 Disclosure:
none
 Objective:
◦ To use a case-based approached to
discuss wise use of laboratory tests in
rheumatic diseases
 Methods—Accenting
…
 Choosing Wisely, Cases, and
Differential Diagnosis
2

Published simultaneously in 2002 in Annals of Internal
Medicine, The Lancet and the European Journal of
Internal Medicine

Charter articulated 3 principles
1.
Primacy of the patient
2.
Autonomy of the patient
3.
Social justice
◦
Includes aspiring to be good stewards of society’s resources
1.
2.
3.
Don’t test ANA sub-serologies without a
positive ANA and clinical suspicion of
immune-mediated disease.
Don’t test for Lyme disease as a cause of
musculoskeletal symptoms without an
exposure history and appropriate exam
findings
Don’t perform MRI of peripheral joints to
routinely monitor inflammatory arthritis
4.
5.
Don’t prescribe biologics for rheumatoid
arthritis before a trial of methotrexate (or
other conventional non-biologic DMARDs)
Don’t routinely repeat DXA scans more
often than once every two years
1.
2.
Don’t do imaging for low back pain within
the first 6 weeks, unless red flags are
present
Don’t use DEXA screening for osteoporosis
in women < 65 or men < 70 with no risk
factors.
CC: 42 y.o. man with acute LBP
HPI: Moved office 48 hrs ago
Awoke with acute LBP; worse with activity,
better with rest. Naprosyn helps some.
ROS: No fever, weakness, bowel/bladder sxs
PMH: negative
Examination: VS normal; tenderness LB; neuro
exam (-)
What tests should you order?
7

Possible fracture
◦
◦
◦
◦

Major trauma, minor trauma > age 50
Long-term corticosteroid use
Osteoporosis
Age > 70
Possible Tumor or Infection
◦ Age > 50, < 20
◦ History of cancer, injection drug use,recent bacterial
infection, constitutional symptoms, immunosuppression
◦ Pain when supine or at night
8
CC: 78 y.o woman with headache
HPI: 2 months fatigue, malaise, 5 lb weight loss
1 month of intermittent dull headache
PMH: hypertension, osteoarthritis
ROS: occasional jaw pain
Medications: HCTZ, acetaminophen
PE: 36.8 145/83 84 pale
Labs: Hct 32, WBC 6,700 Platelets 532k CMP-nl
ESR 105
9




Ancient
Methods: Westergren, Wintrobe
Inexpensive
Uses:
◦ Not diagnostic of any disease
◦ Supports diagnosis of GCA, PMR, Osteomyelitis
◦ Helpful in monitoring (GCA, PMR, RA, Osteomyelitis)
10
Influenced by concentration of [asymmetric
particles] = fibrinogen


Requires fresh sample

Normal values <20 mm
◦
But affected by age (5/decade), gender, hematocrit,
red cell morphology, many plasma proteins,
medications (heparin)
12
Symptom
(+) LR
(-) LR
Jaw claudication
4.2 (2.8-6.2)
0.72 (.57-.81)
Diplopia
Beaded TA
Any TA abnl
ESR abnl
3.4 (1.3-8.6)
4.6 (1.1-18.4)
2.0 (1.4-3)
1.1 (1-1.2)
0.95 (.91-.99)
0.93 (.88-.99)
0.53 (.38-.75)
0.2 (.08-.51)
JAMA 2002;101:287-292
N
Total GCA patients
(1950-1998)
167
# with ESR < 50
mm/hr
18 (11%)
# with ESR < 40
mm/hr
9 (5%)
1.
Can the ESR be normal in GCA?
Yes
2.
Does a ESR > 100 have special significance?
Maybe
3.
In an older person with >100 ESR and no
obvious disease other than GCA, what else
should I consider?
Multiple Myeloma
15
1. What gives false positives?
Pregnancy, multiple myeloma, oral
contraceptives, MGUS
2. What gives false negatives?
Polymyositis. Cryoglobulinemia,
congestive heart failure
16
1. Can the ESR be used as a screening test to
determine if a patient with vague symptoms is
sick?
Not known!
Only 31% of patients with gastric cancer have ESR
> 20
2. What’s the maximum ESR a person can have?
200 – (2 x Hct)
3. Is CRP better than ESR?
17
CC: 19 y.o. AA woman polyarthralgia, fever
HPI: 5 wks polyarthralgia, fever, malar rash, pleuritic
chest pain, nocturia, ankle swelling
FH: Mother had SLE
PMH: negative
Meds: ibuprofen
PE: T=37.9, malar erythema, alopecia, edema
Labs: Hct 32, WBC 2.7 Platelets 110k Creatinine 1.2
Albumin 3.2, Urine 3+ protein, RBC casts, BC/RPR What autoantibodies should you order?
18
What is a positive ANA?
1-10% of well people have ANA >1:80
20 of “sick” people have ANA>1:80
What is value of ANA?
negative ANA excludes SLE; no value monitoring
What autoantibodies are specific for SLE?
ds-DNA antibodies 99% specific; sensitivity 50%
anti-SM specific (95%); sensitivity 30%
low Complement: specificity ~90%, sensitivity 50%
19
Disorder
% (+) ANA
SLE
99
RA
30-50
Fibromyalgia
20
Multiple Sclerosis
20
Thyroid disease
40
20
CC: 24 y.o. woman with polyarthritis
HPI: 5 wks polyarthritis mcps, pips, wrists, knees
2 hrs morning stiffness; fatigue
ROS: (-) fever, weight loss, rash, weakness, chest
pain, back pain, travel, tick exposure, neuropathy
FH: negative
Meds: naproxen
PE: polyarthritis; no nodules
Labs: Hct 35, ESR 58, CMP/UA negative
What autoantibodies should you order?
21
TEST
Sensitivity
RF
40-90%
40-90%
70-80%
85-95%
Anti-CCP
Specificity
RF = rheumatoid factor
Anti-CCP = anti-cyclic citrillinated peptide
22




Is a 26 year old day care worker with faint,
diffuse rash?
Is a 55 year old smoker with new clubbing?
Is a 49 year old with large joint arthritis and
red eye?
Is 34 year injection drug user with recurrent
purpura?
23
CC: 46 yo man oligoarthralgia, nasal stuffiness
HPI: 3 months oligoarthralgia knees, shoulders
nasal stuffiness, crusting, bleeding
red eye, cough, fever, hearing loss left ear
PMH: negative
SH: no cocaine
PE: scleritis, nasal crusting, otitis media, no joint
effusion
Labs: Hct 41, WBC 11k, Creatinine 1.6, urine 10-15
RBC’s; Chest CT: multiple nodules
What autoantibodies should you order?
24
Pattern
C-ANCA
P-ANCA
Antigen
proteinase-3
myeloperoxidase
Disease
GPA
MPA*
Churg-Strauss
Drug-induced
GPA= granulomatosis with polyangiitis
*MPA = microscopic polyangiitis




Choosing wisely is part of professionalism
Avoid ordering imaging for acute LBP unless
red flags are present
Most blood tests in rheumatology should be
ordered when the probability of disease is
intermediate
Don’t test ANA sub-serologies without a
positive ANA and clinical suspicion
29
< 1 mg/dl
Normal
Pregnancy
Depression
Obesity
Gingivitis
1-10 mg/dl
MI
CTD
>10 mg/dl
bacterial INF
vasculitis
30

Do IF first; confirm result with ELISA

C-ANCA = anti-PR3 = GPA

P-ANCA = anti-MPO = GPA, MPA etc

“Atypical” ANCA = anti-Lactoferin, etc = IBD

Cocaine, levamisole can cause vasculitis with
positive C-ANCA, P-ANCA
31




C-Reactive Protein (CRP) is an acute phase
protein whose concentration reflects level of
inflammation
Unaffected by age (?), gender, monoclonal
antibodies; fresh sample not required
Quantification is precise; wide range of
clinically relevant values
May be more sensitive than ESR in GCA, PMR
33
Disease
GPA
MPA
Sensitivity
70-90%
70-90%
Specificity
30-90%?
30-80%
GPA= granulomatosis with polyangiitis
*MPA = microscopic polyangiitis
c-ANCA
p-ANCA