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,
and 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,
and 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 in the body. The epidermis
has a higher concentration than the dermis, owing to
a zinc requirement for the active proliferation and differentiation
of epidermal keratinocytes.(6) Zinc inhibits hair follicle
regression, and helps accelerate 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
the pediatric population in comparison 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 dietary zinc
deficiency.(11) However, serum zinc levels association with 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 pediatric
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 dermatology and pediatric clinics during January
2014 to January 2017. All patients who were complaining of hair loss (partial
or diffuse), change in hair texture or regression of hair growth, or who were
found to have hair loss or scalp disorders on physical examination, and
confirmed to have low 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 pediatric 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, history of any hair changes in other parts of the
body including the eyebrows or eyelashes was taken. The data collected included
age, sex, and clinical presentations. 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, 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. Diatery history focused on piky eaters who
excludes animal

products (ie, meat, poultry, and fish) and having lower
diversity of food. Early-onset picky eating was defined as the first report of
picky eating being at either 2 or 3 y, and late-onset picky eating was defined
as the first report of picky eating being at 4.5 or 5.5 y, Persistent picky
eating was defined as being in the early-onset group and persist.(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) according to the 2000 CDC.(13)
growth charts. 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, 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 (World Health Organization 2001).
(14)

Other
investigations carried out included sweat chloride test for cystic fibrosis, as
well as Tissue Transglutaminase antibody IgA to 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.

Results:

Mention
ANOVA/T-Test

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 seen 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 1 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