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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 168-172

A descriptive case-control study on assessment of iron profile in patients with and without melasma


Department of Dermatology, Venereology and Leprosy, Kempegowda Institute of Medical Sciences, Bengaluru, Karnataka, India

Date of Submission06-Jun-2020
Date of Decision08-Sep-2020
Date of Acceptance23-Nov-2020
Date of Web Publication26-Aug-2021

Correspondence Address:
Megha Prakash
Department of Dermatology, Kempegowda Institute of Medical Sciences, Banashankari, Bengaluru - 560 070, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CDR.CDR_90_20

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  Abstract 


Background: Melasma or chloasma is a common acquired hyper melanosis, characterized by dark, irregular hyperpigmented macules and patches over the malar areas, lips, nose and forehead. Iron overload manifests with skin hyperpigmentation. Therefore, it is important to understand the role of iron in patients with melasma. Objectives: (1) To assess serum iron profile in non-pregnant women and men with melasma. (2) To assess the same parameters in age and sex matched controls. Materials and Methods: A descriptive case–control study with 35 cases of melasma and 35 age and sex-matched controls was conducted between December 2019 and March 2020, to assess the association between melasma and iron deficiency. Results: Among 35 cases of melasma, 85.7% were females, the most common type was the malar type 68.8%, sunlight was the most-common risk factor and 100% had deranged iron profile. Mean ferritin levels in the melasma group was 15.204 ng/ml while in control group it was 71.717 ng/ml. Mean serum iron levels in melasma group was 28.585 μg/dl while in that of controls were 135.018 μg/dl. Other iron parameters also showed significant iron deficiency in melasma patients. Conclusion: Well-known factors implicated in the etiology of melasma include sunlight, Oral contraceptive pills with oestrogen, pregnancy and smoking. This study indicates that iron deficiency is also an important etiological factor and hence treatment of iron deficiency may be a novel therapeutic approach in patients with refractory melasma.

Keywords: Ferritin, iron deficiency, melasma


How to cite this article:
Prakash M, Manjunath NC, Deepali B S. A descriptive case-control study on assessment of iron profile in patients with and without melasma. Clin Dermatol Rev 2021;5:168-72

How to cite this URL:
Prakash M, Manjunath NC, Deepali B S. A descriptive case-control study on assessment of iron profile in patients with and without melasma. Clin Dermatol Rev [serial online] 2021 [cited 2021 Dec 1];5:168-72. Available from: https://www.cdriadvlkn.org/text.asp?2021/5/2/168/324581




  Introduction Top


Melasma is a common acquired hypermelanosis seen mainly in young to middle aged women and rarely in men. Melasma is characterized by dark, irregular to well defined hyper pigmented macules and patches commonly found on the malar areas, lips, nose and forehead.[1] Chloasma is a synonymous term sometimes used to describe the occurrence of melasma during pregnancy. The exact etiology of melasma remains unknown, but some triggering factors are sun exposure, pregnancy, use of oral contraceptives mainly containing estrogen, hormone replacement therapy have been implicated as possible causative factors. It is also seen in women who are exposed to mustard oil while cooking, especially in northern India, as mustard oil is known to increase pigmentation.[2] Other factors include scent and stress, which leads to the release of reactive oxygen species causing damage to the melanocytes and increased pigmentation.[3] Sunlight, one of the most important etiological factors, is known to increase production of alpha-melanocyte-stimulating hormone (MSH) and corticotropin, along with increased interleukin-1 and endothelin 1, all of which contribute to increased melanin production and hyperpigmentation.[4]

In pregnancy, especially in the third trimester, elevation in the hormones such as estrogen, progesterone, and MSH cause increased transcription of tyrosinase leading to increased melanogenesis.[5] The severity of melasma was initially measured by the subjective scoring system called the Melasma Area and Severity Index (MASI), proposed by Kimbrough-Green et al. in 1994. The three parameters measured in the MASI scoring were area of involvement, pigmentation, and homogeneity. However, the reliability and validity of MASI has been tested in a single study which has recommended a modified MASI (mMASI) excluding the homogeneity component.[6] mMASI measures the darkness and the percentage of area involved in the forehead, right malar, left malar and the chin. The score ranges from 0 to 24.

Determination of the modified Melasma Area and Severity Indexscore

The calculation is based on the sum of Forehead mMASI score + Left Malar mMASI score + Right Malar mMASI score + Chin mMASI score = Total mMASI score[Table 1].[7]
Table 1: Determination of the modified melasma area and severity index score

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Melasma is extremely distressing for the patient as it mainly manifests over the face, being easily visible and constantly present in daily life. It causes psychosocial and emotional distress and reducing the quality of life of the affected patients. The treatment for melasma is long term and resistant to many existing modalities.

Hemochromatosis is an iron overload state associated with hyperpigmentation along with other systemic features. Both melasma and hemochromatosis manifest hyperpigmentation however in melasma; hyperpigmentation worsens on exposure to sun. Melasma is the most common cause for skin hyperpigmentation, which is often refractory to treatment with continued exposure to sun. However, there have been few studies which have suggested a relationship between iron deficiency and melasma.[8] It is important to evaluate serum iron, and its metabolites such as ferritin, total iron-binding capacity (TIBC) transferrin saturation and unbound iron binding capacity in melasma patients. Melasma requires prolonged medical treatments and procedures whose results do not always meet the expectations of patients, thus incurring high expenditures for them.[9] In this case–control study, we have analyzed the different iron parameters in patients with melasma compared to age and sex matched controls to evaluate role of iron deficiency in melasma as this may be a novel therapeutic target in patients with refractory melasma.

Objectives

  1. To assess the serum iron, ferritin, TIBC, unsaturated iron binding capacity (UIBC) and transferrin saturation in non-pregnant women and men with melasma
  2. To assess the same parameters in age and sex matched controls.



  Materials and Methods Top


A descriptive case–control study was conducted between December 2019 and March 2020, among outpatients in the Department of Dermatology, Venereology and Leprosy in a tertiary care hospital. Ethical clearance was obtained from the institutional ethical committee.

Inclusion criteria

  • Cases of melasma
  • Controls are age and sex matched, which includes healthy individuals not having features of any systemic disease
  • Patients above 18 years of age
  • Patient willing to give informed consent.


Exclusion criteria

  • Patients below 18 years of age
  • Pregnant and lactating women.
  • Patients not willing to give an informed consent
  • Patients with melasma having any underlying systemic illness e.g.: Anaemia due to other secondary causes such as folate deficiency, renal insufficiency, malnutrition and malabsorption causes.


Study design

The study design is a descriptive case–control study. Informed written consent was taken from both the cases and the controls. The sample size has been estimated using the G-Power software v. 3.1.9.4. developed by Faul, F., Erdfelder, E., Lang, A.-G., & Buchner, A. (2007) from University of Keil , Germany. Considering the effect size to be measured at 61% (based on the study results of Qazi et al., 2017)[11] at Two-Tailed Hypothesis, power of the study at 80% and the margin of the error at 10%, the sample size needed is 68, which will be rounded off to 70. So, it will consist of 35 cases of melasma and 35 cases of controls. A structured questionnaire was designed to collect the patients details such as sociodemographic profile, comprising of their age, sex, educational status, occupation, duration of melasma, presence of any systemic illness' or comorbid conditions, history of any drug intake which exacerbates melasma (e.g., intake of oral contraceptive pills) and history of exposure to any exacerbating factors such as sunlight, steam with added chemicals, stress, scrubbing, usages of scents, steroid application, alcohol and smoking history were noted. A detailed cutaneous examination was conducted for each case. Based on distribution of the hyperpigmentation on the face melasma was divided into three main categories:

  1. Malar type
  2. Centro facial type
  3. Mandibular type.


Photographic documentation of the melasma lesions were done, with the patients consent. The severity of melasma was measured using the mMASI score. Iron profile comprising of serum iron, serum ferritin, hemoglobin, transferrin saturation, TIBC, and UIBC was measured. Similar parameters were measured in age and sex matched controls without any systemic illnesses such as anaemia, malignancies, malnutrition or malabsorption.

The reference ranges of the parameters which were considered as normal in our study were as follows: Serum iron – 37–158 μg/dl, serum ferritin – 30–400 ng/ml, transferring saturation – 16–45%, TIBC – 228–428 μg/dl, UIBC – 110–370 μg/dl and haemoglobin – 11.5–16 g/dl.

Descriptive statistical analysis of all the explanatory and outcome parameters was done using mean and standard deviation for quantitative variables, frequency, and proportions for categorical variables. Inferential statistical analysis was done using the independent student t-test which was used to compare the mean serum iron, ferritin, TIBC and transferrin saturation levels between two groups. Comparison of mean values of different study parameters (iron profile and its indices) between the two groups was done using Mann–Whitney Test. The level of significance (P-value) was set at P < 0.05, with 95% confidence interval. Spearman's correlation test was done to assess the relationship between mMASI scoring and other study parameters in melasma group. A scatterplot was also depicted to derive the relationship with iron profile parameters and mMASI scores in the cases group. The statistical analyses were done using the Statistical Package for Social Sciences for Windows Version 22.0 Released 2013. Armonk, NY, USA: IBM Corp.


  Results Top


In this study, the female melasma patients out-numbered the male melasma patients, 85.7% were females while 14.3% were males. The most common age group of presentation of melasma was between 41 and 50 years (51.4%) followed by 51 and 60 years (28.6%). The mean value of age of both cases and controls was 45.83 with a standard deviation of ±8.96. The oldest patient in this study was 60 years old while the youngest was 23 years old. The occupation of the melasma patients were as follows: 40% of the patients were employees in their respective firms, while the next predominant number of patients of melasma were housewives (37.1%). The highest risk factor to melasma was exposure to sunlight as seen in 32.2% of the cases, followed by the second highest factor being usage of scrubbing techniques over the face (20.3%) [Figure 1].
Figure 1: Distribution of various risk factors among melasma cases

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The types of melasma present in the cases group were classified based on their distribution. The most common was malar type seen in 68.8%, followed by centrofacial type seen in 29.1%, while mandibular type was seen in only 2.1% of the cases. The average mMASI was higher among females than compared to males. (8.09 and 7.44, respectively). There was 100% derangement of iron profile in patients with melasma. The mean ferritin levels in the cases group was 15.204 ± 7.829 ng/ml while in controls the value was 71.717 ± 15.988 ng/ml (normal range 30–400 ng/ml) (P = 0.00003). The mean serum iron levels in melasma cases was 28.585 ± 6.712 μg/dl, while in controls was 135.018 ± 33.493 μg/dl (normal range 37–158 μg/dl) (P = 0.000015). The mean haemoglobin in melasma cases were 12.303 ± 1.551g/dl while in controls it was 13.063 ± 1.182 g/gl (normal range 11.5–16 g/dl). (P = 0.01). The mean transferrin saturation among melasma cases was 6.153 ± 1.58%, while in controls it was 51.113% ± 13.896% (normal range 16–45%) (P = 0.000042). The average TIBC in cases was 467.686 ± 30.543 μg/dl, while in controls it was 272.632 ± 30.543 μg/dl. (normal range 228–428 μg/dl) (P = 0.000018). The UIBC in cases was 438.931 ± 30.54 μg/dl while in controls it was 135.311 ± 60.33 (normal range 110–370 μg/dl) (P = 0.000035). All the iron profile parameters had high statistical significance [Table 2].
Table 2: Comparison of mean values of iron profile parameters between cases and controls

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  Discussion Top


In our study, all the parameters of the iron profile were drastically lower in cases of melasma compared to the age and sex-matched controls. The hemoglobin levels were lower in the study population compared to the controls, with a P = 0.02 which was statistically significant. Other iron profile parameters such as serum iron, ferritin and transferrin saturation were significantly lower in cases compared to controls which was statistically significant (P < 0.01). Parameters such as TIBC and UIBC (which are elevated if the iron stores are depleted) were higher in melasma cases compared to controls with a P < 0.01 which was statistically significant. There was a significant correlation between iron deficiency and melasma in our study. In a study by Babaie et al.[10] 14.3% of the patients with melasma had significant iron deficiency which was independent of Vitamin B12 and folate deficiency. In a cross-sectional case control study by Behrangi et al.,[8] iron deficiency was seen in 27% of the study population.

The low body iron stores in the patients of melasma were correlated with the mMASI scores, using the Spearman's correlation test, which establishes the relationship between the 2 variables. The relation between mMASI and the variables of serum iron, ferritin, transferrin saturation, and hemoglobin showed a negative correlation, thus indicating an inverse relationship between MASI and the above variables [Figure 2], i.e., as the mMASI score increases (indicating the severity of melasma), the iron stores are depleted. A positive correlation was observed in the Spearman test between mMASI and iron-binding parameters TIBC, UIBC which are suggestive of iron deficiency. The P values of all the above variables <0.05 thereby indicating statistical significance [Table 3].
Figure 2: Scatterplot depicting a downward trend, indicating an inverse relationship between MASI scoring and serum iron, transferrin saturation, ferritin and haemoglobin

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Table 3: Spearman's correlation test to assess the relationship between melasma area and severity index and other study parameters in melasma group

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Qazi et al.[11] in 2017 had observed similar findings of low body iron stores in the patients of melasma. Serum iron and ferritin levels were found to be lower as compared to the control population and this difference was found to be statistically significant (P < 0.001). Mean TIBC was found to be higher in the cases compared to the control population. Also, a significant correlation was found between severities of melasma as per the mMASI score with the iron derangements. Hence patient with a higher score of mMASI representing more severe melasma had more derangement in the iron profile compared to the patients with lower mMASI score.

However, Kiayani[12] in 2019 evaluated the association of melasma with iron deficiency anaemia, and found that serum ferritin levels were found to be normal in melasma cases (mean 64.9). Another recent study by Goodarzi et al.[13] where they analysed serum ferritin and serum iron levels in melasma patients, comncluded that melasma is associated with iron deficiency. The mean corpuscular volume, mean corpuscular hemoglobin (MCH) and MCH concentration levels were also in normal range, however this study did not evaluate the complete iron profile parameters such as serum iron, transferrin saturation, TIBC and UIBC, another main limitation of the study was that it had no control groups, hence statistical significance could not be determineded. There is an incomplete understanding of pathogenesis of melasma[9] and studies on how low iron levels contributes to the pathogenic mechanisms in melasma is poorly understood. Further studies are required for the same.


  Conclusion Top


Serum iron, ferritin levels, transferrin saturation, were found to be statistically highly significant as they were lower in patients of melasma as compared to control the population. While Serum TIBC and UIBC levels in cases were higher as compared to the control population. The hemoglobin was also relatively lower in cases compared to controls with statistical significance. This implies that merely checking hemoglobin levels is insufficient and a complete iron profile needs to be measured. The purpose of this study is to demonstrate that melasma is a cosmetically debilitating condition with the necessity for long-term therapies, since recurrence rates are high.[14] Thus devising novel methods such as supplementation of iron in melasma can improve the clinical outcome and prove to be an economical modality. The scope of this study includes further follow up of melasma patients after supplementing them with adequate iron supplements and noting their response to treatment.

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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Behrangi E, Baniasadi F, Esmaeeli S, Hedayat K, Goodarzi A, Azizian Z. Serum iron level, ferritin and total iron binding capacity level among nonpregnant women with and without melasma. J Res Med Sci 2015;20:281-3.  Back to cited text no. 8
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Babaie N, Ajad S, Khodaiiani E, Herizchi H, Mehrabi P. Frequency of Iron deficiency anemia, folate and Vitamin B12 deficiency in patients (965_14) with Melasma. Med J Tabriz Univ Med Sciences 2012;34:12-5.  Back to cited text no. 10
    
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Qazi I, Dogra NK, Dogra D. Serum Iron profile in female patients of melasma – A case control study. Asian Pac J Trop Med 2017;4:141-6.  Back to cited text no. 11
    
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Kiayani AJ. Association of melasma with iron deficiency anemia and thyroid disease in females at a tertiary care hospital of Pakistan. J Pak Assoc Dermatologists 2019;29:354-6.  Back to cited text no. 12
    
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Goodarzi A, Behrangi E, Bazargan AS, Roohaninasab M, Hosseini-Baharanchi FS, Shemshadi M, et al. The association between melasma and iron profile: A case-control study. Russ Open Med J 2020;9:e0202.  Back to cited text no. 13
    
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Sardesai VR, Kolte JN, Srinivas BN. A clinical study of melasma and a comparison of the therapeutic effect of certain currently available topical modalities for its treatment. Indian J Dermatol 2013;58:239.  Back to cited text no. 14
[PUBMED]  [Full text]  


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