Chapter 229: Acanthosis Nigricans

PATIENT STORY

A 13-year-old Hispanic girl presents to her family physician with concerns about "dirty areas" under her arms and on her neck that "can't be cleaned" (Figure 229-1). Her periods have stopped and she is getting new hair growth on her face. She is overweight and has a family history of diabetes. The physician makes the diagnosis of acanthosis nigricans.

INTRODUCTION

• Acanthosis nigricans (AN) is a localized form of hyperpigmentation that involves epidermal alteration. AN is usually associated with insulin resistance or hyperinsulinemia and is seen in patients with endocrine disorders (e.g., type 2 diabetes mellitus [DM], Cushing syndrome, acromegaly), obesity, and polycystic ovary syndrome.^1-3

EPIDEMIOLOGY

• In a cross-sectional study of prevalence conducted in a nationwide underserved practice-based research network (N = 1730), AN was found in 18.2% of children and 19.5% of adults. Those with AN were twice as likely to have DM as those without AN (35.4% vs. 17.6%, p < 0.001).⁴

• Several studies have used AN as a predictor of metabolic syndrome^5,6; AN observed on the knuckles of Latin American youth had been reported as an early clinical indicator.⁷

• AN is sometimes associated with malignancy, primarily adenocarcinoma (60%) of the stomach, gallbladder, colon, ovary, pancreas, rectum, and uterus.^2,8,9

• Although most cases are idiopathic, there are also genetic causes of AN.^2,8

• A condition of hyperandrogenism (HA), insulin resistance (IR), and AN called HAIR-AN syndrome occurs in approximately 1% to 3% of women with HA.¹⁰ This syndrome may also be seen in patients with autoimmune disorders such as Hashimoto thyroiditis.

• AN can be an adverse effect from hormonal therapies.¹¹

ETIOLOGY AND PATHOPHYSIOLOGY

• AN results from long-term exposure of keratinocytes to insulin.²

• Keratinocytes have insulin and insulin-like growth receptors on their surface. The pathogenesis of this condition is linked to insulin binding to insulin-like growth receptors in the epidermis stimulating keratinocyte proliferation.²

• Fibroblast growth factor receptor 3 (FGFR3) gene mutations should be considered in patients with coexistent AN and skeletal dysplasia.¹²

DIAGNOSIS

The diagnosis of AN is made clinically, with histopathology only when confirmation is needed, and can be classified by severity on a scale of 0–4. Increased scores correlate with increased BMI and fasting insulin levels.²

CLINICAL FEATURES

• AN ranges in appearance from diffuse streaky thickened brown velvety lesions to leathery verrucous papillomatous lesions (...