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TO DO - Post-herpetic neuralgia

Updated: Sep 12, 2021

Herpes zoster affects millions worldwide each year and there is significant suffering and disability with the acute pain associated with the rash and chronic pain of post herpetic neuralgia , particularly in older individuals. Herpes Zoster: Average 3-5 cases per 1000 person years - >60 6-8/1000 and >80 12/1000. PHN: Risk of 5-30% post acute infection. 48% persistent at 6 months. 20% at 1 year.

Risk factors for herpes zoster include increasing age; immunocompromised states such as HIV and lymphoproliferative disorders and immunosuppressive therapy. Risk factors for PHN include older age, painful prodrome, greater severity of rash and acute pain, ophthalmic involvement


Mechanism

Herpes Zoster is a viral infection caused by the reactivation of varicella-zoster virus. Primary varicella infection occurs with a chicken pox infection.

Following the resolution of chicken pox, the virus then remains dormant in the dorsal sensory ganglia and cranial nerve ganglia. Individuals are asymptomatic while the virus is dormant. Reactivation of VZV results in a characteristic and painful vesicular dermatomal rash, Some patients with herpes zoster develop post herpetic neuralgia which is a persistent neuropathic pain. Why reactivation occurs is unclear however it is thought to be related to declining cell mediated immunity.


PHN Mechanism

Theories include greater neural damage, predominantly unmyelinated small C fibres with contribution of peripheral and central sensitisation however studies are limited


Acute Presentation

Prodrome

- Fatigue, headache, flu-like symptoms, rash, malaise, nausea

- May be accompanied by a unilateral dermatomal pain and abnormal sensations including pruritis

- This usually precedes the rash by 3-7 days although longer periods have been reported

- Thought to occur due to initiation of viral replication and the inflammatory response

o Results in ganglionitis and destruction of neurons/supporting cells in the DRG and accompanying dermatome

Rash

- Reactivated virus replicates in sensory ganglion and travels to cutaneous nerves to nerve endings in the dermo-epidermal junction

- Results in the appearance of a rash (regional lymphadenopathy can also occur)

o Initially maculopapular

o Then grouped vesicles on an erythematous base

o Then can be a pustular rash with superficial crusting

- Skin may be left with hypo or hyperpigmented scarring

Pain

- Pain can precede or accompany the herpes zoster rash

- Can be accompanied by itching, paraesthesia and dysesthesia

- Constant or intermittent described as burning, throbbing, stabbing, electric shock like

- Allodynia can also be present

- Often interferes with sleep and other aspect of physical and emotional functioning

- Pain that persists beyond the phase of the rash is considered subacute herpetic neuralgia (persists >30 days) and can progress to post herpetic neuralgia (persists >120 days)

Diagnosis is often clinical but can be confirmed by swab of vesicle via PCR


Chronic Pain Presentation

Most common complication of acute infection in the immunocompetent patient.

Definition is dermatomal pain that persists for >90-120 days

- Intermittent, sharp, shooting or electric shock like pain or continuous burning/throbbing pain

- Stimulus evoked pain is also very common including tactile allodynia

- May not be able to tolerate the sensation of clothing against their skin or even tolerate breezes or air conditioning on the affected site

- Hyperalgesia can occur as well as hypoesthesia

- Alterations in temperature sensation have been demonstrated

- Chronic pruritis can also persist

Diagnosis is clinically based. Assessment of location, intensity and characteristics of pain is essential


Management

Acute Herpes Zoster

- Antiviral therapy – most benefit within 72 hours of rash onset

o Inhibits viral replication

o Reduces duration of viral shedding

o Hastens rash healing

o Decrease in degree of neural damage

o Decrease severity and duration of acute pain

o Decreases duration of postherpetic neuralgia

- Analgesic therapy – multimodal therapy

o Paracetamol

o NSAIDS provided no contraindication

o Lignocaine 5% patch – Randomised placebo controlled study showed reduced pain associated with herpes zoster

§ Should only be applied to intact skin after initial rash has completely healed

§ Excellent side effect profile

o Opioids not well studied – one small clinical trial did show that oxycodone was superior to placebo in relieving acute pain within the first 2-3 weeks of rash onset (no evaluation as to effect on PHN)

o TCA – one study showed use acutely reduces the incidence of PHN by 50% compared to placebo

§ Side effects include sedation, dry mouth, blurred vision, weight gain, urinary retention

o Gabapentinoids – efficacy in PHN demonstrated and also some efficacy in acute pain conditions so can be considered acutely

§ Sedation, dizziness, peripheral oedema

o SNRI – have evidence in painful diabetic neuropathy so could be considered a potential therapy


Post Herpetic Neuralgia

- TCA – amitryptilline

o NNT 2.1-2.6 for PHN

o Most widely studied

o Nortriptylline better tolerated but equally effective, so preferred in elderly and frail

o Helpful with sleep due to sedating properties

- Topical Lidocaine

o 5% patch NNT 4.4 to reduce allodynia with no difference in side effects compared to placebo

o Patches can be cut to fit the area, keep patches on for 12 hours on and 12 hours off, only apply on intact skin

- Gabapentin

o Two large clinical trials showed a statistically significant reduction in daily pain as well as improvements in sleep, mood, fatigue and depression

o NNT 4.4 for PHN

o Dose 1800mg-3600mg

- Pregabalin

o Comparable analgesic effect to gabapentin but more convenient dosing

- SNRI

o Duloxetine and venlafaxine studied for Diabetic and other painful neuropathies but not studied in PHN

- Tramadol

o Efficacy from one randomised control trial but yet to be replicated

o NNT 4.8 but low quality evidence

o Second line

- Capsaicin patch

o 8% patch approved for pain associated with PHN

o Low quality evidence NNT 7-8.8

- Opioids

o Reserved as third line due to side effects, tolerance and misuse

o One small trial suggested reductions in allodynia, steady pain and spontaneous paroxysmal pain



Evidence for surgical approaches or blocks are not backed up by evidence.

May be some benefit from botox injections – unsure of mechanism but three studies show a benefit.


Prevention

Herpes zoster can be prevented via vaccination to boost immunity and prevent acute infection, pain, suffering and decreased quality of life

Post herpetic neuralgia – 25mg daily of amitryptilline within 48 hrs for patients over 60 was associated with a 50% decrease in pain at 6 months



Pathophysiology



Presentation


Examination


Investigations


Treatment


Golden pearls


References / Articles / Resources

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