Andrei Metelitsa, MD, FRCPC, FAAD Co-Director, Institute for Skin Advancement Clinical Associate Professor, Dermatology University of Calgary, Canada

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Learning Objectives Hyperpigmentation Melasma Drug-Induced PIH Neurofibromatosis Lentigines Hypo/Depigmentation Vitiligo Tuberous Sclerosis Pityriasis Alba

1. Disorders of Hyperpigmentation

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

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

Neurofibromatosis

iv. Neurofibromatosis

v. Lentigo

2. Disorders of Hypo/Depigmentation

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