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Zinc Has A Role in Pathogenesis of Pityriasis Alba.5

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Zinc Has A Role in Pathogenesis of Pityriasis Alba.5

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Original Article

Zinc has a Role in Pathogenesis of Pityriasis Alba

Abstract Fatma M. Elesawy,


Background: Pityriasis alba (PA) is a common disease of children and seen in most of the Essam M. Akl,
developing countries. The exact pathogenesis of PA is still not well established. Some cases
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Walid A. Abdel
of PA have been associated with atopic dermatitis, while most cases have no association with
it. Objectives: The objective was to evaluate the role played by zinc (Zn) in the pathogenesis Halim1
of PA. Patients and Methods: Sixty patients suffering from PA were included in the study, and Departments of Dermatology,
30 apparently healthy individuals of matching age and sex were recruited as a control group. Venereology and Andrology
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 12/25/2023

and 1Clinical and Chemical


Serum Zn, hemoglobin, and albumin were measured in both groups. In addition, skin phototype Pathology, Faculty of Medicine,
and body mass index were recorded. The American Academy Criteria of atopic dermatitis diagnosis Benha University, Benha, Egypt
were applied to the participants in this study. PA patients were examined dermatologically with a
recording of the site, size, and number of lesions. Results: There was no difference in the presence
of atopic dermatitis between the patient and control groups (P = 0.672). PA lesions were detected
in the faces of all patients. There were no statistically significant differences between patients and
controls regarding serum hemoglobin concentration (P = 0.763) or serum albumin (P = 0.487).
The serum level of Zn was lower in patients with PA than controls (P < 0.001) with statistically
significant positive correlations with both numbers and size of PA lesions (P < 0.001 and P = 0.011,
respectively). Conclusions: The present study showed that Zn may have a role in PA, and oral
supplementation with Zn may be considered as a therapeutic approach in this disease.

Keywords: Diet, pityriasis alba, zinc

Introduction Patients and Methods


Pityriasis alba (PA) is a common Ethical approval
dermatological disease, characterized by
This study was done after approval of
asymptomatic slightly scaly ill‑defined
the Medical Research Ethics Committee
hypopigmented skin patches.[1] PA occurs
on October 2018. The legal guardians of
predominantly in children between 3 and
the children involved in this study were
16 years, and both genders are equally
informed about the nature of this study
affected.[2] The pathogenesis of PA is still not
and had given their informed consent. The Submitted: 03‑Nov‑2019
fully well established,[3] and several theories
infants included in this study were not Revised: 24‑Dec‑2019
have been suggested such as considering
subjected to any harmful procedures, and Accepted: 26‑Apr‑2020
it a part of atopic dermatitis, implicating
their personal data were secured. Published: 30-Jun-2020
infective agents, or environmental
influences.[4] Nevertheless, in most cases, This work was a case–control
it is related to overexposure to sunlight, comparative study done from November
Address for correspondence:
especially in darker skin phototype.[5] 2018 to April 2019. This study included
Dr. Essam M. Akl,
90 children who were divided into two Department of Dermatology,
Zinc (Zn) is one of the most essential
groups: Group A included sixty children Venereology and Andrology,
trace elements in the human body.[6] Zn
with PA and Group B included thirty Faculty of Medicine, Benha
has multiple immunological, endocrinal, University, P. O. 13518, Benha,
age‑ and sex‑matched apparently healthy
reproductive, antioxidant,[7] and Egypt.
children from the same area of the E‑mail: [email protected]
melanogenesis functions.[8]
patients. Patients suffer from PA with
Aim of the work more than 2 months duration and who
did not receive either systemic or topical Access this article online
The objective was to evaluate the serum
treatment for PA for the last month were
level of Zn in patients with PA. Website: www.ijpd.in
included in the study. Patients with
DOI: 10.4103/ijpd.IJPD_109_19
systemic autoimmune diseases; diabetes Quick Response Code:
This is an open access journal, and articles are
distributed under the terms of the Creative Commons mellitus; hepatic, renal, hematological,
Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows
others to remix, tweak, and build upon the work non‑commercially,
as long as appropriate credit is given and the new creations are
licensed under the identical terms. How to cite this article: Elesawy FM, Akl EM,
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer. Halim WA. Zinc has a role in pathogenesis of pityriasis
com alba. Indian J Paediatr Dermatol 2020;21:178-83.

178 © 2020 Indian Journal of Paediatric Dermatology | Published by Wolters Kluwer - Medknow
Elesawy, et al.: Zinc in pityriasis alba

and chronic infectious diseases; or malignancy were monoreagent (Centronic GmbH, Wartenberg, Germany).
excluded from the study. Stool analysis, both macroscopic and microscopic, was
Age, sex, body mass index (BMI), and skin phototype done to both patients and controls.
were determined in patients and controls. Complete Statistical analysis
dermatological examination was done in all patients
Data of this study were statistically analyzed using Statistical
to determine the site, size, and distribution of PA. PA
Package for the Social Sciences (SPSS) software software,
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was diagnosed clinically in patients if lesions were


hypopigmented, have fine scaly macules and/or patches; IBM© Armonk, NY, U.S.A computer program version 20 for
ill‑defined margins; and absence of preceding inflammatory Microsoft Window 7® 64 bit. The t‑test was used to compare
lesions.[9] In addition, the diagnosis of atopic dermatitis the numerical data of normally distributed variables, whereas
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in PA patients was done using the American Academy of categorical variable differences were analyzed with Chi‑square
Dermatology Diagnostic Criteria.[10] test. The Spearman’s correlation test was used to examine
correlations. Logistic regression analysis was used for prediction
The laboratory procedures included serum hemoglobin of risk factors. Receiver operating characteristic (ROC) curve
concentration, serum albumin, serum Zn measurements, was used to categorize cases into one of the two groups. P ≤
and stool analysis.
0.05 was considered statistically significant.
5 millimeters of venous blood sample was taken from
the participants in this study and was used for laboratory Results
investigations. The blood samples were divided into The demographic and clinical data of the participants
two parts: the first part was used freshly to calculate in this study are summarized in Table 1. There were no
serum hemoglobin concentration by Sysmex XP- statistically significant differences between the patients
300® (Sysmex Corporation, Kobe, Japan), and the second and controls regarding age (P = 0.604), BMI (P = 0.559),
part was allowed to clot, then centrifuged (5000 rpm, sex (P = 0.760), skin phototype (P = 0.211), high
25 min, 25°C), and the separated serum was used to
sun exposure frequency (P = 0.837), or having atopic
measure both albumin and Zn. Serum albumin was
dermatitis (P = 0.672).
measured using a Roche Modular D2400 system (Roche
Diagnostics, Indianapolis, IN, USA), and the reference All the patients had a PA in the face (100%), and in
range of our institution is 3.5–5 g/dl. Serum Zn addition to the face affection, some patients had PA in the
was measured spectrophotometrically using Zn fluid neck (6.7%) and arms (3.33%), [Table 1 and Figures 1-4].

Table 1: Demographic data and comparison between pityriasis alba patients and control regarding age, sex, skin
phototype, sun exposure, and atopic dermatitis
PA (n=60) Control (n=30) Test value P
Age (years) 7.9±2.3 7.6±2.2 0.521 0.604
BMI (kg/m2) 15.8±2.1 15.9±3.4 0.587 0.559
Sex, n (%)
Male 36 (60) 19 (63.3) 0.094 0.760
Female 26 (40) 11 (36.7)
Total 60 (100) 30 (100)
Skin phototype, n (%)
II 11 (1.7) 0 (0) 4.314 0.211
III 12 (20) 8 (26.7)
IV 46 (76.7) 19 (63.3)
V 1 (1.7) 3 (10)
High sun exposure, n (%) 51 (85) 25 (83.33) 0.0423 0.837
Atopic dermatitis, n (%) 8 (13.3) 5 (16.66) 0.1798 0.672
PA
Duration (months) 3.2±2.1
Size (cm2) 2±1.3
Number 3±2
Face, n (%) 60 (100)
Neck, n (%) 4 (6.7)
Arms, n (%) 2 (3.33)
Comparison between the two groups was by t‑test numerical data and Chi‑square test for categorical variables differences. P≤0.05 is
statistically significant. PA ‑ Pityriasis alba; BMI ‑ Body mass index

Indian Journal of Paediatric Dermatology | Volume 21 | Issue 3 | July-September 2020 179


Elesawy, et al.: Zinc in pityriasis alba

Comparing laboratory data of PA patients and controls, There is no specialized Zn storage in the body, and its
there were no statistically significant differences of daily intake is required due to its rapid turnover.[12] Meat
infestation by Oxyuris vermicularis (P = 0.09) and and fish are the important sources of Zn with higher
Entamoeba histolytica (P = 0.134). Although there were bioavailability than plant sources, and intake of folate,
no statistically significant differences regarding the
serum albumin level (P = 0.487) or serum hemoglobin
concentration (P = 0.763), there was a statistically
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significant difference between the two groups regarding


serum Zn concentration (P < 0.001) [Table 2].
Using the Spearman’s correlation test, low serum Zn
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level showed statistically significant negative correlations


with the number (P < 0.001) and size of lesions of
PA (P = 0.011) [Figures 5 and 6].
Logistic regression analysis was conducted for prediction
of PA within controls, using age, gender, BMI, laboratory
data, and serum Zn as covariates. Low serum Zn was
considered as a risk factor for the development of PA
within controls (P < 0.001) [Table 3].
Using the ROC curve, serum level of Zn <107 µg/dL was
significantly associated with higher numbers and size of PA Figure 1: A 8-year-old female child with multiple patches of pityriasis alba
in patients [Table 4 and Figure 7].

Discussion
Zn is required for hundreds of metabolically related
enzymes, transcription factors, and gene expression.[11]

Table 2: Comparison between pityriasis alba patients


and control regarding laboratory data
PA (n=60) Control Test P
(n=30) value
Stool analysis, n (%)
Oxyuris vermicularis 7 (11.7) 0 (0) 3.795 0.09
Entamoeba histolytica 36 (60) 13 (43.3) 2.240 0.134
Serum albumin (g/dl) 3.8±0.3 3.9±0.2 0.699 0.487
Hemoglobin (g/dl) 11.1±0.8 11.2±0.9 0.303 0.763
Serum zinc (µg/dL) 78.2±15.8 130.9±42.7 0.066 <0.001
Figure 2: A 5-year-old male child with a large patch of pityriasis alba
Comparison between the two groups was by t‑test numerical data
and Chi‑square test for categorical variables differences. P≤0.05 is
statistically significant. PA ‑ Pityriasis alba

Table 3: Regression analysis for prediction of pityriasis


alba within controls
P OR 95% CI
Age 0.946 1.298 0.940‑1.963
Sex 0.586 1.376 0.694‑1.441
BMI 0.967 0.611 0.248‑1.055
Skin phototype 0.896 1.273 0.692‑1.445
Oxyuris vermicularis 0.897 1.287 0.573‑1.746
Entamoeba histolytica 0.489 1.198 0.694‑1.441
Serum albumin 0.678 0.727 0.446‑2.243
Hemoglobin 0.789 0.923 0.826‑1.211
Serum zinc <0.001 0.965 0.953‑0.978
P≤0.05 is statistically significant. OR ‑ Odds ratio; CI ‑ Confidence
interval; BMI ‑ Body mass index Figure 3: A 12-year-old male child with multiple patches of pityriasis alba

180 Indian Journal of Paediatric Dermatology | Volume 21 | Issue 3 | July-September 2020


Elesawy, et al.: Zinc in pityriasis alba
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nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 12/25/2023

Figure 4: A 6-year-old female child with multiple patches of pityriasis alba

Figure 5: Correlation between the serum level of zinc and the number of
pityriasis alba lesions

Figure 6: Correlation between the serum level of zinc and the size of
pityriasis alba lesions

fiber, and phytochemicals reduces its absorption.[13] Serum


Zn is largely bound to albumin, α2‑macroglobulin, and
transferrin.[14] The most common cause of Zn deficiency is
malnutrition, and >17% worldwide population (especially Figure 7: Receiver operating characteristic curve analysis between the
in developing countries) have Zn deficiency.[15] serum level of zinc and pityriasis alba occurrence

The results of this study showed that a low serum level Table 4: Area under receiver operating characteristic curve
of Zn is associated with PA. Zn is found in human skin and performance criteria of serum zinc for discrimination
with a concentration in the epidermis (60 μg/g) that is between pityriasis alba case and control groups
more than that in the dermis (40 μg/g).[16] Zn has multiple AUC (95% CI) 0.862 (0.758‑0.966)
functions in human skin such as keratinocyte proliferation P <0.001
and differentiation, melanocyte function, and immune Cutoff <107
regulations.[17] Serum Zn deficiency has been reported in Sensitivity (%) 91.7
hypopigmented[18,19] and dry, rough skin disorders,[20] which Specificity (%) 80
are commonly seen in PA(1). PPV (%) 90.2
NPV (%) 82.8
A minority of patients enrolled in this study had atopic
Accuracy (%) 87.8
dermatitis. PA is classified into endemic PA that has P≤0.05 is statistically significant. ROC ‑ Receiver operating
an inflammatory nature, [21] occurring in developing characteristic curve; AUC ‑ Area under ROC curve; CI ‑ Confidence
countries, [22] and hypopigmentation type, occurring in interval; PPV ‑ Positive predictive value; NPV ‑ Negative predictivae
atopic dermatitis infants in developed countries. [23] value
Indian Journal of Paediatric Dermatology | Volume 21 | Issue 3 | July-September 2020 181
Elesawy, et al.: Zinc in pityriasis alba

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the possible role of overexposure to the sun in PA entity: Up‑to‑date review of the literature. Pediatr Dermatol
2015;32:786‑91.
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6. Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME.
the protection of keratinocyte to ultraviolet radiation[25]
Zinc and human health: An update. Arch Toxicol 2012;86:521‑34.
and can facilitate inflammation.[26] In addition, oral
7. Gupta M, Mahajan VK, Mehta KS, Chauhan PS. Zinc therapy in
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activity in human melanocytes. Cell Physiol Biochem 2017;43:1‑6.
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9. Vargas‑Ocampo F. Pityriasis alba: A histologic study. Int J
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stool analysis between the participants, the low serum Zn Consensus conference on pediatric atopic dermatitis. J Am Acad
can be attributed to low meat and high plant diets, which Dermatol 2003;49:1088‑95.
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Zn may induce skin hypopigmentation.[33] In addition, low 2015;14:277‑85.
serum Zn has been associated with skin inflammation.[34] 13. King JC, Brown KH, Gibson RS, Krebs NF, Lowe NM,
Both hypopigmentation and skin inflammation are essential Siekmann JH, et al. Biomarkers of nutrition for
features of PA.[5] development (BOND) – Zinc review. J Nutr 2016;146:858S‑85S.
14. Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune
Conclusions function. Nutrients 2017;9. pii: E1286.
15. Wessells KR, Brown KH. Estimating the global prevalence of
The serum level of Zn is lower in patients with PA with a zinc deficiency: Results based on zinc availability in national food
positive correlation with disease severity in the form of the supplies and the prevalence of stunting. PLoS One 2012;7:e50568.
size and number of lesions. Oral Zn supplementations may 16. Inoue Y, Hasegawa S, Ban S, Yamada T, Date Y, Mizutani H,
be used in cases of PA. et al. ZIP2 protein, a zinc transporter, is associated with
keratinocyte differentiation. J Biol Chem 2014;289:21451‑62.
Declaration of patient consent 17. Ogawa Y, Kinoshita M, Shimada S, Kawamura T. Zinc and skin
disorders. Nutrients 2018;10. pii: E199.
The authors certify that they have obtained all appropriate
18. Mogaddam MR, Ardabili NS, Maleki N, Chinifroush MM,
patient consent forms. In the form the patient(s) has/have
Fard EM. Evaluation of the serum zinc level in patients with
given his/her/their consent for his/her/their images and vitiligo. Postepy Dermatol Alergol 2017;34:116‑9.
other clinical information to be reported in the journal. The 19. Shameer P, Prasad PV, Kaviarasan PK. Serum zinc level in
patients understand that their names and initials will not vitiligo: A case control study. Indian J Dermatol Venereol Leprol
be published and due efforts will be made to conceal their 2005;71:206‑7.
identity, but anonymity cannot be guaranteed. 20. Prasad AS. Zinc in growth and development and spectrum of
human zinc deficiency. J Am Coll Nutr 1988;7:377‑84.
Financial support and sponsorship 21. Carneiro FR, Amaral GB, Mendes MD, Quaresma JA. Tissue
Nil. immunostaining for factor XIIIa in dermal dendrocytes of
pityriasis alba skin lesions. An Bras Dermatol 2014;89:245‑8.
Conflicts of interest 22. Ruiz‑Maldonado R. Hypomelanotic conditions of the newborn
and infant. Dermatol Clin 2007;25:373‑82, ix.
There are no conflicts of interest.
23. Fenner J, Silverberg NB. Skin diseases associated with atopic
dermatitis. Clin Dermatol 2018;36:631‑40.
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Indian Journal of Paediatric Dermatology | Volume 21 | Issue 3 | July-September 2020 183

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