Acanthosis Nigricans: Symptoms, Causes, Treatments

The  acanthosis nigricans is a thickening and hyperpigmentation of the stratum corneum of the skin, especially in areas skinfold, the perianal area and underarms. It is considered more of a symptom than a disease, since when it appears it is usually an indication on the outside of the body (skin) that something is wrong inside. 

In the affected areas, the skin appears warty, thick and darker than the surrounding integument. On many occasions, especially at the beginning, the person with acanthosis nigricans mistakes hyperpigmentation for dirt, so hygiene measures are extreme.

Acanthosis nigricans

However, over time you may notice that pigmentation increases and changes begin to appear in the skin (it becomes thicker due to hyperkeratosis), so that finally the affected person identifies the problem and seeks medical attention.

Symptoms

Thickening of the horny layer

Acanthosis nigricans generally does not have any symptoms other than skin changes; that is, the thickening of the horny layer of the skin associated with its hyperpigmentation, which at first takes a greyish color and then turns dark gray, almost black.

Appears in the folds

The most affected skin is usually the armpits, the perianal region, the nape (posterior region of the neck) and the skin folds, especially the area of ​​flexion of the elbows and groin.

It does not generate pain

An important characteristic is that acanthosis nigricans is not accompanied by any type of pain, itching, redness or discomfort, a fundamental characteristic to be able to make a differential diagnosis with respect to other skin conditions that can generate a similar appearance change in the skin.

Causes 

The most common cause of acanthosis nigricans is insulin resistance, accounting for more than 90% of cases of this condition.

It is believed that insulin resistance stimulates certain receptors at the level of keratinocytes (skin cells), which increase their growth speed, leading to the development of this condition.

However, depending on its type, acanthosis nigricans may be associated with other causes:

Acanthosis nigricans type I (hereditary)

It is the least frequent and the only one that appears during childhood. The lesions are usually much more extensive than in type II acanthosis nigricans and are often associated with scaling.

In these cases, the pattern is hereditary-family, so genetic predisposition plays a preponderant role.

Acanthosis nigricans type II (endocrine)

It is the most frequent and known. As already described, it is a consequence of the stimulation of certain cellular pathways that induce cell proliferation due to insulin resistance.

In addition, it can also be seen in other endocrine diseases such as diabetes mellitus, metabolic syndrome, hypothyroidism, Cushing’s disease, and polycystic ovary syndrome.

All of these medical conditions share at least one of two characteristics: peripheral insulin resistance and increased levels of circulating androgens; both situations are associated with the development of acanthosis nigricans.

Acanthosis nigricans type III (obesity)

It usually occurs in young people with dark skin phototypes (IV-V) and high body mass indexes. In essence, the cause of acanthosis nigricans in these patients is peripheral insulin resistance, such as in type II.

However, it falls into a different category, since insulin resistance in these cases is not primary but secondary to obesity. So, correcting obesity is expected to improve insulin resistance and, therefore, acanthosis nigricans.

Insulin resistance should be suspected in any obese patient with acanthosis nigricans, which is why a glucose tolerance curve is formally indicated.

Acanthosis nigricans type IV (secondary to medications)

Some medications such as glucocorticoids and growth hormone have been associated with the development of acanthosis nigricans. This is because at some point they generate a certain degree of insulin resistance.

Likewise, a causal relationship has been established between treatment with nicotinic acid and combined oral contraceptives (estrogen-progesterone) with this condition.

In all cases, the conditions of the affected skin are expected to improve by discontinuing the drug responsible for acanthosis.

Acanthosis nigricans type V (due to malignancy)

In these cases, acanthosis nigricans develops as a paraneoplastic syndrome. It is the one with the worst prognosis, not because of the acanthosis itself but because of the underlying disease.

The malignant pathologies most frequently associated with acanthosis nigricans are cancer of the stomach, genitourinary tract, breast, ovarian, lung, and some cases of lymphomas.

In any patient who presents with acanthosis nigricans and metabolic causes cannot be determined, screening for malignant diseases is mandatory, since in many cases acanthosis nigricans is the first (and sometimes the only) symptom of a hidden malignant disease.

Treatment 

Acanthosis nigricans does not respond to any local treatment on the skin, so hyperkeratosis (thickening) and hyperpigmentation cannot be reduced with any type of cream or lotion.

However, by correcting or controlling the condition causing acanthosis it is expected that over time the skin in the affected areas will return to normal.

Forecast

As a nosological entity, the prognosis for acanthosis nigricans is good. That is, it does not generate complications, does not modify the quality of life of the patient or is capable of causing death.

However, the final prognosis will depend on the underlying condition that led to the development of acanthosis. For example, the prognosis for type IV acanthosis is much better than for type V.

References

  1. Kahn, CR, Flier, JS, Bar, RS, Archer, JA, Gorden, P., Martin, MM, & Roth, J. (1976). The syndromes of insulin resistance and acanthosis nigricans: insulin-receptor disorders in man. New England Journal of Medicine294 (14), 739-745.
  2. Dunaif, A., Graf, M., Mandeli, J., Laumas, V., & Dobrjansky, A. (1987). Characterization of groups of Hyperaiidrogenic women with Acanthosis Nigricans, impaired glucose tolerance, and / or Hyperinsulinemia. The Journal of Clinical Endocrinology & Metabolism65 (3), 499-507.
  3. Brown, J., & Winkelmann, RK (1968). Acanthosis nigricans: A study of 90 cases. Medicine47 (1), 33-52.
  4. Hud, JA, Cohen, JB, Wagner, JM, & Cruz, PD (1992). Prevalence and significance of acanthosis nigricans in an adult obese population. Archives of dermatology128 (7), 941-944.
  5. Dunaif, A., Hoffman, AR, Scully, RE, Flier, JS, Longcope, C., Levy, LJ, & Crowley, WF (1985). Clinical, biochemical, and ovarian morphologic features in women with acanthosis nigricans and masculinization. Obstetrics and gynecology66 (4), 545-552.
  6. Cruz Jr, PD, & Hud Jr, JA (1992). Excess insulin binding to insulin-like growth factor receptors: proposed mechanism for acanthosis nigricans. Journal of Investigative Dermatology98 (6), S82-S85.
  7. Torley, D., Bellus, GA, & Munro, CS (2002). Genes, growth factors and acanthosis nigricans. British journal of Dermatology147 (6), 1096-1101.

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