ACANTHOSIS NIGRICANS
Acanthosis
nigricans is a commonly encountered skin dermatosis that can be seen in various
clinical scenarios. It is overwhelmingly associated with obesity but can occur
secondary to medications, endocrine disorders such as the HAIR-AN syndrome (hyperandrogenism,
insulin resistance, and acanthosis nigricans),
diabetes, and internal malignancies. This last type is clinically distinctive
and manifests in a unique manner.
Clinical Findings: Classic cases of acanthosis nigricans affect the
nape of the neck, the axillae, and the groin regions. Native Americans and
African Americans are at a significantly increased risk for development of acanthosis
nigricans. The slow, insidious onset of patches and plaques with a velvety,
hyperpigmented, thickened, rough surface is characteristic of acanthosis
nigricans. Maceration with a malodorous smell is often noted. The patients are for
the most part asymptomatic, although some complain of intermittent pruritus.
The clinical findings in association with obesity are enough to make the
diagnosis. A thorough history should be taken to rule out a medication-induced
form of acanthosis nigricans. The only routine laboratory testing performed is
screening for occult diabetes. Patients with obesity are at higher risk for
diabetes later in life, and lifelong follow-up and screening by their primary
care physician is required.
Many medications have been shown to
induce acanthosis nigricans. They include niacinamide, glucocorticoids,
insulin, and some birth control pills. The medication most commonly associated
with acanthosis nigricans is niacinamide. Most cases resolve or improve greatly
with discontinuation of the medication. The appearance is often identical to
that of classic acanthosis nigricans, but the history is suggestive, with the
timing of rash onset related to the introduction of the causative medication.
Malignancy-associated acanthosis
nigricans is often widespread and involves unique areas, including the mucous
membranes, palms, and soles. This form has a rapid onset and affects different
areas of the body than the classic form of acanthosis nigricans does. The palms
and soles are often involved, and the face can be involved. Any case in which
there is rapid onset of acanthosis nigricans in a widespread distribution,
often in a nonobese individual, warrants proper evaluation to rule out an
internal malignancy. Referral to a gastroenterologist and an internist for
cancer screening is of utmost importance.
A few endocrine disorders can be
associated with acanthosis nigricans, most frequently diabetes mellitus and the
HAIR-AN syndrome It is associated with insulin resistance and also with
hyperandrogenism.
Rare causes of acanthosis nigricans
include the familial forms, which are inherited in an autosomal dominant
fashion.
Pathogenesis: The skin thickening and clinical findings are
possibly caused by an increase in insulin-like growth factor receptor,
fibroblast growth factor receptor, and epidermal growth factor receptor and
their subsequent effects on the skin. The reason it affects certain regions
preferentially is unknown. Malignancyassociated acanthosis nigricans is
believed to be caused by some cytokine or growth factor directly secreted by
the tumor, possibly in the fibroblast growth factor receptor class of
molecules. The tumor causes the clinical findings by secreting these
substances. Acanthosis nigricans is believed to be a paraneoplastic process in
these cases. Medication-induced acanthosis nigricans is poorly understood but
is possibly related to the medication’s local effects on the skin in
genetically predisposed individuals.
Histology: Epidermal hyperplasia, acanthosis, and
papillomatosis are present. There is minimal to no inflammatory infiltrate, and
the dermis is essentially normal in appearance. Extensive hyperkeratosis with a
mild excess of melanin production likely explains the hyperpigmentation seen in
acanthosis nigricans.
Treatment: Treatment is often difficult unless the afflicted
individual makes a conscious effort to get to an ideal body weight and to get
his or her diabetes under excellent control. This is the only likely scenario
in which the skin findings of acanthosis nigricans will resolve. Temporizing
methods of therapy include the use of keratolytic agents such as lactic acid to
help thin the plaques and make them less noticeable. These agents are difficult
to use in the axillae because of stinging. The topical use of tretinoin cream
has also been successful. Destructive laser therapies have been used with
varying success.
Treatment of malignancy-associated acanthosis
nigricans is directed at the underlying malignancy. Removal of the tumor ay
result in complete resolution of the skin disease.
