Download click here

3/3/2014
The Patient with Pain
All Over
“All the Pearls in 50 Minutes”
Gerald F. Falasca, M.D.
Rheumatology
Johnson City, TN
March 26, 2014
GOALS
• Become a better diagnostician.
• Diagnose undifferentiated
connective tissue disease
(UCTD) and primary Sjogren
syndrome.
• Understand treatment of UCTD,
polymyalgia, fibromyalgia, and
polymyositis.
A 70 year old woman presents with widespread pain, stiffness and fatigue. She recently started keeping a water bottle at her bedside. Physical exam is remarkable for slight synovitis of hands & wrists, and presence of all fibromyalgia tender points. Lab data is notable for sed rate of 30 mm/hr but normal CRP at 0.7 mg/dl (nl 0 ‐ 1.0 mg/dl), elevated C4 at 36 mg/dl. RF, CCP & ANA are negative. What is the most likely diagnosis?
1
3/3/2014
A. Paraneoplastic syndrome
B. Polymyalgia rheumatica C.
Rheumatoid arthritis
D. Fibromyalgia
E.
Primary Sjogren syndrome
CONDITIONS ASSOC. WITH
WIDESPREAD PAIN
– Fibromyalgia
– Influenza
– Depression
– Hypothyroidism
– Anxiety
– Hepatitis C
– Drugs (statins, fibrates)
– Hyperparathyroidism
– Drug seeking behavior
– Ankylosing spondylitis
– Sjogren’s / UCTD
– Lyme disease
– Rheumatoid arthritis
– Sarcoidosis
– SLE
– Polymyalgia rheumatica
– Hypermobility
– Osteomalacia (<10 ng/ml)
– Peripheral neuropathy
– Bone marrow abnormalities
CONDITIONS ASSOC. WITH
WIDESPREAD PAIN
• Fibromyalgia
• Drugs (statins,
bisphosphonates, aromatase
inhibitors)
• Sjogren’s / UCTD / SLE
• Polymyalgia rheumatica
• Hypermobility
• Ankylosing spondylitis
• Osteomalacia
2
3/3/2014
Primary Sjogren’s
•
•
•
•
Fatigue
Pain all over
Sicca
Many persons with Sjogren’s
fulfill criteria for fibromyalgia.
Iannuccelli C et al. Fatigue and widespread pain in systemic lupus erythematosus and Sjögren's syndrome: symptoms of the inflammatory disease or associated fibromyalgia? Clin Exp Rheumatol. 2012 Nov‐Dec;30(6 Suppl 74):117‐21
What’s in a name??
• Sjogren’s (primary) vs.
undifferentiated connective tissue
disease
– Sometimes hard to distinguish initially
– Both can be associated with
widespread pain.
– As is SLE.
What Are the Clues?
•
•
•
•
•
•
•
•
Sicca symptoms
Acrocyanosis
Raynaud’s
Family history
Puffy hands
Peripheral arthralgias
Photosensitivity
Alopecia
3
3/3/2014
Sjogren’s - History
• Use of eye drops?
• Can you eat crackers w/o water?
• Keep water on night table?
• Physical Exam: Nothing specific!
– Sometimes small joint puffiness
– Peripheral neuropathy
4
3/3/2014
Sjogren’s - Diagnosis
• You Can Diagnose Dry Eyes and
Dry Mouth in Your Office!
• Phenol Red Thread Test
– Zone-Quick™
• Saxon Test of Salivary Flow
Phenol Red Thread Test
(Zone-Quick™)
• Alternative to the Schirmer test
• Takes 15 seconds; convenient
screening test
• A test for dry eyes (not a direct test
for Sjogren’s!)
I De Monchy et al. Combination of the Schirmer I and phenol red thread tests as a rescue strategy for diagnosis of ocular dryness associated with Sjögren's syndrome. Invest Ophthalmol Vis Sci. 2011 Jul 15;52(8):5167‐73.
5
3/3/2014
Saxon Test of Salivary Flow
• Takes 2 minutes
• Requires a scale that can measure
to 0.1 gram (costs $100).
• Uses 4” x 4” medical gauze sponge.
Kohler PF, Winter ME. A Quantitative Test for Xerostomia: The Saxon Test, an Oral Equivalent of the Schirmer Test. Arthritis Rheum. 28(10) 1128‐32, 1985. 6
3/3/2014
Saxon Test
• Weigh the gauze in the cup
• Patient chews gauze for 2 min.
• Weigh gauze again in cup.
Saxon Test
• Most persons produce about 4g of
saliva in 2 minutes.
• Abnormal if < 2.75 g in 2 minutes.
• Should D/C anticholinergic meds
day before to avoid false positive.
• Anxiety may also give false positive.
7
3/3/2014
Sjogren’s / UCTD - Lab
•
•
•
•
•
•
•
•
•
SSA / SSB – insensitive!
ESR often up – a little!
ANA – speckled or negative
CRP high normal (0.7 to 0.9 mg/dl)
Check RNP antibody
Check ACE level
Check ANCA
Check SPEP
Check C4 (may be high or low!)
HIGH ACE LEVELS
•
•
•
•
•
•
•
Sarcoidosis
NIDDM
Hyperthyroidism
Renal disease
Cirrhosis
TB
Gaucher
•
•
•
•
•
•
Sjogren’s
Histoplasmosis ?
Berrylosis
Leprosy
Amyloidosis
Silicosis
Sjogren’s – Systemic Tx*
•
•
•
•
•
Hydroxychloroquine
Low-dose prednisone
Methotrexate
Cyclosporine
Fibromyalgia treatments (for
symptoms)
*None of these is FDA approved for systemic Sjogren’s
8
3/3/2014
Polymyalgia Rheumatica
•
•
•
•
•
•
•
•
Pain all over; sudden onset.
Age > 50 (usually >70!)
Weight loss
Shoulder limitation of motion
(periarthritis)
Proximal muscle tenderness
Sed rate > 50 mm/hr
Anemia
Prompt response to low dose prednisone
Polymyalgia Rheumatica
• 10-15% progress to giant cell
arteritis.
• Responds well to treatment.
• This is a potentially serious disease
that is treatable.
From onmyfrontporch.com
9
3/3/2014
PMR – More Features
• Bilateral shoulder limitation of
motion
• Synovitis (large > small joint)
• Bilateral carpal tunnel synd.
• Profound AM stiffness, gelling
• Strength is normal (just painful).
• Proximal muscle tenderness is
different from FM tender points.
PMR – DDx
(Pain, Stiffness +/- High ESR)
•
•
•
•
•
•
Fibromyalgia
Polymyositis
Rheumatoid arthritis
Lupus
Hypothyroidism
Malignancy
PMR or GCA - Lab Features
• High ESR > 40 mm/hr, often 100.
– Occasionally normal!
• Elevated CRP.
• Anemia, sometimes < 10g/dl.
• High alk phos (1/3 patients), sometimes
ALT, AST.
• Low albumin.
• High globulins (polyclonal)
• CK, ANA, RF normal!
10
3/3/2014
PMR – When to Biopsy?
• 15-20% of PMR patients have GCA.
• PMR + Headache = Biopsy.
• PMR + Any other symptom of
temporal arteritis = biopsy.
• ESR/CRP not normalizing on low
dose pred. (3-4 weeks)
PMR - Treatment
• Prednisone 15-20 mg/d
• Dramatic response (1-2 days)
• Try tapering by 2.5 mg/mo till 10 mg/d,
then more slowly (by 1 mg/mo).
• Follow ESR, CRP monthly. Check BMP,
CBC occasionally.
• Inform patient symptoms of GCA to
report immediately.
PREDNISONE in ELDERLY
•
•
•
•
•
Calcium + Vit D
DEXA
T/C bisphosphonate
Eye exams: cataracts & pressure
↓K, ↑glucose
11
3/3/2014
Amer. College of Rheum.
• Recommendations for the
Prevention and Treatment of
Glucocorticoid-Induced
Osteoporosis 2010
• Arthritis Care & Research, Vol. 62,
No. 11, November 2010, pp 1515–
1526
• DOI 10.1002/acr.20295
PMR - Course
• Many patients don’t follow textbook.
• Many patients require chronic
steroids (2-5 mg/d).
• May progress to GCA, even 5 years
later.
• Relapses occur. ESR may be
normal with relapses.
WIDESPREAD NIGHT PAIN
•
•
•
•
•
PMR
Peripheral neuropathy
Fibromyalgia
Depression
Malignancy (HPO)
12
3/3/2014
CHRONIC INFLAMMATION
The Telltale Signs
• Anemia, normocytic or
slightly microcytic
• High platelets
• Low albumin
• High globulin
Statin Myopathy
• Dose related
• Risk lowest with pravastatin,
fluvastatin, rosuvastatin.
Graham DJ et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid‐lowering drugs. JAMA. 2004;292(21):2585.
Ridker PM et al. Rosuvastatin to prevent vascular events in men and women with elevated C‐reactive protein. N Engl J Med. 2008;359(21):2195
Statin Myopathy Risk Factors
•
•
•
•
•
•
Hypothyroidism
Renal insufficiency
ALS
Congenital myopathies
SLCO1B1*5 variant
Interacting drugs
Vladutiu GD. Genetic predisposition to statin myopathy. Curr Opin Rheumatol. 2008;20(6):648.
13
3/3/2014
Statin Myopathy Syndromes
•
•
•
•
Myalgias
CK elevation, asymptomatic
Myositis, rhabdomyolysis
Persistent autoimmune myopathy
Mohassel P et al. The spectrum of statin myopathy. Curr Opin Rheumatol. 2013 Nov;25(6):747‐52
Thompson PD et al. Statin‐associated myopathy. JAMA. 2003;289(13):1681.
WHAT IS FIBROMYALGIA?
• A syndrome of widespread pain
and fatigue associated with
multiple tender points and nonrestorative sleep.
• More than 3 months
• Normal blood tests
MAJOR SYMPTOMS
•
•
•
•
“Non-restorative” sleep
Chronic fatigue
Ache all over
Presence of “tender points” (1990
criteria)
14
3/3/2014
OTHER SYMPTOMS
• Fatigue
• Sleep Disturbance
• Headaches
(migraine or tension)
• GI symptoms (IBS)
• Irritable bladder
• Panic attacks (20%)
• Vasospasm (40%)
•
•
•
•
•
Dysmenorrhea
Dry mouth
Poor memory
TMJ
Subjective
swelling
The Common Associates
of Fibromyalgia
•
•
•
•
Migraine headaches
Irritable bowel
Irritable bladder
Panic attacks
Who gets FMS?
•
•
•
•
Up to 2% of population.
Most common in middle-aged women
8-9 females to 1 male approx.
Patients with RA, SLE and ankylosing
spondylitis often meet criteria.
• Tends to run in families.
15
3/3/2014
TRIGGERS OF FLARES
The Usual Culprits
•
•
•
•
•
Unaccustomed exertion
Anxiety or emotional stress
Inadequate or unrestful sleep
Cold exposure, changes in weather
Soft tissue injuries
FMS – THE ACR CRITERIA
American College of Rheumatology 1990
(There are also 2010 criteria pending)
• Widespread pain, 3 months duration
• Above and below waist; bilateral
• Axial pain (shoulders, back, chest)
– 10 of 18 tender points
• "Painful," not just "tender"
• 4 kg force (9 lb.) needed
• Wolfe F, Smythe HA: Arthritis Rheum 33:160, 1990
Pathogenesis
16
3/3/2014
THE CONTROL POINTS
– Distal, dorsal third of forearm
– Midfoot, dorsal 3rd metatarsal
– Dorsal, 3rd metacarpal
– Thumbnail
– Forehead
Mimics of Fibromyalgia
•
•
•
•
•
•
Sjogren’s, RA, SLE
Spondyloarthropathy
Polymyalgia rheumatica
Myositis (statin myopathy)
Hypothyroidism
Depression
PREDISPOSED PERSONALITY
TRAITS
•
•
•
•
•
•
•
Reliable, hardworking
Attention to detail, tries to please
People-oriented, sensitive
Internalizes conflict & stress
Slightly higher anxiety level
Difficulty learning to relax
Occupation: elementary school
teacher
17
3/3/2014
Clues that Fibro May Be Due to a
Connective Tissue Disease
•
•
•
•
•
•
•
Acrocyanosis or True Raynaud’s
Dry eyes and mouth
Hand involvement
Family history of autoimmunity
Low C4
Elevated C4
Positive ANA, high ESR
A DIAGNOSTIC CHALLENGE
• More lab evaluations
• More imaging studies
• More surgery (back, neck,
abdominal, gynecologic.)
THE BASIC LAB EVAL.
– CBC
– Comp. metabolic panel
– ANA
– TSH
– ESR, CRP
– CK
18
3/3/2014
THE COMPLETE LAB EVAL.
• CBC
• CMP
• ANA*
• ESR, CRP
• SSA/SSB
•
•
•
•
•
•
TSH
C3, C4, C2
ACE level
SPEP
ANCA*
25 OHD
• RNP
• CK
*If positive, then follow up with subtyping.
Pathogenesis
•
•
•
•
•
•
Genetics
Altered pain processing
Sleep disturbance
Neurohumoral perturbation
Autonomic abnormalities
Immunologic abnormalities
NEUROENDOCRINE
ABNORMALITIES
•
•
•
•
•
Reduced 24 hour free cortisol
Heart rate fluctuations, orthostasis
Blunted pituitary response
Impaired growth hormone secretion
Low IGF-1 levels
19
3/3/2014
• FMS is associated with chronic low
back pain (CLBP).
• 19% of pts with CLBP have FM
tender points
Weiner, DK. J Am Geriatr Soc. 2006 Jan;54(1):11-20.
Does Fibromyalgia Predispose to
a Poorer Surgical Outcome?
A cause of prolonged
post-op recovery in
many studies.
.
TREATMENT PRINCIPLES
FOR FMS
– Patient education
– Improve sleep hygiene
– Aerobic exercise
– Medications
– Possibly treat anxiety, depression
20
3/3/2014
TREATMENT - 1
• Reassurance:
– Not life threatening
– Not crippling
– Can be lived-with
TREATMENT - 2
• IMPROVE SLEEP HYGIENE
– Get enough sleep.
– Don’t take your troubles to
bed.
– Avoid caffeine, nicotine,
alcohol (late in day)
21
3/3/2014
TREATMENT - 3
• PHARMACOLOGIC (FDA
Approved)
– Duloxetine (Cymbalta®)
– Milnacipran (Savella®)
– Pregabalin (Lyrica®)
Duloxetine
ClinicalTrial
TREATMENT - 4
• PHARMACOLOGIC
– Amitriptyline
– Cyclobenzaprine
– Gabapentin
22
3/3/2014
POLYMYOSITIS
– Weakness is the key, not pain
• Stairs, combing hair, getting out of car
– Waddling gait
– May have arthralgias, myalgias
– CK, ESR may be normal in 10%!
23
3/3/2014
A 70 year old woman presents with widespread pain, stiffness and fatigue. She recently started keeping a water bottle at her bedside. Physical exam is remarkable for slight synovitis of hands & wrists, and presence of all fibromyalgia tender points. Lab data is notable for sed rate of 30 mm/hr but normal CRP at 0.7 mg/dl (nl 0 ‐ 1.0 mg/dl), elevated C4 at 36 mg/dl. RF, CCP & ANA are negative. What is the most likely diagnosis?
A. Paraneoplastic syndrome
B. Polymyalgia rheumatica C.
Rheumatoid arthritis
D. Fibromyalgia
E.
Primary Sjogren syndrome
E.Primary Sjogren syndrome
• Sicca
• Synovitis
• Elevated C4, elevated ESR, high normal CRP.
24
3/3/2014
25