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”َ‫ل‬ َ‫م‬ْ‫ل‬ِ‫ع‬ َ‫َل‬ َ‫ك‬َ‫ن‬‫ا‬َ‫ح‬ْ‫ب‬ُ‫س‬‫ ا‬‫ل‬َ‫اع‬ََ ‫ ا‬‫َل‬ِِ ‫ا‬َ‫َن‬‫ا‬َ‫ََن‬َ‫ـ‬ْ‫تْم‬
ُ‫يم‬ِ‫ل‬َ‫ْع‬‫ل‬‫ا‬ َ‫ت‬ْ‫ن‬َ‫أ‬ َ‫ك‬‫ ا‬‫ن‬ُِِ‫يم‬َِِْْ‫ا‬“
Presented by
Alaa Eldin Khalil Ibrahim
M.B., B.Ch.
Ain Shams University
Introduction
 Vitiligo is an autoimmune depigmenting disorder, it is
one of the most common skin disorders with
prevalence of 1-2% of the world's population.
 Reduced serum level of vitamin B12 and folic acid have
been found in patients with vitiligo (Montes et al., 1992;El-
Batawi et al., 2001).
 And, it has been reported that vitiligo improves after
treatment with vitamin B12 and folic acid (Juhlin and
Oslen, 1997).
 vitamin B12 and folic acid are required as cofactors by
the enzyme homocysteine methyltransferase to
convert homocysteine to methionine.
 So nutritional deficiency in either of these two
vitamins can results in increase in homocysteine level
in circulation.
 Homocysteine histidase
tyrosinase
oxidative stress on melanocytes
mediate its destruction
Interfere with
normal
melanogenesis
Aim of the work
 The aim of this work was to estimate the serum level
of homocysteine in vitiligo patients to evaluate its role
in the pathogenesis of the disease and its relation to
disease severity.
 This study was performed on 2 age and sex matched
groups. The first group was patients with vitiligo and
the second group healthy controls.
Patients:
included 30 adult vitiligo patients (group 1) who
were recruited from the outpatients' clinic of Al hud
Al marsod hospital in the period between february
and july 2012.
Exclusion criteria:
1) Patients taking any drug that could alter serum level
of Hcy as: Folic acid, vitamin B, lipid lowering drugs,
antidiabetics, anti parkinson, chemotherapy.
2)Patients with diseases known to affect Hcy level as
Homocystienuria, Hypothyroidism and Chronic renal
failure.
3)Patients who are physically active (manual workers
and athletes) as physical activity lowers plasma Hcy
level .
4)Patients with head and neck affection as vitiligo area
scoring index (VASI) doesn't include head and neck
region severity.
Controls:
Thirty age and sex matched healthy controls (group 2)
for homocysteine level determination.
Methods:
An informed consent was taken before inclusion of
the subjects into the study. All subjects were subjected
to the following:-
1)Full history taking:
 Personal history.
 History of present illness : onset, course, duration of
vitiligo and current treatments.
 Family history of vitiligo.
 Medical and drug history of medical importance.
2) Dermatological examination:
 Clinical assessment of extent of vitiligo in patients
was done according to a quantitative and severity
parametric score named vitiligo area scoring index
(VASI) Which was introduced by Hamzavi et al., 2004.
 The total body VASI is calculated using this formula:
VASI = ∑ Hand Units of all body sites × Residual Depigmentation.
 One hand unit (the palm plus the volar surface of all
the digits) is approximately 1% of the total body
surface area. It is used as a guide to estimate the
extent percentage of vitiligo involvement.
 The body is divided into five regions: upper
extremities , lower extremities, trunk, hands and feet.
The axillary region is included with the upper
extremities while the buttocks and inguinal areas are
included with the lower extremities.
 The residual depigmentation is expressed using VASI
visual chart (0%, 10%, 25%, 50%, 75%, 90%, or 100%).
100% depigmentation….no pigment is present.
90%…only specks of pigment are present.
75%…the depigmented area exceeds than pigmented area.
50%...the depigmented area equals the pigmented area.
25%...the pigmented area exceeds the depigmented area.
10%...only specks of depigmentation are present.
3) Homocysteine level determination:
The laboratory assessment of Hcy used in this study
was enzyme linked immunosorbant assay (ELISA) and
Hcy values are interpreted as follows:
 5 - 15 µmol/L in healthy adults.
 15 - 30 µmol/L in mild homocysteinemia.
 30 - 100 µmol/L in intermediate homocysteinemai.
 >100 µmol/L in severe homocysteinemia.
In this study, there was insignificant difference between
mean age among groups (P value = 0.968).
 there was no difference between gender distribution
among groups (P value = 1.00).
 There was insignificant difference between
indoor/outdoor occupation distribution among
groups (P value = 0.118).
 there was insignificant difference between family
history among groups (P value = 0.150).
 There was insignificant difference between medical
history among groups (P value = 0.206).
 There was insignificant difference between mean Hcy
level among groups (P value = 0.191).
 According to course of the disease, there was
insignificant difference between Hcy level and VASI
(P value = 0.595 & 0.093)
 According to onset of the disease, there was
insignificant correlation between Hcy level and VASI
(P value = 0.459 and 0.906)
 There was insignificant correlation between Hcy level
and gender of groups.(P value = 0.622 and 0.743)
 There was significant correlation between Hcy level
and age of patients and controls.(P value = 0.043 and
0.010)
 There was insignificant correlation between Hcy level
and VASI according to duration of the disease (P
value = 0.966 and 0.654)
 Our study was performed on 30 adult patients with
vitiligo and 30 adult healthy age and sex matched
controls to estimate serum level of Hcy and evaluate its
role in the pathogenesis of the disease and its relation
to disease severity .
 We excluded patients taking drugs or have disease
that can affect serum level of Hcy, patients who are
hyperactive as athletes or manual workers and
patients with head and neck vitiligo affection.
 In this study, There was insignificant difference
between groups regarding to age (P value = 0.96).
 Both patient's and control groups included 15 males and 15
females. So there was insignificant difference between
groups regarding gender (P value = 1.00).
 Family history of vitiligo was found to be positive in 2
patients and negative in 28 patients and it was negative in
all control subjects, This shows insignificant difference
between family history among all groups (P value = 1.15).
 regarding occupation, 16 vitiligo patients were working
indoor and 14 patients were working outdoor, in controls,
there were 10 persons working indoor and 20 were working
outdoor. This shows insignificant difference among
groups( P value= 0.11).
 Regarding medical history, only 1 patient was anaemic
and 2 patients were hypertensive and the medical history
of controls was irrelevant. The medical history relevance
among both groups was insignificant(P value = 0.20).
 Our study showed that there was insignificant difference
between groups regarding mean serum Hcy level (P value
= 0.191).
 Our finding was in agreement with Kim et al., (1999);
Balci et al., (2009); Gönül et al., (2010) who reported
that serum Hcy, vitamine B12 and folic acid levels do not
play a role in the etiopathogenesis of vitiligo
 Balci et al., (2009) performed a Turkish study on 48
patients with vitiligo and 31 age and sex matched healthy
controls. they reported that there was insignificant
correlation between Hcy, folic acid and vitamine B12 and
VASI with p value < 0.05.
 Gönül et al., (2010) also performed a study on 42 vitiligo
patients and 36 sex and age matched healty controls. They
found that vitamine B12 and folic acid do not play a role in
the etiopathogenesis of vitiligo and did not vary according
to the duration and activity of vitiligo.
 Kim et al., (1999) measured the serum levels of folic acid
and vitamin B12 in 100 Korean patients with vitiligo and
found that their was no significant difference compared
to the normal control group.
 Contrary to our results, Shaker and El Tahlawi, (2008);
Silverberg and Silverberg, (2011); Singh et al.,(2011 )
reported that serum Hcy level was significantly more
elevated in patients with vitiligo than in controls.
 The difference with our study may be due to the method of
vitiligo scoring as we used VASI which is a qualitative and
quantitative method that can record vitiligo extent and
severity in the same equation for every patient but Shaker
et al., (2008) recorded only extent of the disease by the
rule of nine.
 Also they excluded patients with vitiligo extent less than
30% of body surface area.
 According to our study, there was a significant correlation
between Hcy level and age of all subjects as Hcy level
increases with age.
 This explained by the deterioration of renal function and
weak renal exceretion of Hcy, this finding was in
agreement with Wilcken and Gupta, (1979); Kang et al.,
(1987); Hu et al.,(2004) and Guo et al., (2006).
 According to this study, there was no correlation between
course of vitiligo and serum level of Hcy, this was in
agreement with Karadag et al., (2012) .
 Also our study found no significant correlation between
duration of vitiligo and serum level of Hcy. This finding
was in agreement with Shaker and El Tahlawi, (2008).
 Our study recorded no significant correlation between
gender of patients or controls with serum level of Hcy,
This was in agreement with Silverberg and Silverberg,
(2011).
This study concludes that:
 serum Hcy may not be a precipitating factor for
vitiligo in the predisposed individuals.
 It has been found that serum Hcy level related to
age of the patients but not for activity, duration of
the disease or gender of patients.
Homocystiene as a biomarker of vitiligo severity.

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Homocystiene as a biomarker of vitiligo severity.

  • 1. ”َ‫ل‬ َ‫م‬ْ‫ل‬ِ‫ع‬ َ‫َل‬ َ‫ك‬َ‫ن‬‫ا‬َ‫ح‬ْ‫ب‬ُ‫س‬‫ ا‬‫ل‬َ‫اع‬ََ ‫ ا‬‫َل‬ِِ ‫ا‬َ‫َن‬‫ا‬َ‫ََن‬َ‫ـ‬ْ‫تْم‬ ُ‫يم‬ِ‫ل‬َ‫ْع‬‫ل‬‫ا‬ َ‫ت‬ْ‫ن‬َ‫أ‬ َ‫ك‬‫ ا‬‫ن‬ُِِ‫يم‬َِِْْ‫ا‬“
  • 2. Presented by Alaa Eldin Khalil Ibrahim M.B., B.Ch. Ain Shams University
  • 3.
  • 4.
  • 5. Introduction  Vitiligo is an autoimmune depigmenting disorder, it is one of the most common skin disorders with prevalence of 1-2% of the world's population.  Reduced serum level of vitamin B12 and folic acid have been found in patients with vitiligo (Montes et al., 1992;El- Batawi et al., 2001).  And, it has been reported that vitiligo improves after treatment with vitamin B12 and folic acid (Juhlin and Oslen, 1997).
  • 6.  vitamin B12 and folic acid are required as cofactors by the enzyme homocysteine methyltransferase to convert homocysteine to methionine.  So nutritional deficiency in either of these two vitamins can results in increase in homocysteine level in circulation.  Homocysteine histidase tyrosinase oxidative stress on melanocytes mediate its destruction Interfere with normal melanogenesis
  • 7.
  • 8. Aim of the work  The aim of this work was to estimate the serum level of homocysteine in vitiligo patients to evaluate its role in the pathogenesis of the disease and its relation to disease severity.
  • 9.
  • 10.  This study was performed on 2 age and sex matched groups. The first group was patients with vitiligo and the second group healthy controls. Patients: included 30 adult vitiligo patients (group 1) who were recruited from the outpatients' clinic of Al hud Al marsod hospital in the period between february and july 2012.
  • 11. Exclusion criteria: 1) Patients taking any drug that could alter serum level of Hcy as: Folic acid, vitamin B, lipid lowering drugs, antidiabetics, anti parkinson, chemotherapy. 2)Patients with diseases known to affect Hcy level as Homocystienuria, Hypothyroidism and Chronic renal failure. 3)Patients who are physically active (manual workers and athletes) as physical activity lowers plasma Hcy level . 4)Patients with head and neck affection as vitiligo area scoring index (VASI) doesn't include head and neck region severity.
  • 12. Controls: Thirty age and sex matched healthy controls (group 2) for homocysteine level determination. Methods: An informed consent was taken before inclusion of the subjects into the study. All subjects were subjected to the following:- 1)Full history taking:  Personal history.  History of present illness : onset, course, duration of vitiligo and current treatments.  Family history of vitiligo.  Medical and drug history of medical importance.
  • 13. 2) Dermatological examination:  Clinical assessment of extent of vitiligo in patients was done according to a quantitative and severity parametric score named vitiligo area scoring index (VASI) Which was introduced by Hamzavi et al., 2004.  The total body VASI is calculated using this formula: VASI = ∑ Hand Units of all body sites × Residual Depigmentation.  One hand unit (the palm plus the volar surface of all the digits) is approximately 1% of the total body surface area. It is used as a guide to estimate the extent percentage of vitiligo involvement.
  • 14.  The body is divided into five regions: upper extremities , lower extremities, trunk, hands and feet. The axillary region is included with the upper extremities while the buttocks and inguinal areas are included with the lower extremities.  The residual depigmentation is expressed using VASI visual chart (0%, 10%, 25%, 50%, 75%, 90%, or 100%).
  • 15. 100% depigmentation….no pigment is present. 90%…only specks of pigment are present. 75%…the depigmented area exceeds than pigmented area. 50%...the depigmented area equals the pigmented area. 25%...the pigmented area exceeds the depigmented area. 10%...only specks of depigmentation are present.
  • 16. 3) Homocysteine level determination: The laboratory assessment of Hcy used in this study was enzyme linked immunosorbant assay (ELISA) and Hcy values are interpreted as follows:  5 - 15 µmol/L in healthy adults.  15 - 30 µmol/L in mild homocysteinemia.  30 - 100 µmol/L in intermediate homocysteinemai.  >100 µmol/L in severe homocysteinemia.
  • 17.
  • 18. In this study, there was insignificant difference between mean age among groups (P value = 0.968).
  • 19.
  • 20.  there was no difference between gender distribution among groups (P value = 1.00).
  • 21.
  • 22.  There was insignificant difference between indoor/outdoor occupation distribution among groups (P value = 0.118).
  • 23.
  • 24.  there was insignificant difference between family history among groups (P value = 0.150).
  • 25.
  • 26.  There was insignificant difference between medical history among groups (P value = 0.206).
  • 27.
  • 28.  There was insignificant difference between mean Hcy level among groups (P value = 0.191).
  • 29.
  • 30.  According to course of the disease, there was insignificant difference between Hcy level and VASI (P value = 0.595 & 0.093)
  • 31.
  • 32.  According to onset of the disease, there was insignificant correlation between Hcy level and VASI (P value = 0.459 and 0.906)
  • 33.
  • 34.  There was insignificant correlation between Hcy level and gender of groups.(P value = 0.622 and 0.743)
  • 35.
  • 36.  There was significant correlation between Hcy level and age of patients and controls.(P value = 0.043 and 0.010)
  • 37.
  • 38.  There was insignificant correlation between Hcy level and VASI according to duration of the disease (P value = 0.966 and 0.654)
  • 39.
  • 40.  Our study was performed on 30 adult patients with vitiligo and 30 adult healthy age and sex matched controls to estimate serum level of Hcy and evaluate its role in the pathogenesis of the disease and its relation to disease severity .  We excluded patients taking drugs or have disease that can affect serum level of Hcy, patients who are hyperactive as athletes or manual workers and patients with head and neck vitiligo affection.  In this study, There was insignificant difference between groups regarding to age (P value = 0.96).
  • 41.  Both patient's and control groups included 15 males and 15 females. So there was insignificant difference between groups regarding gender (P value = 1.00).  Family history of vitiligo was found to be positive in 2 patients and negative in 28 patients and it was negative in all control subjects, This shows insignificant difference between family history among all groups (P value = 1.15).  regarding occupation, 16 vitiligo patients were working indoor and 14 patients were working outdoor, in controls, there were 10 persons working indoor and 20 were working outdoor. This shows insignificant difference among groups( P value= 0.11).
  • 42.  Regarding medical history, only 1 patient was anaemic and 2 patients were hypertensive and the medical history of controls was irrelevant. The medical history relevance among both groups was insignificant(P value = 0.20).  Our study showed that there was insignificant difference between groups regarding mean serum Hcy level (P value = 0.191).  Our finding was in agreement with Kim et al., (1999); Balci et al., (2009); Gönül et al., (2010) who reported that serum Hcy, vitamine B12 and folic acid levels do not play a role in the etiopathogenesis of vitiligo
  • 43.  Balci et al., (2009) performed a Turkish study on 48 patients with vitiligo and 31 age and sex matched healthy controls. they reported that there was insignificant correlation between Hcy, folic acid and vitamine B12 and VASI with p value < 0.05.  Gönül et al., (2010) also performed a study on 42 vitiligo patients and 36 sex and age matched healty controls. They found that vitamine B12 and folic acid do not play a role in the etiopathogenesis of vitiligo and did not vary according to the duration and activity of vitiligo.
  • 44.  Kim et al., (1999) measured the serum levels of folic acid and vitamin B12 in 100 Korean patients with vitiligo and found that their was no significant difference compared to the normal control group.  Contrary to our results, Shaker and El Tahlawi, (2008); Silverberg and Silverberg, (2011); Singh et al.,(2011 ) reported that serum Hcy level was significantly more elevated in patients with vitiligo than in controls.
  • 45.  The difference with our study may be due to the method of vitiligo scoring as we used VASI which is a qualitative and quantitative method that can record vitiligo extent and severity in the same equation for every patient but Shaker et al., (2008) recorded only extent of the disease by the rule of nine.  Also they excluded patients with vitiligo extent less than 30% of body surface area.
  • 46.  According to our study, there was a significant correlation between Hcy level and age of all subjects as Hcy level increases with age.  This explained by the deterioration of renal function and weak renal exceretion of Hcy, this finding was in agreement with Wilcken and Gupta, (1979); Kang et al., (1987); Hu et al.,(2004) and Guo et al., (2006).  According to this study, there was no correlation between course of vitiligo and serum level of Hcy, this was in agreement with Karadag et al., (2012) .
  • 47.  Also our study found no significant correlation between duration of vitiligo and serum level of Hcy. This finding was in agreement with Shaker and El Tahlawi, (2008).  Our study recorded no significant correlation between gender of patients or controls with serum level of Hcy, This was in agreement with Silverberg and Silverberg, (2011).
  • 48.
  • 49. This study concludes that:  serum Hcy may not be a precipitating factor for vitiligo in the predisposed individuals.  It has been found that serum Hcy level related to age of the patients but not for activity, duration of the disease or gender of patients.