in

pigmentation

Hyperpigmentation

Hypopigmentation

Dyschromias

Post-Inflammatory hyperpigmentation

Acne

Melasma

Lichen Planus Pigmentosus

Progressive Macular Hypomelanosis

Vitiligo

Post Inflammatory

Hyperpigmentation: Acne

PIH from Acne

Acne

hyperpigmented

macule

Patients are most

concerned with

pigmentation

Not the acne!!!

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


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%)


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


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

Do retinoids also treat

hyperpigmentation? Yes

Tretinoin

Tazarotene

Adapalene


Common Questions

Tretinoin

Influences melanosome transfer

Tretinoin 0.1% has been demonstrated to

be effective for melasma in a vehicle-

controlled trial

Slow results

Griffiths CE. Finkel LJ. Ditre et al.British Journal of Dermatology 1993;

129(4):415-21

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


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



Tretinoin 0.1% cream achieved

more rapid clearance of

hyperpigmented lesions

compared to vehicle

4 weeks vs 24 weeks


Patient with acne and hyperpigmentation

treated with Tretinoin 0.1% cream


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.

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

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. 2010 May;9(5):549-58

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 16

20 % (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. 2010 May;9(5):549-58

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, post-inflammatory hyperpigmentation.

Kelly, A. Paul, and Darlene D. Sampson. "Recalcitrant nodulocystic acne in black Americans: treatment with

isotretinoin." Journal of the National Medical Association 79.12 (1987): 1266.

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 79.12 (1987): 1266.

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!

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)

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

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 post-inflammatory hyperpigmentation

Pei-Ying Huang, Chia-Yu Chu (2007) Allergic contact dermatitis due to sodium metabisulfite in a bleaching cream Contact Dermatitis 56 (2) , 123–124

Before treatment After 8 weeks of

HQ8%/Tret0.025%/Dex0.1%

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

Post-Inflammatory Hyperpigmentation-

Summary

Prevention is the best therapy

Remember post inflammatory

hyperpigmentation can take an average of

4 months to clear

Melasma

Clinical Pearls in Hyperpigmentation

-Focus on Melasma

Melasma Dialogue

Treatment Plan

Maintenance Plan

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 (specifically-

hormones)

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”

*Our Goal*

Decrease Pigment Size and Intensity and Prevent

Flares

WITH TREATMENT/MANAGEMENTNO TREATMENT

Treatment Plan

Sun avoidance and sun protection

Treatment Phase

Maintenance Phase

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”


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

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 melaninCastanedo‐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): 35-42.

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


colorimetry (L*)


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): 35-42.

Polypodium Leucotomos

Oral Photoprotection

Tropical fern plant

Antioxidant

Provides systemic photoprotection

Significant decrease in erythema

sunburn cells

cyclobutane pyrimidine dimers

Middelkamp-Hup MA, Pathak MA, Parrado C et al. J Am Acad Dermatol. 2004 Dec;51(6):910-8.

Woolery-Lloyd, Martin, Caperton, Poster AAD 2012

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

Photos – Polypodium leucotomos

Baseline Week 12


Treatment Phase

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

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

Maintenance Phase:

The Hydroquinone Holiday

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

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

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

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

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 micro-

needling

Set expectations so that the patient understands the

natural course of melasma

Lichen Planus Pigmentosus

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


Common diagnosis in India

Constituted 4.1% (124 ⁄ 3020) 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): 481-485.

New onset dermal pigmentation on the

neck present for 4 months


“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): 481-485.

Drug Induced

Hyperpigmentation

Drug Induced facial hyperpigmentation

Common in African American

population

Clinically dark brown

hyperpigmentation on the face

(not slate grey)

Most common cause is HCTZ


Consider switching to BP med

that is not photosensitizing

Start HC 2.5% cream and a HQ

free skin brightener

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


Stopped HCTZ and used

Moisturizer/Sunscreen with Soy Daily

June 2007 June 2008

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

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

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


Etiology

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

Relyveld GN. Menke HE. Westerhof W. Progressive macular hypomelanosis: an overview. American Journal of Clinical Dermatology.

8(1):13-9, 2007

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

Progressive Macular Hypomelanosis Etiology

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

Progressive Macular Hypomelanosis-

Wood’s Lamp

P Acnes strains (PMH 5 and PMH7)

Combination therapy with clindamycin and

benzoyl peroxide

UVA three times a week for a period of 12

weeks

NBUVB

Oral doxycyclineChung YL. Goo B. Chung WS. Lee GS. Hann SK. A case of progressive macular hypomelanosis treated with narrow-

band UVB. Journal of the European Academy of Dermatology & Venereology. 21(7):1007-9, 2007 Aug.

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 <0.0001


Treatment

Relyveld GN. Menke HE. Westerhof W. Progressive macular hypomelanosis: an overview. American Journal of Clinical

Dermatology. 8(1):13-9, 2007

BeforeAfter 3 months of

Benzoyl Peroxide 4% wash and

Clindamycin lotion

Vitiligo

Vitiligo

1-2 percent of the

world's population

Over 40 million

people are

affected

Affects all races

More noticeable in

people of color

http://us.f514.mail.yahoo.com/ym/ShowLetter?box=Inbox&MsgId=2060_81240596_3953407_1575_66106_0_35477_88343_3867631964&bodyPart=2&tnef=&YY=70256&y5beta=yes&y5beta=yes&order=down&sort=date&pos=0&view=a&head=b&VScan=1&Idx=0

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. 2007 Mar 22;356(12):1216-25

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

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.

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 15-30

Cover FX

Coverage Make Up

Vitiligo

Support Groups

National Vitiligo Foundation

www.nvfi.org

Thank You!

update on challenging disorders of pigmentation in skin of

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