Herpes Zoster: Recent Aspects of Diagnosis and Control

The Patients Speak in Poetry, Art, and Prose
My Constant Companion
Preface
References
Preface and Acknowledgments
References
Patrick D. Wall (1925–2001): An Appreciation
References
Contents
About the Editors
Contributors
Chapter 1: Introduction
1.1 Fascination
1.2 Frustrations
1.3 Excitement
1.4 Epidemiology, Complications, Pathology
1.5 Vascular Disease
1.6 Three Therapeutic Approaches
1.7 Book Dedications and Caveats
References
Part I: Varicella (Chickenpox)
Chapter 2: Varicella
2.1 Introduction
2.2 Clinical Features of Varicella
2.3 Treatment
2.4 Prevention: Live Attenuated Varicella Vaccine
References
Part II: Herpes Zoster (Shingles)
Chapter 3: Herpes Zoster: A Patient’s Perspective
3.1 About My Pain
3.2 Getting Treatment
3.3 Impact on Life, Family, Work, and Finances
Commentary
References
Chapter 4: The Epidemiology and Natural History of Herpes Zoster and Postherpetic Neuralgia
4.1 Introduction
4.2 Herpes Zoster
4.2.1 Incidence of Herpes Zoster in General Population-Based Studies
4.2.2 Morbidity and Mortality of Herpes Zoster
4.2.3 Risk Factors for Herpes Zoster
4.2.3.1 Age
4.2.3.2 Sex
4.2.3.3 Race and Ethnicity
4.2.3.4 Cellular Immune Deficiency
4.2.3.5 Other Risk Factors
4.2.4 Transmission of Varicella-Zoster Virus (VZV) and Herpes Zoster
4.3 Postherpetic Neuralgia
4.3.1 Definitions of PHN
4.3.2 Incidence and Prevalence of PHN
4.3.3 Risk Factors for PHN
4.3.3.1 Greater Age
4.3.3.2 Greater Acute Pain Severity
4.3.3.3 Greater Rash Severity
4.3.3.4 Sensory Dysfunction
4.3.3.5 Immune Response
4.3.3.6 Sex
4.3.3.7 Dermatome
4.3.3.8 Psychosocial Risk Factors
4.4 Conclusions
References
Chapter 5: Herpes Zoster Ophthalmicus
5.1 Epidemiology
5.2 Acute HZO
5.3 HZO in HIV Patients
5.4 Neurologic Complication
5.5 Management of HZO
5.6 Management of Ocular Complications
5.7 Summary
References
Chapter 6: Neurological Complications of Herpes Zoster
6.1 Introduction
6.2 Subclinical Spread of Inflammation into the Central Nervous System in Herpes Zoster
6.3 Neurological Complications due to Reactivation of Varicella Zoster Virus Without Rash
6.4 Peripheral Motor Paresis
6.5 Involvement of Cranial Nerves
6.5.1 Ophthalmoplegia
6.5.2 Herpes Zoster Oticus
6.6 The Central Nervous System Complications of Herpes Zoster
6.6.1 Meningitis
6.6.2 Encephalitis
6.6.3 Myelitis
6.6.4 Cerebral Vasculopathy
6.6.5 Diagnosis and Treatment of the Central Nervous System Complications of Herpes Zoster
6.7 Neurological Complications of the Fetus Following Maternal Herpes Zoster
6.8 Summary
References
Chapter 7: The Role of Varicella Zoster Virus in Giant Cell Arteritis
7.1 Introduction
7.2 Case Reports of GCA and VZV Vasculopathy
7.3 Retrospective Analysis of Archived GCA-Positive and GCA-Negative Temporal Arteries
7.4 Granulomatous Aortitis
7.5 Treatment of GCA
7.6 Conclusion
References
Chapter 8: Herpes Zoster and Vascular Risk
8.1 Introduction
8.1.1 Complications of Herpes Zoster
8.2 Study Designs
8.3 Epidemiology of Shingles and Stroke
8.4 Epidemiology of Shingles and Other Acute Vascular Complications
8.5 Herpes Zoster Vaccination and Antivirals
8.6 Mechanisms
8.7 What Is Not Known/Future Directions
References
Chapter 9: Antiviral Therapy and Local Treatment for Herpes Zoster
9.1 Local Treatment for Zoster
9.2 Development of Antivirals
9.3 Newer Antivirals Against VZV
9.4 Impact of Antiviral Therapy on PHN
9.5 Future Directions
9.6 Conclusions
References
Chapter 10: Dermatologic Manifestations of Herpes Zoster
10.1 Introduction
10.2 Clinical Features
10.3 Complications
10.3.1 Pain
10.3.2 Cutaneous Complications
10.3.2.1 Bacterial Infection
10.3.2.2 Scarring
10.3.2.3 Post-inflammatory Hyperpigmentation
10.3.2.4 Gangrene
10.3.2.5 Wolf’s Isotopic Response
10.3.3 Ocular Complications
10.4 Histopathology
10.5 Diagnosis of HZ
10.6 Therapy of HZ
10.6.1 General Measures
10.6.2 Systemic Antibacterial Agents
10.6.3 Glucocorticosteroids
10.6.4 Antiviral Agents
10.7 Conclusion
References
Part III: Postherpetic Neuralgia: Assessment, Pathology, Pathophysiology
Chapter 11: The Effect of Herpes Zoster and Postherpetic Neuralgia on Health-Related Quality of Life, Function, Employment-Related Productivity, and the Cost-Effectiveness of the Vaccine
11.1 Introduction
11.2 Health-Related Quality of Life (HRQoL)
11.2.1 General Concept and Definitions
11.2.2 HRQoL Measures
11.2.3 Generic and Disease-Specific Instruments Commonly Used to Examine the Impact of Herpes Zoster and Postherpetic Neuralgia on HRQoL
11.3 Impact of Herpes Zoster on HRQoL
11.3.1 Impact of Herpes Zoster on HRQoL: Generic Instruments
11.3.2 Impact of Herpes Zoster on HRQoL: Disease-Specific Instrument
11.4 Impact of Postherpetic Neuralgia on HRQoL
11.4.1 Impact of Postherpetic Neuralgia on HRQoL: Generic Instruments
11.4.2 Impact of Postherpetic Neuralgia on HRQoL: Disease-­Specific Instrument
11.5 Impact of Herpes Zoster and Postherpetic Neuralgia on Employment-Related Productivity
11.5.1 General Concept and Measures
11.5.2 Productivity Loss Associated with Herpes Zoster and Postherpetic Neuralgia
11.6 Economic Analyses of the Herpes Zoster Vaccine
11.6.1 General Concept and Definitions
11.6.2 Economic Evaluations of Vaccination against Herpes Zoster
11.7 Conclusion
References
Chapter 12: The Pathology of Postherpetic Neuralgia and Postherpetic Itch
12.1 Introduction
12.2 Early Pathological Studies
12.3 Head and Campbell [17]
12.4 Later Pathological Studies of Zoster-Affected Ganglia and Central Nervous Tissue
12.5 Pathological Studies of Nerves Extending from  Zoster-­Affected Ganglia
12.6 Autopsy Attempts to Discover the Pathologic Signature of PHN
12.7 The Pathology of Facial (Trigeminal) Zoster and PHN
12.8 Skin-Biopsy Studies of Living Patients with Prior Shingles
12.9 Bilateral Neuropathology after Unilateral Shingles
12.10 The Pathology of Postherpetic Itch (PHI) and Associated Self-Injury
12.11 Summary
References
Chapter 13: Neural Basis of Pain in Herpes Zoster and Postherpetic Neuralgia: The Ectopic Pacemaker Hypothesis
13.1 Introduction
13.2 Spontaneous and Evoked Neuropathic Pain
13.3 Spontaneous Pain in HZ and PHN
13.3.1 VZV Causes Varicella, HZ, and PHN
13.3.2 Do the Impulses That Cause Spontaneous Pain in HZ and PHN Originate in the Skin?
13.3.3 Ectopic Pacemakers in the Skin
13.3.4 “Deafferentation” and the Spinal Cord as a Pain Driver in HZ and PHN
13.4 Hypersensibility to Applied Stimuli and Tactile Allodynia
13.4.1 Tactile Allodynia: Irritable Nociceptors or Central Sensitization?
13.4.2 The Significance of Dermatomal Overlap
13.5 Summary and Perspective
References
Chapter 14: Persistent VZV Ganglionitis May Be the Cause of Postherpetic Neuralgia
14.1 Zoster and Postherpetic Neuralgia
14.2 Postherpetic Neuralgia, Preherpetic Neuralgia, and Zoster Sine Herpete
14.3 The Possible Viral Cause of Postherpetic Neuralgia (PHN)
14.4 Perspective on Antiviral Therapy for Postherpetic Neuralgia (PHN)
14.5 Conclusion
Editorial Comment
References
Chapter 15: A Comparison of Clinical Features and Mechanisms of Trigeminal Postherpetic Neuralgia and Trigeminal Neuralgia
15.1 Introduction
15.2 Case Studies
15.3 Historical
15.4 Epidemiology, Incidence, and Natural History of TN and TPHN
15.4.1 Clinical Features
15.4.2 Pathology
15.5 Treatment
15.5.1 Medical
15.5.2 Surgery
15.6 Pathophysiology: TN and TPHN Mechanisms
15.6.1 Spinal Neuropathic Pain Models and Mechanisms
15.6.2 Trigeminal Somatosensory System: Normal Features and Neuropathic Processes
15.6.2.1 Normal Features
Trigeminal Primary Afferent Mechanisms
Trigeminal Brainstem Mechanisms
Thalamocortical Mechanisms
Modulation of CNS Nociceptive Processes
15.6.2.2 Trigeminal Neuropathic Pain Models and Mechanisms
Peripheral Trigeminal Neuropathic Pain Processes
Central Trigeminal Neuropathic Pain Processes
Brainstem Processes
Thalamocortical Processes
15.6.2.3 TN Models and Mechanisms
15.6.2.4 TPHN Models and Mechanisms
15.7 Final Perspectives, Future Directions, and Concluding Remarks
References
Part IV: Postherpetic Neuralgia: Treatment
Chapter 16: Treatment of Postherpetic Neuralgia: Subtypes and a Mechanism-Based Treatment
16.1 Introduction
16.2 Where Do We Stand Today?
16.3 Classification of Patients Based on Sensory Abnormalities
16.4 Potential Mechanisms Operating in Different Subgroups
16.4.1 Subgroup 1
16.4.2 Subgroup 2
16.4.3 Subgroup 3
16.5 Treatment Studies Using Mechanism-Based Classification
16.6 Limitations of the Approach
16.7 Future Implications for Therapy and Clinical Trials
16.8 Conclusions
References
Chapter 17: Interventional Approaches to Postherpetic Neuralgia
17.1 Introduction
17.2 General Considerations
17.3 Nerve Blocks
17.3.1 Timing of Interventions
17.3.2 Acute Pain Control
17.3.3 Preemptive Nerve Blocks to Prevent Postherpetic Neuralgia
17.3.4 Treatment of Postherpetic Neuralgia with Nerve Blocks
17.4 Neuromodulation
17.4.1 Spinal Cord Stimulation
17.4.2 Intrathecal Therapy
17.4.3 Radiofrequency Procedures
17.5 Conclusions
References
Chapter 18: Treatment of Postherpetic Neuralgia: The Role of Opioids
18.1 Introduction
18.2 Adaptations to Chronic Opioid Use
18.2.1 Tolerance
18.2.2 Physical Dependence
18.2.3 Tolerance and Dependence Cannot Be Separated
18.2.4 What Is Addiction?
18.2.5 Implications
18.3 Opioid Harms
18.4 Which Patients Are Suitable Candidates?
18.4.1 Prodromal Phase
18.4.2 Acute Phase
18.4.3 Subacute Phase
18.4.4 Postherpetic Neuralgia (PHN)
18.5 Which Opioid, Which Dose?
18.5.1 “Mild” Opioids
18.5.2 Tapentadol
18.5.3 Pure Mu Opioid Agonists
18.5.4 Mixed Agonist Antagonists
18.5.5 Dose
18.5.6 Titrating to Effect: A Bad Idea When Pain Is Chronic
18.6 Sensible Precautions
18.6.1 At the Start of Opioid Therapy/Acute Pain
18.6.2 When Opioid Is Selected as Chronic Pain Treatment
18.6.2.1 The Care Agreement
18.6.2.2 Urine Toxicology
18.6.2.3 Prescription Monitoring
18.7 Conclusions and Controversies
18.7.1 A Palliative Care Construct
18.7.2 What Is Different About Herpes Zoster Pain
18.8 Commentary
References
Chapter 19: Postherpetic Neuralgia: Difficult to Treat, Easier to Prevent
19.1 Introduction
19.2 Clinical Features (Fig. 19.7)
19.2.1 Pain Assessment
19.2.2 Physical Examination
19.2.3 Putative Pain Mechanisms Based on Pathology, Clinical Features and Pharmacodynamics, and Implications
19.3 Management Options
19.4 How Effective Are Pharmacological Agents for PHN in Clinical Practice?
19.5 Practical Guidelines for the Prevention and Treatment of Postherpetic Neuralgia
19.5.1 The Prevention of PHN by Treatment of HZ (Also Chap. 23)
19.5.2 Prevention by Vaccination
19.5.3 A Practical Approach to the Treatment of Postherpetic Neuralgia
19.6 Summary
References
Chapter 20: Postherpetic Neuralgia: Are There Neurosurgical Options?
20.1 Introduction
20.1.1 Definitions
20.1.2 Epidemiology and Natural History (Chap. 4)
20.1.3 Pathology and Putative Pain Mechanisms
20.1.4 Clinical Features (Figs 20.5 and 20.6)
20.1.5 Outcomes: Management Options (Book Sects. IV and V)
20.1.6 Neurosurgical Approaches
20.2 Summary
References
Chapter 21: Designing Randomized Controlled Trials of Oral Analgesics for Chronic Postherpetic Neuralgia
21.1 Introduction
21.2 Elements of Clinical Trials
21.2.1 Selectionof Trial Participants
21.2.2 Study Treatment, Placebo, and Comparator(s)
21.2.3 Trial Designs
21.2.4 Outcome Measures
21.2.5 Trial Duration and Sample Size
21.3 Current Challenges and Future Directions
21.4 Conclusion
References
Part V: The Prevention of Herpes Zoster and Postherpetic Neuralgia
Chapter 22: The Importance of Zoster Prevention Vaccines
22.1 Clinical
22.2 Pathological
22.3 Therapeutic
22.4 Preventative
22.5 Epidemiological
22.6 Conclusion
References
Chapter 23: Aggressive Noninvasive Treatment of Acute Herpes Zoster for the Prevention of Postherpetic Neuralgia
23.1 Introduction
23.2 Systemic Antiviral Therapy
23.3 Oral Glucocorticoids
23.4 Opioid and Non-opioid Analgesic Agents
23.5 Other Agents
23.6 Summary and Recommendations
References
Chapter 24: Herpes Zoster Vaccines
24.1 Introduction
24.1.1 The Nature of Herpes Zoster
24.1.2 Complications
24.1.3 VZV Latency
24.1.4 Reactivation of Latent VZV
24.2 The Central Role of Immunity to VZV in the Pathogenesis of Herpes Zoster
24.3 Live Attenuated Oka VZV Vaccine
24.4 The Challenge of Vaccinating Against Herpes Zoster
24.5 The Shingles Prevention Study (SPS)
24.5.1 Description of the Study
24.5.2 Evaluation of Suspected Cases of Herpes Zoster
24.5.3 Diagnosis of Herpes Zoster
24.5.4 Efficacy End Points
24.5.5 Results: Vaccine Efficacy
24.5.6 Results: Vaccine Efficacy for Zoster-Related Interference with Functional Status and  Quality of Life
24.5.7 Safety of Zoster Vaccine
24.5.8 Immune Responses to Zoster Vaccine
24.6 Persistence of Zoster Vaccine Efficacy
24.7 Immune Response to a Booster Dose of Zoster Vaccine
24.7.1 Intramuscular Versus Subcutaneous Administration
24.8 Efficacy and Safety of Zoster Vaccine in Persons 50–59 Years of Age
24.9 Other Oka Zoster Vaccines
24.9.1 Refrigerator-Stable Zoster Vaccine
24.9.2 Heat-Inactivated Zoster Vaccine
24.10 Safety and Effectiveness of Live Attenuated Zoster Vaccine
24.10.1 Safety of Zoster Vaccine in the General Population
24.10.2 Zoster Vaccine Effectiveness in the General Population
24.10.3 Additional Effectiveness Studies
24.10.4 Safety and Effectiveness of Zoster Vaccine in Persons with Comorbidities
24.10.5 Safety and Immunogenicity of Live Attenuated Oka Vaccine in Persons with HIV Infection
24.10.6 Safety and Immunogenicity of Zoster Vaccine in Immunocompromised Patients
24.11 Concomitant Administration
24.12 New Improved Vaccines
24.13 Barriers to Uptake of Zoster Vaccine
24.14 Future Directions
References
Chapter 25: Conclusion: “All Roads Lead to Rome”
Three Drawings by Susan Telling
Index