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