Description

• An acquired depigmentation of the skin, which correlates with a loss of epidermal melanocytes. There are two major clinical variants, each with subtypes.
• Nonsegmental vitiligo: depigmented macules of varying size
  • Acrofacial: on distal extremities and face
  • Generalized: progressive, with flares, commonly associated with autoimmunity. Common locations are acral, periorificial, and in sites sensitive to pressure/friction (Koebner phenomenon).
  • Mixed: coexistence of nonsegmental and segmental
  • Mucosal (multifocal): only mucosal surfaces
  • Rare variants:
    • Ponctué: discrete, confetti-like macules
    • Inflammatory: peripheral erythematous rim
    • Trichrome: Tan zone is present between normal and depigmented skin.
    • Quadrichrome: as above but with marginal/perifollicular hyperpigmentation
    • Blue: Dermal melanophages give blue hue in areas affected by prior postinflammatory hyperpigmentation.
  • Universal: involves >80% of the body surface area (BSA). Most likely to have family history; comorbidities are common and associated with poorest quality-of-life (QOL).
• Segmental vitiligo: Lesions occur within a dermatome (often trigeminal) or may follow Blaschko lines. Lesions usually stop abruptly at the midline; typically occurs earlier than nonsegmental vitiligo, is rapidly progressive, and involves melanocytes of hair follicles.
  • Bisegmental: bilaterally distributed
  • Plurisegmental: multiple segments
  • Unisegmental: single segment
• Undetermined/unclassified:
  • Focal: few lesions, random distribution; may be able to later classify as one of the forms above after 1 to 2 years
  • Mucosal (focal type): only mucosal surfaces

Epidemiology

• 50% begin before age 20 years; females in 1st decade; males in 5th decade; onset earlier with positive family history; can appear as early as 6th weeks of life
• Predominance: male = female; however, females are more likely to seek treatment.
• No race or socioeconomic predilection

Prevalence
~1% in the United States and Europe (1); 0.1–8% in the world; highest in Gujarat, India at 8.8% (1)

Etiology and Pathophysiology

Most likely, a spectrum of disorders with a common phenotype and multiple mechanisms contribute to the pathology (convergence theory).

• Autoimmune: humoral autoantibodies and skin-homing T cells
• Neural: local or systemic dysregulation leading to excess neurotransmitters
• Viral: direct melanocyte toxicity, cytomegalovirus (CMV), hepatitis C, and Epstein-Barr virus (EBV) found in lesion biopsies
• Oxidative stress from elevated H₂O₂ and NO and decreased catalase and erythrocyte glutathione

Genetics

• Polygenic/multifactorial inheritance
• 20% of patients report affected relative; monozygotic twins have only 23% concordance.
• HLA haplotypes, small nucleotide polymorphisms, and specific genes are all possible contributors.

Risk Factors

• Family history of vitiligo/autoimmune disorders
• Personal history of associated conditions

Commonly Associated Conditions

• Most common
  • Endocrine: thyroid disease (hypo-/hyperthyroidism), hypoparathyroidism, Addison disease, insulin-dependent diabetes
  • Dermatologic: psoriasis, atopic dermatitis, alopecia areata, chronic urticaria, halo nevi, ichthyosis
  • Pernicious anemia
  • Hypoacusis, rheumatoid arthritis
  • Ocular abnormalities in up to 40%
  • High antinuclear antibodies in up to 40%
  • Elevated thyroperoxidase antibodies in 50%
• Less common
  • Systemic lupus erythematosus
  • Inflammatory bowel disease
  • Melanoma and other skin cancers
  • Syndromes: Alezzandrini; mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); Schmidt; and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
• Age >50 years at onset should prompt investigation for associated conditions.

Pediatric Considerations
Associated with Hashimoto thyroiditis in a significant portion of children; screening at onset and possibly annually may be beneficial.