What is the diagnosis for a patient with non-pruritic (non-itchy) palmar skin desquamation (peeling)?

Diagnosis of Non-Pruritic Palmar Desquamation

The most likely diagnosis for non-pruritic palmar desquamation is recurrent focal palmar peeling (keratolysis exfoliativa), an idiopathic benign condition characterized by chronic peeling of the palms without inflammation or itching. 1

Primary Diagnostic Considerations

Recurrent Focal Palmar Peeling (Most Likely)

• This is a common, largely asymptomatic condition characterized by chronic palmar peeling that can be exacerbated by environmental factors 1
• The absence of pruritus is a key distinguishing feature that points away from inflammatory dermatoses 1
• Diagnosis is clinical, based on history and examination, with negative patch testing to exclude contact dermatitis 1
• Often misdiagnosed as chronic contact dermatitis, leading to unnecessary occupational and legal implications 1

Drug-Induced Palmoplantar Erythrodysesthesia Syndrome (PPES)

If the patient is on chemotherapy or targeted cancer therapy, consider:

• PPES from BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) presents as palmoplantar keratoderma with desquamation, blisters, and callus-like hyperkeratosis at pressure-bearing areas 2
• MEK inhibitors and multikinase VEGFR inhibitors (sorafenib, cabozantinib, sunitinib, regorafenib) cause hand-foot skin reaction (HFSR) with well-defined painful hyperkeratosis 2
• PPES typically develops within days to weeks after therapy initiation, starting with dysesthesia and tingling, progressing to erythema, swelling, and desquamation 2
• The absence of pruritus does not exclude drug-induced causes, as PPES is characterized by pain and burning rather than itching 2

Critical Differential Diagnoses to Exclude

Circumscribed Palmar Hypokeratosis

• Presents as well-circumscribed depressed or eroded areas, typically on thenar or hypothenar eminences 3
• Histologically shows abrupt drop-off in cornified layer with hypokeratosis 3
• May respond to topical calcipotriol treatment 4

Acquired Palmoplantar Keratoderma

• Non-hereditary, non-frictional hyperkeratosis involving ≥50% of palmar/plantar surface 5
• Associated with systemic diseases, malignancy, malnutrition, drugs, or infections 5
• Requires systematic evaluation if no obvious cause identified 5

Scabies Surrepticius (Critical to Exclude)

• Can present as atypical palmar lesions, including erythematous pustules, mimicking other conditions 6
• Particularly important in elderly or immunosuppressed patients 6
• Diagnosis requires high index of suspicion; may need deeper tissue biopsy levels to identify mites 6
• The absence of pruritus does not exclude scabies in atypical presentations 6

Diagnostic Algorithm

Step 1: Medication History

• Review all current medications, especially chemotherapy agents (5-FU, capecitabine, doxorubicin, docetaxel), BRAF inhibitors, or MEK inhibitors 2
• If on these agents, diagnosis is likely drug-induced PPES/HFSR 2

Step 2: Clinical Examination

• Assess distribution: focal vs. diffuse involvement 5
• Look for transgrediens (extension beyond palmar skin) 5
• Examine for signs of systemic disease, malignancy, or infection 5
• Check for occupational exposures (fish, marine animals, poultry for erysipeloid) 7

Step 3: Laboratory Evaluation (if no obvious cause)

• Full blood count and ferritin to exclude iron deficiency or polycythemia vera 2
• Liver and renal function tests 2
• Consider thyroid function if clinical features suggest endocrinopathy 2
• Patch testing to exclude allergic contact dermatitis 1

Step 4: Skin Biopsy (if diagnosis unclear)

• Consider biopsy if persistent unexplained desquamation 2
• Request deeper levels to exclude scabies surrepticius 6
• Histology can distinguish between hypokeratosis, hyperkeratosis, and inflammatory conditions 3, 4

Common Pitfalls to Avoid

• Do not misdiagnose recurrent focal palmar peeling as chronic contact dermatitis without performing patch testing, as this has significant occupational and legal implications 1
• Do not overlook scabies surrepticius in elderly patients with atypical palmar lesions, even without classic burrows or pruritus 6
• Do not assume all palmar desquamation is benign; systematically exclude underlying malignancy, systemic disease, and drug causes 5
• In patients on cancer therapy, recognize that PPES severity correlates with treatment response, so management requires balancing efficacy with quality of life 2