Approach to the Achy Patient in her shoulders, knees and feet. - - PDF document

1 Approach to the Achy Patient

Andrew J. Gross, MD Rheumatology Clinic Chief Associate Clinical Professor University of California, San Francisco

Clinical Case # 1

• 52 year old woman with 5 months of

joint pain. Initially she had pain in her

• hands. Over time, she developed pain

in her shoulders, knees and feet. Ibuprofen has been helpful for the pain.

• Review of systems is notable for

moderately severe fatigue, and

• ccasional sharp chest pains. She

also reports symptoms of Raynaud’s phenomenon.

• Past medical, family and social history

are unremarkable.

Clinical Case # 1

• General physical examination is unremarkable.
• On musculoskeletal exam, you are uncertain if there

are any swollen joints. Many joints are tender, particularly her PIP and MCP joints, her wrists and knees.

What is the diagnosis?

Differential Diagnosis

Inflammatory

• Autoimmune

– Lupus/Scleroderma – Rheumatoid Arthritis – Spondyloarthritis

• Crystal Disease
• Infectious

– Viral – Chronic bacterial

• Neoplastic

Non-Inflammatory

• Osteoarthritis
• Endocrine

– Thyroid Disease – Diabetes – Calcium metabolism

• Overuse
• Somatic/Fibromyalgia

– Hypermobility

2

Approach to Arthritis

(clinical clues)

• age
• gender
• family history
• onset of disease (acute/chronic)
• pattern of joint involvement

(& presence of enthesitis)

Pattern of Joint Involvement

All of the following conditions commonly involve PIP & MCP joints, wrists and knees EXCEPT:

• A. Osteoarthritis
• B. Rheumatoid Arthritis
• C. SLE
• D. CPPD disease (“pseudogout”)
• E. Parvovirus B19 induced arthritis

Approach to Arthritis

(clinical clues)

• age
• gender
• family history
• onset of disease (acute/chronic)

Lupus/MCTD/ scleroderma Rheumatoid Arthritis Peri-menopausal

• steoarthritis

Psoriatic Arthritis

• pattern of joint involvement

(& presence of enthesitis)

• extra-articular manifestations
• diagnostic testing

Clinical Case # 1

• Re-examination of

the skin is remarkable for mild erythema of her fingers, particularly between the knuckles.

What is the diagnosis?

Photo courtesy of Maria Dall’era

3

What is the Diagnosis?

• A. Dermatomyositis
• B. Psoriasis
• C. Lupus
• D. Granuloma Annulare
• E. Eczema

Tip

• To help diagnose Inflammatory Arthritis

Search for CLINICAL CLUES

Classification Criteria for Systemic Lupus Erythematosus

• Rashes (~85%)

– Malar rash – Discoid rash (scarring) – Photosensitive

• Oral/nasal ulcers (painless)
• Arthritis (80-90%)

(usually small joints)

• Serositis (~45%)
• Glomerulonephritis (50-

70%)

• CNS disease (25-35%)

(seizures, chorea, stroke)

• Hematologic disorder

Leukopenia, Lymphopenia, Thrombocytopenia, AIHA

• Immunologic disorder

dsDNA, Sm, APL Antibodies

• Antinuclear antibodies

Any combination of 4 or more of 11 criteria, well-documented at any time during a patient's history, makes it likely that the patient has SLE (95% specificity; 75% sensitivity)

Tan EM, et al, Arthritis Rheum 1982

Classification Criteria for Systemic Lupus Erythematosus

Malar rash: Fixed erythema, flat or raised, over the malar eminences Discoid rash: Erythematous circular raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur Photosensitivity: Exposure to ultraviolet light causes rash Oral ulcers: Includes oral and nasopharyngeal ulcers, observed by physician Arthritis: Nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion Serositis: Pleuritis or pericarditis documented by ECG or rub or evidence of effusion Renal disorder: Proteinuria >0.5 g/d or 3+, or cellular casts Neurologic disorder: Seizures or psychosis without other causes Hematologic disorder: Hemolytic anemia, leukopenia (<4000/L) or lymphopenia (<1500/L) or thrombocytopenia (<100,000/L) in the absence of offending drugs Immunologic disorder: Anti-dsDNA, anti-Sm, and/or anti-phospholipid Antinuclear antibodies: An abnormal titer of ANA by immunofluorescence or an equivalent assay in the absence of drugs known to induce ANAs

Any combination of 4 or more of 11 criteria, well-documented at any time during a patient's history, makes it likely that the patient has SLE (95% specificity; 75% sensitivity)

4

Clinical Case # 1 – Alternative Scenario

• General physical examination is unremarkable.
• On musculoskeletal exam, you are unsure if there are

any swollen joints. Many joints are tender, particularly her PIP and MCP joints, her wrists and knees.

• Skin exam is unremarkable

In the absence of clinical clues Are there diagnostic tests that will help identify the diagnosis?

Anti-Nuclear Antibody (ANA) How does an ANA test help me to determine if the patient has “a rheum thing” (like SLE)?

How will an ANA test help me to determine if the patient has “a rheum thing” (like SLE)?

• a. Although an ANA is not specific for any particular

autoimmune disease, the presence of it does suggest the patient has a connective tissue disease.

• b. A positive ANA indicates the patient has a defect in

tolerance mechanisms and will develop an autoimmune disease.

• c. By examining the pattern of the ANA, you can

determine the diagnosis.

• d. Testing for additional autoantibodies can increase

the specificity of testing.

5

ANA Frequencies

100% 0%

Lupus Healthy Scleroderma 1° relatives

• f SLE Pts

Rheumatoid Arthritis & Thyroid Disease

50%

Fibromyalgia

Kavanaugh A, et al, Arch Pathol Lab Med 2000, PMID 10629135

ANA is highly sensitive for Lupus & Somewhat sensitive for other autoimmune conditions

• SLE

95-99%

• Systemic Sclerosis

(Scleroderma) 60-80%

• Sjögrens

40-70%

• Polymyositis &

Dermatomyositis 30-80%

• Rheumatoid

Arthritis 30-50%

• Thyroid disease

30-50%

• Multiple Sclerosis

25%

• ITP

10-30%

• Infectious diseases &

malignancies - varies widely

Kavanaugh A, et al, Arch Pathol Lab Med 2000

People without Autoimmune Disease can have a positive ANA

• Fibromyalgia

15-25%

• Relatives of SLE Pts 5-25%
• Healthy People
• > 1:40

20-30%

• > 1:80

10-12%

• > 1:160

5%

• > 1:320

3%

Kavanaugh A, et al, Arch Pathol Lab Med 2000

Among 100,000 American Women Who has a positive ANA?

Data extrapolated from Kavanaugh A, et al, Arch Pathol Lab Med 2000 & Tan EM, et al, Arthritis Rheum 1997

Condition Number with condition per 100,000 ANA+ Calculated Prevalence of ANA+ people per 100,000 Women with SLE 50 99%

~50

Patients w/ Autoimmune Thyroid Dz 250 40%

~100

Women with Fibromyalgia 3500 20%

~700

Healthy women with ANA ≥1:160

• 5%

~5,000

ANA is not really helpful to screen for autoimmune disease

6

How about the ANA Pattern?

Speckled Cytoplasmic Nucleolar Centromere

ANA patterns

• ANA patterns are not highly predictive of:

– Disease Types – Autoantibody subsets

Disease Suspicion: SLE useful lab tests

• ANA – 95-99% sensitive
• anti dsDNA – seen in 70% of patients (95-100% Specific)
• Smith – only seen in 15-30% of patients (95-100% Specific)
• C3 & C4 levels – depressed in 60% of patients (Sensitive)
• Elevated ESR (CRP usually normal in SLE)
• Lymphopenia, AIHA, thrombocytopenia, leukopenia

Kavanaugh A, et al, Arch Pathol Lab Med 2000, PMID 10629135

Back to Our Patient’s Diagnostic Testing

• ESR 19 mm/hr
• CRP 3.2 (nl <6.3)
• ANA 1:160 speckled pattern
• C3 89, C4 21 (both borderline low)
• Anti-dsDNA Ab, Sm Ab, RNP negative
• WBC 3.2, 0.8 lymphocytes, Hgb 11.1, PLT 104
• Urine Analysis normal

This is consistent with mild SLE

7

Tips to help diagnose SLE

• Search for CLINICAL CLUES!
• Biopsy persistent skin rashes
• Check complement levels
• Check urine for hemoglobin & protein,

especially if the patient has dsDNA Ab

• Look for lymphopenia and thrombocytopenia

Clinical Case # 2

• 52 year old woman with 5 months of

joint pain. Initially she had pain in her

• hands. Over time, she developed pain

in her shoulders, knees and feet. It takes a couple of hours for her joint stiffness to improve in the mornings.

• General physical examination is

unremarkable.

• On musculoskeletal exam, you think a

few fingers and her right wrist might be

• swollen. Many joints are tender,

particularly her PIP and MCP joints, her wrists and shoulders.

Approach to Arthritis

(clinical clues)

• age
• gender
• family history
• onset of disease (acute/chronic)
• pattern of joint involvement

(& presence of enthesitis)

• extra-articular manifestations
• diagnostic testing

Lupus/MCTD/ scleroderma Rheumatoid Arthritis Peri-menopausal

• steoarthritis

Psoriatic Arthritis

Part 2 – Patient’s Diagnostic Testing

• WBC 7.1, Hgb 11.8, PLT 291
• ESR 19 mm/hr
• CRP 7.8 (nl <6.3)
• ANA 1:40 speckled pattern
• C3 128 (normal), C4 36 (slightly elevated)
• Anti-dsDNA Ab, Sm Ab, RNP negative
• Urine Analysis normal

Does not seem like Lupus or Scleroderma. Could this be Rheumatoid Arthritis?

8

Diagnostic Criteria for Rheumatoid Arthritis

• Morning stiffness of >1 hour.
• Arthritis of hand joints
• Symmetric arthritis
• Arthritis & soft-tissue swelling of >3 of 14 joints/joint

groups

• Subcutaneous nodules
• Rheumatoid Factor (and anti-CCP antibody)
• Radiological changes suggestive of joint erosion

Any combination of 4 or more of 7 criteria for >6 weeks, well-documented at any time during a patient's history, makes it likely that the patient has RA

Arnett FC, et al, Arthritis Rheum 1988

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

Criterion Definition

• 1. Morning stiffness

Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement

• 2. Arthritis of 3 or more joint areas

At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a

• physician. The 14 possible areas are right or left PIP, MCP,

wrist, elbow, knee, ankle, and MTP joints

• 3. Arthritis of hand joints

At least 1 area swollen (as defined above) in a wrist, MCP,

• r PIP joint
• 4. Symmetric arthritis

Simultaneous involvement of the same joint areas (as defined in 2) on both sides fo the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry)

• 5. Rheumatoid nodules

Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxtaarticular regions, observed by a physician

• 6. Serum rheumatoid factor

Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in <5% of normal control subjects

• 7. Radiographic changes

Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs, which must include erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify)

How will Rheumatoid Factor & CCP Antibody help me to determine if the patient has Rheumatoid Arthritis?

Which is true?

• A. A negative rheumatoid factor is helpful only if IgA,

IgM and IgG isotypes were tested.

• B. Rheumatoid factor and CCP have similar

sensitivities for Rheumatoid Arthritis, but have very different levels of specificity

• C. CCP is not commonly available and is not routinely

checked.

• D. There is no additional value to checking anti-CCP

and rheumatoid factor

9

Rheumatoid Factor

• False Positives

– 15% of normal persons over the age of 65 – Infections: Hepatitis C, Parvovirus, HIV, SBE – Neoplastic disease (especially hematogenous) – Autoimmune Disease: Sjogren’s, cryoglobulinemia,… – Chronic Inflammation

• IgM directed against the Fc portion of IgG
• Present in ~70% of patients with RA
• Higher titers associated with more erosive disease

anti-CCP antibodies

(anti-Cyclic Citrullinated Peptide antibodies)

• Sensitive (~70%)
• Specific (92%-99%) for diagnosis of RA
• Early marker for RA

Nishimura K, et al Ann Intern Med. 2007;146:797-808

Lab tests can help evaluate for RA

• RF & CCP combined:
• Sensitivity ~80%
• Specificity (depends on which one is positive)

Lee DM, Schur P, Ann Rheum Dis. 2003

RF and CCP are helpful to evaluate patients with joint pain for RA Tests are limited by their sensitivity RF is limited by its non-specificity

TIP:

Recognize the value of the plain x-ray

• Erosions indicate inflammatory arthritis

– Rheumatoid Arthritis – Spondyloarthritis – Crystal Arthritis – Septic Arthritis (Tb)

10

RA Normal

X-rays can show early signs of RA

RA Normal Tips to help diagnose RA

• Search for CLINICAL CLUES!
• Prolonged morning stiffness
• Check RF and CCP Antibodies
• Check x-rays

Clinical Case # 3

• 52 year old woman with 5 months of

worsening joint pain. Initially she had pain in her hands. Pain has developed in her shoulders, neck, lower back, knees and ankles. Pain and stiffness is most severe in the morning.

• General physical examination is

unremarkable.

• On musculoskeletal exam, are unsure

if there are any swollen joints. She is tender in many areas included over her joints and over some muscle groups.

11

Approach to Arthritis

(clinical clues)

• age
• gender
• family history
• onset of disease (acute/chronic)
• pattern of joint involvement

(& presence of enthesitis)

• extra-articular manifestations
• diagnostic testing

Ankylosing Spondylitis Regional Pain syndromes Osteoarthritis Fibromyalgia Prevalence of Rheumatic Disorders in the USA (National Arthritis Data Workgroup)

• Gout

3 million

• Rheumatoid arthritis

1.3 million

• Spondyloarthropathies

0.6 – 2.4 million

• Polymyalgia rheumatica

0.7 million

• Systemic lupus (SLE)

0.2 – 0.3 million

• Giant cell arteritis

0.2 million

Lawrence et al Arthritis & Rheumatism 58(1), 26-35, 2008 Helmick et al Arthritis & Rheumatism 58(1), 15-25, 2008

• Low back pain

59 million

• Neck pain

30 million

• Osteoarthritis

27 million

• Fibromyalgia

5 million

What are the hallmarks of fibromyalgia? (choose 3)

a) Widespread pain b) Joint Pain c) Non-restful sleep d) Depression e) Fatigue f) Obesity Diagnosis of Fibromyalgia

ACR classification criteria – Wolfe F, et al, Arthritis Rheum 1990 ACR diagnostic criteria – Wolfe F, et al, Arthritis Rheum 2010

Widespread Pain

(>3 months)

• Fatigue
• Poor Sleep
• Cognitive

Problems

• Other Sx

12

Tender Point Exam

ACR fibromyalgia classification criteria: pain at 11 of 18 points

www.fibromyalgia- support.net/downloads/NewF ibroCriteriaSurvey.pdf

Fibromyalgia is present when: WPI score ≥7 SS score ≥5 Fibromyalgia Diagnostic Criteria

• r

WPI = 3 – 6 SS score ≥9

Diagnosis of Fibromyalgia

ACR classification criteria – Wolfe F, et al, Arthritis Rheum 1990 ACR diagnostic criteria – Wolfe F, et al, Arthritis Rheum 2010

Widespread Pain

(>3 months)

• Fatigue
• Poor Sleep
• Cognitive

Problems

• Other Sx
• ther

disease

Tip offs that suggest your patient may have fibromyalgia:

• Multiple different pain complains

– Eg. Back pain, knee pain, neck pain

• Activity has consequences

– Eg. If I do ______, I will be in bed for 2 days

• No position relieves pain symptoms
• The person has odd complaints – “my

body feels like it has tinnitus”

• You walk into the room and the lights

are turned down (hypersensitivity).

• “Pan-positive review of systems”
• You feel exhausted after the interview

13

Fibromyalgia

Headache/Migraine TMJ disorder Dermatitis/ pruritis Chronic eye irritation/dryness Atypical chest pain Irritable bowel syndrome Polyuria/frequency (“interstitial cystitis”) Dyspareunia/ vulvodynia Paresthesia Chronic fatigue Muscle Cramps Dypsnea Multiple sensitivities

modified from Aaron LA, et al. Arch Int Med. 2000;160:221-227.

Costs Related to a Diagnose FMS and Failure to Diagnose FMS

Annemans et al, Arthritis Rheum 2008; 58:895 Annemans et al, Arthritis Rheum 2008; 58:895

Costs Related to a Diagnose FMS and Failure to Diagnose FMS

Summary

• Use a systematic approach to evaluating a patient with

joint pain

• Search for clinical clues
• Obtain appropriate (targeted) laboratory testing