What causes a xerotic, hyperkeratotic, desquamating rash between fingers?

Differential Diagnosis of Xerotic, Hyperkeratotic, Desquamating Interdigital Rash

The most common causes of a xerotic, hyperkeratotic, desquamating rash between the fingers include hyperkeratotic hand eczema, interdigital dermatophytosis (tinea manuum) with secondary yeast involvement, hand-foot skin reactions from anticancer agents (if applicable), and frictional hyperkeratotic dermatitis.

Primary Diagnostic Considerations

Hyperkeratotic Hand Eczema (HHE)

• HHE typically presents with hyperkeratosis, fissuring, scaling, and painful fissures on the palms and volar aspects of fingers, though the pathophysiology remains largely unknown 1.
• The condition shows upregulation of K6, K16, and K17 with reduction of K9 and K14, distinguishing it from typical atopic eczema patterns 1.
• Unlike atopic dermatitis, HHE demonstrates evident filaggrin and involucrin expression, suggesting a different underlying mechanism 1.

Interdigital Dermatophytosis with Yeast Involvement

• When hyperkeratosis occurs between digits with yeast involvement, the American College of Dermatology recommends combining topical keratolytics (urea 10-40% or salicylic acid 5-10%) with topical antifungal therapy targeting the specific organism 2.
• Mechanical debridement should be performed first-line for non-fragile hyperkeratotic lesions, with professional blade or scalpel debridement being most effective 2.
• Regular reassessment after 2 weeks of treatment, including mycological testing, is necessary to confirm yeast eradication 2.

Drug-Induced Hand-Foot Skin Reactions (If Oncology Patient)

• Palmar-plantar erythrodysesthesia syndrome (PPES) from chemotherapy agents may affect intertriginous areas including between fingers, presenting with hyperkeratosis, desquamation, and painful fissures 3.
• PPES is associated with 5-fluorouracil (6-34%), capecitabine (50-60%), doxorubicin (22-29%), and PEGylated liposomal doxorubicin (40-50%) 3.
• Hand-foot skin reaction (HFSR) from BRAF inhibitors or MEK inhibitors presents with well-defined painful hyperkeratosis, distinct from classic PPES 3.

Frictional Hyperkeratotic Hand Dermatitis

• This relates to repeated frictional trauma and is often occupationally related 4.
• The condition is typically recalcitrant to standard topical therapies 4.

Clinical Evaluation Strategy

Key Historical Features to Elicit

• Medication history: Specifically inquire about chemotherapy agents (5-FU, capecitabine, doxorubicin, docetaxel, cytarabine), BRAF inhibitors (vemurafenib, dabrafenib, encorafenib), or MEK inhibitors (sorafenib, cabozantinib, sunitinib, regorafenib) 3.
• Occupational exposures: Repetitive friction, mechanical stress, chemical irritants, or moisture exposure 3, 2.
• Timing: PPES develops within days to weeks (up to 6 months) after chemotherapy initiation 3.
• Associated symptoms: Dysesthesia, tingling, burning pain preceding visible changes suggests PPES 3.

Physical Examination Findings

• Distribution pattern: Palmar versus dorsal involvement, pressure-bearing areas, or intertriginous spaces 3.
• Lesion characteristics: Painful fissures, vesicles, blisters, erosions, or callus-like hyperkeratosis 3, 5.
• Signs of infection: Crusting, weeping, or maceration suggesting secondary bacterial or fungal involvement 2, 6.

Diagnostic Testing

• Mycological testing (KOH preparation and fungal culture) to identify dermatophyte or yeast organisms 2.
• Skin biopsy if diagnosis uncertain, though histopathology is often nonspecific showing toxic dermatitis patterns 3.

Treatment Algorithm

First-Line Management for Non-Drug-Induced Cases

Step 1: Emollient Therapy and Keratolytics

• Apply urea 10% cream three times daily to maintain skin hydration and address hyperkeratosis 3, 2, 7.
• For more severe hyperkeratosis, escalate to urea 10-40% or salicylic acid 5-10% 2, 6.
• Urea acts as a hygroscopic component that restores skin hydration and thins hyperkeratosis 8.

Step 2: Anti-inflammatory Therapy

• Apply high-potency topical corticosteroid twice daily for 2-4 weeks if significant inflammation is present 2, 6.
• Reassess after 2 weeks; if no improvement, consider alternative diagnoses or escalate therapy 6.

Step 3: Address Fungal/Yeast Involvement

• If mycological testing confirms yeast or dermatophyte infection, add appropriate topical antifungal therapy 2.
• For infected areas with crusting or weeping, consider antiseptic solutions (silver sulfadiazine 1% or polyhexanide 0.02-0.04%) 6.

Step 4: Mechanical Debridement

• Professional blade or scalpel debridement by podiatrist for non-fragile hyperkeratotic lesions 2.
• After debridement, apply emollients and non-adherent dressings 2.

Management for Drug-Induced HFSR/PPES

Prevention (Grade 0)

• Avoid mechanical stress (long walks, heavy carrying without cushioned shoes/gloves) and chemical irritants 3.
• Apply urea 10% cream three times daily prophylactically 3, 7.
• Treat pre-existing hyperkeratosis before initiating anticancer therapy 3.

Grade 1-2 Treatment

• Continue anticancer drug at current dose 3.
• Apply topical high-potency steroid twice daily 3.
• Add lidocaine 5% patches or cream for pain control 3.
• Reassess after 2 weeks 3.

Grade ≥3 or Intolerable Grade 2

• Interrupt anticancer treatment until severity decreases to grade 0-1 3.
• Continue topical high-potency steroid twice daily 3.
• Add topical keratolytics (salicylic acid 5-10% or urea 10-40%) 3.
• Consider antiseptic solutions for infected areas 3.
• Dose interruption or discontinuation may be necessary if no improvement after 2 weeks 3.

Refractory Cases

For HHE Not Responding to Standard Therapy

• Oral acitretin 30 mg daily demonstrates 51% reduction in symptoms after 4 weeks for hyperkeratotic palmar dermatitis with painful fissures 5.
• Grenz ray therapy is a safe and effective option for frictional hyperkeratotic hand dermatitis resistant to topical modalities 4.

Critical Pitfalls to Avoid

• Do not perform aggressive blade debridement if epidermolytic hyperkeratosis is suspected, as this can cause severe complications 2.
• Avoid chemical plasters for corn removal, especially in diabetic patients 2.
• Do not use alcohol-containing lotions or gels for xerotic skin; oil-in-water creams containing urea are preferable 7.
• Avoid prolonged high-potency corticosteroid use on thin skin areas to prevent atrophy 6.
• Do not assume all hyperkeratotic hand conditions are eczema; HHE may represent a distinct entity requiring different management 1.

Adjunctive Measures

• Pressure redistribution and cushioning, footwear modifications, and moisture control between digits prevent recurrence 2.
• For pruritus, consider oral antihistamines, particularly sedating ones at night 6.
• Optimize barrier protection with gloves during occupational exposures 3, 2.