Acanthosis nigricans (overview) L83

Janovsky, 1890; Politzer & Unna, 1890

Clinical descriptive term for gray-brown, papillomatous-hyperkeratotic, mostly asymptomatic, polyetiologic, extensive growths of the skin, which typically occur intertriginously, more rarely additionally in acral expression (nose, ears, palmoplantar skin, also orally). Basically, it is a uniform, "reaction cutanée" in which the skin responds to various endogenous "growth" stimuli with nonspecific proliferation.

Acanthosis nigricans can be:

• idiopathic
• reactive in obese individuals
• associated with endocrinological diseases or pregnancy (carefully exclude gestational diabetes)
• medicinal
• as a symptom of genetic defects
• paraneoplastic (then often called "acanthosis nigricans maligna") in association with adenocarcinomas

occur in the context of adenocarcinomas.

A distinction is made between:

• Paraneoplastic form: Acanthosis nigricans paraneoplastic (maligna).
• Non-paraneoplastic forms:
  • Acanthosis nigricans "benigna" (acanthosis nigricans in the narrow sense).
  • Acanthosis nigricans in endocrinological disorders (e.g. in obesity and insulin resistance) or obesity(pseudoacanthosis nigricans)
  • Hereditary acanthosis nigricans(acanthosis nigricans in hereditary syndromes)
  • Acral acanthosis nigricans (acral acanthotic anomaly)
  • Unilateral (nevoid) acanthosis nigricans
  • Drug-induced acanthosis nigricans.

The pathogenesis depends on the different forms of the disease. An activation of growth factors is assumed, e.g. by formation and activation of growth factor receptors(epidermal growth factor receptor, insulin-like growth factor receptor and fibroblast growth factor receptor (FGFR)) with mitogenic and anti-apoptotic effects on keratinocytes. It is likely that in acanthosis nigricans there is rarely activation of a single growth factor (see Growth Factors below) but rather orchestration of multiple factors.

Drug-induced acanthosis nigricans results from interactions of certain drugs with lipid metabolism.

Occurring in all age groups. Men and women fall ill about equally often.

In principle, any area of the body can be affected. However, intertrigines, in particular armpits, lateral neck and neck areas, inguinal and genitoanal region are preferentially affected. Less frequently affected are eyelids, nasal entrance, elbows, popliteal or umbilical region. Involvement of palmae, plantae, oral mucosa and tongue is mainly observed in paraneoplastic acanthosis nigricans. In obese women with hyperandrogenism (e.g. in PCOS) without diabetes mellitus, the most frequent localization is the vulvar region.

Mostly symmetrical development of initially yellow-brown to black hyperpigmentation, later area-like, velvety to verrucous enhancement of the skin texture, indistinctly demarcated from the surroundings. Possibly development of warty hyperkeratoses, which according to the current status are not seen as an independent clinical picture, but are partial symptoms of acanthosis nigricans, mostly acanthosis nigricans maligna. The growths may protrude in a cockscomb-like groin. The most severe changes are seen in the centers of the growths and in the intertriginous areas(ptychotropism).

On the mucosa rather rarely pronounced; here formation of planar, leukoplakic and rarely hyperpigmented areas. More rare is the development of cutis verticis gyrata.

The different forms do not differ clinically, but the paraneoplastic variant is often more extensive and clinically more pronounced. Furthermore, in the paraneoplastic variant, in addition to the classic intertriginous accentuated appearance, hyperkeratosis of the palmae and plantae as well as the flexor sides of the fingers and toes with pachydermodactyly may occur. In most cases there are no subjective complaints; in the malignant form itching may well occur.

Papillomatosis and hyperkeratosis, slight mostly irregular acanthosis, basal hyperpigmentation, partially pseudohorn cysts. No significant inflammatory infiltrate in the dermis. Discrete parakeratosis with papillomatosis and epithelial hyperplasia on the mucosa, typically without proliferation of melanocytes in the epithelium. The "malignant" and "benign" forms of acanthosis nigricans do not differ histologically.

• Pemphigus chronicus benignus familiaris; pemphigus vegetans; dyskeratosis follicularis; papillomatosis confluens et reticularis; M. Dowling-Degos; nevus, epidermal painter; Becker nevus; pellagra; haemochromatosis; M. Addison; rarely parapsoriasis en plaques or cutaneous T-cell lymphoma; tinea corporis; atopic eczema.
• For oral acanthosis nigricans: Goltz-Gorlin syndrome; Cowden syndrome; Wegener's granulomatosis; reticulohistiocytosis; hypertrichosis lanuginosa acquisita.

Symptomatically in cooperation with the endocrinologist for the treatment of a possible underlying disease. Consistent hygiene of the intertrigines. In the obesity-associated form (Addison's disease, pseudoacanthosis nigricans), the skin changes usually regress when body weight is normalised. In addition, consistent hygiene of the intertriginous areas, washing with syndets.

Notice! The exclusion of malignoma is obligatory for all forms of acanthosis nigricans!

Unfortunately, the language rules are inconsistent in Acanthosis nigricans. Some authors define Acathosis nigricans - here called Acanthosis nigricans maligna - as originally described strictly and 100% as a paraneoplastic syndrome. The much more frequent benign variant - here called acanthosis nigricans benigna - is called pseudoacanthosis nigricans. There is no clearly discernible trend in the international literature. There are still no clinically proven morphological distinguishing features between these two groups. In this respect the clinical picture is to be considered as a uniform skin reaction to different endogenous proliferation factors. Helpful for the assumption of a paraneoplastic etiology is the exclusion of obesity and hormonal stimuli as well as the advanced age of the (tumor) patients.

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