|Year : 2020 | Volume
| Issue : 3 | Page : 178-183
Zinc has a role in pathogenesis of pityriasis alba
Fatma M Elesawy1, Essam M Akl1, Walid A Abdel Halim2
1 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Benha University, Benha, Egypt
2 Department of Clinical and Chemical Pathology, Faculty of Medicine, Benha University, Benha, Egypt
|Date of Submission||03-Nov-2019|
|Date of Decision||24-Dec-2019|
|Date of Acceptance||26-Apr-2020|
|Date of Web Publication||30-Jun-2020|
Dr. Essam M Akl
Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Benha University, P. O. 13518, Benha
Source of Support: None, Conflict of Interest: None
Background: Pityriasis alba (PA) is a common disease of children and seen in most of the developing countries. The exact pathogenesis of PA is still not well established. Some cases 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 of PA. Patients and Methods: Sixty patients suffering from PA were included in the study, and 30 apparently healthy individuals of matching age and sex were recruited as a control group. Serum Zn, hemoglobin, and albumin were measured in both groups. In addition, skin phototype and body mass index were recorded. The American Academy Criteria of atopic dermatitis diagnosis 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
|How to cite this article:|
Elesawy FM, Akl EM, Abdel Halim WA. Zinc has a role in pathogenesis of pityriasis alba. Indian J Paediatr Dermatol 2020;21:178-83
|How to cite this URL:|
Elesawy FM, Akl EM, Abdel Halim WA. Zinc has a role in pathogenesis of pityriasis alba. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Sep 22];21:178-83. Available from: http://www.ijpd.in/text.asp?2020/21/3/178/288481
| Introduction|| |
Pityriasis alba (PA) is a common dermatological disease, characterized by asymptomatic slightly scaly ill-defined hypopigmented skin patches. PA occurs predominantly in children between 3 and 16 years, and both genders are equally affected. The pathogenesis of PA is still not fully well established, and several theories have been suggested such as considering it a part of atopic dermatitis, implicating infective agents, or environmental influences. Nevertheless, in most cases, it is related to overexposure to sunlight, especially in darker skin phototype.
Zinc (Zn) is one of the most essential trace elements in the human body. Zn has multiple immunological, endocrinal, reproductive, antioxidant, and melanogenesis functions.
Aim of the work
The objective was to evaluate the serum level of Zn in patients with PA.
| Patients and Methods|| |
This study was done after approval of the Medical Research Ethics Committee on October 2018. The legal guardians of the children involved in this study were informed about the nature of this study and had given their informed consent. The infants included in this study were not subjected to any harmful procedures, and their personal data were secured.
This work was a case–control comparative study done from November 2018 to April 2019. This study included 90 children who were divided into two groups: Group A included sixty children with PA and Group B included thirty age- and sex-matched apparently healthy children from the same area of the patients. Patients suffer from PA with more than 2 months duration and who did not receive either systemic or topical treatment for PA for the last month were included in the study. Patients with systemic autoimmune diseases; diabetes mellitus; hepatic, renal, hematological, and chronic infectious diseases; or malignancy were excluded from the study.
Age, sex, body mass index (BMI), and skin phototype were determined in patients and controls. Complete dermatological examination was done in all patients to determine the site, size, and distribution of PA. PA was diagnosed clinically in patients if lesions were hypopigmented, have fine scaly macules and/or patches; ill-defined margins; and absence of preceding inflammatory lesions. In addition, the diagnosis of atopic dermatitis in PA patients was done using the American Academy of Dermatology Diagnostic Criteria.
The laboratory procedures included serum hemoglobin concentration, serum albumin, serum Zn measurements, and stool analysis.
5 millimeters of venous blood sample was taken from the participants in this study and was used for laboratory investigations. The blood samples were divided into two parts: the first part was used freshly to calculate serum hemoglobin concentration by Sysmex XP-300® (Sysmex Corporation, Kobe, Japan), and the second part was allowed to clot, then centrifuged (5000 rpm, 25 min, 25°C), and the separated serum was used to measure both albumin and Zn. Serum albumin was measured using a Roche Modular D2400 system (Roche Diagnostics, Indianapolis, IN, USA), and the reference range of our institution is 3.5–5 g/dl. Serum Zn was measured spectrophotometrically using Zn fluid monoreagent (Centronic GmbH, Wartenberg, Germany). Stool analysis, both macroscopic and microscopic, was done to both patients and controls.
Data of this study were statistically analyzed using Statistical Package for the Social Sciences (SPSS) software software, IBM© Armonk, NY, U.S.A computer program version 20 for Microsoft Window 7® 64 bit. The t-test was used to compare the numerical data of normally distributed variables, whereas categorical variable differences were analyzed with Chi-square test. The Spearman's correlation test was used to examine correlations. Logistic regression analysis was used for prediction of risk factors. Receiver operating characteristic (ROC) curve was used to categorize cases into one of the two groups. P ≤ 0.05 was considered statistically significant.
| Results|| |
The demographic and clinical data of the participants in this study are summarized in [Table 1]. There were no statistically significant differences between the patients and controls regarding age (P = 0.604), BMI (P = 0.559), sex (P = 0.760), skin phototype (P = 0.211), high sun exposure frequency (P = 0.837), or having atopic dermatitis (P = 0.672).
|Table 1: Demographic data and comparison between pityriasis alba patients and control regarding age, sex, skin phototype, sun exposure, and atopic dermatitis|
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All the patients had a PA in the face (100%), and in addition to the face affection, some patients had PA in the neck (6.7%) and arms (3.33%), [Table 1] and [Figure 1], [Figure 2], [Figure 3], [Figure 4].
|Figure 1: A 8-year-old female child with multiple patches of pityriasis alba|
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|Figure 3: A 12-year-old male child with multiple patches of pityriasis alba|
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|Figure 4: A 6-year-old female child with multiple patches of pityriasis alba|
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Comparing laboratory data of PA patients and controls, there were no statistically significant differences of infestation by Oxyuris vermicularis (P = 0.09) and Entamoeba histolytica (P = 0.134). Although there were no statistically significant differences regarding the serum albumin level (P = 0.487) or serum hemoglobin concentration (P = 0.763), there was a statistically significant difference between the two groups regarding serum Zn concentration (P < 0.001) [Table 2].
|Table 2: Comparison between pityriasis alba patients and control regarding laboratory data|
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Using the Spearman's correlation test, low serum Zn level showed statistically significant negative correlations with the number (P < 0.001) and size of lesions of PA (P = 0.011) [Figure 5] and [Figure 6].
|Figure 5: Correlation between the serum level of zinc and the number of pityriasis alba lesions|
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|Figure 6: Correlation between the serum level of zinc and the size of pityriasis alba lesions|
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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].
|Table 3: Regression analysis for prediction of pityriasis alba within controls|
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Using the ROC curve, serum level of Zn<107 μg/dL was significantly associated with higher numbers and size of PA in patients [Table 4] and [Figure 7].
|Table 4: Area under receiver operating characteristic curve and performance criteria of serum zinc for discrimination between pityriasis alba case and control groups|
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|Figure 7: Receiver operating characteristic curve analysis between the serum level of zinc and pityriasis alba occurrence|
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| Discussion|| |
Zn is required for hundreds of metabolically related enzymes, transcription factors, and gene expression. There is no specialized Zn storage in the body, and its daily intake is required due to its rapid turnover. Meat and fish are the important sources of Zn with higher bioavailability than plant sources, and intake of folate, fiber, and phytochemicals reduces its absorption. Serum Zn is largely bound to albumin, α2-macroglobulin, and transferrin. The most common cause of Zn deficiency is malnutrition, and >17% worldwide population (especially in developing countries) have Zn deficiency.
The results of this study showed that a low serum level of Zn is associated with PA. Zn is found in human skin with a concentration in the epidermis (60 μg/g) that is more than that in the dermis (40 μg/g). Zn has multiple functions in human skin such as keratinocyte proliferation and differentiation, melanocyte function, and immune regulations. Serum Zn deficiency has been reported in hypopigmented, and dry, rough skin disorders, which are commonly seen in PA(1).
A minority of patients enrolled in this study had atopic dermatitis. PA is classified into endemic PA that has an inflammatory nature, occurring in developing countries, and hypopigmentation type, occurring in atopic dermatitis infants in developed countries.
All of our patients had PA on the face. This indicates the possible role of overexposure to the sun in PA pathogenesis. The decreased Zn concentration may limit the protection of keratinocyte to ultraviolet radiation and can facilitate inflammation. In addition, oral Zn supplementations have been used in multiple skin inflammatory diseases.
There was no significant difference in serum hemoglobin and albumin concentration in this study, and this was similar to other studies in developing countries and in vegetarians., As there was no significant difference in stool analysis between the participants, the low serum Zn can be attributed to low meat and high plant diets, which contain large quantities of phytate and phytic acid that decrease intestinal absorption of Zn.
Zn has a role in skin pigmentation,, and low serum Zn may induce skin hypopigmentation. In addition, low serum Zn has been associated with skin inflammation. Both hypopigmentation and skin inflammation are essential features of PA.
| Conclusions|| |
The serum level of Zn is lower in patients with PA with a positive correlation with disease severity in the form of the size and number of lesions. Oral Zn supplementations may be used in cases of PA.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jadotte YT, Janniger CK. Pityriasis alba revisited: Perspectives on an enigmatic disorder of childhood. Cutis 2011;87:66-72.
Vinod S, Singh G, Dash K, Grover S. Clinico epidemiological study of pityriasis alba. Indian J Dermatol Venereol Leprol 2002;68:338-40.
] [Full text]
In SI, Yi SW, Kang HY, Lee ES, Sohn S, Kim YC. Clinical and histopathological characteristics of pityriasis alba. Clin Exp Dermatol 2009;34:591-7.
Blessmann Weber M, Sponchiado de Avila LG, Albaneze R, Magalhães de Oliveira OL, Sudhaus BD, Cestari TF. Pityriasis alba: A study of pathogenic factors. J Eur Acad Dermatol Venereol 2002;16:463-8.
Miazek N, Michalek I, Pawlowska-Kisiel M, Olszewska M, Rudnicka L. Pityriasis alba–ommon disease, enigmatic entity: Up-to-date review of the literature. Pediatr Dermatol 2015;32:786-91.
Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME. Zinc and human health: An update. Arch Toxicol 2012;86:521-34.
Gupta M, Mahajan VK, Mehta KS, Chauhan PS. Zinc therapy in dermatology: A review. Dermatol Res Pract 2014;2014:709152.
Rudolf E, Rudolf K. Increases in intracellular zinc enhance proliferative signaling as well as mitochondrial and endolysosomal activity in human melanocytes. Cell Physiol Biochem 2017;43:1-6.
Vargas-Ocampo F. Pityriasis alba: A histologic study. Int J Dermatol 1993;32:870-3.
Eichenfield LF, Hanifin JM, Luger TA, Stevens SR, Pride HB. Consensus conference on pediatric atopic dermatitis. J Am Acad Dermatol 2003;49:1088-95.
Ackland ML, Michalczyk AA. Zinc and infant nutrition. Arch Biochem Biophys 2016;611:51-7.
Bonaventura P, Benedetti G, Albarède F, Miossec P. Zinc and its role in immunity and inflammation. Autoimmun Rev 2015;14:277-85.
King JC, Brown KH, Gibson RS, Krebs NF, Lowe NM, Siekmann JH, et al
. Biomarkers of nutrition for development (BOND) – Zinc review. J Nutr 2016;146:858S-85S.
Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients 2017;9. pii: E1286.
Wessells KR, Brown KH. Estimating the global prevalence of zinc deficiency: Results based on zinc availability in national food supplies and the prevalence of stunting. PLoS One 2012;7:e50568.
Inoue Y, Hasegawa S, Ban S, Yamada T, Date Y, Mizutani H, et al
. ZIP2 protein, a zinc transporter, is associated with keratinocyte differentiation. J Biol Chem 2014;289:21451-62.
Ogawa Y, Kinoshita M, Shimada S, Kawamura T. Zinc and skin disorders. Nutrients 2018;10. pii: E199.
Mogaddam MR, Ardabili NS, Maleki N, Chinifroush MM, Fard EM. Evaluation of the serum zinc level in patients with vitiligo. Postepy Dermatol Alergol 2017;34:116-9.
Shameer P, Prasad PV, Kaviarasan PK. Serum zinc level in vitiligo: A case control study. Indian J Dermatol Venereol Leprol 2005;71:206-7.
] [Full text]
Prasad AS. Zinc in growth and development and spectrum of human zinc deficiency. J Am Coll Nutr 1988;7:377-84.
Carneiro FR, Amaral GB, Mendes MD, Quaresma JA. Tissue immunostaining for factor XIIIa in dermal dendrocytes of pityriasis alba skin lesions. An Bras Dermatol 2014;89:245-8.
Ruiz-Maldonado R. Hypomelanotic conditions of the newborn and infant. Dermatol Clin 2007;25:373-82, ix.
Fenner J, Silverberg NB. Skin diseases associated with atopic dermatitis. Clin Dermatol 2018;36:631-40.
Burkhart CG, Burkhart CN. Pityriasis alba: A condition with possible multiple etiologies. Open Dermatol J 2009;3:7-8.
Takahashi H, Hashimoto Y, Aoki N, Kinouchi M, Ishida-Yamamoto A, Iizuka H. Copper, zinc-superoxide dismutase protects from ultraviolet B-induced apoptosis of SV40-transformed human keratinocytes: The protection is associated with the increased levels of antioxidant enzymes. J Dermatol Sci 2000;23:12-21.
Kawamura T, Ogawa Y, Nakamura Y, Nakamizo S, Ohta Y, Nakano H, et al
. Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency. J Clin Invest 2012;122:722-32.
Bae YS, Hill ND, Bibi Y, Dreiher J, Cohen AD. Innovative uses for zinc in dermatology. Dermatol Clin 2010;28:587-97.
Ferreira AA, Santos RV, Souza JA, Welch JR, Coimbra CE Jr. Anemia and hemoglobin levels among Indigenous Xavante children, Central Brazil. Rev Bras Epidemiol 2017;20:102-14.
Ingenbleek Y, McCully KS. Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis. Nutrition 2012;28:148-53.
Sandstead HH, Freeland-Graves JH. Dietary phytate, zinc and hidden zinc deficiency. J Trace Elem Med Biol 2014;28:414-7.
Denecker G, Vandamme N, Akay O, Koludrovic D, Taminau J, Lemeire K, et al
. Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression. Cell Death Differ 2014;21:1250-61.
Lim HS, Jin S, Yun SJ. Modulation of melanogenesis by heme oxygenase-1 via p53 in normal human melanocytes. Chonnam Med J 2016;52:45-52.
Biesemeier A, Julien S, Kokkinou D, Schraermeyer U, Eibl O. A low zinc diet leads to loss of Zn in melanosomes of the RPE but not in melanosomes of the choroidal melanocytes. Metallomics 2012;4:323-32.
Kim JE, Yoo SR, Jeong MG, Ko JY, Ro YS. Hair zinc levels and the efficacy of oral zinc supplementation in patients with atopic dermatitis. Acta Derm Venereol 2014;94:558-62.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4]