Vitiligo: Mechanistic insights lead to novel treatments

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Presentation transcript:

Vitiligo: Mechanistic insights lead to novel treatments Michael L. Frisoli, BS, John E. Harris, MD, PhD Journal of Allergy and Clinical Immunology Volume 140, Issue 3, Pages 654-662 (September 2017) DOI: 10.1016/j.jaci.2017.07.011 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 White patches of depigmentation characteristic of vitiligo (A), perifollicular repigmentation after successful treatment of disease (B and C), and difficulty repigmenting bony prominences of the knuckles relative to the dorsum of the hands (D). Journal of Allergy and Clinical Immunology 2017 140, 654-662DOI: (10.1016/j.jaci.2017.07.011) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 IFN-γ signals to keratinocytes and Langerhans cells, stimulating production of CXCL9 and CXCL10. CXCR3 recognizes these chemokines, leading to recruitment of CXCR3+CD8+ T cells. Autoreactive T cells kill melanocytes and establish long-lived resident memory within the skin. Drugs that target aspects of this pathway are shown in red. Journal of Allergy and Clinical Immunology 2017 140, 654-662DOI: (10.1016/j.jaci.2017.07.011) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 UV light, melanogenesis, and vitiligo-associated genetic polymorphisms (shown in red) can contribute to intrinsic melanocyte stress. Several environmental phenols also interact with melanogenic enzymes to induce stress, which then leads to secretion of damage-associated molecular patterns (DAMPs) that stimulate nearby innate immune cells through pattern recognition receptors (PRRs). Shown in red, vitiligo-associated genetic polymorphisms can affect both melanocyte stress and innate immune response. Hypothesized pathways are denoted with ?, and significant stress from exogenous insult is denoted by thick arrows. Journal of Allergy and Clinical Immunology 2017 140, 654-662DOI: (10.1016/j.jaci.2017.07.011) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Segmental vitiligo is characterized by unilateral depigmentation that does not cross the midline. Journal of Allergy and Clinical Immunology 2017 140, 654-662DOI: (10.1016/j.jaci.2017.07.011) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Repigmentation is impaired at anatomic sites where there is little hair growth. A, Lack of repigmentation on the volar wrists in a patient whose entire forearms were otherwise successfully treated. B, White hairs do not support perifollicular repigmentation relative to pigmented hairs. Journal of Allergy and Clinical Immunology 2017 140, 654-662DOI: (10.1016/j.jaci.2017.07.011) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions