Introduction - Vitiligo is the most frequent acquired hypomelanosis, but it's etiology is still uncertain. Many patients conect the onset to physical trauma, stress or illness. Nowadays new thoeries have been undertaken. It is clear that several different processes are involved in the etiology of vitiligo.
Aims & Scope - to analyse possible conections between the onset of vitiligo with other associated diseases, that have occurred in our patient’s life. The aim is also to mention about the new theory of the pathogenesis of vitiligo. There are some myths about the vitiligo, because of the misconnection of the vitiligo lesions and that occurs in for example leprosy or in sexually transmitted diseases. That myths have made the vitiligo a stigma in many societies.That problem has also been mention in the presentation.
Results - there have been revealed that the onset of vitiligo in this patient may be conected with the prevalence of others autoimmune disorders like thyroid disease, diabetes mellitus, alopecia areata. There was also family history of vitiligo – three patient’s daughters suffered from late onset vitiligo. Additionally there was a significant stress related trigger factor in patient’ life, that could have the influence on the onset of the disease.
Comments – Vitiligo is a disorder with a genetic background. The genes of susceptibility to the vitiligo are also connected with other autoimmune disorders. The environmental triggering factors play also a significant role in the onset of the vitiligo. Both melanocytes and nerves arise from a neural crest cells, and this is a basis of the neurohumoral hypothesis of the etiology of vitiligo. Oxidative stress hypothesis is based on a fact that this process may lead to melanocyte destructions and there are high H2O2 levels throughout the epidermidis in patients with vitiligo. The melanocytorragy hypothesis may be the explenation for the Koebner phenomenon in vitiligo. The decreased melanocyte survival hypothesis is associated with the decreased number of tyrosine kinase receptor c-kit in perilesional melanocytes, and with the lower expression of stem cell factor from surrounding keratinocytes. That may lead to vitiligo onset, causing the deficiency in survival signals leading to the melanocyte apoptosis.
Questions –
1. Is the Koebner phenomenon connected with the:
- Oxidative stress hypothesis
- Decreased melanocyte survival hypothesis
- Melanocytorragy hypothesis ?
2. What play the significant role in the oxidative stress hypothesis :
- Elevated levels of tenascin in the vitiligonous skin
- Decreased number of tyrosine kinase receptor c-kit in perilesional melanocytes
- Low levels of catalase enzyme in the skin of vitiligo patients ?
- Disclaimer-
This PPT is loaded as student material "as is", from the Vitiligo Master Class Barcelona November 2011; VRF does not endorse or otherwise approve it.
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Title - Vitiligo etiology – facts, theories and myths – based on a case report.
1. Vitiligo etiology – facts, theories
and myths – based on a case report
Joanna Bobkiewicz
University of Medical Sciences in Po
Department and Clinic of Dermatolo
2. Taking a history
76 year old female
A 25 years history of vitiligo – late onset vitiligo
„Chalk”, pale white macules, different in size and
shape
At the beginning - single lesions located in the
wrists, the palms and the forearms
Progression of the macules aroud the trunk and
the upper and lower limbs
Since 5 years – same lesions on the face – around
the eyes, around the mouth, on the forehead
3.
4.
5.
6. Physical examination
Numerous erosions, crusts and pruritus in the
elbows, forearms, and the wrists
Generalized pruritus from several months
From 3 months erythema, then bullae on the
upper and lower extremities with severe
pruritus
9. Associated diseases
Diabetes Melitus type 2 for 20 years.
Insulin human: 14-0-6 unitsc/day
Glucose profile: 137-155-181-150 mg/dl
Hypothyroidism for 13 years
Levothyroxinum natricum 100 µg/day
The last check-up: TSH 3,78 µU/ul
Alopecia areata 10 years ago
Leukotrichia
10. Autoimmune theory
Up to 30 % cases conected with thyroid disease
Numerous of the other autoimmune disorders
associated with vitiligo
Skin biopsy – lypmhocytic infiltrates, increased
CD 8/ CD 4 ratio
Serum IgG antibodies from vitiligo patients are
able to penetrate cultured melanocytes and cause
apoptosis
Increased expression in IL-17 and COX-2 genes in
vitiligo patiensts’ neutrophils
B.Esmaeili, SA. Rezaee, P. Layegh, J. Tavakkol Afshari, P.Dye, E. Ghayoor
Karimiani, F. Kalalinia, H. Rafatpanah
Vagh-Koyanagi-Harada disease occured during
pegylated IFN alfa2b and ribavirin therapy
J.H. Lim, Y.N. Lee, Y. S. Kim, S.G. Kim, S.W. Jeong, J.Y. Jang, H.S.
Kim, S.H. Lee, T.K. Park
11. Family history
3 of Patient’s daughters suffer from vitiligo
Late – onset vitiligo (the onset of the disease
> 50 years old)
One of daughter suffer also from psoriasis, and
have very quick progression of the vitiligo lesions
Patient son doesn’t have any vitiligo lesions
12. Genetic linkage
Vitiligo is inherited in a non-
Mendelian, multifactorial, polygenic pattern with
incomplete penetrance
HLA haplotypes are thought to correlate with
vitiligo susceptibility
1. HLAs – A2
2. DR-4
3. DR-7 are the most frequent
Various ethnicities have different HLA –
associated susceptibilities
13. Genetic linkage
Numerous candidate genes, genetic loci that
are believed to be associated with vitiligo
1. The gene for lymphoid protein tyrosinase
phosphatase – regulates T cell activity
2. The NALP-1 – key regulator of the immune
system
3. Mannose – binding lectin – when abberant
predisposed to infections and autoimmune
diseases
These genes and genetic loci can be also
associated with numerous autoimmune
disorders
14. Multifactorial etiology
Different phenotypes are correlated with various
genetic susceptibility and with different environmental
exposure
Autoimmune disorders involves interactions between
genetic risk factors and environmental triggering
factors
1. Emotional stress
2. Exposure to the sun , severe sunburn
3. Skin trauma ( Koebnerization ) or
4. Drugs, toxins and chemicals (..) may precede the
onset
The melanocytes are more susceptible to damage
factors than keratinocytes
15. Stress
Life long history of husband’s disease, that
have a strong influence on quality of patient’s
life, on the level of emotional stress in her
life
This situation also affected patient’s
daughters, having the same infulence on their
quality of life
The influence of the stress may also be seen
in Patients history
16. Associated diseases
Angina pectoris diagnosed 27 years ago
Myocardial infarction in 1994, 1998, 2008
Hypertension diagnosed 3 years ago
Paroxysmal supraventricular tachycardia
Chronic heart falilure, NYHA scale II
Chronic venosus insufficiency
17. Breast cancer
Carcinoma mucinosum invasivum of right
breast (2005)
Fibroadenoma of left breast (2005)
Surgical resection of breast cancer and
following radiotherapy of affected area
Every year check-up – abdominal
ultrasonography , mammography
18. Neurohumoral hypothesis
Dissregulation of the nervous system may
lead to the damage of the melanocytes
Both melanocytes and nerves arise from
neural crest cells
There are increased
epinephrine, norepinephrine and
neuropeptyde Y levels in vitiligo lesions ( in
immunohistochemical test ) – direct
damage, vasoconstriction, hypoxia
In patients with recent onset or progressive
disease urine levels of homovanilic and
vanillmandelic acid are significantly high
A. Alikhan, L.M. Felsten, M. Daly, V. Petronic-Rosic
19. Sun exposure
In 70’s during seaside the Patient had severe
sunburn on the majority of the skin surface.
She was covered by clothes during this one
day
The vitiligo lesions occur esspecialy in the
area with high sun exposure during summer
or spring – the dorsal surface of the
hands, the face - periorificial
20. After the Patient gave birth to her first child, she
suffered from severe hemmorhagy and she
needed an allogenic peripheral blood transplant
58 year old female who was diagnosed with the
acute myelogenous leukemia received a HLA-
idendtical allogenic peripheral stem cell
transplant
After 18 months post transplant she presented
with patchy depigmentation of the skin, involving
her face, trunk, upper and lower extremities
The donor – her sister – had vitiligo for several
years before
A. Campbell-Fontaine, J.E.Coad, R. Kovach, S.C. Ericson
21. Newer theories
Oxidative stress hypothesis
1. Both lesional and non-lesional skin from
vitiligo patients has abnormally low levels of
catalase enzyme, which correlates with high
H2O2 levels throughout the epidermidis
2. A single nucleotide polymorphism in the
catalase gene is more frequent among the
vitiligo patients
3. H₂O₂ acummulation degrades the activity of
the catalase enzyme
A. Alikhan, L.M. Felsten, M. Daly, V. Petronic-Rosic
22. Newer theories
Melanocytorragy hypothesis
1. Melanocytes are weakly anchored – minor
friction and/or stress can induce upward
migration and loss ( Koebnerization
phenomenon )
2. Several minutes of light friction on the
nonlesional skin of vitiligo patients produced
melanocyte detachment after 4-24h
3. Tenascin – extracellular matrix
molecule, inhibiting adhesion of the
melanocytes to fibronectin, is elevated in
vitiligonous skin. This may contribute to loss of
melanocytes, or ineffective repopulation
A. Alikhan, L.M. Felsten, M. Daly, V. Petronic-Rosic
23. Newer theories
Decreased melanocyte survival hypothesis
1. Significantly decreased number of tyrosine
kinase receptor c-kit in perilesional
melanocytes
2. Lower expression of stem cell factor from
surrounding keratinocytes
3. Keratinocyte-derived stem cell factor
regulates melanocytes growth and survival
by binding to membrane tyrosine kinase c-
kit receptor
A. Alikhan, L.M. Felsten, M. Daly, V. Petronic-Rosic
24. Myths
Poor medical care
Personal behaviour
Diet
State of mind
Pollution
A sign of leprosy
A sign of sexually transmitted infections
Profound impact on patients’ self-
esteem, self- image, interpersonal
relationship, quality of life !
25. Hope for melanoma therapy
„The selective destruction of pigment cells that occurs
in vitiligo may by therapeutic goal in melanoma
research”
„Vitiligo patients might represent a unique source of
therapeutic cells, to be used in allotransfer for HLA
matched melanoma patients”
„High frequencies of self-reactive T lymphocytes
directed toward melanocyte differentation antigens are
found in vitiligo patients, might be directly responsible
of the disease”
„T lymphocytes specific for different melanocyte
differentation antigens are fuond in vitiligo and
represent the effective anti-melanocyte reactivity, that
is often innefective in melanoma”
B. Palremo, S. Garbelli, S. Mantovani, C. Giachino