Acanthosis nigricans: Signs and symptoms, causes
The prevalence of the syndrome is unclear and varies markedly between populations. Acanthosis nigricans is a valuable marker of hyperinsulinemia and insulin resistance in adults and children.
In the folds of the body, the skin thickens, gray-black. It is usually symmetrical and feels as smooth as velvet to the touch. Or appear on the back of the neck, armpits, groin, abdominal folds.
Type 2 diabetes.
Polycystic ovary syndrome (PCOS).
Other causes of hyperinsulinemia.
Figure: Acanthosis nigricans
The mechanism is complex, with insulin resistance being the predominant factor. This increases blood insulin, stimulates hyperplasia of keratinocytes (mainly containing melanin) and fibroblasts.
Figure: Mechanism of Acanthosis nigricans
Normal keratinocytes multiply from the thick stratum corneum of the skin. During that process, the pigment melanin is carried into their nucleus. The overgrowth of these cells, due to increased peripheral insulin, makes the skin thicker, as well as darker, because more melanin is present.
Similarly, fibroblasts produce collagen. Excessive proliferation leads to collagen deposition and when combined with a proliferative stratum corneum, can produce the distinctive sensation of acanthosis nigricans.
Hyperinsulinemia stimulates proliferation by:
Direct stimulation of insulin-like growth factor-1 (IGF-1) receptors on fibroblasts and cell keratinocytes lead to proliferation.
Decreased levels of IGF-1 binding protein.
This reduces blood levels of free IGF-1, stimulates IGF-1 receptors on fibroblasts and keratinocytes leading to proliferation.
Some other mediators may include:
Epidermal growth factor receptor (EGFR)
Fibroblast growth factor receptor (FGFR)
The three types of insulin resistance include:
Type A – the abnormal function of insulin receptors.
Type B – the appearance of antibodies against insulin receptors.
Type C – structural defect in the insulin receptor. Such deficiencies may be responsible for peripheral hyperinsulinemia, thereby leading to acanthosis nigricans.
There is evidence that in obese patients there is an abnormal function of insulin receptors, leading to compensatory increases in insulin levels. High concentrations of insulin stimulate IGF-1 receptors in keratinocytes, causing proliferation.
In acromegaly, two pathways contribute to acanthosis nigricans. Firstly, there is an excessive increase in the concentration of growth hormone, which increases the production of IGF-1, stimulates the IGF-1 receptor in keratinocytes. Second, there is insulin resistance, leading to increased peripheral insulin levels, causing the proliferation of keratinocytes and fibroblasts.
Some malignancies can lead to acanthosis nigricans because they either produce antibodies against the insulin receptor (stimulate insulin secretion) or produce growth factors such as epidermal growth factor, which contribute to the above symptoms.
The prevalence of the syndrome is unclear and varies markedly between populations. Acanthosis nigricans is a valuable marker of hyperinsulinemia and insulin resistance in adults and children. In addition, acanthosis nigricans is strongly associated with risk factors for type 2 diabetes, and progression of metabolic syndrome, and is correlated with obesity severity. It is considered an independent risk factor for the progression of diabetes. Studies continue to show acanthosis nigricans as a prognostic indicator in children. Several recent studies have shown that, in young patients (8-12 years) with acanthosis nigricans, more than 25% have a change in glucose metabolism.