From: jay on
Following abstracts from www.pubmed.gov

Below pubmed abstract proriasis and vitiligo responded to an
immunosuppressive drug which interferes with lymphocyte activation.

Familial coexisting and colocalized psoriasis and vitiligo responding
to alefacept. BACKGROUND:Psoriasis is an immune-mediated, chronic,
inflammatory disease that significantly impairs both physical and
emotional aspects of an individual's quality of life. Vitiligo leads
to depigmentation of skin, in which some or all melanocytes in the
interfollicular epidermis and occasionally those in the hair follicles
are selectively destroyed. The coexistence of the two disorders is
rarely seen.OBJECTIVE:To report two cases of the rare coexistence of
psoriasis and vitiligo in a family.METHODS:After providing informed
written consent, both patients were given alefacept 15 mg/kg weekly
injections for 12 weeks. The patients were monitored both clinically
and with all relevant laboratory investigations. These patients were
then followed up once a month for 2 years. RESULTS:Treatment with
alefacept led to complete clearance of vitiligo along with the
expected improvement in psoriasis. In the 2-year follow-up, vitiligo
did not recur, although psoriasis relapsed and was appropriately
treated.CONCLUSION:Use of alefacept in vitiligo may turn out to be a
possible novel off-label treatment option in vitiligo. But the results
need to be reproduced in larger studies. PMID: 19426629
From: jay on
> Following abstracts fromwww.pubmed.gov

Following abstract says, catalase is low in active vitiligo. Catalase
is a common enzyme found in nearly all living organisms which are
exposed to oxygen, where it functions to catalyze the decomposition of
hydrogen peroxide to water and oxygen.

Antioxidant enzymes and lipid peroxidation at the tissue level in
patients with stable and active vitiligo. BACKGROUND: The
pathogenetic mechanisms in vitiligo have not been clarified
completely. One of the major hypotheses in the pathogenesis of
vitiligo is the oxidative stress hypothesis. The active and stable
phases of vitiligo are defined as the progression or appearance of new
lesions in the last 3 months and the absence of new lesions or
progression in the last 6 months, respectively. METHODS: We examined
the levels of malondialdehyde, catalase, glutathione peroxidase, and
superoxide dismutase in the tissues of 10 patients with active
vitiligo, 10 patients with stable vitiligo, and 20 matched healthy
controls. RESULTS: The results revealed that the levels of superoxide
dismutase, glutathione peroxidase, and malondialdehyde in tissues were
increased significantly in patients with active vitiligo relative to
those in patients with stable vitiligo and matched controls; however,
the levels of catalase in tissues were decreased significantly in
patients with active vitiligo relative to those in patients with
stable vitiligo and matched controls. CONCLUSIONS: Our study shows
that oxidative stress is involved in the pathophysiology of both
active and stable vitiligo, but an increased imbalance of antioxidants
is observed in the tissues of patients with active vitiligo. PMID:
19416376

-------------------------------------
Following abstract says Narrow-Band UVB Phototherapy can be used in
management of vitiligo.

Evaluation of narrow-band UVB phototherapy in 150 patients with
vitiligo.
BACKGROUND: Very few studies have been performed to evaluate the
efficacy and safety of narrow-band ultraviolet B (NBUVB) therapy in
Indian patients with vitiligo and are of small sample size. Aims: The
purpose of this study is to know the efficacy and safety of NBUVB in
150 vitiligo patients of various age groups. METHODS: One hundred
fifty patients (69 males, 81 females), aged 3-70 years, with vitiligo
were treated twice weekly with NBUVB. The starting dose was 250 mJ/cm2
in adults and 150 mJ/cm2 in children, with 20% dose increments at each
subsequent visit given for a maximum period of 1 year and were
followed-up for 6 months for stability of repigmentation. Statistical
methods were employed to establish the relation between the response
and the number of exposures, duration of treatment, cumulative dose
and the compliance. RESULTS: Analysis of our study showed that a
majority of our cases, about 73, achieved 25-75% repigmentation, with
an average of 51+/-19 exposures, 51 had <25% repigmentation, with an
average of 19+/-11 exposures and 26 had >75% repigmentation, with an
average of 74+/-24 exposures. Good response to therapy was directly
associated with good compliance, more number of exposures and
increasing cumulative dose, which was statistically significant
(P<0.01). Adverse effects were minimal. Only three patients developed
depigmentation of repigmented sites during follow-up. CONCLUSION: Our
study proves that NBUVB therapy is an effective and safe tool in the
management of vitiligo, with good stability of repigmentation and
cosmetic appearance.PMID: 19293504


--------------
Following abstract says that cytotoxic T cells can specifically target
and eradicate pigment cells.

Autoimmune Destruction of Skin Melanocytes by Perilesional T Cells
from Vitiligo Patients. In vitiligo, cytotoxic T cells infiltrating
the perilesional margin are suspected to be involved in the
pathogenesis of the disease. However, it remains to be elucidated
whether these T cells are a cause or a consequence of the
depigmentation process. T cells we obtained from perilesional skin
biopsies, were significantly enriched for melanocyte antigen
recognition, compared with healthy skin-infiltrating T cells, and were
reactive to melanocyte antigen-specific stimulation. Using a skin
explant model, we were able to dissect the in situ activities of
perilesional T cells in the effector phase of depigmentation. We show
that these T cells could infiltrate autologous normally pigmented skin
explants and efficiently kill melanocytes within this
microenvironment. Interestingly, melanocyte apoptosis was accompanied
by suprabasal keratinocyte apoptosis. Perilesional T cells did,
however, not induce apoptosis in lesional skin, which is devoid of
melanocytes, indicating the melanocyte-specific cytotoxic activity of
these cells. Melanocyte killing correlated to local infiltration of
perilesional T cells. Our data show that perilesional cytotoxic T
cells eradicate pigment cells, the characteristic hallmark of
vitiligo, thereby providing evidence of T cells being able to mediate
targeted autoimmune tissue destruction. PMID: 19242513

-----------------
Following abstract says a patient receiving organs developed vitiligo
possibly due to incompatible T cells from donor.

Vitiligo following a combined liver-kidney transplant.
We report an Afro-Caribbean male who developed vitiligo 10 days
following a combined liver-kidney transplant from a Caucasian donor.
Neither the donor nor the recipient had any previous history of
vitiligo, nor of autoimmunity. The depigmentation gradually resolved
by 8 weeks post-transplant with topical corticosteroids and standard
maintenance immunosuppression. We propose that the skin depigmentation
occurred due to the destruction of melanocytes by donor-derived
alloreactive cytotoxic T-lymphocytes or antibody transferred during
transplantation. Although vitiligo has been described in patients
receiving allogeneic bone marrow transplantation for haematological
malignancy, there are no previous reports of vitiligo post-solid organ
transplantation. PMID: 19042928

-------------------------
Following abstract says a boy may have developed vitiligo after
receiving bone marrow from his father.

Possible transfer of vitiligo by allogeneic bone marrow
transplantation: A case report. Abstract: Among the cases yet
published of development of vitiligo after BMT, only two can claim as
possible adoptive transfer of such disease. We report a case of a
patient with sickle cell disease in whom vitiligo developed after
allogeneic BMT from his HLA identical father affected by vitiligo. We
reviewed and searched for some particularities in the reported cases
of post-BMT vitiligo. PMID: 19032413
From: jay on
> Following abstracts from www.pubmed.gov

Another case of vitiligo improvement with immunosuppresive drugs.

Vitiligo improvement in a patient with ankylosing spondylitis
(inflammatory arthritis) treated with infliximab.
Ankylosing spondylitis (AS) is a disabling disease affecting the
enthesis and joints of the spine and peripheral sites. Tumour necrosis
factor alpha (TNF-alpha) is a proinflammatory mediator which plays a
significant role in the pathogenesis of AS. Infliximab (a chimeric
monoclonal antibody which blocks the activity of TNF-alpha) is one of
the most effective therapies of AS thus far. Vitiligo is a
depigmenting disorder of the skin of unknown aetiology affecting
0.5-1% of the population. Here we describe the effect of infliximab on
vitiligo in a patient with AS. PMID: 18182816
---------------------

Use of anti-tumor necrosis factor agents: a possible therapy for
vitiligo.
Vitiligo is a depigmenting skin disorder resulting from the loss of
melanocytes in the epidermis. Although the exact aetiology of vitiligo
has not yet been established, the abnormal immune responses have been
frequently observed in vitiligo patients. Moreover, some vitiligo
patients show higher lesion levels of tumor necrosis factor (TNF)-
alpha. TNF-alpha is an important pleiotropic cytokine that exerts
potent pro-inflammatory effects. There is growing evidence that TNF-
alpha plays an important role in the pathomechanism process of some
autoimmunity diseases, including ankylosing spondylitis (AS). Treated
with anti-TNF agents infliximab, with the improvement of AS, a
patient's vitiligo lesions also faded out. Therefore, we hypothesized
that TNF-alpha play an important role in vitiligo. On the one hand,
TNF-alpha destroys melanocytes through induction of various apoptotic
pathways. On the other hand, TNF-alpha inhibits melanocyte stem cells
differentiation. Anti-TNF therapy may be an effective treatment for
vitiligo.
PMID: 19201101


-----------------------
The analysis of genetics and associated autoimmune diseases in Chinese
vitiligo patients.
Vitiligo is a common skin and hair depigmentary disorder that results
from selective destruction of melanocytes. It occurs in a typical
multifactorial, polygenic inheritance. Several studies have indicated
that vitiligo is associated with some autoimmune diseases. In this
paper we examined 6,516 vitiligo patients including clinical
characteristics, familial involvement, and their association with
other autoimmune diseases. Compared with sporadic vitiligo probands,
familial vitiligo probands have earlier age onset and longer disease
duration. The prevalences of four autoimmune diseases namely
rheumatoid arthritis, chronic urticaria, alopecia areata and
psoriasis, were significantly elevated in generalized vitiligo
probands and their first-degree relatives. The prevalences of chronic
urticaria, rheumatoid arthritis, psoriasis were much higher in
familial generalized vitiligo probands. In addition, the prevalences
of diabetes mellitus and asthma were also higher in familial vitiligo
probands. These findings indicate that generalized vitiligo may share
common genetic aetiologic links with other autoimmune diseases, and
the genetic component of familial generalized vitiligo is stronger.
PMID: 18839195

------------------------
Apoptosis of melanocytes in vitiligo results from antibody
penetration.
Vitiligo is a rather common disease characterized by depigmentation of
skin and mucosae due to the loss of melanocytes, most likely as a
result of autoimmune phenomena. In this study we demonstrated
apoptotic markers in residual melanocytes in skin biopsies of patients
with vitiligo, as well as the presence of serum antibodies to
melanocyte-specific antigens in the vast majority of patients.
Moreover, we were able to prove that serum IgG antibodies from
vitiligo patients, but not from healthy controls, were capable to
penetrate into cultured melanocytes in vitro, and trigger them to
engage in apoptosis. Our results are consonant with the theory that
melanocyte-specific antibodies are responsible for the deletion of
melanocytes through antibody penetration and apoptosis.PMID: 17888626

------------------
Vitiligo puzzle: the pieces fall in place.
Based on existing research, we propose that vitiligo has a multi-
factorial etiology, characterized by multiple steps, but always
involving an increase of external or internal phenol/catechol
concentration, serving as a preferred surrogate substrate of
tyrosinase, competing with its physiological substrate tyrosine. The
conversion of these substrates into reactive quinones is reinforced by
a disturbed redox balance (increasing hydrogen peroxide). Such
reactive quinones can be covalently bound to the catalytic centre of
tyrosinase (haptenation). This could give rise to a new antigen,
carried by Langerhans cells to the regional lymph node, stimulating
the proliferation of cytotoxic T cells. However, the activation of
such cytotoxic cells is only a first step in skin melanocyte killing,
which also depends on a shift in the balance between immune defence
and tolerance, e.g. resulting from a decrease in properly functioning
T-regulatory cells. A similar complex mechanism may also lead to some
other autoimmune diseases. PMID: 17850508

---------------------
Phenol and related compounds can trigger vitiligo.

4-Tertiary butyl phenol exposure sensitizes human melanocytes to
dendritic cell-mediated killing: relevance to vitiligo.
The trigger initiating an autoimmune response against melanocytes in
vitiligo remains unclear. Patients frequently experience stress to the
skin prior to depigmentation. 4-tertiary butyl phenol (4-TBP) was used
as a model compound to study the effects of stress on melanocytes.
Heat shock protein (HSP)70 generated and secreted in response to 4-TBP
was quantified. The protective potential of stress proteins generated
following 4-TBP exposure was examined. It was studied whether HSP70
favors dendritic cell (DC) effector functions as well. Melanocytes
were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in
response to 4-TBP exposure was partially released into the medium by
immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70
in turn induced membrane tumor necrosis factor-related apoptosis-
inducing ligand (TRAIL) expression and activation of DC effector
functions towards stressed melanocytes. Melanocytes exposed to 4-TBP
demonstrated elevated TRAIL death receptor expression. DC effector
functions were partially inhibited by blocking antibodies to TRAIL.
TRAIL expression and infiltration by CD11c+ cells was abundant in
perilesional vitiligo skin. Stressed melanocytes may mediate DC
activation through release of HSP70, and DC effector functions appear
to play a previously unappreciated role in progressive vitiligo. PMID:
15816839

-------------------
Seems to say, vitiligo could be caused a tyrosiane-related protein
resulting form a virus infection!

Vaccination with a recombinant vaccinia virus encoding a "self"
antigen induces autoimmune vitiligo and tumor cell destruction in
mice: requirement for CD4(+) T lymphocytes.
Many human and mouse tumor antigens are normal, nonmutated tissue
differentiation antigens. Consequently, immunization with these "self"
antigens could induce autoimmunity. When we tried to induce immune
responses to five mouse melanocyte differentiation antigens, gp100,
MART-1, tyrosinase, and tyrosinase-related proteins (TRP) 1 and TRP-2,
we observed striking depigmentation and melanocyte destruction only in
the skin of mice inoculated with a vaccinia virus encoding mouse
TRP-1. These mice rejected a lethal challenge of B16 melanoma,
indicating the immune response against TRP-1 could destroy both normal
and malignant melanocytes. Cytotoxic T lymphocytes specific for TRP-1
could not be detected in depigmented mice, but high titers of IgG anti-
TRP-1 antibodies were present. Experiments with knockout mice revealed
an absolute dependence on major histocompatibility complex class II,
but not major histocompatibility complex class I, for the induction of
both vitiligo and tumor protection. Together, these results suggest
that the deliberate induction of self-reactivity using a recombinant
viral vector can lead to tumor destruction, and that in this model, CD4
(+) T lymphocytes are an integral part of this process. Vaccine
strategies targeting tissue differentiation antigens may be valuable
in cancers arising from nonessential cells and organs such as
melanocytes, prostate, testis, breast, and ovary. PMID: 10077623

-----------------------
Vitiligo as a post-bone marrow transplantation complication.
Vitiligo is an autoimmune condition in which T cells recognize and
destroy melanocytes. We present a case of a 20-year-old male who
developed generalized vitiligo 4 years after allogeneic (from another
person) bone marrow transplantation (BMT) for Fanconi anemia. Although
other autoimmune conditions have been well characterized as post-BMT
complications, vitiligo is very rare. We review the 9 previously
reported cases of post-BMT vitiligo. PMID: 17609627

------------------------
Association of vitiligo with HLA-A2: a meta-analysis.
BACKGROUND: Linkage and association studies suggest that the human
leucocyte antigen (HLA) region may be involved in the genetic
susceptibility of vitiligo. HLA-A2 has been reported to be associated
with vitiligo in some, but not all, studies. ...CONCLUSION: These
findings strongly suggest an association between HLA-A2 and vitiligo.
PMID: 17243956

----------------------
Following abstract says tyrosinase-related protein, phenol, catalase
and oxidative stress may be related to vitiligo.

A role for tyrosinase-related protein 1 in 4-tert-butylphenol-induced
toxicity in melanocytes: Implications for vitiligo.
Vitiligo presents with depigmented cutaneous lesions following
localized melanocyte death. Multiple factors contribute to cell death,
including genetically determined susceptibility to trauma, and
environmental factors, such as exposure to 4-tert-butylphenol (4-TBP).
We demonstrate that 4-TBP induces oxidative stress that is more
readily overcome by melanocytes from normally pigmented individuals
than from two individuals with vitiligo. The antioxidant catalase
selectively and significantly reduced death of melanocytes derived
from two individuals with vitiligo, indicating a role for oxidative
stress in vitiligo pathogenesis. In normal melanocytes, oxidative
stress results in reduced expression of microphthalmia-associated
transcription factor (MITF). Melanocyte-stimulating hormone-induced
expression of MITF protein caused increased sensitivity to 4-TBP,
whereas sensitivity of melanomas correlated with MITF expression. MITF
stimulates melanin synthesis by up-regulating expression of
melanogenic enzymes such as tyrosinase-related protein-1 (Tyrp1).
Although melanin content per se did not affect sensitivity to 4-TBP,
expression of Tyrp1 significantly increased sensitivity. Melanocytes
and melanomas that express functional Tyrp1 were significantly more
sensitive to 4-TBP than Tyrp1-null cells. Thus, normal melanocytes
respond to 4-TBP by reducing expression of MITF and Tyrp1. We
hypothesize that melanocytes in vitiligo demonstrate reduced ability
to withstand oxidative stress due, partly, to a disruption in MITF
regulation of Tyrp1. PMID: 17071589
From: jay on
On May 12, 3:59 pm, jay <jaym1...(a)hotmail.com> wrote:
> Following abstracts fromwww.pubmed.gov

Antioxidants in vitiligo treatment.
Oxidative stress has a definite role in genesis of several diseases
and there is a possibility of its correction. In the latest period
oxidative stress in the skin related with vitiligo is the subject of
special interest. Experimentally has been proven that keratinocytes
obtained from the vitiligo areas generate big amount of superoxide
anions - reactive forms of oxygen and nitric oxide. It is known that
in patients suffering from generalized form of vitiligo there is a
disbalance between oxidative and antioxidative systems. Considering
above, the preparation vitix (containing antioxidants, superoxide
dismutaze and catalase) for treatment of vitiligo is important. 25
patients (5-63 years old) with different clinical forms of vitiligo
with duration of 1-5 years were included in the study. The drug was
prescribed in tablet form for using 1 times a day irrespective of
ingestion and 2-times a day for local application on affected sites.
Homogeneous repigmentation of affected areas, without sharp contrast
between affected, newly pigmented and normal skin areas were observed.
Absence of side effects and good tolerance allow us to recommend Vitix
for the treatment of vitiligo. PMID: 16783073

--------------------
Psoriasis confined strictly to vitiligo areas--a Koebner-like
phenomenon?
Vitiligo and psoriasis are both common skin disorders. However,
psoriasis strictly confined to pre-existing vitiligo areas is rare and
suggests a causal relationship. We report here on two patients with a
strict anatomical colocalization of vitiligo and psoriasis. The
histopathological examinations showed typical changes for both
diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By
immunohistochemistry, intracytoplasmatic granzyme B and tumour
necrosis factor alpha (TNF-alpha) were detected within the T-cell
population, suggesting the functional activity of these cells and the
creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in
one patient we could identify anti-melanocytic T cells by tetramer
staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-
infiltrating lymphocytes might trigger, by the local production of
Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the
eruption of psoriatic plaques in patients with a genetic
predisposition for psoriasis. PMID: 16441627


----------------------------
Audiological abnormalities in patients with vitiligo.
BACKGROUND: Accumulating evidence suggests that vitiligo is a systemic
disease affecting the entire pigmentary system. AIM: To investigate
the subclinical abnormalities of melanin-containing cellular elements
of the auditory system in patients with vitiligo. METHODS: We studied
the conventional audiometric investigations and brainstem auditory
evoked responses (BAERs) of 57 active patients with vitiligo and 50
healthy human subjects. The I, III and V latencies, and I-III, III-V
and I-V interpeak latencies (IPL) between the groups were compared.
RESULTS: A mild degree of sensorineural hypoacusis was found in eight
patients with vitiligo (14%), whereas no controls demonstrated
abnormal audiological results (P =0.006). A statistically significant
increase in both ears of the third peak latency (P =0.02, P = 0.01,
respectively) and IPL I-III (P = 0.04, P = 0.008, respectively), and a
significant increase of the fifth peak latency in the right ear (P =
0.04) were found, compared with controls, but no differences were
found for other latencies and IPLs. CONCLUSIONS: Melanin may play a
significant role in the establishment and/or maintenance of the
structure and function of the auditory system and may modulate the
transduction of the auditory stimuli by the inner ear. PMID: 16309498

----------------
Physiopathology and genetics of vitiligo.
Generalized vitiligo is an acquired disorder in which white patches of
skin and overlying hair result from autoimmune loss of melanocytes
from involved areas. The autoimmune pathogenesis of vitiligo has
become a rapidly evolving field of research. A humoral immune reaction
has been implicated through the detection of circulating antibodies.
However, recent research focuses on a melanocyte-specific cytotoxic-T-
cell immune reaction in the melanocyte destruction. Several candidate
genes have been proposed for vitiligo susceptibility. They include
genes important for melanin biosynthesis, response to oxidative stress
and/or regulation of autoimmunity. A recent genome-wide scan performed
on families with numerous members presenting vitiligo has clearly
revealed linkage of susceptibility loci. PMID: 16298511

-----------------------------
Contact vitiligo following a strong patch test reaction to triglycidyl-
p-aminophenol in an aircraft industry worker: case report and review
of the literature.
Epoxy resin systems (ERSs) are a frequent cause of occupational
allergic contact dermatitis. A 50-year-old patient developed
eczematous skin lesions on the back of his hands, lower arms and eye
lids, 2 months after he had started working in aircraft construction.
Patch tests showed positive reactions at day 3 to nickel sulfate,
epoxy resin based on diglycidyl ether of bisphenol F (DGEBF) and 1,4-
butanediol diglycidyl ether (1,4-BDDGE). The chemical triglycidyl-p-
aminophenol (TGPAP) applied at 1% and 0.1% induced the strongest (+++
positive) reaction. About 4 months after the patch test with TGPAP,
the patient presented with 2 circular depigmented spots in the former
TGPAP-patch test areas. Dermatohistopathology confirmed the diagnosis
of contact vitiligo. PMID: 16033402
From: jay on
> Following abstracts from www.pubmed.gov

Early disease onset and increased risk of other autoimmune diseases in
familial generalized vitiligo. Generalized vitiligo is an autoimmune
disorder in which acquired white patches of skin and overlying hair
result from autoimmune loss of melanocytes from involved areas.
Although usually sporadic, family clustering of vitiligo may occur, in
a non-Mendelian pattern typical of multifactorial, polygenic
inheritance. Sporadic vitiligo is associated with autoimmune thyroid
disease, pernicious anemia, Addison's disease, and lupus; these same
disorders occur at increased frequency in patients' first-degree
relatives. Here, we studied 133 'multiplex' generalized vitiligo
families, with multiple affected family members. The age of onset of
vitiligo is earlier in these 'multiplex' families than in patients
with sporadic vitiligo. Affected members of the multiplex vitiligo
families have elevated frequencies of autoimmune thyroid disease,
rheumatoid arthritis, psoriasis, adult-onset insulin-dependent
diabetes mellitus, pernicious anemia, and Addison's disease. Probands'
unaffected siblings have elevated frequencies of most of these same
autoimmune diseases, particularly if the proband had non-vitiligo
autoimmune disease. Familial generalized vitiligo is thus
characterized by earlier disease onset and a broader repertoire of
associated autoimmune diseases than sporadic vitiligo. This mostly
likely reflects a greater inherited genetic component of autoimmune
susceptibility in these families. These findings have important
implications for autoimmune disease surveillance in families in which
multiple members are affected with vitiligo. PMID: 16029422

-----------------------
Aspirin may be helpful.

Decreased proinflammatory cytokine production by peripheral blood
mononuclear cells from vitiligo patients following aspirin treatment.
OBJECTIVE: Limited studies have shown that treatment of cells with
aspirin modulates their cytokine production. Consequently, the aim of
the present study is to investigate the pattern of important
proinflammatory cytokines production by stimulated peripheral blood
mononuclear cells (PBMC) from patients with active vitiligo following
long-term treatment with low-dose oral aspirin. METHODS: The study was
conducted at the Vitiligo Unit, King Abdul-Aziz University Medical
Center, Jeddah, Kingdom of Saudi Arabia between March and October
2003. Thirty-two patients (18 females and 14 males) with non-segmental
vitiligo were divided into 2 equal groups, one group received a daily
single dose of oral aspirin (300 mg) and the other group received
placebo for a period of 12 weeks. The concentrations of interleukin
(IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha)
were determined in the supernatant of isolated cultured PMBC after
being stimulated with bacterial lipopolysaccharide (LPS), before the
start of aspirin treatment and at end of treatment period. Cytokine
levels were measured using the quantitative sandwich enzyme-linked
immunosorbent assay (ELISA) technique, utilizing commercially
available kits. RESULTS: The proinflammatory cytokine production by
the PBMC of patients with active vitiligo was significantly increased
compared to normal controls. Thus, the relative percentage increase in
the production of IL-1beta, IL-6, IL-8 and TNF-alpha was: 39.4%,
110.5% (p<0.05), 91.5% (p<0.01), and 37% (p<0.05). At the end of
treatment, proinflammatory cytokine production in the aspirin-treated
group of active vitiligo patients was significantly decreased compared
to the placebo group. Thus, the relative percentage decrease in the
production of IL-1beta IL-6, IL-8 and TNF-alpha was: 42.5%, 45.2%
(p<0.05), 30.8% (p<0.01), and 50.6% (p<0.05). The vitiligo activity
was arrested in all aspirin-treated patients, while 2 patients
demonstrated significant repigmentation. CONCLUSION: Chronic
administration of low-dose oral aspirin can down-regulate the PBMC
proinflammatory cytokine production in active vitiligo with
concomitant arrest of disease activity. PMID: 15951873

----------------
Some chemicals can trigger immune response

4-Tertiary butyl phenol exposure sensitizes human melanocytes to
dendritic cell-mediated killing: relevance to vitiligo.
The trigger initiating an autoimmune response against melanocytes in
vitiligo remains unclear. Patients frequently experience stress to the
skin prior to depigmentation. 4-tertiary butyl phenol (4-TBP) was used
as a model compound to study the effects of stress on melanocytes.
Heat shock protein (HSP)70 generated and secreted in response to 4-TBP
was quantified. The protective potential of stress proteins generated
following 4-TBP exposure was examined. It was studied whether HSP70
favors dendritic cell (DC) effector functions as well. Melanocytes
were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in
response to 4-TBP exposure was partially released into the medium by
immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70
in turn induced membrane tumor necrosis factor-related apoptosis-
inducing ligand (TRAIL) expression and activation of DC effector
functions towards stressed melanocytes. Melanocytes exposed to 4-TBP
demonstrated elevated TRAIL death receptor expression. DC effector
functions were partially inhibited by blocking antibodies to TRAIL.
TRAIL expression and infiltration by CD11c+ cells was abundant in
perilesional vitiligo skin. Stressed melanocytes may mediate DC
activation through release of HSP70, and DC effector functions appear
to play a previously unappreciated role in progressive vitiligo. PMID:
15816839


Relevance of thyroiditis and of other autoimmune diseases in children
with vitiligo.
CONCLUSION: In paediatric patients with non-segmental vitiligo, a
significant incidence of thyroid dysfunction was found. Since vitiligo
usually appears before the development of the thyroid disease, it may
be useful to screen thyroid autoantibodies in all paediatric patients
with non-segmental vitiligo who present symptoms related to thyroid
disease. PMID: 15604541

------------------
Vitamin D3 ointment may help.

New aspects on vitamin D3 ointment: vitamin D3 therapy for vitiligo.
Recently, there are some reports that combination therapy with topical
vitamin D(3) ointment and PUVA (psonalen ultraviolet A) or vitamin D
(3) alone improved vitiligo. We conducted an open trial on 27
patients, most of whom had poor clinical responses to the prior
therapies, topical steroid ointment and PUVA. The clinical effect
revealed that 13 of 27 patients showed more than 30% improvement.
Combination therapy with topical vitamin D(3) ointment and linear
polarrised infrared, UVA, solar irradiation, can be used as an
alternative therapy for vitiligo vulgaris. PMID: 15577147

------------------------
Antioxidants may help.

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo.
Vitiligo is an acquired pigmentary disorder of the skin of unknown
aetiology. The autocytotoxic hypothesis suggests that melanocyte
impairment could be related to increased oxidative stress. Evidences
have been reported that in vitiligo oxidative stress might also be
present systemically. We used the comet assay (single cell alkaline
gel electrophoresis) to evaluate DNA strand breaks and DNA base
oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-
sensitive sites, in peripheral blood cells from patients with active
vitiligo and healthy controls. The basal level of oxidative DNA damage
in mononuclear leukocytes was increased in vitiligo compared to normal
subjects, whereas DNA strand breaks (SBs) were not changed. This
alteration was not accompanied by a different capability to respond to
in vitro oxidative challenge. No differences in the basal levels of
DNA damage in polymorphonuclear leukocytes were found between patients
and healthy subjects. Thus, this study supports the hypothesis that in
vitiligo a systemic oxidative stress exists, and demonstrates for the
first time the presence of oxidative alterations at the nuclear level.
The increase in oxidative DNA damage shown in the mononuclear
component of peripheral blood leukocytes from vitiligo patients was
not particularly severe. However, these findings support an adjuvant
role of antioxidant treatment in vitiligo. PMID: 15491637

The role of oxidants and antioxidants in generalized vitiligo at
tissue level.
BACKGROUND: The role of oxidative stress has not been fully understood
in the aetiopathogenesis of vitiligo in different studies. AIM: We
aimed to investigate the role of the oxidative stress in the
pathogenesis of vitiligo. METHODS: In this study, we examined levels
of superoxide dismutase, glutathione peroxidase, malondialdehyde and
nitric oxide in tissue of 25 patients with generalized vitiligo and 25
healthy controls. RESULTS: Our results revealed that levels of
superoxide dismutase, glutathione peroxidase and malondialdehyde in
tissue were significantly increased in patients with generalized
vitiligo (P < 0.05). However, there was no statistically significantly
difference between two groups at tissue level of nitric oxide (P >
0.05). CONCLUSION: Our results demonstrate the presence of an
imbalance in the oxidant-antioxidant system in vitiligo at tissue
level and provide further support for a free radical-mediated damage
as an initial pathogenic event in melanocyte degeneration in vitiligo.
PMID: 15482295

----------------------
Autoimmune aspects of depigmentation in vitiligo.
Autoimmune depigmentation of the skin, vitiligo, afflicts a
considerable number of people, yet no effective therapeutic modalities
have been developed to treat it. In part, this can be attributed to
the obscure etiology of the disease, which has begun to reveal itself
only recently. It is known that pigment is lost as a function of
reduced melanocyte numbers in the epidermis, and that depigmentation
is accompanied by T cell influx to the skin in the vast majority of
patients. Characterizing such infiltrating T cells as type 1
proinflammatory cytokine-secreting cells reactive with melanocyte-
specific antigen is a major step toward effective therapy. Melanoma
research has shown that differentiation antigens, also expressed by
normal melanocytes, can be immunogenic when expressed in the
melanosomal compartment of the cell. Similar reactivity to melanosomal
antigens is apparent for T cells infiltrating vitiligo skin. It may
eventually be possible to treat patients with decoy antigens that
anergize such Tcells, or to prevent recruitment of the T cells to the
skin altogether. In this respect, it is important that T cells are
recruited to the skin as a function of dendritic cell activation and
that dendritic cells are likely activated at sites of epidermal trauma
as a consequence of stress proteins that spill over into the
microenvironment. Stress proteins chaperoning antigens representative
of the cells from which they were derived are then processed by
dendritic cells and contribute to their activation. Activated
dendritic cells not only migrate to draining lymph nodes to recruit T
cells but may execute cytotoxic effector functions as well. The
contribution of the effector functions to actual depigmentation of the
skin remains to be investigated. PMID: 14870989