Acanthosis nigricans is a type of acquired skin dystrophy characterized by papillomatosis, hyperkeratosis and hyperpigmentation of the skin. Clinically, it proceeds with the presence of foci of dark skin color in natural folds, papillary or warty outgrowths. For morphological confirmation of the diagnosis, a skin biopsy is performed. In order to determine the cause of skin dystrophy, laboratory, tomographic, ultrasound examination is performed. Local treatment is carried out with the help of keratolytics, laser therapy, dermabrasion. Therapy of the underlying pathology is indicated.
L83 Acanthosis nigricans
Acanthosis nigricans (pigmented papillary dystrophy of the skin) was first described in 1889 by the German dermatologist P. Unna and his American colleague S. Politzer. It is mainly found in blacks (13.3%) and Latinos (5.5%), among representatives of the European race the frequency does not exceed 1%. The disease is somewhat more often registered in women. It is considered a sensitive marker of insulin resistance among overweight people. Malignant acanthosis nigricans occurs in people with oncological diseases (2:12,000), mostly older than 40-50 years.
Acanthosis nigricans most often develops a second time, against the background of hormonal disorders, tumor processes, toxic influences. In some cases, there is no connection with other factors, such a condition is regarded as an idiopathic form. The causes of the condition are grouped into several groups:
- Endocrinopathy. The most common cause of acanthosis nigricans is hyperinsulinemia and associated pathologies: metabolic syndrome, obesity, type 2 diabetes. Insulin resistance also often accompanies PCOS, acromegaly, Itsenko-Cushing syndrome, hypothyroidism.
- Side effect of pharmacotherapy. Skin dystrophy can occur when taking elevated doses of nicotinic acid, COCs, steroid hormones, growth hormone.
- Malignant neoplasms. In most cases, malignant acanthosis is etiologically associated with adenocarcinoma of the stomach, rectum, pancreas, ovaries, lungs. It appears less often with lymphoma, osteogenic sarcoma, breast cancer. It is considered as paraneoplastic dermatosis.
- Hereditary diseases. Acanthosis nigricans can occur in the structure of ectodermal hydrotic dysplasia ‒ Clawston syndrome, which is also characterized by hypotrichosis, nail dystrophy, hyperkeratosis. Another related pathology is Mischer syndrome (DM, imbecility).
Acanthosis nigricans develops under the influence of factors simulating the proliferation of keratinocytes of the epidermis and dermal fibroblasts. Such a factor, in particular, may be hyperinsulinemia, which leads to the activation of insulin-like growth factor-1 receptors. This, in turn, triggers the processes of uncontrolled proliferation of the epithelial cover. It is also possible to stimulate other receptors involved in cell proliferation ‒ epidermal growth factor (EGF-R) and fibroblast growth factor (FGF-R).
The appearance of a malignant form of acanthosis nigricans is facilitated by an increase in the level of transforming growth factor alpha, which stimulates EGF-R receptors in melanocytes and keratinocytes, causing hyperpigmentation and proliferation of cellular elements.
In histological preparations, foci of hyperkeratosis and acanthosis, uneven deposition of melanin in basal epidermocytes are found. In the dermal layer, papillary hypertrophy, an increase in the number of capillaries, lymphocytic infiltration around the vessels is determined.
Taking into account the identified etiofactor, in clinical dermatology it is customary to distinguish several types of acanthosis nigricans:
- I ‒ benign hereditary – is not associated with endocrine and oncological pathologies, manifests in childhood or puberty;
- II – benign endocrine–dependent – associated with insulin resistance and endocrinopathies;
- III – false acanthosis nigricans or pseudoacanthosis – is characteristic of patients with obesity and dark skin;
- IV – drug-associated – occurs against the background of taking hormonal drugs, vitamin PP;
- V – malignant – is detected against the background of cancer, sometimes precedes the detection of a tumor.
The condition under consideration is characterized by a triad of clinical signs: papillomatosis, local pigmentation enhancement, hyperkeratosis. The most common areas of localization of acanthosis nigricans are skin folds in the axillary zone, groin, and abdomen. Elbow bends, hips, nasolabial area, back of hands, anal area are affected somewhat less often.
The skin in these areas acquires a “dirty” color: grayish, brown color. Over time, it thickens, becomes dense with a pronounced skin pattern, velvety to the touch. The altered area of the skin is covered with papillomatous outgrowths 5-8 mm high. Sometimes skin changes are accompanied by itching. Freckles, seborrheic keratoma, fibroids, and nevi often form around the affected area.
In half of patients with malignant acanthosis nigricans, there is a lesion of the mucous membranes (pronounced furrows, papillary growths) and the skin of the palms. With remission of cancer, the manifestations subside, with relapses – they increase.
Acanthosis nigricans in most cases serves as a marker of diseases of the endocrine glands. This condition is considered a high risk factor for insulin-dependent diabetes mellitus. It may indicate the presence of dysfunction of the ovaries, adrenal glands, thyroid gland. The malignant variant is an indicator of the development of the neoplastic process and, as a rule, is associated with its unfavorable course: aggressive growth of neoplasm, metastasis, multiple tumor lesions.
Patients with clinical manifestations of acanthosis nigricans require a comprehensive laboratory and instrumental examination with the involvement of a group of specialists: a dermatologist, an endocrinologist, an oncologist, a geneticist. It is necessary to conduct the following studies:
- Biochemical and hormonal analyses. They help determine the cause of acanthosis nigricans. This requires the determination of insulin and blood glucose, thyroid hormones, TSH, cortisol, testosterone. If necessary, drug monitoring is carried out, cancer markers are examined.
- Skin biopsy. Histological examination of the area of the altered skin allows to identify pathognomonic morphological changes (hyperkeratosis, acanthosis, accumulation of melanin, etc.).
- Instrumental visualization. With a suspected paraneoplastic syndrome, a tumor is searched. For this purpose, endoscopic (gastroscopy, colonoscopy, laparoscopy), ultrasound (ultrasound of the genitals, kidneys, abdominal organs), X-ray diagnostics (CT of the lungs, mammography) can be prescribed. It is possible to conduct an MRI of the whole body in the oncoscreening mode.
Acanthosis nigricans has to be differentiated from other pathologies occurring with the phenomena of keratinization, changes in skin color, the appearance of growths:
- senile keratosis ‒ characterized by the appearance of dry warty growths on open areas of the skin;
- Addison’s disease – hyperpigmentation is formed on the skin areas exposed to insolation; the skin is thinning, there is no papillomatosis;
- pellagroi – erythema, keratosis and peeling of the epithelium is noted on the exposed areas of the body;
- hemochromatosis – bronze staining of the skin is combined with damage to internal organs;
- Darye’s disease – the axillary and inguinal area is not affected, however, the scalp is often involved;
- ichthyosis is characterized by peeling of the skin, but not papillomatosis;
- toxic melasma – skin staining occurs in the area of contact with an irritant substance.
Acanthosis nigricans еreatment
Therapy of the underlying disease
Correction of background disorders is a necessary condition for combating skin manifestations. Taking into account the cause of acanthosis nigricans ,the following tactics can be used:
- Cancellation of medications. If the connection of acanthosis nigricans with an overdose of drugs is found, the dose is adjusted or replaced with other drugs.
- Correction of endocrine disorders. In order to normalize weight and eliminate hyperinsulinemia, a low-calorie diet is prescribed, taking biguanides. With hypothyroidism, levothyroxine may be required. The methods of choice for PCOS are hormone therapy, cauterization, and wedge-shaped ovarian resection.
- Antitumor treatment. In the malignant form of acanthosis nigricans, removal of the tumor formation is indicated. Depending on the localization of the process, gastrectomy, hemicolectomy, nephrectomy, pneumonectomy, mastectomy and other types of radical operations can be performed. Surgical treatment is combined with radiation therapy, chemotherapy courses.
Local therapy is aimed at the cosmetic elimination of such phenomena as hyperpigmentation, papillomas, excessive keratinization of the skin. Usually topical retinoids with keratolytic action, brightening creams are used for this. Similar products are applied to the affected skin at night, and sunscreens are used during the day. Among the methods of hardware cosmetology, dermabrasion and laser skin whitening are effective. Electrocoagulation, laser, and radio wave destruction are used to remove multiple papillomas.
Prognosis and prevention
The course of benign acanthosis nigricans is favorable. Manifestations regress after the root cause is eliminated (withdrawal of medications, correction of endocrine disorders). With a malignant type, the prognosis is unfavorable: a fatal outcome usually occurs in the next 2 years due to the neglect of the cancer process.
Prevention involves maintaining a normal weight, correcting metabolic disorders, taking drugs strictly in accordance with the prescriptions of the attending doctor. It is necessary to consult a dermatologist early if the pigmentation or relief of the skin changes.