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Integumentary system

Vitiligo

Acquired, idiopathic de-pigmentation disorder of the skin caused by dysfunction/destruction of melanocytes.

Acquired, idiopathic de-pigmentation disorder of the skin caused by dysfunction/destruction of melanocytes.

  • M/C depigmenting skin disorder

Epidemiology

Vitiligo is the commonest cause of depigmentation. It can appear at any age from child to adulthood but peak incidence is reported in the second and third decade. The age of onset usually varies between the sexes. Its prevalence is approximately 0.1-2% of people including adults and children worldwide and it affects all races equally.

Vitiligo age-of-onset is bimodal
Vitiligo age-of-onset is bimodal: The distribution of vitiligo age-of-onset and resultant finite mixture model is shown for the total 4523 cases from our three previous vitiligo GWAS and replication study. The blue line shows the full distribution, the red line the early-onset distribution (mean 10.3, SD 5.6 years; 38.4%), and the green line the late-onset distribution (mean 34.0, SD 14.5 years; 61.6%). The overall and sex-specific distributions, resultant finite mixture models, and overall and sex-specific mean ages-of-onset were very similar among the four constituent case cohorts. | Jin, Y., Roberts, G. H. L., Ferrara, T. M., Ben, S., van Geel, N., Wolkerstorfer, A., … Spritz, R. A. (2019). Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression. Nature Communications, 10(1), 391. https://doi.org/10.1038/s41467-019-08337-4

Etiopathogenesis

The exact etiology of vitiligo is unknown. It is frequently associated with multiple autoimmune diseases. There are various theories about its pathogenesis and the etiology is multifactorial. It is characterized by incomplete penetrance, genetic heterogeneity, and multiple susceptibility loci. Family and other twin studies have shown that inheritance is complex and also involves both environmental and genetic factors. Additionally, it is hypothesized that genetic factors can influence the age of onset of vitiligo. The inheritance of vitiligo may also include genes associated with the biosynthesis of melanin, regulation of autoantibodies, and response to oxidative stress.

  • Neural hypothesis: Neurochemical mediator destroys melanocytes and decreases production of melanin
  • Oxidative stress hypothesis: Oxidant and anti-oxidant mechanism intermediate or metabolic product of melanin synthesis causes destruction of melanocytes
  • Genetic theory: Intrinsic defect of melanocyte results in an inherent abnormality that impedes their growth and differentiation
  • Autoimmune/cytotoxic hypothesis: Alteration in humoral and cellular immunity causes destruction/dysfunction of melanocytes
Major theories implicated in the pathogenesis of vitiligo
A summary of the major theories implicated in the pathogenesis of vitiligo and its Recent updates | Arora, A., & Kumaran, M. (2017). Pathogenesis of vitiligo: An update. Pigment International, 4(2), 65–77. https://doi.org/10.4103/2349-5847.219673

Autoimmune/cytotoxic hypothesis

This theory supports the hypothesis that nonsegmental vitiligo is commonly associated with autoimmune disorders than the segmental type of vitiligo.
  • Autoimmune thyroid disease (M/C)
  • Type 1 diabetes
  • Pernicious anemia
  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE)
  • Addison disease

Presentation

Vitiligo presents clinically with signs and symptoms of white spots on the body distributed symmetrically and more obvious in people with dark skin. The lesions are characterized by well-demarcated pearly white or depigmented macules and patches, oval, round, or linear-shaped, and the borders are convex, range from the size of few millimeters to centimeters and enlarge centrifugally.

The severity of the disease is scored by the body surface area affected. The course of the disease is often unpredictable and varies in response to the treatment.

Bordeaux Vitiligo Global Issues Consensus Conference (VGICC) classification:

Subtypes
Non-segmental vitiligo (NSV)Acrofacial
Mucosal (more than one mucosal site)
Generalized
Universal
Mixed (associated with SV)
Rare variants
Segmental VitiligoUni-, bi-, or plurisegmental
Undetermined/unclassified VitiligoFocal
Mucosal (one site in isolation)
NSV, non-segmental vitiligo; SV, segmental vitiligo; VGICC, Vitiligo Global Issues Consensus Conference.

Non-segmental vitiligo( NSV):

Characterized by depigmented macules that vary in size from a few to several centimeters in diameter, often involving both sides of the body with tendency toward symmetrical distribution
  • Acrofacial: Only extremities and/or face involved
  • Mucosal: Oral and genital mucosae
  • Generalized/common: Symmetric, bilateral, depigmented macules in a random distribution over the entire body surface
  • Universal (M/C form in adulthood): Affects largest extent of tegument (80-90% body surface). The generalized or common form usually precedes it
  • Mixed: Concomitant involvement of segmental and non-segmental vitiligo. Most often, the segmental form precedes NSV.
  • Rare forms: vitiligo punctata, minor and follicular. These types were also considered unclassifiable.

Segmental Vitiligo

Unilateral, asymmetric distribution of white macules that match a cutaneous segment (dermatomal distribution) usually respecting the body midline, and there is also involvement of body hair (leukotrichia) besides rapid onset of the condition.
  • Mono/unisegmental (M/C form)
  • Bisegmental
  • Plurisegmental

Koebner’s phenomenon “isomorphic response”:

Development of lesions at sites of specifically traumatized uninvolved skin of patients with cutaneous diseases
Classification of Koebner’s phenomenon as proposed by the Vitiligo European Task Force in 2011
Classification of Koebner’s phenomenon as proposed by the Vitiligo European Task Force in 2011 | van Geel N, Speeckaert R, Taieb A, et al. Koebner’s phenomenon in vitiligo: European position paper. Pigment Cell Melanoma Res. 2011b;24:564–573.

Complications:

Complications of vitiligo are social stigmatization and mental stress, eye involvement like iritis, depigmented skin is more prone to sunburn, skin cancer, and hearing loss because of loss of cochlear melanocytes. Other complications are related to medications like skin atrophy after prolonged use of topical steroids.


Diagnosis

The diagnosis of vitiligo is usually made on clinical features . The severity of the disease is scored by the body surface area affected. The course of the disease is often unpredictable and varies in response to the treatment.

Wood lamp examination:

Differentiate vitiligo from other hypopigmented or depigmented disorders
Woods light for vitiligo patient showed depigmented patch. | Contributed by Daifallah Al Aboud, MD

Skin biopsy:

The histopathological examination of the skin reveals the absence of melanocytes and complete epidermal pigmentation loss. Superficial perifollicular and perivascular lymphocytic infiltrates may be present at the margin of the vitiligo lesions, due to the cell-mediated process that destroys the melanocytes.
Vitiligo showing the absence of melanocytes in basal layer of the epidermis
(a) Fontana-Masson showing the presence of melanin pigment and melanocytes in the epidermis (X400). (b) Fontana-Masson showing the absence of melanin pigment and melanocytes in the epidermis (x400). | Yadav, A. K. (2019). Histopathology and Molecular Pathology of Vitiligo. In Depigmentation. IntechOpen. https://doi.org/10.5772/intechopen.84258

Differential diagnosis:

Differentiate vitiligo from other hypopigmented or depigmented disorders.
Differential diagnosis of vitiligo
Differential diagnosis of vitiligo |

Management

Various types of topical and systemic medications, phototherapy, laser therapy, and surgical therapy are used for the treatment of vitiligo.

Current and emerging treatments address 3 major goals in vitiligo treatment
Current and emerging treatments address 3 major goals in vitiligo treatment. Current treatments are listed in black, emerging treatments in red. | Rashighi, M., & Harris, J. E. (2017). Vitiligo Pathogenesis and Emerging Treatments. Dermatologic Clinics, 35(2), 257–265. https://doi.org/10.1016/j.det.2016.11.014

Topical treatments:

First-line vitiligo treatment includes moderate-to-high strength topical corticosteroids and calcineurin inhibitors, both of which dampen the cellular immune response

Systemic medications:

Systemic corticosteroids are generally employed in rapidly progressive cases to help with disease stabilization.
Proposed therapeutic algorithm for childhood vitiligo
Proposed therapeutic algorithm for childhood vitiligo | Ezzedine, K., & Silverberg, N. (2016). A Practical Approach to the Diagnosis and Treatment of Vitiligo in Children. Pediatrics, 138(1), e20154126. https://doi.org/10.1542/peds.2015-4126

Prognosis:

It is a chronic skin condition with an unpredictable disease course and some patients may notice spontaneous repigmentation over the depigmented areas. The prognosis depends upon the age of onset and the extent of disease. Early disease onset is usually associated with the involvement of greater body surface area and rate of progression. Few types and certain locations may be responsive to treatment. Refractory cases have been noted in patients presenting with segmental vitiligo and younger than 14 years of age. Most of the patients on treatment usually experience intermittent cycles of pigment loss and disease stabilization.


Summary:

41572_2015_article_bfnrdp201546_figa_html
Vitiligo. (2015). Nature Reviews Disease Primers, 1(1), 15046. https://doi.org/10.1038/nrdp.2015.46

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