What is the differential diagnosis and management for a 28-year-old female with hyperpigmentation of the toes upon cold exposure, accompanied by mild itching but no pain?

Differential Diagnosis and Management of Cold-Induced Hyperpigmentation of Toes in a 28-Year-Old Female

This presentation is most consistent with chilblains (pernio), a cold-induced inflammatory condition causing hyperpigmentation and pruritus without pain, which should be managed with cold avoidance, rewarming protocols, and consideration of topical anti-inflammatory therapy.

Primary Differential Diagnosis

Chilblains (Pernio) - Most Likely

• Cold-triggered hyperpigmentation with pruritus but no pain is pathognomonic for chilblains, a localized inflammatory response to cold exposure affecting acral sites, particularly toes 1
• The absence of pain distinguishes this from frostbite, which typically presents with numbness and pain 1
• Hyperpigmentation develops as a sequela of the inflammatory process, representing postinflammatory hyperpigmentation in affected areas 2, 3
• Mild itching is characteristic of the inflammatory phase and irritation of chilblains 1

Frostbite - Less Likely

• Frostbite typically presents with numbness, pain, and tissue damage rather than isolated hyperpigmentation with pruritus 1
• The absence of pain and presence of only hyperpigmentation makes superficial frostbite (frostnip) possible but less likely 1
• Severe frostbite would show tissue necrosis, blistering, or color changes from pale to dark, which is not described here 1

Raynaud's Phenomenon - Consider

• Can cause color changes in digits with cold exposure, but typically presents with triphasic color changes (white-blue-red) rather than persistent hyperpigmentation 4
• The absence of pain and presence of persistent hyperpigmentation makes primary Raynaud's less likely 4

Acrocyanosis - Consider

• Presents with persistent blue-purple discoloration of extremities with cold exposure 4
• However, this is typically symmetric, painless, and without the hyperpigmentation pattern described 4

Postinflammatory Hyperpigmentation from Other Causes

• Could result from previous inflammatory dermatoses, but the specific cold-exposure trigger points away from this 2, 3
• Lack of history of preceding inflammatory skin conditions makes this secondary 3

Critical Diagnostic Steps

Immediate Assessment

• Evaluate for the "6 P's" to exclude critical ischemia: Pain, Pallor/Purple discoloration, Pulselessness, Paresthesias, Paralysis, and Poikilothermia 4
• Check bilateral pedal pulses—normal pulses with hyperpigmentation and pruritus support chilblains over arterial occlusion 4
• Measure ankle-brachial index (ABI) if pulses are diminished; ABI <0.4 indicates critical ischemia requiring emergent vascular consultation 4

Exclude Serious Pathology

• Rule out melanoma if any pigmented lesion shows irregular borders, irregular pigmentation with multiple shades, diameter >1 cm, or growth 1
• Assess for systemic disease: Check thyroid function given association of autoimmune conditions with pigmentation disorders 1
• Consider vasculitis or thrombophilia in young patients with unexplained digital discoloration, as these can occur even in young adults 4

Distinguish from Mechanical Hyperkeratosis

• Paring of lesions can help distinguish from corns or calluses, which would show a central keratin plug rather than uniform hyperpigmentation 5
• Absence of pain with pressure distinguishes from corns, which cause pain described as "walking on a small stone" 5

Management Algorithm

Immediate Interventions

1. Cold avoidance is the cornerstone of treatment—instruct patient to avoid cold exposure, wear warm socks and properly fitting footwear 1
2. Gradual rewarming if acute cold exposure: Use lukewarm water (37-40°C) for 20-30 minutes if recent cold exposure occurred 1
3. Never use hot water or direct heat sources, as temperatures above 40°C can cause burns 1

Pharmacologic Management

• Ibuprofen 400-600mg orally may be reasonable to prevent further tissue damage and treat inflammation associated with chilblains 1
• Topical corticosteroids (potent or very potent) can be considered for a trial period of no more than 2 months to reduce inflammation 1
• Topical pimecrolimus or tacrolimus should be considered as alternatives with better safety profiles than potent steroids 1

Treatment of Hyperpigmentation

• Topical depigmenting agents including hydroquinone, azelaic acid, or kojic acid can be initiated once acute inflammation resolves 2, 3
• Photoprotection with sunscreen is essential to prevent worsening of hyperpigmentation 3
• Urea 10% cream applied three times daily can help with any associated hyperkeratosis 5

Preventive Measures

• Avoid walking barefoot or in thin-soled footwear in cold environments 5
• Wear properly fitting, cushioned footwear that accommodates foot shape and provides insulation 5
• Keep extremities warm and dry—remove wet clothing immediately and use warm (not hot) socks 1

Critical Pitfalls to Avoid

• Never assume young age excludes vascular disease—thrombophilia and vasculitis can occur in young patients 4
• Never assume absence of pain rules out serious pathology—some conditions may be painless despite significant tissue compromise 4
• Do not apply chemical warmers directly to affected tissue, as they can reach temperatures causing burns 1
• Avoid aggressive debridement without first ruling out vascular compromise or infection 5
• Do not attribute findings solely to benign causes without excluding melanoma in any pigmented lesion with concerning features 1

When to Escalate Care

Urgent Vascular Surgery Consultation Required If:

• Absent pulses with discoloration 4
• Motor deficits develop 4
• ABI <0.4 on Doppler assessment 4
• Rapid progression of necrosis or tissue changes 4

Dermatology Referral Indicated If:

• Pigmented lesions show irregular borders, multiple colors, or growth concerning for melanoma 1
• Hyperpigmentation does not improve after 2-4 weeks of appropriate therapy 5
• Atypical presentation requiring expert assessment 1

Additional Testing If No Improvement:

• Consider autoimmune workup including ANA, rheumatoid factor, and cryoglobulins if vasculitis suspected 1
• Skin biopsy may be warranted if diagnosis remains unclear or lesions are atypical 2, 6