Vitiligo

Fernanda Regina Lemos Bebber

Reunião Departamental

Serviço de Dermatologia

Hospital Universitário Evangélico de Curitiba

DEFINIÇÃO

Amelanodermia idiopática adquirida

Caracterizada por manchas acrômicas

Resultantes da destruição gradual de melanócitos

HISTÓRICO

1500 a. C. Referências a lesões cutâneas caracterizadas

por perda de pigmentação Escritos egípcios e indianos

Termo vitiligo foi utilizado pela primeira vez pelo médico romano Celsus Livro De Medicina Escrito no primeiro século da era cristã

HISTÓRICO

Muitas hipóteses sobre a origem da palavra vitiligo Latim vitium – defeito Latim vitelius - aludindo à coloração

característica do pêlo dos novilhos A Bíblia se refere a certas doenças cutâneas

utilizando a palavra hebraica zara’at - mancha branca

HISTÓRICO

Muitas hipóteses sobre a origem da palavra vitiligo Em 250 a.C., Septuagint traduziu zara’at como

lepra - estigma social em algumas culturas No final do século 19, foi definida como uma

distrofia pigmentar por Moritz Kaposi Características histológicas: falta de grânulos de

pigmento

EPIDEMIOLOGIA

Cerca de 1% da população

Independentemente da raça

Afeta homens e mulheres igualmente Alguns estudos mostram predominância no

sexo feminino Procura por atendimento devido a problemas

cosméticos é maior entre as mulheres

EPIDEMIOLOGIA

O vitiligo acomete aproximadamente 1% da população, independentemente da raça. Afeta homens e mulheres igualmente, apesar de alguns estudos mostrarem predominância no sexo feminino. Contudo, como a procura por atendimento devido a problemas cosméticos é maior entre as mulheres, pode ser que essa maior incidência não seja real. A idade de início das primeiras manifestações é variável. Muitos casos surgem antes dos 5 anos, sendo que em 50% dos pacientes a doença se manifesta antes dos 20 anos. Formas congênitas são excepcionais, mas existem evidências de que o surgimento precoce do vitiligo está associado à maior extensão das lesões e à ocorrência de casos familiares ou de canície precoce. A acromia característica da doença pode surgir espontaneamente ou ser precipitada por fatores externos como queimadura solar intensa e situações de trauma físico ou emocional graves. Contudo, esta relação causal é dificilmente comprovável, pois são circunstâncias de ocorrência comum, muitas vezes indicadas como fatores desencadeantes de diversas afecções.

Overview

Vitiligo affects approximately 1% of the worldwide population.

Depigmented patches on the hands, neck, genitalia, limbs, and face.

Subtypes of Vitiligo

Differ by anatomical location, and size of lesions

Focal - a few isolated lesionsSegmental – unilateral distributionAcrofacial – fingers and around mouthUniversal – almost total depigmentationGeneralized – most common, symmetrical

distribution, form that will be discussed

Psychological Aspects

Can cause severe psychological and social damage

Can result in discrimination especially in 3rd world countries.

Can be confused with Leprosy

Cytology

Normal skin is pigmented with melanin that is produced by melanocytesDetection by Masson Silver StainTherefore white spots are due to melanocyte death

Hypothesized Causes

Neural – Neuron terminates on melanocyte and causes neurotransmitter toxicity

Autocytotoxic – Defective enzyme in Hydrogen Peroxide breakdown. H2O2 disrupts melanin production pathway

Autoimmune – Patient’s own immune system attacks and destroys the melanocytes

Support for Autoimmune Theory

Presence of Vitiligo increases the chances of developing other autoimmune diseases

Examples – Hashimoto’s Thyroiditis, Pernicious Anemia, Insulin-dependant Diabetes, Systemic Lupus Erythemetosus.

Autoimmunity

Patient’s immune system attacks healthy tissues within the body

It has been shown that both Cell-mediated and Humoral immunity are active in Vitiligo

The two types work cooperatively to produce melanocyte destruction

Humoral Immunity

B cell mediated production and excretion of proteins called antibodies to fight extra-cellular pathogens (example - bacteria)Antibodies bind to the target and initiate a complex immune reaction that culminates in target cell destructionHumoral immunity was proven to be active in Vitiligo by the discovery of Melanocyte reactive auto-antibodies (IgG-anti-MC)

Immunoglobulin Structure

ELISA

Melanocyte

Optical Density of patient’s serum was significantly different from controls

Cell-Mediated Immunity

T cells recognize and destroy abnormal cellsMost effective against intra-cellular pathogens (example - viruses)A correlation has been made between T cell concentration and melanocyte deathThis shows that cell-mediated immunity is active in Vitiligo.

How was this discovered?

Different cell types were identified by staining for specific cell surface proteinsThis showed that the highest concentration of T cells was within .6 mm of the lesional borderThis shows that T cell concentration is significantly correlated with melanocyte death suggesting that T cells are the true melanocyte killers

Proposed Cooperativity

The current theory for vitiligo pathogenesis is that humoral immunity promotes cell-mediated destruction of melanocytes

Anti-melanocyte antibodies induce macrophages to produce cytokines that attract T cells.

T cells then infiltrate and kill the melanocytes

Cytokines

Cytokines are small signaling molecules important in cell to cell communication

These cytokines increase the amount of intercellular adhesion molecules (ICAMS) on blood vessel walls

ICAMS allow lymphocytes, in this case T cells, to escape the vasculature

Extravasation

Melanocyte Killers

These cytokine activated T cells escape the vasculature and infiltrate the skin

They then move toward the source of the cytokines, which in Vitiligo, is the dermis

This puts the T cells and melanocytes in close proximity and facilitates lethal cell-cell interactions

Recap of Autoimmune Theory

Autoimmunity - B cells produce Anti-melanocyte antibodies that attach to the surface of a melanocyte and induce local macrophages to produce cytokines

These cytokines attract T cells into the area, and it is believed that these cells mediate destruction of the melanocytes.

Don’t Forget These are People