Acanthosis nigricans (overview) L83

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 18.12.2020

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Synonym(s)

acanthosis nigricans; Black usury skin; dystrophia papillaris pigmentosa

History
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Janovsky, 1890; Politzer & Unna, 1890

Definition
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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.

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Classification
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A distinction is made between:

Etiopathogenesis
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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.

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

Localization
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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.

Clinical features
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  • 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.

Histology
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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.

Diagnosis
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Clinical picture and typical localization (the neck is often affected in early stages) are diagnostically groundbreaking.

General therapy
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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!

External therapy
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Mainly symptomatic therapy. Local therapy with covering, possibly zinc-containing powder or creams for dehydration (e.g. R294, R025 ). If necessary, keratolytic external therapy with creams containing salicylic acid(e.g. R216 ) or urea(e.g. R102 or basodexan); if necessary, low doses of vitamin A acid (e.g. R256 or Cordes VAS, Airol cream).

Internal therapy
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Therapy trials with acitretin (neotigason) or isotretinoin (e.g. isotretinoin-ratiopharm; acne normin) in low dosages have been described. In case of itching use antihistamines if necessary.

Operative therapie
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In the case of papillomatous growths, electrocaustic ablation can be attempted as a palliative measure, but this is usually only temporarily effective, as the skin changes can quickly reappear postoperatively.

Tables
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Malignant form

Benign forms

Localization

in addition to the typical localisations, frequent infestation of Palmae, plantae, oral mucosa, tongue and eyelids

often vulva area in overweight women with hyperandrogenemia

Expansion

mostly extensive infestation, partly generalized

less extensive infestation

Clinic

in addition to the classic appearance, hyperkeratoses, especially on palmae and plantae as well as on the flexion sides of the fingers and toes with pachydermatoglyphy ("tripe palms") can occur

Mucosal involvement

more frequently

less frequently

Subjective complaints

localised or generalised itching; in case of mucosal papillomatosis, pain and possibly dysphagia may occur

mostly none

Associated symptoms

Malignoma of the internal organs, mostly stomach carcinoma. Other paraneoplastic syndromes such as reader Trélat's sign, hypertrichosis lanuginosa, pemphigus, palmoplantar keratoses or "tripe palms" may be optional.

Diabetes mellitus, insulin resistance, overweight, hyperhidrosis, fibroma pendulans, hyperandrogenemia

History

Acute occurrence and rapid spread, variable course, often fading after the underlying malignancy has been cleared up with inflammation in the event of metastasis

often improvement in weight loss or regulation of endocrinological disorders

Note(s)
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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.

Literature
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  1. Ceylan C, Alper S, Kilinc I. (2002) Reader's Trelat sign. Int J Dermatol 41: 687-688
  2. Janovsky V (1890) Acanthosis nigricans. In: Unna PG et al (Ed.) International Atlas of Rare Skin Diseases. Volume 11, Voss, Leipzig
  3. Lenzner U et al (1998) Acanthosis nigricans maligna. Case description and literature review. Dermatologist 49: 41-47
  4. Mellor-Pita S, Yebra-Bango M, Alfaro-Martinez J, Suarez E (2002) Acanthosis nigricans: a new manifestation of insulin resistance in patients receiving treatment with protease inhibitors. Clin Infect Dis 34: 716-717
  5. Pollitzer S (1890) Acanthosis nigricans. In: Unna PG et al (Ed.) International Atlas of Rare Skin Diseases. Volume 11, Voss, Leipzig
  6. Pollitzer S (1891) Acanthosis nigricans. In: Unna PG et al (eds.) International Atlas of Rare Skin Diseases. Lewis, London, pp. 1-3
  7. Schroeder B, Ding X, Pfaff-Amesse T (2002) From HAIR-AN to eternity. J Pediatr Adolesc Gynecol 15: 235-240
  8. Schwartz RA (1994) Acanthosis nigricans. J Am Acad Dermatol 31: 1-22
  9. Stulberg DL et al (2003) Common hyperpigmentation disorders in adults: Part II. Melanoma, seborrheic keratosis, acanthosis nigricans, melasma, diabetic dermopathy, tinea versicolor, and postinflammatory hyperpigmentation. On Fam Physician 68: 1963-1968
  10. Torley D, Bellus GA, Munro CS (2002) Genes, growth factors and acanthosis nigricans. British Journal of Dermatology 147: 1096-1101
  11. Yamazaki H et al (2003) Acanthosis nigricans is a reliable cutaneous marker of insulin resistance in obese Japanese children. Pediatric Int 45: 701-705

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

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Last updated on: 18.12.2020