A descriptive case-Control study of 100 patients of acanthosis nigricans and its utility to detect metabolic syndrome

Nisha Prakash; Yadalla Hari Kishan Kumar; PR Belliappa

doi:10.4103/CDR.CDR_56_18

ORIGINAL ARTICLE

Year : 2020 | Volume : 4 | Issue : 1 | Page : 17-22

A descriptive case-Control study of 100 patients of acanthosis nigricans and its utility to detect metabolic syndrome

Nisha Prakash, Yadalla Hari Kishan Kumar, PR Belliappa
Department of Dermatology, Raja Rajeswari Medical College and Hospital, Bengaluru, Karnataka, India

Date of Submission	03-Dec-2018
Date of Decision	03-Feb-2019
Date of Acceptance	03-Jun-2019
Date of Web Publication	06-Jan-2020

Correspondence Address:
Yadalla Hari Kishan Kumar
Skin Care Clinic, 70, Padma Nivasa, 3^rd Cross MG Extension, HV Halli, Raja Rajeswari Nagar, Bengaluru - 560 098, Karnataka
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/CDR.CDR_56_18

Abstract

Background: Acanthosis nigricans (AN) is a dermatosis that manifests as asymptomatic and symmetrical darkening in intertriginous areas and is associated with endocrine disturbances or malignancy. The features of metabolic syndrome (MetS) include hyperglycemia, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, central obesity, and hypertension. Aims and Objectives: (1) To study the fasting and postprandial blood sugar level, lipid profile, blood pressure, and waist circumference (WC) in patients with AN and compare the values in healthy controls.(2) To determine the association between the presence of benign acquired AN and MetS (biochemical parameters and anthropometric variables). Materials and Methods: A descriptive case–control study with 100 cases of AN and 100 healthy controls without AN was conducted between December 2016 and November 2017 to assess the association between AN and metabolic variables. Results: In this study, out of the 100 cases evaluated, 57% had MetS diagnosed by the National Cholesterol Education Program and Adult Treatment Panel III, of which 35 were females and 22 males. Among 100 cases of AN, 31 had hypertension (P = 0.438), 57 had elevated triglycerides (P = 0.007), 33 had elevated fasting blood sugar (P = 0.061), 76 had decreased HDL cholesterol (P = 0.000045), and 78 had increased WC (P = 0.00463). The association of AN with MetS was highly significant in the study population (P = 0.000017; as P < 0.05-significant; P < 0.01-highly significant). Conclusion: In this study, 57 patients with AN had deranged metabolic variables suggesting the presence of MetS. This study shows that AN could be a marker for MetS. Hence, clinicians should assess patients with AN for metabolic and biochemical parameters to advise regarding lifestyle modification and prevent future cardiovascular complications.

Keywords: Acanthosis nigricans, case–control study, metabolic syndrome

How to cite this article:
Prakash N, Kishan Kumar YH, Belliappa P R. A descriptive case-Control study of 100 patients of acanthosis nigricans and its utility to detect metabolic syndrome. Clin Dermatol Rev 2020;4:17-22

How to cite this URL:
Prakash N, Kishan Kumar YH, Belliappa P R. A descriptive case-Control study of 100 patients of acanthosis nigricans and its utility to detect metabolic syndrome. Clin Dermatol Rev [serial online] 2020 [cited 2020 Oct 30];4:17-22. Available from: https://www.cdriadvlkn.org/text.asp?2020/4/1/17/275250

Introduction

Acanthosis nigricans (AN) is a dermatological condition characterized by hyperpigmentation, hyperkeratosis, and papillomatosis and is associated with hyperinsulinemia.^{[1],[2],[3],[4],[5],[6],[7],[8]} Burke et al.^[9] developed and validated a scale for grading the severity of AN. The typical areas of involvement of AN include the posterior neck, axillae, elbows, and knees.^{[9],[10],[11]} Benign AN is very common and affects up to 20% of adults and 7% of children.^[12],[13] It is often associated with obesity, hyperinsulinemia, and insulin resistance.^[14],[15] The interaction among insulin, insulin-like growth factor 1, and androgens may further explain the association among AN, obesity, and endocrinopathies/hormonal treatment.^[16] Schwartz ^[17] had classified AN as benign AN, AN associated with obesity, syndromic AN, malignant AN, acral AN, unilateral AN, drug-induced AN, and mixed AN.^[18]

Mixed-type acanthosis nigricans occurs when a patient with one of the above types of AN develops new AN lesions of a different etiology. An example would be an overweight patient with obesity-associated AN who subsequently develops malignant AN.^[19]

The metabolic syndrome (MetS) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease and diabetes mellitus. Its major features include central obesity, hypertriglyceridemia, low levels of high-density lipoprotein (HDL) cholesterol, hyperglycemia, and hypertension.^[20] It was first named as “Syndrome X” by Reaven.^[21] Recent data show that about one-third of the urban population in large cities in India have MetS.^[22],[23]

As there is a paucity of data in the Indian population, this study was intended to evaluate the association of benign acquired AN with MetS and to compare with the healthy control group, in a subpopulation of the rural background of South India.

Materials and Methods

A descriptive case–control study was conducted between December 2016 and November 2017 on patients attending as outpatients and inpatients to the Department of Dermatology at a tertiary care hospital. Ethical clearance for the study was taken from the Institutional Ethics Committee.

Inclusion criteria

Patients with AN in the age group of 11–40 years and comprising of both sexes
The control group included healthy individuals without AN in the age group of 11–40 years and comprising both sexes.

Exclusion criteria

Participants with a history of intake of drugs including nicotinic acid, oral contraceptives, systemic steroids, diethylstilbestrol, and anti-retroviral drugs which can cause AN were excluded from the study
Pregnancy and the postpartum period up to 6 months
Participants with AN due to malignancy associated conditions
Participants with autoimmune causes of AN
Participants with inherited causes of AN.

Study design

The study design involves descriptive case–control study.

Informed written consent was obtained from the patients and healthy controls. Medical records for the past 3 years were checked and the sample size was estimated by adding 10% to last year's prevalence rate of AN patients attending our department, satisfying the inclusion and exclusion criteria in a duration of 1 year and thereby, a sample size of 100 each for cases and controls was chosen. Semi-structured questionnaire was used to collect information regarding sociodemographic profile, clinical history, and investigative work-up. The study participants were subjected to thorough history taking and clinical examination. Age, sex, occupation, age of onset of AN, duration of AN, family history of AN, diabetes, hypertension, dyslipidemia, history of smoking, alcohol intake, and history of drug intake were noted.

Complete cutaneous and systemic examination was done for each of the study participants. The diagnosis of AN was made through clinical findings. Lesions of AN were described in terms of site, size, shape, color, texture, morphological appearance, and parts of the body surface involved. Skin biopsy for histopathological examination was done among consenting patients. Measurement of height, weight, body mass index (BMI), blood pressure, and waist circumference (WC) was done. BMI grading was done as per the WHO criteria ^{[24],[25],[26],[27],[28]} as follows:

Underweight: 15–19.9
Normal weight: 20–24.9
Overweight: 25–29.9 (preobesity)
Class I obesity: 30–34.9
Class II obesity: 35–39.9
Class III obesity: ≥40.

Photographic documentation of the lesions was done through clinical photographs taken with patients' consent. Fasting blood sugar, postprandial blood sugar, and lipid profile investigations were done among the study participants and values of the corresponding reports were recorded. WC was measured using a nonstretchable flexible tape in the horizontal position, just above the iliac crest, at the end of normal expiration, with the subject standing erect and looking straight forward and observer sitting in front of the subject. BMI was calculated as a ratio of weight in kilograms divided by height in meters squared (kg/m ²).

The diagnosis of MetS was based on the National Cholesterol Education Program and Adult Treatment Panel III by the presence of three or more of the following criteria.^[29]

Central obesity:
Hypertriglyceridemia:
Triglyceride level ≥150 mg/dl or specific medication.
Low HDL cholesterol:
≤40 mg/dl in males and ≤50 mg/dl in females or specific medication.
Hypertension:
Blood pressure ≥130 mmHg systolic or ≥85 mmHg diastolic or specific medication.
Fasting plasma glucose level ≥100 mg/dl or specific medication or previously diagnosed type 2 diabetes mellitus.

Descriptive and inferential statistical analysis was carried out in the present study. Results on continuous measurements were presented as mean ± standard deviation (minimum-maximum), and results on categorical measurements were presented in terms of frequency and percentage. Categorical data were assessed using the Chi-square test of significance. With 95% of the confidence interval, P < 0.05 was considered as statistically significant. Student's t-test (two-tailed, independent) was used to find the significance of the study parameters between two groups (intergroup analysis) on metric parameters. Chi-square test/Fisher's exact test was used to find the significance of the study parameters on categorical scale between two or more groups, the nonparametric setting for qualitative data analysis.

The statistical software, namely Statistical Package for the Social Sciences (SPSS) 18.0 and R environment version 3.2.2, (IBM Crop., New York, USA) was used for the analysis of the data. Microsoft Word and Excel were used to generate graphs and tables.

Results

In our study, females outnumbered the males among cases; about 67% of the cases were females and 33% were males and in the controls studied, 41% were female and 59% were male. The female:male ratios in cases and controls were 2.03:1 and 0.694:1, respectively. Maximum number of cases and controls belonged to the age group of 31–40 years (54 and 62%, respectively). The mean value of the age of the patients of AN cases studied was 29.83 ± 8.44. The youngest patient was 11 years old and the eldest was 40 years old.

In our study, among the cases, 14% had normal BMI, 39% were preobese, and 47% were obese. Among the controls, 18% had normal BMI, 39% were preobese, and 43% were obese. The association of BMI among the cases and control groups was not statistically significant (P = 0.622).

The values of triglycerides, HDL, WC in cases of AN were statistically significant when compared to the controls as shown in [Table 1]. The values of systolic and diastolic blood pressure (SBP and DBP) and fasting blood sugar were not statistically significant between cases of AN and controls, as summarized in [Table 1].

Table 1: Comparison of mean±standard deviation and p value of metabolic syndrome parameters in cases and controls

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The prevalence of MetS in cases of AN (57%) was statistically highly significant when compared to that of controls (27%) (P = 0.000017, P < 0.01) as shown in [Table 2] and [Figure 1]. A higher prevalence of MetS was seen in AN cases when compared to that of controls.

Table 2: Comparison of prevalence of metabolic syndrome in cases and controls

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Figure 1: Prevalence of metabolic syndrome in cases and controls

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Among the cases of AN, majority of the patients had lesions on the nape of the neck. AN in the perioral area showing hyperpigmentation, classical hyperkeratosis, and hyperpigmentation with velvety appearance seen in AN lesions on the nape of the neck and AN lesions presenting with hyperpigmentation localized to the knuckle area are depicted in [Figure 2], [Figure 3], [Figure 4], respectively. The distribution of the affected sites in the study population was as follows:

Figure 2: Acanthosis nigricans in the perioral area

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Figure 3: Classical hyperkeratosis and hyperpigmentation with velvety appearance seen in acanthosis nigricans lesions in the nape of the neck

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Figure 4: Acanthosis nigricans in the knuckle area

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Only nape of the neck: 56%
Nape of the neck along with other sites: 37%
Only axillae: 5%
Only the perioral area: 2%.

Biopsy was performed in patients with the varied clinical profile. Histological findings consistent in all the cases were papillomatosis, hyperkeratosis, and hyperpigmentation of the basal layer. Follicular plugging was noted, and upward finger-like projections of dermal papillae were seen. The valleys between papillae showed mild acanthosis and were filled with keratotic material. Dermal melanophages were also visualized [Figure 5].

Figure 5: Histopathology findings in acanthosis nigricans showing papillomatosis, hyperkeratosis and hyperpigmentation of the basal layer, follicular plugging and finger-like projections of dermal papillae (H and E, ×40)

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Discussion

AN is a condition characterized by hyperpigmentation, hyperkeratosis, papillomatosis, and typical areas of involvement of AN include the posterior neck, axillae, elbows, and knees.^{[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11]} The most common associations with benign AN are obesity and insulin resistance. Insulin at low concentration binds to classic insulin receptors. With insulin resistance and compensatory hyperinsulinemia, insulin binds to insulin-like growth factor-1 (IGF-1) receptors,^[30] which have been found in keratinocytes and fibroblasts.^[31] IGF-1 receptors are overexpressed in obese patients with hyperinsulinemia and insulin resistance. A high concentration of insulin results in direct and indirect activation of IGF-1 receptors in keratinocytes and fibroblasts, leading to their proliferation.^[11] Major features of MetS include central obesity, hypertriglyceridemia, low levels of HDL cholesterol, hyperglycemia, and hypertension.^[20]

In this study, 100 cases with AN and 100 controls without AN were investigated for conditions such as hypertension, dyslipidemia, and hyperglycemia and assessed for various anthropometric variables. They were subjected to blood investigations for measuring HDL, triglyceride, fasting blood sugar levels, and anthropometric measurements such as WC, height, and weight were taken from both the cases and controls.

In our study, among the cases of AN, the mean age group involved was 29.83 ± 8.44 which was similar to the study conducted by Huang et al.^[32] where the mean age group was 30.25 ± 9.28.

In this study, the value of triglycerides in cases was statistically significant (57%) when compared to that of controls (37%). Similar results were seen in studies conducted by Sharquie et al.,^[33] Vieira et al.,^[34] and Dassanayake et al.^[35] In our study, the number of cases of AN with deranged value of HDL and WC (76%) and (74%), respectively, was higher and statistically very highly significant when compared to the controls, which was similar to the results seen in studies conducted by Vieira et al.,^[34] Dassanayake et al.,^[35] and Koh et al.^[36]

In our study, the value of SBP was not statistically significant when cases were compared with that of controls. A similar result was seen in a study conducted by Vieira et al.^[34] and Kong et al.^[37] In our study, the distribution of DBP was not statistically significant when compared between cases and controls. In contrast to our study, results reported by Verma et al.^[38] showed statistically significantly higher values of DBP, when cases were compared to that of controls.

The prevalence of MetS in cases (57%) was statistically very highly significant when compared to the control group (27%). Similar results were seen in studies conducted by Vieira et al.,^[34] Koh et al.,^[36] Dassanayake et al.,^[35] Balaji et al.,^[39] and Shivpuri et al.^[40]

Limitations

We were able to perform biopsies only in consenting patients. Further studies on clinicopathological correlations of AN are required. It is important to identify whether any histological finding has a correlation with the severity of AN and underlying systemic diseases. Although we know that the morphology of AN is expressed with varying severity, we could not perform a grading according to clinical presentation, association with metabolic markers, and histopathological findings.

Conclusion

The prevalence of MetS in cases of AN (57%) was statistically highly significant when compared to the controls (27%) (P = 0.000017, P < 0.01). This study shows that AN could be a clinical marker for MetS, and hence, early screening is advisable. Clinicians should assess patients with AN for related metabolic and biochemical parameters to advise regarding lifestyle modification to prevent future cardiovascular complications. This study highlights the importance of evaluating associated risk factors of MetS in patients with AN.

Declaration of patient consent

The informed consent was obtained for participation in the study and publication of data and images for research and educational purposes.

Acknowledgment

The authors would like to acknowledge the valuable contribution of Dr. Srinivas N, Assistant Professor, Department of Community Medicine, Dr. Naveen Kumar P, Tutor, Department of Community Medicine and Dr. Suresh K.P., Scientist (Biostatistics) in the statistical analysis of the data.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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