Why do toenails turn black during chemotherapy?

Why Toenails Turn Black During Chemotherapy

Toenails turn black during chemotherapy primarily due to direct cytotoxic damage to the nail bed epithelium, causing onycholysis (separation of the nail from the nail bed) where the detached part becomes opaque and discolored, often appearing black. 1

Mechanisms of Nail Discoloration During Chemotherapy

Chemotherapy affects the rapidly dividing cells of the nail matrix, leading to various nail changes including black discoloration through several mechanisms:

1. Direct cytotoxic damage:

   • Chemotherapy drugs directly damage the nail bed epithelium, causing epidermolysis and loss of adhesion between the nail plate and nail bed 1
   • The separated space can collect debris and become discolored

2. Specific causes of black discoloration:

   • Subungual hemorrhage: Blood accumulation under the nail appears black
   • Melanonychia: Increased melanin production in the nail matrix
   • Secondary infection: Bacterial or fungal growth in the detached space

3. Most common causative agents:

   • Taxanes: Docetaxel and paclitaxel are the most frequent chemotherapeutic agents causing nail toxicity, with severe onycholysis almost exclusively occurring with these drugs 1, 2
   • Other agents: Cyclophosphamide, doxorubicin, and 5-fluorouracil can also cause nail pigmentation changes 3, 4

Clinical Presentation

The nail changes typically develop after several weeks of treatment due to the slow growth rate of nails 1. The presentation includes:

• Onycholytic nail plate becomes opaque and loses transparency
• Discoloration ranges from black to white or brown-red 1
• Fingernails are more commonly affected than toenails, though both can be involved
• Pain may occur due to trauma, detachment progression, or development of subungual hematoma/abscess
• May be associated with inflammatory changes around the nail

Risk Factors

Several factors increase the risk of developing black toenails during chemotherapy:

• Dose-related: Higher cumulative doses increase risk 1
• Treatment schedule: Weekly regimens (particularly with taxanes) have higher incidence than 3-weekly regimens 1
• Peripheral neuropathy: Integrity of peripheral nerves appears to be a substantial factor 1
• Multiple agent therapy: Combinations of chemotherapeutic agents increase risk 3

Prevention

Preventive measures can significantly reduce the risk of nail changes:

• Cryotherapy: Frozen gloves and socks (10-30°C for 90 minutes) significantly reduce nail changes (from 21% to 0% in toenails with taxanes) 1
• Nail care:
  • Daily application of topical emollients to cuticles and periungual tissues
  • Regular trimming of nails (straight across, not too short)
  • Avoiding trauma and excessive pressure
  • Wearing comfortable, well-fitting shoes and cotton socks 1
  • Avoiding prolonged water exposure 1

Management

When black toenails develop during chemotherapy:

1. Assessment: Determine if the nail change is purely cosmetic or if there are signs of infection or significant pain

2. For painful or severe lesions:

   • Removal of the nail plate may be necessary, especially with pressure hematoma or subungual abscess
   • Clean the nail bed and obtain cultures if infection is suspected
   • Treat infections promptly with appropriate antibiotics 1

3. For mild to moderate cases:

   • Keep nails clean and dry
   • Continue regular trimming until the nail plate grows reattached
   • Apply topical antimicrobials if secondary infection is present

Prognosis

Most chemotherapy-induced nail changes are temporary:

• Changes typically resolve after completion of chemotherapy
• Complete resolution may take several months due to slow nail growth
• In some cases, chronic onycholysis may lead to nail bed keratinization and persistent subungual hyperkeratosis 1

Special Considerations

• Patient education: Inform patients about potential nail changes before starting chemotherapy
• Quality of life impact: Nail changes can significantly affect body image and quality of life
• Treatment modification: Severe nail toxicity may occasionally require chemotherapy dose reduction or schedule modification 5
• Monitoring: Regular assessment of nails during chemotherapy to detect early signs of infection or severe changes

The black discoloration of toenails during chemotherapy, while often distressing to patients, is usually manageable with proper preventive measures and care during treatment.