PMR & GCA
Polymyalgia Rheumatica (PMR)
Giant-Cell Arteritis (GCA) which is also called:
Temporal Arteritis (TA)
Janet Pope
Professor of Medicine
Division of Rheumatology
University of Western Ontario
Objectives
1. Define polymyalgia rheumatica (PMR) & giant
cell arteritis or temporal arteritis (GCA or TA).
2. Describe the underlying pathophysiology of
PMR and GCS.
3. Discuss risk factors, clinical features and
treatment.
4. Discuss the prognosis of PMR & GCA
Polymyalgia Rheumatica
• Poly = many
• Myalgia = sore muscles
• Rheumatica = something to do with
rheumatism
Case
• 70 year old woman, previously healthy
• She has an active lifestyle and is taking only a
multivitamin
• January – she began to notice pain and stiffness
in her shoulders
• She was told it was just “old age” by her family
doctor and a friend told her it was probably
“rheumatism” caused by the cold weather
• By February the pain and stiffness had become
worse
Case
• The pain and stiffness was around her
hips and low back and into her shoulders
and neck
• She complained of fatigue which was new
• She was very stiff in the morning taking
hours if not all day to get going
• She had lost her appetite and lost 4Kg
• What else do you want to know or ask?
Ask PMR patient about
• Temporal arteritis symptoms
– HA, scalp tenderness, visual problems, jaw
claudication, tongue pain, weight loss, fever
Fracture history
Diabetes
Other medical problems
Case
• She was worried that she had cancer or
something dreadful
• In March she went back to see you
Case 1 – P/E
• Afebrile, HR 88, BP 160/70, in NAD
• General exam – normal
• MSK exam normal ROM of joints,
– no swelling, pain on ROM of hips and
shoulders
• What investigations would you do?
Case
•
•
•
•
CBC, ESR (CRP maybe)
TSH
Glucose
Creatinine, liver enzymes, (maybe: lytes,
CK)
• Maybe RF, ANA
Labs
•
•
•
•
•
•
•
WBC 6.4
Hbg 103
Plt 489
ESR 73
CRP 65
RF and ANA were both negative
Normal serum protein electrophoresis
What is the most likely
diagnosis?
PMR
• Older woman (> 50, often far older)
– Increases with age
– It does not occur in the young
•
•
•
•
•
•
Pain & stiffness in the hips and shoulders
Profound morning stiffness
Insidious onset (half are sudden onset)
Associated Fatigue
Weight Loss in less than half
Inflammatory Markers (ESR, CRP, could
also have anemia, thrombocytosis)
Polymyalgia Rheumatica
Polymyalgia Rheumatica
• There is NOTHING wrong with the
muscles
• Proximal achiness is from the joints
• We see inflammation of joints and periarticular structures such as bursae
• PMR is a history of shoulder and hip girdle
symmetrical stiffness, no findings usually
on exam and a high ESR
How would you treat her?
• Write the prescription
Polymyalgia Rheumatica
• It is Exquisitively Sensitive to
Corticosteroids like prednisone
Case
• 15 or 20 mg of prednisone per day
• Report back in a couple of days
• There should be nearly 100% improvement in
72 hours or less
• In 12 hours she felt almost completely normal
and couldn’t believe it
• How long do we usually need to treat it?
Duration of Treatment for PMR
• Usual treatment (median) is 2 years
• Decrease prednisone to lowest dose that
controls the symptoms
• Do we need to follow the ESR?
• What other treatment may you want to
add?
PMR: Initial Treatment
• Prednisone 15-20 mg per day
• The patient must be virtually back to
normal of you don’t have the correct
diagnosis
• Slowly wean down the steroids (example
after a few weeks) and keep decreasing
as symptoms are controlled
• Often after 10 mg, patients need to
reduce more slowly (ex 1mg every month
or two)
PMR: Steroid Weaning
•
•
•
•
•
Prednisone 15 mg x 1 month
Prednisone 12.5 mg x 1 month
Prednisone 10 mg x 1 month
Below 10 mg I reduce by 1 mg per month
TOTAL: 16 – 18 months
Prevention of corticosteroid
induced OP
• Steroids can “thin” the bones and anyone
you expect to take >7.5 mg of prednisone
for >3 months should be protected
• Calcium: 1500 mg calcium per day
• Vitamin D: 1000 to 3000 IU per day
• Bisphosphonate
• Likely order a baseline BMD if one has not
been done over the last couple of years
Prognosis of PMR
• Average duration of corticosteroid use is
about 2 years
• A sub-group of patients will require lowdose prednisone for much longer
• Occasionally Rheumatoid arthritis can
present very much like PMR
• If we can’t reduce prednisone or if patient
has DM or severe OP, then Mtx can be
used as a steroid sparing drug
• How often is PMR of sudden onset?
• What proportion of PMR develops GCA?
• What would you warn her about?
• How often is PMR of sudden onset?
– 50%
• What proportion of PMR develops
GCA?
– 10%
• What would you warn her about?
– Visual changes – decreased colour
vision, missing part of visual field, TIA
– Get seen ASAP if this occurs
– Side effects of prednisone
Case 2
•
•
•
•
77 year old woman
HTN on HCT
Borderline hyperlipidemia, treated by diet
Hysterectomy at age 45 for
metromenorrhagia
Case 2
• She noticed the onset of right sided
headaches, new and constant like a
vice grip over her entire head
• These were associated with pain
over the temple and it actually hurt to
brush her hair
Case 2
• She also was quite fatigued and had
noticed low grade fevers
• No visual symptoms (i.e. loss of
vision) or no symptoms of stroke
(cerebrovascular accident)
• No PMR symptoms
Case 2
• What is the most likely diagnosis?
• How do you treat immediately?
• What investigations would you do?
Case 2
•
•
•
•
Prednisone 50 to 60 mg per day
Started on low dose ASA
Sent immediately to the lab
To return to the office the next day for
preliminary results
• What would you order?
Case 2: labs
•
•
•
•
Complete Blood Count (CBC)
Erythrocyte Sedimentation Rate (ESR)
C-Reactive Protein (CRP)
Glucose, creatinine, AST, ALT
Case 2: labs
•
•
•
•
•
Hbg 99
WBC normal
Platelets normal
ESR 130 mm/hr
CRP 120
The Next Day
• The patient is feeling a bit better
• She is referred urgently to a rheumatologist (you
phone and ask for apt ASAP) or general
medicine
• What else should be done?
Temporal artery biopsy
Treatment
• High dose steroids until ESR normalizes
• Ischemic pain may take a long time to improve
• There is a risk of visual loss or stroke so taper is usually
according to the inflammatory markers
• ASA especially is visual changes
• Prevention of ulcer (PPI) with ASA
• Rx or prevention of OP with bisphoshonate
• Steroid sparing drugs
– There are data with Mtx to reduce overall amount of prednisone
needed
• Treatment is often for 1.5 to 3 years but in some it may
last forever
• 50% of GCA have PMR, but10% of PMR have GCA
Temporal (Giant-Cell) Arteritis
• Chronic granulomatous vasculitis affecting
large arteries in older people
• Most are >60 years of age (average 72)
• Inflammation of the walls of large arteries
– Cranial arteritis (most common): Temporal,
occipital, ophthalmic
– Subclavian, iliac/femoral
– Aorta
Temporal (Giant-Cell) Arteritis
• Physical Examination
– Very tender over temples (common)
– Swollen, rope like temporal artery (rare)
– Optic disc swelling due to ischemia
Temporal (Giant-Cell) Arteritis
Vision Loss
Vision Loss
• Transient repeated episodes of diminished
vision are usually reversible.
• Sudden loss of vision is an ominous sign
and is almost always permanent.
•
• If loss of vision in one eye, patient has a
high risk of losing vision in other eye
• EMERGENCY: give iv 100mg solumedrol
and make sure pt is taking ASA
Temporal (Giant-Cell) Arteritis
• Investigations
– Complete Blood Count (CBC)
• Normochromic, normocytic anemia
• Reactive thrombocytosis
• WBC is usually normal
– Erythrocyte Sedimentation Rate (ESR)
• Significantly elevated
– C-Reactive Protein (CRP)
• Significantly elevated
Temporal Artery Biopsy
Temporal Artery Biopsy
Inflammation
Multi-Nucleated
Giant Cell
GCA pathology
• There is a ring of granulomanous inflammation
centered around the elastic lamellae within and
bounding the media.
• Disruption of internal elastic lamina
• multinucleated giant cells
• intimal thickening and fibrosis as well as the
central acute thrombus.
• nonspecific inflammatory infiltrate in the
adventitia
• Fibrinoid necrosis
Disruption of internal elastic
lamina
GCA biopsy
• If you treat prior to biopsy, what would be
the chance of having a positive biopsy in
one week,
• How about in one month?
• What does the classic biopsy show?
GCA biopsy
• If you treat prior to biopsy, what would be the
chance of having a positive biopsy in one week,
highly likely
• How about in one month? Still can be positive
but partially healed, try not to wait more than 2
weeks but do not with hold treatment if suspicion
is high (40% + when Rx with pred for >1 month
• What does the classic biopsy show?
• Disruption of internal elastic lamina,
inflammation, maybe giant cells
GCA: Initial Treatment
• Prednisone 50-60 mg per day (1mg/kg/d)
• I start at 50-60 mg per day and hold on
that dose until
– The patient is feeling well
– The inflammatory markers have normalized
• I then begin to slowly wean down the
steroids (usually after a month or two)
GCA: Steroid Weaning
• Prednisone 50 mg x 1-2 month
• Then reduce by 5 mg every 2 weeks until
@ 20 mg (3 months)
• Then reduce by 2.5 mg every 4 weeks
until at 10 mg (4 months)
• Then reduce by 1 mg every month (10
months)
• TOTAL: 18+ months
Prognosis of GCA
• Average duration of corticosteroids is 2.4
years
• A sub-group of patients who will have
smoldering disease activity for much
longer (7-10 years)
• Thoracic aneurysms can appear up to 15
years after initial diagnosis
Prognosis of GCA
• Most significant complications include:
– Visual loss
– Cerebrovascular accident (stroke)
• Mortality is due to vascular complications
relating to inflammation
• What should you ask if you suspect GCA?
Case 2 - GCA
• PMR, other neurologic symptoms, duration
of visual change, location of HA, jaw
claudication, weight loss, fever, scalp
tenderness, illness prior
• Other health issues: CAD, HTN, smoking,
etc
Mortality in GCA
• Is mortality increased?
• What proportion of GCA has PMR?
• Is there a role for a steroid sparing drug in
the treatment?
• What would you follow?
• How long is the median treatment of PMR
and or GCA?
• Is mortality increased? yes
• What proportion of GCA has PMR?
50%
• Is there a role for a steroid sparing
drug in the treatment? maybe
• What would you follow? ESR
• How long is the median treatment of
PMR and or GCA?
2+ years with a wide range
Seasonal Variation of GCA
• Chart review of GCA (bx proven and or met
ACR criteria) between 1980-2004, N=206
• Peaks in May – June in Jerusalem
• 3 peaks over 20 yrs but no increase in
incidence
• 1.4 women to 1 man
• 11.3 per 100,000 incidence over 25 years
• Seasonal changes and ocassional peaks
suggest an infectious or other environmental
agent but none identified
Breuer #1927
GCA
•
•
•
•
•
•
•
•
•
•
Jaw claudication
Scalp tenderness
Anemia
Fever
Weight loss
Visual change
Swollen temporal arteries
Pulseless temporal arteries
Tender temporal arteries
A positive biopsy
GCA
•
•
•
•
•
•
•
•
•
•
Jaw claudication - uncommon
Scalp tenderness - common
Anemia - common
Fever – 25%
Weight loss – 25%
Visual change – less than 10%
Swollen temporal arteries – totally rare
Pulseless temporal arteries - uncommon
Tender temporal arteries - common
A positive biopsy – depends on bx size and time after
treatment – 75%
Conclusions
• PMR is common and patients should be
virtually 100% better at most 72 hrs after
starting prednisone (ex 15mg a day)
• Usual treatment is for a couple of years
• Use the lowest dose possible to control
symptoms
• Temporal arteritis is an emergency
• Usually referral to a specialist after starting
prednisone 50mg a day and ASA if
diagnosis is strongly suspected