What are the possible causes and treatment options for nail infection with negative fungal consult and iron deficiency?

Nail Dystrophy with Negative Fungal Testing: Differential Diagnosis and Management

With negative fungal testing, you should consider non-dermatophyte mould infection, bacterial infection (particularly Pseudomonas), Candida infection, or non-infectious causes including psoriasis, lichen planus, chronic trauma, and importantly in this patient with low ferritin—iron deficiency-related nail changes. 1, 2, 3

Diagnostic Approach for Negative Fungal Testing

Repeat Fungal Testing is Critical

• 94% of clinically suspected onychomycosis cases with initial negative testing eventually test positive after up to four consecutive laboratory investigations including PCR. 4
• The British Association of Dermatologists emphasizes that good nail specimens are crucial—material should be taken from discoloured, dystrophic or brittle parts, cutting the nail as far back as possible through the entire thickness including any crumbly material. 1
• Consider requesting PCR testing if standard microscopy and culture remain negative, as this significantly improves diagnostic yield. 4

Alternative Infectious Causes to Consider

Bacterial Infection:

• Green or black nail discoloration suggests Pseudomonas aeruginosa infection (Green Nail Syndrome). 1, 2, 5
• Treatment: Keep affected area dry and apply topical povidone iodine 2% twice daily. 2, 5
• Bacterial superinfection commonly complicates other nail conditions and may be the primary pathology. 1, 6

Non-Dermatophyte Moulds:

• Account for approximately 5% of onychomycosis in the UK and 20% in North America. 1
• Should be suspected when previous antifungal treatment has failed on several occasions, direct microscopy is positive but no dermatophyte isolated, and there is no associated skin infection. 1
• These moulds are generally secondary invaders rather than primary pathogens (except Neoscytalidium species). 1

Candida Infection:

• Accounts for 5-10% of all onychomycosis cases. 1
• Fingernails are more commonly affected than toenails (opposite pattern from dermatophytes which affect toenails in 80% of cases). 1
• More common in women and those with occupations requiring repeated hand immersion in water. 1
• Candida paronychia presents with swollen, erythematous, painful periungual skin with nail involvement following—unlike dermatophyte infections, pressure and movement of the nail is painful. 1

Non-Infectious Causes

Iron Deficiency-Related Nail Changes (Highly Relevant to This Patient):

• Koilonychia (spoon nails) is a classic sign of iron deficiency and may appear even before anemia develops. 3
• Iron deficiency causes brittle nails with longitudinal ridging and splitting. 5
• This patient's documented low ferritin makes iron deficiency a significant contributor to nail dystrophy. 3

Other Non-Infectious Causes:

• Psoriasis, lichen planus, chronic trauma, and yellow nail syndrome can all mimic fungal infection. 1, 2
• Key distinguishing feature: the nail surface typically doesn't become soft and friable in non-infectious conditions (unlike fungal infections). 1, 2
• Lichen planus produces nail thinning with subungual hyperkeratosis and longitudinal ridging. 5

Treatment Algorithm

Step 1: Confirm or Exclude Fungal Infection

• Obtain repeat fungal testing with proper sampling technique before abandoning fungal diagnosis. 4
• Request PCR if available, as 94% of initially negative cases eventually test positive. 4
• If three consecutive tests remain negative, fungal infection is unlikely. 4

Step 2: Address Iron Deficiency (Critical in This Patient)

• Initiate iron supplementation as already planned—this alone may improve nail appearance significantly. 3
• Monitor ferritin levels and continue supplementation until stores are replete. 3
• In men or postmenopausal women with iron deficiency, investigate for gastrointestinal blood loss. 3

Step 3: Empiric Treatment Based on Clinical Pattern

If bacterial infection suspected (green/black discoloration):

• Topical povidone iodine 2% twice daily. 2, 5
• Keep area dry. 2, 5

If Candida suspected (fingernail predominance, paronychia, wet occupation):

• Itraconazole 400 mg daily for 1 week per month for 2 months (fingernails). 1
• Azoles are preferred for Candida species. 2

If non-dermatophyte mould suspected (treatment failure, no skin involvement):

• These do not respond to conventional antifungals. 7
• Requires specific identification and targeted therapy. 7

Step 4: Supportive Nail Care

• Apply daily topical emollients to cuticles and periungual tissues. 2, 5
• Use protective nail lacquers to limit water loss. 5
• Avoid trauma, prolonged water soaking, and harsh chemical exposure. 5

Common Pitfalls to Avoid

• Do not assume negative fungal testing definitively excludes fungal infection—repeat testing with proper technique is essential. 4
• Do not overlook iron deficiency as a significant contributor to nail dystrophy, especially when documented. 3
• Do not start systemic antifungals without mycological confirmation, but recognize that clinical suspicion may warrant empiric treatment after multiple negative tests. 4
• Do not ignore bacterial superinfection, which commonly complicates other nail conditions. 1, 6
• Do not diagnose fungal infection based on appearance alone—50% of nail dystrophy cases are non-fungal despite similar clinical presentation. 2

Face-to-Face Examination Priorities

When the patient sees the provider in person, specifically assess:

• Exact pattern of nail involvement (proximal vs. distal, fingers vs. toes). 1
• Presence of paronychia or periungual inflammation. 1
• Nail color (green/black suggests Pseudomonas, white suggests superficial infection). 1, 2
• Nail texture (soft and friable suggests infection, hard suggests non-infectious). 1, 2
• Signs of koilonychia (spoon-shaped nails from iron deficiency). 3
• Evidence of psoriasis or lichen planus elsewhere on body. 1, 5