What could be the reason for a patient with multiple myeloma on a VCD (Vincristine, Cyclophosphamide, and Bortezomib) regimen to experience itching and a rash?

Rash and Itching in Multiple Myeloma Patient on VCD Regimen

The most likely cause of itching and rash in a patient on VCD (Vincristine, Cyclophosphamide, Bortezomib, Dexamethasone) regimen is bortezomib-induced cutaneous hypersensitivity, which occurs in up to 58.8% of patients and requires immediate evaluation to determine if dose modification or drug discontinuation is necessary. 1, 2

Primary Culprit: Bortezomib

Bortezomib is the most common cause of cutaneous reactions in the VCD regimen, presenting with variable manifestations:

• Rash patterns include erythematous eruptions, pruriginous rash, reticular eruptions at injection sites, and purpuric rash 1, 3, 2
• Distribution typically starts in palms and soles, then spreads to the whole body in severe cases 1
• Timing varies, with reactions occurring at any point during treatment, though onset can be delayed 4
• Severity ranges from mild pruritus to severe drug-induced hypersensitivity syndrome (DRESS) requiring drug discontinuation 4, 2

Clinical Presentation Patterns

Common Bortezomib-Related Skin Reactions

• Simple rash and pruritus: Most frequent presentation, occurring in approximately 58.8% of patients receiving bortezomib 2
• Reticular eruption: Unique pattern appearing at subcutaneous injection sites, confirmed by biopsy showing superficial perivascular dermatitis with lymphocytes and rare eosinophils 3
• Drug-induced hypersensitivity syndrome: Rare but severe delayed reaction requiring permanent drug discontinuation 4

Cyclophosphamide Contribution

While less common than bortezomib reactions, cyclophosphamide can cause:

• Skin rash occurring occasionally during therapy 5
• Pigmentation changes of skin and nails 5
• Allergic reactions as part of hypersensitivity spectrum 5

Immediate Management Algorithm

Step 1: Assess Severity

• Mild (localized, non-progressive): Continue therapy with symptomatic treatment 3, 2
• Moderate (widespread but no systemic symptoms): Consider dose reduction or temporary hold 2
• Severe (systemic symptoms, mucosal involvement, fever): Discontinue bortezomib immediately and evaluate for DRESS syndrome 4, 2

Step 2: Pharmacologic Treatment

For mild to moderate reactions:

• Topical corticosteroids: Betamethasone dipropionate 0.05% cream is highly effective for bortezomib-induced reticular eruptions 3
• Systemic corticosteroids: Mainstay of treatment for more severe allergic reactions 1
• Antihistamines: For symptomatic pruritus relief 2

Step 3: Bortezomib Dose Modification

If continuing bortezomib is essential:

• Switch to subcutaneous administration if currently using IV route, as this reduces overall toxicity including skin reactions 6
• Reduce dose to 1.0 mg/m² for Grade 1-2 reactions 6
• Consider weekly dosing instead of twice-weekly to reduce toxicity burden 6

Critical Pitfalls to Avoid

• Do not automatically discontinue bortezomib for mild reticular eruptions at injection sites, as these can be managed with potent topical corticosteroids while maintaining optimal myeloma treatment 3
• Do not delay dermatology consultation for accurate diagnosis, as cutaneous reactions are often under-reported by hematologists/oncologists and may be more frequent than documented 2
• Do not rechallenge with bortezomib if drug-induced hypersensitivity syndrome is confirmed, as recurrence is likely and potentially more severe 4
• Do not overlook infection risk in patients with severe rash, as myelosuppression from VCD increases susceptibility to sepsis 1

Differential Considerations

Other Potential Causes in VCD Regimen

• Dexamethasone: Can cause acneiform eruptions and skin fragility, though less commonly associated with pruritic rash 7
• Infection-related rash: Given immunosuppression from cyclophosphamide and bortezomib, consider viral reactivation (herpes zoster) or fungal infections 7, 5
• Herpes virus reactivation: Patients on proteasome inhibitors should be taking acyclovir/valacyclovir prophylaxis; absence of prophylaxis increases risk 7

Monitoring and Follow-Up

• Dermatology evaluation should be performed for all patients with cutaneous reactions to accurately characterize and manage the eruption 2
• Skin biopsy may be necessary to confirm diagnosis and rule out other etiologies, particularly for atypical presentations 1, 3
• Monitor for systemic symptoms including fever, eosinophilia, and organ involvement that would indicate DRESS syndrome 4
• Document timing and pattern of rash relative to drug administration to establish causality 3, 2

Long-Term Management Strategy

If bortezomib must be discontinued:

• Alternative proteasome inhibitors: Consider carfilzomib or ixazomib, which have lower rates of cutaneous toxicity 7
• Carfilzomib has rare reports of rash but significantly lower incidence than bortezomib 7
• Ixazomib is associated with rash in some patients but may be better tolerated than bortezomib 7

If continuing bortezomib with modifications:

• Maintain close monitoring with dermatology involvement throughout treatment course 2
• Optimize supportive care with prophylactic topical corticosteroids at injection sites 3
• Ensure viral prophylaxis with acyclovir or valacyclovir to prevent additional cutaneous complications 7