What is the most appropriate next step for an immunocompromised patient with multiple myeloma, presenting with burning and tingling pain on the forehead, blurred vision, and a pustular, vesicular rash, suggestive of herpes zoster?

Intravenous Acyclovir is the Most Appropriate Next Step

This immunocompromised patient with multiple myeloma presenting with herpes zoster ophthalmicus (HZO) requires immediate intravenous acyclovir, not oral therapy, due to the high risk of dissemination and vision-threatening complications.

Clinical Reasoning

Why Intravenous Acyclovir is Mandatory

For disseminated, multi-dermatomal, ophthalmic, visceral, or complicated herpes zoster in immunocompromised patients, intravenous acyclovir 5-10 mg/kg every 8 hours is the standard of care 1, 2. This patient has multiple high-risk features:

• Active chemotherapy with daratumumab, bortezomib, melphalan, and prednisone creates profound immunosuppression 3
• Ophthalmic involvement (right eyelid erythema, crusting, discharge) indicates herpes zoster ophthalmicus, which threatens vision 1, 2
• Vesicular rash extending from forehead to nose suggests involvement of the nasociliary branch of the ophthalmic division of the trigeminal nerve (Hutchinson's sign) 2
• Blurred vision indicates potential intraocular involvement requiring urgent intervention 2

Dosing and Duration

• Intravenous acyclovir 10 mg/kg every 8 hours (some sources suggest 5-10 mg/kg range, but 10 mg/kg is preferred for VZV in severely immunocompromised hosts) 3, 1, 4
• Continue treatment for a minimum of 7-10 days and until clinical resolution is attained 1, 2
• Switch to oral therapy only after clinical improvement occurs, then complete the full treatment course 1
• Monitor renal function closely during IV acyclovir therapy with dose adjustments as needed 2, 4

Why Oral Valacyclovir is Inadequate

While oral valacyclovir 1 gram three times daily for 7 days is appropriate for uncomplicated herpes zoster in immunocompetent patients 1, this patient has:

• Severe immunocompromise from multiple myeloma and active chemotherapy 3, 5
• Ophthalmic involvement requiring more aggressive therapy 1, 2
• Risk of disseminated VZV infection given the immunosuppressive regimen 5

All immunocompromised patients with herpes zoster require antiviral treatment regardless of timing, and ophthalmic involvement mandates IV therapy 1.

Why Not Antibiotics

Intravenous vancomycin and cefepime would be appropriate for bacterial superinfection, but the clinical presentation is classic for herpes zoster ophthalmicus:

• Vesicular rash in dermatomal distribution 2
• Burning and tingling pain (prodromal symptoms) 2
• Unilateral presentation 2

If bacterial superinfection develops, antibiotics can be added, but the primary pathogen is VZV 1.

Why Not Ophthalmic Corticosteroids Initially

Ophthalmic corticosteroids are contraindicated as initial therapy without concurrent antiviral coverage, as they can:

• Facilitate viral replication 3
• Worsen the infection in the absence of adequate antiviral therapy 3

Corticosteroids may have a role as adjunctive therapy after antiviral treatment is established, particularly if there is a vasculitic component 3, but they should never be used alone.

Management of Immunosuppression

Temporarily discontinue or reduce immunosuppressive therapy (daratumumab, bortezomib, melphalan, prednisone) in severe cases of disseminated VZV infection 1, 2. Immunosuppression may be restarted after the patient has commenced anti-VZV therapy and skin vesicles have resolved 1.

Critical Monitoring

• Assess for dissemination (multi-dermatomal involvement, visceral complications) 1, 2
• Ophthalmology consultation is essential for herpes zoster ophthalmicus to evaluate for keratitis, uveitis, or other intraocular complications 2
• Monitor renal function closely during IV acyclovir therapy 2, 4
• Continue treatment until all lesions have completely scabbed, not just for an arbitrary 7-day period 1, 2

Common Pitfalls to Avoid

• Do not use oral antivirals for ophthalmic herpes zoster in immunocompromised patients 1, 2
• Do not delay treatment waiting for laboratory confirmation; clinical diagnosis is sufficient to initiate therapy 2
• Do not use topical antiviral therapy, as it is substantially less effective than systemic therapy 2
• Do not start corticosteroids without adequate antiviral coverage 3

Long-Term Prophylaxis

After resolution of acute infection, acyclovir or valacyclovir prophylaxis is recommended for patients receiving proteasome inhibitor-based therapies (bortezomib) 3. Daily acyclovir 400 mg appears effective at preventing herpes zoster in myeloma patients receiving bortezomib 6.