Varicella from reading 1

Question 1

What is the main complication of herpes zoster (Shingles)?

Answer 1

Post herpetic neuralgia

Question 2

When should antiviral therapy be started?

Answer 2

72 hours of rash onset

Rapid antiviral therapy initiated within 72 h of rash onset has been shown to accelerate rash healing, reduce the duration of acute pain and, to some extent, attenuate the development and duration of PHN

Question 3

What is the incubation period of varicella zoster virus?

Answer 3

Following an incubation period of 14 to 21 days, the primary infection is varicella (chickenpox).

Question 4

Where does the virus migrate to after it has had the primary infection?

Answer 4

The virus then migrates via retrograde axonal transport to sensory ganglia, where it establishes lifelong latency.

Question 5

What is more important to preventing development of zoster?

Answer 5

Cell-mediated immunity (CMI) to VZV antigens is more important than humoral response (ie, antibody levels) in preventing the development of zoster.

Question 6

What causes a decrease in VZV specific CMI that predisposes a person to zoster?

Answer 6

Aging and immunosuppressive conditions?

Question 7

How long does the zoster rash last?

Answer 7

7 to 10 days and involves one or two adjacent dermatomes.

Question 8

What are the most common dematones affected in shingles?

Answer 8

Thoracic dermatomes are the most frequently affected, accounting for up to 50% of cases, whereas ophthalmic zoster is seen in 1% to 10% of cases

Question 9

What is the chance of a patient experiencing prodromal pain before shingles rash sets in?

Answer 9

Almost three of four patients report having prodromal pain, which can precede the rash by days to weeks and is termed zoster sine herpete.

Question 10

What are common other conditions that may be confused with Zoster rash?

Answer 10

• HSV, impetigo, scabies, folliculitis, contact dermatitis, urticaria, or drug eruption

Question 11

Which groups of patients may display atypical symptoms of zoster?

Answer 11

the rash may be atypical in immunocompromised patients due to dissemination or chronicity. A laboratory diagnostic test may be needed when atypical lesions are present or when it is unclear whether VZV or HSV is causal.

Question 12

What type of test can be done to confirm zoster?

Answer 12

Swabs and cell scrapings from the base of the lesions are used for direct fluorescent antibody staining, cell culture or polymerase chain reaction. Direct fluorescent antibody staining is rapid, with relatively good sensitivity (90%) when lesions are at the vesicular stage

Because of the lability of the virus, cell culture is not sensitive (60% to 75%) and typically takes one week to perform (3). Polymerase chain reaction, which is not available in all clinical laboratories, is the most sensitive diagnostic method to distinguish wild-type VZV from the vaccine Oka strain (3).

Question 13

What is the most frequent complication associated with zoster?

Answer 13

PAIN - three phases
1. Acute - within 30 days of rash onset
2. Subacute - 30 to 90 days
3. and PHN - significant pain that lasts longer than 90-120 days after rash

Question 14

What other complications can zoster be associated with?

Answer 14

Keratitis occurs in approximately two-thirds of patients with herpes zoster (HZ) ophthalmicus (involvement of the ophthalmic division of the trigeminal nerve).
- Ramsay Hunt syndrome
- Neurological complications - myelitis, aseptic meningitis, acute or chronic encephalitis, and cranial nerve palsies such as Bell’s palsy.
- HZ opthalmicus (AKA Granulomatous arteritis) - Presents similar to stroke ( Hemiplegia) contralateral to the original rash.
- VZV viremia - leading to cutaneous dissemination and seeding of the internal organs - lungs, liver and brain. Case fatality is 5-15%

Because complications of ophthalmic zoster can be sight threatening, patients with this condition should be immediately referred to an ophthalmologist.

Question 15

What is ramsay hunt syndrome?

Answer 15

The Ramsay Hunt syndrome refers to HZ of the facial nerve, with vesicles on the ear, palate or tongue leading to facial paresis, hearing loss and vertigo

Question 16

What is a cumulative HZ lifetime risk of HZ?

Answer 16

25%

Question 17

What is the incidence of getting zoster for those >60?

Answer 17

1/3 of patients

Question 18

What are the goals of therapy for antiviral treatment if HZ?

Answer 18

The main objectives of antiviral treatment for HZ are to reduce viral replication, duration of rash and acute pain as well as to prevent complications seen mostly in immunocompromised patients. In addition, early antiviral therapy may also attenuate development of PHN.

Question 19

what are the three antiviral agents approved for treatment HZ?

Answer 19

acyclovir with its prodrug valacyclovir and famciclovir.

Question 20

What is the MOA of the antivirals used in VZV treatment?

Answer 20

These agents are guanosine analogues that need to be first phosphorylated by the viral thymidine kinase and then by cellular kinases to their active triphosphate forms. The latter compounds inhibit viral DNA polymerase, which is essential for VZV replication.

Question 21

Why is valacyclovir and famciclovir preferred to acyclovir?

Answer 21

increased bioavailability, which allows a reduction in daily doses.

It is important to note that higher drug concentrations are required to inhibit VZV than HSV, which translates into higher doses for treatment of HZ compared with genital herpes (Table 2). Only acyclovir is available as an intravenous formulation that can be used to treat central nervous system complications (eg, encephalitis) or disseminated infections in immunocompromised patients. In general, these drugs are well tolerated and the most frequent side effects consist of nausea and headache. Dosage adjustment is required for all agents in the presence of renal insufficiency.

Question 22

What is the dosing for:
1. Acyclovir
2. Famciclovir
3. Valacyclovir

Answer 22

Question 23

What have Randomized control trials shown in terms of benefits of early antiviral therapy for VZV?

Answer 23

In immunocompetent patients, randomized trials have shown that orally administered acyclovir, valacyclovir and famciclovir can reduce the duration of viral shedding, accelerate rash healing and decrease the duration of acute pain

By inhibiting viral replication, antiviral agents could also decrease neuronal damage and, thus, alter the development of PHN if they are administered rapidly after rash onset. Indeed, the results of meta-analyses for acyclovir (27,28) and of randomized clinical trials for valacyclovir (29) and famciclovir (30,31) have confirmed the concept that early antiviral treatment (in less than 72 h of rash onset) can reduce the duration and, in some cases, the incidence of PHN. In one trial (30), famciclovir decreased the median time to cessation of pain from 119 (placebo) to 63 days. In another study (29), the median time to loss of pain was 38 days for valacyclovir compared with 51 days for acyclovir. A trial (32) that directly compared valacyclovir and famciclovir treatments found no difference in time to complete cessation of pain.

Question 24

What is first line therapy for all immunocompetent patients who consult rapidly (within 72 hours) and who fulfill any of the following criteria: 50 years of age or older; moderate or severe acute pain; moderate or severe rash, or nontruncal involvement?

Answer 24

ORAL antivirals!

Question 25

What about opthalmic zoster for treatment?

Answer 25

Because of its potential complications, ophthalmic zoster should be treated more aggressively, including referral for ophthalmological assessment and institution of antiviral therapy even beyond the 72 h recommended window period.

Question 26

What is the therapy of choice for immunocompromised patients seeing as they are at greater risk of developing disseminated and/ or recurring HZ?

Answer 26

IV acyclovir 10mg/kg every 8 hours - remains the therapy of choice for these patients. ## Footnote When the infection is under control (ie, when there are no new vesicles), therapy can be switched to an oral agent. In less severely immunocompromised patients, an option would be to initiate therapy with oral agents (especially valacyclovir or famciclovir) coupled with close monitoring. It is recommended to continue treatment until all lesions are crusted, which is often longer than the standard seven-day course

Question 27

What can clinical failure result (or recurrent HZ Lesions result in)?

Answer 27

Clinical failure or recurrent HZ lesions in immunocompromised hosts such as in patients with AIDS may be caused by acyclovir-resistant VZV strains (35). In such cases, phenotypic and/or genotypic resistance tests may be ordered, and alternative therapy with foscarnet at a dosage of 40 mg/kg intravenously every 8 h should be considered.

Question 28

How can ZAP (zoster-associated pain) be described?

Answer 28

ZAP may be described as continuous or paroxysmal, evoked or spontaneous, burning or lancinating, and is often associated with other sensory abnormalities in the skin. ## Footnote This variability implies different pain mechanisms (36). The two primary pain mechanisms are believed to be increased excitability of damaged primary afferent neurons causing irritable nociceptors and central sensitization, resulting in pain and allodynia; and degeneration of nociceptive neurons in dorsal root ganglia or the spinal cord, leading to deafferentation with central hyperactivity, causing pain but typically without allodynia (37).

Question 29

What office based tool can be used to assist clinician to assess and document the pattern of pain, severity of pain and impact on functino and quality of life?

Answer 29

Zoster brief pain inventory ## Footnote It is especially useful in providing a baseline snapshot of pain and function before therapeutic trials. All patients should have a medical and psychosocial evaluation and targeted physical examination to confirm the diagnosis, document comorbid illness and provide a basis for treatment. Elderly patients may be socially isolated, may have cognitive impairment, depression or other life stressors that may impact treatment compliance and outcome. Anxiety or depression may also develop secondary to severe ZAP and can influence suffering.

Question 30

Can ZAP get worse?

Answer 30

ZAP changes over time and can become more severe as the acute infection progresses

Question 31

Is there a single treatment that has been shown to be completely effective for all sufferers of PHN?

Answer 31

No single treatment has been shown to be completely effective for all sufferers of PHN, and clinical experience suggests that combinations of analgesic drugs are usually required to achieve even partial pain relief

Question 32

What are first, second and third line treatments for PHN?

Answer 32

Question 33

Why are TCAs considered a first line treatment?

Answer 33

Tricyclic antidepressants have well-established efficacy in the treatment of PHN (41). The results of one placebo-controlled trial (42) of amitriptyline (25 mg once daily for three months beginning within 48 h of rash onset) and a reanalysis examining the subgroup of patients also treated with an antiviral suggested that amitriptyline reduced the incidence of PHN at six months by at least 50%.

Question 34

Why are gabapentin or pregabalin first line for PHN?

Answer 34

Multiple studies have demonstrated the efficacy of gabapentin or pregabalin in patients with PHN (44). The combination of satisfactory tolerability, safety and lack of drug interactions distinguish them from other oral medications used in the treatment of neuropathic pain. One open-label study (3) reported that treatment with the combination of gabapentin and valacyclovir reduced the incidence of PHN at three and six months compared with traditional antiviral monotherapy.

Question 35

WHen are topical agents indicated?

Answer 35

Topical lidocaine patch 5%, applied twice a day on painful but intact skin, may serve as a well-tolerated and effective modality to relieve moderate to severe pain associated with acute HZ (46). For PHN, a recent Cochrane review (47) of topical therapy concluded that “there is insufficient evidence to recommend topical lidocaine as a first-line agent in the treatment of postherpetic neuralgia with allodynia”. Nonetheless, topical treatments have a lower potential for systemic adverse effects; therefore, some clinicians consider the early use of topical lidocaine or capsaicin, especially where quantitative sensory testing has indicated that the patient has ‘irritable nociceptors’ as opposed to ‘deafferentation’ pain.

Question 36

Are opioids good for acute HZ and PHN?

Answer 36

The combination of opioids with acetaminophen or nonsteroidal anti-inflammatory drugs has not been systematically studied in patients with HZ. Tramadol, a weak muopioid agonist that also inhibits the reuptake of noradrenaline and serotonin, has not been studied as a treatment for acute HZ but has shown evidence of activity in PHN (45). There is evidence from randomized controlled trials to support the use of potent opioids such as morphine and oxycodone in PHN (40).

Question 37

What does the evidence say about pts with severe pain?

Answer 37

Patients with the most severe pain may benefit from hospitalization and administration of epidural analgesics. The results of a randomized trial (49) involving patients with HZ treated with oral antiviral therapy demonstrated that a single epidural injection of steroids and local anesthetics relieved acute pain within the first month after rash onset significantly better than standard care, but did not reduce the risk of developing PHN. Continuous epidural infusion of local anesthetic with intermittent additional epidural anesthetic boluses was superior to continuous infusion of saline and intermittent anesthetic boluses in reducing the time to complete cessation of pain in patients with HZ treated with acyclovir (50). However, treatment of HZ patients with multiple epidural injections or continuous epidural infusions is unlikely to be feasible in most settings.