Eruptive Lichen Planus, a Marker of Metabolic Syndrome.

BACKGROUND: Chronic inflammatory diseases take an important place in dermatology and their effects range from mild itching to grave metabolic complications. In psoriasis, association with metabolic syndrome (MS) has been proved in many studies. Chronic inflammation is a trigger of MS, and in turn, the components of MS, namely obesity and dyslipidemia, promote a pro-inflammatory milieu. Thus, chronic inflammation causes MS and vice versa. Hence, the study focuses on association of MS with lichen planus (LP), another chronic inflammatory disease. AIM: The aim of this study is to find the association of MS with all variants of LP.
MATERIALS AND METHODS: An observational study for MS in all patients with LP who attended skin outpatient department (OPD) for 6 months from February 2016. International Diabetes Federation criteria 2005 were used. The confounding variables of MS such as smoking, alcohol, and physical activity were assessed for its significance in the association of LP with MS.
RESULTS: Out of 113 cases, 21 cases were found to be associated with MS. Among them, 8 cases (38.09%) were of eruptive LP, which showed significant association with MS when compared to other variants. MS cases were significantly high in females and in the age group of 41-50 (57.1%). Due to unequal distribution of smoking and alcohol habits, they were not taken into account for analysis. Physical activity had no significant association with MS in our study population. Waist circumference (WC) being the mandatory criterion in all variants associated with MS, dyslipidemia was the next frequently encountered criteria except in eruptive LP. High BP was less commonly noted criteria.
CONCLUSION: Eruptive LP showed significant association with MS. Further studies with large sample size in each variant and control group are needed to confirm it which are the limitations in our study.

Introduction

Lichen planus (LP) is a papulosquamous disorder involving skin and mucous membranes.[1] Main pathogenesis is keratinocyte apoptosis by CD8 cell augmented by CD4 cell Th1 cytokines IL-2, 4, 6, 10, and TNF-α.[23] These cytokines also play causal role in insulin resistance and obesity, components of metabolic syndrome (MS). Obesity causes adipocyte hypertrophy and on rupture releases pro-inflammatory cytokines TNF-α, IL-6, and TGF-β.[4] Thus, there exists association of MS with inflammation. Baykal et al. showed association of MS with oral LP.[5] The aim of our study is to find the association of MS with cutaneous variants of LP.

Materials and Methods

The study was conducted from February 2016 to July 2016. Newly diagnosed patients of LP with classical clinical features attending the OPD during this period were included. In case of diagnostic dilemma, biopsy was done to confirm the diagnosis.

Exclusion criteria

LP patients of age group less than 10 years, patients on treatment for diabetes mellitus and hypertension, old cases of LP on treatment, and those who did not give consent were excluded.

International Diabetes Federation – 2005 criteria

International Diabetes Federation (IDF) criteria 2005 for diagnosis of metabolic syndrome (MS) were used in the study.[6] Patients with waist circumference (WC) >90 cm for male and >80 cm for female were screened for other features of MS. As per the IDF criteria 2005, two of the adult criteria were used for adolescents aged 16 years, while a modified version of these criteria was applied to those aged 10–16 years (use 90th percentile cutoff point for WC).[7] Country/Ethnic group values for WC were included in this criteria.

IDF criteria for MS in children older than 16 years and adult

Central obesity [(WC) >80 cm for women, >90 cm for men].

Plus any two of the following factors:

Triglyceride (TGL) >150 mg/dl

High-density lipoprotein (HDL) <40 mg/dl in male, <50 mg/dl in female

Fasting blood sugar (FBS) >100 mg/dl

Blood pressure (BP) >130/85 mmHg.

IDF criteria for MS in children aged 10–16 years

Central obesity (WC >90th percentile).

Plus any two or more of the following features:

FBS >100 mg/dl

TGL >150 mg/dl

HDL <40 mg/dl in male, <50 mg/dl in female

BP >130/85.

A detailed clinical history, which included the duration, drug intake, family history, and personal history (smoking, alcohol, and occupation), was elicited. A complete general, systemic, and dermatological examination were made. Their WC was measured in a horizontal plane, midway between the inferior margin of the ribs and the superior border of the iliac crest and BP was measured. The morphology of the skin lesions, its distribution, and involvement of hair, nail, palms, soles, and mucosa were noted. Laboratory investigations like FBS, fasting TGL, and HDL were done. A total of 113 cases of LP were included in the study. Among them, four clinically doubtful cases were proved histopathologically, and in one case of follicular LP in a 53-year-old female, dermascopy findings supplemented for the diagnosis.

The data were compiled and the statistical analysis was carried out with SPSS 16 and Sigma Stat 3.5 version. One way ANOVA, Chi-square test were used for detection of significance. P<0.05 was considered as significant.

Results

Out of the total of 113 cases, classical LP (63.7%) was the commonest type followed by hypertrophic LP, eruptive LP, oral LP, linear LP, follicular LP, lichen planus pigmentosus (LPP), and annular LP in the decreasing order of frequency. Majority of the patients were in the fifth decade (41–50 years). Females (62%) were more commonly affected when compared to males (38%) in all age groups. Hypertrophic LP and linear LP were more common in males. In all other variants, female preponderance was seen. Out of 113, 21 cases were found to be associated with MS [Table 1]. In consideration to the confounding variables, all females in our study had no smoking and alcohol habit, and in a total of 43 males, 14 and 7 had history of smoking and alcohol, respectively. As these variables were not equal in distribution, they were not taken into account for the analysis of association between MS and LP [Table 2]. Other confounding variable physical activity was analyzed and found no statistically significant association between cases with MS and physical activity in our study [Table 3].

Table 1

Demographic characteristics and clinical types

Type of LP	Total	With MS	10-20				21-30				31-40				41-50				51-60				61-70
			Total		With MS		Total		With MS		Total		With MS		Total		With MS		Total		With MS		Total		With MS
			M	F	M	F	M	F	M	F	M	F	M	F	M	F	M	F	M	F	M	F	M	F	M	F
C	72	10	6	14	0	1	4	7	0	0	3	8	0	1	7	11	2	5	5	4	0	1	2	1	0	0
H	14	1	1	0	0	0	3	2	0	0	4	1	0	0	1	2	0	1	0	0	0	0	0	0	0	0
E	13	8	0	2	0	0	0	2	0	0	1	2	1	1	0	4	0	4	1	1	1	1	0	0	0	0
M	5	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	0	2	0	1
L	3	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
F	3	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
LPP	2	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	1	0	0	0	0
A	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Total	113	21	8	16	0	1	7	12	0	0	10	12	1	2	9	18	2	10	7	9	1	3	2	3	0	1

C: Classic, H: Hypertrophic, E: Eruptive, M: Mucosal, L: Linear, F: Follicular, LPP: Lichen planus pigmentosus, A: Annular

Table 2

Number of cases with smoking and alcohol in each age group

Sex	10-20		21-30		31-40		41-50		51-60		61-70
	M	F	M	F	M	F	M	F	M	F	M	F
Smoking	Nil	Nil	2	Nil	5	Nil	2	Nil	4	Nil	1	Nil
Alcohol	Nil	Nil	Nil	Nil	3	Nil	3	Nil	1	Nil	Nil	Nil
Both	Nil	Nil	Nil	Nil	2	Nil	2	Nil	Nil	Nil	Nil	Nil

Table 3

Association of MS and Non MS cases with physical activity

Activity	MS	Non-MS	Total	P
Moderate	15	80	95	0.07
Vigorous	6	11	17

Discussion

LP is a chronic inflammatory disease involving skin, mucous membrane, nail, and hair follicle. Th1 cytokines IL-2, 4, 6, 10, and TNF-α involved in the pathogenesis of LP also play a causal role in risk factors of MS including central obesity, dyslipidemia, hypertension, and insulin resistance. These risk factors are the strong predictor of diabetes, cardiovascular diseases, and stroke.[89] Few studies proved the association of oral LP with MS and also with its components, namely, dyslipidemia.[510]

This was an observational study in which a total of 113 newly diagnosed cases of all variants of LP presented in the age group of 10 and above were included.

Classical LP was the commonest type seen which was consistent with the study conducted by Parihar et al.,[11] followed by hypertrophic LP, eruptive LP, oral LP, linear LP, follicular LP, LPP, and annular LP in decreasing order of frequency.

Majority of the patients affected were in the fifth decade (24.8%), whereas in the study conducted by Omal et al.,[12] majority of the patients were in third and sixth decade. Females (62%) were predominantly affected when compared to males (38%) similar to the study conducted by Parihar et al.[11]

In 113 patients, 21 (18.6%) cases had MS. In a total of 21 cases of MS, 17 (81%) were females and 4 (19%) were males. Therefore, MS was significantly higher in females compared to males (P<0.001).

Prevalence of increased WC was high among LP patients when compared to other MS criteria similar to the study done by Kurian et al.[13] Regarding distribution of MS cases in different age groups, more number of cases [12 (57.1%)] were found to be in the age group of 41–50. Thus, association of LP with MS in the fifth decade was significantly (P=0.007) high, whereas the study conducted by Prasad et al. showed higher prevalence of MS in the seventh decade.[14]

Among the 21 cases associated with MS, 10 cases were of classical LP, 8 cases were of eruptive type, and the remaining 3 cases were one each of hypertrophic LP, mucosal LP, and LPP.

In a total of 13 cases of eruptive LP, 8 cases were found to be associated with MS. Among them, four belonged to the age group of 41–50 and two were in the age group of 31–40 and 51–60. On comparing other variants, eruptive LP had significant association with MS (P<0.001).

The confounding variables, smoking and alcohol with its unequal distribution, are not taken into account for the analysis. According to their occupation, physical activity was classified[15] among cases associated with MS and non-MS in different age groups. There was no statistically significant association between physical activity and MS cases and with variants of LP (P= 0.07 and 0.412, respectively) [Tables 3 and 4]. Thus, confounding variables like smoking, alcohol, and physical activity had no significant association with MS cases in our study.

Table 4

Association of variants of LP with physical activity

Activity	Eruptive LP	Other variants of LP	Total	P
Moderate	10 (10.4%)	86 (89.5%)	96	0.412
Vigorous	3 (17.6%)	14 (82.4%)	17

With WC as a mandatory criterion in MS cases, in eruptive LP, increased FBS was frequently found to be associated criterion. There existed statistically significant association between WC and FBS in eruptive LP associated with MS (P=0.032) when compared to cases not associated with MS.

In a case-control study by Baykal et al., prevalence of MS was higher in mucosal LP than without mucosal involvement, and in a study by Krishnamurthy et al.,[10] dyslipidemia was significantly high in oral LP patients, whereas in our study in a total of five cases of mucosal LP, only one case in the age group of 61–70 years was found to be associated with MS. Hence, more numbers of oral LP cases are to be studied to find any association.

Conclusion

Eruptive LP was found to be significantly associated with MS when compared to other variants. Females in the age group of 41–50 were more commonly affected. Physical activity had no significant association with eruptive LP in our study. With central obesity as a common factor, insulin resistance, one of the components of MS, showed significant association in these individuals. Thus, obesity, a pro-inflammatory condition, leads to metabolic changes which may play a part in pathogenesis of eruptive LP. Hence, eruptive LP may be considered as a marker of MS, to be proved with large sample size in each variant and a control group, which are the limitations in our study.

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

Nil.

Conflicts of interest

There are no conflicts of interest.