Acanthosis nigricans AN is a common dermatologic manifestation of systemic disease that is associated with insulin resistance, diabetes mellitus, obesity, internal malignancy, endocrine disorders, and drug reactions. Treatment of AN primarily focuses on resolution of the underlying disease processes causing the velvety, hyperpigmented, hyperkeratotic plaques found on the skin. While the goal of therapy is to treat the primary cause, cosmetic resolution of AN lesions can be important for patients and their quality of life. Treatment options for AN have not been extensively studied; however, smaller powered clinical trials and case reports exist in the literature. Our review aims to explore and evaluate the current treatment options that exist for AN. Acanthosis nigricans AN is a common cutaneous condition that can be a manifestation of systemic disease that is associated with insulin resistance, diabetes mellitus, obesity, internal malignancy, endocrine disorders, and drug reactions.
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Assistant Professor, Department of Dermatology, L. Acanthosis nigricans AN is characterized by dark, coarse and thickened skin with a velvety texture, being symmetrically distributed on the neck, the axillae, antecubital and popliteal fossae, and groin folds, histopathologically characterized by papillomatosis and hyperkeratosis of the skin. A high prevalence of AN has been observed recently.
Different varieties of AN include benign, obesity associated, syndromic, malignant, acral, unilateral, medication-induced and mixed AN. Diagnosis is largely clinical with histopathology needed only for confirmation. The most common treatment modalities include retinoids and metformin. The term AN was originally proposed by Unna, but the first case was described by Pollitzer and Janovsky in Due to the rising prevalence of obesity and diabetes a high prevalence of AN has been observed recently.
Hud et al. Malignant AN is less common. Curth classified AN into malignant, benign, and syndromic or pseudo AN. Hernandez-Perez proposed more simplified classification: simple AN not related to malignancy and paraneoplastic AN. Burke et al. This scale is easy to use, having a high inter-observer reliability that correlates with fasting insulin and body mass index BMI. Insulin has been demonstrated to cross dermoepidermal junction DEJ to reach keratinocytes.
At higher concentrations, however, insulin can exert more potent growth-promoting effects through binding to insulin-like growth factor 1 receptors IGF-1Rs that are similar in size and subunit structure to insulin receptors, but bind IGF-1 with to fold greater affinity than insulin.
The binding stimulates proliferation of keratinocytes and fibroblasts, leading to AN [ Figure 1 ]. Etiopathogenesis of acanthosis nigricans Image courtesy of Dr. Hyperinsulinemia not only causes AN by exerting a direct toxic effect,[ 2 ] but indirectly by increasing free IGF-1 levels in circulation. Unknown autoantibodies other than insulin-receptor antibody have been implicated; this could explain the effectiveness of cyclosporine in treating AN with autoimmune manifestations.
Insulin and IGF-1 levels are affected by hepatitis C infection and both of them may be implicated in etiogenesis of acrochordons and AN through their proliferative and differentiating properties. The receptor for EGF is found on normal epidermal cells, particularly on actively proliferating cells of the basal layer where it is involved in growth and differentiation of normal keratinocytes.
When these growth factors are produced by the primary tumor and circulate in large quantities, they may cause epidermal cell proliferation, leading to AN. Systemic immunologic response to the primary tumor as a cause cannot be discarded.
As thickening increases, skin lines are further accentuated and the surface becomes mammilated and rugose, with the development of larger warty excrescences. Involvement of mucous membranes is uncommon, but oral mucous membrane may show delicate velvety furrows. Tripe palms presents as rugose hyperkeratosis and prominent dermatoglyphics of palms, likened to bovine gut lining.
Periocular distribution is seen in insulin resistance IR. Obesity is the most common cause of AN. Lesions may appear at any age, but are more common in adulthood. Lesions are weight dependent, with regression following weight reduction. Insulin resistance is often present in these patients. This may appear as an adverse effect of several medications [ Table 1 ] that promote hyperinsulinemia.
Lesions regress following discontinuation of the offending medication. Erickson et al. Prescription of the correct insulin and use of proper technique will prevent AN development. It may occur as two types: type A and Type B. The Type B syndrome occurs in women with uncontrolled diabetes mellitus, ovarian HA, or autoimmune disease.
It is due to the development of antibodies to insulin receptors in autoimmune diseases such as systemic lupus erythematosus. It occurs in otherwise healthy patients. It is most common in dark-skinned individuals African American descent , lesions being prominent over the dorsal aspects of hands and feet. It is a rare form of AN, inherited as an autosomal dominant trait. Lesions are unilateral along lines of Blaschko and may become evident during infancy, childhood, or adulthood.
Lesions occur over the face, scalp, chest, abdomen, especially periumbilical area, back and thigh. Lesions can enlarge gradually before stabilizing or regressing. It is a rare autosomal dominant genodermatosis beginning during early childhood, but may manifest at any age.
The condition often progresses until puberty after which it stabilizes or regresses. It is a rare autosomal dominant disorder presenting at birth or developing during childhood without endocrinopathy.
Onset may be related to medication usage. It is clinically indistinguishable from benign forms, but ANM appears abruptly and exuberantly. Acrochordons are often found in affected areas [ Figure 4 ].
Lesions may be present over the oral, nasal and laryngeal mucosa, esophagus and areola of nipple. Papillomatous lesions on the eyelids and conjunctiva may occur. Leukonychia and nail hyperkeratosis has been reported. In one-third of cases skin changes occur before signs of cancer, in another one-third AN and neoplasm arise simultaneously and in remaining one third, skin findings manifest after diagnosis of cancer. Reappearance may suggest recurrence or metastasis of the primary tumor.
It occurs when a patient with one of the above types of AN develops new AN lesions of a different etiology. An example would be an overweight patient with obesity-associated AN who subsequently develops malignant AN.
Histological findings are similar in all forms of AN with papillomatosis, hyperkeratosis and hyperpigmentation of the basal layer. The dermal papillae project upwards as finger-like projections.
The valleys between papillae show mild acanthosis and are filled with keratotic material. Clinically observed hyperpigmentation is due to hyperkeratosis and clinical thickening rather than to melanin. Spectroscopic and colorimetric measurements combined with chemometric analysis methods provide sensitive and specific diagnosis of AN.
Table 3 mentions the differential diagnoses of AN. Urrutia-Rojas et al. They suggested that screening children for AN is an effective strategy for identifying adults with prediabetes. Insulin resistance is a metabolic disorder in which target cells fail to respond to normal levels of circulating insulin, resulting in compensatory hyperinsulinemia. IR has been associated with AN and acrochordons which may represent an easily identifiable sign of IR and noninsulin-dependent diabetes. AN is so closely associated with IR that it has been called a clinical surrogate for laboratory determined hyperinsulinemia.
They concluded that neck texture exhibits both greater sensitivity and specificity than neck pigment for AN detection, because visible roughness of the neck is recognizable without touching or disrobing patient, affording an instant assessment of AN.
Furthermore, texture grading avoids possible confounding by sun-induced pigmentation. They suggested that all patients with elevated BMI should be examined for insulin neck and if neck texture is normal, IR is less likely to be present. Types of IR are mentioned in Table 4. Obese patients and patients with polycystic ovary syndrome have Type A IR.
This technique is a gold standard and reference method for quantifying insulin sensitivity because it directly measures effects of insulin in promoting glucose utilization under steady-state conditions in vivo. However, its calculation is complicated and impractical. HOMA was first developed in by Matthews et al. It has been proved to be a robust clinical and epidemiological tool for the assessment of IR.
It has a good and linear correlation with the hyperinsulinemic-euglycemic clamp method. Measurement of fasting insulin level has been considered most practical approach for the measuring of IR as it correlates well with IR.
Its use is limited because of a high proportion of false-positive results and lack of standardization. This ratio has been used in studies as an index of IR. It is a highly sensitive and specific measurement of insulin sensitivity. It provides a consistent and precise index of insulin sensitivity with better positive predictive power.
It is calculated as:. Product of plasma glucose and insulin concentrations has been considered an index of whole-body insulin sensitivity and it provides better index of insulin sensitivity.
If plasma glucose level is higher, along with higher plasma insulin response, state of IR tends to be more severe.
Insulin resistance is thought to be a primary etiological factor in the development of cardiac dysfunction, higher prevalence being reported in nonischemic heart failure population. It predates the development of cardiovascular disease and independently defines a worse prognosis.
Reduction in endothelial function may be a link between IR and decline in cardiovascular performance. Acanthosis nigricans patients have hyperinsulinemia and may be at greater risk of atherosclerotic cardiovascular disease.
Obesity is commonly associated with type 2 diabetes, coronary artery disease, and hypertension, coexistence of which is termed the metabolic syndrome.
IR lies at the heart of the metabolic syndrome. Elevated serum triglycerides commonly associated with IR represent a valuable clinical marker of metabolic syndrome. Decrease in adiponectin levels by genetic and environmental factors contributes to the development of the metabolic syndrome. Adiponectin is important because of its antidiabetic and antiatherogenic effects; hence it is expected to be a novel therapeutic tool for the metabolic syndrome.
The thiazolidinedione TZD class of antidiabetic drugs, having pleiotropic effects on cardiovascular diseases and lipid metabolism exert their effects partly through increasing levels of adiponectin. Adiponectin expression and levels in circulation are upregulated by rosiglitazone. Weight loss and exercise have shown to increase insulin sensitivity and reduce insulin levels causing improvement in obesity associated AN.
An approach to acanthosis nigricans
Acanthosis nigricans as an indicator of insulin resistance in Chilean adult population. Pinheiro 1, 2 , P. Rojas 1 , F. Carrasco 1 , P. Mayas 1 and I.
Translation of "acantosis pigmentaria" in English
Acanthosis nigricans is a medical sign characterised by brown-to-black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds,  such as the posterior and lateral folds of the neck , the armpits , groin , navel , forehead and other areas. It is associated with endocrine dysfunction , especially insulin resistance and hyperinsulinaemia , as seen in diabetes mellitus. This activates the insulin-like growth factor receptors , which leads to proliferation of keratinocytes , fibroblasts and other cells in the skin. Activation of other growth factor receptors such as fibroblast growth factor receptors or epidermal growth factor receptor can also be responsible. Acanthosis nigricans may present with thickened, velvety, relatively darker areas of skin on the neck, armpit and in skin folds. It typically occurs in individuals younger than age 40, may be genetically inherited and is associated with obesity or endocrinopathies, such as hypothyroidism , acromegaly , polycystic ovary disease , insulin-resistant diabetes or Cushing's disease.
Acanthosis Nigricans. Pero, aparte de esto, la acantosis nigricans es inofensiva. En casos excepcionales, la acantosis nigricans se puede desarrollar tras la toma de algunos medicamentos, como los anticonceptivos orales y los medicamentos para tratar el colesterol. En aquellos casos en que se identifica una causa subyacente a la acantosis nigricans, el tratamiento de esta causa puede permitir que las manchas oscuras de la piel acaben desapareciendo por completo. Estimule a su hijo a seguir una dieta equilibrada y a hacer cambios saludables en su estilo de vida.