dr wong cheuk lun chairman: dr mak ying fai

Dr Wong Cheuk Lun

Chairman: Dr Mak Ying Fai

Interhospital Geriatrics Meeting

28 Apr 2015

A painful experience

Background

Mr Au-yeung

M / 81

NKDA

Ex smoker; ex drinker

Lives with wife and daughter in a public housing estate; lift landing flat

Walks unaided

Basic and instrumental ADL independent

Works as a hawker

Past Medical History

Chronic obstructive pulmonary disease

Hypertension

Impaired fasting glycaemia

Dyslipidaemia

Peripheral vascular disease

Benign prostatic hyperplasia

Regular follow-up at the family medicine and urology clinic

Regular Medications

Aspirin 80 mg daily

Famotidine 20 mg bd

Lisinopril 10 mg daily

Simvastatin 20 mg nocte

Terazosin 1 mg nocte

Beclomethasone 250mcg/dose 2 puff bd

Ipratropium 2 puff qid prn

Terbutaline sustained release 5 mg nocte

Theophylline sustained release 150 mg bd

Admitted 6 Dec 2014 for left sided headache. Initial workup did not point to any diagnosis.

Appearance of left scalp rash and eye pain 3 days after admission left herpes zoster ophthalmicus with blepharitis, complicated with secondary cutaneous infection Oral acyclovir 800 mg five times/day, acyclovir eye drops and

ointment for herpes zoster

Ampicillin 500 mg qid and cloxacillin 500 mg qid for secondary infection

Gabapentin 300 mg nocte for pain

Discharged on 16 Dec 2014

History of Presenting Illness

Admitted on 11 Jan 2015 for fall at home

Rushed to toilet after getting up with a strong desire to void

Slipped and fell after stepping on a slippery surface

Fell forward, on a outstretched left hand

Right forehead hit against the washing basin

Generalised weakness and malaise

No dizziness or LOC

No chest pain or palpitations


Wife and daughter came in and helped

Could get up by himself with minimal assistance

Left wrist pain +

Right eyebrow abrasion +

No headache

No hip pain


No history of fall

Not much mobilisation during previous hospital stay

Still significant pain over area affected by herpes zoster – poorly controlled

Sleep disturbed at night


Visited family clinic on 24 Dec 2014 (8 days after discharge)

Gabapentin stepped up to 300 mg BD

Tramadol 50 mg QID PRN added


Pain improved but did not go away

Seek medical advice from a private doctor on 30 Dec 2014 (6 days later)

Gabapentin further stepped up to 300 mg QID


Nausea +

Loss of appetite

Drowsy +

Reduced energy level

Immobilised

Homebound

Not going out to work anymore

Finally he had a fall which results in this admission on 11 Jan 2015

Physical Examination

Afebrile

E4V5M6

BP 140 / 74 P 78 SpO2 98% (RA)

No orthostatic blood pressure drop

No pallor, jaundice or cyanosis

Hydration just fair

Clinically euthyroid


Vision Right 6 / 24

Left 6 / 36

Bilateral conjuctivae clear

No facial rash, vesicle or cellulitis

Hearing satisfactory without aid

Minor abrasion over right eyebrow


Cardiovascular: HS dual, no murmur, distal pulses intact, no carotid bruit

Respiratory: Chest clear

Abdomen: soft and non-tender


Reduced light touch and pin-prick sensation over left V1 dermatome, bilateral cranial nerves otherwise intact

Upper limbs:

Power 5 / 5 over all muscle groups

Normal tone and reflexes

No tremor, rigidity or cogwheel rigidity

No pass-pointing or dysdiadochokinesia

Left wrist slight soft tissue swelling. Active and passive range of motion full and non-tender. No crepitus.


Lower limbs:

Power 5 / 5 over all muscle groups

Normal tone

Normal pin-prick sensation and proprioception

Romberg’s test negative

Reflexes preserved; bilateral flexor plantars response; SLR full

Gait not ataxic, stable

Hips range of motion full; non-tender on rocking or axial loading

Knees NAD

Investigations

Hb 12.7 WCC 8.4 Plt 136

MCV 87.7

Na 137 K 4.0 Ur 3.9 Cr 109

Albumin 38

LFT unremarkable

Ca 2.17 PO4 1.02

TnI < 0.03

Investigations

ECG sinus rhythm 71/min QTc 410ms no ischaemic change or conduction delay

CXR: Clear

XR left wrist, hand and scaphoid: No fracture or bony lesion seen

CT Brain: Cerebral atrophy. Small old vascular insults in both basal ganglia.

Progress

Abbreviated Mental Test (AMT) 9 / 10

Elderly Mobility Scale (EMS) 17 / 20

Barthel Index (BI) 20 / 20

Progress

Ophthalmologist assessment

No new eye complaints

No recurrence of zoster in eye

FU HKEH as scheduled

Progress

Home safety advices

Disease nature and clinical course of herpes zoster and possibility of postherpetic neuralgia explained

Gabapentin reduced to 300 mg BD. Adverse effects explained

Progress

Herpes zoster vaccine introduced

Early discharge with referral to geriatric day hospital (GDH) for symptom monitoring and rehabilitation

Summary of Problems

Herpes zoster and neuralgia

Iatrogenesis

Physical deconditioning due to hospitalisation and immobilisation

Adverse effects of medications

Fall (with left wrist and head injury)

Herpes Zoster

Varicella-zoster virus (VZV)

Human α-herpesvirus

Double-stranded, linear DNA virus encoding approximately 75 proteins

Lipid-containing envelope with glycoprotein spikes

Varicella-zoster virus (VZV)

Causes two clinically distinct forms of disease

Primary infection = chickenpox

Viraemia

Diffused rash

Seeding of multiple sensory ganglia

Lifelong latency

Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.

Herpes zoster (HZ)

= Shingles

Reactivation of latent VZV in the cranial nerve or dorsal root ganglia

Then spread along the sensory nerve to the dermatome


Herpes zoster (HZ)

Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med. 2007 Mar 29;356(13):1338-43.

HZ: Epidemiology

> 1 million cases of HZ in the United States each year

Annual rate of 3 to 4 cases per 1000 persons

Up to 3% requires hospitalization

Lifetime risk ~ 30%

> 85 years of age and unvaccinated: 50% risk of HZ



HZ: Epidemiology

Postherpetic neuralgia. J R Coll Gen Pract. 1975 Aug;25(157):571-5.

HZ: Risk factors

Increasing age

Immunosenescence – progressive decline in VZV-specific cell mediated immunity with advancing age

Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient. Drugs Aging. 2008;25(12):991-1006.

HZ: Risk factors

Immunocompromised with impaired T-cell immunity

Recipients of organ or haematopoietic stem-cell transplants

Immunosuppressive therapy

Lymphoma

Leukaemia

HIV infection

F > M

Whites > blacks


HZ: Clinical features

Prodrome

Headache, photophobia, malaise

Rarely fever

Prodromal pain

Pain, tingling or itching for 2 – 3 days before rash

Misdiagnosis and unnecessary investigations

Herpes Zoster. N Engl J Med 2002; 347:340-346



Rash Macules and papules

Vesicles and pustules

New lesions filling in the dermatome over 3 – 5 days

Dries with crusting in 7 – 10 days

Usually heals in 2 - 4 weeks

But often scarring and pigmentation changes persist



Herpes zoster: epidemiology, natural history, and common complications. J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S130-5.


Rash (cont’d) Any area of the skin can be

involved

Thoracic, trigeminal, lumbar and cervical dermatomes – most frequent sites

Non-immunocompromised hosts: limited to one dermatome

adjacent dermatomes in 20%

a few scattered lesions outside the affected dermatome



“Zoster sine herpete” – pain without rash

HZ associated pain

Constant or intermittent

Various

Sharp, stabbing, shooting, burning, throbbing, tender, boring, itching and/or hot

Allodynia – pain associated with nonpainful stimuli



HZ: Diagnosis

Clinical in most cases

Direct immunofluorescence assay for VZV antigen

Sensitivity 82%; Specificity 76%

Polymerase-chain-reaction (PCR) assay for VZV DNA

Sensitivity 95%; Specificity 100%


HZ: Complications

Neurologic

Postherpetic neuralgia

Bell’s palsy

Ramsay Hunt syndrome

Hearing impairment

Motor neuropathy

Aseptic meningitis

Transverse myelitis

Encephalitis


HZ: Complications

Ocular

Herpes zoster ophthalmicus

Keratitis, episcleritis, iritis, conjunctivitis, uveitis, acute retinal necrosis, optic neuritis, acute glaucoma

Cutaneous

Bacterial superinfection


HZ: Complications

Disseminated disease

Immunocompromised patient

Cutaneous

Visceral (e.g. lung, liver, brain and gastrointestinal tract)


HZ: Treatment

Antivirals Age ≥50 yr, moderate or severe pain, severe rash, involvement

of the face or eye, other complications of herpes zoster and immunocompromised state

Acyclovir, valacyclovir and famciclovir

Oral availability, dose frequency, cost

< 72 hours after the onset of the rash

Hasten the resolution of lesions, reduce the formation of new lesions, reduce viral shedding and decrease the severity of acute pain


HZ: Treatment

Antivirals

Acyclovir 800 mg orally five times daily for 7–10 days

CrCl 10 – 25 mL/min: 800 mg every 8 hours

CrCl < 10 mL/min: 800 mg every 12 hours

IV acyclovir for immunocompromised persons who require hospitalization and for persons with severe neurologic complications


HZ: Treatment

Antivirals (cont’d)

Valacyclovir 1 g orally three times daily for 7 days

CrCl 30 – 50 mL/min: 1 g every 12 hours

CrCl 10 – 30 mL/min: 1 g every 24 hours


Famciclovir 500 mg orally three times daily for 7 days





HZ: Treatment

Glucocorticoids

Tapering course of predisone or prednisolone

With concomitant antiviral therapy

Controversial

Modestly reduce the severity and duration of acute symptoms

Caution: hypertension, diabetes mellitus, peptic ulcer disease, osteoporosis

Herpes zoster (shingles) and postherpetic neuralgia. Mayo Clin Proc. 2009 Mar;84(3):274-80.


HZ: Treatment

Analgesics

Acetaminophen

Nonsteroidal antiinflammatory drugs (NSAIDs)

Opioides e.g. oxycodone, tramadol

Anticonvulsants e.g. gabapentin, pregabalin

Tricyclic antidepressants e.g. nortriptyline

Ligocaine patch


HZ: Prevention

Herpes zoster vaccine

Postherpetic Neuralgia

Postherpetic neuralgia (PHN)

Most frequent chronic complication of herpes zoster

Complex neuropathic pain condition

Direct consequence of the response to peripheral-nerve damage sustained during the herpes zoster attack

Dermatomal pain persisting at least 90 days after the appearance of the acute herpes zoster rash

Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.

PHN: Epidemiology

Depends on the definition used

Prevalence

500,000 - 1 million cases in the USA

100,000 to 200,000 cases in the UK

Frequency of PHN increases dramatically with age


PHN: Epidemiology

Postherpetic neuralgia. J R Coll Gen Pract. 1975 Aug;25(157):571-5.

PHN: Risk factors

Advanced age (>50 years)

Female sex

Presence of a prodrome

Severe or disseminated rash

Severe pain at presentation (visual analogue score >5)

Polymerase chain reaction detectable varicella zoster virus viraemia

Herpes zoster. BMJ. 2007 Jun 9;334(7605):1211-5.

PHN

PAIN

Spontaneous, constant, deep burning, throbbing, aching pain

Intermittent sharp, stabbing, shooting, lancinating pain

Mechanical allodynia

Mechanical hyperalgesia

Zoster Brief Pain Inventory



PHN: Impact

Loss of employment

Depression

Social isolation

Functional dependence

Medical costs

Health care burden at both the individual and societal levels

Herpes zoster. BMJ. 2007 Jun 9;334(7605):1211-5.

，，

PHN: Treatment

Lignocaine (lidocaine) patch 5%

Block voltage-dependent sodium channels

Maximum 3 patches for 12 hours / day

Numbers needed to treat (NNT) for ≥ 50% pain relief = 2 (1.4 – 3.3)

Side effects: local erythema


PHN: Treatment

Capsaicin

Active component of chili peppers

Transient receptor potential vanniloid 1 (TRPV1) agonist

Capsaicin 0.075% cream

4 applications / day

NNT = 3.3 (2.3–5.8)

Side effects: pain on application, local erythema and rash


PHN: Treatment

Capsaicin patch 8%

Application time of 30–90 min

NNT = 11.0 (6.1–62.0)

Side effects: pain on application, local erythema and rash


PHN: Treatment

Antiepileptics (gabapentin & pregabalin)

Act on the α2δ-subunit of calcium channels located on the spinal presynaptic terminals of primary afferent nociceptive neurons

FDA approved for PHN

Gabapentin: NNT = 4.4 (3.3–6.1)

Pregabalin: NNT = 4.2 (3.4–5.4)

Side effects: sedation, dizziness and peripheral edema


PHN: Treatment

Tricyclic antidepressants (amitriptyline, desipramine & nortriptyline)

Inhibit reuptake of monoaminergic transmitters, potentiating their effects in CNS pain-modulating pathways

Off-label use

NNT = 2.6 (2.1–3.5)

Side effects: sedation, dry mouth, blurred vision, weight gain and urinary retention

Avoid in cardiac disease, glaucoma or seizure disorder

Avoid concomitant use of tramadol


PHN: Treatment

Opioids (morphine & oxycodone)

Opioid μ receptor agonist

Morphine: NNT = 2.8 (2.0–4.6)

Oxycodone: NNT = 2.5 (1.7–4.4)

Convert to long-acting opioid following dose titration

Side effects: nausea, vomiting, constipation, drowsiness, dizziness, mood change and disorientation

Risk of abuse


PHN: Treatment

Tramadol

Opioid μ receptor agonist, norepinephrine and serotonin reuptake inhibitor

NNT = 4.8 (2.6–27.0)

Side effects: nausea, vomiting, constipation, drowsiness, dizziness and seizures

Avoid concomitant use of SSRIs, SSNRIs and TCAs


PHN: Treatment

Others

NMDA receptor antagonists

Neurolytic blocks of the sympathetic nervous system

Acupuncture

Repeated intrathecal methylprednisolone

One RCT

Results not replicated

Safety concern



PHN: Prevention


Antivirals

Glucocorticoids


Herpes Zoster Vaccine


Incidence and severity of HZ and PHN increases with age

≥ 50% of all recognized cases of HZ and most cases of clinically significant PHN occur in immunocompetent persons ≥ 60 years of age

Disabling, severely compromising the patient’s quality of life and capacity to carry out activities of daily living

Effects of treatment suboptimal in general

No existing intervention prevents HZ and PHN

Vaccination against Herpes Zoster and Postherpetic Neuralgia. J Infect Dis. 2008 Mar 1;197 Suppl 2:S228-36.

Herpes zoster vaccine: Zostavax®

Live, attenuated herpes zoster vaccine

Same Oka/Merck strain of VZV used in varicella vaccine (live) Varivax®

Not less than 19,400 plaque forming units (PFU)

14x potency of Varivax®

Single subcutaneous dose

Licensed in 2006

Keating GM. Drugs. 2013 Jul;73(11):1227-44. doi: 10.1007/s40265-013-0088-1.

Shingles Prevention Study (SPS)

Double-blind, placebo-controlled, multicenter trial, 22 sites

Study timeline: Nov 1998 to Apr 2004

38,546 subjects ≥60 years of age

Age-stratified (60 to 69 years, ≥70 years)

90% had one or more underlying medical conditions

Randomized 1:1 to receive live attenuated Oka/Merck VZV vaccine or placebo

Monthly follow-up by an interactive automated telephone-response system to identify HZ cases

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84.

Herpes zoster vaccine: Efficacy

Herpes zoster (HZ) vaccine efficacy for the HZ Burden of Illness (HZ BOI).



Herpes zoster (HZ) vaccine efficacy for the incidence of postherpetic

neuralgia (PHN).



Herpes zoster (HZ) vaccine efficacy for the incidence of HZ.



Reduced the incidence of HZ by 51%

Reduced the incidence of PHN by 67%

Reduced the BOI associated with HZ by 61%

In vaccinated subjects who developed HZ, pain was significantly shorter in duration and less severe


Herpes zoster vaccine: Safety

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84.

Herpes zoster vaccine: Contraindications

History of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine

Primary or acquired immunodeficiency states (e.g. acute or chronic leukaemia, lymphoma or immunosuppression associated with HIV infection or AIDS);

Patients receiving immunosuppressive therapy (including high-dose corticosteroids)

Pregnancy

Herpes zoster vaccine: Recommendations

Food and Drug Administration (FDA)

Indicated for use among adults aged ≥50 years (2011)

20% of HZ occurred in 50 – 59 years of age

Zostavax Efficacy and Safety Trial (ZEST)

Zoster vaccine reduced the incidence of herpes zoster by almost 70 % in adults aged 50–59 years

Advisory Committee on Immunization Practices (ACIP)

For adults aged ≥60 years

Keating GM. Drugs. 2013 Jul;73(11):1227-44. doi: 10.1007/s40265-013-0088-1.

Back to our patient…

Started rehabilitation in the geriatric day hospital (GDH) on 23 Jan 2015

Stable and well

Self feeding satisfactory

Walks unaided

ADL independent

Refused to come after few sessions and discharged from GDH on 4 Feb 2015

Latest condition

Seen by family medicine clinic Feb 2015 (regular FU)

Still have some shooting pain over left scalp – tolerable

Sleep well

Returned to work, coping well

Take home messages

HZ and PHN are often debilitating in the elderly, with negative impact on their quality of life, physical functioning, and psychological well-being.

Iatrogenesis is still a geriatric giant. HZ or PHN associated pain should be handled promptly to avoid immobilisation and subsequent physical deconditioning. Adverse effects of the treatment are common in older patients and ought to be watched out for.

Take home messages (cont’d)

Management of PHN is often challenging as the pain can persist for months or even years and refractory to available therapies.

Prevention is better than cure. Herpes zoster vaccination significantly reduces the incidence of both HZ and PHN for those who indicated.

This the end of my presentation.

Thank you for your kind attention.

dr wong cheuk lun chairman: dr mak ying fai

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