Acanthosis Nigricans Clinical Presentation

Patients usually present with an asymptomatic area of darkening and thickening of the skin. Pruritus occasionally may be present. Lesions begin as hyperpigmented macules and patches and progress to palpable plaques.

In approximately one third of cases of malignant acanthosis nigricans, patients present with skin changes before any signs of cancer. In another one third of cases, the lesions of acanthosis nigricans arise simultaneously with the neoplasm. In the remaining one third of cases, the skin findings manifest sometime after the diagnosis of cancer. Malignant acanthosis nigricans has been reported to appear abruptly and exuberantly and may be associated with a higher rate of pruritus.^[1]

Onset may be related to medication or supplement usage.

Acanthosis nigricans is characterized by symmetrical, hyperpigmented, velvety plaques that may occur in almost any location but most commonly appear on the intertriginous areas of the axilla, groin, and posterior neck. The posterior neck is the most commonly affected site in children.

Acrochordons (skin tags) are often found in and around the affected areas. Occasionally, lesions of acanthosis nigricans may be present on the mucous membranes of the oral cavity, nasal and laryngeal mucosa, and esophagus. The areola of the nipple also may be affected. Eye involvement, including papillomatous lesions on the eyelids and conjunctiva, may occur. Nail changes, such as leukonychia and hyperkeratosis, have been reported.

The lesions of malignant acanthosis nigricans are clinically indistinguishable from benign acanthosis nigricans.

Note the images below.

The definitive cause for acanthosis nigricans has not yet been ascertained, although several possibilities have been suggested. Nine types of acanthosis nigricans have been described.

Obesity-associated acanthosis nigricans

Obesity-associated acanthosis nigricans, once labeled pseudo–acanthosis nigricans, is the most common type of acanthosis nigricans. 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.

Obesity-associated acanthosis nigricans may be a marker for higher insulin needs in obese women with gestational diabetes.^[15] Acanthosis nigricans has been shown to be a reliable early marker for metabolic syndrome in pediatric patients.^[16]

Syndromic acanthosis nigricans

Syndromic acanthosis nigricans is the name given to acanthosis nigricans that is associated with a syndrome. In addition to the widely recognized association of acanthosis nigricans with insulin resistance, acanthosis nigricans has been associated with numerous syndromes (see the Table in Pathophysiology). The type A syndrome and type B syndrome are special examples.

The type A syndrome also is termed the hyperandrogenemia, insulin resistance, and acanthosis nigricans 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 acanthosis nigricans 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, Sjögren syndrome, or Hashimoto thyroiditis. Circulating antibodies to the insulin receptor may be present. In these patients, the lesions of acanthosis nigricans are of varying severity.

Acral acanthosis nigricans

Acral acanthosis nigricans (acral acanthotic anomaly) occurs in patients who are in otherwise good health. Acral acanthosis nigricans is most common in dark-skinned individuals, especially those of African American or sub-Saharan African descent. The hyperkeratotic velvety lesions are most prominent over the dorsal aspects of the hands and feet, with knuckle hyperpigmentation often most prominent.

Unilateral acanthosis nigricans

Unilateral acanthosis nigricans, sometimes referred to as nevoid acanthosis nigricans, 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. Unilateral acanthosis nigricans lesions may represent a unilateral epidermal nevus.

Generalized acanthosis nigricans

Generalized acanthosis nigricans is rare and has been reported in pediatric patients without underlying systemic disease or malignancy.^[17]

Familial acanthosis nigricans

Familial acanthosis nigricans 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. Familial acanthosis nigricans often progresses until puberty, at which time it stabilizes or regresses.

Drug-induced acanthosis nigricans

Drug-induced acanthosis nigricans, although uncommon, may be induced by several medications, including nicotinic acid, insulin, pituitary extract, systemic corticosteroids, and diethylstilbestrol. Nicotinic acid is most widely recognized association, with acanthosis nigricans, developing on abdomen and flexor surfaces and resolving within 4-10 weeks of discontinuation.^[1] Rarely, triazinate, oral contraceptives, fusidic acid, and methyltestosterone have also been associated with acanthosis nigricans. Fibroblast growth factor receptor ligands such as palifermin may cause drug-induced acanthosis nigricans.^[7]

The lesions of acanthosis nigricans may regress following discontinuation of the offending medication.

Malignant acanthosis nigricans

Malignant acanthosis nigricans, which is associated with internal malignancy, is the most worrisome of the variants of acanthosis nigricans because the underlying neoplasm is often an aggressive cancer (see the Table in Pathophysiology).

Acanthosis nigricans 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 acanthosis nigricans, 92% had an underlying abdominal cancer, of which 69% were gastric. Another study reported 94 cases of malignant acanthosis nigricans, of which 61% were secondary to a gastric neoplasm.

Malignant acanthosis nigricans in pediatric patients has been described with gastric adenocarcinoma, Wilms tumor, and osteogenic sarcoma.^[1]

In 25-50% of cases of malignant acanthosis nigricans, 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 acanthosis nigricans seldom are pigmented.

Tripe palms may show altered dermatoglyphics due to alteration of epidermal rete ridges

Malignant acanthosis nigricans 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.

Regression of acanthosis nigricans has been seen with treatment of the underlying malignancy, and reappearance may suggest recurrence or metastasis of the primary tumor.

Mixed-type acanthosis nigricans

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