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Herpes Zoster and Post-Herpetic Neuralgia

Herpes Zoster and Post-Herpetic Neuralgia. C arol Sue Carlson, MD March 28, 2008. Zoster (AKA “Shingles”). Case – MR. 53 yo ♂ C5 Tetraplegic 2 o to Spinal Cord Infarct PMHx: NonHodgkins Lymphoma s/p Chemo/RT on Decadron po c/o burning, achy pain in posterior neck

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Herpes Zoster and Post-Herpetic Neuralgia

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  1. Herpes Zoster and Post-Herpetic Neuralgia Carol Sue Carlson, MD March 28, 2008

  2. Zoster (AKA “Shingles”)

  3. Case – MR • 53 yo ♂ • C5 Tetraplegic 2o to Spinal Cord Infarct • PMHx: NonHodgkins Lymphoma s/p Chemo/RT • on Decadron po • c/o burning, achy pain in posterior neck • ~36-48 hrs later  rash • Dx: CN V3 Herpes Zoster • Pain!! • PCA, Acyclovir, Amitryptiline, Oxcarbazepine, Pregabalin, Duloxetine, Capsaicin, Lidoderm 5% patch, Methadone, Hydrocortisone Cream, Triamcinolone Cream

  4. Case – MR

  5. Overview (1)Herpes Zoster Pathogenesis Epidemiology Natural History and Infectivity Complications Treatment Prevention (2) PostHerpetic Neuralgia Epidemiology Risk Factors Clinical Manifestations Pathogenesis Prevention Treatment (3) EMG studies

  6. Varicella-Zoster Virus

  7. Varicella Zoster Virus • Varicella Zoster Virus • Varicella  “Chicken Pox” • Zoster  “Shingles”

  8. Varicella Zoster Virus – Pathogenesis • Viral Latency • Limited # of Proteins Expressed • Emergence from Latency • Not Well-Understood • Reactivation • Spreads w/in Ganglion • Multiple Sensory Neurons • Infection of Skin

  9. Varicella Zoster Virus – Pathogenesis

  10. Acute Zoster Pathogenesis • 1st -Hemorrhagic Inflammation • Peripheral Nerve • Dorsal Root • DRG • Spinal Cord • Leptomeninges • Nociceptor Activation • Poorly Localized Pain • “Pre-Herpetic Neuralgia” • Nociceptor Sensitization • Clinical Ramifications

  11. Acute Zoster Pathogenesis • 2nd -Fibrosis • DRG • Nerve Root • Peripheral Nerve • Autopsy Results • Similar +/- PHN

  12. Zoster Pathogenesis • Pain of Acute Herpetic Neuralgia • (1) Inflammation 2o to Movement of Virus • (2) Hyperexcitability of Dorsal Horn Neurons • Spontaneous Activity • Exaggerated Responses • Allodynia, Hyperalgesia • Interneuron Spread

  13. Intercostal Nerve Histology Normal Post-Zoster

  14. Zoster Pathogenesis – Reactivation • DRG and Dorsal Horn • Intense Inflammation • Hemorrhagic Necrosis of Nerve Cells • Neuronal Loss • Fibrosis

  15. Zoster Pathogenesis • Neurotransmitters: • Substance P • Transmission • Serotonin, NE • Inhibition • Therapeutic Implications • Studies • No Difference Side to Side

  16. Zoster – Cell Mediated Immunity • Cell-Mediated Immune Responses • Control Viral Latency • Limit Potential for Re-activation • ↓ Skin Reactivity to VZV by 40 yo • Severely ↓ by 60 yo • ↑ Rates of Herpes Zoster In: • Older Individuals • Lymphoproliferative Malignancies • BUT No ↑ Rates of Zoster or Protracted Varicella In: • Children w/ Hypogammaglobulinemia

  17. Overview (1)Herpes Zoster Pathogenesis Epidemiology Natural History and Infectivity Complications Treatment Prevention (2) PostHerpetic Neuralgia Epidemiology Risk Factors Clinical Manifestations Pathogenesis Prevention Treatment (3) EMG studies

  18. Zoster Epidemiology • Cumulative Lifetime Incidence • 10-20% of Population • Older Age Groups • 30% > 55 yo • Incidence ↑ w/Age • 1 per 1000 in Pts < 20 yo • 5-10X Greater in Pts > 80 yo • ***Highest Incidence after 6th decade*** • ♂ = ♀

  19. Zoster Epidemiology • Immunocompromised at ↑↑↑ Risk • Age • Disease • Chemotherapy • Several Times More Common in Pts w/ Ca, HIV, Transplant Recipients

  20. Zoster Epidemiology

  21. Zoster Epidemiology

  22. Overview (1)Herpes Zoster Pathogenesis Epidemiology Natural History and Infectivity Complications Treatment Prevention (2) PostHerpetic Neuralgia Epidemiology Risk Factors Clinical Manifestations Pathogenesis Prevention Treatment (3) EMG studies

  23. Zoster – Natural History and Infectivity

  24. Zoster – Natural History • 75% have Prodromal Pain • Grouped Vesicles or Bullae w/in 3-4 days • Crusting in 7-10 Days • No Longer Infectious • Scarring, Hypo- or Hyperpigmentation • Recurrence is Rare

  25. Zoster Rash

  26. Zoster – Natural History • PAIN – Most Common Sx • Deep, “Burning”, “Throbbing”, “Stabbing” • Dermatomal • Thoracic, CN V, Cervical – Most Common • Zoster Keratitis, Zoster Ophthalmicus (CN V1) • Systemic Sx – Rare (<20%) • Most Cases – Self-Limited BUT: • Can Interfere w/ Sleep, Appetite, Sexual Fnxn • Psychosocial Dysfunction

  27. Zoster Dermatomal Distribution

  28. Zoster – Infectivity • Immunocompetent Host Via: • Direct Contact w/ Lesion • Contact Precautions Recommended in Hosp. Pts • Until Lesions Crust • VZV Naïve Pts Exposed to Zoster • At Risk to Develop 1o Varicella NOT Zoster

  29. Zoster – Infectivity • Immunocompromised Pt w/ Either: • (1) Disseminated HZ • (2) Local HZ in Pt at Risk for Dissemination • Hospitalized, Strict Isolation • Rx ~ Varicella (in which Airborne Spread is Possible)

  30. Herpes Zoster

  31. Herpes Zoster

  32. Herpes Zoster

  33. Overview (1)Herpes Zoster Pathogenesis Epidemiology Natural History and Infectivity Complications Treatment Prevention (2) PostHerpetic Neuralgia Epidemiology Risk Factors Clinical Manifestations Pathogenesis Prevention Treatment (3) EMG studies

  34. Zoster Complications • POSTHERPETIC NEURALGIA • ***Most Common*** (10-15%) • Ocular • Neurologic • Motor Neuropathies – 2nd most common (2-3%) • CN palsies • Meningitis • Myelitis • Encephalitis • Bacterial Superinfection • Ramsey-Hunt Syndrome

  35. Zoster Ophthalmicus

  36. Zoster – Motor Paresis

  37. Zoster – Motor Paresis

  38. Zoster – Motor Paresis

  39. Zoster – Bacterial Superinfection

  40. Ramsey-Hunt Syndrome

  41. Zoster Complications – Immunosuppressed • Includes: • HIV-infected pts • Transplant Recipients • Hematologic Malignancies • ↑↑↑ Risk for Severe Complications • Cutaneous Dissemination • Visceral Involvement • Pneumonitis, Hepatitis, Pancreatitis, Meningo-encephalitis

  42. Overview (1)Herpes Zoster Pathogenesis Epidemiology Natural History and Infectivity Complications Treatment Prevention (2) PostHerpetic Neuralgia Epidemiology Risk Factors Clinical Manifestations Pathogenesis Prevention Treatment (3) EMG studies

  43. Uncomplicated Herpes Zoster Treatment • Antiviral Therapy • Goals: • (1) Promote Rapid Healing • (2) ↓ Severity and Duration of Pain • (3) ↓ Incidence and Severity of PHN • Prompt Use of Anti-Virals • ↓ Duration of Pain by ½ • ↓ Overall Incidence of PHN

  44. Acyclovir • Oral Acyclovir 800 mg 5X/day • Excellent Safety Profile • Mainstay of Rx BUT: • Poor Bioavailability • Frequent Dosing • Within 48-72 Hrs of Rash Onset • Accelerates Resolution of Pain (Esp. in Pts > 50 yo) • 1 Meta-Analysis – Sig. ↓ in PHN at 6 months by 46% Archives of Internal Medicine Vol 157 Apr 28, 1997, pp 909-911

  45. Acyclovir with Corticosteroids • Rx of Uncomplicated Acute HZ • Study: • ACV 800 mg po 5X/day X 21 days + Prednisone X 21 days • ACV + Placebo • Prednisone + Placebo • 2 Placebos • ACV + Prednisone: • Less Time to Crusting, Healing, Sleep, Return to Prior Activity • Faster Resolution Acute Neuralgia • Earlier D/C of Analgesics • Drawbacks

  46. Valacyclovir • Valacyclovir 1000 mg po tid X 7-14 days vs. ACV • Accelerated Resolution of Pain • 38 days vs. 51 days • ↓ Duration of PHN • Similar Adverse Events

  47. Anti-Viral Recommendations • Initiate w/in 72 hrs • Esp. in Pts > 50 yo • In Pts < 50 yo, Consider Risk Factors for Developing PHN • Valacyclovir 1000 mg po tid X 7 days • More Rapid Resolution Acute Neuritis • Shorter Duration of PHN • Lower Pill Burden  Improved Compliance • BUT↑ $$$ • Higher Cost than ACV

  48. Anti-Viral Recommendations • Steroids Have Only Been Studied w/ ACV • Moderate Acceleration of Healing and Resolution of Pain • No Effect on PHN • ↑ Adverse Effects w/ Steroids • May ↑ Risk of Bacterial Superinfection • Recommend Prednisone 40 mg Taper over 7-10 days • ONLY in Pts: • (1) w/ Severe Sx at Onset • (2) w/o Specific Contraindication • Last Dose Should Coincide w/ End of Anti-Viral Rx

  49. Overview (1)Herpes Zoster Pathogenesis Epidemiology Natural History and Infectivity Complications Treatment Prevention (2) PostHerpetic Neuralgia Epidemiology Risk Factors Clinical Manifestations Pathogenesis Prevention Treatment (3) EMG studies

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