Introduction: of epidermal keratinocytes.(6) Zinc has been shown to

Introduction:

Zinc is
a trace element essential to countless metabolic pathways and cellular
functions of the body. It is involved in protein and nucleic acid synthesis, it
also plays a role in immune function, wound healing, DNA synthesis and cell division.(1,2)
Due to the importance of these functions a deficiency of zinc poses a major
health problem worldwide.(3) Zinc deficiency can
occur from a lack of adequate dietary intake, decreased intestinal absorption, as
well as increased losses in the gastrointestinal tract, urine, and sweat.(4)
Zinc deficiency has been noted to occur in patients with
malabsorption syndromes, chronic renal disease, cirrhosis of the liver, sickle
cell disease, and in patients with malnutrition, alcoholism, and inflammatory
bowel disease.(5)

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The skin
has the third highest abundance of zinc of any organ in the body. The
epidermis has a higher concentration of zinc than the dermis, owing to
a zinc requirement for the active proliferation and differentiation
of epidermal keratinocytes.(6) Zinc has been shown to inhibit hair
follicle regression, and help in accelerating hair follicle recovery.(7)
Cutaneous manifestations typically occur in moderate to severe
zinc deficiency and present as alopecia and dermatitis in
the perioral, acral, and perineal regions.(8)

Studies
arguing that zinc deficiency can negatively affect the growth of hair in adults
have been emerging since the 1990s, with even a few studies having reported
that zinc deficiency has correlations with alopecia areata and telogen
effluvium.(9) Little is known about zinc deficiency and hair loss in
children in contrast to adults. In 1985 Collipp, P J, et al. investigated the
association between zinc levels in the hair of normal infants with
scalp hair quantity and the presence of a diaper rash. The study
indicated that hair loss and diaper rash in normal infants are
significantly associated with a reduction in hair zinc concentration.(10)
Another case reported progressive diffuse hair
loss with hair dryness and brittleness due to a deficiency in
dietary zinc.(11) However, an association between serum zinc levels and
hair loss has not been well studied in the pediatric population. Therefore, the
aim of this study is to assess serum zinc levels in children with hair loss and
to find characteristics that predict particularly low zinc levels.

Materials and methods:

Patient
population:

This was
an out-patient clinic based prospective observational study done in pediatrics
and dermatology clinics in Al-Karak teaching hospital affiliated with Mutah
University, Jordan. The ethical committee approved the study protocol. Informed
consent from the patients’ parents was obtained prior to enrolment in the
study.

A
protocol was developed and implemented to collect the data of all pediatric
patients who were seen at the pediatrics and dermatology clinics from January
2014 to January 2017. All patients who were complaining of hair loss (partial
or diffuse), change in hair texture, regression of hair growth, or who were
found to have hair loss or scalp disorders on physical examination, as well as
having confirmed low serum zinc levels were included in this study. Patients
with normal hair, normal serum zinc levels, or were taking multivitamin
supplementations were excluded from the study. The total number of patients
screened was 5200 (2800 in dermatology clinics and 2400 in pediatrics clinics).

History
taking and physical exam methodology:

A
detailed history was taken regarding hair symptoms including; the type of hair
loss (partial or diffuse), scalp symptoms, changes in hair texture and the
growth of hair. In addition, a history of any hair changes in other parts of
the body including the eyebrows or eyelashes was taken. The way patients
presented themselves to their physician was classified into three groups. Group
1 was defined as those who complained of hair loss as their primary concern,
group 2 was defined as those who complained of hair loss as a secondary concern
alongside another more significant concern to them, and group 3 was defined as
those who did not complain of hair loss. In addition, a detailed history was
taken about hair grooming/habit tics, nail changes, other cutaneous changes,
systemic diseases (e.g. cystic fibrosis, celiac disease, cow milk allergy, and
enteritis), family history of similar conditions or autoimmune disease, and
drug history. Economic status was assessed by the family income per capita, and
was classified according to the World Bank new data on July 1, 2017, as high,
upper-middle, lower-middle, or low income. Dietary history was also taken, and focused mainly on picky
eating behavior that excluded animal products (e.g. meat, poultry, and fish) as
well as having a lower diversity of food. Patients that showed signs of picky
eating at around the ages of 2 to 3 years were considered to have early-onset
picky eating, whereas patients that started at about 4.5-5.5 years were
considered to have late-onset picky eating. Patients who started off in the
early-onset picky eating category and continued to have picky eating behavior
were considered to be persistent picky eaters.(12).{ Macro- and micronutrient intakes in
picky eaters}

Scalp
examination included the skin of the scalp (presence of erythema, scales, and
follicular plugging). Hair examination included the recording of hair color,
texture, fragility, and examination of the hair root. In addition to the scalp,
other hairy sites were examined for hair loss (including eyebrows and eyelashes).
Nails and teeth were also examined for any abnormalities.

Anthropometric
measures assessed included weight for height, height for age, and weight for
age. The values for each nutritional index were converted into Z scores
(Standard deviations) using the data provided by the 2000 CDC growth charts.(13)
Z scores between +1 and -1 were considered normal, between -1 and -2 low,
and below -2 very low.

Biochemical
methodology:

Total
zinc concentration in the patients’ serum was measured using an automated
chemistry analyzer (Biosystem BT-350 module, Spain) according to the
manufacturer protocol (is the manufacturer protocol
related to the method of measuring zinc, or related to the definition of low
zinc levels? I guessed the former), low zinc level was defined by serum
zinc less than 70 µg/dL. Hemoglobin, ferritin, and vitamin D levels were also
obtained to assess nutritional status. Anemia was defined as a hemoglobin level
less than 11 g/dL. Ferritin was considered to be deficient when below 12 ng/mL
for children less than 5 years of age and below 15 ng/mL for those above 5
years. Vitamin D was considered to be deficient when below 25 nmol/L.(14)

Other
investigations carried out included a sweat chloride test for cystic fibrosis, as
well as a Tissue Transglutaminase antibody IgA screen for celiac disease. These
tests were performed in some cases to further confirm the presence of systemic
diseases. Blood tests for thyroid function, antinuclear antibody, and other auto
antibodies were also performed where necessary in
some cases.

Statistical
methodology:

In this
study four main statistical tests were used. Namely, the independent Student’s
T-test, the ANOVA, the Pearson Chi-Square test, and the Fisher exact test. The Student’s
T-test and the ANOVA were used to analyze the mean zinc levels. The Chi-Square
test was used to find an association between two categorical variables. The Fisher
exact test was used when a Chi-Square test was not a viable option.

The
tolerated maximum probability of a type 1 error in this study was 0.05 (i.e. ?
= 0.05). Any P-value below 0.05 is considered to be statistically significant. SPSS
V. 21.0 software was used for the statistical analysis in this study.

Results:

Of the
5200 cases screened, 401 cases had hair loss. Of those with hair loss 162 had
zinc deficiency. Therefore, the prevalence of zinc deficiency in this pediatric
population with hair loss was 40.4%. Figure x demonstrates
the distribution of patients in detail.

Among
the 162 patients analyzed in this study, 61% were female and 39% male. The age
ranged from 1 month to 14 years with a mean of 4.8 ± 3.1 years. When categorizing the patients based on how they
presented to the physician 21.6% were within group 1, 32.1% were within group
2, and 46.3% were within group 3. On physical examination 31.5% had diffuse
hair loss, 14.2% had patchy hair loss, 58% had a scaly scalp, 95.1% had hair
texture or color changes, and 30.2% had other skin manifestations.

7.4% had
an underlying systemic illness. 51.5% had no family history of hair loss. 10.5%
had a family history pertaining to the mother only, 25.9% to a sibling, and
12.3% the mother and a sibling. According to the World Bank organization
classification 4.9% had a low household income, 59.9% had a lower-middle
household income, 33.3% had an upper-middle household income, and 1.9% had a
high household income. 42.6% had a low or very low weight to age z score, 29%
had a low or very low height to age z score, 48.8% had a low or very low weight
to height z score.

The mean
zinc level was 51.3 ± 11.2 ?g/dL. Table x
summarizes the factors associated with differences in mean zinc levels. There
was no statistically significant difference between the mean zinc level in
males and females, or between the age groups. Although the sex of the patient
had no significant association with zinc levels when looking at the patient
sample overall, when looking only at patients who complained primarily of hair
loss (i.e. Group 1), it was found that males had a significantly lower mean
zinc level than females. Furthermore, females were almost 5 times more likely
to complain primarily of hair loss than males (P

x

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