Association between acrochordons and the components of metabolic syndrome

ARTICLE

ejd.2011.1572

Auteur(s) : Fatma Akpіnar profdrak@yahoo.com, Emine Dervіs

Haseki Training and Research Hospital, Adivar Caddesi PK 34096, Aksaray, 34096 Istanbul, Turkey

Reprints: F. Akpіnar

Acrochordons (skin tags) are the most common fibroepithelial tumors of the skin. Flesh-colored to brown, pinhead-sized and larger papillomas commonly occur in the natural folds of the skin [1, 2]. They have been reported in association with skin aging, acromegaly, colonic polyps, Birt-Hogg-Dube syndrome, nevoid basal cell carcinoma syndrome, obesity, diabetes mellitus (DM), pregnancy, and genetic susceptibility [3, 4].

Metabolic syndrome (MS) is a condition constituted by major risk factors such as obesity, dyslipidemia, hypertension, insulin resistance (IR) and prothrombotic and proinflammatory states [5]. MS is the most important risk factor for the development of DM and/or cardiovascular disease [6].

The association of skin tags with DM was first mentioned by Touraine [7]. Since then, a few clinical studies have been conducted to investigate the relationship between skin tags and the components of MS (DM, hypertension, obesity, and dyslipidemia) with conflicting results [3, 8-20]. Patients with acrochordons have been proposed for the investigation of atherosclerotic risk factors because of the possible correlation between acrochordons and the components of MS and high risk of cardiovascular disease [10, 13].

This study was performed to evaluate and compare the components of MS in patients with skin tags and healthy controls.

Material and methods

The patients who attended the Haseki Training and Research Hospital Dermatology outpatient clinic from January to May 2010 and who were 18 years and older were included in this study. Informed consent was obtained from the subjects who agreed to participate. The ethics committee approval was obtained from the aforementioned hospital. Patients with at least one skin tag were included in the acrochordon group and those without skin tags were included in the control group. The cases with a personal history of endocrine disease (Cushing syndrome, acromegaly, pheochromocytoma, hyperthyroidism, glucagonoma), cases with pregnancy, acute infection, erythroderma and/or psoriasis, cases taking medicine causing hyperglycemia (steroids, thyroid hormone, α-adrenergic and β-adrenergic drugs, thiazide, dilantin), and cases with a personal history of isotretinoin use in last six months were excluded. A total of 192 patients with skin tags and 104 controls of a similar age and sex were included.

All the blood samples were taken after an eight-hour starvation, at 8:00-9:00 am. All subjects underwent an oral glucose tolerance test (OGTT). Serum total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) levels were measured. Age, sex, height, weight, and body mass index (BMI), waist circumference, blood pressure values, personal history of DM, and hypertension were recorded. For the acrochordon group, number, localization, size, colour and family history of acrochordons were also noted.

Height and weight were measured standing in light clothing and BMI was calculated (BMI: weight/height²: kg/m²). According to World Health Organization (WHO) recommendations, overweight is defined as a BMI 25-29.99 kg/m², and obesity is defined as a BMI ≥30 kg/m² [21].

Blood pressure was measured through both arms with a mercury sphygmomanometer in a sitting position at least 10 minutes after resting, and the higher value was recorded. According to The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) criteria, a blood pressure of 140/90 mm Hg or higher is considered as hypertension [22].

Fasting and 2-h plasma glucose levels were measured by enzymatic calorimetric assay (Abbott Diagnostics, Wesbaden, Germany). Diagnosis of DM was based on American Diabetes Association (ADA) criteria [23]. DM was defined as fasting plasma glucose (FPG) ≥126 mg/dL or 2.hour plasma glucose (PG) ≥200 mg/dL. Impaired fasting glucose (IFG) was defined as FPG levels of 100 mg/dL to 125 mg/dL. Impaired glucose tolerance (IGT) was defined as 2-h PG values of 140 mg/dL to 199 mg/dL.

TC, TG, and HDL-C levels were measured by photometric assay using the Architect C8000 device (Abbott, Illinois, USA). LDL-C levels were calculated by Friedewald's Formula [LDL-C=TC-(HDL-C)-(TG/5)]. According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) classification, the borderline value was 200 mg/dL for TC, 150 mg/dL for TG, 130 mg/dL for LDL-C, and 50 mg/dl (women) and 40 mg/dL (men) for HDL-C levels [5].

Metabolic syndrome was defined according to NCEP ATP III criteria as the presence of three of the five following conditions; waist circumference >88 cm (women) and >102 cm (men), TG ≥150 mg/dL, HDL-C <50 mg/dl (women) and <40 mg/dL (men), blood pressure ≥130/85 mmHg, and fasting glucose ≥110 mg/dL [5]. The patients were informed about association of acrochordons with bowel polyps.

Statistical analysis was performed using the SPSS Windows 16.0 program. Frequencies of categorical variables were compared using the non-parametric chi-square test. Sample size was adequate to utilize parametric statistical tests as there were 192 patients in the acrochordon group and 104 patients in the control group. Distribution between the two groups for continuous variables were compared with the parametric Student's t test. Correlation analysis was done by Pearson's correlation test. Regression analysis was used to determine factors associated with the number of acrochordons. The Analysis of Variance (ANOVA) method was used to determine the association of BMI and DM with the localization of acrochordons. A p value of <0.05 was considered significant.

Results

Of the 192 patients with acrochordons, 124 (64.6%) were female and 68 (35.4%) were male (age range 18-75 years, mean 48.6). There were 62 (59.6%) females and 42 (40.4%) males in the control group (age range 18-83 years, mean 47.5). 38.5% of the patients with acrochordons had a family history. The clinical characteristics of acrochordons are shown in table 1.

Table 1 Distribution of acrochordons according to localization and number

Family history of DM was 30.2% in the acrochordon group and 30.7% in the control group.

Thirty patients (15.6%) with acrochordons had a history of DM. Twenty-eight patients (14.6%) had IFG, 30 (15.6%) had IGT, 8 (4.1%) had undiagnosed DM, and 4 (2.1%) had hypoglycemia. In the control group, 12 (11.5%) patients had a history of DM, 16 (15.3%) had IFG, 4 (3.8%) had IGT, 2 (1.9%) had undiagnosed DM, and 2 (1.9%) had hypoglycemia. IFG, IGT, and hypoglycemia were considered as prediabetic states. Thus, 62 patients (32.3%) had a prediabetic state, and 38 (19.8%) had DM. In the control group, 22 (21.1%) had a prediabetic state, and 14 (13.4%) had DM. DM was significantly more frequent in the acrochordon group than the control group (p<0.001).

The difference between the mean±SD fasting plasma glucose levels of the groups was not statistically significant (115.90±7.70 in the acrochordon group and 109.59±12.20 in the control group, p=0.396). The difference between 2-h plasma glucose levels was statistically significant (115.16±4.46 in the acrochordon group and 103.46±4.19 in the control group, p<0.001).

The mean number of acrochordons was 6.85±1.79 in patients with FPG<100 mg/dl and 9.87±2.93 in those ≥100 mg/dL. The difference was statistically significant (p=0.043).

Patients with DM had 22 more acrochordons than normoglycemic ones (p=0.006). Patients with DM had more acrochordons under the breast compared to prediabetic patients (p=0.041).

A personal history of hypertension was 29.1% and family history of hypertension was 30.1% in the acrochordon group. The personal history of hypertension was 11.5% and family history of hypertension was 28.8% in the control group. Hypertension was significantly more frequent in the acrochordon group than the control group (p<0.001). The mean number of acrochordons was 8.97±4.14 in hypertensive patients and 7.96±1.29 in normotensive patients. The difference was not statistically significant (p=0.675). Metabolic findings in acrochordon and control groups are shown in table 2.

Table 2 Metabolic findings in the acrochordon and control groups.

BMI: body mass index; FPG: fasting plasma glucose; 2-hr PG: second hour plasma glucose; TC: total cholestrol; TG: total triglyceride; LDL-C: low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol

BMI values of the acrochordon group were significantly higher than the control group (p<0.001). For the patients with acrochordons, 70 (36.4%) were overweight, and 94 (48.9%) were obese, while in the control group, 48 (46.1%) were overweight, and 22 (21.1%) were obese. We found that the number of acrochordons was significantly increased in patients with higher BMI value (r=0.277, p<0.001). The mean number of acrochordons was 2.07±0.67 in patients with BMI < 25 kg/m² and 9.40±1.95 in patients with BMI ≥ 25 kg/m². The difference was statistically significant (p<0.001). Obese patients had 10 more acrochordons than overweight patients (p=0.003), and 13 more acrochordons than those with normal weight (p=0.006). The number of acrochordons in the neck (p=0.005), axilla (p=0.001) and extremities (p=0.014) was significantly increased in the patients with higher BMI values.

Serum TC, TG, LDL-C levels were significantly higher in the acrochordon group than the control group (p<0.001), and serum HDL-C levels were significantly lower (p=0.009). The mean number of acrochordons was 7.69±1.80 in patients with serum TC <200 mg/dL and 8.84±2.73 in those ≥200 mg/dL. The difference was not statistically significant (p=0.246). The mean number of acrochordons was 6.61±1.40 in patients with serum TG <150 mg/dl and 10.84±3.63 in those ≥150 mg/dL. The difference was statistically significant (p=0.016). The mean number of acrochordons was 8.32±1.78 in patients with serum LDL-C <130 mg/dL and 8.34±3.23 in those ≥130 mg/dL. The difference was not statistically significant (p=0.497).

Metabolic syndrome was found in 108 patients with acrochordons (56.2%), and 26 (25.0%) controls. Metabolic syndrome was significantly more frequent in the acrochordon group than the control group (p<0.001). The mean number of acrochordons was 8.85±1.68 in patients with metabolic syndrome and 7.66±3.27 in those without metabolic syndrome. The difference was not statistically significant (p=0.736). The patients with metabolic syndrome had 11 more acrochordons than the patients without metabolic syndrome (p=0.02).

According to regression analysis, the number of acrochordons was significantly increased in patients with a higher BMI value (p=0.015), 2-h PG (p=0.012), TC (p=0.010), TG (p=0.008), LDL-C (p<0.001) levels, and lower HDL-C levels (p=0.011). The number of acrochordons was increased by the personal history of DM (p=0.006) and metabolic syndrome (p=0.002).

Discussion

There was a female preponderance in this study (64.6% females, 35.4% males) as in other Turkish studies [4, 9-11, 13, 14]. This result may be related to hormonal differences, and previous pregnancies. However, males were affected more than females in various other studies [17-20, 24]. The risk of getting acrochordons was found to increase with age in this study, in agreement with Thappa [17] and Banik-Lubach [24]. Our study revealed a family history in 38.5% of the patients with acrochordons, consistent with a study in Iran [3].

Skin tags commonly develop in individuals with obesity and their prevalence correlated positively with the severity of the obesity [25]. There was a positive correlation between the number of skin tags and BMI in the majority of the studies [4, 8, 10, 12-14, 16], but some investigators failed to find such a relationship [3, 11, 19].

We found that BMI values in the acrochordon group were significantly higher than in the control group. The number of acrochordons was significantly increased in patients with higher BMI values, consistent with the studies by Kocak et al. [4] and Demir [14]. Although Sari et al. [10] did not find a relationship between the distribution of acrochordons and the parameters in their study, we found that the number of acrochordons in the neck, axilla, and extremities was significantly increased in the patients with higher BMI values. This may be due to the effect of the increase in friction as BMI increases.

A few clinical studies which aimed to investigate the relationship between skin tags and DM detected 9.3% to 81.7% DM frequency [3, 8-20]. The frequency of DM in our study was 19.8%, but higher frequencies were reported by Demir [14] and Margolis [20]. Higher frequencies may be due to hospitalized nature of patients.

Norris et al. reported a greater association with insulinemia than with fasting glucose in patients with skin tags [26]. In agreement with Norris et al., Jowkar et al. found that non-diabetic patients with acrochordons had higher insulin levels than controls [27]. Sudy et al. added that postprandial insulin levels were more sensitive than fasting insulin and fasting glucose levels to evaluate impaired carbohydrate metabolisms [12]. Mathur defined insulin resistance (IR) as the ratio of fasting insulin to fasting glucose level and did not find any difference between acrochordon and control groups [15]. Thus, contrary to Norris et al., they reported that acrochordons were not a sign of IR. This result may be due to their study population which consisted of a limited number of non-diabetic patients (10 cases, 10 controls).

Tamega et al. [8], Sari et al. [10], and Erdogan et al. [13] calculated insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. The HOMA-IR values of the patients with acrochordons were higher than those of the controls. They concluded that skin tags may represent a marker for the identification of IR prior to the manifestation of diseases resulting from the hypermetabolic syndrome [8].

Acrochordons, pseudoacanthosis nigricans and seborrheic keratosis represent proliferative skin conditions where role of growth factors has been suggested. Insulin like growth factors have also been known to cause keratinocytes and dermal fibroblast proliferation. In view of this evidence, Bhargava proposed an association of obesity, multiple skin tags, abnormal glucose tolerance, pseudoacanthosis nigricans and seborrheic keratosis in the form of a syndrome [16].

In our study, DM was significantly more frequent in the acrochordon group than the control group. Consistent with Gorpelioglu et al. [11], but contrary to Rasi et al. [3], the difference between FPG levels of the groups was not statistically significant, but the difference between 2-h PG levels was statistically significant. In agreement with Rasi et al., but contrary to Dogramaci et al. [9] and Demir [14], patients with IGT or DM had a greater number of acrochordons compared to normoglycemic ones. Contrary to Demir [14], patients with DM had more acrochordons under the breast compared to prediabetic patients, consistent with the study by Rasi et al. [3].

In the study by Rasi et al., 1/3 of the diabetic patients and all of the patients with IGT were previously undiagnosed. This underlies the importance of considering skin tags as a diagnostic clue to a possibly impaired carbohydrate metabolism. Inclusion of patients with more than 3 skin tags might have increased the chance of finding a positive correlation between the presence of skin tags and diabetes. In our study, patients with at least one skin tag were involved. Eight patients in the acrochordon group together with 2 controls were undiagnosed before. The difference was not statistically significant (p>0.05).

There have been a few reports in the literature about the relationship between acrochordons and atherogenic lipid profiles. Crook detailed four patients with multiple acrochordons who had increased serum triglyceride and decreased serum HDL-C levels [28]. Hyperlipidemia accompanied acrochordons in 45.8% of the patients in the study by Demir [14]. Erdogan et al. found serum TC levels higher in the acrochordon group than the control group [13]. Serum TC and LDL-C levels were higher in the acrochordon group than the control group in the study by Gorpelioglu et al. [11]. Tamega et al. reported higher serum TG levels in the acrochordon group than the control group [8].

In this study, serum TC, TG, LDL-C levels were significantly higher in the acrochordon group than in the control group and serum HDL-C levels were significantly lower, consistent with Sari et al. [10].

The relationship between acrochordons and metabolic syndrome was not investigated until Sari et al. [10] reported that 39.3% of the patients with acrochordons had metabolic syndrome. Vena et al. found a significant association of psoriasis with components of metabolic syndrome [29]. Metabolic syndrome was significantly more frequent in the acrochordon group than the control group in our study. In addition, the number of acrohordons increased in the presence of metabolic syndrome.

Adult patients with skin tags should be alerted to the risk of developing insulin resistance, hypertriglyceridemia, overweight and possibly DM and associated cardiovascular complications, such as acute myocardial infarction, cerebrovascular disease, peripheral arterial disease, erectile dysfunction, cognitive decline, fatty liver and renovascular disease. Moreover, IR has been associated with the development of malignant neoplasias such as adenocarcinoma of the bowel, breast, endometrium, kidney, esophagus and prostate, which may be explained by the increased levels of tissue growth factors in these patients [8].

In conclusion, it is beneficial to evaluate patients with more than 9 skin tags for the presence of diabetes mellitus, hypertension, obesity, dyslipidemia, and metabolic syndrome.

Disclosure

Financial support: none. Conflicts of interest: none.

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