Posted by: Chris Maloney | October 5, 2011

White Like Michael: Vitiligo, Causes and Treatments.

Michael Jackson performing The Way You Make Me...

Image via Wikipedia

Jermaine Jackson came out with a book in which he mentions that Michael Jackson’s son Prince is already showing signs of vitiligo just like his father.

I think a large number of people never really realized that Michael Jackson suffered from vitiligo, a disfiguring disease in which the skin pigment gradually deteriorates.  A grumpy person on Youtube has documented his loss of pigment.  The NIH recommends the steroids and phototherapy (sunlight to the rest of us).  I’m sure Michael looked at all his options before aiming for complete loss rather than patches.  Were all the nose jobs necessary?  Well, I didn’t say he was perfect.

So what causes vitiligo?  We don’t know.  But we’ve got some ideas.  “Prevalent
hypotheses include the autoimmune, genetic, neural, self-destruction, growth
factor deficiency, viral, and convergence theories” but I prefer the idea that the darker skin cells simply cannot convert one amino acid to another rapidly enough.  If phenylalanine cannot be converted to tyrosine, then the pigment cell dies over time.  The inability of the cells to convert may be affected by any number of factors, but the goal is to find a treatment that works.  Currently our options combine phototherapy with a number of agents, which can be effective.  But simply using ginkgo biloba or phototherapy with topical phenylalanine may be useful.  I didn’t see any studies on topical tyrosine, which would make more sense.

Here, for anyone who suffers from vitiligo, are a few studies on the topic.

Mol Genet Metab. 2005 Dec;86 Suppl 1:S27-33. Epub 2005 Sep
6. Links

Decreased phenylalanine uptake and turnover in patients with
vitiligo.Schallreuter KU, Chavan B, Rokos H, Hibberts N, Panske A, Wood JM.

Clinical and Experimental Dermatology, Department of
Biomedical Sciences, University of Bradford, UK.

The human epidermis has the full machinery for autocrine
L-phenylalanine turnover to L-tyrosine in keratinocytes and melanocytes.
Phenylalanine hydroxylase (PAH) activities increase linearly with inherited
skin colour (skin phototype I-VI, Fitzpatrick classification) yielding
eightfold more activities in black skin compared to white skin. Moreover, UVB
irradiation (1 MED) significantly increases epidermal PAH activities 24 h after
exposure. Importantly, L-phenylalanine uptake and turnover in the pigment
forming melanocytes is vital for initiation of melanogenesis. In this context
it was shown that the uptake of this amino acid is regulated by calcium. The
depigmentation disorder vitiligo provides a unique model to follow impaired
L-phenylalanine turnover in the skin as well as in serum because affected
individuals hold an impaired epidermal 6BH4 de novo synthesis/recycling and
regulation including low epidermal PAH activities. After overnight fasting and
oral loading with L-phenylalanine (100 mg/kg body weight), 29.6% of 970
patients tested (n=287/970) yielded serum phenylalanine/tyrosine ratios
>or=4 and 35.3% (n=342/970) had mild to moderate hyperphenylalaninaemia
(HPA), while 9.3% (n=90/970) had both serum L-phenylalanine levels >or=2.0
mg/dl and phe/tyr ratios >or=4.0. Isolated HPA was found in 26% (n=252/970),
whereas 20.3% had only increased ratios (n=197/970). None of the patients had
phenylketonuria and the family history for this metabolic disease was negative.
The IQ followed normal Gaussian distribution. In vitro L-phenylalanine
uptake/turnover studies on primary epidermal melanocytes originating from these
patients demonstrated a significantly decreased calcium dependent
L-phenylalanine uptake and turnover compared to healthy control cells. Based on
our observation, we would like to propose that phenylalanine uptake/turnover is
under tight control by calcium which in turn could offer an additional novel
mechanism in the aetiology of HPA.

PMID: 16143555

G Ital Dermatol Venereol. 2010 Feb;145(1):57-78.

Topical treatment and combination approaches for vitiligo: new
insights, new developments.

Hossani-Madani AR, Halder RM.


Department of Dermatology, Howard University College of
Medicine, Washington, DC 20060, USA.


Despite much research done involving elucidation of the
pathogenesis of vitiligo, a precise cause is still not known. Prevalent
hypotheses include the autoimmune, genetic, neural, self-destruction, growth
factor deficiency, viral, and convergence theories, which have served as the
basis for treatment formulation. Topical therapies have been a mainstay of
vitiligo treatment, with or without phototherapy. Topical treatments used in
the treatment of vitiligo include steroids, calcineurin inhibitors, vitamin D
analogues, pseudocatalase, and depigmenting agents. Combination therapies are
used to improve the success rate of repigmentation. In this article, we have
examined randomized controlled trials utilizing topical treatments used as
monotherapy or combination therapy. Although psoralen and khellin can be used
as topical agents, used in conjunction with UV radiation, we have not included
them in the review due to their inability to be used as monotherapy. We have
also excluded less used or ineffective topical agents, such as melagenina,
topical phenylalanine, topical L-DOPA, coal tar, anacarcin forte oil and
topical minoxidil. According to current guidelines, a less than two month trial
of potent or very potent topical corticosteroids or topical calcineurin
inhibitors may be used for therapy of localized vitiligo (<20% skin surface
area). Combinations of topical corticosteroids with excimer laser and UVA seem to
be more effective than steroids alone. Pseudocatalase plus NB-UVB does not seem
to be more effective than placebo with NB-UVB. Combinations of vitamin D
analogues have varied efficacy based on which type is used and the type of UV
light. Efficacy of calcineurin inhibitor combinations also vary based on the
type used and UV light combined, with tacrolimus being more effective with
excimer laser. Pimecrolimus has been effective with NB-UVB and excimer laser on
facial lesions, and microdermabrasion on localized areas.

PMID: 20197746

Dermatol Ther. 2008 Jul;21 Suppl 1:S20-6.

Targeted and combination treatments for vitiligo.
Comparative evaluation of different current modalities in 458 subjects.

Lotti T, Buggiani G, Troiano M, Assad GB, Delescluse J, De
Giorgi V, Hercogova J.


Department of Dermatological Sciences, University of
Florence, Florence, Italy.


The current treatment of vitiligo is not satisfactory
according to the opinions of both the patient population and the
dermatologists. Recently, combination therapies have been introduced, which are
both systemic and targeted (microphototherapy). To evaluate the effects of
topical treatments given alone or in combination with 311-nm narrow-band
microphototherapy. We evaluated the efficacy and safety of: (1) 311-nm
narrow-band microphototherapy;(2) tacrolimus 0.1% ointment twice a day; (3)
pimecrolimus 1% cream twice a day; (4) betamethasone dipropionate 0.05% cream
twice a day; (5) calcipotriol ointment 50 microg/g twice a day; and (6)
10%l-phenylalanine cream twice a day, for the treatment of exclusively vitiligo
patches. A 311-nm narrow-band microphototherapy (Bioskin) was given alone or in
combination with the above-mentioned popular local treatments. Four hundred and
seventy patients suffering from vitiligo that affected less than 10% of the
skin surface were evaluated. The patients were divided into 11 groups according
to the selected treatment modalities. Four hundred and fifty-eight patients
completed the study period of 6 months. Excellent repigmentation (> 75%) was
achieved by 72% of the patients in group 1, 76.5% in group 2, 76.1% in group 3,
90.2% in group 4, 75.6% in group 5, 74.8% in group 6, 61% in group 7, 54.6% in
group 8, 71.2% in group 9, 59.1% in group 10, and 29.3% in group 11. Marked
repigmentation (50-75%) was evident in 19.8% of the patients in group 1, 18.2%
in group 2, 20.1% in group 3, 6.7% in group 4, 14.1% in group 5, 11.3% in group
6, 16.1% in group 7, 18.4% in group 8, 25% in group 9, 10.6% in group 10, and
8.1% in group 11. Moderate results (25-50% repigmentation) were seen in 4.6% of
the patients in group 1, 3.3% in group 2, 2.7% in group 3, 2.2% in group 4,
7.4% in group 5, 10.1% in group 6, 18.4% in group 7, 21.7% in group 8, 2.1% in
group 9, 27.1% in group 10, and 55% in group 11. Finally, minimal (< 25%) or
no response was achieved in 3.6% of the patients in group 1, 2% in group 2,
1.1% in group 3, 0.9% in group 4, 2.9% in group 5, 3.8% in group 6, 4.5% in
group 7, 5.3% in group 8, 1.75% in group 9, 3.2% in group 10, and 7.6% in group
11. Side effects were skin atrophy (76% in group 4 and 81% in group 9),
stinging and burning (groups 2, 3, 7, and 8). Targeted combination therapies in
vitiligo are remarkably more effective than single treatments. When single
treatments are considered alone, 311-nm narrow-band UVB microfocused
phototherapy and 0.05% betamethasone dipropionate cream are the most effective
treatments in our study. When combined therapies are chosen, 0.05%
betamethasone dipropionate cream plus 311-nm narrow-band UVB microfocused
phototherapy apparently give the highest repigmentation rate. In the short
term, the only side-effects registered have been cutaneous atrophy with
corticosteroid cream, and stinging and burning with 0.1% tacrolimus ointment
and, less frequently, with 1% pimecrolimus cream.

PMID: 18727812

BMC Dermatol. 2008 May 22;8:2.

A systematic review of natural health product treatment for

Szczurko O, Boon HS.


Leslie Dan Faculty of Pharmacy, University of Toronto,



Vitiligo is a hypopigmentation disorder affecting 1 to 4% of
the world population. Fifty percent of cases appear before the age of 20 years
old, and the disfigurement results in psychiatric morbidity in 16 to 35% of
those affected.


Our objective was to complete a comprehensive, systematic
review of the published scientific literature to identify natural health
products (NHP) such as vitamins, herbs and other supplements that may have
efficacy in the treatment of vitiligo. We searched eight databases including
MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective
controlled clinical human trials were identified and assessed for quality.


Fifteen clinical trials were identified, and organized into
four categories based on the NHP used for treatment. 1) L-phenylalanine
monotherapy was assessed in one trial, and as an adjuvant to phototherapy in
three trials. All reported beneficial effects. 2) Three clinical trials
utilized different traditional Chinese medicine products. Although each
traditional Chinese medicine trial reported benefit in the active groups, the
quality of the trials was poor. 3) Six trials investigated the use of plants in
the treatment of vitiligo, four using plants as photosensitizing agents. The
studies provide weak evidence that photosensitizing plants can be effective in
conjunction with phototherapy, and moderate evidence that Ginkgo biloba
monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the
use of vitamins in the therapy of vitiligo. One tested oral cobalamin with
folic acid, and found no significant improvement over control. Another trial
combined vitamin E with phototherapy and reported significantly better
repigmentation over phototherapy only. It was not possible to pool the data
from any studies for meta-analytic purposes due to the wide difference in
outcome measures and poor quality of reporting.


Reports investigating the efficacy of NHPs for vitiligo
exist, but are of poor methodological quality and contain significant reporting
flaws. L-phenylalanine used with phototherapy, and oral Ginkgo biloba as
monotherapy show promise and warrant further investigation.

PMID: 18498646





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