Vitiligo: An Update on Pathophysiology and Treatment Options

Abstract and Introduction

Abstract

The pathophysiology of vitiligo is becoming increasingly clarified. In non-segmental vitiligo, early factors include activation of innate immunity, inflammasome activation, oxidative stress, and loss of melanocyte adhesion. Nonetheless, the main mechanism leading to non-segmental vitiligo involves an immune-mediated destruction of melanocytes. Anti-melanocyte-specific cytotoxic T cells exert a central role in the final effector stage. Genetic research revealed a multi-genetic inheritance displaying an overlap with other autoimmune disorders. However, some melanocyte-specific genes were also affected. Segmental vitiligo carries a different pathogenesis with most evidence indicating a mosaic skin disorder. Current management includes topical corticosteroids and immunomodulators. Narrow-band ultraviolet B can be used in patients not responding to topical treatment or in patients with extensive disease. Pigment cell transplantation offers an alternative for the treatment of segmental vitiligo or stable non-segmental lesions. Recent findings have revealed new targets for treatment that could lead to more efficient therapies. Targeted immunotherapy may halt the active immune pathways, although combination therapy may still be required to induce satisfying repigmentation. A recently established core set of outcome measures, new measurement instruments, and biomarker research pave the way for future standardized clinical trials.

Introduction

Vitiligo is the most frequently occurring depigmentary disorder affecting approximately 0.5–1% of individuals worldwide. It can develop at any age, although half of the patients have vitiligo before the age of 20 years. No difference in prevalence exists according to sex, skin type, or race. Nonetheless, some reports indicate that vitiligo develops in women at an earlier age and marked geographic differences in prevalence rates have been described.^[1]

Historically, the cause of vitiligo has been shrouded in mystery. The earliest known reference to vitiligo dates from 2200 BC and vitiligo was also mentioned in the Ebers Papyrus (1550 BC). The development of white spots on the skin has been described in the Old Testament and Buddhist literature.^[2] Vitiligo has carried many misconceptions, especially in countries where whitening of the skin is associated with infectious diseases such as leprosy. To date, the resulting social stigmata remain embedded in some cultures, leading to a high psychological burden in patients with vitiligo.^[3]

Apart from cultural influences, vitiligo has been shown to exert a detrimental influence on the quality of life. This impact has long been underestimated because of the lack of vitiligo-specific impact scales. Most dermatology qualityof-life measures such as the Dermatology Quality of Life Index focus on subjective symptoms such as pruritus or pain. Moreover, these indices focus on acute disease flares that are not applicable for vitiligo (e.g., Dermatology Quality of Life Index: assessment of patients' complaints in the previous week). Recently, new impact scales have been developed for vitiligo such as the Vitiligo Impact Patient Scale, which may better reflect the burden caused by vitiligo.^[4] The psychological impact of vitiligo is clear because of the high rate of depressive symptoms. A recent meta-analysis showed a pooled odds ratio of 5.05 for depression compared with controls. More than a third of patients with vitiligo had experienced some type of depressive symptom without necessary fulfilling all criteria for clinical depression.^[5]

Table 1. Medical management of vitiligo
	Treatment	Expected results	Comments
Non-segmental vitiligo
First-line option	Topical potent corticosteroids	Disease stabilization Some chance of repigmentation (face > rest of body > acral areas)	Discontinuous scheme preferred (e.g., 2/4 weeks) Long-term treatment (at least 6 months)
Topical immunomodulators (tacrolimus, pimecrolimus)	Disease stabilization Some chance of repigmentation (face > rest of body > acral areas)	More expensive compared with topical corticosteroids Twice daily more efficient than once daily
First-line option in extensive disease or second-line option in the case of lack of repigmentation using topical treatment	NB-UVB/excimer laser	Repigmentation in the majority of patients, although complete repigmentation is rare	Effective treatment often requires 7–12 months of phototherapy Number of safe treatments is limited because of possible increased risk of skin cancer Often relapse after discontinuation if untreated
Stable disease	Pigment cell transplantation	Inferior success rates in non-segmental vitiligo compared with segmental vitiligo	Results are dependent on disease stability and location Only reserved for a limited area
Very active disease with high impact	Oral corticosteroids	Most patients achieve disease stabilization, although limited repigmentation in monotherapy	Important possible side effects (weight gain, hypertension) Only for a limited duration (3–6 months)
Very extensive disease with high impact	Depigmentation therapy (laser therapy, cryotherapy, MBEH)	Removal of remaining pigmented areas	Recurrence of pigment possible (importance of sun protection)
Segmental vitiligo
Active disease (in most patients up to 6 months to 2 years after onset)	Topical potent corticosteroids	Disease stabilization	Discontinuous scheme preferred (e.g., 2/4 weeks)
Topical immunomodulators (tacrolimus, pimecrolimus)	Disease stabilization	More expensive compared with topical corticosteroids
Stable disease	Pigment cell transplantation	Very high success rates	Results are dependent on disease stability
			Only reserved for a limited area

Table 1. Medical management of vitiligo

Treatment

Expected results

Comments

Non-segmental vitiligo

First-line option

Topical potent corticosteroids

Disease stabilization
Some chance of repigmentation (face > rest of body > acral areas)

Discontinuous scheme preferred (e.g., 2/4 weeks)
Long-term treatment (at least 6 months)

Topical immunomodulators (tacrolimus, pimecrolimus)

Disease stabilization Some chance of repigmentation (face > rest of body > acral areas)

More expensive compared with topical corticosteroids
Twice daily more efficient than once daily

First-line option in extensive disease or second-line option in the case of lack of repigmentation using topical treatment

NB-UVB/excimer laser

Repigmentation in the majority of patients, although complete repigmentation is rare

Effective treatment often requires 7–12 months of phototherapy
Number of safe treatments is limited because of possible increased risk of skin cancer
Often relapse after discontinuation if untreated

Stable disease

Pigment cell transplantation

Inferior success rates in non-segmental vitiligo compared with segmental vitiligo

Results are dependent on disease stability and location
Only reserved for a limited area

Very active disease with high impact

Oral corticosteroids

Most patients achieve disease stabilization, although limited repigmentation in monotherapy

Important possible side effects (weight gain, hypertension)
Only for a limited duration (3–6 months)

Very extensive disease with high impact

Depigmentation therapy (laser therapy, cryotherapy, MBEH)

Removal of remaining pigmented areas

Recurrence of pigment possible (importance of sun protection)