What is the differential diagnosis and recommended evaluation for isolated hyperpigmentation of the right hand in an otherwise healthy adult?

Isolated Unilateral Hand Hyperpigmentation: Differential Diagnosis and Evaluation

Your relative needs urgent dermatology evaluation to exclude melanoma, particularly acral lentiginous melanoma, which can present as darkening of the hand and carries significant mortality risk if not diagnosed early.

Immediate Action Required

Any suspicious pigmented lesion on the hand requires referral to a dermatologist within 2 weeks 1. The unilateral distribution is particularly concerning and demands expert evaluation to rule out malignancy before considering benign causes.

Critical Red Flags to Assess

Examine the darkened area for these melanoma warning signs:

• Irregular borders – wiry, beaded, or markedly irregular outline 2
• Color variation – multiple shades of brown, black, or blue-gray 3
• Asymmetry – one half doesn't match the other
• Diameter >6mm or any changing lesion
• Evolution – any change in size, shape, or color over time 4

If ANY of these features are present, this is a dermatology emergency 1, 4.

Differential Diagnosis by Pattern

Malignant Causes (Must Exclude First)

• Acral lentiginous melanoma – can present as diffuse darkening of palmar/dorsal hand surface; unilateral presentation is highly suspicious 5
• Lentigo maligna melanoma – though more common on face, can occur on sun-exposed dorsal hand 1

Benign Causes (Only After Malignancy Excluded)

• Post-inflammatory hyperpigmentation (PIH) – requires history of prior trauma, burn, rash, or inflammation on that hand 6, 3, 7
• Solar lentigo – typically multiple discrete spots, not diffuse darkening; bilateral distribution more common 8, 2
• "Ink spot" lentigo – black with irregular outline but usually solitary small lesion, not entire hand 2
• Contact dermatitis with PIH – requires exposure history (chemicals, plants, jewelry) 6, 3

Systemic Causes (Rare for Unilateral Presentation)

• Addison's disease – causes hyperpigmentation but typically bilateral and involves palmar creases, mucosa 9
• Drug-induced – certain medications cause hyperpigmentation but rarely unilateral

Diagnostic Workup Algorithm

Step 1: Urgent Dermatology Referral

Schedule within 2 weeks for any suspicious pigmented lesion 1. The dermatologist will perform:

• Complete skin examination including all body surfaces and lymph nodes 5, 1
• Dermoscopy to characterize the pigmentation pattern 9
• Wood's lamp examination to differentiate epidermal (enhances under Wood's lamp) from dermal pigmentation (doesn't enhance) 9
• Clinical photography for documentation and monitoring 1

Step 2: Biopsy Decision

If melanoma cannot be clinically excluded, excisional biopsy is mandatory 1, 4:

• Full-thickness excisional biopsy with 2-5mm margins including subcutaneous fat 1, 4
• Never use shave, punch, cryotherapy, or laser – these destroy tissue needed for Breslow thickness measurement and staging 5, 4
• All excised tissue must go to pathology – this is non-negotiable 5, 4

Step 3: History Taking (Performed by Dermatologist)

Key questions to differentiate causes:

• Timeline – sudden vs gradual onset, duration 9
• Trauma history – burns, cuts, rashes, insect bites on that hand 6, 3
• Occupational/chemical exposure – cleaning products, plants, sun exposure patterns 9
• Systemic symptoms – fatigue, weight loss, salt craving (Addison's) 9
• Medications – antimalarials, chemotherapy, minocycline 8
• Family history – autoimmune disease, melanoma, pigmentation disorders 9

Step 4: Laboratory Testing (If Indicated)

Only order if systemic disease suspected after dermatology evaluation 9:

• Thyroid function tests – if family history of autoimmune disease 9
• Morning cortisol/ACTH – if bilateral involvement or systemic symptoms suggesting Addison's
• Antinuclear antibodies – if features suggest autoimmune condition

Critical Pitfalls to Avoid

Never treat pigmented lesions with destructive methods (cryotherapy, laser) without histological confirmation 4. This represents a significant medicolegal risk and eliminates the ability to:

• Measure Breslow thickness (most important prognostic factor) 4
• Assess ulceration and mitotic rate (determines staging) 4
• Confirm diagnosis histologically 5, 4

Never assume benign cause based on appearance alone – melanoma can mimic benign lesions 1, 4.

Never delay referral for "watchful waiting" – early melanoma detection dramatically improves survival 1, 4.

Management Pending Dermatology Evaluation

While awaiting specialist assessment:

• Apply broad-spectrum SPF 30+ sunscreen daily to prevent UV-induced darkening 9
• Avoid further trauma to the affected hand 6, 7
• Document with photographs to track any changes 1, 9
• Do not apply bleaching creams or other treatments before diagnosis 6, 3

The unilateral distribution makes this presentation atypical for most benign causes and mandates expert evaluation to exclude life-threatening melanoma 1, 4.