Acanthosis nigricans

Overview

Acanthosis nigricans (AN) is a skin disorder in which there is darker, thick, velvety skin in body folds and creases. This condition usually appears slowly and doesn't cause any symptoms other than skin changes. Eventually, dark, velvety skin with very visible markings and creases appears in the armpits, groin and neck folds, and over the joints of the fingers and toes. Less commonly, the lips, palms, soles of the feet, or other areas may be affected.

Symptoms

Acanthosis nigricans usually appears slowly and doesn't cause any symptoms other than skin changes. Eventually dark, velvety skin with very visible markings and creases appears in the armpits, groin, and neck. Sometimes, the lips, palms, soles of feet, or other areas may be affected.

Causes

The exact cause of this condition is not well understood; but it can be inherited or related to medical problems such as obesity, diabetes mellitus (insulin- resistance), some prescription drugs, and cancer.

Eight types of AN have been described.

  Obesity-associated AN,

once labeled pseudo-AN, is the most common type of AN.

  • Lesions may appear at any age but are more common in adulthood.
  • The dermatosis is weight dependent, and lesions may completely regress with weight reduction.
  • Insulin resistance is often present in these patients; however, it is not universal.

Syndromic AN:

It is the name given to AN that is associated with a syndrome. In addition to the widely recognized association of AN with insulin resistance, AN has been associated with numerous syndromes. The type A syndrome and type B syndrome are special examples.

  • The type A syndrome also is termed the hyperandrogenemia, insulin resistance, and AN syndrome (HAIR-AN syndrome). This syndrome is often familial, affecting primarily young women (especially black women). It is associated with polycystic ovaries or signs of virilization (eg, hirsutism, clitoral hypertrophy). High plasma testosterone levels are common. The lesions of AN may arise during infancy and progress rapidly during puberty.
  • The type B syndrome generally occurs in women who have uncontrolled diabetes mellitus, ovarian hyperandrogenism, or an autoimmune disease such as systemic lupus erythematosus, scleroderma, Sj√∂gren syndrome, or Hashimoto thyroiditis. Circulating antibodies to the insulin receptor may be present. In these patients, the lesions of AN are of varying severity.

Acral AN (acral acanthotic anomaly):

It occurs in patients who are in otherwise good health.

  • Acral AN is most common in dark-skinned individuals, especially those of African American descent.
  • The hyperkeratotic velvety lesions are most prominent over the dorsal aspects of the hands and feet.

Unilateral AN:

sometimes referred to as nevoid AN, is believed to be inherited as an autosomal dominant trait.

  • Lesions are unilateral in distribution and may become evident during infancy, childhood, or adulthood.
  • Lesions tend to enlarge gradually before stabilizing or regressing.

Familial AN:

It is a rare genodermatosis that seems to be transmitted in an autosomal dominant fashion with variable phenotypic penetrance.

  • The lesions typically begin during early childhood but may manifest at any age.
  • The condition often progresses until puberty, at which time it stabilizes or regresses.

Drug-induced AN:

Although uncommon, may be induced by several medications, including nicotinic acid, insulin, pituitary extract, systemic corticosteroids, and diethylstilbestrol.

  • Rarely, triazinate, oral contraceptives, fusidic acid, and methyltestosterone also have been associated with AN.
  • The lesions of AN may regress following the discontinuation of the offending medication.

Malignant AN:

Which is associated with internal malignancy, is the most worrisome of the variants of AN because the underlying neoplasm is often an aggressive cancer.

  • AN has been reported with many kinds of cancer, but, by far, the most common underlying malignancy is an adenocarcinoma of gastrointestinal origin, usually a gastric adenocarcinoma. In an early study of 191 patients with malignant AN, 92% had an underlying abdominal cancer, of which 69% were gastric. Another study reported 94 cases of malignant AN, of which 61% were secondary to a gastric neoplasm.
  • o In 25-50% of cases of malignant AN, the oral cavity is involved. The tongue and the lips most commonly are affected with elongation of the filiform papillae on the dorsal and lateral surfaces of the tongue and multiple papillary lesions appearing on the commissures of the lips. Oral lesions of AN seldom are pigmented.
  • o Malignant AN is clinically indistinguishable from the benign forms; however, one must be more suspicious if the lesions arise rapidly, are more extensive, are symptomatic, or are in atypical locations.
  • o Regression of AN has been seen with treatment of the underlying malignancy, and reappearance may suggest recurrence or metastasis of the primary tumor.

Mixed-type AN:

It refers to those situations in which a patient with one of the above types of AN develops new lesions of a different etiology. An example of this would be an overweight patient with obesity-associated AN who subsequently develops malignant AN.

Diagnosis

Acanthosis nigricans is typically detected during a skin exam. Rarely, a small skin sample is removed (biopsied) for examination in a lab. If the cause of acanthosis nigricans is unclear, your doctor may recommend blood tests, X-rays or other tests to look for possible underlying causes.

Prognosis

Acanthosis nigricans is likely to improve in circumstances where a known cause is removed. For example, obesity-related acanthosis nigricans will improve with weight loss, and drug-induced acanthosis nigricans is likely to resolve when the drug is ceased. Hereditary variants may or may not fade with age, and malignancy-associated variants may, after a malignancy is removed, fade.[

Treatment

There is no specific treatment for AN. Treatments are used mostly to improve cosmetic appearance and include topical retinoids, vitamin D creams (such as calcipotriol), dermabrasion and laser therapy. Oral retinoid pills have also been used to treat AN, but are not used for most patients because of the multiple side effects and development problems associated with the treatment. Treatment may also focus on trying to correct the underlying disease that causes AN to develop. Often correcting the underlying disease improves the skin symptoms. Some steps that can be taken depending on the underlying disease include: correcting hyperinsulinaemia through diet and medication, losing weight with obesity-associated AN, removing or treating a tumor, or stopping medications that cause AN.

Resources

  • NIH