What could cause dark discoloration under fingernails (nail bed) and around eyes in a non-hypoxemic patient?

Dark Discoloration Under Fingernails and Around Eyes in Non-Hypoxemic Patient

The most likely causes are drug-induced pigmentation (particularly from chemotherapy agents like taxanes or targeted therapies), systemic disease with melanin deposition, or Addison's disease, and you must immediately evaluate for underlying malignancy, endocrine disorders, or medication exposure before considering infectious or traumatic etiologies. 1, 2

Immediate Diagnostic Priorities

Drug-Induced Causes (Most Critical to Identify)

• Chemotherapy-related melanonychia is extremely common with taxanes (docetaxel, paclitaxel), causing dark brown-to-black nail discoloration in 43.7% and 34.9% of patients respectively, and this can affect multiple nails simultaneously 1

• Targeted therapies including EGFR inhibitors, mTOR inhibitors, and MEK inhibitors also cause nail pigmentation changes, though typically less severe than taxanes 1

• The discoloration appears weeks after treatment initiation due to slow nail growth rates, and fingernails are more commonly affected than toenails 1

• Critical pitfall: Drug-induced changes can mimic melanoma, so obtain detailed medication history including chemotherapy, antimalarials, tetracyclines, and zidovudine 1, 2

Systemic Disease Manifestations

• Addison's disease causes diffuse hyperpigmentation including periorbital darkening and longitudinal melanonychia due to elevated ACTH stimulating melanocytes 2

• Chronic renal failure produces nail discoloration (half-and-half nails) and can cause periorbital darkening from uremic pigmentation 2

• HIV infection presents with longitudinal melanonychia in multiple nails, and this finding warrants HIV testing if risk factors present 2

• Hemochromatosis and ochronosis cause gray-brown pigmentation of skin and nails from dermal chromogen deposition 3

Differential Diagnosis by Pattern

Multiple Nail Involvement with Periorbital Changes

• Systemic autoimmune CTD (systemic sclerosis, SLE, dermatomyositis) shows nail fold erythema (48.1%) and telangiectasia (44.4%), though these typically don't cause dark discoloration 2

• Lichen planus pigmentosus and erythema dyschromicum perstans cause gray-brown skin discoloration but rarely affect periorbital areas prominently 3

Infectious Causes (Lower Priority in This Presentation)

• Bacterial infection from Pseudomonas aeruginosa causes green-to-black discoloration but typically affects lateral nail edges, not periorbital areas, and requires keeping area dry with topical povidone iodine 2% twice daily 1, 4

• Fungal onychomycosis causes yellow-brown discoloration with nail thickening and friability, but never diagnose based on appearance alone—50% of dystrophic nails are non-fungal and require KOH preparation and culture confirmation 1, 4

• Fungal infection does not explain periorbital pigmentation, making this diagnosis unlikely in your patient 1

Essential Diagnostic Workup

Immediate Laboratory Testing

• Complete medication history including all prescription drugs, supplements, and recent chemotherapy 1

• Morning cortisol and ACTH levels to evaluate for Addison's disease 2

• HIV testing if risk factors present 2

• Renal function tests (BUN, creatinine) and liver function tests 2

• Iron studies and ferritin if anemia suspected 2

Nail-Specific Evaluation

• Dermoscopy of affected nails to assess pigmentation pattern—longitudinal melanonychia wider than 5mm or with irregular borders suggests melanoma and requires urgent dermatology referral 5

• Look for Hutchinson's sign (pigmentation extending to proximal or lateral nail fold), which strongly suggests subungual melanoma 5

• Examine all 20 nail units systematically, as pattern of involvement guides diagnosis 6

• If fungal infection suspected despite systemic findings, obtain nail clippings from discolored areas for KOH preparation and fungal culture on Sabouraud's agar—calcofluor white staining enhances visualization 1, 4

Critical Red Flags Requiring Urgent Referral

• Longitudinal melanonychia wider than 5mm, especially with irregular borders or Hutchinson's sign—this mandates immediate dermatology referral for biopsy to rule out subungual melanoma 5

• Progressive nail dystrophy with bleeding mass suggests malignancy 5

• New-onset pigmentation in single digit of adult patient warrants melanoma evaluation 5

Management Algorithm

1. First: Obtain complete drug history and consider drug-induced cause if patient on chemotherapy or other pigment-inducing medications 1

2. Second: Evaluate for systemic disease with morning cortisol/ACTH, renal function, and HIV testing based on clinical context 2

3. Third: Perform dermoscopy and assess for melanoma features—refer urgently if concerning findings present 5

4. Fourth: Only after excluding above, consider infectious causes with appropriate laboratory confirmation 1, 4

Common Diagnostic Pitfalls

• Never assume fungal infection without laboratory confirmation—appearance alone is unreliable and 50% of dystrophic nails are non-fungal 4, 7

• Do not overlook medication history, as drug-induced pigmentation is reversible if identified early 1

• Failure to recognize melanoma warning signs (Hutchinson's sign, irregular borders, width >5mm) leads to delayed diagnosis and worse outcomes 5

• Periorbital pigmentation combined with nail changes points to systemic disease, not isolated nail pathology 3, 2