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ORIGINAL ARTICLE
Year : 2014  |  Volume : 59  |  Issue : 6  |  Page : 558-561
Altered serum uric acid level in lichen planus patients


1 Department of Biochemistry, Murshidabad Medical College and Hospital, Berhampore, West Bengal, India
2 Department of Dermatology, Murshidabad Medical College and Hospital, Berhampore, West Bengal, India

Date of Web Publication30-Oct-2014

Correspondence Address:
Dr. Goutam Chakraborti
Department of Biochemistry, Murshidabad Medical College and Hospital, Berhampore - 742 101, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.143510

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   Abstract 

Background: Lichen planus (LP) is a common disorder whose etiopathogenesis is not clear. Recently, it has been suggested that increased reactive oxygen species (ROS) play important roles in the underlying mechanism of LP. Objectives: The principal aim of this study was to evaluate serum uric acid (UA) levels as a measure of the antioxidant defense status in LP patients. Methods: Serum UA levels were determined in 58 LP patients and 61 controls. Results: Serum UA levels were significantly decreased in patients with respect to controls. Moreover, serum UA level was decreased according to increasing duration of disease. Conclusions: The results of our study suggest that LP is associated with decrease of UA levels in serum. UA may be a potential, useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring.


Keywords: Antioxidant, free radical, lichen planus, oxidative stress, uric acid


How to cite this article:
Chakraborti G, Biswas R, Chakraborti S, Sen PK. Altered serum uric acid level in lichen planus patients. Indian J Dermatol 2014;59:558-61

How to cite this URL:
Chakraborti G, Biswas R, Chakraborti S, Sen PK. Altered serum uric acid level in lichen planus patients. Indian J Dermatol [serial online] 2014 [cited 2020 Apr 3];59:558-61. Available from: http://www.e-ijd.org/text.asp?2014/59/6/558/143510

What was known?
Free radicals have an important role in the underlying mechanism of LP.



   Introduction Top


Lichen planus (LP) is a subacute to chronic, inflammatory, papulosquamous disorder characterized by typical lesions. Small, shiny, flat-topped, polygonal, faintly erythematous to violaceous papules that may coalesce into plaques involve the skin, mucous membrane, and nail. LP can clinically present in various forms including classical, hypertrophic, actinic, annular, follicular, eruptive, and linear types. It affects all races and occurs usually from 30 to 70 years of age. [1]

An abnormal immune response is probably the basis of this disease and the pathogenesis includes lymphocytic infiltration and keratinocyte necrosis. [2] Recently, it has been suggested that free radicals have an important involvement in the underlying mechanism of various skin diseases. [3] In LP, the inflammatory cellular infiltrate, which consists mainly of CD4+ lymphocytes, is a well-known source of reactive oxygen species (ROS). [4] In high concentrations ROS damages endothelial cells, and subsequently intercellular adhesion molecule (ICAM) 1 is further upregulated and expressed. T lymphocytes are recruited at the site of inflammation by this expression of ICAM-1. This process may cause perivascular infiltration of T-cells and exocytosis of lymphocytes as observed in LP. [5] Also oxidative stress may activate nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), which is an important transcription factor. NFκB controls transcription of various cytokine genes that include interleukin (IL)-2 and tumor necrosis factor (TNF)-α, and also major histocompatibility complex (MHC) class 1 gene and IL-2 receptor gene. TNF-α may produce H 2 O 2 and superoxide anions in epidermal keratinocytes. [6] Also, oxidative stress is involved in both pro- and antiapoptotic signaling in response to TNF-α. [7] Further, oxidative stress and increased inflammatory mediators release effector molecules including granzyme that can promote local tissue damage. [8]

The primary defense mechanisms against oxidative stress include antioxidants like some enzymes, vitamins, uric acid (UA), etc. [9],[10] UA is one of the important antioxidants in plasma. [11] UA can scavenge ROS and can chelate metal ions. [12] Thus, monitoring UA level in serum as an indicator of the antioxidant defense (oxidative balance) could be important for the clinicians' treatment strategy.

There is paucity of data available in the literature regarding serum UA levels in LP patients, particularly from our country. There are conflicting reports of association of UA levels among LP patients: Some found decreased levels of UA suggesting oxidative stress, while others failed to find any difference. [13],[14] So, the present study was designed to determine whether LP was accompanied by change in serum UA levels, and if so, whether there is any correlation between the duration of disease and degree of change in UA levels in serum.


   Materials and Methods Top


This study was a hospital-based, case-control study conducted in the Departments of Dermatology and Biochemistry of Murshidabad Medical College and Hospital, Berhampore, West Bengal. The study was approved by the local ethical committee and all patients and control subjects gave their informed consent to take part in this investigation.

The duration of the present study was 3 months and included 61 LP patients attending the Dermatology outpatient department (OPD), duration ranging from 1 month to 12 months. In addition, 61 patients who were age- and sex-matched with the subjects served as controls. The controls had attended the OPD with minor ailments like scabies, minor pyoderma, tinea, etc., Complete history and physical examination of all cases and controls were undertaken, and wherever necessary, skin biopsy was taken to confirm the diagnosis. Exclusion criteria included subjects who had received any systemic steroid or other immunosuppressive drugs and nonsteroidal anti-inflammatory drugs (NSAIDs) within the last 4 weeks and topical medications within the last 2 weeks. Other exclusion criteria included smokers, patients with history of trauma or any surgery within 1 month prior to sampling, and those suffering from systemic or other dermatologic diseases affecting immune system or any malignancy. Lastly, subjects having febrile illness, gout, pregnancy, kidney and liver dysfunction, obesity, ketosis, familial hyperuricemia, and blood dyscrasias were excluded.

Five milliliter of venous blood sample was collected from each case and control after 12 h of fasting. All samples were coded and assayed in a blind fashion by an investigator who was unaware of the subjects' clinical status.

Serum UA was assayed using Siemens, Mumbai, India and Coralab 3000 semiautoanalyser, by uricase method. [15]

Statistical analysis of the data was performed by using Statistical Package for Social Sciences (SPSS version 16) and inferences were drawn. P < 0.05 was considered to be significant.


   Results Top


Blood was drawn from 30 male patients and 28 female patients because three patients dropped out from the study. The age of patients ranged from 27 to 65 years.

No significant correlation was found between the patients' age and serum UA levels.

There was no significant difference in UA levels between male and female patients.

Mean duration of disease in patients (including recurrences and remissions) was 15 months (ranging from 1 month to 3 years and 11 months).

The different types of LP among the study group were as follows: Classical (58%), hypertrophic (19%), eruptive (10%), linear (8%), actinic (2%), annular (2%), and follicular (1%).

The differences of UA levels between the different subsets of LP were not statistically tested because of the low number of patients in the individual subsets.

Mean serum UA levels in patients and controls were 3.6033 and 3.9484 mg%, respectively and the difference was found to be significant (P < 0.001) [Table 1]. Similarly, analysis of the duration of the disease and the level of UA estimated at different periods of suffering showed that there was significant lowering of UA level with increasing duration of the disease [Table 2] and [Table 3]. Again, analysis of age of patients with UA levels elicited no difference (P = 0.3), but analysis of duration of disease and UA levels elicited significant difference (P < 0.001) [Table 4].
Table 1: Paired sample test of uric acid (UA) levels of patients' and controls' serum explaining the significance in difference

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Table 2: Paired sample test table showing correlation between duration of disease and serum uric acid (UA) levels

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Table 3: One-way ANOVA table showing correlation between duration of disease and serum UA levels

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Table 4: Correlations table showing correlation between duration of disease and serum UA levels

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Mean serum UA levels in patients and in controls were 3.60 and 3.94 mg/dl, respectively and the difference between the mean of the two groups was 0.34 mg/dl. This difference is highly significant.

The comparison of paired data of duration of LP and serum UA level for each patient shows significant decrease (difference) in UA levels with increasing duration of the disease.

One-way analysis of variance (ANOVA) table showing correlation between duration of disease and serum UA levels, showing similar change as in [Table 2].

Correlations table showing correlation between duration of disease and serum uric acid (UA) levels

This shows that there is much less correlation between age and UA levels (correlation coeffiecient −0.07); whereas, there is high correlation between UA levels and duration of the disease (coefficient −0.525).


   Discussion Top


UA being a powerful free radical scavenger as well as being able to act as a chelator of metal ions such as iron and copper by converting them to poorly reactive forms which are unable to catalyze free-radical reactions, is one of the important antioxidants in human biological fluids. [16],[17] Though the primary defense mechanisms against oxidative stress include antioxidants like some enzymes, vitamins, etc., it is thought that UA contributes to >50% of the antioxidant capacity of blood. [9],[10],[16],[18] UA prevents peroxynitrite formation by neutralizing cellular superoxide and preventing its (superoxide) reaction with nitric oxide. [19] It is a scavenger of free radicals, such as NO 2 , which is formed from the breakdown of peroxynitrite, [20] and may assist in the removal of superoxide by preventing the degradation of superoxide dismutase, the enzyme that is responsible for clearing superoxide from the cell. UA is also very effective at preventing peroxynitrite from nitrating the tyrosine residues of proteins; thereby, preventing the inactivation of cellular enzymes and modification of the cytoskeleton. [19] Some studies have revealed the antioxidant role of UA in other conditions. [21],[22]

In our study, serum UA levels were significantly decreased in patients with respect to controls [Table 1]. Mean serum UA levels in patients and controls were 3.6 and 3.94 mg/dl, respectively. The difference of means is 0.34 mg/dl. These results point towards a pathological relation of decreased UA levels with LP and its duration, which is further explained in [Table 2] and [Table 4].

(Paired sample test, as shown in [Table 2], is applied to paired data of independent observations. Here duration of LP disease and serum UA are paired data. It was analyzed to study the role of duration of the disease on oxidative defense systems of the cases. If the two-tailed significance is more than 0.05, the difference observed has no significance, because such a difference can occur commonly due to chance. Thus, the factor under study may have no influence on the variable. But if the two-tailed significance is less than 0.05, the difference observed is significant, because such a difference is less likely to occur by chance. Influence of the factor to which the sample is exposed may be accepted as an alternative to null hypothesis). Moreover, [Table 2] and [Table 3] show significant correlation between the serum UA levels and duration of disease. A significant decrease of UA levels was also observed in study of LP patients from Italy. [14] On the contrary, a report from Israel found higher prevalence of hyperuricemia than that of general population, though LP was not considered as a cause of overproduction of uric acid. [23]

Lastly, [Table 4] shows that serum UA levels were decreased with increasing duration of disease, particularly when the duration exceeded 6 months. (When associated variables of serum UA, i.e., age and duration of disease, are normally distributed, the correlation coefficient calculated is called Pearson's correlation coefficient though it is meant for larger sample size. From the table above it is evident that 'r' between UA and duration is −0.525; whereas, it is only −0.07 between UA and age.) So, duration of the disease may have greater impact on oxidative damage in comparison to age of the patients.

Thus, our results point towards a pathological relation of decreased UA levels with LP and its duration.

Indirect evidence of increased oxidative stress in LP is strengthened from the fact that saliva UA is decreased in oral LP patients. [24] Also, vitamin E and C levels are decreased in LP, and supplementation of these may have a role in the management of LP. [25]

As free radical-induced damage is thought to be one of the important factors in the etiopathogenesis of LP, in our opinion, treatment guidelines should include optimal strengthening of antioxidant defense. Serum UA is a potent free radical scavenger, and it has been demonstrated, using two methodologically distinct assays, that systemic administration of UA increases ex vivo serum free radical scavenging capacity to a significantly greater extent than vitamin C, another important aqueous physiologic antioxidant. [26] Also, antioxidant administration increases UA levels. [27]

This study has limitations that must be considered. To assess UA, uricase method was used. UA can be estimated by various methods, but the present method was employed as it is the most commonly used, time tested and standard method. Also, number of patients in the study groups was not large. Thus, care must be taken in extrapolating the present findings to other populations. Patients were taking a number of medications (other than steroids, immunosuppressive drugs, and NSAIDs) to control LP. However, these treatments are characteristic of patients with LP and do not affect serum UA levels. Despite these limitations, we believe that our study points towards using it as an important, promising antioxidant marker for LP. As our findings point to a decrease in the antioxidant UA, the problem of oxidative stress in LP should also be further investigated in a larger number of patients, and other markers of oxidative stress and antioxidants should be assessed.

The results of our study suggest that LP may be related to depletion of UA levels in serum. UA may be considered as a useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring.

 
   References Top

1.Gupta SB, Chaudhari ND, Gupta A, Talanikar HV. Lichen planus: An update. Int J Pharm Biomed Sci 2013;4:59-65.  Back to cited text no. 1
    
2.Anderson BE. Lichen planus. The netter collection of medical illustrations: Integumentary system. 1 st ed. Australia: Saunders; 2012. p. 114.  Back to cited text no. 2
    
3.Lademann J, Schanzer S, Meinke M, Sterry W, Darvin ME. Interaction between Carotenoids and Free Radicals in Human Skin. Skin Pharmacol Physiol 2011;24:238-44.  Back to cited text no. 3
    
4.Sander CS, Ali I, Dean D, Thiele JJ, Wojanarowaka F. Oxidative stress is implicated in the pathogenesis of lichen sclerosis. Br J Dermatol 2004;151:627-35.  Back to cited text no. 4
    
5.Sezer E, Ozugurlu F, Ozyurt H, Sahin S, Etikan I. Lipid peroxidation and antioxidant status in lichen planus. Clin Exp Dermatol 2007;32:430-4.  Back to cited text no. 5
    
6.Fuchs J, Zollner TM, Kaufmann R, Podda M. Redox modulated pathways in inflammatory skin diseases. Free Radic Biol Med 2001;30:337-53.  Back to cited text no. 6
    
7.Shakibaei M, Schulze-Tanzil G, Takada Y, Aggarwal BB. Redox regulation of apoptosis by members of the TNF Superfamily. Antioxid Redox Signal 2005;7:482-96.  Back to cited text no. 7
    
8.Hendel A, Hiebert PR, Boivin WA, Williams SJ, Granville DJ. Granzymes in age-related cardiovascular and pulmonary diseases. Cell Death Differ 2010;17:596-606.  Back to cited text no. 8
    
9.Venkateshappa C, Harish G, Mahadevan A, Srinivas Bharath MM, Shankar SK. Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: Implications for Neurodegeneration in Alzheimer's Disease. Neurochem Res 2012;37:1601-14.  Back to cited text no. 9
    
10.Frei B, Birlouez-Aragon I, Lykkesfeldt J. Authors' Perspective: What is the optimum intake of vitamin C in humans? Crit Rev Food Sci Nutr 2012;52:815-29.  Back to cited text no. 10
    
11.Yasuda D, Takahashi K, Kakinoki T, Tanaka Y, Ohe T, Nakamura S, et al. Synthesis, radical scavenging activity and structure-activity relationship of uric acid analogs. Med Chem Commun 2013;4:527-9.  Back to cited text no. 11
    
12.Eberhardt MK. Reactive oxygen metabolites. In: Chemistry and Medical Consequences. 1 st ed. Florida: CRC Press; 2000. p. 261-302.  Back to cited text no. 12
    
13.Azzam H, Bergman R, Friedman-Birnbaum R. Lichen planus associated with metformin therapy. Dermatology 1997;194:376.  Back to cited text no. 13
    
14.Battino M, Greabu M, Totan A, Bullon P, Bucur A, Tovaru S, et al. Oxidative stress markers in oral lichen planus. Biofactors 2008;33:301-10.  Back to cited text no. 14
    
15.Trivedi RC, Rebar L, Berka E, Strong L. New enzymatic method for serum uric acid at 500 nm. Clin Chem 1978;24:1908-11.  Back to cited text no. 15
    
16.Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA. Uric acid and oxidative stress. Curr Pharm Des 2005;11:4145-51.  Back to cited text no. 16
    
17.Pasalic D, Marinkovic N, Feher-Turkovic L. Uric acid as one of the important factors in multifactorial disorders-facts and controversies. Biochem Med (Zagreb) 2012;22:63-75.  Back to cited text no. 17
    
18.Parmar MS. Uric acid and cardiovascular risk. N Engl J Med 2009;360:539.  Back to cited text no. 18
    
19.Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007;87:315-424.  Back to cited text no. 19
    
20.Kutzing MK, Firestein BL. Altered uric acid levels and disease states. J Pharmacol Exp Ther 2008;324:1-7.  Back to cited text no. 20
    
21.Waring WS, McKnight JA, Webb DJ, Maxwell SR. Uric acid restores endothelial function in patients with type 1 diabetes and regular smokers. Diabetes 2006;55:3127-32.  Back to cited text no. 21
    
22.Hooper DC, Scott GS, Zborek A, Mikheeva T, Kean RB, Koprowski H, et al. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. FASEB 2000;14:691-8.  Back to cited text no. 22
    
23.Shai A, Halevy S. Lichen planus and lichen planus-like eruptions: Pathogenesis and associated diseases. Int J Dermatol 1992;31:379-84.  Back to cited text no. 23
    
24.Miricescu D, Greabu M, Totan A, Didilescu A, Rãdulescu R. The antioxidant potential of saliva: Clinical significance in oral diseases. Ther Pharmacol Clin Toxicol 2011;15:139-43.  Back to cited text no. 24
    
25.Rai B, Khar S, Jain R, Anand SC. Salivary vitamin E and C in lichen planus. Gomal J Med Sci 2008;6:91-2.  Back to cited text no. 25
    
26.Waring WS, Webb DJ, Maxwell SR. Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol 2001;38:365-71.  Back to cited text no. 26
    
27.Mathur A, Mathur L, Manohar B, Mathur H, Shankarapillai R, Shetty N, et al. Antioxidant therapy as monotherapy or as an adjunct to treatment of periodontal diseases. J Indian Soc Periodontol 2013;17:21-4.  Back to cited text no. 27
[PUBMED]  Medknow Journal  

What is new?
LP is associated with decrease of UA levels in serum suggesting increased oxidative stress, which may be addressed in treatment schedule.



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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