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Original Article

Acanthosis Nigricans: A Cutaneous Marker for Metabolic Syndrome

Nirali Girish Shah, Swapna S. Khatu, Neeta R. Gokhale, Yuvraj E. More, Deepak Khismatrao1

Departments of Dermatology Background: Acanthosis Nigricans (AN) is an easily identifiable dermatoses

Abstract
and 1Preventive and Social
Medicine, Smt. Kashibai
characterized by thickened, hyperpigmented plaques. Metabolic syndrome refers to
Navale Medical College a clustering of metabolic risk factors including central obesity, glucose intolerance,
and General Hospital, Pune, hyperinsulinemia, low HDL cholesterol, high triglycerides and hypertension. AN is a
Maharashtra, India 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.

Received: 08‑03‑2018
Keywords: Acanthosis nigricans, metabolic syndrome, severity of acanthosis
Accepted: 08-10-2018 nigricans

Introduction Metabolic syndrome

A canthosis 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]
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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
Address for correspondence: Dr. Nirali Girish Shah,
Department of Dermatology, Smt. Kashibai Navale Medical
College and General Hospital, Pune, Maharashtra, India.
E‑mail: nirali_101@hotmail.com
This is an open access journal, and articles are distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is
given and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com

DOI: How to cite this article: Shah NG, Khatu SS, Gokhale NR, More YE,
10.4103/mjdrdypu.mjdrdypu_44_18 Khismatrao D. Acanthosis nigricans: A cutaneous marker for metabolic
syndrome. Med J DY Patil Vidyapeeth 2019;12:16-21.

16 © 2019 Medical Journal of Dr. D.Y. Patil Vidyapeeth | Published by Wolters Kluwer ‑ Medknow

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Shah, et al.: Acanthosis nigricans
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:
i. To study clinicoepidemiological features of
100 patients with AN
ii. To study the relation of severity of AN with MS
iii. To compare the prevalence of MS in patients with
AN as compared to control population.
Subjects and Methods
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
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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
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%) [Tables 1 and 2, Graph 1].
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].
(P value= 0.000).
On comparing the severity of AN with components
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Shah, et al.: Acanthosis nigricans

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].
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].
Waist circumference
Graph 1: Age and sex distribution Out of the 100 cases, 69% had increased waist circumference
as compared to 22% of the controls (P = 0.000).
Table 1: Age distribution of the participants Blood pressure
Type of n Mean S.D S.E of t df P
Out of the 100 cases, 55% had hypertension, whereas
patient Mean
Cases 100 32.47 9.815 0.981 0.000 198 1.000^
only 21% of the controls had hypertension (P = 0.000).
Controls 100 32.47 9.815 0.981 Fasting blood sugar
^Statistically no significant difference The FBS level was high in 61% of the cases, whereas
only 27% of the controls had raised levels (P = 0.000).
Table 2: Sex distribution of the participants Serum triglyceride level
Sex Type of Patient
The serum TG level was high in 64% of the cases as
Cases Controls Total
Male n 38 38 76 compared to 29% of the controls (P = 0.000).
% 38.0% 38.0% 38.0% Serum high‑density lipoprotein‑cholesterol level
Female n 62 62 124 The serum HDL‑C levels were lower than the normal
% 62.0% 62.0% 62.0% level in 61% of the cases as compared to only 19% of
the controls (P = 0.000).
Table 3: Comparison of the severity of acanthosis Body mass index
nigricans with metabolic syndrome Out of the 100 cases of AN, 46% cases were obese
Severity of Acanthosis Metabolic Syndrome
(BMI >24) and as compared to 33% obese controls. The
Nigricans Yes No Total
difference was statistically significant [Table 6].
Grade I 7 (29.2%) 17 (70.8%) 24
Grade II 12 (54.4%) 10 (45.5%) 22 Metabolic syndrome
Grade III 22 (91.7%) 2 (8.3%) 24 Considering all the components of MS and comparing
Grade IV 29 (96.7%) 1 (3.3%) 30 the results between the cases and the controls,
Total 70 30 100 70 patients with AN had MS and only 17 controls had

Table 4: Comparison of the severity of acanthosis nigricans with each component of metabolic syndrome
Components of Metabolic Severity of Acanthosis Nigricans χ2 df P
Syndrome Grade I Grade II Grade III Grade IV
Cases (%) n=24 Cases (%) n=22 Cases (%) n=24 Cases (%) n=30
HDL Normal HDL 58.3 50.0 33.3 20.0 9.766 3 0.021*
Low HDL 41.7 50.0 66.7 80.0
Waist Normal 62.5 42.5 16.7 6.7 23.892 3 0.000***
Circumference Increased 37.5 57.5 83.3 93.3
Hypertension No 58.3 63.6 25.0 36.7 9.532 3 0.023*
Yes 41.7 36.4 75.0 63.3
Fasting Blood Normal 54.2 59.1 33.3 16.7 12.667 3 0.005**
Sugar Level High 45.8 40.9 66.7 83.3
Triglyceride Normal 66.7 36.4 25.0 20.0 14.391 3 0.002**
Level High 33.3 63.6 75.0 80.0
*Statistically significant as P<0.05

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Shah, et al.: Acanthosis nigricans

MS. The odds ratio was 11.39, and thus the difference
was statistically significant [Table 7].
Discussion
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%
Graph 2: Comparison of the severity of acanthosis nigricans with each
component of metabolic syndrome
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

Table 5: Comparison of each component of metabolic syndrome between cases and controls
Components of Metabolic Syndrome Cases % (n=100) Controls % (n=100) χ2 df P
HDL Normal HDL 39.0 81.0 36.750 1 0.000***
Low HDL 61.0 19.0
Waist Normal 31.0 78.0 44.541 1 0.000***
Circumference Increased 69.0 22.0
Hypertension No 45.0 79.0 24.533 1 0.000***
Yes 55.0 21.0
Fasting Blood Normal 39.0 73.0 23.458 1 0.000***
Sugar Level High 61.0 27.0
Triglyceride Normal 36.0 71.0 24.621 1 0.000***
Level High 64.0 29.0
***Statistically very highly significant as P<0.001

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Shah, et al.: Acanthosis nigricans
Table 6: Body mass index: Cases and controls comparison
Type of n Mean S.D S.E of t df P
patient Mean
Cases 100 29.42 4.555 0.455 5.900 198 0.000***
Controls 100 25.74 4.243 0.424
***Statistically very highly significant as P<0.001
Table 7: Comparison of metabolic syndrome between
cases and controls
Acanthosis Metabolic Syndrome
Nigricans Yes No
Yes 70 (a) 30 (b)
No 17 (c) 83 (d)
Total 87 113
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
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.
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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
Total Larger sample size needs to be studied. The data were
100 analyzed cross sectionally, and thus long‑term outcomes
100 cannot be ascertained. Patients were not investigated for
200 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.
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