How should I diagnose and manage onychomycosis in a patient undergoing cytotoxic chemotherapy?

Onychomycosis in Chemotherapy Patients: Diagnosis and Management

Critical First Step: Confirm True Fungal Infection Before Treatment

In patients undergoing cytotoxic chemotherapy with nail changes, you must first distinguish chemotherapy-induced nail toxicity from true onychomycosis through microscopy and fungal culture, because most nail changes during chemotherapy are drug-induced rather than infectious. 1, 2

Why This Distinction Matters

• Taxane chemotherapy causes nail changes in 34.9–43.7% of patients, including true leukonychia (white nails from matrix injury), apparent leukonychia from onycholysis, melanonychia, and Beau's lines 3, 2
• These chemotherapy-induced changes typically appear several weeks after treatment initiation and are dose-related and cumulative 3, 2
• Fingernails are affected more frequently than toenails in chemotherapy-induced toxicity 3
• Other agents like capecitabine, etoposide, and cytarabine also produce nail changes that may mimic fungal infection 3

Diagnostic Algorithm

Step 1: Clinical Assessment

Examine for features that distinguish fungal infection from drug toxicity:

• Onychomycosis typically presents with: discolored nails, nail plate thickening, nail separation from the bed, and foul-smelling nails 4
• Chemotherapy toxicity presents with: nail-fold edema/erythema, cuticle disruption, pain, discharge, and often affects multiple nails symmetrically 2
• Melanonychia can be caused by both fungal infection and chemotherapy, requiring careful differentiation 5

Step 2: Mandatory Laboratory Confirmation

Never treat presumed onychomycosis in chemotherapy patients without laboratory confirmation because:

• Potassium hydroxide (KOH) preparation with confirmatory fungal culture is the preferred diagnostic approach 4
• Alternative confirmatory tests include periodic acid-Schiff (PAS) stain or polymerase chain reaction (PCR) if culture is not available 4
• Obtain bacterial, viral, and fungal cultures if infection is suspected in Grade 2 or higher nail toxicity 2
• Biopsy may be required when conditions like psoriasis are in the differential 6

Step 3: Special Consideration for Immunocompromised State

In severely immunocompromised chemotherapy patients, onychomycosis can serve as a portal for disseminated fungal infection:

• Careful evaluation for onychomycosis and removal of the focus is mandatory in patients who are or will become immunocompromised 1
• Cases exist where onychomycosis has been the source of subsequent disseminated infection in immunocompromised patients 1
• Thorough evaluation and treatment of skin lesions should be undertaken before antineoplastic therapy, as skin may be the primary source of life-threatening infections 1

Management Algorithm for Confirmed Onychomycosis

If Fungal Infection is Confirmed:

Oral terbinafine 250 mg daily is the preferred treatment over topical therapy due to better effectiveness and shorter duration, but requires careful consideration of the patient's chemotherapy status 4, 7

Treatment Considerations:

• Standard terbinafine course: 12 weeks for toenails provides 70% cure rate with <10% relapse risk 7
• Monitor for drug-drug interactions if patient is taking tricyclic antidepressants, SSRIs, atypical antipsychotics, beta blockers, or tamoxifen 4
• Alternative oral agents: itraconazole or fluconazole if terbinafine is contraindicated 8, 6

Topical Therapy Option:

Use topical agents (ciclopirox 8%, efinaconazole 10%, or tavaborole 5%) for mild to moderate disease when systemic therapy poses excessive risk 4, 8

• Topical therapy has fewer adverse effects and drug-drug interactions but is less effective than oral agents 4
• Nail trimming and debridement used concurrently with pharmacologic therapy improve treatment response 4

Timing Relative to Chemotherapy:

Consider postponing cytotoxic therapy if severe fungal infection is present, as reversal of immunocompromised state is essential for successful treatment 1

• Secondary prophylaxis should be considered (voriconazole, posaconazole, or amphotericin B lipid formulation) in immunosuppressed patients with prior fungal infections 1
• Use of granulocyte colony-stimulating factor to shorten neutropenia may be warranted 1

Management of Chemotherapy-Induced Nail Changes (Non-Fungal)

If Fungal Culture is Negative:

Follow the severity-graded algorithm for chemotherapy-induced nail toxicity:

Grade 1 (Mild):

• Continue chemotherapy at current dose 2
• Apply topical povidone-iodine 2% as first-line therapy 2
• Add topical antibiotics and corticosteroids for enhanced effect 2
• Reassess after 2 weeks 2

Grade 2 (Moderate):

• Maintain current chemotherapy dose 2
• Apply topical povidone-iodine 2% plus beta-blocking agents, antibiotics, and corticosteroids 2
• Initiate oral antibiotics for possible secondary infection 2
• Obtain cultures if infection suspected 2

Grade 3 (Severe):

• Interrupt chemotherapy until toxicity improves to Grade 0-1 2
• Continue comprehensive topical regimen 2
• Consider partial nail avulsion for refractory cases 2

Prevention Strategies

Implement these measures for all chemotherapy patients:

• Gentle skin care: comfortable footwear, gloves for cleaning, avoid nail biting or overly short trimming 2
• Daily topical emollients to cuticles and periungual skin 2, 5
• Biotin supplementation may improve nail strength 2
• Frozen gloves (10-30°C for 90 minutes) during taxane infusions significantly reduce nail changes 5
• Regular topical antifungal prophylaxis may prevent tinea pedis and onychomycosis recurrence 7
• Avoid walking barefoot in public places and disinfect shoes and socks to reduce 25% relapse rate 4

Critical Pitfalls to Avoid

• Never assume nail changes in chemotherapy patients are fungal without laboratory confirmation—most are drug-induced 3, 2
• Do not delay evaluation of onychomycosis in patients about to start chemotherapy, as it can become a source of disseminated infection 1
• Distinguish true leukonychia (cosmetic, self-limited) from apparent leukonychia/onycholysis (requires prompt treatment to prevent permanent nail-bed keratinization) 3, 2
• Secondary bacterial or fungal superinfection occurs in up to 25% of chemotherapy-induced nail toxicity cases, requiring culture and antimicrobial therapy 2