Acanthosis nigricans (AN) is a skin condition characterized by abnormally increased coloration (hyperpigmentation) and "velvety" thickening (hyperkeratosis) of the skin, particularly of skin fold regions, such as of the neck and groin and under the arms (axillae). Various benign (non-cancerous) forms of AN have been identified in which the disorder may be inherited as a primary condition or associated with various underlying syndromes, an excess accumulation of body fat (obesity), or the use of certain medications (i.e., drug-induced AN). In other instances, AN may occur in association with an underlying cancerous tumor (i.e., malignant AN).
Experts suggest that AN, may be a skin manifestation of insulin resistance, which is a condition characterized by impaired biological responses to insulin. Insulin, a hormone produced by the pancreas, regulates blood glucose levels by promoting the movement of glucose into cells for energy production or into the liver and fat cells for energy storage. (Glucose is a simple sugar that is the body's primary source of energy for cell metabolism.) Some clinicians suggest that insulin resistance causes a build-up of the hormone in the blood and then it finds its way into skin cells. Insulin resistance may be associated with various disorders, including obesity and non-insulin-dependent (type II) diabetes mellitus. In individuals with type II diabetes mellitus, the pancreas produces insulin but the body becomes resistant to its effects, leading to insufficient absorption of glucose and abnormally increased glucose levels in the blood (hyperglycemia) and urine. As a result, there may be a gradual onset of certain symptoms, including excessive urination (polyuria) and increased thirst (polydipsia), and the development of particular complications without appropriate treatment.
Acanthosis nigricans (AN) is characterized by increased coloration or pigmentation (hyperpigmentation) and abnormal thickening of the skin. The most commonly affected areas include the sides and back of the neck, under the arms (axillae), the groin, and the anal/genital region. In some instances, other body fold (i.e., flexure) regions may also be involved, such as behind the knees, in front of the elbows, under the breasts, and/or the navel (umbilicus) region. There have also been some reports in which almost all of the skin is affected.
In individuals with AN, initial changes may include the development of greyish brown or black pigmentation, excessive roughness and dryness, and noticeable thickening or overgrowth (hyperkeratosis) of the skin. Affected areas are covered with relatively small, elevated, “warty” (verrucous) tissue growths (papillomatous elevations), resulting in an unusual, velvety texture. With increasing skin thickening, regional skin lines become more accentuated, the skin surface may appear unusually wrinkled or ridged; and larger, wart-like outgrowths develop.
Benign AN may occur as a primary, isolated condition (known as hereditary benign AN) or be associated with various underlying disorders, conditions, or syndromes. (For more information, please see the “Causes” section of this report below.) In some cases of benign AN, associated skin abnormalities may be present at birth (congenital). However, they more commonly appear during childhood or puberty. The skin changes tend to develop slowly, may worsen during adolescence, and eventually stabilize or improve. In some affected individuals, the skin abnormalities may affect only one side of the body (unilateral). In addition, reports suggest that involvement is typically less severe and extensive than that seen in malignant AN (see below).
A benign variant of AN has also been described in which the condition occurs as a reversible skin manifestation associated with obesity. Known as “pseudoacanthosis nigricans,” the condition is thought to be most frequent in African-American or Hispanic individuals. Associated findings include relatively small regions of increased pigmentation and thickening as well as outgrowths of skin (skin tags) in body folds, particularly the groin, under the arms, and the cleft between the buttocks where the anus opens (anal or natal cleft). Reports suggest that certain skin changes may improve with weight loss; however, pigmentary abnormalities may tend to remain.
Benign AN has also been described in association with the use of certain medications. For further information on drug-induced AN, please see the “Causes” section below.
In some instances, AN occurs in association with an underlying cancerous tumor. Known as “malignant AN,” this form of the condition is most common in adults, particularly those over age 40, and appears to affect men and women relatively equally. The underlying malignancy is often derived from glandular tissue (adenocarcinoma), particularly of the stomach (gastric adenocarcinoma), or, less commonly, the intestines, pancreas, uterus, lung, ovary, bladder, breast, or prostate. Rarely, AN may occur in association with malignancy of the lymphatic system (lymphoma).
In individuals with malignant AN, skin changes are typically more extensive and severe than seen in benign AN. Findings may include thickening, unusual roughness and dryness, and/or potentially severe itching (pruritus) and irritation of affected skin regions. Pigmentary changes may be more pronounced than seen in benign AN and are not restricted to areas of hyperkeratosis. Malignant AN is also frequently associated with involvement of the mucous membranes and distinctive abnormalities of the mouth (oral) region. For example, reports indicate that there may be an unusually “shaggy” appearance of the lips and the back and sides of the tongue, potentially with elevated, wart-like, non-pigmented tissue growths (papillomatous elevations). Malignant AN is also commonly characterized by wart-like thickening around the eyes; unusual ridging or brittleness of the nails; thickening of the skin on the palms of the hands; hair loss; and/or other symptoms. Investigators indicate that the development of malignant AN, may occur as much as five years before the onset of other symptoms, although the time span is typically of shorter duration.
A variety of medically related factors can cause acanthosis nigricans. However, it can also appear in otherwise healthy individuals. Acanthosis nigricans is most commonly found in people of African descent and some cases are genetically inherited as an autosomal dominant trait. (Only one parent needs to have an abnormal gene in order for the child to inherit the disease.)
The medically related factors of AN include diabetes. Obesity, which leads to diabetes and other endocrine disorders, is also a medically related cause. Certain drugs such as human growth hormone or oral contraceptives can be a cause. Lymphoma or cancers of the gastrointestinal or genitourinary tract have been known to bring on severe cases of AN.
Acanthosis nigricans is a condition that may become apparent at any age. Many benign forms develop during childhood or puberty, while the onset of malignant AN, most frequently occurs after 40 years of age. However, there have been a few rare cases in which malignant AN occurred during childhood.
The frequency of occurrence of AN in the United States is not well known, although one study of more than 1400 children showed that about 7.1 percent showed signs of the condition. Another study of obese adults found that among patients weighing at least twice their “ideal body weight” more than 50 percent showed evidence of AN.
Acanthosis nigricans (AN) may be diagnosed based upon a thorough clinical evaluation, identification of characteristic physical findings, a complete patient history (including a careful medication history), a thorough family history, and various specialized tests. The age at detection may vary, depending upon the form of AN present and other factors. For example, benign forms of AN, often become evident during childhood or puberty. Less commonly, benign AN, may be apparent at birth or develop after puberty. The latter cases most typically involve AN in association with obesity (pseudoacanthosis nigricans).
In contrast, the onset of malignant AN, usually occurs after 40 years of age. According to experts, various factors may be suggestive of malignant AN in association with an underlying cancer. These include symptom onset in adulthood that is not associated with the use of particular medications, obesity, a positive family history, nor certain underlying disorders known to be associated with AN. Rarely, malignant AN may develop during childhood. In such instances, experts indicate that warning signs may include rapidly progressive skin changes and involvement of the mucous membranes.
In individuals with skin changes suggestive of AN, diagnostic assessment may include the use of various laboratory tests, such as analysis of insulin levels in the fluid portion of the blood (plasma); tests to measure glucose levels in the urine and blood; and/or assessment of glucose levels in blood and urine samples following consumption of a glucose dose by mouth (glucose tolerance test). Diagnostic evaluation may also include additional laboratory studies or other specialized tests to help detect or rule out certain underlying disorders, including various endocrine, autoimmune, and/or other conditions, that may be associated with AN and insulin resistance. Such analysis may include blood and urine tests to measure the levels of certain hormones; blood studies to detect antibodies directed against insulin receptors and/or other of the body's own cells (i.e., suggestive of certain autoimmune diseases); and/or other tests. In addition, in some cases, particularly for those with signs suggestive of malignant AN, testing may include removal (biopsy) and microscopic evaluation of small samples of affected skin tissue.
The treatment of acanthosis nigricans (AN) is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals. Depending on the age at symptom onset, the form of AN present, and/or the condition's underlying cause, such medical professionals may include pediatricians or internists; physicians who specialize in skin disorders (dermatologists); endocrine disorder specialists (endocrinologists); physicians who diagnose and treat cancer (medical oncologists), physicians who specialize in the use of radiation to treat cancers (radiation oncologists), surgeons, dietitians; and/or other professionals.
AN may resolve with therapy directed toward correcting or managing an underlying disorder or other causative condition, such as appropriate hormone replacement therapy for those with certain endocrine disorders; removal of medications that may cause drug-induced AN, if possible; and/or other measures to help reduce insulin resistance. In addition, in some cases, such as for those with insulin resistance associated with diabetes mellitus, disease management may include making appropriate dietary adjustments; regularly monitoring blood levels; taking certain medications by mouth (orally), receiving appropriate insulin replacement therapy; and/or other measures. As mentioned above, for those with pseudoacanthosis nigricans, sufficient weight loss under a physician's care may improve certain skin changes associated with AN. However, the pigmentary changes may tend to persist. In addition, for some with AN, recommended treatment may include the use of certain synthetic, vitamin A-like compounds (retinoids) administered by mouth or applied to the skin (topically).
For individuals with malignant AN, disease management requires treatment by cancer specialists (oncologists). Depending upon the specific form, stage, and grade of the malignancy and other factors, recommended treatment may include surgical removal of the malignancy; administration of certain anticancer drugs (chemotherapy); radiation therapy, and/or other measures. During radiation therapy, radiation (via x-rays or other sources of radioactivity) is passed through selected regions of the body to destroy cancer cells and shrink tumors. Reports indicate that AN has improved with therapy to treat underlying malignancies and has reappeared with tumor recurrences.
Genetic counseling may sometimes be of benefit for affected individuals and their families (e.g., for those with hereditary benign AN, or other underlying genetic causes of AN). Other treatment for this disorder is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
As of August 2006, there was one clinical study listed within the NIH information. This Yale University study focuses on carbohydrate intolerance in lean and obese children. Among other aspects, obese children from families with a history of diabetes who are affected by acanthosis nigricans are being studied. For information, contact Sonia Caprio, MD at (203) 785-4648.
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