A Vitiligo Update for Pharmacists: Current Practices and Future Advances Dalal Hammoudi Halat, RPh, MSc, PhD Assistant Professor School of Pharmacy, Lebanese International University
Disclosure Dalal Hammoudi Halat declares to meeting attendees that there are no financial relationships with any for-profit companies that are directly or indirectly related to the subject of this presentation. 2
Learning Objectives Define pathophysiology, symptoms, and risk factors for vitiligo. Elaborate available medications, with emphasis on their proper use. Identify phototherapy and surgery options. Discuss combination of pharmacologic and other therapies. Highlight future treatment approaches. Prepare pharmacists to discuss vitiligo management with patients and offer proper education and counseling. 3
Overview Most common skin depigmentation disorder. Affects 0.5-2 % of the population. Associated with cosmetic disfigurement and considerable psychological distress. Dillon et al. J Clin Aesthet Dermatol 2017 4
Epidemiology No predilection to race Average age of onset is 20 years Slight predominance in females Bleuel & Eberlein. J German Society Dermatol 2018 5
Pathophysiology Complex, multifactorial destruction of melanocytes 6
Pathophysiology Appearance of white patches on the skin 7
Etiology Autoimmune/ cytotoxic mechanisms Oxidative stress on melanocytes Intrinsic melanocyte defects Neural destruction Roncone et al. Medscape 2018 8
Heritability in Vitiligo Familial occurrence 6-8% in first degree relatives HLA classes I and II genes Immunoregulatory genes Melanocyte-specific genes Speeckaert and van Geel. Am J Clin Dermatol 2017 9
Etiology in Summary Predisposing factors Melanocytes vulnerability /injury Loss or decreased melanin production Signs of vitiligo Immune system disorders Single traumatic event Sunburn Emotional distress Physical illness Family history 10
Question 1 Which of the following do you think is involved in vitiligo? a. Immune mechanisms b. Genetics c. Stress d. Physical trauma e. All of the above 11
Clinical Manifestations Vitiligo lesion characteristics: White or depigmented patches Usually well demarcated Round, oval, or linear Few millimeters to few centimeters in size Enlarge centrifugally over time at an unpredictable rate Depigmentation may involve hair, genital area and nipples. Koebner phenomenon vitiligo in sites of trauma, like a cut, burn, or abrasion (20-60% of vitiligo patients). 12
Patterns of Vitiligo Non-segemental Segmental Occurrence More common (85 to 90%) Less common (10%) Clinical features Course Associated disorders Depigmentaion of both body sides, usually symmetric chronic course with a continuing chance of progression throughout life Autoimmune disorders, primarily thyroid diseases; others like alopecia areata, psoraisis, diabetes, rheumatoid arthritis Depigmentation on one body side, usually not crossing midline Rapid onset, progresses for 1-2 years, then stops, and persists unchanged for life Not common Focal Generalized Roncone et al. Medscape 2018 13
Vitiligo Management: What the patient should expect? 14
Treatment Approach General measures Topical treatments - Avoiding friction and trauma - Sun protection - Camouflage and tattooing - Psychological support Oral agents Phototherapy Depigmentation Surgery 15
Topical Treatments (1) Topical corticostroids Produce 33-75% repigmentation Limited, extra-facial involvement Dark skin Recent lesions Clobetasole Use once daily Mometasone Methylprednisone aceponate Betamethasone dipropionate Use for maximum of 3 months Side effects: skin atrophy, acneiform eruptions, striae, risk of systemic absorption Taieb et al. Br J Dermatol 2013 16
Topical Treatments (2) Topical immunomodulators (calcineurin inhibitors) TACROLIMUS (0.1%) & PIMECROLIMUS (1%) Attenuate T-cell activity and decrease production of proinflammatory cytokines. Mainly useful for lesions on face and neck. Apply BID for 6 months. Side effects are local (burning, erythema, pruritus) Speeckaert and van Geel. Am J Clin Dermatol 2017 17
Topical Treatments (3) Topical vitamin D 3 (calcipotriene) In combination with betamethasone dipropionate, calcipotriene BID may be effective in patients with vitiligo. Sometimes used with ultraviolet light, but rarely as monotherapy. Xing & Xu. J Dugs Dermatol 2012 Zhang et al. Medicine 2018 18
Oral Treatments (1) Systemic corticosteroids Spare reports exist in literature about systemic steroid use in vitiligo. Arrest the activity of the disease, but are not effective in repigmenting stable vitiligo. Dose: 2-10 mg of dexamethasone qd on 2 consecutive days per week for 3-6 months 20 mg of prednisone qd for 2-3 months (in combination with topical tacrolimus) Lee D-Y et al. J Dermatol 2010 Taieb et al. Br J Dermatol 2013 19
Oral Treatments (2) Other systemic medications Drug Dose Outcome Reference Methotrexate 10-25 mg weekly for 6 months Minor improvement in limiting spread of progressive vitiligo Alghamdi and Khurrum. Saudi Pharm J 2013 Singh et al. Dermatology 2015 Minocycline 100 mg daily for 6 months Halting of actively spreading disease Singh et al. Ind J Dermatol Venereol Leprol 2014 Simvastatin 80 mg daily for 6 months Vitiligo regression Agarwal et al. J Invest Dermatol 2015 20
Question 2 Among the treatment modalities below, which is effective to administer as a minipulse dose to repress vitiligo progression in a female patient? a. Tacrolimus ointment b. Pimecrolimus ointment c. Mometasone furoate cream d. Dexamethasone po e. Methotrexate po 21
Phototherapy (1) Photochemotherapy (psoralen plus UVA or PUVA) Long-wave UVA (320-340 nm) Psoralen (oral or topical) 2-3 treatments per week for 12-24 months are required before repigmentation Nausea and ocular toxicity with oral psoralen Blistering and burns with topical psoralen Taieb et al. Br J Dermatol 2013 22
Phototherapy (2) Narrowband UVB (311-312 nm) First choice for adults and children with generalized vitiligo. Total body treatment is suggested for lesions involving more than 15 20% of the body area. Usually continued over a maximum period of 1 or 2 years. - Repigmentation - Stabilization Roncone et al. Medscape 2018 Speeckaert and van Geel. Am J Clin Dermatol 2017 23
Phototherapy (3) Targeted UVB (excimer laser - 308 nm) Monochromatic rays For limited, stable patches of segmental and non-segmental (<20% BSA) vitiligo. Twice weekly for an average of 24-48 sessions Safe in pediatric vitiligo Lopez et al. Am J Clin Dermatol 2016 Ezzedine & Silverberg. Pediatrics 2016 24
Surgical Management Pigment cell transplantation (autologous donor site) Stable lesions for at least 2 years No Koebner phenomenon Segmental recalcitrant vitiligo Localized recalcitrant vitiligo Razmi et al. Exp Dermatol 2018 25
Topical steroids TCIs Topical vitamin D analogues After surgery Ezzedine et al. JAMA 2016 Taieb et al. Br J Dermatol 2013 26
Depigmentation Therapy Monobenzene ethyl ester of hydroquinone Lightens the unaffected parts of skin to match the areas that have already lost color. Useful for: Vitiligo covering more than 50% of the skin surface Unsatisfactory repigmentation Dark-skinned patients Burning and itching Allergic contact dermatitis Permanent photosensitivity Repigmentation of bleached skin (so sun protection is needed) Ocular toxicity AlGhamdi & Kumar. Eur J Acad Dermatol Venereol 2011 27
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AFAMELATONIDE An emerging vitiligo treatment Stimulates melanocyte proliferation and melanogenesis. Subcutaneous implant inserted deep into skin above the hip. Adverse reactions: hyperpigmentation of normal skin, nausea, dizziness and abdominal pain. Contraindications: pregnancy, liver or kidney disease, ages under 17 or above 70 years. 29
JANUS KINASE(JAK) INHIBITORS Yet another promising Treatment! Ruxolitinib Tofacitinib Twice-daily topical ruxolitinib 1.5% cream was used to treat vitiligo in a small group of patients, with promising results, specifically on facial lesions. Rothstein et al. J Am Acad Dermatol 2017 30
LATANOPROST Prostaglandin, used to reduce elevated intro-ocular pressure in open-angle glaucoma Comparable effect to UVB in repigmentation 31
Significant progress has been made in understanding vitiligo. Treatment is often long term and requires adherence and psychological support. Advances in pharmacological, light, and surgical modalities, or combinations of these have undergone massive progress. A new arsenal of therapeutic options and clinical trials is underway. The future looks promising for this challenging and stigmatizing disorder. 32
dalal.hammoudi@liu.edu.lb