Download - 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
History of Presenting Illness
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
History of Presenting Illness
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
History of Presenting Illness
Visited family clinic on 24 Dec 2014 (8 days after discharge)
Gabapentin stepped up to 300 mg BD
Tramadol 50 mg QID PRN added
History of Presenting Illness
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
History of Presenting Illness
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
Physical Examination
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
Physical Examination
Cardiovascular: HS dual, no murmur, distal pulses intact, no carotid bruit
Respiratory: Chest clear
Abdomen: soft and non-tender
Physical Examination
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.
Physical Examination
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
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med. 2007 Mar 29;356(13):1338-43.
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
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
HZ: Clinical features
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
Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med. 2007 Mar 29;356(13):1338-43.
HZ: Clinical features
Herpes zoster: epidemiology, natural history, and common complications. J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S130-5.
HZ: Clinical features
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
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
HZ: Clinical features
“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
Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient. Drugs Aging. 2008;25(12):991-1006.
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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%
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
HZ: Complications
Neurologic
Postherpetic neuralgia
Bell’s palsy
Ramsay Hunt syndrome
Hearing impairment
Motor neuropathy
Aseptic meningitis
Transverse myelitis
Encephalitis
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
HZ: Complications
Ocular
Herpes zoster ophthalmicus
Keratitis, episcleritis, iritis, conjunctivitis, uveitis, acute retinal necrosis, optic neuritis, acute glaucoma
Cutaneous
Bacterial superinfection
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
HZ: Complications
Disseminated disease
Immunocompromised patient
Cutaneous
Visceral (e.g. lung, liver, brain and gastrointestinal tract)
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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
CrCl < 10 mL/min: 500 mg every 24 hours
Famciclovir 500 mg orally three times daily for 7 days
CrCl 40 – 59 mL/min: 500 mg every 12 hours
CrCl 20 – 39 mL/min: 500 mg every 24 hours
CrCl < 20 mL/min: 250 mg every 24 hours
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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.
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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
Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63.
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
Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient. Drugs Aging. 2008;25(12):991-1006.
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
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient. Drugs Aging. 2008;25(12):991-1006.
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
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
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
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
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
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
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
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
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
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
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
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
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
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
PHN: Treatment
Others
NMDA receptor antagonists
Neurolytic blocks of the sympathetic nervous system
Acupuncture
Repeated intrathecal methylprednisolone
One RCT
Results not replicated
Safety concern
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient. Drugs Aging. 2008;25(12):991-1006.
PHN: Prevention
Herpes zoster vaccine
Antivirals
Glucocorticoids
Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014 Oct 16;371(16):1526-33.
Herpes Zoster Vaccine
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).
Vaccination against Herpes Zoster and Postherpetic Neuralgia. J Infect Dis. 2008 Mar 1;197 Suppl 2:S228-36.
Herpes zoster vaccine: Efficacy
Herpes zoster (HZ) vaccine efficacy for the incidence of postherpetic
neuralgia (PHN).
Vaccination against Herpes Zoster and Postherpetic Neuralgia. J Infect Dis. 2008 Mar 1;197 Suppl 2:S228-36.
Herpes zoster vaccine: Efficacy
Herpes zoster (HZ) vaccine efficacy for the incidence of HZ.
Vaccination against Herpes Zoster and Postherpetic Neuralgia. J Infect Dis. 2008 Mar 1;197 Suppl 2:S228-36.
Herpes zoster vaccine: Efficacy
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
Vaccination against Herpes Zoster and Postherpetic Neuralgia. J Infect Dis. 2008 Mar 1;197 Suppl 2:S228-36.
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: 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.