What is the differential diagnosis for thick toenails in adults, considering various underlying medical conditions such as fungal infections (e.g. onychomycosis), psoriasis, eczema, poor circulation, diabetes, and immunocompromised state?

Differential Diagnosis for Thick Toenails

The most common cause of thick toenails is onychomycosis (fungal infection), but you must systematically rule out psoriasis, trauma-related changes, vascular insufficiency, and less common conditions like lichen planus before assuming fungal etiology. 1

Primary Infectious Causes

Onychomycosis (Fungal Infection)

• Distal and lateral subungual onychomycosis (DLSO) is the most common presentation, where fungus invades through the distal or lateral nail margins causing thickening, discoloration, and onycholysis with subungual hyperkeratosis 1
• Dermatophytes account for the majority of cases, with Trichophyton rubrum being the most prevalent organism (64% of cases), followed by T. mentagrophytes and Epidermophyton floccosum 2, 3
• Candida species cause nail thickening primarily in immunocompromised patients (presenting as total dystrophic onychomycosis) or in those with chronic paronychia and occupational moisture exposure 1
• Proximal subungual onychomycosis (PSO) is uncommon in the general population but serves as a marker for HIV infection/AIDS, where it spreads rapidly from the proximal margin 1
• Nondermatophyte molds account for approximately 5% of UK cases and 20% of North American cases, typically as secondary invaders of already damaged nails 1

Critical diagnostic pitfall: 50% of dystrophic nails are non-fungal despite similar clinical appearance—never diagnose fungal infection based on appearance alone 2, 4

Bacterial Infection

• Green Nail Syndrome from Pseudomonas aeruginosa or Proteus species causes discoloration and thickening, requiring topical povidone iodine 2% twice daily with keeping the area dry 2, 4

Inflammatory/Dermatologic Causes

Psoriasis

• Produces nail thickening with subungual hyperkeratosis, pitting, onycholysis, and oil drop discoloration 1
• Secondary candidal onychomycosis commonly occurs in psoriatic nails 1

Lichen Planus

• Causes thinning of the nail plate with subungual hyperkeratosis and longitudinal ridging, which can progress to thickening 4

Vascular and Metabolic Causes

Poor Circulation/Vascular Insufficiency

• Distal Candida nail infection occurs almost exclusively in patients with Raynaud phenomenon or other vascular insufficiency, presenting with less subungual hyperkeratosis than dermatophyte infection 1
• Peripheral circulation disorders predispose to onychogryphosis (ram's horn nail deformity with extreme thickening) 5

Diabetes Mellitus

• Increases susceptibility to onychomycosis through impaired blood circulation and peripheral neuropathy 3
• Onychomycosis in diabetics can lead to foot ulcers, osteomyelitis, cellulitis, and gangrene 1

Trauma-Related Causes

Onychogryphosis

• Extreme nail thickening with oyster-like or ram's horn appearance, marked by longitudinal and transverse striations 5
• Associated with repeated minor trauma, pressure from improper footwear, hallux valgus, self-neglect, dementia, and central nervous system diseases 5

Chronic Trauma

• Repeated minor trauma makes nails susceptible to secondary fungal invasion 3

Immunocompromised States

HIV/AIDS

• Proximal subungual onychomycosis spreads rapidly with gross white discoloration 1
• Primary total dystrophic onychomycosis from Candida species occurs in severely immunocompromised patients 1

Chronic Mucocutaneous Candidosis

• Causes gross nail thickening amounting to Candida granuloma, with mucous membrane involvement 1

Diagnostic Algorithm

Step 1: Obtain mycological confirmation before assuming fungal infection

• Direct microscopy with potassium hydroxide (KOH) preparation 2
• Fungal culture on Sabouraud's glucose agar 2
• Calcofluor white staining enhances visualization of fungal elements 2

Step 2: Examine for distinguishing features

• Soft, friable texture suggests fungal infection versus hard, brittle texture of non-infectious causes 4
• Assess for paronychia (nail fold swelling/erythema) suggesting Candida infection with occupational moisture exposure 4
• Look for pitting, oil drop discoloration (psoriasis), or longitudinal ridging (lichen planus, aging) 4

Step 3: Screen for predisposing conditions

• Check for concomitant tinea pedis, tinea capitis in the patient and examine family members 2
• Assess vascular status, diabetes, immunocompromised state, occupational moisture exposure 1, 3
• Evaluate for trauma history, improper footwear, peripheral neuropathy 3, 5

Step 4: Consider systemic workup if non-infectious causes suspected

• Thyroid function tests and complete blood count for brittle nails 4
• HIV testing if proximal subungual onychomycosis is present 1

Common Pitfalls to Avoid

• Never assume fungal infection without laboratory confirmation—the nail surface in non-infectious conditions typically doesn't become soft and friable as in fungal infection 4
• Don't overlook examination of family members for fungal infections, as household transmission is common 2
• Avoid treating empirically before confirming diagnosis, as 50% of dystrophic nails are non-fungal 2, 4
• Don't miss secondary Candida infection in patients with psoriasis or other nail diseases 1