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

• Acanthosis Nigricans, Syndromic Type
• Syndromic AN

What is Syndromic 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). It commonly affects the skin of the armpits, the groin region, head and neck (back of the neck), and anal/genital region. The knuckles also can show the changes of AN
• Acanthosis Nigricans is not contagious, and it cannot be transmitted from one individual to another. It is associated with many disorders, such as obesity, diabetes, and malignancy
• Acanthosis Nigricans, Syndromic Type is one among the 7 types of Acanthosis Nigricans. It is especially linked to syndromes, which are a group of signs and symptoms that occur together and characterize a particular abnormality
• Syndromic Acanthosis Nigricans is associated with a variety of conditions including insulin resistance such as Cushing’s syndrome, polycystic ovary syndrome (PCOS), total lipodystrophy, and autoimmune disorder such as lupus erythematosus
• There are 2 types of Syndromic Acanthosis Nigricans and these include:
  • Type A (HA-IR-AN syndrome) presents with hyperandrogenemia (HA), insulin resistance (IR) and Acanthosis Nigricans (AN)
  • Type B presents with diabetes mellitus and ovarian hyperandrogenemia; which is observed in women
• Syndromic 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
• If diabetes is suspected as an underlying cause of Syndromic Acanthosis Nigricans, then testing for blood glucose and HbA1c levels may be performed
• There is no definitive treatment for Syndromic Acanthosis Nigricans. Certain treatment modalities may be used for cosmetic reasons. Also, treatment of the associated underlying condition is warranted and is typically undertaken
• The prognosis of skin lesions as such is excellent with no known major complication being observed. However, the overall prognosis of Syndromic Acanthosis Nigricans, depends on the underlying/associated condition and the severity of the signs and symptoms

Who gets Syndromic Acanthosis Nigricans? (Age and Sex Distribution)

• Individuals of any age group can be affected by Syndromic Acanthosis Nigricans, but it is most commonly seen in the adult population
• Both males and females of all races and ethnicities can be affected. A notable exception is Type B Syndromic Acanthosis Nigricans, which is only seen in females
• Acanthosis Nigricans is seen all over the world; there is no particular geographical restriction observed. Nevertheless, the condition is more common in individuals with darker skin tone

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

Following are some of the known risk factors for Syndromic Acanthosis Nigricans:

• Cushing’s syndrome
• Total lipodystrophy
• Autoimmune states such as systemic lupus erythematosus or inflammatory bowel diseases
• Prader-Willi syndrome
• Alstrom syndrome
• Polycystic ovary syndrome (PCOS)
• Poorly-functioning thyroid gland (hypothyroidism)
• Adrenal gland malfunction
• Hyperandrogenemia
• Poorly-controlled diabetes
• Rabson-Mendenhall syndrome
• Berardinelli-Seip syndrome
• Dunnigan syndrome
• Beare-Stevenson syndrome
• Crouzon syndrome

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 Syndromic Acanthosis Nigricans? (Etiology)

Syndromic Acanthosis Nigricans can be caused by multiple mechanisms. This subset of Acanthosis Nigricans, in particular, is a sign of an underlying syndrome.

• In this type and certain other subtypes of Acanthosis Nigricans, the lesions can be caused due to insulin resistance. Insulin resistance results when the activity of insulin hormone is impaired at the site of its action
  • In Type A Syndromic Acanthosis Nigricans, insulin receptor present on the surface of the cell is defective
  • In Type B Syndromic Acanthosis Nigricans, there are autoantibodies to the insulin receptor. Such individuals usually have other autoimmune diseases
  • Insulin resistance is also common in those with diabetes type 2, PCOS, and obesity
• Some scientists also believe that it is caused by certain growth factors which stimulate the proliferation of cells of the skin (namely keratinocytes and dermal fibroblast)
• It can also be due to mutation in the fibroblast growth factor genes, such as FGFR 2 (Beare-Stevenson syndrome) and FGFR 3 (Crouzon syndrome)

What are the Signs and Symptoms of Syndromic Acanthosis Nigricans?

The signs and symptoms of Syndromic Acanthosis Nigricans may include:

• It most commonly presents as hyperpigmented, velvety, poorly-defined skin lesions, most commonly on the skin folds such as the axilla (armpits), groin, and back of the neck
• The hyperpigmentation can be either brown or black
• Like other benign types of Acanthosis Nigricans, the skin lesions appear gradually
• Since Syndromic Acanthosis Nigricans has been associated with insulin resistance, individuals with conditions, such as obesity and or hypothyroidism, may get classic skin lesions
• The affected individuals may have other manifestations of the syndromes associated with AN

How is Syndromic Acanthosis Nigricans Diagnosed?

The following procedures may be used to diagnose Syndromic 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
• Various tests and imaging studies depending on the type of syndrome associated (or suspected) with the condition
• Diabetes screening by checking fasting blood glucose or HbA1C levels may be undertaken
• 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 Syndromic Acanthosis Nigricans?

Complications due to Syndromic Acanthosis Nigricans 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
• Complications due to the underlying conditions associated with Syndromic Acanthosis Nigricans (such as due to Cushing’s syndrome for instance)

How is Syndromic Acanthosis Nigricans Treated?

The treatment measures for Syndromic Acanthosis Nigricans may include the following:

• Dermatologist consultation: It is often necessary, as they are the experts in dealing with various skin conditions
• Topical retinoid, 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
• In individuals with insulin resistance, physicians may prescribe appropriate medications. Sometimes, dietary fish oils may also be prescribed
• If diabetes is the underlying cause of Acanthosis Nigricans, appropriate management of diabetes is essential

Treatment of the underlying condition/syndrome is essential and is considered more important than treating the skin lesions alone.

How can Syndromic Acanthosis Nigricans be Prevented?

• In majority of cases of Syndromic Acanthosis Nigricans, development of the skin lesions cannot be prevented
• In some individuals, they may be kept in control by good blood sugar control and weight reduction

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

• In general, Acanthosis Nigricans is a skin sign, which in 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
• The prognosis of Acanthosis Nigricans, Syndromic Type depends on the underlying cause of the condition and the severity of the signs and symptoms
• If Syndromic Acanthosis Nigricans is caused by an underlying benign condition, then the prognosis of the skin lesions is excellent with appropriate therapy. However, management of the underlying syndrome is essential for better outcomes of overall health

Additional and Relevant Useful Information for Syndromic 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 fewer acanthosis with no hyperpigmentation that do not fit the histologic terminology. The hyperpigmented appearance is actually due to hyperkeratosis
• Microscopically, all the 7 types of Acanthosis Nigricans share similar features