Differential Diagnoses for Proximal Onychomycosis
When you encounter proximal nail involvement, your primary differential should include HIV/AIDS-related immunosuppression, other immunocompromised states, chronic paronychia with secondary nail dystrophy, psoriasis, and lichen planus—but always obtain mycological confirmation before assuming fungal etiology, as 50% of dystrophic nails are non-fungal. 1, 2
Key Clinical Context
Proximal subungual onychomycosis (PSO) is the least common presentation of dermatophyte nail infection in the general population but becomes common in persons with AIDS and has been considered a useful marker of HIV infection. 1 The infection originates either in the proximal nail fold with subsequent penetration into the newly forming nail plate, or beneath the proximal nail plate, with the distal portion remaining normal until late in disease. 1
Primary Differential Diagnoses
1. Immunocompromised States (Most Critical to Exclude)
HIV/AIDS: PSO is common in AIDS patients, where infection often spreads rapidly from the proximal margin and upper surface to produce gross white discoloration without obvious thickening. 1
Other immunodeficiencies: PSO occurs in renal transplant patients on immunosuppressive therapy, patients with systemic lupus erythematosus on systemic steroids, and those with defects in polymorphonuclear chemotaxis. 3
Clinical pearl: The presence of PSO should trigger immediate evaluation for immunodeficiency, including HIV testing, even in apparently healthy individuals. 4
2. Chronic Paronychia with Secondary Nail Dystrophy
Chronic paronychia occurs in patients with wet occupations or children with thumb-sucking habits, where chronic water immersion causes cuticle detachment and loss of water-tight properties. 1
Microorganisms (both yeasts and bacteria) enter the subcuticular space, and infection/inflammation in the nail matrix area leads to proximal nail dystrophy that can mimic PSO. 1, 2
Distinguishing features: Look for swollen, erythematous posterior nail fold, occupational moisture exposure history, and associated paronychia—these point toward Candida rather than dermatophyte infection. 2
3. Candidal Onychomycosis
Candida nail infections characteristically begin proximally with associated paronychia, unlike dermatophyte infections which start distally. 2
Virtually all patients with distal Candida nail infection have Raynaud phenomenon, vascular insufficiency, or are on oral corticosteroids. 1
Primary total dystrophic onychomycosis caused by Candida species typically affects immunocompromised patients. 1
4. Psoriasis
Psoriasis is the most common disease producing nail changes and can present with proximal involvement, nail pitting, onycholysis, and subungual hyperkeratosis. 2, 5
Key distinguishing features: Typically affects multiple nails bilaterally with associated cutaneous psoriatic plaques and nail pitting. 5
Secondary candidal onychomycosis occurs in psoriatic nails, complicating the clinical picture. 1
5. Lichen Planus
Produces thinning of the nail plate with subungual hyperkeratosis and longitudinal ridging that can involve the proximal nail. 2
May require nail biopsy for definitive diagnosis when clinical features are ambiguous. 2
6. Medication-Induced Nail Changes
Taxanes (docetaxel, paclitaxel) cause dose-dependent nail toxicity including onychorrhexis, ridging, thinning, and nail fragility, affecting fingernails more than toenails. 2
Other chemotherapeutic agents (capecitabine, etoposide, cytarabine, cyclophosphamide, doxorubicin) and targeted therapies (mTOR inhibitors, EGFR inhibitors, MEK inhibitors) can cause proximal nail alterations. 2
Diagnostic Algorithm
Step 1: Assess Texture and Associated Features
Soft, friable texture with thickening and discoloration strongly suggests fungal (dermatophyte) infection. 2
Paronychia (nail fold swelling/erythema) with occupational moisture exposure points toward Candida infection. 2
Hard, brittle texture without friability suggests non-infectious causes. 2
Step 2: Obtain Mycological Confirmation (Mandatory)
Never initiate antifungal therapy without laboratory confirmation—50% of dystrophic nails are non-fungal. 2, 6
Collect subungual debris from the most proximal part of the infection using a dental scraper, as dermatophyte infections primarily affect the nail bed. 2
Submit specimens for both KOH preparation with microscopy (first-line screening) and fungal culture on Sabouraud's glucose agar (incubated at 28°C for at least 3 weeks). 2
Step 3: Screen for Immunodeficiency
Obtain HIV testing, complete blood count, thyroid function, and consider screening for diabetes mellitus and peripheral vascular disease. 2, 3, 4
Assess for systemic conditions: renal transplant status, autoimmune disease, immunosuppressive medications. 3
Step 4: Examine for Inflammatory Dermatoses
Look for nail pitting, onycholysis in multiple nails, and cutaneous psoriatic plaques. 2, 5
Assess for associated skin findings of lichen planus or other inflammatory conditions. 2
Consider nail biopsy if inflammatory disease is suspected but clinical features are ambiguous. 2
Critical Pitfalls to Avoid
Do not assume fungal infection based on clinical appearance alone—topical steroids are more effective than antifungals for chronic paronychia, and incorrect diagnosis is the most common cause of treatment failure. 2, 6
Do not overlook occupational counseling—failure to eliminate causative wet-work exposure leads to treatment failure in chronic paronychia. 6
Do not miss the opportunity to diagnose HIV/AIDS—PSO in an apparently immunocompetent patient should trigger comprehensive immunodeficiency workup. 3, 4
Inadequate specimen collection from superficial nail plate rather than proximal subungual debris contributes to false negatives. 2