Autoimmune Disease Skin Disorder

name	description	evidence
Non-Segmental Vitiligo (NSV)	Most common form, characterized by symmetrical depigmented patches on both sides of the body. Includes generalized, acrofacial, and universal variants.	TRUNCATED
Segmental Vitiligo (SV)	Patches are restricted to one side of the body or one area, such as a limb or the face. Typically has an earlier onset and progresses for a few years before stabilizing.	TRUNCATED
Mixed Vitiligo	A combination of segmental and non-segmental types occurring simultaneously or sequentially in the same individual.	TRUNCATED

0

name

Melanocyte Destruction

description

Autoimmune-mediated destruction where the immune system targets melanocytes, leading to loss of skin pigment.

cell_types

• Melanocyte
• CD8+ T Lymphocyte

evidence

reference	supports	snippet	explanation
PMID:33200838	SUPPORT	Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction...self-responsive immune function directly contributes to the bulk of melanocyte deaths in vitiligo...CD8(+) cytotoxic T lymphocytes finally execute the killing of melanocytes.	The literature describes the autoimmune-mediated destruction of melanocytes involving CD8+ T lymphocytes, consistent with the provided statement.
PMID:31209143	SUPPORT	Vitiligo is an autoimmune skin disease mediated by autoreactive CD8(+) T cells that destroy the pigment-producing cells of the epidermis, melanocytes, leading to areas of depigmentation.	The reference confirms the autoimmune-mediated destruction mechanism, mentioning both CD8+ T lymphocytes and melanocytes.
PMID:25184918	SUPPORT	The main histopathological finding in vitiligo is the total absence of functioning melanocytes in the lesions, while the inflammatory cells most commonly found on the edges of the lesions are CD4+ and CD8+ T lymphocytes.	The literature supports the involvement of CD8+ T lymphocytes and the destruction of melanocytes in vitiligo.
PMID:35653192	SUPPORT	Vitiligo is an autoimmune skin disease characterized by the destruction of melanocytes by autoreactive CD8+ T cells.	This source directly mentions the destruction of melanocytes by CD8+ T cells.
PMID:18460889	SUPPORT	Vitiligo is characterized by progressive skin depigmentation resulting from an autoimmune response targeting epidermal melanocytes...Type I cytokine-mediated immunity to melanocytes in vitiligo involves T cells reactive with melanosomal antigens...	The source elaborates on the autoimmune nature of vitiligo, involving T cells and targeting melanocytes.

1

name

Genetic Predisposition

description

A complex interplay of multiple genes contributes to susceptibility to vitiligo.

evidence

reference	supports	snippet	explanation
PMID:28317533	SUPPORT	Vitiligo reflects simultaneous contributions of multiple genetic risk factors and environmental triggers. Genomewide association studies have discovered approximately 50 genetic loci contributing to vitiligo risk.	The literature clearly states that multiple genetic risk factors contribute to vitiligo, aligning with the statement's claim of a complex interplay of genes.
PMID:28206724	SUPPORT	Contrary to the Northern part of Europe but likewise to the Mediterranean area, the frequency of the CAT genotypes in Sicily is equally distributed. Out of all CAT genotypes, only CAT-89 T/T frequency was found to be significantly higher amongst vitiligo patients than controls.	The study mentions the association of specific gene polymorphisms with vitiligo, supporting the notion of a genetic predisposition.
PMID:29704874	SUPPORT	The viewpoint that vitiligo is not caused only by predisposing mutations, or only by melanocytes responding to chemical/radiation exposure, or only by hyperreactive T cells, but rather results from a combination of aetiologic factors that impact melanocyte viability, has certainly stood the test of time.	The convergence theory supports the idea that multiple genetic and environmental factors contribute to vitiligo.
PMID:33278065	SUPPORT	The complex interplay between non-immunological and immunological factors in vitiligo is key for the development of the disease.	This underscores the multifactorial nature of vitiligo, consistent with the statement's emphasis on a complex genetic interplay.

2

name

Autoimmune Reaction

description

Vitiligo often coexists with other autoimmune disorders, such as thyroid disease, suggesting a common autoimmune etiology.

evidence

reference	supports	snippet	explanation
PMID:25838868	SUPPORT	Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis.	The article indicates a strong association between vitiligo and autoimmune thyroid disorders, supporting a common autoimmune etiology.
PMID:26769615	SUPPORT	Vitiligo in children is a distinct subset of vitiligo and differs from adult vitiligo... The most commonly associated autoimmune disease is thyroiditis.	The reference confirms a frequent coexistence of vitiligo and autoimmune thyroid disorders, supporting the common autoimmune etiology theory.
PMID:26724277	SUPPORT	Vitiligo can also be associated with several autoimmune diseases, including autoimmune thyroid diseases, alopecia areata, and halo nevi.	This reference indicates the association of vitiligo with multiple autoimmune diseases, further supporting the shared autoimmune etiology.
PMID:20578892	SUPPORT	Generalized vitiligo is an autoimmune disease of skin pigmentation that is associated with increased prevalence of other autoimmune diseases, particularly autoimmune thyroid disease.	The increased prevalence of autoimmune thyroid disease among vitiligo patients supports the notion of a shared autoimmune mechanism.
PMID:11681494	SUPPORT	In brief, the disease is frequently associated with other disorders which have an autoimmune origin such as autoimmune thyroiditis and insulin-dependent diabetes mellitus.	The frequent association of vitiligo with other autoimmune disorders aligns with the concept of a common autoimmune etiology.

3

name

Oxidative Stress

description

Increased oxidative stress in the skin may contribute to melanocyte vulnerability and destruction.

evidence

reference	supports	snippet	explanation
PMID:36980277	SUPPORT	Oxidative stress is considered to play a crucial role in activating consequent autoimmune responses related to vitiligo.	The literature supports the statement that increased oxidative stress in the skin contributes to melanocyte vulnerability and destruction.
PMID:33098225	SUPPORT	Hydrogen peroxide (H2O2) and malondialdehyde (MDA) were significantly higher in patients than controls (p-value < .001, <.001, respectively); on the other hand, total antioxidant capacity (TAC) was significantly lower in patients than controls (p-value = .001).	This study supports the idea that oxidative stress biomarkers are elevated in vitiligo patients, contributing to melanocyte vulnerability.
PMID:33346939	SUPPORT	Apoptosis is the most widely studied cell death pathway in vitiligo. In addition, other forms of cell death, including necroptosis, pyroptosis, and ferroptosis, may also participate in the pathogenesis of vitiligo.	This supports the involvement of oxidative stress-induced mechanisms in melanocyte death.
PMID:37230937	SUPPORT	We found that the expression levels of collagen-related genes and anti-oxidative enzymes were upregulated in vitiligo-derived fibroblasts.	The study highlights the role of oxidative stress and its impact on melanocyte vulnerability, contributing to their destruction in vitiligo.

0

category

Dermatological

name

Depigmented Patches

frequency

FREQUENT

diagnostic

True

sequelae

Social Stigma Increased Sensitivity To Sunlight Skin Cancer Risk Reduction

evidence

reference	supports	snippet	explanation
PMID:25572727	SUPPORT	Vitiligo is an acquired cutaneous disorder of pigmentation... Recent data provide strong evidence supporting an autoimmune pathogenesis of vitiligo.	The document confirms that vitiligo is characterized by depigmented patches and addresses the negative impact on quality of life, which can include social stigma.
PMID:35166101	SUPPORT	Vitiligo is a skin disorder characterized by selective loss of melanocytes resulting in circumscribed, depigmented macules and patches... its effects can be psychological, leading to stigmatization and suicidal ideation.	This supports the statement by confirming the presence of depigmented patches and social stigma.
PMID:17250545	SUPPORT	Vitiligo is the most common depigmenting disorder, which affects 0.5-1% of the worldwide population, causing disfigurement and serious disturbances in well being.	This supports the statement regarding the commonality of depigmented patches and associated social stigma.
PMID:23796814	SUPPORT	Vitiligo is an acquired, idiopathic skin disease characterized by the mostly progressive loss of the inherited skin color leading to white patches... The disease burden includes stigmatization, depression, impaired quality of life, lack of self-confidence, embarrassment and self-consciousness.	This supports the statement regarding depigmented patches and social stigma.
PMID:32462299	PARTIAL	Vitiligo was causally associated with reduced risks of several cancers... melanoma (OR 0.9983; 95% CI 0.9976-0.9990; p < 0.001), non-melanoma skin cancer (OR 0.9997; 95% CI 0.9995-0.9999; p < 0.001).	Supports the reduction in the risk of skin cancer but does not address increased sensitivity to sunlight.

1

category

Dermatological

name

Premature Hair Whitening

frequency

OCCASIONAL

evidence

reference	supports	snippet	explanation
PMID:26769615	SUPPORT	Vitiligo in children is a distinct subset of vitiligo and differs from adult vitiligo. Characteristic features include family history of autoimmune or endocrine disease, higher incidence of segmental vitiligo, development of early or premature graying, increased incidence of autoantibodies and poor response to topical PUVA.	The excerpt lists 'development of early or premature graying' as a characteristic feature of vitiligo in children, supporting the statement that premature hair whitening is occasionally associated with vitiligo.

name	presence	evidence	frequency	context
Autoantibodies to Melanocytes	Elevated	TRUNCATED	Variable	None
Inflammatory Cytokines	Elevated	TRUNCATED	Variable	Lesional skin

0

name

NALP1

evidence

reference	supports	snippet	explanation
PMID:17637824	SUPPORT	This study confirms genetic association of generalized vitiligo with variation in NALP1, which contains at least two independent risk signals.	The study identified and confirmed a genetic association between generalized vitiligo and variations in the NALP1 gene. This supports the statement.

association

Associated

1

name

TYR

evidence

reference	supports	snippet	explanation
PMID:20410501	SUPPORT	We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07x10(-15)) and GZMB (P=3.44x10(-8)), and in a locus containing TYR (P=1.60x10(-18)), encoding tyrosinase.	The study identified a significant association between generalized vitiligo and a genetic locus containing the TYR gene.
PMID:32838589	SUPPORT	The tyrosinase levels were significantly elevated in patients. The TT genotype was the most prevalent one in the patients... MiRNA 196a-2 C/T (11614913) gene polymorphism and the elevated serum tyrosinase levels might be related to the pathogenesis of vitiligo and may affect its therapeutic response.	Elevated serum tyrosinase levels in vitiligo patients suggest a genetic association involving the TYR gene with vitiligo.

association

Associated

2

name

PTPN22

evidence

reference	supports	snippet	explanation
PMID:21515266	SUPPORT	The PTPN22 locus is one of the strongest risk factors outside of the major histocompatibility complex that associates with autoimmune diseases...including vitiligo.	The literature specifically mentions that PTPN22 is associated with vitiligo as part of its association with several autoimmune diseases.
PMID:28164884	PARTIAL	Several studies have demonstrated the association of protein tyrosine phosphatase, non-receptor type 22 +1858C-->T polymorphism with vitiligo... limited ethnic-based studies... In conclusion, protein tyrosine phosphatase, non-receptor type 22 +1858 T allele predisposes European individuals to vitiligo.	This source confirms the association but notes that the genetic association is specific to the European population and not found in the Asian population, suggesting partial support.

association

Associated

3

name

MC1R

evidence

reference	supports	snippet	explanation
PMID:20197744	SUPPORT	Genome-wide association studies (GWAS) have unveiled single nucleotide polymorphisms (SNPs) or genetic variants in MC1R, TPCN2, ASIP, KITLG, NCKX5, TYR, IRF4, OCA2, and TYRP1 pigmentation genes.	This reference provides evidence of an association between the MC1R gene and vitiligo.
PMID:33757175	SUPPORT	MC1R was found as a key gene in vitiligo and involved in the melanogenesis.	This reference identifies MC1R as a key gene involved in vitiligo, providing further support for its genetic association.

association

Associated

4

name

HLA-A

evidence

reference	supports	snippet	explanation
PMID:17243956	SUPPORT	Meta-analysis showed a significantly increased frequency of HLA-A2 in vitiligo among cases [OR = 2.07, 95% confidence interval (CI) 1.67-2.58].	The meta-analysis strongly suggests an association between HLA-A2, a specific allele of HLA-A, and vitiligo.
PMID:27821860	SUPPORT	It remains unclear whether the HLA-G variants associated with vitiligo were detected because of the high linkage disequilibrium (LD) with HLA-A*02.	This study also points to a possible association between HLA-A*02 and vitiligo due to high linkage disequilibrium with HLA-G variants.

association

Associated

5

name

HLA-DRB1

evidence

reference	supports	snippet	explanation
PMID:34686989	SUPPORT	In this study, we have evaluated the association and role of HLA-DRB4*01:01, -DRB1*07:01, and -DQB1*03:03:2 genes in different clinical subtypes of Vitiligo in the Iranian population.	The study discusses the association of different HLA-DRB1 allelic genes, including HLA-DRB1, with vitiligo.
PMID:20526339	SUPPORT	Further analyses suggested that the strong association at rs11966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles...	The findings of the genome-wide association study indicate an association of HLA-DRB1 alleles with vitiligo.
PMID:6600753	SUPPORT	Association of HLA-DR4 with vitiligo.	Although this specifically mentions HLA-DR4, it generally supports the connection between HLA class II genes and vitiligo, which includes HLA-DRB1.

association

Associated

0

name

UV Exposure

evidence

reference	supports	snippet	explanation
PMID:29124690	PARTIAL	This chapter focuses on the use of ultraviolet light in vitiligo as an established therapeutic option.	The reference suggests that UV light is used to treat vitiligo, which implies it can promote repigmentation. However, it does not address the exacerbation of contrast.
PMID:34245476	PARTIAL	Targeted phototherapy with EL demonstrated better repigmenting efficacy than TUVB in vitiligo.	This reference supports UV exposure aiding in repigmentation but does not discuss exacerbating contrast.
PMID:34806278	PARTIAL	Patients received Nb-UVB three times per week for 6 months... 90% of lesions showed variable degrees of repigmentation and 10% showed increase in size, indicating increased activity of the disease.	UVB treatments result in repigmentation in most cases, though some lesions increased in size, indicating potential exacerbation.

description

Promotes the repigmentation process in some cases, but can exacerbate the contrast in others.

1

name

Stress

evidence

reference	supports	snippet	explanation
PMID:26057504	SUPPORT	Psychological stressors should be considered as potential disease triggers in vitiligo patients.	The study identifies psychological stressors as potential triggers for the onset of vitiligo.
PMID:37481827	SUPPORT	Psychological stress triggers onset and development of vitiligo in humans.	The study confirms that psychological stress promotes vitiligo onset.
PMID:31986193	SUPPORT	Perceived stress was significantly higher among vitiligo individuals compared to those without vitiligo.	The data supports the notion that stress is a precipitating factor in vitiligo development.
PMID:7036910	NO_EVIDENCE		The title 'Vitiligo. It is important.' doesn't provide information related to stress or its impact on vitiligo.
PMID:38160837	NO_EVIDENCE		The focus of the ViCEKb is on chemical triggers, and no evidence is provided about the role of psychological stress in vitiligo.

description

Psychological stress is implicated in the exacerbation or onset of the disease.

2

name

Chemical Exposure

evidence

reference	supports	snippet	explanation
PMID:36433836	SUPPORT	In the binary logistic regression model, household chemicals/colored toothpaste use, [...] and an occupational exposure to phenol/catechol derivatives were significantly associated with vitiligo (three to fourfold increase).	The study identifies phenol derivatives as significant risk factors for the development of vitiligo.
PMID:33039241	SUPPORT	Chemicals like Monobenzyl Ether of Hydroquinone (MBEH) and 4-Tertiary Butyl Phenol (4-TBP) have been widely recognized to induce clinical lesions that resemble vitiligo.	The study demonstrates that phenol-based compounds can induce vitiligo-like lesions.
PMID:28317525	SUPPORT	Chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. [...] these chemicals have been used to induce melanocyte autoimmunity.	The study mentions the use of chemicals, including phenols, to induce vitiligo for therapeutic purposes, supporting the role of phenolic compounds in inducing or exacerbating vitiligo.

description

Certain phenolic compounds and other chemicals can induce or exacerbate vitiligo.

chemicals

Phenol

0

name

Topical Corticosteroid

description

Common first-line treatment to reduce inflammation and potentially stimulate repigmentation.

evidence

reference	supports	snippet	explanation
PMID:19178066	SUPPORT	Topical corticosteroids are one of the oldest and most useful treatments for dermatologic conditions... evidence of effectiveness exists only for select conditions, such as psoriasis, vitiligo...	The use of topical corticosteroids as a treatment for vitiligo is supported, indicating it as a common and effective treatment option.
PMID:38477910	SUPPORT	Evidence supports the use of... topical corticosteroids... as effective therapeutics for vitiligo...	The recommendations include topical corticosteroids as a first-line treatment for vitiligo in pediatric, adolescent, and young adult patients.
PMID:33350506	SUPPORT	The mainstay of treatment for unstable vitiligo has been topical agents (corticosteroids, calcineurin inhibitors)...	This article highlights topical corticosteroids as a primary treatment for vitiligo, supporting the statement.
PMID:20445292	SUPPORT	Topical therapy is employed as first-line treatment in localized vitiligo. Currently, several topical agents are available... corticosteroids...	Topical corticosteroids are mentioned as a first-line treatment, aligning with the provided statement.

1

name

Phototherapy

description

UVB light or PUVA treatment can stimulate melanocyte regeneration and pigment production.

evidence

reference	supports	snippet	explanation
PMID:27638438	SUPPORT	Acting on multiple steps in vitiligo pathogenesis, narrowband ultraviolet B is one of the few therapies that can effectively induce stabilization and stimulate repigmentation.	The article supports the use of narrowband UVB for stimulating repigmentation in vitiligo.
PMID:28317529	SUPPORT	The most potent stimulus for repigmentation is the UV light.	This reference directly supports that UV light, including UVB, is a potent stimulus for repigmentation in vitiligo.
PMID:20149899	SUPPORT	There have been many treatments to cure vitiligo such as use of steroid creams, PUVA (psoralen and ultraviolet A light), narrow band UVB (ultraviolet B), various surgical techniques, vitamin D analogues and pseudocatalase.	It lists both PUVA and narrowband UVB as standard treatments for vitiligo.
PMID:34806278	SUPPORT	OBJECTIVE: To study whether the colorimeter and point counting technique can be used as objective methods in monitoring vitiligo lesions during treatment with Nb-UVB...	The study demonstrates the effectiveness of narrowband UVB in increasing the melanin index, indicating pigment production in vitiligo lesions.

2

name

Skin Graft

description

can be used for stable vitiligo.

evidence

reference	supports	snippet	explanation
PMID:38038734	SUPPORT	For patients with stable vitiligo who have not achieved satisfactory results with medical treatments, the melanocyte-keratinocyte transplantation procedure (MKTP) is a viable option.	MKTP is a type of autologous non-cultured cellular grafting procedure used for treating stable vitiligo.
PMID:37000977	SUPPORT	Surgical therapies are effective methods to treat resistant stable vitiligo, with each method having advantages and disadvantages.	This study compares ultrathin skin grafting (UTSG) and suction blister epidermal grafting (SBEG), both of which are skin grafting methods used to treat stable vitiligo.
PMID:34169570	SUPPORT	Cultured epidermal autografts (CEA) are surgical therapeutic alternatives for patients with stable vitiligo resistant to conventional medical treatments.	CEA is mentioned as an option for treating stable vitiligo, indicating the use of skin grafting.
PMID:22994670	SUPPORT	A number of new therapeutic options for vitiligo have become available ... One among them is smashed skin grafting or simply smash grafting.	This reference discusses smash grafting as a method used in vitiligo treatment.
PMID:27274556	SUPPORT	Medical treatments are usually reasonably effective for nonstable vitiligo patches; however, for vitiligo patches that have been stable for a substantial period of time, surgical intervention should be considered.	It supports the use of surgical interventions, including skin grafting, for stable vitiligo.

context

Stable vitiligo

3

name

Melanocyte Transplantation

description

can be used for stable vitiligo.

evidence

reference	supports	snippet	explanation
PMID:12709002	SUPPORT	This surgical treatment gives its best results in segmental and focal vitiligo, even with large affected areas, and in at least 50% of patients with generalized vitiligo.	This implies that melanocyte-keratinocyte transplantation can be effective for stable vitiligo.
PMID:26728804	SUPPORT	Melanocyte-keratinocyte transplantation procedure: A few insights.	The procedure involves melanocyte transplantation which supports the statement for treating stable vitiligo.
PMID:28445194	SUPPORT	Cultured autologous melanocyte transplantation (CMT) is an effective treatment for stable vitiligo.	This confirms the use of melanocyte transplantation for stable vitiligo.
PMID:35457678	SUPPORT	Both the development of new techniques and modifications to the already available treatment of cell and tissue transplantation give hope to numerous patients around the world.	Surgical treatments including melanocyte transplantation are viable for stable vitiligo according to the literature.

context

Stable vitiligo

4

name

Monobenzone Cream

description

Treatment with monobenzone cream to remove remaining pigment in cases of extensive vitiligo.

evidence

reference	supports	snippet	explanation
PMID:3168334	SUPPORT	When large areas of skin are involved or when the patient is unresponsive to therapy, serious consideration should be given to depigmentation with monobenzone (Benoquin).	This supports the use of monobenzone cream for removing remaining pigment in cases of extensive vitiligo.
PMID:21054565	SUPPORT	If vitiligo involves most of the body, it might be easier to depigment the normal remaining skin rather than to attempt repigmentation. Our review revealed that... Monobenzyl ether of hydroquinone (MBEH) is the most widely used depigmenting agent and has few side-effects.	The reference supports the use of monobenzone (MBEH) for depigmentation in extensive vitiligo cases.

species	genotype	genes	associated_phenotypes
Zebrafish	MO1-zmiz1a/MO1-zmiz1b	zmiz1a zmiz1b	Pigmentation