Acanthosis nigricans (overview) L83

Janovsky, 1890; Politzer & Unna, 1890

Clinically descriptive term for gray-brown, papillomatous-hyperkeratotic, mostly asymptomatic, polyetiological, large-area growths of the skin, which typically occur intertriginously, more rarely also in acral form (nose, ears, palmoplantar skin, also oral). Basically, it is a uniform cutaneous reaction in which the skin responds to various endogenous "growth" stimuli with non-specific proliferation.

Acanthosis nigricans can be:

• idiopathic
• reactive in obese individuals
• in association with endocrinological diseases or pregnancy (in this case, gestational diabetes should be carefully excluded)
• induced by medication
• as a symptom of genetic defects
• paraneoplastic (then often referred to as "acanthosis nigricans maligna") in connection with adenocarcinomas

occur.

A distinction is made between:

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

The pathogenesis depends on the various forms of the disease. It is assumed that growth factors are activated, e.g. through the 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. Acanthosis nigricans probably only rarely leads to the activation of a single growth factor (see growth factors below), but rather to the orchestration of several factors.

Drug-induced acanthosis nigricans is caused by the interaction 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 formation of initially yellow-brown to black hyperpigmentation, later extensive, velvety to verrucous intensification of the skin texture, blurred against the surrounding area. Possible development of warty hyperkeratoses, which are currently not seen as an independent clinical picture, but are a partial symptom of acanthosis nigricans, usually acanthosis nigricans maligna. The growths can form cockscomb-like ridges. The most pronounced changes are seen in the centers of the growths and in the intertriginous areas(ptychotropism).

Rarely pronounced on the mucosa, where flat, leukoplakic and rarely hyperpigmented areas form. The development of cutis verticis gyrata is rarer.

The different forms do not differ significantly from each other clinically, but the infestation is often more extensive and clinically more pronounced in the paraneoplastic variant. In addition to the classic, intertriginously accentuated appearance, hyperkeratosis of the palmae and plantae as well as the flexor sides of the fingers and toes with pachydermodactyly can also occur in the paraneoplastic variant. There are usually no subjective symptoms; itching may occur in the malignant form.

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 terminology used for acanthosis nigricans is inconsistent. Some authors define acanthosis nigricans - referred to here as acanthosis nigricans maligna - strictly as a paraneoplastic syndrome, as originally described. The much more common benign variant - referred to here as acanthosis nigricans benigna - is referred to as pseudoacanthosis nigricans. There is no clearly recognizable trend in the international literature. There are still no definite clinical and morphological distinguishing features between these two groups. In this respect, the clinical picture must be regarded as a uniform skin reaction to different endogenous proliferation factors. The exclusion of obesity and hormonal stimuli as well as the advanced age of the (tumor) patients is helpful for the assumption of a paraneoplastic genesis.

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