A Clinico-epidemiological study of patients with lichen planus and associated metabolic complications at a tertiary care centre

Background: An association between lichen planus and systemic disorders such as diabetes mellitus, dyslipidemia and metabolic syndrome has been reported. Aim: To assess the clinico-epidemiological profile of lichen planus, evaluate prevalence of underlying metabolic complications and compare the clinical profile of patients with and without metabolic syndrome. Material and methods: All the patients with lichen planus attending dermatology out patient department of a tertiary care centre in South Rajasthan over a period of one year were studied. Patients with lichenoid drug eruptions and those receiving systemic treatment for lichen planus were excluded from the study. Statistical analysis was done using the chi – square test. A p value < 0.05 was considered significant. Results: A total of 270 patients of lichen planus were enrolled. Male to female ratio was found to be 0.76: 1. Maximum (64; 23.7%) patients belonged to the age group of 31 – 40 years. Classical morphology was the most common (128; 47.4%) cutaneous pattern. Mucosal and nail involvement was seen in 80 (29.6%) and 87 (32.2%) patients respectively. Koebner phenomenon was present in 57 (21.1%) patients. The investigations were completed by 175 (64.8%) patients. Diabetes mellitus and hypertension were found in 12.6% (22/175) and 14.3% (25/175) patients respectively. The diagnostic criteria for dyslipidemia and metabolic syndrome were fulfilled by 39.4% (69/175) and 27.4% (48/175) patients respectively. Majority (81.2%) of the patients with metabolic syndrome belonged to age group 40 years and above, and oral and nail involvement was found to be more common in them. It is recommended that these patients should be screened for complications like diabetes, hypertension, dyslipidemia and metabolic syndrome. Conclusion: Significant numbers of lichen planus patients were found to have dyslipidemia and metabolic syndrome. Patients aged 40 years and above, with oral and nail involvement have higher propensity to be associated with metabolic syndrome and therefore such patients should be screened for metabolic complications. Timely screening and early intervention may reduce the risk of related morbidity and mortality. Limitations: Lack of control group is the drawback of our study. Age and sex matched comparative studies are required for confirmation of the results.

inflammation seen in LP may play a role in the pathogenesis of dyslipidemia and MS.
This study was carried out to determine the clinicoepidemiological profile of LP, to evaluate the prevalence of underlying metabolic complications, and compare the clinical profile of these patients with and without MS.

MATERIALS AND METHODS
This was a descriptive study with cross sectional analysis of patients of LP with and without MS. Approval for study was obtained from the Institutional ethics committee. Both male and female patients of all age groups presenting with clinical features of LP at the dermatology out patient department (OPD) over a period of one year were enrolled. Patients with lichenoid drug eruptions and those receiving systemic treatment for LP were excluded from the study.
After obtaining an informed written consent, a detailed history taking, cutaneous and mucosal examination and relevant investigations were done. Patients were evaluated for the presence of DM, hypertension (HT), obesity, dyslipidemia and MS.
Diabetes mellitus and HT were diagnosed as per the American Diabetes Association guidelines (ADA) [9] and the seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (JNC VII) criteria [10] respectively. Body mass index (BMI) was calculated as weight (in kg)/ height² (in m²) and values were interpreted as per World Health Organization (WHO) [11] guidelines ( Table 1).
The presence of dyslipidemia was defined as per National Cholesterol Education Program Adult Treatment Plan (NCEP ATP) III criteria [12], if one of the following parameters were present: • Total cholesterol (TC)>200 mg/dl • Triglycerides (TG) >150mg/dl • Low density lipoprotein cholesterol (LDL-C) > 130 mg/dl • Patient on antihyperlipidemic drugs Metabolic syndrome was diagnosed using NCEP ATP III criteria [13]. Diagnosis was made when three or more criteria were present, including: • Waist circumference of more than 102 cm in men or more than 88 cm in women • Blood pressure level > 130 / 85 mmHg or use of antihypertensive medication • Fasting plasma glucose (FPG) levels > 100 mg/dl or on drug treatment for elevated glucose • Fasting triglyceride (TG) levels > 150 mg/dl or on drug treatment for elevated TG • Fasting high density lipoprotein cholesterol (HDL-C) levels < 40 mg/dl in men or < 50 mg/ dl in women or on drug treatment for reduced HDL-C.
Based on the fulfillment of these criteria, the patients were divided into two groups -patients with MS and patients without MS. The two groups were compared with each other with respect to age and sex distribution, duration, initial site of onset, associated symptoms, clinical variants, mucosal and nail affection. Chi -square test was used to carry out statistical analysis. p value < 0.05 was considered statistically significant.

RESULTS
A total of 270 patients of LP were enrolled and their clinico-epidemiological profile was studied. Of these, 175 (64.8%) patients returned with investigation reports to get evaluated for metabolic complications. A prevalence of 0.34% was found in our OPD during the study period. Female preponderance was seen with male: female ratio being 0  Comparison of clinico-epidemiological profile of patients with and without MS revealed that maximum (81.2%) number of patients fulfilling the criteria of MS were in age group 40 years and more. The patients with oral mucosal and nail involvement were more commonly associated with MS. However, statistically significant difference was not noticed in patients with and without MS with respect to the duration, initial site, symptomatology and types of cutaneous variants (Table 4).

DISCUSSION
Lichen planus mostly affects the middle-aged adults. Maximum number of patients belonged to the age group of 31-40 years as observed in other reports [14][15][16][17]. Female predominance was recorded; M:F ratio being 0.76:1. This is in accordance with some other studies [17][18][19][20]. Extremities (64.8%) were the most common initial site of affection, as reported in some studies [14,21]. Compared to upper extremity, lower extremity (98/270; 36.3%) was more commonly involved as reported by others [16][17][18]. Like in most other studies [14][15][16][17][18][19][20]22], classical LP was the most common variant. However, Anbar et al [21], in a study from tropical area of Egypt, found actinic LP as the most common variant. Nail affection has been reported to occur with variable frequency ranging from 6.4% to 18% [14,16,18,21]. A relatively higher occurence (32.2%) of nail involvement was seen in our study. Koebner phenomenon which presents as development of similar pathologic lesions along the line of trauma, is frequently seen in LP. It was present in 21.1% (57/270) patients, compared to 37.5% in a study by Khondker et al [22]. Lichen planus is an immune-mediated disease involving Langerhans cells and T lymphocytes. The stimulated lymphocytic infiltrate is epidermotropic and attacks keratinocytes, resulting in generation of reactive oxygen species and release of cytokines such as TNF-α, IL-6, IL-10, and IL-4. This could explain the association of LP with dyslipidemia, as chronic inflammation has been suggested as a component of the metabolic syndrome [6]. Dreiher et al [5] showed the connection between dyslipidaemia and LP in a large number of study participants. Santiago et al [6] analysed various parameters of metabolic syndrome and found a similar association with dyslipidemia. But no significant differences were observed in glucose levels, blood pressure and abdominal obesity in their study. However Saleh et al [7] showed that patients with lichen planus had higher markers of both metabolic and cardiovascular risk factors. A recent Indian study by Panchal et al [8], also demonstrated dyslipidemia in LP compared to controls. As per NCEP ATP III criteria for dyslipidemia, 39.4% (69/175) patients, comprising of  [24] reported a prevelance of 6%.
Increased oxidative stress has also found to be associated with LP [8,26]. As uric acid is one of the important antioxidants in plasma, level of serum uric acid is expected to be reduced. A few studies [26,27]  have reported significantly decreased levels of serum uric acid. However, mean serum uric acid levels were within normal range in our patients.
On comparing the profile of patients of LP with or without MS, it was observed that majority of the patients with MS belonged to the age groups above 40 years. This observation was highly significant statistically. Oral mucosal and nail involvement was more common in patients with MS than patients without MS and this too was statistically significant.
Thus, patients of LP aged 40 years and above, with oral mucosal and nail affection should be evaluated for complications like diabetes, hypertension, dyslipidemia and metabolic syndr ome.
As significant numbers of patients were found to have dyslipidemia and metabolic syndrome in our study, a routine screening and early intervention may reduce the risk of related morbidity and mortality. Lack of control group is the major drawback of the study. Further age and sex matched case-control studies are required to confirm the association of LP with dyslipidemia and MS.

Statement of Human and Animal Rights
All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 2008 revision of the Declaration of Helsinki of 1975.

Statement of Informed Consent
Informed consent for participation in this study was obtained from all patients