What is the diagnosis and management for a patient with sudden onset non-pruritic (non-itchy) palmar skin desquamation (shedding of skin)?

Sudden Onset Non-Pruritic Palmar Desquamation: Diagnosis and Management

The most critical first step is to determine if this represents a life-threatening drug reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) or chemotherapy-induced hand-foot syndrome, which requires immediate evaluation of medication history, presence of systemic symptoms, and extent of skin involvement. 1

Immediate Assessment Priority

Rule Out Life-Threatening Causes First

• Evaluate for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) by assessing for prodromal fever, malaise, upper respiratory symptoms, multisite mucositis, and cutaneous pain—which is a prominent early feature that should alert you to incipient epidermal necrolysis 1
• Check for the Nikolsky sign (gentle lateral pressure causes epidermis to slide over dermis), though this is not specific for SJS/TEN, it indicates epidermal necrolysis 1
• SJS/TEN characteristically presents with atypical targets and/or purpuric macules that progress to blistering and desquamation, with prominent involvement of palms and soles 1
• The earliest lesions are dark red centers surrounded by pink rings, which can become confluent over days 1

Distinguish Drug-Induced Causes

Chemotherapy-induced hand-foot syndrome (palmar-plantar erythrodysesthesia) must be considered if the patient is on:

• Capecitabine, 5-fluorouracil (6-34%), doxorubicin (22-29%), or PEGylated liposomal doxorubicin (40-50%), which cause hand-foot syndrome in 6-60% of patients 2, 3
• BRAF/MEK inhibitors (vemurafenib, dabrafenib) or multikinase VEGFR inhibitors (sorafenib 10-62%, cabozantinib 40-60%, sunitinib 10-50%, regorafenib 47%) 2
• The progression differs from SJS/TEN: it starts with dysesthesia and tingling, then burning pain, swelling, erythema, and eventually desquamation, developing within days to weeks after treatment initiation 2

Methotrexate epidermal necrosis (MEN) presents similarly to SJS/TEN but occurs in patients with increased risk factors including advanced age, chronic kidney disease, and increased methotrexate dosing 4

• The key distinguishing feature is bone marrow suppression with leukopenia, which makes MEN more likely than SJS/TEN (since SJS/TEN is T-cell mediated) 4

Diagnostic Algorithm

Step 1: Medication History

• Document all current medications, particularly recent antibiotic use (SJS/TEN trigger), chemotherapy agents, methotrexate, amiodarone, gemfibrozil, cholestyramine, topiramate, or albuterol 5, 6
• Determine timing of symptom onset relative to drug initiation 2

Step 2: Assess Systemic Involvement

• Fever, malaise, and multisite mucositis (eyes, mouth, nose, genitalia) indicate SJS/TEN requiring immediate hospitalization 1
• Absence of systemic symptoms and presence of isolated palmar involvement suggests chemotherapy-induced hand-foot syndrome or other localized causes 2

Step 3: Characterize the Desquamation Pattern

• Superficial exfoliation with pitting edema may indicate erythrodermic psoriasis 3
• Well-defined painful hyperkeratosis followed by desquamation suggests hand-foot skin reaction from BRAF inhibitors or multikinase inhibitors 3
• Sterile pustules with desquamation indicate palmoplantar pustulosis 7

Step 4: Obtain Tissue Diagnosis When Indicated

• In immunocompromised patients or when diagnosis is unclear, aggressive biopsy of skin lesions should be performed early for histological and microbiological evaluation 1
• Submit tissue for cytological/histological assessment, microbial staining, and cultures 1

Management Based on Diagnosis

For Suspected SJS/TEN

• Immediately discontinue all potentially causative medications 1
• Transfer to burn unit or intensive care setting for supportive care 1
• Consider early dermatology consultation 1

For Chemotherapy-Induced Hand-Foot Syndrome

• Grade 1-2: Continue drug and apply topical low/moderate potency corticosteroid 3
• Grade ≥3: Interrupt treatment until symptoms resolve to Grade 0-1, use oral doxycycline 100mg twice daily for 6 weeks, topical steroids, and consider systemic corticosteroids 3
• Implement behavioral modifications including avoiding friction, heat exposure, and tight-fitting footwear 2

For Methotrexate Epidermal Necrosis

• Discontinue methotrexate immediately 4
• Check complete blood count for bone marrow suppression 4
• Provide supportive care similar to SJS/TEN management 4

For Other Acquired Causes

• If no drug cause is identified, evaluate for underlying systemic disease including liver cirrhosis (23% have palmar erythema), rheumatoid arthritis (>60%), thyrotoxicosis (18%), diabetes mellitus (4.1%), and malignancy (15% of brain tumors) 6
• Obtain liver function tests, rheumatoid factor, thyroid function tests, and fasting glucose as initial screening 8, 6

Critical Pitfalls to Avoid

• Do not wait for the complete clinical picture before acting on suspected SJS/TEN—cutaneous pain with new palmar desquamation and any systemic symptoms warrants immediate drug discontinuation and hospitalization 1
• Do not assume non-pruritic desquamation is benign—both SJS/TEN and chemotherapy-induced hand-foot syndrome are typically non-pruritic but require urgent intervention 1, 2
• In immunocompromised patients, do not delay biopsy—skin lesions that appear innocuous may represent systemic or life-threatening infection 1
• Leukopenia in a patient with desquamating skin lesions increases likelihood of methotrexate toxicity over SJS/TEN 4