Vitiligo

Vitiligo is a benign skin condition characterized by well-demarcated macules and patches of complete depigmentation. This condition is commonly associated with autoimmune diseases and is believed to be a result of autoimmune destruction of melanocytes, oxidative stress, and/or intrinsic melanocyte defects in genetically predisposed individuals. Nonsegmental vitiligo is the most common subtype with a bilateral and symmetric distribution. Lesions may be limited to specific areas (e.g., acral areas) or widespread. It has a chronic course with unpredictable periods of disease progression. Segmental vitiligo is characterized by lesions with a unilateral distribution and an early phase of rapid spread, followed by long-term stability. Vitiligo is typically a clinical diagnosis, but Wood lamp examination and/or skin biopsy are useful in case of diagnostic uncertainty. Initial management typically includes topical immunosuppressants (e.g., corticosteroids and/or calcineurin inhibitors) alone or in combination with phototherapy. Low-dose oral corticosteroids may be considered for rapidly progressive disease. Surgical therapy (e.g., cellular grafts, tissue grafts) or depigmentation therapy is reserved for refractory stable lesions. Camouflage cosmetics can be offered to patients. Regardless of therapy, depigmentation is often recurrent.

• Prevalence: 0.4–2% of the general population worldwide ^[1]
• Peak incidence: 10–30 years; can occur in any age group ^[2]
• Sex: ♂ = ♀

Epidemiological data refers to the US, unless otherwise specified.

• Vitiligo is characterized by an absence of melanocytes in the depigmented lesions. ^[2]
• The etiology is unknown but is thought to be multifactorial. ^[3][4]
  • Genetic predisposition
  • Autoimmune destruction of melanocytes
  • Oxidative stress (free radicals)
  • Intrinsic defects of melanocytes (early apoptosis, defective cell-to-basement membrane adherence)
• May be triggered by stress or skin injury (e.g., sunburn) ^[4]

Mixed vitiligo refers to a combination of nonsegmental and segmental vitiligo. ^[5]

Nonsegmental vitiligo ^[5][6]

• Most common type of vitiligo
• Typically bilateral and symmetric distribution
• Chronic course with unpredictable periods of progression
• Spontaneous repigmentation may occur, but is often temporary. ^[7]
• Subtypes include:
  • Generalized (involving multiple areas of the body)
  • Universal (involving all or nearly all of the body)
  • Acrofacial (mainly limited to the face, hands and feet)
  • Mucosal (involving the oral and genital mucosa)

Segmental vitiligo ^[5]

• More common in children than in adults ^[8]
• Typically unilateral distribution
• Initial phase of rapid spread which:
  • Includes early leukotrichia
  • Can last up to 2 years ^[5]
• Lesions typically remain stable after the initial phase.

• Irregular, well-demarcated, depigmented (white) macules or patches, surrounded by normal skin
  • Unilateral (segmental vitiligo) or bilateral and symmetrical distribution (nonsegmental vitiligo)
  • Commonly on the face (e.g., perioral and periocular regions), neck, scalp, acral surfaces (e.g., hands), extensor surfaces, or genitalia
  • May manifest on areas that repeatedly sustain mechanical trauma (Koebner phenomenon) or are sun-exposed
• Depigmented hair within vitiliginous macules (leukotrichia) ^[10]
• Coexisting autoimmune diseases
  • Most common (∼ 20% of patients): Hashimoto thyroiditis, Graves disease ^[11]
  • Other disorders: type 1 diabetes, psoriasis, inflammatory bowel disease, alopecia areata, pernicious anemia, Addison disease
• Ocular manifestations (e.g., retinal pigmentary changes, dry eyes) can occur, but vision is typically unaffected. ^[12]

• Typically a clinical diagnosis
• Dermoscopy may show: ^[10]
  • White hypopigmented lesions
  • Perilesional and perifollicular hyperpigmentation
  • Leukotrichia
• If there is diagnostic uncertainty, refer to dermatology for the following.
  • Wood lamp examination: blue-white appearance of lesions ^[13]
  • Skin biopsy and histology: absence of melanocytes in otherwise normal skin
• Consider testing for associated autoimmune disorders (see “Clinical features”) based on clinical suspicion.

• Pityriasis alba: a common hypopigmented scaly patch seen in sun-exposed areas, especially in children (resolves spontaneously or with topical steroids) ^[14]
• Pityriasis versicolor: a fungal infection characterized by scaly hypopigmented macules on the trunk
• Idiopathic guttate hypomelanosis: multiple hypopigmented macules on the sun-exposed areas, common in older individuals
• Nevus depigmentosus: a well-defined area of depigmentation, present since birth or early childhood, which does not enlarge and requires no treatment
• Chemical leukoderma: loss of skin pigment due to contact with chemicals

The differential diagnoses listed here are not exhaustive.

General principles ^[4][6][15]

• All patients
  • Refer to dermatology for early management.
  • Recommend photoprotective measures.
  • Recommend cosmetic camouflage products if desired.
  • Refer for psychotherapy. ^[16]
• Initial treatment may include: ^[7][17][18]
  • Topical immunosuppressants
  • Phototherapy
  • Oral corticosteroids for rapidly progressive disease
• Maintenance therapy may be needed to prevent relapse following repigmentation.
• Advanced treatment for patients with refractory stable disease may include:
  • Surgical therapy
  • Depigmentation therapy

Regardless of the treatment used, disease recurrence is common. ^[7][15]

Immunosuppressants ^[6][15][18]

• Topical corticosteroids
  • Ultra-high potency or high potency corticosteroids (e.g., fluocinonide 0.05% ointment): for lesions on the trunk and extremities ^[4][6]
  • Medium potency corticosteroids (e.g., mometasone 0.1% ointment): for large or thin-skinned (e.g., intertriginous) treatment areas ^[17]
• Topical calcineurin inhibitors: may be preferred for lesions on the face or thin-skinned areas
  • Tacrolimus 0.1% ointment in adults and 0.03% ointment in children (off-label) ^[6]
  • Pimecrolimus 1% cream (off-label) ^[7]
• Topical Janus kinase inhibitors: ruxolitinib for limited nonsegmental vitiligo in patients ≥ 12 years of age ^[15]
• Oral low-dose corticosteroids: may be used as short-term therapy for rapidly progressive vitiligo

Regular breaks from using topical or oral corticosteroids are recommended to reduce adverse effects. ^[6]

Phototherapy ^[6]

• Narrowband (NB)-UVB phototherapy: typically preferred ^[15]
  • Whole body NB-UVB phototherapy: for widespread or rapidly progressive disease
  • Excimer laser therapy (targeted NB-UVB): for disease affecting < 10% of total body surface area ^[6]
• Whole body psolaren and UVA phototherapy (PUVA) may be considered for:
  • Treatment-resistant vitiligo
  • Vitiligo in individuals with darker skin

Surgical therapy ^[6][15]

• Tissue grafts
  • Mini-punch grafts
  • Split-thickness skin grafts
• Cellular grafts: melanocyte-keratinocyte transplantation

Depigmentation therapy ^[4][6]

The goal of depigmentation therapy is permanent removal of pigmentation of unaffected skin so skin color is consistent. Options include:

• Monobenzone cream
• Cryotherapy
• Laser therapy