What are the other Names for this Condition? (Also known as/Synonyms)

• AN (Acanthosis Nigricans)

What is Acanthosis Nigricans? (Definition/Background Information)

• Acanthosis Nigricans (AN) is a skin condition that causes thick, velvety, and darkened skin areas (due to increased thickness of epidermis). Etymologically, acanthosis indicates ‘thorn’ in Greek and nigricans indicates ‘becoming black’ in Latin
• It commonly affects the skin of the armpits, the groin region, head and neck (back of the neck), and anal/genital region. This skin condition typically presents in a symmetric manner (i.e., equally in either sides of the body)
• Acanthosis Nigricans is not contagious, and it cannot be transmitted from individual to another. It is associated with many disorders, such as obesity, diabetes, and malignancy. Hence, it is not described as a disease in itself, but rather as a sign that can be seen due to other conditions
• There are seven different types and causes of Acanthosis Nigricans that include:
  • Malignancy-Associated Acanthosis Nigricans 
  • Mixed-Type Acanthosis Nigricans 
  • Syndromic Acanthosis Nigricans 
  • Obesity-Associated Acanthosis Nigricans: It is the most common type of AN
  • Acral Acanthotic Anomaly 
  • Hereditary Benign Acanthosis Nigricans
  • Drug-Induced Acanthosis Nigricans 
• Acanthosis Nigricans is usually diagnosed by a thorough clinical history and physical examination. Even though it is a benign condition, dermatologist consultation and testing is necessary to rule out other causes of Acanthosis Nigricans and identify the specific type of AN. It can also help prevent long-term complications due to these associated conditions
  • If obesity or diabetes is present or suspected, blood glucose level, HbA1c, leptin, lipid profile, and insulin levels may be assessed
  • If malignancy is suspected as an underlying cause, appropriate workup, such as imaging studies and blood tests, may be necessary
• There is no definitive treatment for Acanthosis Nigricans. Certain treatment modalities may be used for cosmetic reasons. The treatment of any associated underlying condition is warranted and is undertaken
• The prognosis of skin lesions, as such, is excellent with no known major complication being observed. However, the overall prognosis of Acanthosis Nigricans, depends on the underlying/associated condition (if any) and the severity of the signs and symptoms

Who gets Acanthosis Nigricans? (Age and Sex Distribution)

• Acanthosis Nigricans (AN) is seen all over the world, though some subtypes are more common among certain age groups, certain parts of the world, or among certain racial or ethnic populations
  • The benign type is more commonly observed in sub-Saharan regions
  • Hereditary-Type Acanthosis Nigricans may be present at birth or may develop later during childhood
  • Malignancy-Associated Acanthosis Nigricans is usually seen in individuals over 40 years of age
• In general, individuals of any age group can be affected. AN is more common in individuals with darker skin tones
• Both males and females of all races and ethnicities can be affected
• Acanthosis Nigricans of benign type and obesity-associated type is more common in individuals with darker skin tones such as Africans, Native Americans, and Latin American populations

What are the Risk Factors for Acanthosis Nigricans? (Predisposing Factors)

Acanthosis Nigricans generally occur in healthy individuals. Following are some of the known risk factors for various types of Acanthosis Nigricans:

• Syndromic Acanthosis Nigricans is associated with certain syndromes (that are constellation of signs and symptoms that occur together and characterize a particular abnormality) such as Prader Willi syndrome and Alstrom syndrome. In these syndromes, there is abnormality in the functioning of some of the endocrine glands 
• Medications such as nicotinic acid (niacin), oral contraceptives, systemic corticosteroids and insulin injection (localized to injection site) may precipitate Drug-Induced Acanthosis Nigricans 
• In Malignancy-Associated Acanthosis Nigricans, cancers of stomach (most common), colon, liver, endometrium, and other sites may be risk factors
• In Hereditary-Type Acanthosis Nigricans, the disease is inherited in an autosomal dominant pattern. An autosomal dominant trait means that either of the parent can carry an abnormal gene and pass on the disorder to their offspring

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Acanthosis Nigricans? (Etiology)

Acanthosis Nigricans is seen in a variety of clinical conditions and can be caused by multiple mechanisms.

• Some scientists believe that it is caused by certain growth factors which stimulate the proliferation of cells of the skin (called keratinocytes and dermal fibroblast)
• In certain types of Acanthosis Nigricans, the lesions can form due to insulin resistance
  • Insulin resistance results when the activity of insulin hormone is impaired at the site of its action. Insulin resistance is common in those with diabetes type 2 and obesity
  • Because of insulin resistance, the body secretes more insulin (a condition termed as hyperinsulinemia) as a compensatory mechanism which causes thickening of the epidermis. Insulin, as such, has growth promoting properties, stimulating the proliferation of cells of skin
• The Acanthosis Nigricans type that is associated with malignancies is caused by mutation of a substance, called transforming growth factor-alpha (TGF-alpha), which is either secreted by the tumor cells or by the body, in response to the tumor. Increased levels of TGF-alpha cause a proliferation of the skin cells. TGF-alpha levels in blood and urine may drop after the malignant tumor is removed
• Acanthosis Nigricans can also be due to mutation in the fibroblast growth factor genes, such as FGFR 2 (Beare-Stevenson syndrome) and FGFR 3 (Crouzon syndrome)
• Certain medications, such as insulin injections and palifermin, presumably cause Drug-Induced Acanthosis Nigricans due to activation of fibroblast growth factor receptor. Other causes of Drug-Induced Acanthosis Nigricans are nicotinic acid, systemic steroids, growth hormone therapy, etc.

What are the Signs and Symptoms of Acanthosis Nigricans?

The signs and symptoms of Acanthosis Nigricans include:

• It most commonly presents as hyperpigmented, velvety, poorly-defined skin lesions, mostly found on the skin folds such as the axilla (armpits), groin, back of the neck, and anal/genital region
• Sometimes, it can affect areas behind the knees, front of elbows, under the breasts, or navel region. Some have reported Acanthosis Nigricans to have involved the entire skin of the body. With time, the lesions can become warty in appearance
• In Acral-Type Acanthosis Nigricans, the lesions are limited to the top portion of the feet, elbows, knuckles, and knees
• The hyperpigmentation can be either brown or black in color. The skin lesions may cause itching and may even have a foul smell
• With the exception of Malignancy-Induced Acanthosis Nigricans, the individuals are usually healthy. In this type, the severity of skin lesion is greater; it may also involve the mucosal membranes, the palms, and the soles of the feet. The lesions may appear suddenly (when there is a cancer background), whereas in other subtypes, they appear gradually over a period of time
• In Obesity-Associated Acanthosis Nigricans, the severity of the lesion is proportional to the body weight of the individual

How is Acanthosis Nigricans Diagnosed?

The following may be used to diagnose Acanthosis Nigricans:

• Thorough evaluation of the individual’s medical history and a complete physical examination
• During history-taking, the physicians may enquire about the following:
  • When the symptoms began and whether they are becoming worse
  • List of prescription and over-the-counter medications currently being taken
  • About one’s personal and family history of cancer, diabetes, thyroid abnormalities, ovarian and adrenal gland problems, etc.
• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Since Acanthosis Nigricans can be associated with cancer, workup for the same may be indicated if clinical conditions warrant it. The tests may include blood workup, endoscopy, radiological imaging studies such as CT and MRI scans
• Diabetes screening by checking fasting blood glucose or HbA1C levels may be indicated
• Measuring insulin levels in blood may be necessary, if insulin resistance is suspected. The insulin levels in such individuals may be high
• A skin biopsy (of the affected skin area) is performed and sent to a laboratory for a pathological examination, who examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

Note: A skin biopsy is only rarely performed, when the diagnosis is questionable, or if it resembles other similar skin conditions.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Acanthosis Nigricans?

Complications due to Acanthosis Nigricans (AN) may include:

• The skin lesions of AN generally do not cause any medically-related problems, but it can result in low self-esteem due to cosmetic concerns
• Children who develop AN have a greater tendency to develop diabetes mellitus type 2 later in their life

How is Acanthosis Nigricans Treated?

Treatment measures for Acanthosis Nigricans depend on the subtype and associated conditions. It may include the following:

• Dermatologist consultation: It is often necessary, as they are the experts in dealing with various skin conditions
• Topical retinoids, bleaching cream, dermabrasion therapy, and long-pulsed alexandrite laser skin therapy are used for addressing the cosmetic issues only. However, they are not a definitive treatment for Acanthosis Nigricans 
• If AN presents with bad odor, then antibacterial soap or antibiotic cream may be helpful
• If diabetes is the underlying cause of Acanthosis Nigricans, appropriate management of diabetes is essential
• When obesity is the underlying cause, weight loss management is recommended
• In individuals with insulin resistance, physicians may prescribe appropriate medications. Sometimes, dietary fish oils may also be prescribed
• With insulin resistance, consistent dietary restriction of sugars and carbohydrates over a moderately long time can reverse the metabolic condition, and the AN improves 
• If malignancy is the reason, then treatment of malignancy may help resolve the skin lesions
• Treatment of the underlying syndrome is essential and is considered more important than treating the skin lesions
• If Acanthosis Nigricans is caused as a side effect of a medication, stopping the medication or recommending other alternatives can resolve the condition

In case Acanthosis Nigricans is caused due to hereditary factors/conditions, there are currently no specific treatment options available to address them.

How can Acanthosis Nigricans be Prevented?

The prevention of Acanthosis Nigricans depends on the underlying cause of the condition.

• In majority of cases, Acanthosis Nigricans may not be preventable
• Certain types of benign Acanthosis Nigricans may be prevented through proper blood sugar control and weight reduction
• Individuals, who are obese or overweight, may take suitable lifestyle measures to reduce their weight

What is the Prognosis of Acanthosis Nigricans? (Outcomes/Resolutions)

• In general, Acanthosis Nigricans is a skin sign, and by itself is benign. Thus, the prognosis of Acanthosis Nigricans is excellent with adequate (skin) treatment. However, the overall prognosis depends upon the underlying cause of the condition
• If Acanthosis Nigricans is caused by an underlying benign condition, then the prognosis is excellent with appropriate therapy
• If Acanthosis Nigricans is caused due to underlying malignancy, the prognosis depends on the stage of the cancer and response to treatment

Additional and Relevant Useful Information for Acanthosis Nigricans:

• When the biopsied skin tissue is seen by a pathologist under the microscope, the lesions may demonstrate a benign epidermis with hyperkeratosis, papillomatosis, thickening of epidermis (Acanthosis), hyperkeratosis, increased number of melanocytes (melanocytic hyperplasia), and lymphocytic inflammation
• Interestingly, there are only a few conditions with acanthosis with no hyperpigmentation that do not fit the histologic terminology. The hyperpigmented appearance is actually due to hyperkeratosis
• Microscopically, all the seven types of Acanthosis Nigricans share similar features
• Acanthosis Nigricans was first described in 1889 by Unna and Pollitcer in Germany