Dermatology: Practical and Conceptual


Original Article | Dermatol Pract Concept. 2023;13(1):e2023017 1

The Role of Ischemia-modified Albumin 
and Ischemia-Modified Albumin to Albumin Ratios 

in Patients with Alopecia Areata
Efsun Tanacan1, Aynure Oztekin2, Unsal Savcı3, Engin Senel2, Coskun Oztekin4, 

Salim Neselioglu5, Ozcan Erel5

1 Department of Dermatology and Venerology, Ufuk University Hospital, Ankara, Turkey

2 Department of Dermatology and Venerology, Hitit University Faculty of Medicine Çorum, Turkey

3 Department of Microbiology, Hitit University Faculty of Medicine, Çorum, Turkey

4 Department of Family Medicine, Hitit University Faculty of Medicine, Çorum, Turkey

5 Department of Clinical Biochemistry, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey

Key words: alopecia areata, ischemia-modified albumin, IMA/albumin, disease severity

Citation: Tanacan E, Oztekin A, Savci U, et al. The Role of Ischemia-modified Albumin and Ischemia-modified Albumin to Albumin Ratios 
in Patients with Alopecia Areata. Dermatol Pract Concept. 2023;13(1):e2023017. DOI: https://doi.org/10.5826/dpc.1301a17

Accepted: September 7, 2022; Published: January 2023

Copyright: ©2023 Tanacan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, 
distribution, and reproduction in any medium, provided the original authors and source are credited.

Funding: None.

Competing Interests: None.

Authorship: All authors have contributed significantly to this publication.

Corresponding Author: Efsun Tanacan, Department of Dermatology and Venerology, Ufuk University Hospital, Ankara, Turkey. 
Tel: +903122044151 E-mail: efsunkln@yahoo.com

Introduction:

Objective: To investigate the role of ischemia-modified albumin (IMA) and IMA/albumin levels in 
patients with AA.

Methods: The present prospective crossectional study includes patients ≥18 who were admitted to 
the Dermatology and Venerology Department of Hitit University Hospital between April 1, 2021, and 
September 30, 2021. 70 patients participated in the study (n=34 for the study group and n=36 for the 
control group). Demographic features, clinical characteristics, IMA, and IMA/albumin levels were 
compared between the groups. The study group was divided into subgroups based on the number 
of patches, disease duration, and the number of disease attacks. IMA and IMA/albumin levels were 
compared between each subgroup.

Results: The study and control groups were similar with regard to demographic features and clinical 
characteristics. Significant differences were observed between the mean IMA and IMA/albumin ratio 
(p=0.004 and 0.012, respectively). The study subgroups were comparable in the number of patches, 
disease duration, and number of disease attacks.

Conclusion: Although oxidative stress is an important component in the etiology of AA, IMA and 
IMA/albumin may not be useful in the prediction of disease severity in patients with AA.

ABSTRACT



2 Original Article | Dermatol Pract Concept. 2023;13(1):e2023017

Introduction

Alopecia areata (AA) is a chronic, immune-mediated dis-

ease resulting in non-scarring hair loss with an approximate 

prevalence of 1/1000 [1]. Hair follicles in the anagen phase 

prematurely transform into catagen and telogen phases by 

autoimmune and inflammatory mechanisms resulting in a 

sudden hair loss in patients with AA [2]. Although the patho-

physiological mechanisms behind AA have not been clearly 

revealed yet, immune dysregulation, genetic predisposition, 

and excessive oxidative stress seem to be the main predispos-

ing factors behind the development of AA [3].

Oxidative stress and free radical damage alter the 

chemical structure of albumin, leading to the production 

of ischemia-modified albumin (IMA) [4]. Hence, the util-

ity of IMA and IMA/albumin were investigated in various 

studies for revealing the oxidative stress-related events be-

hind the etiology of autoimmune and inflammatory dis-

eases [5, 6].

The role of IMA was also investigated in several derma-

tologic diseases like psoriasis, Behçet’s disease, and alopecia 

areata [7-9]. However, no consensus has been reached on the 

utility of IMA in daily dermatology practice. For this reason, 

more data is necessary to reach more precise results.

The aim of the present study is to investigate the role of 

IMA and IMA/albumin levels in patients with AA.

Material and Methods

The present prospective crossectional study consisted of pa-

tients ≥18 who were admitted to the Dermatology and Ven-

erology Department of Hitit University Hospital between 

April 1, 2021, and September 30, 2021. Seventy patients 

participated in the study (n=34 for the study group and n=36 

for the control group). Patients with alopecia areata served 

as the study group. Thirty-six gender and age-matched pa-

tients with dermatologic complaints other than inflamma-

tory skin diseases were used as the control group. Cases 

with pregnancy, lactation, history of malignancy, and active 

or chronic infection were excluded from the study. Written 

informed consent was signed by all participants. The insti-

tutional ethics committee approved the study protocol with 

reference number 449. Firstly, the clinical characteristics 

of AA patients were evaluated. Gender, pattern of alopecia 

area, duration of disease, family history with AA, involved 

area (scalp, beard, eyebrow) and the number of disease at-

tacks were evaluated for each AA patient. Both study and 

control groups were evaluated for gender, age, height (m), 

weight (kg), Body mass index (BMI), smoking and alcohol 

consumption, IMA, and albumin levels. The IMA/albumin 

ratio of all participants was calculated. Afterwards, the 

study group was divided into subgroups based on number 

of patches, disease duration, and number of disease attacks. 

IMA and IMA/albumin levels were compared between each 

subgroup. All the blood samples (peripheral venous blood) 

from all participants were collected after overnight fast. Sta-

tistical analyses were performed by Statistical Package for 

the Social Sciences (SPSS.22, IBM SPSS Statistics for Win-

dows, Version 22.0 Armonk, NY: IBM Corp.).

Student t-test was used for comparing the mean values 

between the groups as the data was normally distributed. 

Chi-square test was conducted to compare the categorical 

variables. Pearson correlation test was performed for cor-

relation analyses. A two-tailed P value < 0.05 was regarded 

as statistically significant.

Results

The clinical characteristics of the patients with Alopecia 

Areata were shown in Table 1. In the alopecia areata group, 

most of the participants were male. Approximately 60% of 

the patients had a single patch. Disease duration was less 

than one year in 19 patients. Only three patients had a fam-

ily history of alopecia areata.

Table 1. Demographic features and Disease 
Characteristics of the patients with Alopecia 

Areata.

N %

Gender

 Female 12 35.3%

 Male 22 64.7%

Patern of AA

 Single patch 20 58.8%

 Multiple patch 14 41.2%

Duration of illnes

 < 1 year 19 55.9%

 1-4 years  9 26.5%

 ≥5 years  6 17.6%

Family history of AA

 Yes  3  8.8%

 No 31 91.2%

Involvement area

 Scalp 22 64.7%

 Beard  8 23.5%

 Eyebrow  2  5.9%

 ≥2  2  5.9%

Number of attacks

 1 20 58.8%

 2 10 29.4%

 3  4 11.8%



Original Article | Dermatol Pract Concept. 2023;13(1):e2023017 3

The patients’ most common areas of disease involvement 

were scalp, beard, and eyebrows, respectively. In addition, 

58.8% of the patients had an alopecia attack for the first 

time, while the other 4 in 10 patients had an alopecia attack 

for the third time.

Comparison of the gender distribution, mean age, height, 

weight, BMI, smoking, alcohol consumption, IMA, and 

albümin levels between the study and control groups are 

shown in Table 2.

Significant differences were observed between the mean 

IMA and IMA/albumin ratio (p=0.004 and 0.012, respec-

tively). The study subgroups were comparable for the num-

ber of patches, disease duration, and number of disease 

attacks, as shown in Table 3.

Discussion

The pathogenetic mechanisms of AA have still not been clar-

ified. Impaired immune system activation and genetic predis-

position seem to be the main events behind AA. Destruction 

of hair follicles by immune-mediated cells and inflammatory 

products results in reversible hair loss in a specific pattern [1]. 

Excessive oxidative stress is considered to be another trigger-

ing event in the development of AA. There are many studies 

showing the effect of oxidative stress on AA and many other 

dermatological diseases [10-17]. Degradation products re-

sulting from oxidative stress may damage hair follicles and 

they may alter the balance between the anagen, telogen and 

catagen phases. Furthermore, some of these products may be 

used as biological markers of oxidative stress [18-20].

IMA (ischemic modified albumin) is produced by the 

modification of albumin due to the reactive oxygen spe-

cies (ROS). A higher level of IMA was observed in various 

diseases like ischemic heart disease, pulmonary embolism, 

cancer, and stroke [21-24]. The role of IMA was also evalu-

ated in dermatological diseases. Elevated levels of IMA were 

shown in psoriasis, hair diseases, and vitiligo. In recent years, 

some studies have addressed the risk of thrombosis, acute 

myocardial infarction, and stroke in AA with various results 

[25-28]. Shakoei et al. found elevated D- Dimer levels and in-

creased risk of thromboembolism in AA. Kang et al. defined 

that patients with AA were associated with a higher risk of 

stroke in the 3-year follow-up period. However, some data 

do not support the risk of heart attack and stroke in alopecia 

Table 2. Comparison of the gender distribution, mean age, height, weight, BMI, smoking, alcohol 
consumption, IMA, and albümin levels between the study and control groups.

Patients (n=34) Controls (n=36) P value

Gender

 Female 12 13 0.57

 Male 22 23

Mean age 31.56±8.5 31±8.5 0.78

Height 170.8±9.5 169.7±9.9 0.72

Weight 72.6±12.8 72.2±10.04 0.86

BMI 24.79±3.3 25.05±2.8 0.72

Smoking 0 0 N/A

Alcohol consumption 0 0 N/A

Family history of AA 3 0 N/A

IMA 0.71±0.17 0.50±0.14 0.04

Albumin 4.09±0.10 4.08±0.11 0.62

IMA/Albumin 0.17±0.04 0.12±0.03 0.012

Table 3. Comparison of IMA, Albumin, and IMA/Albumin according to number of patches, disease 
duration, and number of disease attacks.

Single 
patch 
(n=20)

Multiple 
patch 
(n=14) P value

<6 
months 
(n=19)

>6 
months 
(n=15) P value

Number 
of attack 
1 (n=20)

Number 
of attack 
≥2 (n=14) P value

IMA 0.70±0.20 0.72±0.10 0.76 0.75±0.21 0.66±0.09 0.13 0.73±0.21 0.68±0.08 0.39

Albumin 4.09±0.11 4.10±0.09 0.65 4.05±0.10 4.13±0.09 0.04 4.08±0.13 4.11±0.05 0.38

IMA/Albumin 0.17±0.05 0.17±0.02 0.81 0.18±0.05 0.16±0.02 0.11 0.18±0.05 0.16±0.02 0.35



4 Original Article | Dermatol Pract Concept. 2023;13(1):e2023017

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9. Incel-Uysal, P., et al., Assessment of metabolic profile and 

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A case–control study. Indian journal of dermatology, 2019. 

64(1): p. 12.

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activity and severity in alopecia areata? An analytical study. 

J Cosmet Dermatol, 2021.

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13. Qiu, L., Z. Song, and V. Setaluri, Oxidative stress and vitiligo: 

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14. Shah, A.A., et al., Increased oxidative stress in pemphigus 

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15. Emre, S., et al., The association of oxidative stress and disease 

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16. Narendhirakannan, R.T. and M.A. Hannah, Oxidative stress and 

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17. Okayama, Y., Oxidative stress in allergic and inflammatory skin 

diseases. Curr Drug Targets Inflamm Allergy, 2005. 4(4): p. 517-9.

18. Akar, A., et al., Antioxidant enzymes and lipid peroxidation in 

the scalp of patients with alopecia areata. Journal of dermato-

logical science, 2002. 29(2): p. 85-90.

19. Naziroglu, M. and I. Kokcam, Antioxidants and lipid peroxida-

tion status in the blood of patients with alopecia. Cell Biochem-

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20. Abdel Fattah, N., A. Ebrahim, and E. El Okda, Lipid peroxidation 

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areata [27, 28]. On the other hand, recently, in alopecia 

areata, literature data show a tendency to thrombosis and an 

increased risk of heart attack and stroke. In addition, studies 

have found elevated levels of cardiac biomarker troponin I 

and congestive heart disease biomarker BNP in patients with 

alopecia areata [29, 30].

There are publications in the literature indicating the 

association of IMA with the severity and deterioration of 

AA [9, 31]. These reports focused on the pathophysiological 

pathways related to increased oxidative stress in patients with 

AA. As excessive oxidative stress was reported to be an im-

portant triggering event in the development of AA, markers 

associated with oxidative stress might increase with disease 

severity [32]. Moreover, although the utility of IMA/albumin 

was investigated in various conditions like chronic liver dis-

ease and hemorrhagic shock, to the best of our knowledge, 

it has not been studied in cases with AA [6, 33]. However, 

similar to other autoimmune and inflammatory diseases, the 

etiology of AA is complex, and using a single oxidative bio-

marker may be insufficient to predict the severe course of the 

disease [34]. In the present study, no significant differences 

were observed for IMA and IMA/albumin between the cases 

with regard to patch characteristics, duration of the disease 

and number of attacks per year. In our opinion, more studies, 

including a larger number of cases and many more study 

parameters, are necessary to reach more reliable results for 

the role of IMA in the prognosis of AA.

The main strengths of the present study were its prospec-

tive design and investigation of IMA/albumin levels in patients 

with AA. On the other hand, the relatively low number of 

cases and single-center experience were the main limitations.

In conclusion, although oxidative stress seems to play an 

important role in the etiology of AA, IMA and IMA/albumin 

may not be useful in the prediction of disease severity in pa-

tients with AA.

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