Table 2

Summary of Study Results

Study ID Year & Country

Study Design

JADAD score (0–5)

N (n = total;

a = active;

c = control)

Dropouts

Inclusion/Exclusion Criteria

Intervention

Main Outcome Measure

Results


Akyol 2002 [32]

Turkey

controlled

0

n = 30

a = 15

c = 15

not reported

    Inclusion

patients with active, extensive & generalized vitiligo

14–60 years old

skin type II, III, IV

    Active

PUVA + vit E (900 IU/day)

    Control

PUVA 3x/wk, 315–400 nm emission spect increased by 20% up to erythema

    Duration
: 6 months

front and back total body photographs

pigmentation rated as:

- bad (0–25%)

- moderate (25–74%)

- good (75% or more)

PUVA + Vit E allowed good improvement in 60% of patients, with no significant oxidation.

Active

bad 3 (20%)

moderate 3 (20%)

good 9 (60%)

Control

bad 5 (33%)

moderate 4 (27%)

good 6 (40%)


Bedi 1989 [26]

India

placebo, controlled

0

n = 32

c = "self controlled" placebo for 1 month every 3 months

2 participants lost to follow up

    Inclusion

- male and female

- 6–42 years old

- methoxsalen tablets 10–20 mg QD + methoxsalen ointment/lotion-0.75% + P. kurroa rhizomes – 200 mg dried herb BID + exposure to sunlight

    Duration:
36–1.8 months; 12.13 months average treatment length

response rated as:

- 4 = complete cure

- 3 = fast & continuous reduction in patches

- 2 = slow, continues reduction in patches

- 1 = v. slow progress

- 0 = 0 progress

93% responded to treatment, 27% achieved complete cure.

4 = 8/30

3 = 17/30

2 = 2/30

1 = 3/30


Cheng 1987 [23]

China

randomized, controlled

1

n = 329

A: 16 = needle

B: 9 = medication

C: 5 = phototherapy

D: 128 = needle + medication

E: 61 = needle + medication + suntan

F: 110 = needle + medication + phototherapy

not reported

not reported

- needle = 1 g/2 ml bottle, injected 2–4 mL QD

- medication = 235 used "Vitiligo medication"; 48 used 8-MOP; 25 used "vitiligo cream"; rest prescribed egg yolk before suntan or phototherapy

- suntan = mid-May to end of Sept whole body naked suntan, 1–3 hr per day, 8–10 am, or 4–6 pm

- phototherapy = long wave phototherapy, every 2–3 days 5–25 cm2 or 1–10% of body surface

response rated as:

- excellent = color of lesion turns to normal

- very good = color of lesion turns normal for over 60% of body surface

- good = lesion gets smaller and appearance of black granules

- bad = lesion identical to that before the treatment

Treatment with suntan effective after 60 days.

Group A:

2 = excellent

5 = very good

9 = good

Group B

1 = excellent

2 = very good

6 = good

Group C

4 = good

1 = bad

Group F

16 = excellent

35 = very good

58 = good

1 = bad

109 = overall good result

Group D

8 = excellent

37 = very good

79 = good

4 = bad

124 = overall good result

Group E

12 = excellent

26 = very good

23 = good

61 = overall good result


Cormane 1985 [20]

Netherlands

controlled by run in over 4 months

0

n = 19

not reported

    Inclusion

- male and female

- generalized vitiligo

- above 18 years old

    Exclusion

- past spontaneous improvement

- CI to phenylalanine

l-phe 50 mg/kg after a low protein breakfast + UVA 2x/wk

    Duration
: 6–8 months

Controlled by run in with l-phe 50 mg/kg 2x/wk for 4 months

repigmentation was classified as dense, sparse or none

Repigmentation achieved in 94.7% of patients.

dense repigmentation in 26.3% (5 pts)

sparse 68.4% (13 pts)

none 5.2 (1 pt)


Jin 1983 [25]

China

randomized, controlled

1

n = 232

A: n = 100

B: n = 51

C: n = 52

D: n = 28

not reported

not reported

A: Chinese Herb/Medicine 1

Ingredients: multi herb formula

B: Corticoids

15 mg per day, oral (if effective decrease 5 mg every 2–4 weeks)

C: Chinese Herb/Medicine 2 + Corticoids

Ingredients different from Chinese Herb/Medicine 1* Group A,B,C also applies 30% Psoralen topically

D: Control

apply 30% Psoralen topically

    Duration
: 2 months

response rated as:

- Excellent = all lesions disappear, normal skin color reappears

- Very good = reduction in lesion, >60% of damaged skin surface regains normal skin color

- Good = reduction in lesion, 10–60% of damaged skin surface regains normal skin color

- Bad = lesion shows no change in appearance or size, <10% of damaged skin surface regains normal skin color

Chinese medicine 2 & corticoids provided the best treatment.

Group A

13% = excellent

17% = very good

34% = good

36% = bad

Group C

31% = excellent

14% = very good

28% = good

27% = bad

Group B

18% = excellent

13% = very good

29% = good

40% = bad

Group D

0% = excellent

6% = very good

27% = good

67% = bad


Khemis 2004 [30]

France

randomized, double blind

2

n = 30

self controlled by contralateral side

13 dropped out

    Inclusion

participants with 2 vitiliginous lesions each with at least 10 cm in diameter

    Exclusion

unstable vitiligo

    Active

Vitix + UVB

    Control

Placebo + UVB

primary:

- reduction of lesion surface area by 50%

- photographs under normal and Woods Lamp

The difference between control and active was not significant

4 participants did not repigment

4 participants received a reduction

6 achieved a reduction of more than 50% of lesion with Vitix and UVB but not with control

3 achieved had a reduction of more than 50% of lesion with control but not with Vitix and UVB.


Liu 2003 [24]

China

randomized, controlled

1

n = 74

a = 41

c = 33

not reported

not reported

    Active

- Xiaobai mixture orally (30 g walnut, 10 g red flower, 30 g black sesame, 30 g black beans, 10 g zhi bei fu ping, 10 g lu lu tong, 5 plums)1 mL is equivalent to 0.1 g raw medication, 160 mL once a day

    Control

- 10 mg 8-MOP TID

    Duration
: 3 months

repigmentation rated as:

- Excellent = normal skin color reappears

- Very good = >50% of damaged skin surface regains normal skin color

- Good = 10–50% of damaged skin surface regains normal skin color

- Bad = <10% of damaged skin surface regains normal skin color

95% of active and 79% of control group showed good results.

    Active

- 12 = excellent results

- 16 = very good results

- 11 = good results

- 2 = bad results

- Overall 95.12% showed good results

    Control

- 3 = excellent results

- 14 = very good results

- 9 = good results

- 7 = bad results


Middelkamp-Hup 2007 [28]

Netherlands

placebo controlled, randomized, double blind

5

n = 50

a = 25

c = 24

1 lost to follow up at last session

    Inclusion

- 18 years and older

- vitiligo vulgaris

    Exclusion

- history of skin cancer

- photosensitive

- pregnancy or lactation

- segmental vitiligo

- phototherapy 3 months prior

- use of topical treatments

- starting vitamins during the study

    Active

Polypodium leucotomos 250 mg TID + NB-UVB 2x/wk (210–360 j/cm2 at start & gradually increased)

    Control

placebo TID + NB-UVB

    Duration
: 25–26 weeks

severity of vitiligo rated as:

- very severe

- severe

- more severe

- less severe

- not so severe

secondary measures:

- digital photography of all vitiligo lesions

- patient self assessment scale 0–10

- monitored at w0, w6, w12, w26

- for quality of life used skin index-29

Clear trend toward increase in repigmentation in head and neck area with NB-UVB and oral P. leucotomos treatment.

Percent Repigmentation :

Head & Neck

active = 44%

control = 27%

Extremities

active = 30%

control = 26%

Trunk

active = 36%

control = 30%

Hands and Feet

active = 24%

control = 19%


Parsad 2003 [2]

India

randomized, placebo controlled, double blind

2

n = 52

a = 26

c = 26

1 active

2 control

"withdrew for reasons unrelated to the study"

    Inclusion

gradually progressive slow spreading vitiligo

    Exclusion

more than 3 lesions or surface area of depigmentation greater than 10 cm2 over last 1 month

    Active

40 mg Ginkgo biloba with 9.6 mg ginkgoflavone glycosides, TID

    Control

sugar capsule TID

    Duration
: 6 months

- photographs at 6-weekly intervals

- repigmentation judged as minimal (25%), moderate (50%), marked (75%), complete (100%)- degree of repigmentation was determined by comparison of paper tracings, written descriptions, and actual measurement of vitiliginous areas

Gingko biloba was significantly more effective.

    Active

-20 pts stopped progression of disease (out of 25)

- 10 pts showed marked to complete repigmentation (75–100%) (out of 25)

    Control

- 8 pts arrested progression of disease (out of 22)

- 2 pts showed marked to complete repigmentation (75–100%) (out of 22)


Rojas-Urdaneta 2007 [22]

Venezuela

randomized, double blind

3

n = 100

divided into 5 groups

all completed the study

    Inclusion

- stable vulgar vitiligo

- no treatment for 5 months before study

- 18 to 50 years old

- male or female

- no other pathology

- provided consent for study and treatment

    Exclusion

- concomitant disease

- treatment of vitiligo 5 months prior to study

- not complying with instructions

A: antioxidant and mitochondrial stimulating cream & oral antioxidants & phenylalanine

B: placebo cream and oral antioxidants and phenylalanine

C: oral administration of antioxidants and phenylalanine

D: placebo cream

E: antioxidant and mitochondrial stimulating cream

cream = VitilVenz

phenylalanine = 500 mg q12 hrs for 5 months

oral antioxidants = Vit A 20,000 IU

Vit C 1000 mg

Vit E 400 IU

Zinc 15 mg

Selenium 50 μg

Magnesium 2 mg

CoQ10 75 mcg

pygnogenol 1 mg

main outcome measures:

- clinical area of newly formed pigment every 30 days

- point system for classifying size

- histological presence of melanocytes at beginning and end

The use of antioxidant and mitochondrial cream, and oral antioxidants and phenylalanine provided best results.

group A

- best results, 10.4 points (p < 0.001)

group E

- second best results 9.77 points (p < 0.001)

group B, C

- 4 points (p < 0.05)

group D

- comparison placebo group


Siddiqui 1994 trial 1 [21]

Netherlands

randomized, controlled, open label

0

n = 149

A: no tx = 11

B: l-phe +UVA = 132

C: l-phe alone = 6

out of 132 l-phe + UVA, 60 dropped out because they were unable to attend every 3 months for evaluations)

    Inclusion

- disseminated vitiligo over 10–40% of body

- age 18–61 yrs

    Exclusion

- only distal vitiligo

- only acrofacial vitiligo

- contraindications (same as Carmane 1985)

- patients in the open trial were not enrolled in the blind trial

A: l-phe 50–100 mg/kg + UVA 2x/wk; 30–45 min after l-phe ingestion daily

B: l-phe 100 mg alone

C: no tx

    Duration
: 1.5 yrs

length & width measures + color photographs every 3 months

Repigmentation Classification:

- partial 25–40%

- incomplete 40–60%

- good 60–80%

L-phenylalanine + UVB provided better results than L-phenylalanine alone.

Group A

positive 94

stable 20

deterioration 18

n = 132

Group C

positive 0

stable 7

deterioration 4

n = 11

Group B

positive 0

stable 5

deterioration 1

n = 6


Siddiqui 1994 trial 2 [21]

Netherlands

placebo controlled, randomized, double blind

3

n = 32

5 in placebo

3 active (2 stopped for personal reasons)

    Inclusion

18–56 years old

vitiligo for 1–33 years

l-phe 100 mg/kg/day or placebo

UVA 2–3x/wk or no irradiation

    Duration
: 6 months

length and width measured + color photographs every 3 months

Repigmentation Classification:

- partial 25–40%

- incomplete 40–60%

- good 60–80%

L-phenylalanine + UVB provided best results.

l-phe + UVA

positive 6

stable 1

deterioration 1

% repigmentation 30–60

n = 8

dropouts 0

l-phe

positive 1

stable 3

deterioration 1

% repig 25

n = 5

dropouts 3

placebo + UVA

positive 0

stable 4

deterioration 2

% repig 0

n = 6

dropouts 2

placebo

positive 0

stable 3

deterioration 2

% repig 0

n = 5

dropouts 3


Tjioe 2002 [31]

Sweden

randomized, open label, controlled

2

n = 27

a = 14

c = 13

1 active and 1 control did not repigment more than 5% after 4 months and were advised to stop

    Inclusion

- male & female over 18 yrs

- stable vitiligo vulgaris (1 year with no changes)

- fitzpatrick's skin II – IV

    Exclusion

- other vitiligo treatment

- history of skin cancer

- on photosensitizing medications

- Psychiatric/epileptic disorders

- renal failure or allergies to substances in trial

    Active

- UVB 3x/wk

- oral cobalamin 1000 ug sustained release BID

- folic acid 5 mg BID

    Control

- UVB (311 nm) 3x/wk, started at 0.10 J/cm2 increased by 0–30% on individual basis

    Duration
: 12 months

primary:

visually scored as percentage of repigmentation of depigmented lesions primary criterion were areas showing most active repigmentation

secondary:

before and after photographs with % repigmentation visually estimated

No significant difference between the two groups.

25 out of 27 total showed prominent repigmentation in some areas, 1 in each group did not respond more than 5%


Valkova 2004 [27]

Bulgaria

controlled

(group assignment by alternation)

0

n = 33

a = 16

c = 17

not reported

    Inclusion

-vitiligo

- male & female and 8 kids

- age 6–59 (mean 24.3 years)

- photo-type II-IV

- 2–21 years of disease

    Active

- local KUVA

- 5% khellin in water/oil applied to lesion area

- 1 hr later – UVA – 2–2.5 j/cm2

    Control

- systemic PUVA

- oral psoralen (0.4 mg/kg)

- 2 hrs later-UVA – 1–1.5 j/cm2

- 3x/wk

    Duration
: 4.1 months

- % of repigmentation measured by planimetry (actual measurement)- % repigmentation according to rule of three

Both KUVA and PUVA treatment lead to similar results, but KUVA is local, therefore with potentially with less adverse events.

active n

90–100% 3(18.8%)

60–80% 4(25.0%)

20–50% 7(56.2%)

no effect 2

Signs of repigmentation appeared between 10–16 procedures

control n

90–100% 2 (11.8%)

60–80% 7 (41.2%)

20–50% 7 (41.2%)

no effect 1


anonymous 2006 [29]

Japan

randomized,

double blind

0

n = 19

a = 10

c = 9

not reported

    Inclusion

generalized vitiligo

    Exclusion

acral or segmental vitiligo

    Active

PUVA + Polypodium leucotomos

    Control

PUVA + placebo

    Duration
: 12 wks

repigmentation scored as:

- none or minimal (<25% repigmentation)

- mild (25–50%)

- moderate to excellent (>50%)

Percentage of patients with skin repig. greater than 50% was significantly higher in PUVA + Polypodium

    active

none = 2

mild = 3

moderate = 5

    Control

none = 5

mild = 4

moderate = 0


Szczurko and Boon BMC Dermatology 2008 8:2   doi:10.1186/1471-5945-8-2

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