This is a rare skin disease characterized by skin pigmentation, velvety thickening, hyperkeratosis, and warty proliferation. Non-malignant cases may occur at birth, during adolescence and early adulthood. Malignant cases are mainly seen in the elderly and are mostly associated with gastric cancer.
I. Etiology and pathogenesis
It may be related to the elevated level of a cytokine that stimulates keratin-forming cells and dermal fibroblasts at the cellular receptor level. The main ones are resistance to insulin, i.e. pre-insulin receptor resistance; receptor resistance; and post-receptor resistance. Some of these resistances are related to genetic inheritance qualities. Tumor secretory products with insulin-like activity, acting at the level of cellular receptors, may be the etiology of malignant acanthosis nigricans. Increased epidermal growth factor receptors and significant transforming growth factor-a staining in tumor tissues are known to cause significant proliferation of keratinocytes and trigger the disease by the interaction of these two substances. In addition, the disease can also be triggered by other factors acting at the level of cell receptors, such as drugs or autoimmune phenomena.
Clinical manifestations
The rash starts with hyperpigmentation, dryness, coarsening of the skin, and gray-brown or black color, with marked thickening and small papillary elevations like velvet on the surface, followed by deepening of the skin lines and papilloma-like hyperplasia. They occur on the face, neck, axillae, back, external genitalia, groin and other skin folds such as under the breast and axillae. The disease is divided into eight types, and the lesions are basically the same in each type, but the severity and extent of invasion differ. In severe cases, the lesions can involve almost the whole body, and there can be palmoplantar skin thickening.
1.Benign acanthosis nigricans: It is a rare genetic skin disease. It occurs in neonatal or early childhood, with a family tendency, and the lesions are unilateral at the beginning, with mild lesions and no involvement of the distal extremities. The oral mucosa is seen to have fine folds, resembling velvet, and the disease progresses slowly, and after puberty the lesions stop expanding and remain stable or fade. This type is related to multiple melanocytic nevi, and is an autosomal dominant disease with different phenotypic epiphenomenon rates.
2.Obesity acanthosis nigricans: it was called pseudoacanthosis nigricans in the past. It is the most common type of the disease. Both men and women can develop. Most commonly seen in people aged 25-60. Obese people with dark skin are more likely to develop. The lesions are mostly found in the folds, with the axillae, groin, and labia being the most common. Irregular pigmentation is seen in the upper thighs or labia majora, and with weight loss, the lesions may fade completely. However, pigmentation persists.
3, symptomatic acanthosis nigricans: this type is a rash manifestation of certain syndromes and is seen in type A, type B syndromes and other syndromes.
4, Type A syndrome: It occurs in young women with masculine signs or overgrowth, also known as HAIR-acanthosis nigricans syndrome, hyperandrogenemia, and insulin-resistant acanthosis nigricans. Some may have hirsutism and polycystic ovaries, as well as acromegaly, clitoral hypertrophy, and muscle spasms. This type is familial and is most often seen in black women who developed acanthosis nigricans in infancy or childhood. R-M syndrome, pseudohypertrophy syndrome or dwarf leprechaun syndrome can also be clinical features of this disease in men.
5, type B syndrome: occurs in middle-aged and older women with autoimmune diseases = the average age of onset is 39 years. Acanthosis nigricans manifestations vary in severity and can be associated with systemic lupus erythematosus, scleroderma, sj?gren syndrome, mixed connective tissue disease, vitiligo or Hashimoto’s thyroiditis. However, most have only laboratory abnormalities of immunity, such as leukopenia and high titers of anti-DNA antibodies.
6, Hirschowitz syndrome: This syndrome includes familial complete neurological deafness in childhood, progressive peripheral sensory nerve demyelination, loss of peristalsis in the gastric sinus, multiple diverticulae in the ileum and low jejunum, and may present with extensive acanthosis nigricans. The etiology is unknown.
7. Lipodystrophy with acanthosis nigricans: In addition to acanthosis nigricans, this syndrome has a generalized complete subcutaneous fat deficiency with severe insulin resistance.
In addition, other syndromes associated with acanthosis nigricans include: hepatomegaly, Alstr?n syndrome, Crouzon syndrome, Capozucca syndrome, Costello syndrome, Rud syndrome, Bloom syndrome, etc.
8, malignant acanthosis nigricans: skin lesions are often induced by tumors. The rash develops rapidly and severely and can involve the extremities, with more significant pigmentation and palmoplantar or extensive hyperkeratosis. The nails are brittle and fragile or crested. Hair may be lost. Verrucous or papillomatous proliferations are seen around the eyes and lips. The incidence of this type is equal in men and women, and it is more common in middle-aged and elderly people, and occasionally in children. Almost all of them are associated with visceral cancer, mostly adenocarcinoma, among which stomach cancer is the most common, followed by pancreatic cancer, liver and bile duct cancer, colon cancer, rectal cancer, uterine cancer, ovarian cancer, prostate cancer, esophageal cancer, breast cancer or lung cancer. Skin lesions are closely related to tumors. Curth et al. reported that 61% of skin lesions and tumors occurred together. Recently, most patients with acanthosis nigricans preceded by tumors were reported. The disease can be associated with three other cutaneous landmarks of visceral malignancies, namely Leser-Trelat syndrome, bright red skin papilloma and palmoplantar hyperkeratosis.
9, acanthosis nigricans: this type is mostly seen in dark skin. Prevalent on the back of the hands and feet, it shows velvety hyperkeratosis with pigmentation. The general general health is good.
10, Unilateral acanthosis nigricans: It may be nevus-like acanthosis nigricans. This type is considered to be an irregular autosomal dominant disorder. It often occurs at birth, during childhood or adolescence, and may be an early manifestation of benign acanthosis nigricans. However, most of them are persistent unilateral rashes, which may gradually expand and remain stable or subside naturally after a period of time.
11, drug acanthosis nigricans: this type of pathogenic drugs systemic administration of corticosteroids, niacin, estrogens such as hexestrol, pituitary leachate, insulin and triazinobenzamide, methyltestosterone, oral contraceptives and clostridium perfringens. Topical application of clostridium perfringens can cause acanthosis nigricans-like lesions, and local injection of insulin can also cause limited acanthosis nigricans.
Pathological changes
The epidermis is moderately hyperkeratotic and papillomatous hyperplasia. The papillae of typical lesions appear to be finger-like upwardly protruding, with mild or moderate hypertrophy of the spiny layer in the interpapillary depressions and filled with keratin, while the top and lateral base of the papillae are thinned and the skin crest is obvious. The basal cell layer is hyperpigmented. Melanocytes are visible in the dermis. There is a small infiltration of lymphocytes around the blood vessels.
Prevention and treatment
For malignant acanthosis nigricans, the visceral malignant tumor must be actively explored and surgically removed. For benign type, treatment is generally not needed. If the skin lesion causes cosmetic defects, cosmetic surgery can be done. For pseudo-obese patients, the rash can mostly subside naturally after correcting obesity and restoring normal weight. The rash will heal after the drug-induced drugs are discontinued. In symptomatic cases, type A syndrome with insulin resistance should be treated for hyperinsulinemia and hyperandrogenism. Insulin-like growth factor I is effective in treating certain severe insulin resistance. Oral contraceptives can also bring about remission of acanthosis nigricans. Application of phenytoin sodium can treat muscle spasms in type A syndrome. The associated autoimmune disease should be treated for type B syndrome. Topical keratolytic or pediculosis lipids can be applied topically. 0.1% retinoic acid gel twice daily can improve the lesions after two weeks of treatment. Oral cycloheximide may be effective in malignant acanthosis nigricans by the mechanism of inhibition of released tumor products. Eating foods containing fish oil may also improve the disease.