Acanthosis nigricans (overview) L83

Janovsky, 1890; Politzer & Unna, 1890

Clinically descriptive term for grey-brown, papillomatous-hyperkeratotic, mostly asymptomatic, polyätiological, extensive skin growths, which typically occur intertriginously, more rarely additionally in an acral form (nose, ears, palmoplantar skin, also orally). Basically it is a uniform "reaction cutanée" in which the skin responds to various endogenous "growth" stimuli with an unspecific proliferation.

Acanthosis nigricans can:

• idiopathic
• reactive in obese individuals
• in association with endocrinological diseases
• medicinal
• as a symptom of genetic defects
• paraneoplastic (then often called "acanthosis nigricans maligna") in connection with adenocarcinomas

occur.

A distinction is made between:

• Paraneoplastic form: Acanthosis nigricans maligna.
• Non-paraneoplastic forms:
  • Acanthosis nigricans benigna (in the narrower 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. It is assumed that growth factors, e.g. the growth factor receptors(epidermal growth factor receptor, insulin-like growth factor receptor and fibroblast growth factor receptor (FGFR)) are activated with mitogenic and anti-apoptotic effects on keratinocytes. Probably, acanthosis nigricans rarely leads to a solitary activation of a single receptor. In the context of tumor diseases, for example, in addition to TGF-alpha, the fibroblast growth factor and the insulin-like growth factor are elevated in serum (see below growth factors). Drug-induced acanthosis nigricans results from interactions of certain drugs with the lipid metabolism.

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

Basically any part of the body can be affected. Preferably, however, intertrigines, especially armpits, lateral neck and neck areas, inguinal and genitoanal areas are affected. Less frequently affected are the eyelids, nasal entrance, elbows, hollow of the knee or navel region. Infestation of palmae, plantae, oral mucosa and tongue is mainly observed in acanthosis nigricans maligna. In overweight women with hyperandrogenism (e.g. in PCOS) without diabetes mellitus, the most frequent localisation is the vulva region.

• Mostly symmetrical formation of initially yellow-brown to black hyperpigmentations, later on flat, velvety to sour reinforcement of the skin texture, blurred against the surroundings. Possible development of warty hyperkeratoses which are not considered as an independent clinical picture according to current knowledge but are part of the symptom of acanthosis nigricans, mostly of acanthosis nigricans maligna. The growths can heal cockscomb-like groins. The strongest changes are seen in the centres of the growths and in the intertriginous areas (ptychotropism).
• On the mucosa rather rarely pronounced; here formation of flat, leukoplakic and rarely hyperpigmented areas. The development of a cutis verticis gyrata is rarer.
• The different forms do not differ clinically from each other significantly, but in the case of a malignant underlying disease, the infestation is often more extensive. In the paraneoplastic variant hyperkeratoses of the palmae and plantae as well as of the flexor sides of the fingers and toes with pachydermodactyly may occur in addition to the classic appearance. In most cases there are no subjective complaints; in the malignant form itching may 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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