What is the cause and treatment of darkening skin around the neck, considering factors such as insulin resistance, diabetes, hormonal imbalances, age, ethnicity, and body mass index (BMI)?

Darkening Skin Around the Neck: Acanthosis Nigricans

Darkening skin around the neck is most commonly acanthosis nigricans (AN), a cutaneous manifestation of insulin resistance that requires screening for diabetes and metabolic syndrome, with treatment focused on weight loss, metformin, and topical retinoids. 1, 2

Clinical Recognition and Diagnosis

Acanthosis nigricans presents as dark, coarse, thickened skin with a velvety texture, symmetrically distributed on the neck, axillae, and body folds. 2 The diagnosis is primarily clinical, characterized by hyperpigmentation with a rippled pattern that may extend to the groin, antecubital and popliteal fossae 2. Histopathology shows papillomatosis and hyperkeratosis, though biopsy is rarely needed for confirmation 2.

Key Physical Examination Findings

• Look for associated skin tags (acrochordons) around the eyelids, neck, or axillae, which strongly suggest insulin resistance 3
• Central/visceral adiposity is a critical finding that indicates underlying metabolic dysfunction 1
• The presence of AN in pigmented ethnic groups (African American, Hispanic/Latino, Asian/Pacific Islander) is particularly common and clinically significant 4, 1

Underlying Causes and Risk Assessment

AN is fundamentally a marker of insulin resistance and the obesity syndrome, not merely a cosmetic issue. 3 The condition results from compensatory hyperinsulinemia, where elevated insulin levels stimulate keratinocyte and fibroblast proliferation 2, 3.

Mandatory Screening Tests

• Fasting plasma glucose (100-125 mg/dL indicates impaired fasting glucose and insulin resistance) 1
• Fasting insulin levels (>15 mU/L directly confirms insulin resistance) 1
• Hemoglobin A1C (5.7-6.4% suggests prediabetes with underlying insulin resistance) 1
• Oral glucose tolerance test (2-hour glucose 140-199 mg/dL indicates impaired glucose tolerance) 1
• Lipid profile (HDL <35 mg/dL, triglycerides >250 mg/dL indicate dyslipidemia) 1
• Hemoglobin and alanine aminotransferase for obesity-associated AN 2

High-Risk Populations Requiring Testing

• BMI ≥25 kg/m² (or ≥23 kg/m² for Asian Americans) with additional risk factors 1
• First-degree relatives with type 2 diabetes 1
• Women with polycystic ovary syndrome (PCOS) or history of gestational diabetes 1, 5
• Patients with hypertension or dyslipidemia 1

Critical Differential Diagnosis

While obesity-associated AN is most common, rapidly progressive or extensive AN may indicate malignancy and requires urgent radiological investigation (plain radiography, ultrasonography, MRI/CT). 2, 5 This paraneoplastic form is rare but potentially life-threatening 5.

In atopic dermatitis patients, consider "dirty neck" appearance (ripple pigmentation), which results from melanin incontinence rather than insulin resistance. 6 This presents with a similar rippled hyperpigmentation pattern but occurs in the context of chronic eczema without metabolic abnormalities 6.

Treatment Algorithm

First-Line: Lifestyle Modification

Achieve 5-7% weight loss through structured calorie reduction and at least 150 minutes of moderate-intensity aerobic activity weekly, plus resistance training twice weekly. 7 This directly addresses the underlying insulin resistance and is the most effective intervention for morbidity and mortality reduction 7.

Dietary Modifications

• Limit saturated fat to <7% of total calories and minimize trans fat intake 7
• Consume 14 g of fiber per 1,000 kcal, emphasizing whole grains (at least half of grain intake) 7
• Limit alcohol to ≤1 drink daily for women, ≤2 drinks daily for men 7

Pharmacological Treatment

When lifestyle changes are insufficient after 3 months, initiate metformin as the preferred first-line agent, starting at low dose with gradual titration to minimize gastrointestinal side effects. 7, 2, 5 Metformin improves insulin sensitivity and directly treats the underlying pathophysiology 5.

Topical Therapy for Cosmetic Improvement

Topical retinoids are the most effective agents for improving the appearance of AN. 2 Azelaic acid can be used as an adjunctive treatment for postinflammatory dyspigmentation 4.

Long-Term Monitoring and Complications

Patients with AN require ongoing surveillance for progression to type 2 diabetes, cardiovascular disease, and cerebrovascular disease. 3 The presence of AN identifies individuals at particularly high risk for developing the full obesity syndrome spectrum 3.

Follow-Up Schedule

• Repeat glucose testing every 3 years minimum if initial tests are normal 4
• Monitor for development of hypertension, dyslipidemia, and diabetes mellitus type II 3
• Assess for complications of obesity and hyperinsulinemia, including infertility in women 5

Common Pitfalls to Avoid

Normal fasting glucose does not exclude insulin resistance—hyperinsulinemia can exist with euglycemia. 1, 8 Always measure fasting insulin levels in addition to glucose 1.

Do not dismiss AN as purely cosmetic—it is an early warning sign of serious metabolic disease with significant mortality implications. 3 The condition offers critical opportunities for preventative intervention before progression to diabetes and cardiovascular disease 3.

In rapidly progressive or extensive AN, especially in non-obese patients, rule out malignancy before attributing it to insulin resistance. 2, 5