Description

• An acquired depigmentation of the skin, which correlates with a loss of epidermal melanocytes. There are three clinical variants, each with subtypes.
• Localized: often in childhood, rapid onset then stabilizes. Involvement of hair is common early in the course; lacks associated autoimmune diseases
  • Focal: few lesions, random distribution
  • Segmental: Lesions occur within a dermatome (mostly trigeminal) or may follow Blaschko lines. Lesions usually stop abruptly at the midline.
  • Mucosal: only mucosal surfaces involved
• Generalized/nonsegmental (most common variant): progressive, with flares, commonly associated with autoimmunity. Common locations are acral, periorificial, and in sites sensitive to pressure/friction (Koebner phenomenon).
  • Vulgaris: most common subtype; scattered macules; often symmetric, wide distribution; mostly hands, axillae, and groin
  • Acrofacial: on distal extremities and face
  • Mixed: coexistence of above
• 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) scores.
• Other 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.
• System(s) affected: skin, mucous membranes
• Synonym(s): leukoderma

Epidemiology

• 50% begin before age 20 years, peak in females: 1st decade; males: 5th decade. Onset earlier with positive family history; can appear as early as 6 weeks
• 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),(2)

Etiology and Pathophysiology

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

• Genetic: See “Genetics.”
• 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 lesional biopsies
• Oxidative stress from elevated H₂O₂ and NO and decreased catalase and erythrocyte glutathione

• Polygenic/multifactorial inheritance
• 20% of patients report affected relative, but 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%
  • Elevated antinuclear antibodies in up to 40%
  • Elevated thyroperoxidase antibodies in 50%
• Less common
  • Systemic lupus erythematosus
  • Inflammatory bowel disease
  • Melanoma (may be a sign of positive outcome of 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.