Andrei Metelitsa, MD, FRCPC, FAAD

Co-Director, Institute for Skin Advancement

Clinical Associate Professor, Dermatology

University of Calgary, Canada

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Faculty/Presenter Disclosure

Faculty: [Andrei Metelitsa MD FRCPC FAAD]

Relationships with commercial interests:

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3

Learning Objectives

Hyperpigmentation

▪ Melasma

▪ Drug-Induced

▪ PIH

▪ Neurofibromatosis

▪ Lentigines

Hypo/Depigmentation

▪ Vitiligo

▪ Tuberous Sclerosis

▪ Pityriasis Alba

▪ Tinea Versicolor

1. Disorders of Hyperpigmentation

i. Melasma

i. Melasma

i. Melasma

Melasma

Seen primarily in women

▪ at least 90% of patients

Increased prevalence in individuals who are

Hispanic, Asian or of African descent

Most common location is the face, followed by

the forearms

Symmetric patches of hyperpigmentation with

irregular borders due to increased melanin

within the epidermis and/or dermis

Melasma Treatment

Daily sun protection is critical

▪ Sunblock is preferred

Topical agents

▪ Hydroquinone

▪ Azelaic Acid

▪ Kojic Acid

▪ Retinoids

▪ Kligman formula

Chemical peels

Lasers

▪ Fractionated non-ablative

Melasma Treatment

Modified Kligman Formula▪ 2%HC + 5%HQ +0.05% tretinoin cream

8 week data▪ Triple combo: 26% clearance

▪ HQ + tretinoin 9% clearance

▪ HQ + fluocinolone 1.9% clearance

Triple combo vs HQ alone▪ 35% vs 4% improvement

Hydroquinone

Typically 4% preparation▪ Usually suggest limiting use to 3 months

Exogenous ochronosis (blue-gray discoloration) is very rare▪ Usually associated with higher concentration of hydroquionone

(8%)

▪ More prolonged use

ii. Drug-Induced Pigmentation

Minocycline Antidepressants (imipramine) Amiodarone Antimalarials Chlorpromazine Heavy metals

Drug-Induced Pigmentation

Drug-Induced Pigmentation

iii. Postinflammatory Hyperpigmentation

Postinflammatory Hyperpigmentation

Very common Typically affects dark-skinned people Usually develops following previous inflammation

or injury to the skin Typically resolves within 1 year

iv. Neurofibromatosis

iv. Neurofibromatosis

iv. Neurofibromatosis

Neurofibromatosis

iv. Neurofibromatosis

iv. Neurofibromatosis

v. Lentigo

2. Disorders of Hypo/Depigmentation

a) Vitiligo

a) Vitiligo

Vitiligo

Acquired, idiopathic disorder characterized by circumscribed depigmented macules and patches

Usually asymptomatic Clinical variants include localized, generalized

and universal Association with immune disorders

▪ especially thyroid Wood’s lamp accentuates areas of vitiligo

Vitiligo Treatment

General measures

▪ Sun Protection, Makeup

Topical steroids

Topical calcineurin inhibitors

Phototherapy

Laser

Depigmentation therapy

Woman in her 50’s with progressive vitiligo > 1 year

Increasing involvement of hands and face

Past treatments: triamcinolone, tacrolimus and short course of nUVB

▪ Poor efficacy

Patient requested alternate therapy

Craiglow BG, King BA. Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy. JAMA Dermatol. 2015 Jun 24.

Oral tofacitinib citrate 5 mg every other day

3 weeks, the dosage was increased to 5 mg/d

▪ half the approved dose for RA which is 5 mg twice daily

2 months of therapy, partial repigmentation of the face and upper extremities was evident

5 months, repigmentation of the forehead and hands was nearly complete

▪ Remaining involved areas demonstrated partial repigmentation

Forehead photos

Hands photos

Tofacitinib is a JAK 1/3 inhibitor that was FDA approved in 2012 for the treatment of moderate to severe rheumatoid arthritis

Recently described in the treatment of alopecia universalis

Alopecia areata and vitiligo share genetic risk and appear to share pathogenesis

Interferon-gamma–induced expression of C-X-C motif chemokine 10 (CXCL10) in keratinocytes is an important mediator of depigmentation in vitiligo

Hypothesis: Tofacitinib effectively leads to blockade of interferon gamma signaling and downstream CXCL10 expression, thus giving rise to repigmentation in vitiligo

Interferon-gamma–induced expression of C-X-C motif chemokine 10 (CXCL10) in keratinocytes is an important mediator of depigmentation in vitiligo

Oral Tofacitinib (Jak 1/3 inhibitor) Topical Ruxolitinib (Jak 1/2 inhibitor)

b) Tuberous Sclerosis

Tuberous Sclerosis

c) Pityriasis Alba

Pityriasis Alba

Low grade dermatosis Minor feature of atopic dermatitis More common among dark-skinned

children Presents with ill-defined hypopigmented

patches▪ Face most common site

▪ Initially can be more erythematous

▪ More apparent in summer

Pityriasis Alba - Treatment

▪ May persist for months-years

▪ Resolves spontaneously

▪ Topical Steroids

▪ Topical Calcineurin Inhibitors

d) Tinea Versicolor

Tinea Versicolor

Etiology: Common superficial cutaneous fungal eruption caused by Malassezia furfur

History: ▪ Usually affects young adults

▪ Humid Environments Physical:

▪ Oval macules and patches on the trunk

▪ Hyperpigmented and hypopigmented variants Diagnosis:

▪ KOH – classic spaghetti and meatballs (hyphae and spores)

Tinea Versicolor

Treatment:

▪ Topical antifungals▪ E.g. ketoconazole, terbinafine

▪ Systemic antifungals▪ Itroconazole, ketoconazole, fluconazole

PEARLs

Sunprotection is critical

Increased pigmentation

▪ Brown vs. slate-grey (medication induced)

Loss of pigmentation

▪ Depigmentation (vitiligo) vs. hypopigmentation