Rheumatology Diagnostics 101

Planning the Diagnostic Work-up for suspected

Rheumatic Disease

Evelyn O. Salido, MD, MScAssociate Professor

Division of Rheumatology

UP College of Medicine

Objectives

Given a patient with arthritis, the

participants will be able to:

• Create an appropriate diagnostic plan.

• Interpret the results of common tests.

Most common tests for patients

with arthritis (my experience)

• Serum uric acid

• ESR + CRP

• Joint x-ray

• Rheumatoid factor

• ASO

Diagnostic steps for a patient

with joint pains

TREATMENT

LABORATORY TESTS

DIAGNOSIS

PHYSICAL EXAM

HISTORY

Why we do diagnostic tests

NEW PATIENTS

• Confirm diagnosis

• Rheumatic disease

• Comorbidities

• Establish prognosis

FOLLOW-UP PATIENTS

In addition--

• Determine effects of

treatment

• Disease activity

• Adverse drug effects

TREATMENT

Case 1

Renato, 65/M, L knee pain

• Chronic (10 years)

• Progressive

• Use-related pain

TREATMENT

LABORATORY TESTS

DIAGNOSIS

PHYSICAL EXAM

HISTORY

65/M, L knee pain

• chronic & progressive use-related pain, NRS 5-6/10

• NSAID-use, acid reflux, HPN

History

• Bilateral genu varus, crepitus, no tenderness

Physical Exam

• Confirm rheumatologic diagnosis: knee apl, bilateral?

• Establish prognosis: ?

• Check comorbidities: Hgb, urinalysis, crea, SGPT, albumin

Diagnostic tests

OSTEOARTHRITIS

50/F, factory worker,

obese

• Moderate knee

pain on rising,

prolonged

standing and

walking

• Crepitus

• No tenderness

DOES normal XRAY

RULE OUT

OSTEOARTHRITIS?

60/F, teacher, obese

• Mild knee pain on

arising, prolonged

standing and

walking

• Pain worse since

2 weeks ago

• Has tenderness

infero-medial to

the knee

DOES abnormal XRAY RULE IN

Osteoarthritis as cause of knee pain?

Joint radiograph

• Useful in assessing integrity of bony

structures

• May or may not be needed in diagnosis

of arthritis

• Physician must have clear expectation

of how it will aid management

• Clinical correlation is a must

When is plain radiograph most useful

in diagnosis of joint pain?

• Suspected OA of unusual sites

• History of trauma

• History of cancer

• Chronic inflammatory arthritis of

peripheral and axial joints

• Pain extends beyond the joint along

bony areas

Case 1: OAJudicious use of joint radiographs

• Indication

• Choice of joints to image

• Clinical correlation

Case 2

Olivia,42/F, hand pain

• chronic & progressive rest-related pain and stiffness (“morning stiffness”)

• Prn NSAID almost daily for a month

History

• Swelling, tenderness, increased warmth at joints- shoulders, elbows, wrists, fingers, knees, ankles, toes

Physical Exam

RHEUMATOID ARTHRITIS

42/F, pain at hands

• Chronic (4 months) and Progressive

• Rest-related pain (inflammatory)

• Symmetrical polyarthritis

Rheumatoid Arthritis (ACR-EULAR 6)

• Confirm rheumatologic diagnosis and determine prognosis

• ESR, CRP, RF, ACPA, joint xray, MRI (atypical)

• Check comorbidities

• Hgb, urinalysis, crea, SGPT, albumin, Hbs ag, CXR, PPD

Diagnostic tests

Erythrocyte Sedimentation Rate

• Rate of sedimentation of RBC in 1 hr

• Normal Rate 20 mm/hr

• Inflammation: increase in proteins

(fibrinogen) that make red blood cells

clump together

Erythrocyte Sed Rate

Increase Decrease

Inflammation Polycythemia

Infections Leukemia

Lymphoma Hyperviscosity

Multiple myeloma Low plasma protein

Anemia Sickle cell anemia

Old age CHF

Obesity

High cholesterol

Renal failure

Thyroid disease

Age

(yrs)

Male Female

0-50 <15 <20

51-85 <20 <30

>85 <30 <42

Sox H.C., Liang M.H. The ESR:

guidelines for rational use. Ann Int

Med1986;104:515-23

1. Sensitive in detecting inflammation

2. Non-specific

3. Reflects degree of inflammation,

response to therapy- monitoring

C-reactive protein

• Protein produced by liver

• Binds to surface of dead/dying cells, activates complement

and promotes their clearance

• Starts to rise by 4-6 hrs, peaks at 48 hrs, t½ 19 hrs

• Returns to normal more quickly than ESR

INTERPRETATION

Normal 0.8 -10 mg/L

Viral Infections 10-40 mg/L

Bacterial infection 40-200 mg/L

Severe bacterial infections, Burn >200 mg/L

High in malignancy, allergy, older age, late pregnancy

Autoantibodies: Rheumatoid factor

• Antibody for Fc portion of IgG

• Laboratory techniques

• ELISA- iu/ml

• Latex fixation- +/- (1:80)

• Diagnosis of RA

• Low positive- <3x ULN

• High positive- >3x ULN

• RA: + in 50% during 1st 6 mos

+ in 85% during 1st 2 yrs

• Prognosis of RA

• Higher titer- more erosive

disease, poorer prognosis

Positive RF

• IE

• TB

• Hepatitis C

• SLE

• Sjogren’s

syndrome

• Primary biliary

cirrhosis

• Post-vaccination

arthropathy

• Old age

Autoantibodies: ACPA

anti-citrullinated protein antibody

• Antibody against citrullinated peptides

• Measured in serum through ELISA

• Diagnosis of RA• Low positive- <3x ULN

• High positive- >3x ULN

• Detected as early as 10 years before onset

of symptoms of RA

• Not increased during infections

• May be positive in 15% of PsA, SLE, MCTD

• Prognosis: Marker of severe RA disease

2 Egerer K, Feist E, Burmester GR. The serological diagnosis of rheumatoid arthritis: antibodies to citrullinated

antigens.Dtsch Arztebl Int 2009; 106:159–163.

3 Conrad K, Roggenbuck D, Reinhold D, Dörner T. Profiling of rheumatoid arthritis associated autoantibodies.

Autoimmun Rev 2010; 9:431–435.

Autoantibodies

CHOICE OF TEST

• Duration of symptoms

• Typical or atypical manifestations

• Prior tests done

• Resources

Olivia, 42F, pain at hands

• Chronic (4 months)

• Progressive

• Rest-related pain

• Symmetric polyarthritis

RHEUMATOID ARTHRITIS

What test to do?

• Referral to rheumatologist is strongly advised.

• Prior to referral

Hgb, u/a, crea, SGPT, albumin, Hbs ag, CXR, PPD

ESR/quantitative CRP, anti-CCP >> RF

x-ray of both hands AP and oblique views

CLINICAL CORRELATION is very important.

Case 2: RA• Acute phase reactants (ESR, CRP) are non-

specific markers of inflammation & more

useful for monitoring.

• Autoantibodies are more specific (RF, ACPA)

• Tests for general health, latent infections

Case 3

Rene, 44/M, foot pain

• 1st episode of severe pain with swelling at L foot for 2 days

• Pain & swelling at R ankle 6 months ago, 1 dose NSAID, sprain?

History

• Swelling, tenderness, redness, increased warmth at L 1st MTP joint

• Hypertensive, obese

Physical Exam

GOUT

Uncontrolled Hyperuricemia in Gout

The consequences are Crystal Deposition,

Inflammation, and Damage in Organs

Adapted from Kippel et al, eds. In: Primer on the Rheumatic Diseases. 12th ed. Arthritis foundation;2001:313

Serum uric acid

• Source: By-product of cell breakdown (80%); Diet (20%)

• Excretion: urine (80%), feces (20%)

• Normal values

• Males 7 mg/dl, Females 6 mg/dl

• Determinants

• Genetics>>diet

• Intrinsic factors- sex, age, weight

• Diseases with increased cell turnover

• Medications

Serum uric acid in gout

• Elevated in blood and in tissues

• Poor correlation between serum levels

and symptoms

• May be low during acute gout arthritis due to

uricosuric effects of some inflammatory

cytokines or intake of urate-lowering drug

• May be high in the absence of gout:

asymptomatic hyperuricemia

• An obese menopausal woman with knee pain

from Osteoarthritis

• Symptomatology + SUA level = Gout DX

Rene, 44/M

• 2 episodes of acute inflammatory monoarthritis at the foot, the first resolved after 3 days, no apparent renal disease but with metabolic syndrome

Diagnosis: Gout

• Confirm rheumatologic diagnosis

• Uric acid- serum, synovial fluid

• Kidney structure & function tests

• Check comorbidities

• Hgb, urinalysis, crea, SGPT, FBS, lipids

Do tests? Consider stage of gout

Case 3: Gout• Serum uric acid does not always reflect total

body pool (blood & tissue deposits) of urate

• Check renal function & metabolic syndrome.

• Monitor SUA to achieve optimal level for

dissolution of deposited crystals.

Case 4

Cristina, 32/F, hand pain

• 4 months- pains, stiffness, and swelling (elbows, wrists, fingers, knees, ankles)

• 2 weeks- facial rashes, fever & weakness

History

• Macules at cheeks, forehead, neck

• Pale, tachypneic, tachycardic, with Gr I bipedal pitting edema

• Swollen, tender, warm joints

Physical Exam

Multisystemic disease- SLE?

Cristina, 32/F

• Inflammatory polyarthritis

• Malar rashes, pallor

• Fever, pedal edema

SLE or other AICTD

• Extent of organs involvement

• Serologic tests

• Comorbidities

Do tests?

2018

ACR- EULAR

classification

criteria for SLE

1. ANA > 1:80

2. > 1 clinical

criterion

3. Score > 10

* no other likely

explanation for

criterion

Anti-nuclear antibody: ANA

• Autoantibody test

• Gold standard:

Immunofluorescent technique

using Hep 2 cell line

• Sensitive but not specific for SLE

• Repeatedly Negative test- less

likely SLE unless (+) other ab

Positive in

SLE

Other AICTDs

TB

Leprosy

Cancer

Old age

Healthy people

titre 1:40 32%

titre 1:80 13%

titre 1:160 5%

32/F, pain at hands

• Inflammatory polyarthritis

• Malar rashes, pallor

• Fever, pedal edema

Suspicion of SLE or other CTD

• Extent of organ involvement- CBC, urinalysis (protein, sediments), creatinine, albumin, CXR

• Autoantibodies: ANA, anti-dsDNA, anti-Smith, anti-Ro, anti-cardiolipin, lupus anti-coagulants, serum C3

• Comorbidities- SGPT, FBS, lipids, Hbs ag, CXR, PPD

Do tests? Refer to a rheumatologist.

Case 4: SLE• Establish + multisystemic disease

• CBC, urinalysis, creatinine, SGPT, CXR, Hbs

ag, ANA-IF

When planning diagnostic work-up for

suspected rheumatic disease

• Detailed history & thorough PE

• Working impression and differentials

• Have a clear rationale for ordering

each test

• Anticipate what the results will show

and the corresponding planned action.

• There is no de cajon “rheuma package”

Thank you