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ORIGINAL ARTICLE
Year : 2019  |  Volume : 12  |  Issue : 1  |  Page : 16-21  

Acanthosis nigricans: A cutaneous marker for metabolic syndrome


1 Department of Dermatology, Smt. Kashibai Navale Medical College and General Hospital, Pune, Maharashtra, India
2 Department of Preventive and Social Medicine, Smt. Kashibai Navale Medical College and General Hospital, Pune, Maharashtra, India

Date of Submission17-Feb-2018
Date of Acceptance15-May-2018
Date of Web Publication18-Jan-2019

Correspondence Address:
Nirali Girish Shah
Department of Dermatology, Smt. Kashibai Navale Medical College and General Hospital, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_44_18

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  Abstract 


Background: Acanthosis Nigricans (AN) is an easily identifiable dermatoses characterized by thickened, hyperpigmented plaques. Metabolic syndrome refers to a clustering of metabolic risk factors including central obesity, glucose intolerance, hyperinsulinemia, low HDL cholesterol, high triglycerides and hypertension. AN is a skin marker associated with this syndrome. Aims and Objectives: This study aimed to determine the relationship between AN and metabolic syndrome by studying its clinico-epidemiological features and also the relation of severity of AN over neck with metabolic syndrome. Methodology: This is a case-control study. One hundred consecutive patients of AN attending dermatology OPD of a tertiary care hospital were included in this study. They were evaluated for AN and severity of AN over neck was assessed. Age and sex matched 100 controls were included in the study. Epidemiological, clinical and anthropometric characteristics (height, weight, waist circumference) were measured of all the cases and controls. Body Mass Index (BMI) was calculated. Fasting Blood Sugar, High Density Lipoprotein and Serum Triglyceride levels were estimated. Result: The average age of the patients was 32.4 years and females (62%) were more than the males (38%). Neck was involved in all the patients. There was statistically significant correlation of increasing severity of AN with each component of Metabolic syndrome. On comparing between cases and controls, each component of metabolic syndrome was raised in cases as compared to the controls. 70% cases had Metabolic syndrome which was statistically significant. Conclusion: There was a high prevalence of AN in subjects with metabolic syndrome. Also there was a positive correlation between severity of AN and Metabolic syndrome.

Keywords: Acanthosis nigricans, metabolic syndrome, severity of acanthosis nigricans


How to cite this article:
Shah NG, Khatu SS, Gokhale NR, More YE, Khismatrao D. Acanthosis nigricans: A cutaneous marker for metabolic syndrome. Med J DY Patil Vidyapeeth 2019;12:16-21

How to cite this URL:
Shah NG, Khatu SS, Gokhale NR, More YE, Khismatrao D. Acanthosis nigricans: A cutaneous marker for metabolic syndrome. Med J DY Patil Vidyapeeth [serial online] 2019 [cited 2019 Sep 18];12:16-21. Available from: http://www.mjdrdypv.org/text.asp?2019/12/1/16/250442




  Introduction Top


Acanthosis nigricans (AN) is characterized by symmetrical hyperpigmented and hyperkeratotic plaques of the skin mainly affecting the folds of the axillae, groin, and back of the neck.[1] It may also affect the antecubital and popliteal fossae and umbilical region. Sinha and Schwartz have classified AN into various types such as benign AN, obesity-associated AN, syndromic AN, malignant AN, acral AN, unilateral AN, medication-induced AN, and mixed-type AN.[2] AN is normally a clinical diagnosis. Its recognition should prompt the clinician to further evaluate the patient clinically to determine the underlying cause, be that benign (obesity related, hereditary, or endocrine) or malignant. Its frequency is often underestimated being asymptomatic.[3]

Metabolic syndrome

Metabolic syndrome (MS) refers to a clustering of metabolic risk factors including central obesity, glucose intolerance, hyperinsulinemia, low high-density lipoprotein-cholesterol (HDL-C), high triglycerides (TGs), and hypertension.[4]

The National Cholesterol Education Program Expert Panel and Adult Treatment Panel III published a working definition in 2001 which requires at least three out of five parameters such as waist circumference >102 cm/40 inches for male and >88 cm/36 inches for female; TG >1.7 mmol/L (150 mg/dL); HDL-c <40 mg/dL for male and <50 mg/dL for female; blood pressure (BP) >130/85 mmHg; and fasting glucose >6.1 mmol/L (110 mg/dL).[4]

People with MS are twice as likely to die from and three times as likely to develop myocardial infarction or stroke compared to people without MS. They also have a fivefold greater risk of developing type 2 diabetes (if not already present). MS is increasingly being recognized as risk factor for cardiovascular disease and cardiovascular mortality.[4]

Lipoatrophy, AN, skin tags, and psoriasis are common skin markers associated with this syndrome. Since these physical findings typically are associated with severe insulin resistance, other components of the MS should be expected.[4]

AN is most commonly associated with disorders associated with insulin resistance, including obesity, type 2 diabetes, and polycystic ovary syndrome. In these cases, hyperinsulinemia is thought to play a pivotal role. Acrochordons (skin tags) are often found in and around the affected areas.[5]

Understanding the connection between AN and MS is critical for clinicians since patients with AN are at risk for all of the components of the MS.[4]

Aims and objective

The aims of this study were as follows:

  1. To study clinicoepidemiological features of 100 patients with AN
  2. To study the relation of severity of AN with MS
  3. To compare the prevalence of MS in patients with AN as compared to control population.



  Subjects and Methods Top


This study was performed after clearance from the ethical committee. One hundred consecutive patients of AN attending the dermatology outpatient department (OPD) of a tertiary care hospital from December 2015 to September 2017 were included in this study after an informed written consent. Patients were diagnosed clinically by a dermatologist. All the patients included in the study were above 18 years of age. Patients suffering from diabetes mellitus, hypertension, dyslipidemia, or any other comorbidities were excluded from the study. Patients with a history of addictions and pregnant females were excluded from the study.

All patients underwent a detailed physical examination including anthropometry (height, weight, and waist circumference). From these data, body mass index (BMI) was calculated. The BMI was calculated by weight in kilograms divided by height in meters squared (kg/m2). All the patients were investigated for fasting blood sugar levels (FBS), HDL-C, and serum TG level.

One hundred cases of AN were studied further for sites involved. AN over the neck was graded based on the standard scale of 0–4 as described by Burke et al. Neck grading scale was taken as follow as: Grade 0 – not visible; Grade 1 – present: clearly present on close visual inspection, not visible to the causal observer, and extent not measurable; Grade 2 – mild; limited to the base of the skull, not extending to the lateral margin of the neck (usually 3 inches in breadth); Grade 3 – extending to the lateral margins, not visible from the front; and Grade 4 – extending anteriorly. The severity of AN was then correlated with each component of MS, and the results were statistically analyzed.

Age- and sex-matched 100 controls were included in the study and all criteria of MS were compared between the two groups. Chi-square test was used for statistical analysis of case–control study, to compare each component of MS with AN. The odds ratio was used to measure the association between AN and MS. The odds ratio can be used to determine whether a particular exposure is a risk factor for a particular outcome. The odds ratio >1 implies that the exposure is associated with higher odds of outcome.


  Results Top


Clinicoepidemiological features

Age and sex:

The average age of the patients with AN was 32.4 years. Females (62%) were more commonly affected as compared to males (38%) [Table 1] and [Table 2], [Graph 1].
Table 1: Age distribution of the participants

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Table 2: Sex distribution of the participants

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Sites

The predominant sites affected were neck in 100% of the cases, axilla in 31%, face in 21%, and groins in 9% of the cases. Other sites such as antecubital fossa (4%), knuckles (3%), and submammary areas (1%) were also affected.

Mean duration of acanthosis nigricans

The mean duration of AN was 32.21 months, that is, 2.7 years.

Relation of severity of acanthosis nigricans with metabolic syndrome

  • Grade 1 – 29.2% had MS, whereas 70.8% did not have MS
  • Grade 2 – 54.4% had MS, whereas 45.5% did not have MS
  • Grade 3 – 91.7% had MS, whereas 8.3% did not have MS
  • Grade 4 – 96.7% had MS, whereas 3.3% did not have MS [Table 3].
Table 3: Comparison of the severity of acanthosis nigricans with metabolic syndrome

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(P value= 0.000).

On comparing the severity of AN with components of MS and BMI, we found that AN neck severity grading has statistically significant correlation with all the components of MS and BMI [Table 4] and [Graph 2].
Table 4: Comparison of the severity of acanthosis nigricans with each component of metabolic syndrome

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Prevalence of metabolic syndrome in cases and controls

The prevalence of metabolic syndrome in cases and controls was determined by comparing each component of MS between the cases and controls [Table 5].
Table 5: Comparison of each component of metabolic syndrome between cases and controls

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Waist circumference

Out of the 100 cases, 69% had increased waist circumference as compared to 22% of the controls (P = 0.000).

Blood pressure

Out of the 100 cases, 55% had hypertension, whereas only 21% of the controls had hypertension (P = 0.000).

Fasting blood sugar

The FBS level was high in 61% of the cases, whereas only 27% of the controls had raised levels (P = 0.000).

Serum triglyceride level

The serum TG level was high in 64% of the cases as compared to 29% of the controls (P = 0.000).

Serum high-density lipoprotein-cholesterol level

The serum HDL-C levels were lower than the normal level in 61% of the cases as compared to only 19% of the controls (P = 0.000).

Body mass index

Out of the 100 cases of AN, 46% cases were obese (BMI >24) and as compared to 33% obese controls. The difference was statistically significant [Table 6].
Table 6: Body mass index: Cases and controls comparison

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Metabolic syndrome

Considering all the components of MS and comparing the results between the cases and the controls, 70 patients with AN had MS and only 17 controls had MS. The odds ratio was 11.39, and thus the difference was statistically significant [Table 7].
Table 7: Comparison of metabolic syndrome between cases and controls

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  Discussion Top


This study was carried out in an unselected population of patients with AN who sought evaluation for possibly cosmetic purpose in the dermatology OPD of a tertiary care center.

Clinicoepidemiological profile

Mean age in our study was 32.47 years which was comparable to studies carried out by Amira Zayed et al. (31.5),[6] Ehsani et al. (28.5 ± 4.9 years),[7] and Varthakavi et al. (26.3 ± 1.7 years).[8]

Mean age found in studies carried out by Treesirichod et al.(13.4 ± 1.4 years)[9] was less than found in our study, whereas in studies by Patidar et al.,[10] the mean age was 45.2 years and by Hoffmann et al.,[11] it was 49.1 years which was more than found in our study.

In this study, females (62%) outnumbered males (38%). This is comparable to studies carried out by Stoddart et al. (females – 37.1% and males – 30.5%),[12] Varthakavi et al. (females – 77.8% and males – 22.2%),[8] Alberta S. Kong et al.[13] (females – 61.6 and males – 38.4), Treesirichod et al.[9] (female – 62.5%), Patidar et al.[10] (females – 86.92% and males – 56.67%), and Kamel et al.[14] (females – 90% and males – 10%). In studies by Grandhe et al.[15] and Karadağ et al.,[16] they found no significant difference in the prevalence of AN among men and women.

The higher prevalence of AN in the age group of 25–34 years and in female population might be attributed to the fact that the psychological burden of AN on the quality of life is important and also they are relatively more conscious cosmetically.

In this study, nape of the neck was the most common site involved (100%), followed by axilla (31%), face (21%), and groin (18%). Other sites such as antecubital fossa (5%), knuckles (3%), and submammary areas (1%) were also involved. This was comparable to several other studies carried out by various authors: in a study by Varthakavi et al.,[8] neck (100%), axilla (80.6%), and groin (61.1%); in a study by Puri,[5] neck (93.3%) and axilla (66.6%); in a study by Grandhe et al.,[15] nape of the neck (93.5%); in a study by Hoffmann et al.,[11] neck (94%), followed by the axillae (45%); and in a study by Kamel et al.,[14] neck (100%) and axilla (76.7%) were the most common sites involved.

The predilection of AN for areas such as the neck and axillae suggests that perspiration and/or friction may also be necessary cofactors.

In our study, the mean duration of AN was 32.21 (months), that is, 2.7 years, whereas in a study by Zayed et al.,[6] the mean duration was 9.4 years which was more than found in our study.

Relation of severity of acanthosis nigricans with metabolic syndrome

The severity of AN was assessed using Burke Scale of AN.

There was a statistically significant correlation of increasing severity of AN over the neck with each component of MS. We observed a very strong association between raised waist circumference with increase in the severity of AN (P < 0.0001). In addition, there was a positive correlation between the severity of AN over the neck with MS.

This is comparable with Grandhe et al.[15] who also reported a statistically significant correlation of increasing severity of AN with increasing BMI, waist circumference, hip circumference, waist–hip ratio, skinfold thickness, and body fat percentage in diabetic patients. Kamel et al.[14] also reported a positive correlation between the neck severity score with systolic pressure, diastolic BP, total cholesterol, and TG. Patidar et al.[10] reported a significant correlation of increasing severity of AN neck with FBS levels.

Compare the prevalence of metabolic syndrome in patients with acanthosis nigricans as compared to the control population

In this study, we calculated each parameter of MS as per the US National Cholesterol Education Program Adult Treatment Panel III (2001). We observed that each of the parameter (waist circumference, BP, FBS, serum TG level, and HDL-C levels) had a positive correlation in cases as compared to the controls. Furthermore, MS had a statistically significant correlation in cases (70%) as compared to the controls (17%) with the odds ratio of 11.39.

This is comparable to studies carried out by Balaji et al.[4] who reported 90.9% cases had MS as compared to 26.8% controls.

Our study emphasizes on the established fact that AN is a predictor of MS.


  Conclusion Top


MS is typically not associated with symptoms in the early stages. AN may be one of the presenting complaints of MS for which the patient might present to the dermatologist for cosmetic purpose. These patients should be investigated further for MS.

Obesity, hypertension, and dyslipidemia are the contributing factors to MS. Correcting these factors will assist in the clinical improvement of AN, which is very difficult and frustrating to treat with available treatment options.

Thus, patients with AN can be targeted for lifestyle and behavioral modifications at an early stage to avoid the serious consequences of MS.

Limitations

Larger sample size needs to be studied. The data were analyzed cross sectionally, and thus long-term outcomes cannot be ascertained. Patients were not investigated for insulin levels, and thus association of AN with IR was not studied. Furthermore, histopathological and genetic evaluation of the patients was not done which may help to improve the further understanding of pathogenesis and changes in the treatment options available for AN.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sinha S, Schwartz RA. Juvenile acanthosis nigricans. J Am Acad Dermatol 2007;57:502-8.  Back to cited text no. 1
    
2.
Barbato MT, Criado PR, Silva AK, Averbeck E, Guerine MB, Sá NB, et al. Association of acanthosis nigricans and skin tags with insulin resistance. An Bras Dermatol 2012;87:97-104.  Back to cited text no. 2
    
3.
Guran T, Turan S, Akcay T, Bereket A. Significance of acanthosis nigricans in childhood obesity. J Paediatr Child Health 2008;44:338-41.  Back to cited text no. 3
    
4.
Balaji C, Vindhya M, Gurukul S. Significance of acanthosis nigricans as marker for metabolic syndrome. World J Med Sci 2014;10:295-8.  Back to cited text no. 4
    
5.
Puri N. A study of pathogenesis of acanthosis nigricans and its clinical implications. Indian J Dermatol 2011;56:678-83.  Back to cited text no. 5
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6.
Zayed A, Sobhi RM, Abdel Halim DM. Using trichloroacetic acid in the treatment of acanthosis nigricans: A pilot study. J Dermatolog Treat 2014;25:223-5.  Back to cited text no. 6
    
7.
Ehsani A, Noormohammadpour P, Goodarzi A, Mirshams Shahshahani M, Hejazi SP, Hosseini E, et al. Comparison of long-pulsed alexandrite laser and topical tretinoin-ammonium lactate in axillary acanthosis nigricans: A case series of patients in a before-after trial. Caspian J Intern Med 2016;7:290-3.  Back to cited text no. 7
    
8.
Varthakavi PK, Waingankar A, Patel KL, Wadhwa SL, Khopkar U, Sengupta RA, et al. Acanthosis nigricans: A dermatologic marker of metabolic disease. Indian J Dermatol Venereol Leprol 2002;68:67-72.  Back to cited text no. 8
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Treesirichod A, Chaithirayanon S, Wongjitrat N, Wattanapan P. The efficacy of topical 0.1% adapalene gel for use in the treatment of childhood acanthosis nigricans: A pilot study. Indian J Dermatol 2015;60:103.  Back to cited text no. 9
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Patidar PP, Ramachandra P, Philip R, Saran S, Agarwal P, Gutch M, et al. Correlation of acanthosis nigricans with insulin resistance, anthropometric, and other metabolic parameters in diabetic Indians. Indian J Endocrinol Metab 2012;16:S436-7.  Back to cited text no. 10
    
11.
Hoffmann M, Visser WI, Hough FS, Africa S. The prevalence and clinical significance of acanthosis nigricans in diabetic and non-diabetic women of mixed ancestry. J Endocrinol Metab Diabetes South Afr 2015;20:87-91.  Back to cited text no. 11
    
12.
Stoddart ML, Blevins KS, Lee ET, Wang W, Blackett PR, Cherokee Diabetes Study. et al. Association of acanthosis nigricans with hyperinsulinemia compared with other selected risk factors for type 2 diabetes in cherokee Indians: The cherokee diabetes study. Diabetes Care 2002;25:1009-14.  Back to cited text no. 12
    
13.
Kong AS, Vanderbloemen L, Skipper B, Leggott J, Sebesta E, Glew R, et al. Acanthosis nigricans predicts the clustering of metabolic syndrome components in hispanic elementary school-aged children. J Pediatr Endocrinol Metab 2012;25:1095-102.  Back to cited text no. 13
    
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Kamel AM, Hassan MA, Ibrahim MY. Relation between the severity of acanthosis nigricans and metabolic syndrome components. J Egypt Women's Dermatol Soc. 2013;10:75-80.  Back to cited text no. 14
    
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Grandhe NP, Bhansali A, Dogra S, Kumar B. Acanthosis nigricans: Relation with type 2 diabetes mellitus, anthropometric variables, and body mass in Indians. Postgrad Med J 2005;81:541-4.  Back to cited text no. 15
    
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Karadağ AS, You Y, Danarti R, Al-Khuzaei S, Chen W. Acanthosis nigricans and the metabolic syndrome. Clin Dermatol 2018;36:48-53.  Back to cited text no. 16
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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