Herpes Zoster (aka Shingles) Protocol

Shingles can be a devastating disease for patients. I vividly remember a friend who developed shingles across her beautiful, model-like face after turning 40. Her husband was equally devastated. She was admitted to the hospital likely because her husband was a well-known figure in the area. I visited her to show my support, knowing how challenging it could be, especially for someone to break out with the Zoster rash at a young age. At the time, she was receiving IV antivirals. She had not had the shingles vaccine, Shingrix— the old discontinued Zostavax (as Shingrix is better at preventing Zoster, but has its own risk profile as noted below**). 

As I walked in, her husband was reading a mutual friend, Guangcheng Chen’s, remarkable book, “The Barefoot Lawyer,” to her. It was hard not to question her doctors at the local hospital where she was being treated. However, I was truly shocked that they weren’t providing her with more significant protection against postherpetic neuralgia (PHN).

A couple of years later, another dear friend, a high-powered venture capitalist, also contracted herpes zoster on his face. He was far away in a different state, so I didn’t learn about it until his wife mentioned it to me a few months after the episode. She described him as being extremely depressed for months both during and after the outbreak. She said that the most distressing aspect of the experience was the postherpetic neuralgia pain. When I asked if they had treated that to prevent it, she confirmed that they hadn’t. I was not surprised this time as many doctors, especially in the emergency room, forget to talk about this devastating part of herpes zoster.

Both cases were difficult to comprehend. In the first case mentioned earlier, I did tell my friend to ask about Post heretic neuralgia. She did and they eventually started amitriptyline.

Lastly, a friend a couple of years ago shared that the first symptom she experienced before her mild zoster outbreak on her face was intense ear pain. Fortunately, her doctor was aware of the connection between severe ear pain and Ramsay Hunt syndrome, as noted below, and he immediately started her on 1 gram of Valtrex. This prevented a severe episode for her.

Dr. Cremers Herpes Zoster Protocol:

Medical disclaimer:

Always check with your PCP before following any of my advice. Some of these medications have to be decreased, depending on your kidney or liver function. 

Latest Recommended Treatment for Shingles (Herpes Zoster) - Step-by-Step

Step 1: Initiate Antiviral Therapy

• When: Start within 72 hours of rash onset to maximize efficacy and in some patients with intense ear pain: tell patient to look out for the beginning of any rash on the scalp or ear area. Treatment may still benefit beyond this window in severe cases or immunocompromised patients.

Herpes Zoster (Shingles)

Cause: Varicella-zoster virus (VZV), a highly contagious DNA virus.
Note: Initiate antiviral therapy within 72 hours of rash onset to optimize healing, reduce pain, and lower the risk of postherpetic neuralgia (PHN). Refer to specialists (e.g., ophthalmologist, ENT) for complications.

Step 1: Initiate Antiviral Therapy

• When: Start within 72 hours of rash onset to maximize efficacy and in some patients with intense ear pain, tell them to look out for the beginning of any rash on the scalp or ear area. Treatment may still benefit beyond this window in severe cases or immunocompromised patients.
• Medications:
• Valacyclovir: 1,000 mg three times daily (TID) for 7 days (preferred due to better bioavailability and dosing convenience).
• Famciclovir: 500 mg TID for 7 days.
• Acyclovir: 800 mg five times daily for 7–10 days (less preferred due to frequent dosing).
• Purpose: Speeds healing, reduces viral shedding, and decreases acute pain and risk of postherpetic neuralgia (PHN).

Step 2: Manage Pain

• Acute Pain:
• Analgesics: Acetaminophen or NSAIDs (e.g., ibuprofen 400–600 mg TID) for mild pain.
• Moderate to Severe Pain: Consider tramadol (50–100 mg every 4–6 hours) or short-term opioids (e.g., oxycodone 5–10 mg every 4–6 hours) with caution.
• Postherpetic Neuralgia (PHN):
• First-Line:
• Gabapentin: Start at 300 mg/day, titrate to 1,800–3,600 mg/day in divided doses.
• Pregabalin: Start at 150 mg/day (50 mg TID), increase to 300–600 mg/day based on tolerability.
• Preferred-Line: Tricyclic antidepressants (e.g., amitriptyline or nortriptyline 10–25 mg at bedtime, titrate to 75–150 mg/day). I prefer amitriptyline because of the risk benefit. Please see the risks of amitriptyline and gabapentin below. I have had a couple of patients that had suicidal ideation on gabapentin. Thus I switched amitriptyline years ago.
• Topical Therapy:
• Lidocaine 5% patch: Apply to intact skin up to 12 hours/day.
• Capsaicin 8% patch: Single application by a healthcare provider, repeated every 3 months if needed.

Step 3: Treat Skin Involvement

• Rash Care:
• Keep lesions clean and dry to prevent bacterial superinfection.
• Apply topical antibacterial ointment (e.g., bacitracin or erythromycin) 4 times daily (QID) if secondary infection is suspected.
• Itching/Pain: Consider antihistamines (e.g., hydroxyzine 25 mg at bedtime) or H2 antagonists (e.g., cimetidine 400 mg twice daily) for symptomatic relief (evidence limited).

Step 4: Manage Ocular Involvement (Herpes Zoster Ophthalmicus)

• Consult Ophthalmologist: Urgent referral if eye involvement is suspected (e.g., rash on forehead, eyelid, or nose tip: Known as Hutchinson sign). 
• Corneal Involvement:
• Antiviral: Valacyclovir 1,000 mg TID or acyclovir 800 mg 5x/day for 7–10 days.
• Topical Steroids: Prednisolone acetate 1% QID or difluprednate 0.05% QID, tapered slowly to prevent recurrence.
• Cycloplegics: May need Cyclopentolate 1% TID or atropine 1% daily to reduce ciliary spasm and pain.
• Conjunctivitis/Episcleritis: Cool compresses, erythromycin ointment BID–TID.
• Scleritis: Oral NSAIDs (e.g., flurbiprofen 100 mg TID) or prednisone 1 mg/kg/day for 2 weeks, then taper.

Step 5: Address Ramsay Hunt Syndrome (if Present)

• Signs: Facial paralysis, ear pain, vesicles in ear canal, hearing loss, or vertigo.
• Treatment:
• Antiviral: Valacyclovir 1,000 mg TID or acyclovir 800 mg 5x/day for 7–10 days.
• Corticosteroids: Prednisone 60 mg/day for 7 days, then taper over 7 days.
• Pain Management: As above (gabapentin, lidocaine patches, or prescription analgesics).
• Vertigo: Diazepam 2–5 mg as needed (short-term).
• Referral: ENT or neurologist for persistent symptoms.

Step 6: Vaccination and Prevention

• Shingrix Vaccine: Recombinant zoster vaccine recommended for adults ≥50 years, including those previously vaccinated with Zostavax or who have had shingles.
• Dosing: Two doses (0.5 mL each) 2–6 months apart.
• Efficacy: >90% effective in preventing shingles and PHN.

Step 7: Monitor and Follow-Up

• Immunocompromised Patients: May require longer antiviral therapy (10–14 days) or IV acyclovir (10 mg/kg every 8 hours) for disseminated disease.
• Complications: Monitor for PHN, bacterial superinfection, or neurological issues (e.g., encephalitis).
• Follow-Up: Weekly for severe cases or ocular involvement; monthly for PHN management.

MORE Notes:

Treatment by Manifestation

1. Skin Involvement

• Antiviral Therapy (7–10 days):
• Valacyclovir: 1,000 mg TID (preferred).
• Famciclovir: 500 mg TID.
• Acyclovir: 800 mg 5x/day.
• Topical Therapy:
• Antibacterial ointment (e.g., bacitracin or erythromycin) QID to prevent secondary infection.
• Keep lesions clean and dry.
• Itch/Pain Relief:
• Antihistamines (e.g., hydroxyzine 25 mg at bedtime) or H2 antagonists (e.g., cimetidine 400 mg BID) for symptomatic relief (limited evidence).

2. Ocular Involvement (Herpes Zoster Ophthalmicus)

• Urgent Referral: Consult ophthalmologist if rash involves forehead, eyelid, or nose tip.
• Corneal Involvement (Necrotizing Stromal Keratitis):
• Antiviral: Valacyclovir 1,000 mg TID, famciclovir 500 mg TID, or acyclovir 800 mg 5x/day (7–10 days).
• Topical Steroids: Prednisolone acetate 1% QID or difluprednate 0.05% QID, tapered slowly.
• Cycloplegics: Cyclopentolate 1% TID, scopolamine 0.25%, or atropine 1% daily for pain relief.
• Endotheliitis & Non-Necrotizing Stromal Keratitis:
• Topical steroids (prednisolone 1% QID or difluprednate 0.05% QID), tapered slowly; long-term low-dose steroids may prevent recurrence.
• Conjunctivitis/Episcleritis:
• Cool compresses, erythromycin ointment BID–TID.
• Scleritis:
• Oral NSAIDs (e.g., flurbiprofen 100 mg TID) or prednisone 1 mg/kg/day for 2 weeks, then taper.

3. Pain Management (Acute and PHN)

• Acute Pain:
• Mild: Acetaminophen or NSAIDs (e.g., ibuprofen 400–600 mg TID).
• Moderate to Severe: Tramadol (50–100 mg every 4–6 hours) or short-term opioids (e.g., oxycodone 5–10 mg every 4–6 hours).
• Postherpetic Neuralgia (PHN):
• First-Line:
• Gabapentin: Start 300 mg/day, titrate to 1,800–3,600 mg/day.
• Pregabalin: Start 150 mg/day (50 mg TID), titrate to 300–600 mg/day.
• Second-Line: Tricyclic antidepressants (e.g., amitriptyline or nortriptyline 10–25 mg at bedtime, titrate to 75–150 mg/day).
• Topical Therapy:
• Lidocaine 5% patch (apply up to 12 hours/day).
• Capsaicin 8% patch (provider-applied, repeat every 3 months if needed).

4. Ramsay Hunt Syndrome

• Indications: Facial paralysis, ear pain, vesicles in ear canal, hearing loss, or vertigo.
• Treatment:
• Antiviral: Valacyclovir 1,000 mg TID or acyclovir 800 mg 5x/day (7–10 days).
• Corticosteroids: Prednisone 60 mg/day for 7 days, then taper over 7 days.
• Vertigo: Diazepam 2–5 mg as needed (short-term).
• Pain: Gabapentin, lidocaine patches, or prescription analgesics (e.g., oxycodone).
• Referral: ENT or neurologist for persistent facial weakness or hearing loss.

5. Special Populations

• Immunocompromised Patients:
• May require extended antiviral therapy (10–14 days) or IV acyclovir (10 mg/kg every 8 hours) for disseminated disease.
• Monitor for complications (e.g., encephalitis, pneumonitis).
• Pregnancy: Acyclovir is preferred (Category B); consult OB/GYN.

6. Prevention

• Shingrix Vaccine: Recommended for adults ≥50 years, including those with prior shingles or Zostavax vaccination.
• Dosing: Two doses (0.5 mL) 2–6 months apart.
• Efficacy: >90% effective against shingles and PHN.

7. Monitoring and Follow-Up

• Severe Cases: Weekly follow-up for ocular involvement or immunocompromised patients.
• PHN: Monthly follow-up to adjust pain management.
• Complications: Monitor for bacterial superinfection, neurological issues, or persistent pain.

Side effects:

Side Effects of Zoster and PHN Meds (With Percentages Where Known)

No treatment is risk-free, but transparency empowers. Below, a comprehensive list modeled on gabapentin’s profile—categorized by frequency, drawn from 2025 prescribing data and trials. Percentages reflect zoster/PHN contexts where specified; many are dose-dependent and transient.    Consult your doc for personalization.

Antivirals (Acute Zoster)

Valacyclovir:

•  Common (≥1-10%): Headache (8-17%), nausea (6-13%), abdominal pain (2-11%), vomiting (1-8%), diarrhea (3-7%), dizziness (2-4%), fatigue (2-5%).  

•  Less common (0.1-1%): Depression (0.5-1%), arthralgia (0.5%), rash (0.3%), insomnia (0.2%).

•  Serious/rare (<0.1%): Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (<0.01%), acute kidney injury (esp. elderly/dehydrated, 0.1-0.5%), hallucinations (0.01%), anaphylaxis.

Famciclovir:

•  Common (≥1-10%): Headache (5-10%), nausea (8-13%), diarrhea (4-9%), abdominal pain (3-8%), fatigue (2-5%), dizziness (1-3%).  

•  Less common (0.1-1%): Vomiting (1-5%), pruritus (0.5-1%), dysmenorrhea (women, 1-4%).

•  Serious/rare (<0.1%): Thrombocytopenia (0.04%), hallucinations (0.01%), renal failure (0.1% in impaired).

Acyclovir:

•  Common (≥1-10%): Nausea (4-12%), vomiting (2-8%), diarrhea (3-7%), headache (5-10%), malaise (2-6%).

•  Less common (0.1-1%): Dizziness (1-3%), rash (0.5-2%), insomnia (0.5%).

•  Serious/rare (<0.1%): Neurotoxicity (confusion/hallucinations, 0.1-1% IV, esp. renal impairment), crystalluria/nephrotoxicity (0.5-2% if dehydrated), anaphylaxis (<0.01%).

Neuromodulators (Acute Pain/PHN Prevention & Treatment)

Gabapentin (Neurontin):

•  Common (≥1-10%): Somnolence/drowsiness (21-30%), dizziness (17-28%), ataxia (12-13%), fatigue (11%), peripheral edema (8%), nystagmus (8%), tremor (8%), diplopia (6-8%), weight gain (3-10%), nausea (3-8%), dry mouth (5%).   

•  Less common (0.1-1%): Confusion (1%), depression (1%), headache (5-8%), dysarthria (2%), amnesia (1%), impotence (1%), rhinitis (5%).

•  Serious/rare (<0.1%): Suicidality (black-box, 0.01-0.1%), respiratory depression (with opioids, <0.1%), Stevens-Johnson syndrome (<0.01%), rhabdomyolysis (<0.01%), acute kidney injury.

Pregabalin (Lyrica):

•  Common (≥1-10%): Dizziness (29-45%), somnolence (22-36%), dry mouth (11-15%), edema (6-14%), blurred vision (6-12%), weight gain (7-16%), constipation (4-10%), headache (9%).

•  Less common (0.1-1%): Ataxia (1-5%), euphoria (1-4%), vertigo (2-3%).

•  Serious/rare (<0.1%): Angioedema (<0.1%), hypersensitivity (0.1%), suicidality (0.01%), myopathy (<0.01%).

Amitriptyline (Elavil):

•  Common (≥1-10%): Dry mouth (40-80%), constipation (10-30%), drowsiness (20-40%), dizziness (10-20%), weight gain (5-15%), blurred vision (10-20%), orthostasis (5-10%).  

•  Less common (0.1-1%): Headache (5-10%), sweating (5%), urinary retention (2-5%).

•  Serious/rare (<0.1%): Arrhythmias/QT prolongation (0.1-1%, cardiac risk), suicidality (black-box, 0.01%), seizures (0.1%), serotonin syndrome.

Nortriptyline (Pamelor, TCA alternative to amitriptyline for PHN):

•  Common (≥1-10%): Dry mouth (20-50%), drowsiness (10-20%), constipation (10-15%), dizziness (5-10%), tremor (5%).  

•  Less common (0.1-1%): Weight gain (2-5%), blurred vision (3-5%).

•  Serious/rare (<0.1%): Cardiac toxicity (0.1-0.5%), suicidality (0.01%), orthostatic hypotension.

Topicals (PHN)

Lidocaine 5% Patch (Lidoderm):

•  Common (≥1-10%): Application site erythema (12-16%), rash (5-10%), pruritus (3-5%).  

•  Less common (0.1-1%): Headache (1-3%), nausea (1%), dizziness (0.5%).

•  Serious/rare (<0.1%): Systemic absorption toxicity (methemoglobinemia, seizures <0.01% if >3 patches), contact dermatitis.

Capsaicin 8% Patch or 0.025-0.075% Cream (Qutenza/Zostrix):

•  Common (≥1-10%): Application site pain/burning (42-58%), erythema (40-50%), pruritus (10-20%), edema (5-10%).  

•  Less common (0.1-1%): Cough (1-3%), nausea (1%).

•  Serious/rare (<0.1%): Severe dermatitis (<1%), hypertension during application (<0.1%).

A Separate Word on Oral Steroids: Proceed with Caution

In most zoster cases (80-90%), oral corticosteroids like prednisone aren’t needed—they don’t prevent PHN and may prolong viral shedding. Reserve for select scenarios: Severe acute pain (≥7/10) in immunocompetent adults >50, or Ramsay Hunt syndrome (facial palsy)—e.g., prednisone 40 mg/day tapered over 7-21 days, always with antivirals to mitigate dissemination risk. Evidence shows modest acute pain relief (20-30% faster resolution) but no PHN benefit; weigh against GI upset, hyperglycemia, and infection flare (5-10% risk).

Shingrix risks:**

Common Local Reactions (within 7 days, from ZOE-50/70 trials, n>10,000; higher in 50-59 yo):

•  Injection-site pain: 69-88%

•  Injection-site redness: 38-39%

•  Injection-site swelling: 23-31%

Common Systemic Reactions (within 7 days):

•  Fatigue: 37-57%

•  Myalgia (muscle pain): 35-57%

•  Headache: 29-51%

•  Shivering: 20-36%

•  Fever: 14-28%

•  Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain): 14-24%

Severe (Grade 3) Reactions (preventing normal activity):

•  Overall: ~17% (higher in younger adults: up to 25% for pain/fatigue)

Less Common (1-10%):

•  Arthralgia (joint pain): 5-10%

•  Injection-site pruritus (itching): 3-7%

•  Malaise: 2-5%

Rare/Serious Risks (<0.1-1%):

•  Anaphylaxis: <0.01%

•  Guillain-Barré Syndrome (excess cases): 3-5 per million doses

•  Herpes zoster-like rash (post-vaccination): 0.1-0.5%

•  Potential immune-mediated events (e.g., Bell’s palsy): 0.6%

Other Notes:

•  Most resolve in 2-3 days; no increased mortality (0.8% similar to placebo).

•  Percentages from clinical trials; post-marketing (VAERS) may vary due to reporting bias.

Went to do a full blood work up for underlying autoimmune disease or malignancy?

We used to do blood work on all patients less than 50 when I was a resident. We don’t do that anymore unless there’s certain issues going on:

Shingles isn’t always just “bad luck”—it can be a canary in the coal mine for waning immunity. Why did patients under 50 used to get a full workup for autoimmune diseases or other hidden foes? Back in the pre-vaccination, pre-ART era (1980s-2000s), zoster was rare in young healthy adults (1-3 cases per 1,000 person-years), often flagging serious cell-mediated immunosuppression: think undiagnosed HIV (7-15x risk), lymphomas/leukemias, or autoimmune conditions like SLE or RA requiring steroids/immunosuppressants (20-100x risk).    The AIDS crisis amplified this—zoster became a sentinel for HIV testing, with guidelines urging broad evaluation to catch malignancies or rheumatologic issues early. 

Fast-forward to 2025: With vaccination and better HIV control, routine sleuthing has dialed back. For a 55-year-old like our hypothetical patient? No blanket bloodwork needed—incidence spikes post-50 due to natural T-cell decline, making it “normal” aging, not alarm bells.   But trigger a deeper dive if: under 50 at onset, recurrent episodes, disseminated rash (beyond one dermatome), severe/systemic symptoms, or personal risks (e.g., unexplained weight loss, night sweats).

Recommended blood tests for underlying malignancy or autoimmune: If you are a healthy person, check with your medical doctor to see if you need these blood tests:  complete blood count (CBC) for anemia/lymphopenia, HIV serology (mandatory if <50 or risks), erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) for inflammation. Escalate to antinuclear antibody (ANA) for autoimmune screen, serum protein electrophoresis (SPEP)/urine protein electrophoresis (UPEP) for paraproteins (myeloma clue), and lactate dehydrogenase (LDH) as a tumor marker. If red flags persist: Flow cytometry, chest X-ray/CT, or rheumatology/hematology referral. Evidence? No routine benefit in healthy >50, but early detection in young saves lives—coincidental in elders.    Why not over-test? False positives cascade into anxiety and unnecessary biopsies.

References

1.  Medscape: Herpes Zoster Treatment (2025). 

2.  UpToDate: Treatment of Herpes Zoster (2025). 

3.  NCBI: Herpes Zoster StatPearls (2025). 

4.  AAFP: HZ and PHN Prevention (2017/updated 2025).    

5.  CDC: Shingles Clinical Overview (2024/2025).  

6.  QLD Health: HZ Guideline (2025). 

7.  US Pharmacist: Shingles Pain Prevention (2025).  

8.  BMJ Best Practice: HZ Infection (2025). 

9.  CID: HZ Management Recommendations (2008/updated). 

10.  NCBI: PHN StatPearls (2025). 

11.  Medscape: PHN Treatment (2025). 

12.  UpToDate: PHN (2025). 

13.  ASRA: PHN (2019/updated). 

14.  CID: PHN Treatment Advances (2003/updated). 

15.  IASP: S2k HZ/PHN Guidelines (2024). 

16.  MDPI: HZ Diagnosis/Treatment (2024). 

17.  Wiley: HZ/PHN Review (2024). 

18.  Mayo Clinic: Valacyclovir SE (2025). 

19.  Drugs.com: Valacyclovir SE (2025). 

20.  GoodRx: Valacyclovir SE (2024). 

21.  NCBI: Famciclovir StatPearls (2025). 

22.  Drugs.com: Famciclovir SE (2025). 

23.  GoodRx: Famciclovir SE (2024). 

24.  Drugs.com: Acyclovir SE (2025).

25.  WebMD: Acyclovir (2024).

26.  NHS: Gabapentin SE (2025). 

27.  GoodRx: Gabapentin SE (2025). 

28.  PubMed: Gabapentin Pooled Analysis (2004/updated). 

29.  NCBI: Pregabalin StatPearls (2025).

30.  MedCentral: Pregabalin (2025).

31.  AAFP: Pregabalin for PHN (2006/updated).

32.  NCBI: Amitriptyline StatPearls (2025). 

33.  Drugs.com: Amitriptyline SE (2025). 

34.  GoodRx: Nortriptyline SE (2023). 

35.  NCBI: Nortriptyline StatPearls (2025). 

36.  GoodRx: Lidocaine Patch SE (2025). 

37.  FDA: Lidoderm Label (2015/updated). 

38.  Healthline: Capsaicin Cream (2018/updated). 

39.  PMC: Topical Capsaicin Review (2012/updated). 

40.  Mayo Clinic: PHN Complications (2023).

41.  Cleveland Clinic: PHN (2025).

42.  CDC: Shingles Complications (2024).

43.  NHS: Post-Herpetic Neuralgia (2025).

44.  Medscape: HZ Corticosteroids (2025).

45.  Dr. Oracle: Steroids in HZ (2025).

46.  US Pharmacist: Steroids in HZ (2025).

47.  Medscape: HZ Workup (2025).