In an 85‑year‑old man with chronic brown‑black velvety plaques on the face, neck and dorsal hands, central obesity, pre‑diabetic HbA1c, benign prostatic hyperplasia treated with finasteride, and donepezil for cognition, what is the most likely diagnosis and recommended management?

Diagnosis: Acanthosis Nigricans with Metabolic Syndrome

The most likely diagnosis is acanthosis nigricans (AN) secondary to insulin resistance and metabolic syndrome, and management should prioritize addressing the underlying metabolic dysfunction through weight reduction, diabetes prevention, and topical therapy for cosmetic improvement. 1, 2

Clinical Diagnosis

The presentation of brown-to-black, velvety, thickened patches over the face, neck, and dorsum of hands in an 85-year-old man with central obesity and pre-diabetic HbA1c is pathognomonic for acanthosis nigricans. 1, 2

• Classic features present: symmetric, hyperpigmented, velvety plaques with ill-defined borders in typical distribution (neck, face, and dorsal hands—an acral variant) 2, 3
• Duration >10 years with gradual progression correlates with chronic insulin resistance and progressive weight gain 1
• Central obesity (abdominal fat+++) is the most common cause of AN and serves as a cutaneous marker of insulin resistance 2

Key Differential Considerations to Exclude

While the clinical presentation strongly suggests benign obesity-associated AN, several important differentials warrant consideration:

• Malignancy-associated AN: Rare but critical to exclude, particularly given the patient's age. However, the 10-year duration and absence of constitutional symptoms make this unlikely, as malignant AN typically has rapid onset and progression 2, 3
• Erdheim-Chester Disease (ECD): The presence of xanthelasma-like lesions on the face could represent ECD, which occurs in 25-33% of ECD patients and may present with diabetes insipidus, bone pain, or cardiovascular symptoms 4, 5
• Drug-induced hyperpigmentation: Finasteride is not typically associated with AN, though medication review is prudent 6

Diagnostic Workup

Essential Laboratory Investigations

Metabolic screening (already partially completed with pre-diabetic HbA1c):

• Fasting glucose and repeat HbA1c: To confirm pre-diabetes status and guide diabetes prevention strategies 2
• Fasting lipid panel: 60-75% of AN patients have dyslipidemia; screen for familial hypercholesterolemia even if lipids appear normal 7, 4
• Thyroid function tests (TSH, free T4): Hypothyroidism can cause secondary dyslipidemia and contribute to AN 8, 4

Additional screening based on clinical context:

• Insulin and C-peptide levels: To quantify degree of insulin resistance if diagnosis uncertain 1
• Wood's lamp examination: To exclude erythrasma (coral-red fluorescence) in axillary/neck involvement 8

When to Consider Tissue Diagnosis

• Skin biopsy is NOT routinely required for typical AN presentation 2
• Consider biopsy if: atypical morphology, unusual location, rapid progression suggesting malignancy, or systemic symptoms suggesting ECD 2, 4
• If ECD is suspected, shave biopsy of facial lesions is the least invasive diagnostic approach 4

Management Strategy

Primary Treatment: Address Underlying Metabolic Dysfunction

Weight reduction is the cornerstone of therapy for obesity-associated AN:

• Target: Gradual weight loss through caloric restriction and maintained physical activity (patient already achieving 7-10k steps/day—excellent) 2, 3
• Diabetes prevention: Intensive lifestyle modification given pre-diabetic HbA1c to prevent progression to type 2 diabetes 1
• Dietary counseling: Focus on reducing insulin resistance through low glycemic index diet 2

Topical Therapy for Cosmetic Improvement

While treating the underlying cause is paramount, cosmetic improvement is important for quality of life:

First-line topical agents:

• Topical retinoids (tretinoin 0.05-0.1% cream): Applied nightly to affected areas; improves hyperkeratosis and hyperpigmentation 2, 3
• Keratolytic agents:
  • Urea 10-20% cream applied twice daily for hyperkeratosis 3
  • Alpha-hydroxy acids (lactic acid, glycolic acid 12%) for exfoliation 1, 3

Second-line options for refractory lesions:

• Vitamin D analogs (calcipotriene): May improve pigmentation 2
• Chemical peels: For localized lesions unresponsive to topical therapy 2

Medication Review

• Continue finasteride for BPH: No evidence linking finasteride to AN; benefits for BPH management outweigh theoretical concerns 6
• Continue donepezil: No association with AN; cognitive benefits are important in this 85-year-old patient
• Avoid medications that worsen insulin resistance: NSAIDs, corticosteroids if possible 1

Monitoring and Follow-up

• Repeat HbA1c every 3-6 months: Monitor for progression to diabetes 2
• Annual lipid panel and thyroid function: Screen for emerging metabolic abnormalities 4, 8
• Monitor for malignancy: While unlikely given 10-year duration, remain vigilant for rapid progression, new systemic symptoms, or lesions unresponsive to therapy that might suggest malignant AN 2, 3
• Assess for ECD if systemic symptoms develop: Bone pain, diabetes insipidus, exophthalmos, or cardiovascular symptoms warrant further evaluation 4, 5

Common Pitfalls to Avoid

• Do not assume all hyperpigmentation is benign: While obesity-associated AN is most common, failure to screen for underlying malignancy or systemic disease can delay critical diagnoses 2
• Do not rely solely on topical therapy: Without addressing underlying insulin resistance and obesity, AN will persist and progress despite cosmetic treatments 1, 3
• Do not overlook familial hypercholesterolemia: Standard lipid panels can miss FH; if xanthelasma-like lesions are present, pursue advanced lipid testing and genetic evaluation 4
• Complete cure is difficult to achieve: Set realistic expectations with the patient that improvement requires sustained lifestyle modification and topical therapy may provide only partial cosmetic benefit 2