What is the recommended treatment for herpes zoster in a patient with multiple sclerosis?

Treatment of Shingles in a Patient with Multiple Sclerosis

For a patient with MS who develops shingles, initiate oral valacyclovir 1 gram three times daily for 7-10 days immediately, continuing until all lesions have completely scabbed, with careful consideration of their immunosuppression status from MS disease-modifying therapies. 1, 2, 3

Initial Assessment and Risk Stratification

Determine the severity and extent of herpes zoster infection:

• Uncomplicated shingles (single dermatome, no dissemination): Oral antiviral therapy is appropriate 1, 2
• Complicated/disseminated disease (>3 dermatomes, visceral involvement, CNS complications, or facial/ophthalmic involvement): Requires intravenous acyclovir 10 mg/kg every 8 hours 1, 2, 4
• Assess immunosuppression level: MS patients on disease-modifying therapies—particularly alemtuzumab, ocrelizumab, fingolimod, cladribine, natalizumab, and rituximab—have significantly elevated herpes zoster risk and may require more aggressive treatment 5

First-Line Antiviral Treatment for Uncomplicated Shingles

Valacyclovir is the preferred oral agent due to superior bioavailability and convenient dosing:

• Valacyclovir 1 gram orally three times daily for 7-10 days 1, 2, 3
• Alternative: Acyclovir 800 mg orally five times daily for 7-10 days if valacyclovir is unavailable 1, 2, 3
• Alternative: Famciclovir 500 mg orally three times daily for 7 days 1
• Critical timing: Initiate treatment within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating healing, and preventing postherpetic neuralgia 1, 2
• Treatment endpoint: Continue therapy until ALL lesions have completely scabbed, not just for an arbitrary 7-day period 1, 2

Management of MS Disease-Modifying Therapies During Active Shingles

Temporary modification of immunosuppressive therapy is essential in severe cases:

• For uncomplicated shingles: Continue MS DMTs while on antiviral therapy, with close monitoring 1
• For disseminated or invasive herpes zoster: Temporarily reduce or discontinue immunosuppressive medications until all vesicular lesions have crusted, fever has resolved, and clinical improvement is evident on antiviral therapy 1, 4
• Do NOT initiate or continue immunomodulatory therapy during active chickenpox or herpes zoster infection 1
• Restart immunosuppression only after: Patient has commenced anti-VZV therapy AND skin vesicles have completely resolved 2

Special Considerations for Specific MS DMTs:

• B-cell depleting therapies (ocrelizumab, rituximab, ofatumumab): These carry the highest risk for severe herpes zoster and may require longer treatment duration or IV therapy even for seemingly uncomplicated cases 6, 5
• Alemtuzumab: Has the greatest reporting risk for herpes zoster (ROR 11.1) and warrants aggressive antiviral treatment 5
• Fingolimod, cladribine, natalizumab: Also associated with significantly elevated herpes zoster risk 5

Escalation to Intravenous Therapy

Switch to IV acyclovir 10 mg/kg every 8 hours for:

• Disseminated herpes zoster (>3 dermatomes, visceral involvement) 1, 2
• Facial/ophthalmic involvement with risk of cranial nerve complications 1
• CNS complications (encephalitis, meningitis, transverse myelitis) 1, 4
• Severely immunocompromised patients on active MS DMTs 1, 2
• Failure to respond to oral therapy within 7-10 days 1
• Continue IV therapy for minimum 7-10 days and until clinical resolution, then switch to oral therapy to complete treatment course 1, 2

Critical Monitoring During IV Acyclovir:

• Baseline and weekly renal function monitoring with dose adjustments for renal impairment 1
• Maintain adequate hydration to prevent acyclovir-induced nephrotoxicity 7
• Monitor for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients 1
• Assess for visceral dissemination: respiratory symptoms (pneumonia), elevated liver enzymes (hepatitis), neurological changes (CNS involvement) 1

Management of Severe Neurological Complications

For post-zoster transverse myelitis or other CNS complications:

• Immediate high-dose IV acyclovir PLUS high-dose corticosteroids (methylprednisolone 1 gram IV daily for 3-5 days for severe cases) 4
• Permanently discontinue the causative MS DMT 4
• Consider IVIG 2 g/kg over 5 days for Grade 3-4 severity 4
• Continue antiviral treatment until complete resolution of neurological symptoms 4

Renal Dose Adjustments

For patients with renal impairment, adjust valacyclovir dosing:

• CrCl 30-49 mL/min: 1 gram every 12 hours 3
• CrCl 10-29 mL/min: 1 gram every 24 hours 3
• CrCl <10 mL/min: 500 mg every 24 hours 3

Acyclovir-Resistant Herpes Zoster

If lesions fail to improve after 7-10 days of appropriate antiviral therapy:

• Suspect acyclovir resistance and obtain viral culture with susceptibility testing 1
• Switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution 1, 2
• All acyclovir-resistant strains are also resistant to valacyclovir and most to famciclovir 1
• Foscarnet requires close monitoring of renal function and electrolytes (hypocalcemia, hypophosphatemia, hypomagnesemia, hypokalemia) 2

Infection Control Measures

Prevent transmission to susceptible individuals:

• Avoid contact with susceptible individuals (those without chickenpox history or vaccination) until all lesions have crusted 1
• Cover lesions with clothing or dressings to minimize transmission risk 1
• For disseminated zoster: Implement both airborne and contact precautions in healthcare settings 1
• Physical separation of at least 6 feet from other patients in healthcare settings 1

Post-Recovery Vaccination

After complete recovery from acute herpes zoster:

• Strongly recommend recombinant zoster vaccine (Shingrix) for all MS patients aged ≥50 years, regardless of prior herpes zoster episodes 1, 2
• Shingrix provides >90% efficacy in preventing future recurrences 1
• Ideally administer BEFORE initiating immunosuppressive MS DMTs, but can be given after recovery from acute infection 6, 1
• Live-attenuated vaccine (Zostavax) is CONTRAINDICATED in immunocompromised MS patients 1
• Vaccination should occur at least 4 weeks before the next course of B-cell depleting therapy if already on such treatment 6

Common Pitfalls to Avoid

• Do NOT use topical acyclovir: It is substantially less effective than systemic therapy and is not recommended 1, 2
• Do NOT stop treatment at exactly 7 days if lesions are still forming or have not completely scabbed 1, 2
• Do NOT use corticosteroids alone during active shingles without adequate antiviral coverage, as this can worsen infection and increase dissemination risk 1
• Do NOT delay treatment waiting for laboratory confirmation in immunocompromised patients with typical presentation 1
• Do NOT use inadequate dosing: Acyclovir 400 mg TDS is only appropriate for genital herpes, NOT for shingles (requires 800 mg five times daily) 1