What is the best course of treatment for a 30-year-old male with onycholysis, overgrowth of skin over the nails, and absent nail regrowth on his middle toes, along with a persistent bleeding spot on one toe, who has tested negative for dermatophytes?

Management of Absent Toenails with Persistent Bleeding and Skin Overgrowth

This patient requires urgent biopsy of the persistent bleeding spot to rule out squamous cell carcinoma in situ (SCC in situ) of the nail unit, which can present with ulceration, bleeding, and failure to heal even when dermatophyte testing is negative. 1

Critical Diagnostic Considerations

Malignancy Must Be Excluded First

• The presence of ulceration, bleeding, or failure to heal is indicative of transformation to invasive carcinoma in periungual lesions. 1
• SCC in situ of the nail unit frequently presents with periungual swelling, fissure or ulceration of the lateral nail groove, sometimes with granulation-like tissue beneath and scabbing. 1
• Diagnosis tends to be delayed because of initial misdiagnosis as benign lesions or delay in performing biopsy—maintain a low threshold for biopsy. 1, 2
• Unilateral, persistent lesions that fail to respond to treatment raise significant concern for malignancy. 2

Alternative Diagnoses to Consider

• Chronic paronychia can cause absent cuticle and nail dystrophy, but typically presents bilaterally in patients with chronic moisture exposure or wet occupations. 2
• The unilateral nature and persistent bleeding spot in this case make chronic paronychia less likely. 2
• Traumatic onycholysis with disappearing nail bed (DNB) can occur after trauma and lead to permanent nail loss if the nail bed becomes keratinized. 1, 3

Immediate Management Algorithm

Step 1: Biopsy the Bleeding Lesion

• Perform punch biopsy of the persistent bleeding spot and any surrounding abnormal tissue to obtain full-thickness nail bed specimen. 1
• Because histopathological diagnosis of SCC versus SCC in situ may be difficult with periungual lesions, specimens indicating SCC in situ should be treated as if there is concurrent invasive component. 1
• If biopsy confirms malignancy, management requires local excision, Mohs micrographic surgery, or distal phalanx amputation with multidisciplinary approach. 1

Step 2: Mycological Confirmation Despite Negative Initial Testing

• Repeat mycological testing with proper sampling technique—scrape subungual debris from the most proximal part of any remaining nail or nail bed. 1
• Submit material for both KOH microscopy and fungal culture on Sabouraud's glucose agar incubated for at least 3 weeks. 1, 4
• Nondermatophyte molds should be suspected when dermatophyte testing is negative, only one nail is affected, and previous treatment has failed. 5

Step 3: Address Skin Overgrowth and Promote Healing

• Apply urea 40% cream twice daily to the affected areas to dissolve hyperkeratotic tissue and promote normal healing. 6
• Urea gently dissolves the intracellular matrix, resulting in loosening of the horny layer and shedding of scaly skin, thereby softening hyperkeratotic areas. 6
• This is particularly useful for treatment of hyperkeratotic conditions and damaged, ingrown, and devitalized nails. 6

Step 4: Prevent Permanent Nail Bed Keratinization

• If onycholysis is confirmed without malignancy, it is fundamental to promote nail reattachment as early as possible—otherwise onycholysis may become permanent due to nail bed keratinization. 1
• Chronic onycholysis leads to nail bed keratinization and persistent subungual hyperkeratosis, resulting in disappearing nail bed. 1, 3
• Daily application of topical emollients to periungual folds and nail bed to maintain hydration. 1, 5

Critical Pitfalls to Avoid

• Do not assume this is simple traumatic onycholysis or fungal infection without tissue diagnosis—the persistent bleeding spot is a red flag for malignancy. 1, 2
• Do not delay biopsy to complete empiric antifungal treatment, as this prolongs morbidity and risks missing malignancy. 7
• Do not rely on negative dermatophyte testing alone to exclude fungal infection—sampling technique and laboratory experience significantly affect results. 1
• Avoid topical antibiotics as first-line treatment, as they can cause allergic contact dermatitis and are less effective than addressing the underlying pathology. 2

If Malignancy Is Ruled Out

Conservative Management for Traumatic Onycholysis with DNB

• Combined treatment with urea-based keratolytic cream, nail bed massages, and protective taping can successfully treat long-standing onycholysis with disappearing nail bed. 3
• The key is using several methods with different effects on the nail apparatus, though treatment duration is prolonged due to slow nail growth. 3
• Gentle filing with an emery board after softening in warm water to reduce tissue buildup. 5

If Fungal Infection Is Confirmed

• Terbinafine 250 mg daily for 12 weeks is the preferred systemic antifungal for toenail onychomycosis. 1, 7, 5
• Mechanical debridement during any surgical intervention can remove fungal-laden tissue. 7
• Continue antifungal therapy for the full course even after healing to prevent recurrence. 7