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Table of Contents
ORIGINAL ARTICLE
Year : 2017  |  Volume : 8  |  Issue : 2  |  Page : 65-67

Zinc level is a poor predictor of leg ulcer in patients with sickle cell anemia


Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria

Date of Web Publication21-Feb-2018

Correspondence Address:
Dr. Aliyu Dahiru Waziri
Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/atp.atp_8_17

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  Abstract 

Background: Sickle cell leg ulcers (SCLUs) are a major chronic debilitating complication in patients with sickle cell anemia (SCA). These ulcers lead to stigmatization and depression. Zinc deficiency has been implicated as a cause of SCLU. This study determined the predictability of leg ulcers and zinc levels among SCA patients in Zaria. Methods: This was a case–control study in which 100 participants (50 patients with HbSS and 50 controls with HbAA) were enrolled over a 3-month period by convenience sampling technique. Semi-structured questionnaires were used to obtain participants' ages, gender, and presence or absence of leg ulcers. Serum zinc levels were assayed using spectrophotometry. Data obtained were analyzed using IBM SPSS software version 20.0. Means and standard deviations were used to summarize the data, independent sample t-test was used to compare means, and logistic regression was used to assess whether zinc levels can predict the prevalence of leg ulcer among patients. P ≤ 0.05 was considered statistically significant. Results: The mean age of the participants was 24.92 ± 6.2 years while that of the control was 22.92 ± 4.9 (P = 0.172) with a range of 18–42 years in both groups. Leg ulcers were present in 10/50 (20.0%) of the patients with SCA. The mean zinc levels of patients with SCA with and without leg ulcers were 12.0 ± 4.0 μmol/l versus 15.5 ± 7.4 μmol/l (t = 2.060, P = 0.050). A binary logistic regression model using zinc as a predictor could explain only 4.7%–7.5% of the variability in leg ulcers but did not improve classification of cases. There was a negative nonsignificant association between zinc levels and leg ulcers, B = −0.098, odds ratio = 0.906, 95% confidence interval (0.789, 1.042), P = 0.167. Conclusion: Serum Zinc level is a poor predictor of leg ulcers in patients with SCA, thus suggesting other yet unstudied factors as likely better predictors.

Keywords: Sickle cell anemia, sickle cell leg ulcer, zinc


How to cite this article:
Waziri AD, Muktar HM, Hassan A, Awwalu S, Ibrahim IN, Kusfa IU. Zinc level is a poor predictor of leg ulcer in patients with sickle cell anemia. Ann Trop Pathol 2017;8:65-7

How to cite this URL:
Waziri AD, Muktar HM, Hassan A, Awwalu S, Ibrahim IN, Kusfa IU. Zinc level is a poor predictor of leg ulcer in patients with sickle cell anemia. Ann Trop Pathol [serial online] 2017 [cited 2018 May 27];8:65-7. Available from: http://www.atpjournal.org/text.asp?2017/8/2/65/225921


  Introduction Top


Sickle cell disease (SCD) is the most common single gene disorders in humans. It has varying clinical presentations that range from acute recurrent vaso-occlusive crisis which may cause hypoxic injury or infarction that can affect the brain, eyes, lungs, spleen, bone marrow, penis, or other tissues, leading to sequelae such as acute cerebral syndrome, acute chest syndrome, splenic infarction, or priapism.[1] Other complications such as leg ulcer, cholelithiasis, and osteomyelitis can also be found. Sickle cell leg ulcer (SCLU) is a major complication that is relatively common, often debilitating and a cause of stigmatization among affected individuals.[2]

SCLU is seen in those with the hemolytic phenotype associated with increased serum lactate dehydrogenase levels, increased serum bilirubin, reticulocytosis, and reduced nitric oxide level.[3] Chronic hemolysis, which increases demand and utilization, along with the secondary loss of zinc in the urine due to renal tubular damage following recurrent infarction had been implicated as a cause of abnormal zinc levels in plasma, erythrocytes, and hair due to increased urinary excretion, compared with controls.[4]

Zinc has been found to improve wound healing, decrease the incidence of infection, improve the age of attaining secondary sexual characteristics, reverse dark adaptation of the eyes, and accelerate growth.[5],[6] However, local data are scarce regarding the role of zinc in leg ulcers. Hence, we aimed determined the predictability of serum Zinc levels on the presence of SCLUs among patients with sickle cell anemia (SCA).


  Methods Top


It was a case–control study using semi-structured questionnaires, physical examination, and laboratory investigations. One hundred participants (50 each of steady state adult SCA patients who were confirmed by alkaline hemoglobin electrophoresis and age- and sex-matched Hb AA controls attending sickle cell clinic of Ahmadu Bello University Teaching Hospital, Zaria) were enrolled into this study after obtaining informed written consent. Consenting patients with SCA aged ≥18 years in steady state were recruited. Those in crisis or on zinc supplementation were excluded from the study. Similarly, consenting Hb AA individuals with age ≥18 years were recruited as control excluding persons on zinc supplementation. Ethical approval for this study was obtained from the Health Research Ethics Committee of Ahmadu Bello University Teaching Hospital Zaria.

Three milliliters of venous blood was collected into a plain sample bottle from each participant while observing standard aseptic procedures. The sample was allowed to stand for 1 h at room temperature to clot and subsequently centrifuged at 3000 g for 5 min using the universal 320 Hettich benchtop centrifuge (Hettich, Germany). The serum was transferred to another plain bottle and stored at −20°C in a chest freezer for colorimetric zinc estimation within 2 days with a spectrophotometer (Spectro UV-11, MRC Israel). Data obtained were analyzed using IBM SPSS version 20.0 (Armonk, NY: IBM Corp.). Means and standard deviations were used to summarize the data, Independent sample t-test to compare means, and logistic regression to determine if zinc levels can predict leg ulcers. P ≤ 0.05 was considered statistically significant.


  Results Top


The mean age of the participants was 24.9 ± 6.2 years. The mean zinc levels for SCA and controls were 14.86 ± 3.38 μg/mol and 17.00 ± 6.76 μg/mol, respectively (P = 0.04). The zinc status among participants was classified into low, normal, and high using the reference interval calculated from the control group (reference level = 10.24–23.76). Of the 50 patients, 8 (16.0%) had high zinc levels, 15 (30.0%) had low, while 27 (54.0%) had normal zinc levels [Figure 1].
Figure 1: Distribution of zinc levels among all the participants. Key: (1) Low: <10.24 μg/mol, (2) Normal: 10.24–23.76 μg/mol, (3) High: >23.76 μg/mol

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Leg ulcers were present in 10/50 (20.0%) of patients with SCA [Table 1]. The mean zinc levels of SCA patients with and without leg ulcers were 12.0 ± 4.0 μmol/l versus 15.5 ± 7.4 μmol/l (t = 2.060, P = 0.050). Binary logistic regression model using zinc as a predictor could explain only 4.7% to 7.5% of the variability in leg ulcers but did not improve classification of cases (χ2 = 4.903, df = 8, P = 0.768 with Cox and Snell R2 = 0.047, Nagelkerke R2 = 0.075). However, the model did not improve classification of cases (80.8% before and after inclusion of the predictor). There was a negative nonsignificant association between zinc levels and leg ulcers, B = −0.098, odds ratio = 0.906, 95% confidence interval (0.789, 1.042), P = 0.167.
Table 1: Sex distribution of leg ulcer in the patients studied

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  Discussion Top


Ten (20.0%) participants had leg ulcers of which 6 (60%) were males. Chronic leg ulcer was found to be common in the age group of 18–25 years with a decreasing prevalence with age. This could be explained by the fact that, this age group is very active and prone to injuries most especially at the lower extremities. This is significantly higher than the 0.45% report by Hassan et al. in Zaria and 9.6% and 7.6% reported by Bazuaye et al. and Idaewor et al., respectively.[7],[8],[9] This may be due to the different seasons of patient recruitment and geographical location of the studies. The difference in sex and ages may be due to release of injurious cytokines due to interaction between sickle cells and granulocytes, anemia, thrombocytosis, lower fetal hemoglobin, trauma, and genetic factors (HLA B35, CW47, Male sex).[8] Zinc levels could not predict those who were likely to develop leg ulcers because many factors play a role in causation of ulcers in patients with sickle anemia.

It was observed in this study that the mean zinc levels for participants were lower than that of controls (4.86 ± 7.63 and 17.00 ± 6.7 (μmol/l), respectively, and P = 0.04). The mean zinc levels found in the participants are higher than the observation by Edamisan et al., with a mean value of 4.94 ± 2.1 μmol/l.[10] Twenty-seven participants (54.0%) had normal levels and 15 (30.0%) had low zinc levels. The relatively normal values seen in our participants could be as a result of increased awareness about health status and diets. Moreover, the staple foods in the community such as whole grain cereals, legumes, and pulses have high zinc concentration.[11] While others such as rice, fish, root and tubers, and green leafy vegetable have moderate amounts of zinc.[12] Fifteen (30.0%) of our study participants have low zinc levels, and this is also in keeping with the findings by Prasad et al., Leonard et al. and Ogunrinde et al., who all reported zinc deficiency among SCA patients.[4],[6],[13] Low zinc level is caused by chronic hemolysis which increases demand and utilization and zincuria due to renal tubular damage following recurrent infarcts.[14]


  Conclusion Top


Zinc level is a poor predictor of leg ulcers in patients with SCA, thus suggesting other yet unstudied factors as likely better predictors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Lal A, Vichinsky PE. Sickle cell disease. In: Hoffbrand AV, Catovsky D, Tuddenham DG, editors. Postgraduate Haematology. 5th ed. USA: Blackwell Publishing; 2005. p. 104-18.  Back to cited text no. 1
    
2.
Delaney KM, Axelrod KC, Buscetta A, Hassell KL, Adams-Graves PE, Seamon C, et al. Leg ulcers in sickle cell disease: Current patterns and practices. Hemoglobin 2013;37:325-32.  Back to cited text no. 2
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3.
Nolan VG, Adewoye A, Baldwin C, Wang L, Ma Q, Wyszynski DF, et al. Sickle cell leg ulcers: Associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/BMP pathway. Br J Haematol 2006;133:570-8.  Back to cited text no. 3
[PUBMED]    
4.
Prasad AS, Beck FW, Kaplan J, Chandrasekar PH, Ortega J, Fitzgerald JT, et al. Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD). Am J Hematol 1999;61:194-202.  Back to cited text no. 4
[PUBMED]    
5.
Temiye EO, Duke ES, Owolabi MA, Renner JK. Relationship between painful crisis and serum zinc level in children with sickle cell anaemia. Anemia 2011;2011:698586.  Back to cited text no. 5
[PUBMED]    
6.
Leonard MB, Zemel BS, Kawchak DA, Ohene-Frempong K, Stallings VA. Plasma zinc status, growth, and maturation in children with sickle cell disease. J Pediatr 1998;132:467-71.  Back to cited text no. 6
    
7.
Hassan A, Dogara LG, Ibrahim A, Musa AU, Dahiru LI, Babadoko AA. Chronic leg ulcers in sickle cell disease patients in Zaria. Arch Int Surg 2014;4:141-5.  Back to cited text no. 7
  [Full text]  
8.
Bazuaye GN, Nwannadi AI, Olayemi EE. Leg ulcer in adult SCD patients in Benin city Nigeria. Gormal J Med Sci 2010;8:190-4.  Back to cited text no. 8
    
9.
Idaewor PO, Enosolease MC, Momoh MI. Leg ulceration in a population of Nigerian patients with sickle cell anaemia- Twenty years' experience. Int Med Biomed 2002;1:18-21.  Back to cited text no. 9
    
10.
Edamisan OT, Edem SD, Mbang AO, James KR. Relationship between painful crisis and serum zinc level in children with sickle cell anaemia. Anemia. 2011;3:1-7.  Back to cited text no. 10
    
11.
Umar M, Stephen SH, Abdullahi M. Levels of Fe and Zn in staple cereals: Micronutrient deficiency implications in rural Northeast Nigeria. Food Public Health J 2012;2:28-33.  Back to cited text no. 11
    
12.
Onianwa PC, Adeyemo AO, Idowu OE, Ogabiela E. Copper and zinc contents of Nigerian foods and estimates of the adult dietary intakes. Food Chem 2001;72:89-95.  Back to cited text no. 12
    
13.
Ogunrinde GO, Yakubu AM, Akinyanju OO. Anthropometric measures and zinc status of children with sickle cell Anaemia. Niger J Paediatr 2000;27:64-9.  Back to cited text no. 13
    
14.
Salgueiro MJ, Zubillaga MB, Lysionek AE, Caro RA, Weill R, Boccio JR, et al. The role of zinc in the growth and development of children. Nutrition 2002;18:510-9.  Back to cited text no. 14
    


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