Question 1 of 10

    Acanthosis Nigricans (Keratosis Nigricans)


    Acanthosis nigricans is a skin disorder characterized by abnormal hyperpigmentation and hyperkeratosis, common in the neck, axilla and groin. Acanthosis nigricans may be a benign condition, but possibly also associated with a malignancy.


    In general, patients show an area of darkening and thickening of skin without any symptoms. Occasionally, pruritus may be seen. The lesions often start as hyperpigmented macules and patches and progress into plaques that are palpable [6] [7].

    In one out of three average cases of malignant acanthosis nigricans, the patients show skin changes before the signs of cancer become visible. In another one out of three of cases, the lesions of the acanthosis nigricans arise at the same time as the neoplasm. In other cases, the skin findings only become visible after cancer has been diagnosed. Cases of abrupt and exuberant appearance of acanthosis nigricans are common and they are associated with a higher rate of pruritus.

    The onset of the disorder can be traced to medication or supplement usage.

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  • Workup

    For patients with the adult onset of acanthosis nigricans, a basic workup for an underlying malignancy is carried out.

    The individual also has to be screened for diabetes using a glycosylated hemoglobin level or glucose tolerance test.

    The next screening to be done is for insulin resistance. One good screening test for insulin resistance is a plasma insulin level and this is often high in those with insulin resistance [8]. This test is the most sensitive in detecting a metabolic abnormality like this because younger patients do not have overt diabetes mellitus as well as a glycosylated hemoglobin level but they often show a high level of plasma insulin.


    There is no choice treatment for acanthosis nigricans. The major aim of therapy is to ensure that the underlying disease process is corrected. The treatment of the lesions is only for cosmetic reasons. The burden of hyperkeratotic lesions is reduced by the correction of hyperinsulinemia [9]. Also, weight reduction in obesity associated acanthosis nigricans may lead to a resolution of the dermatosis.

    For drug induced acanthosis nigricans, cessation of the inciting agent brings about a resolution of the condition. Nicotinic acid may be replaced by acipimox to bring about the regression of acanthosis nigricans even as the lipid profile continues to improve. Even if niacin is continued, dietary fish oil has been reported to be beneficial in patients with lipodystrophic diabetes and generalized acanthosis nigricans.


    Benign acanthosis nigricans generally fades off after the cause is detected and treated. For patients with malignant acanthosis however, the prognosis is often poor. The malignancy associated with it is frequently advanced and in in general, the average survival of the patients is approximately 2 years [5].


    Endocrine Dysfunction
    • Acanthosis nigricans associated with endocrine dysfunction is more insidious in its onset, is less widespread, and the patients are often concurrently obese. [8] : 676 Type III – obesity and pseudoacanthosis nigricans [7] : 86 [ edit ] In young persons[]
    • Acanthosis nigricans juvenilis associated with obesity: report of a case, with observations on endocrine dysfunction in benign acanthosis nigricans.[]
    Prader-Willi Syndrome
    • Causes malignancy (especially gastric cancer) – esophageal, colon, renal, bladder lymphoma acromegaly insulin resistance e.g. type 2 diabetes mellitus, steroids, polycystic ovarian syndrome Prader Willi syndrome References and Links Sam AH.[]
    • […] polycystic ovarian disease Addison's disease and hypothyroidism Rare diseases, including pinealoma , leprechaunism , lipoatrophic diabetes , pineal hyperplasia syndrome, pituitary basophilism, ovarian hyperthecosis, stromal luteoma, ovarian dermoid cysts, Prader-Willi[]
    • […] nigricans (Lawrence-Seip syndrome) - Congenital generalized lipodystrophy (Seip-Berardinelli syndrome) - Familial partial lipodystrophy (Kobberling-Dunnigan syndrome) - Mental retardation, overgrowth, remarkable faces, and acanthosis nigricans (MORFAN) - Prader-Willi[]
    • 7] : 87 On biopsy, hyperkeratosis, epidermal folding, leukocyte infltration, and melanocyte proliferation may be seen. [2] : 979 [7] : 87 Differential diagnosis [ edit ] Acanthosis nigricans should be distinguished from the casal collar appearing in pellagra[]
    • Differential Diagnosis Differential diagnoses should also be done to rule out other similar disorders such as Pellagra, Hemochromatosis and Addison’s disease among others.[]
    Paraneoplastic Syndrome
    • ‘Malignant’ AN is a paraneoplastic syndrome and not a malignancy in itself.[]
    • They suggested that acanthosis nigricans with AIDS behaves like a paraneoplastic syndrome. [3] Another AIDS case has been described by Mellor-Pita et al ., in which the patient developed insulin resistance, diabetes mellitus and acanthosis nigricans after[]
    • syndrome associated with a cancer.[]
    • In this case acanthosis nigricans is a paraneoplastic syndrome.[]
    • Given the high prevalance of obesity, malignancy-associated AN is less common, however, it represents an important paraneoplastic syndrome.[]
    • It may even be mistaken for psoriasis or appear in conjunction with psoriasis.[]
    • Ocular manifestations are primarily papillomatous lesions of the lid margins, which may be so extensive as to cause punctal occlusion, as well as papillary conjunctivitis.[]
    • TGF acts on epidermal tissue via the EGFR . [7] : 86 In conjunction with increased end levels of ILGF, it is likely that perspiration and friction may be necessary predeterminants for lesions. [16] Diagnosis [ edit ] Acanthosis nigricans is typically[]


    The condition may be inherited genetically and it is associated with obesity. It can also be caused by endocrinopathies like hypothyroidism, acromegaly, polycystic ovary disease, insulin resistant diabetes or Cushing’s disease.


    Myocardial Infarction
    • An administered questionnaire was used to collect data on: age; sex; self-reported ethnicity; previous history of hypercholesterolemia, hypertension, myocardial infarction (MI) and/or cerebrovascular accident (CVA); family history of T2DM; duration of[]


    In the United States, the exact figure for the incidence of acanthosis nigricans is unknown. Within an unselected population of over 1400 children, the acanthosis changes were only visible amongst 7.1%. Obesity is closely linked with this disorder and so more than half of adults who weigh more than 200% of their ideal body weight have lesions that are closer to acanthosis nigricans.

    Internationally, epidemiologic studies that were performed in Iran, United Arab Emirates and Japan all present significant increases in the resistance of insulin amongst obese patients that have the condition in comparison to matched obese controls without the disorder. This shows that acanthosis nigricans is a very useful marker when looking at insulin resistance among obese patients irrespective of geographic setting [3].

    In patients with the benign form of acanthosis nigricans, there is very little complication on their skin lesions. Malignant complications on the other hand are often associated with significant complications because an aggressive tumor is often the underlying malignancy. For patients with the signs of malignant acanthosis, the average survival time is 2 year.

    However, there have been cases where patients survived for another 12 years. Virtually all older patients with new-onset acanthosis nigricans have an associated internal malignancy.

    This disorder is mostly seen amongst people with darker pigmentations of the skin. In whites, the prevalence is less than 1%. In Latinos, the prevalence was placed at 5.5% and in African Americans the prevalence is higher. It is placed at 13.3%. Amongst the Native American populace, one study showed that 34.2% of Cherokee patients aged 5-40 years with acanthosis nigricans. The figure increased to 73% amongst Cherokee patients with diabetes.
    Unlike the benign form, malignant acanthosis nigricans doesn’t have any racial predilection.

    The incidence of acanthosis nigricans is the same for both men and women so it doesn’t have a confirmed sex predilection.
    The benign lesions of acanthosis nigricans may be seen at any age even at birth. However, it is found more commonly amongst the adult population.

    Sex distribution
    Age distribution


    Factors that stimulate epidermal keratinocyte and proliferation of the dermal fibroblast have been pointed out as the main cause of fibroblast protection. With the benign form of acanthosis nigricans, the epidermal cell propagation is incited by insulin or insulin growth like factor [4]. Other mediators that have been proposed include tyrosine kinase receptors and fibroblast growth receptor.

    Insulin may exert potent proliferative effects via high-affinity binding to the IGF-1 receptors under high concentrations. Additional free IGF-1 levels may get elevated in obese patients with hyperinsulinemia. This leads to accelerated cell growth and differentiation.

    As suggested by the predilection of acanthosis nigricans, perspiration or friction may equally play a contributory role


    The help reduce chances of getting acanthosis nigricans, individuals are advised to take conscious steps towards maintaining a healthy body weight. Insulin levels should also be checked regularly to ensure that it is kept at a normal level [10].


    This is a skin condition that is characterized by areas of dark and velvety discolorations around creases and body folds. The affected area of skin thickens and in some cases, smells bad. In many cases, acanthosis nigricans is seen around the armpit, neck and groins [1].

    This type of changes in the skin is mostly seen in individuals who are either obese or have diabetes. When seen in children, it means that they have an increased risk of developing type 2 diabetes. On rare occasions, acanthosis nigricans depicts the possibility of a cancerous tumor in an internal organ like the stomach or liver.

    Even though Addison may have come across a case of acanthosis nigricans in 1885, misdiagnosing it as the Addison disease, the first case of acanthosis nigricans was recorded in 1889 in Germany. It was described by Unna and Pollitzer [2]. By 1909, acanthosis nigricans has been described in approximately 50 patients and it was suspected to be closely linked with internal malignancy. It was in 1976 that Khan et al published their landmark study in which the relationship between acanthosis nigricans and insulin was first described. In 2000, the American diabetes association proved acanthosis nigricans as a formal risk factor for the development of diabetes amongst children.

    Patient Information

    Keep in mind that acanthosis nigricans is not a skin disease. Instead it is a sign of an underlying problem. If the acanthosis nigricans case you are looking at has been proven by medical experts to be on the basis of insulin resistance, treating this metabolic abnormality will bring about an improvement in the appearance of the skin. With the right dietary changes and weight loss, acanthosis nigricans can be forced to regress almost completely [11].

    Other symptoms

    • Screening for insulin resistance with an evaluation of plasma insulin level can detect insulin resistance in younger patients who do not yet have an abnormal glycosylated hemoglobin level. 7 Addison’s disease, hypothyroidism and disorders of androgen[]
    • […] endocrine [4] : 506–7 [ edit ] Endocrine syndromes associated with acanthosis nigricans can develop in many conditions, particularly: [2] : 978 [7] : 86 starts with insulin resistance , such as diabetes mellitus and metabolic syndrome excess circulating androgens[]
    • Symptoms of cutaneous virilism due to hyperandrogenism include hirsutism, acne vulgaris, hidradenitis suppurativa and androgenic alopecia.[]
    • FSH and LH were significantly depressed, and she had elevated testosterone and free androgen index.[]
    • Insulin resistance with acanthosis nigricans: the roles of obesity and androgen excess.[]
    Rabson Mendenhall Syndrome
    • […] type 2 Nutritional / Metabolic Obesity , metabolic syndrome , hyperglycemia , peroxisome proliferator-activated receptor disorders, Rabson-Mendenhall syndrome , Bangstad syndrome , congenital generalized lipodystrophy type 1, congenital generalized lipodystrophy[]
    • Acanthosis nigricans has been reported to be associated with many different syndromes including Hirschowitz syndrome, Lawrence-Seip syndrome, Bloom syndrome, Rud syndrome and Rabson-Mendenhall syndrome.[]
    • […] syndrome) - Cushing syndrome - Diabetes Mellitus Type 2 - Gonadal dysfunction - Ovarian hyperthecosis - Polycystic ovary syndrome (PCOS, Stein-Leventhal syndrome) - Hyperplasia of the adrenal cortex, diabetes mellitus, and hypertrophy of the pineal body (Rabson-Mendenhall[]
    Donohue Syndrome
    • […] generalized lipodystrophy type 1, congenital generalized lipodystrophy type 2 Drug Side Effect Glucocorticoids , growth hormone therapy, insulin , niacin , oral contraceptives , protease inhibitors Ear Nose Throat No underlying causes Endocrine Acromegaly , Donohue[]
    • […] acanthosis nigricans Insulin resistance Diabetes mellitus Cushing’s syndrome HAIR-AN syndrome Hyperandrogenism Ataxia-telangectasia syndrome Bloom syndrome Cardio-facio-cutaneous syndrome Costello syndrome Following is a partial list of other causes: Donohue[]
    Dermoid Cyst
    Congenital Generalized Lipodystrophy Type 1
    • generalized lipodystrophy type 1, congenital generalized lipodystrophy type 2 Environmental No underlying causes Gastroenterologic Colon cancer , liver cancer , stomach cancer , congenital generalized lipodystrophy type 1, congenital generalized lipodystrophy[]


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    8. Nguyen TT, Keil MF, Russell DL, et al. Relation of acanthosis nigricans to hyperinsulinemia and insulin sensitivity in overweight African American and white children. J Pediatr 2001; 138:474.
    9. Stuart CA, Pate CJ, Peters EJ. Prevalence of acanthosis nigricans in an unselected population. Am J Med 1989; 87:269.
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    11. Brickman WJ, Binns HJ, Jovanovic BD, et al. Acanthosis nigricans: a common finding in overweight youth. Pediatr Dermatol 2007; 24:601.

    • Gastric carcinoma with acanthosis nigricans: An endocrine effect of TGF α in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the - S Koyama, K Ikeda, M Sato, K Shibahara - Journal of , 1997 - Springer

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