BENJAMIN BARANKIN, MD, FRCPC
Contributing editor
Dermatologist in private practice, Toronto, Ontario; and member, Patient Care Subspecialist Advisory Board.
Brown thickened skin on the neck and axillae
A 14-year-old male presents with concerns regarding brown thickened skin affecting his neck and, more recently, his axillae.
He is overweight and being worked up by an endocrinologist for a possible diagnosis of diabetes. He takes no medications and
has a family history of psoriasis and heart disease.
What is your diagnosis?
What are the treatment options?
Acanthosis nigricans
This disorder is most likely caused by factors that stimulate epidermal keratinocyte and dermal fibroblast proliferation.
In the benign form, the factor is probably insulin or an insulin-like growth factor that incites epidermal cell proliferation.
In malignant acanthosis nigricans (AN), which is quite rare, the stimulating factor is hypothesized to be a substance secreted
either by the tumor or in response to the tumor. Exogenous medications have also been implicated as etiologic factors.
(IMAGE: BENJAMIN BARANKIN, MD, FRCPC)
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Obesity is closely associated with AN. Patients with the benign form of it have few to no complications of their skin lesions.
However, many of them have an underlying insulin-resistant state that is the cause of their condition. The severity of the
insulin resistance is highly variable and can range from an incidental finding on routine blood studies to overt diabetes
mellitus. The severity of skin findings may parallel the degree of insulin resistance, and a partial resolution may occur
with treatment of the insulin-resistant state. Insulin resistance is the most common association of AN in the younger population.
Malignant AN is associated with significant complications because the underlying malignancy is often an aggressive tumor.
Average survival time of patients with signs of malignant AN is approximately 2 years. In older patients with new-onset AN,
most have an associated internal malignancy. There is no racial predilection. The lesions of malignant AN are clinically indistinguishable
from the benign forms.
AN is much more common in people with darker skin pigmentation. The prevalence in decreasing order is African Americans, Hispanics,
Native Americans, and Caucasians. Male and female incidence is similar.
Lesions of benign AN may present at any age, although they are more common in adults. Malignant AN occurs most frequently
in the elderly. Patients usually present with an asymptomatic area of darkening and thickening of the skin; pruritus is uncommon.
Lesions begin as hyperpigmented macules and patches and progress to palpable plaques. Skin findings of AN can precede, be
concurrent with, or occur subsequent to diagnosis of malignancy, in equal proportions.
AN is characterized by symmetrical, hyperpigmented, and velvety plaques that may occur in almost any location but most commonly
appear on the intertriginous areas of the axillae, groin, and posterior neck. The posterior neck is the most commonly affected
site in children (7% of children). Skin tags, as in this patient, often are found in and around the affected areas.
The definitive cause of AN has not yet been determined. Obesity-associated AN (pseudoacanthosis nigricans) is the most common type. Lesions can appear at any age, and the dermatosis is weight dependent,
with lesions completely regressing in some patients with weight reduction. Insulin resistance is often present. Syndromic AN has been associated with endocrinopathies (eg, polycystic ovary syndrome, hyperthyroidism or hypothyroidism, acromegaly,
Cushing's disease), familial lipodystrophies, congenital syndromes (eg, Bloom syndrome), and autoimmune diseases (eg, systemic
lupus erythematosus, scleroderma).
Acral AN occurs predominantly in dark-skinned patients who are in otherwise good health and manifests itself as hyperkeratotic velvety
lesions over the dorsal aspects of the hands and feet. Unilateral AN is believed to be inherited as an autosomal dominant trait and can present at any age with lesions enlarging gradually before
stabilizing or regressing. Familial AN is a rare, likely autosomal dominant genodermatosis that typically begins during early childhood and progresses until puberty,
when it stabilizes or regresses. Drug-induced AN, although uncommon, may be caused by several medications, including nicotinic acid, systemic corticosteroids, methyltestosterone,
and diethylstilbestrol (no longer available). The lesions of AN may regress following the discontinuation of the offending
medication.
Malignant AN has been reported with many kinds of cancer, but by far the most common underlying malignancy is an adenocarcinoma of GI
origin, usually a gastric adenocarcinoma. Of associated tumors, 75% are abdominal adenocarcinomas, of which 60% arise in the
stomach. Less commonly, lung, pituitary, and liver malignancies have caused AN.
In 25% to 50% of cases of malignant AN, the oral cavity is involved. The tongue and lips are most commonly affected, with
elongation of the filiform papillae on the dorsal and lateral surfaces of the tongue and multiple papillary lesions appearing
on the commissures of the lips. Although malignant AN is clinically indistinguishable from the benign forms, one must be more
suspicious if the lesions arise rapidly or if they are more extensive, symptomatic, or in atypical locations (eg, oral, palmoplantar).
Regression of AN has been seen with treatment of the underlying malignancy, and reappearance may suggest recurrence or metastasis
of the primary tumor.
For patients with adult-onset AN, perform a basic workup for underlying malignancy. The physical examination should evaluate
obesity, masculinization, lymphadenopathy, and visceromegaly. A screen for diabetes with a fasting blood glucose, A1c level, or glucose tolerance test should be performed. A good screening test for insulin resistance is a plasma insulin level,
which will be high in those with insulin resistance. Depending on the history, screen for thyroid and ovarian disease with
thyroid-stimulating hormone/T4 and luteinizing hormone/follicle-stimulating hormone tests. If malignant AN is suspected, a CBC, stool screen for occult
blood, chest and abdominal x-rays, and GI endoscopic procedures are warranted.
Treatment of the lesions of AN is for cosmetic reasons only. Correction of hyperinsulinemia and weight reduction in obesity-associated
AN may result in resolution of the dermatosis. Treatment of endocrinopathies (eg, hypothyroidism) can result in improvement
or resolution of AN. There is no treatment of choice, and therapies are anecdotal, including topical options such as tretinoin,
calcipotriol, hydroquinone, corticosteroids, and keratolytics. Dermabrasion, oral isotretinoin and oral contraceptives, and
carbon dioxide laser are other more aggressive and less commonly employed options. In the very hypertrophic types of AN, especially
on the neck, carbon dioxide laser ablation has provided some improvement in appearance, but it may only be temporary in nature.
The patient was treated with a modified Kligman's formulation (topical corticosteroid, retinoid, and hydroquinone) with a
25% improvement after 3 months, according to the patient. The endocrinologist warned the patient that, in light of his weight
and family history of heart disease, he needs to focus on a healthier, portion-controlled diet and on exercise. His fasting
glucose was slightly elevated, and he is being followed by the endocrinologist.
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