How should acanthosis nigricans be treated in adults, including management of underlying insulin resistance, endocrine disorders, possible malignancy, and appropriate topical or procedural skin therapies?

Treatment of Acanthosis Nigricans

The primary treatment of acanthosis nigricans is addressing the underlying cause—weight reduction for obesity-associated cases, managing insulin resistance, screening for and treating malignancy in atypical presentations, and discontinuing causative medications—with topical therapies reserved for cosmetic improvement after systemic factors are controlled. 1, 2, 3

Immediate Diagnostic Priorities

Rule Out Malignancy First

• Urgent malignancy screening is mandatory when AN presents with sudden onset, rapid progression, extensive involvement beyond typical intertriginous areas, mucosal involvement, or in non-obese patients without clear metabolic risk factors 4
• Malignant AN most commonly associates with gastric adenocarcinoma and other intra-abdominal malignancies, though endometrial adenocarcinoma has been reported even in young patients 4
• Atypical features in presumed benign AN warrant extensive investigation regardless of patient age or body habitus 4

Assess Insulin Resistance and Metabolic Status

• Use HOMA-IR (Homeostasis Model Assessment-Insulin Resistance) as the preferred tool for quantifying insulin resistance 3
• Screen for diabetes mellitus, polycystic ovary syndrome, and other endocrine disorders that drive hyperinsulinemia 1, 5
• Evaluate for medication-induced AN (corticosteroids, nicotinic acid, insulin, oral contraceptives, protease inhibitors) 2, 3

Algorithmic Treatment Approach

Step 1: Address Underlying Etiology (Primary Treatment)

Weight reduction is the most scientific and practical management strategy for obesity-associated AN and should be the cornerstone of therapy 3

• For obesity-associated AN with insulin resistance: Implement structured weight loss through caloric restriction and increased physical activity; even modest weight reduction can lead to significant improvement 1, 3, 5
• For medication-induced AN: Discontinue or substitute the causative drug when clinically feasible 3, 5
• For endocrine disorders: Treat the underlying endocrinopathy (hypothyroidism, Cushing syndrome, acromegaly) to resolve hyperinsulinemia 1, 5
• For malignant AN: Treatment or removal of the underlying malignancy is essential; MAN often improves with successful cancer therapy 4

Step 2: Pharmacologic Management of Insulin Resistance

• Consider insulin-sensitizing agents (metformin) for patients with documented insulin resistance and inadequate response to lifestyle modification alone 3
• This addresses the pathophysiologic driver of AN—compensatory hyperinsulinemia stimulating keratinocyte and fibroblast proliferation 1, 3

Step 3: Topical Therapies for Cosmetic Improvement

Topical treatments improve cosmesis and reduce plaque thickness but do not address the underlying pathophysiology 1, 2

First-Line Topical Agents

• Topical retinoids (tretinoin 0.05-0.1%): Reduce hyperkeratosis and normalize keratinocyte proliferation; apply nightly to affected areas 2, 3, 5
• Keratolytic agents: Salicylic acid, urea, or lactic acid preparations thin hyperkeratotic plaques 1, 3
• Vitamin D analogs (calcipotriene): May reduce epidermal proliferation when used in combination with retinoids 3, 5

Second-Line Options

• Topical alpha-hydroxy acids: Improve skin texture and reduce pigmentation 1
• Chemical peels (trichloroacetic acid 10-20%): For localized lesions unresponsive to topical therapy 3

Step 4: Systemic and Procedural Therapies (Refractory Cases)

• Oral retinoids (isotretinoin, acitretin): Reserved for extensive or generalized AN unresponsive to topical therapy and underlying cause management 3, 5
• Laser therapy: Long-pulsed alexandrite (755 nm), fractional 1550-nm erbium fiber, or CO2 lasers may improve pigmentation and texture in select cases 3
• Dermabrasion or surgical excision: Rarely indicated and only for highly localized, cosmetically distressing lesions 5

Critical Pitfalls and Caveats

Common Management Errors

• Treating AN as purely cosmetic without investigating underlying causes leads to missed diagnoses of diabetes, malignancy, or endocrinopathies 5, 4
• Assuming all AN in obese patients is benign: Sudden onset, rapid progression, or extensive involvement warrants malignancy screening even in obesity 4
• Expecting complete resolution with topical therapy alone: Complete cure is difficult to achieve without addressing systemic drivers 3, 5

Realistic Outcome Expectations

• AN is treatable but rarely completely resolves; lesions typically improve but persist to some degree even with optimal management 3, 5
• Weight reduction produces the most durable improvement but requires sustained lifestyle modification 3
• Recurrence is common if underlying metabolic abnormalities are not controlled 5

Monitoring Strategy

• Regular follow-up to assess response to underlying cause treatment and detect early recurrence 5
• Ongoing surveillance for development of diabetes in patients with insulin resistance 1, 5
• Repeat malignancy screening if initially negative but clinical suspicion remains high or lesions progress despite appropriate management 4