CLINICAL RESEARCH STUDY

Cardiovascular Risk Factors in Patients with Lichen Planus

Salvador Arias-Santiago, PhD,
a,b
Agustn Buenda-Eisman, PhD,
b
Jos Aneiros-Fernndez, MD,
c
Mara Sierra Girn-Prieto, MD,
d
Mara Teresa Gutirrez-Salmern, PhD,
a,b
Valentn Garca Mellado, PhD,
d
Ramn Naranjo-Sintes, PhD
a,b
a
Department of Dermatology, San Cecilio University Hospital, Granada, Spain;
b
Department of Dermatology and
c
Department of
Histopathology, School of Medicine, Granada University, Spain;
d
Department of Dermatology, Virgen de las Nieves University
Hospital, Granada, Spain.
ABSTRACT
BACKGROUND: Chronic inammation was found to play an important role in the development of cardio-
vascular risk factors. Recently a case-control study found that lichen planus was associated with dyslip-
idemia in a large series of patients. However, no data were presented about lipid values, glucose levels, or
blood pressure.
OBJECTIVE: The objective of this case-control study was to evaluate cardiovascular risk factors included
in Adult Treatment Panel III criteria for metabolic syndrome in men and women with lichen planus and
in healthy controls.
PATIENTS AND METHODS: This case-control study included 200 patients, 100 with lichen planus (50 men
and 50 women) and 100 controls consecutively admitted to the outpatient clinic in Dermatology depart-
ments in Granada, Spain.
RESULTS: Analysis of metabolic syndrome parameters revealed a higher signicant prevalence of dyslip-
idemia in patients with lichen planus. No signicant differences were observed in glucose levels, abdom-
inal obesity, or blood pressure. Elevated levels of C-reactive protein, erythrocyte sedimentation rate, and
brinogen were noted in patients with lichen planus. Adjusted odds ratio for dyslipidemia in patients with
lichen planus was 2.85 (95% condence interval, 1.33-5.09; P.001).
CONCLUSION: Chronic inammation in patients with lichen planus may explain the association with
dyslipidemia. Lipid levels screening in men or women with lichen planus may be useful to detect
individuals at risk and start preventive treatment against the development of cardiovascular disease.
2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 543-548
KEYWORDS: Cardiovascular risk factors; Comorbidity; Dyslipidemia; Lichen planus; Metabolic syndrome
Lichen planus is an idiopathic inammatory disease that af-
fects the skin and the mucous membranes. Although the etiol-
ogy and pathogenesis are not fully understood, it is believed
that lichen planus represents a T-cell-mediated inammatory
disorder. Inammation produces disturbances of lipid metab-
olism such as serum increases of triglycerides or decreases of
high-density lipoprotein cholesterol. These lipid disturbances
linked to chronic inammation participate in the increase of
cardiovascular risk associated with dyslipidemia.
Some skin diseases such as androgenetic alopecia
1-4
and
psoriasis
5-7
have been associated with cardiovascular risk fac-
tors; the proinammatory situation that underlies alopecia and
psoriasis may explain this association. Recently, a case-control
study found that lichen planus was associated with dyslipide-
mia in a large series of patients;
8
however, no data were
presented about lipid values, glucose levels, abdominal obe-
sity, or blood pressure in patient or controls. Also, authors did
not differentiate between lichen planus and lichenoid drug
reactions that in some cases are related to several drugs, in-
cluding HMG-CoA reductase inhibitors (uvastatin and lova-
statin), which are used to treat dyslipidemia,
9,10
or other drugs
prescribed for hypertension.
11
In addition, some drugs used to
Funding: None.
Conict of Interest: None.
Authorship: All authors participated sufciently to take public respon-
sibility for appropriate portions of the work, had access to the data and a
role in writing the manuscript, and approved the submission of the man-
uscript.
Requests for reprints should be addressed to Salvador Arias-Santiago,
PhD, San Cecilio University Hospital, Av Dr. Oloriz 16, Granada 18012,
Spain.
E-mail address: salvadorarias@hotmail.es
0002-9343/$ -see front matter 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2010.12.025
treat lichen planus, such as retinoic acid, methotrexate, or
systemic corticosteroids, can elevate lipid levels.
Psoriasis, which is a chronic inammatory skin disease
like lichen planus, is associated with an increased risk for
cardiovascular risk factors
5-7
including hypertension, diabe-
tes, obesity, metabolic syndrome,
and dyslipidemia. Several cyto-
kines (tumor necrosis factor
[TNF -], interleukin [IL]-2,
IL-6) have been implicated in the
increased lipid levels in these pa-
tients. Also, TNF- and interferon-
have been shown to be present at
high concentrations in cutaneous le-
sions of lichen planus.
Knowledge of the distribution
of cardiovascular risk factors in
patients with lichen planus would
allow appropriate primary and
secondary preventive measures to
be applied. The objective of this
retrospective case-control study
was to analyze the presence of the
cardiovascular risk factors in-
cluded in the Adult Treatment
Plan (ATP)-III metabolic syndrome criteria in males and
females with lichen planus and in healthy controls, exclud-
ing lichen planus-like eruption and systemic treatment for
lichen planus.
SUBJECTS AND METHODS
Study Subjects
This case-control study included 200 patients consecutively
admitted to the outpatient clinic (Dermatology departments of
San Cecilio and Virgen de las Nieves Hospitals, Granada,
Spain), 100 with lichen planus (50 women and 50 men) and
100 controls (50 women and 50 men) with other skin diseases
other than lichen planus (mainly nevi, seborrheic keratosis,
actinic keratosis, verruca, or basal cell carcinoma). Patients
with lichen planus are likely to be representative of patients
with lichen planus who present at our hospitals. Diagnosis of
lichen planus was based on clinical ndings conrmed with
biopsy. Inclusion criteria were: men and women 18 years
old, presence of lichen planus affecting the skin or mucosa, and
signing of informed consent to study participation. Exclusion
criteria were: lichenoid drug eruption and receiving treatment
for lichen planus such as systemic corticosteroids, retinoic
acid, or methotrexate.
Clinical Parameters and Lipids Levels
Measurements
The weight, height, and abdominal circumference of sub-
jects were measured, and their body mass index (BMI,
kg/m
2
) was calculated. Systolic and diastolic blood pressure
was measured after a 5-minute rest and again 10 minutes
later, recording the mean value. Serum total cholesterol,
triglycerides, high-density lipoprotein cholesterol (HDL-C),
low-density lipoprotein cholesterol (LDL-C), glucose lev-
els, brinogen, erythrocyte sedimentation rate (ESR), and
C-reactive protein (CRP) levels were studied in samples
drawn between 8 and 9 AM after a
12-hour fasting period.
In addition, cholesterol total/
HDL-C and LDL-C/HDL-C were
calculated. These data were col-
lected before starting systemic treat-
ment for the disease to avoid dys-
lipidemia associated with treatment.
Data also were gathered on age, sex,
smoking, alcohol consumption, sed-
entarism, hypothyroidism, and per-
sonal or familial history of cardio-
vascular disease. Prevalence of
metabolic syndrome (MS) was cal-
culated according to ATP-III crite-
ria; MS was dened by the presence
of 3 of the following:
12
(abdominal
circumference 102 cm in males
and 88 cm in females; hypertri-
glyceridemia 150 mg/dL, HDL-C
40 mg/dL in males and 50 mg/dL in females, blood pres-
sure 130/85 mm Hg, or glucose levels 110 mg/dL).
The presence of dyslipidemia was dened if one of the
following parameters were present: triglycerides 150 mg/
dL, total cholesterol 200 mg/dL, LDL-C 130 mg/dL, or
the patient received treatment for dyslipidemia.
Statistical Analyses
The statistical analyses were performed with the SPSS/PC
software (Version 15.0 for Windows; SPSS Inc., Chicago,
Ill). Two-sample Students t test was used to compare mean
values of quantitative variables as the 2 samples were
obtained independently, the Shapiro-Wilk test to examine
the normality of their distribution, and the Levene test to
study the variance. Qualitative variables were analyzed
with chi-squared test. Correlations among variables were
studied by using the Pearson coefcient and exponential
regression technique. Binary logistic regression models
(Wald method), obtaining estimates adjusted odds ratios
(OR) and their 95% condence intervals were used to mea-
sure the association between lichen planus and dyslipidemia
in a multivariate analysis. P .05 was considered signi-
cant in all analyses.
RESULTS
A total of 200 patients were studied, 100 with lichen planus
and 100 controls. All of the patients had cutaneous involve-
ment, 69% (64% of men and 74% of women, P.38)
presented lesions in oral mucosa, 10% ungueal affection,
and 7% presented lichen planus pilaris. Twelve patients
were replaced because they had lichen planus-like reaction
CLINICAL SIGNIFICANCE
Cardiovascular risk factors have been
associated with some inammatory skin
diseases such as psoriasis.
Patients with lichen planus presented
higher lipid levels and acute phase re-
actants; chronic inammation may ex-
plain these ndings.
Cardiovascular risk factors screening in
patients with lichen planus may be use-
ful to detect individuals at risk and start
preventive treatment.
544 The American Journal of Medicine, Vol 124, No 6, June 2011
associated with drugs according to the method proposed by
Naranjo et al
13
and Edwards scale.
14
Hepatitis C virus
infection was detected in 12% of patients and all of them
had oral mucosa affection.
Mean age was 47.8 (SD 9.4) years for women with lichen
planus and 46.9 (SD 8.7) years for men with lichen planus
(P.62). Mean time since lichen planus onset was 1.8
years (SD 0.9) for women and 1.6 years (SD 1.1) for men
(P.32). Mean age, weight, height, BMI, tobacco, and
sedentarism are summarized in Table 1 for patients with
lichen planus and their respective controls. Men and women
with lichen planus differed in some of the above parameters,
as men with lichen planus showed higher height (172.8 vs
161.8 cm; P .0001) and weight (79.9 vs 67.8 kg;
P .0001) than women with lichen planus.
No signicant differences between groups were found in
tobacco or alcohol consumption, sedentarism, familial dys-
lipidemia, hypothyroidism, or personal or familial history of
cardiovascular disease. Also, no signicant differences were
found in antihypertensives (13% vs 16%; P.6), anticho-
lesterolemics (11% vs 7%; P.45), or oral antidiabetics
intake (9% vs 6%; P.59) between patients with lichen
planus and controls, respectively.
ATP-III criteria for MS were met by 27% of the patients
with lichen planus versus 20% of the controls (P.31). MS
was not signicantly more frequent (P.65) in the lichen
planus males (30%) than in lichen planus females (24%).
Differences in MS parameters between patients with lichen
planus and controls are listed in Table 2. Men with lichen
planus presented higher signicant abdominal perimeter
(P.0001), systolic and diastolic blood pressure (P
.0001), and lower signicant HDL-C values (P.0015)
than women with lichen planus. The MS criteria most fre-
quently recorded in males and females with lichen planus
were hypertriglyceridemia, abdominal obesity, and HDL-C
(Table 3).
LDL-C, total cholesterol, total cholesterol/HDL-C, and
LDL-C/HDL-C are listed in Table 4. Men and women with
lichen planus showed higher signicant mean values than
controls for all the parameters. Men with lichen planus
presented higher signicant total cholesterol/HDL (P.02)
and LDL-C/HDL-C (P.01) than women with lichen pla-
nus. There were no signicant differences in lipid levels
between patients with oral and cutaneous lichen planus and
patients with hepatitis C virus infection (P .05).
Table 1 Mean (SD) Age, Weight, Height, BMI, Mean Time with Lichen Planus, Tobacco (%), and Sedentarism (%) in Men and
Women with Lichen Planus and their Respective Controls
Patients (n 200)
P Value
Men (n 100)
P Value
Women (n 100)
P Value LP No LP LP No LP LP No LP
Age (years) 47.4 (9.0) 48.3 (7.0) .40 46.9 (8.7) 47.3 (8.9) .82 47.8 (9.4) 49.3 (4.1) .30
Weight (kg) 73.9 (12.7) 73.6 (15.1) .89 79.9 (11.5) 78.8 (12.7) .63 67.8 (10.9) 68.1 (15.7) .91
Height (cm) 167.4 (9.5) 168.9 (9.6) .30 172.8 (8.9) 174.9 (7.7) .20 161.8 (6.4) 162.5 (6.9) .62
BMI (Kg/m
2
) 26.4 (4.5) 25.8 (4.9) .32 26.8 (3.9) 25.8 (4.5) .23 26.1 (5.0) 25.7 (5.3) .77
Sedentarism (%) 56% (56) 53% (53) .77 54% (27) 50% (25) .84 58% (29) 56% (28) .9
Tobacco (%) 25% (25) 26% (26) .9 22% (11) 26% (13) .81 28% (14) 26% (13) .9
Mean time with
LP (years)
1.7 (1) 1.8 (0.9) 1.6 (1.1)
BMI body mass index; LP lichen planus.
Table 2 Analysis of the ATP-III Metabolic Syndrome Criteria (Mean, SD) in Men and Women with Lichen Planus and their
Respective Controls
Patients (n 200)
P
Value
Men (n 100)
P
Value
Women (n 100)
P
Value LP No LP LP No LP LP No LP
Abdominal perimeter (cm) 91.2 (9.0) 89.4 (9.5) .17 97.8 (8.9) 96.5 (9.2) .47 84.6 (9.4) 82.8 (10.1) .35
Triglycerides (mg/dL) 149.5 (86.6) 103.7 (81.2) .0002 159.4 (90.1) 115.3 (88.3) .01 139.5 (83.3) 92.2 (75.3) .003
HDL-C (mg/dL) 54.5 (12.9) 62.2 (14.4) .0001 50.3 (12.2) 56.9 (13.3) .01 58.8 (13.7) 67.5 (15.5) .002
Systolic BP (mm Hg) 117.8 (15.1) 114.6 (15.5) .14 124.5 (15.6) 121.3 (16.3) .31 111.2 (14.9) 107.9 (14.6) .26
Diastolic BP (mm Hg) 76.6 (8.5) 75.3 (8.3) .27 81.4 (9.2) 80.2 (8.8) .50 71.9 (8.1) 70.5 (7.7) .37
Glucose levels (mg/dL) 91.4 (36.1) 84.3 (33.2) .14 92.7 (36.6) 84.5 (35.3) .25 90.1 (35.7) 84.2 (31.2) .39
ATP-III Adult Treatment Plan III; LP lichen planus; HDL-C high-density lipoprotein cholesterol; BP blood pressure.
545 Arias-Santiago et al Risk Factors and Lichen Planus
Table 5 shows the mean brinogen, ESR, and CRP
values in the study groups. Elevated levels of CRP, ESR,
and brinogen were noted in patients with lichen planus. A
positive signicant correlation was found between triglyc-
eride levels and CRP (r 0.34, P.01).
The prevalence of dyslipidemia in patients with lichen
planus was 61%, and 33% for controls (P.0001; OR 3.17;
95% condent interval [CI], 1.77-5.66). Sixty-eight percent
(OR 3.46; 95% CI, 1.52-7.9; P.002) of men with lichen
planus and 54% (OR 3.01; 95% CI, 1.31-6.92; P.014) of
women with lichen planus presented dyslipidemia (P
.21). A multivariate binary regression model demonstrated
that lichen planus was associated with dyslipidemia, even
after controlling for confounders including age, sex, BMI,
glucose levels, and CRP (OR 2.85; 95% CI, 1.33-5.09;
P.001).
DISCUSSION
Prevalence of MS was similar in patients with lichen planus
and controls; however, this study found higher lipid levels
and acute phase reactants in patients with lichen planus.
Lipid parameters were different in men and women with
lichen planus. After controlling for sex, age, BMI, glucose
levels, and CRP, patients with lichen planus presented
higher risk for dyslipidemia.
The association of lichen planus with dyslipidemia has
been reported in a case report
15
and in a case-control study;
8
however, no data were specied about lipids levels or treat-
ments, and some drugs used for dyslipidemia are associated
with lichen planus-like eruption, and many drugs used for
the treatment of lichen planus (systemic corticosteroids,
retinoic acid, or methotrexate) also are associated with dys-
lipidemia. We have avoided this bias, excluding lichenoid
drug eruptions, and all the patients enrolled in the study had
not received systemic treatment for the disease. Also, lichen
planus has been associated with hyperglycemia and diabe-
tes,
16,17
but we have not found signicant differences in
glucose levels between patients and controls.
Inammation plays a very important role in the devel-
opment of dyslipidemia. Patients with chronic diseases (eg,
systemic lupus erythematous, rheumatoid arthritis) show
decreased levels of HDL-C and hypertriglyceridemia, with
a positive correlation with cytokine levels.
18
In the present
study, we found a positive signicant correlation between
triglyceride levels and CRP. Psoriasis, which is another
chronic inammatory skin disease, has been recently related
to dyslipidemia in the context of MS.
5-7
The more frequent
presence of chronic inammation parameters in patients
with psoriasis has been cited to explain the relationship with
cardiovascular disease. Several cytokines such as TNF-,
IL-2, and IL-6 have been implicated in the increased lipids
levels in these patients. IL-6 also is linked to dyslipidemia,
MS, and atherosclerosis. Otherwise, lichen planus is an
immune-mediated disease and antigens are processed by
Langerhans cells and then presented to T lymphocytes. This
stimulated lymphocytic inltrate is epidermotropic and at-
Table 3 Prevalence of Metabolic Syndrome Criteria (%) in Men and Women with Lichen Planus and their Respective Controls
Men (n 100)
P Value
Women (n 100)
P Value LP No LP LP No LP
Abdominal perimeter 44% 38% .68 46% 40% .68
Triglycerides 62% 30% .002 48% 20% .006
HDL-C 42% 18% .016 44% 20% .018
Systolic BP 32% 28% .82 28% 22% .64
Diastolic BP 34% 28% .66 22% 18% .80
Glucose levels 16% 12% .77 14% 10% .75
LP lichen planus; HDL-C high-density lipoprotein cholesterol; BP blood pressure.
Table 4 Mean (SD) LDL-C (mg/dL), Total Cholesterol (mg/dL), Total Cholesterol/HDL and LDL-C/HDL-C in Patients with Lichen
Planus and their Respective Controls
Patients (n 200)
P
Value
Men (n 100)
P
Value
Women (n 100)
P
Value LP No LP LP No LP LP No LP
LDL-C (mg/dL) 120.1 (30.0) 103.9 (28.9) .0001 124.2 (29.2) 107.6 (33.5) .01 115.7 (30.5) 100 (22.7) .006
Total cholesterol (mg/dL) 200.1 (35.6) 183.4 (35.8) .001 201.3 (32.1) 185.1 (37.8) .023 198.8 (39.4) 181.7 (33.8) .026
Total cholesterol/HDL-C 3.7 (1.2) 2.9 (1.1) .0001 4.0 (1.2) 3.2 (1.2) .0012 3.4 (1.4) 2.6 (0.7) .0006
LDL-C/HDL-C 2.2 (1.0) 1.6 (0.8) .0001 2.4 (0.9) 1.8 (0.9) .0012 1.9 (1.1) 1.4 (0.7) .081
LDL-C low-density lipoprotein cholesterol; HDL-C high-density lipoprotein cholesterol; LP lichen planus.
546 The American Journal of Medicine, Vol 124, No 6, June 2011
tacks keratinocytes, resulting in generation of reactive
oxygen species. During this lymphocytotoxic process, the
keratinocytes release more cytokines that attract more
lymphocytes. These cytokines such as TNF-, IL-6, IL-10,
and IL-4, involved in lichen planus pathogenesis, could
explain the association with dyslipidemia, as chronic in-
ammation has been suggested as a component of the MS.
Similar to psoriasis, lichen planus might be a marker for
dyslipidemia.
Increased LDL-C/HDL-C ratio has already been consid-
ered as a sensitive predictor of cardiovascular risk, and
recently, total cholesterol/HDL-C ratio has been found an
even better predictor metabolic index for cardiovascular risk
in large study.
19
In the present study, patients with lichen
planus presented higher values of both ratios. Sharrett et al
20
stated that higher values of triglycerides and low levels of
HDL-C were associated with the transition from atheroma
to atherothrombosis and therefore, control of these 2 car-
diovascular risk factors is essential in patients with subclin-
ical disease. MS, according to APT-III criteria, is associated
with a higher risk of a cardiovascular event (OR 2.59) in the
next 10 years, according to some authors.
21
In the present
study, patients with lichen planus presented higher preva-
lence of MS, but these differences were not statistically
signicant. As dyslipidemia is a very important component
of MS, prospective studies with longer follow-up periods
may show a higher signicant prevalence of MS in these
patients.
Although case-control studies can show a possible selec-
tion bias, the distribution of the potentially confounding
factors as age, weight, height, BMI, tobacco use, sedenta-
rism, hypothyroidism, and drug intake were homogeneous
in the 2 groups. In the present study, binary logistic regres-
sion model showed a higher risk for dyslipidemia in patients
with lichen planus after controlling for age, sex, BMI, glu-
cose levels, and CRP. Also, case-control studies do not
allow the directionality of the association to be ascertained,
so more prospective studies with larger numbers of patients
are required to conrm these ndings and to analyze the
pathogenic mechanisms underlying the increase in cardio-
vascular risk in patients with lichen planus.
In conclusion, the results obtained indicate an association
between lichen planus in male or female patients and dys-
lipidemia. Chronic inammation and acute phase reactants
may explain these ndings. Lipid levels screening in males
or females with lichen planus may be useful to detect
individuals at risk and start preventive treatment against the
development of cardiovascular disease.
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Table 5 Mean (SD) CRP, Fibrinogen, ESR in Men and Women with Lichen Planus and their Respective Controls
Patients (n 200)
P
Value
Men (n 100)
P
Value
Women (n 100)
P
Value LP No LP LP No LP LP No LP
CRP (mg/dL) 0.53 (0.56) 0.31 (0.45) .004 0.59 (0.72) 0.32 (0.57) .03 0.46 (0.32) 0.31 (0.28) .018
Fibrinogen (mg/dL) 357.9 (77.9) 305.1 (89.3) .001 336.6 (72.2) 292.9 (99) .013 380.5 (78.1) 318.1 (76.7) .0001
ESR (mm/h) 14.2 (12.5) 9.9 (7.5) .004 12.7 (11.6) 7.7 (4.1) .005 15.8 (13.3) 12.3 (9.4) .13
CRP C-reactive protein; ESR erythrocyte sedimentation rate; LP lichen planus.
547 Arias-Santiago et al Risk Factors and Lichen Planus
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548 The American Journal of Medicine, Vol 124, No 6, June 2011