Case Report

Case ReportCase Report

39-year-old white male, diagnosed with Rf+ rheumatoid arthritis at the age of 17, presented to his primary care physician with shortness of breath and intermittent nausea.

He had reduced his daily prednisone dose from 20 mg to 10 mg because of nausea, was on diclofenac 50 mg bid, tramadol 100 mg tid.

39-year-old white male, diagnosed with Rf+ rheumatoid arthritis at the age of 17, presented to his primary care physician with shortness of breath and intermittent nausea.

He had reduced his daily prednisone dose from 20 mg to 10 mg because of nausea, was on diclofenac 50 mg bid, tramadol 100 mg tid.

Peter Härle et al, Department of Internal Medicine I, University of Regensburg, Franz-Josef-Strauss-Allee , 11, D-93042 Regensburg, Germany

In addition to steroid therapy, several different disease-modifying drugs were given over the years since diagnosis, including sulfasalazine, oral gold, chloroquine, methotrexate, and TNF-inhibitors.

A total of 16 orthopedic operations had been performed including excision of rheumatic nodules, tendon repair, and bilateral knee- and unilateral hip-replacement.

In addition to steroid therapy, several different disease-modifying drugs were given over the years since diagnosis, including sulfasalazine, oral gold, chloroquine, methotrexate, and TNF-inhibitors.

A total of 16 orthopedic operations had been performed including excision of rheumatic nodules, tendon repair, and bilateral knee- and unilateral hip-replacement.

On exam, he showed signs of extensive rheumatoid arthritis, most marked on hand, foot, and shoulder joints as well as rheumatic nodules on both elbows.

HR regular at 105/min

BP 130/90 mm Hg

ESR 82 mm/h

On exam, he showed signs of extensive rheumatoid arthritis, most marked on hand, foot, and shoulder joints as well as rheumatic nodules on both elbows.

HR regular at 105/min

BP 130/90 mm Hg

ESR 82 mm/h

A CT-scan and echo revealed a pericardial effusion (1.5 cm), a thickened pericardium (5 mm), and basal bilateral low-grade lung fibrosis.

Diuretic therapy and increased prednisone dose controlled his symptoms

The pericardial effusion was almost undetectable 4 weeks later.

A CT-scan and echo revealed a pericardial effusion (1.5 cm), a thickened pericardium (5 mm), and basal bilateral low-grade lung fibrosis.

Diuretic therapy and increased prednisone dose controlled his symptoms

The pericardial effusion was almost undetectable 4 weeks later.

Four months later, he was admitted to the hospital because of a sudden onset of abdominal pain.

A perforated NSAID/steroid-induced ulcer was diagnosed and the patient required emergency surgery.

During anesthesia, severe cardiovascular problems developed including low blood pressure, tachycardia, and pre-renal kidney failure.

A left and right heart catheterization was performed subsequently which showed a cardiac index of 2.4 l/min/m2, equalization of elevated left and right ventricular diastolic pressures.

Four months later, he was admitted to the hospital because of a sudden onset of abdominal pain.

A perforated NSAID/steroid-induced ulcer was diagnosed and the patient required emergency surgery.

During anesthesia, severe cardiovascular problems developed including low blood pressure, tachycardia, and pre-renal kidney failure.

A left and right heart catheterization was performed subsequently which showed a cardiac index of 2.4 l/min/m2, equalization of elevated left and right ventricular diastolic pressures.

Coronary angiography revealed a 75% obstruction of the diagonal branch.

An MRI-scan showed a thickened pericardium (5 mm), a small pericardial effusion, enlarged right atrium, and bilateral pleural effusions.

Coronary angiography revealed a 75% obstruction of the diagonal branch.

An MRI-scan showed a thickened pericardium (5 mm), a small pericardial effusion, enlarged right atrium, and bilateral pleural effusions.

Patient was diagnosed with constrictive pericarditis without a hemodynamic relevant pericardial effusion.

He was referred to CT Surgery

Pericardectomy was suggested.

The patient was informed about the prognosis of this RA-associated complication but declined surgery and was discharged in improved physical condition.

Patient was diagnosed with constrictive pericarditis without a hemodynamic relevant pericardial effusion.

He was referred to CT Surgery

Pericardectomy was suggested.

The patient was informed about the prognosis of this RA-associated complication but declined surgery and was discharged in improved physical condition.

Repeated hospitalizations were necessary because of clinically dominant right heart failure.

On his last admission, p/w cachexia, extensive edema, tachycardia of 122/min, blood pressure of 105/55 mm Hg, orthopnea, and ascites.

Follow-up heart catheterization revealed a reduced ventricular function with a cardiac index of 1.46 l/min/m2.

Repeated hospitalizations were necessary because of clinically dominant right heart failure.

On his last admission, p/w cachexia, extensive edema, tachycardia of 122/min, blood pressure of 105/55 mm Hg, orthopnea, and ascites.

Follow-up heart catheterization revealed a reduced ventricular function with a cardiac index of 1.46 l/min/m2.

Surgical intervention was recommended repeatedly but the patient still declined any further procedures.

In the following weeks, the patient had three episodes of renal failure attributable to low median blood pressure (40–60 mm Hg) together with diuretic therapy Intermittently required vasopressor medication.

The CT-scan of the chest did not show a hemodynamically relevant pericardial effusion.

Surgical intervention was recommended repeatedly but the patient still declined any further procedures.

In the following weeks, the patient had three episodes of renal failure attributable to low median blood pressure (40–60 mm Hg) together with diuretic therapy Intermittently required vasopressor medication.

The CT-scan of the chest did not show a hemodynamically relevant pericardial effusion.

Fig. 1. This CT-scan was conducted without contrast because of recurring prerenal kidney failure. A thickened pericardium (~5 mm) could be seen next to a small pericardial and bilateral pleural effusion. The pericardial effusion did not seem to be of hemodynamic relevance

Fig. 1. This CT-scan was conducted without contrast because of recurring prerenal kidney failure. A thickened pericardium (~5 mm) could be seen next to a small pericardial and bilateral pleural effusion. The pericardial effusion did not seem to be of hemodynamic relevance

Pt was noted to be adrenally insufficient and have pancreatic insufficiency

In the following weeks, cardiovascular and renal functions were increasingly difficult to stabilize and intermittent dialysis was necessary.

He developed a DVT despite the use of prophylactic heparin and a bilateral pneumonia despite broad-spectrum antibiotic therapy.

The patient died in septic shock combined with multi-organ failure.

Pt was noted to be adrenally insufficient and have pancreatic insufficiency

In the following weeks, cardiovascular and renal functions were increasingly difficult to stabilize and intermittent dialysis was necessary.

He developed a DVT despite the use of prophylactic heparin and a bilateral pneumonia despite broad-spectrum antibiotic therapy.

The patient died in septic shock combined with multi-organ failure.

The patient died 2 years after the onset of extra-articular cardiac symptoms.

Pericarditis is a frequent extra-articular manifestation of rheumatoid arthritis showing a post-mortem prevalence of 30%–50%.

These findings correlate well with echocardiographic diagnosis in living patients. However, clinically relevant symptoms are rare with a prevalence of 0.06%–3% of all RA patients

This case demonstrates the devastating course of progressive constrictive pericarditis under sole medical therapy and emphasizes the importance of early radical pericardectomy to avoid progression of disease and secondary complications with fatal outcome.

The patient died 2 years after the onset of extra-articular cardiac symptoms.

Pericarditis is a frequent extra-articular manifestation of rheumatoid arthritis showing a post-mortem prevalence of 30%–50%.

These findings correlate well with echocardiographic diagnosis in living patients. However, clinically relevant symptoms are rare with a prevalence of 0.06%–3% of all RA patients

This case demonstrates the devastating course of progressive constrictive pericarditis under sole medical therapy and emphasizes the importance of early radical pericardectomy to avoid progression of disease and secondary complications with fatal outcome.

Rheumatoid Arthritis

Julie Schwartzman, MD


Julie Schwartzman, MD

Rheumatoid ArthritisRheumatoid Arthritis

A systemic, inflammatory polyarthritis that leads to joint destruction, deformity, and loss of function

Several potentially severe extra-articular manifestations

Pathology of RA involves the synovial membranes and periarticular structures of multiple joints, resulting in:

Pain

Swelling

Stiffness

Uncontrolled inflammation that can lead to irreversible damage and deformity

Functional limitation

A systemic, inflammatory polyarthritis that leads to joint destruction, deformity, and loss of function

Several potentially severe extra-articular manifestations

Pathology of RA involves the synovial membranes and periarticular structures of multiple joints, resulting in:

Pain

Swelling

Stiffness

Uncontrolled inflammation that can lead to irreversible damage and deformity

Functional limitation

ACR Subcommittee on RA Guidelines. Arthritis Rheum. 2002;46:328–346; Goronzy JJ, Weyand CM. In: Klippel JH, et al, eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation; 2001:209–217; Anderson RJ. ibid. 218–225; Arnett FC, et al. Arthritis Rheum. 1988;31:315–324.

ACR Subcommittee on RA Guidelines. Arthritis Rheum. 2002;46:328–346; Goronzy JJ, Weyand CM. In: Klippel JH, et al, eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation; 2001:209–217; Anderson RJ. ibid. 218–225; Arnett FC, et al. Arthritis Rheum. 1988;31:315–324.

I.2I.2

ACR 1987 Classification Criteria For Rheumatoid Arthritis

ACR 1987 Classification Criteria For Rheumatoid Arthritis

Patients Must have Four of Seven Criteria

Morning Stiffness Lasting at Least 1 Hour*

Swelling in 3 or More Joints*

Swelling in Hand Joints*

Symmetric Joint Swelling*

Erosions or Decalcification on X-Ray of Hand

Rheumatoid Nodules

Abnormal Serum Rheumatoid Factor

* Must Be Present at Least 6 Weeks

Patients Must have Four of Seven Criteria

Morning Stiffness Lasting at Least 1 Hour*

Swelling in 3 or More Joints*

Swelling in Hand Joints*

Symmetric Joint Swelling*

Erosions or Decalcification on X-Ray of Hand

Rheumatoid Nodules

Abnormal Serum Rheumatoid Factor

* Must Be Present at Least 6 Weeks

Epidemiology of RAEpidemiology of RA

Prevalence 0.5 - 2%

2 –3 times more prevalent in women

Increased prevalence with advancing age

100,000 – 200,000 New Cases/yr

4 –6 million current cases of RA

Prevalence 0.5 - 2%

2 –3 times more prevalent in women

Increased prevalence with advancing age

100,000 – 200,000 New Cases/yr

4 –6 million current cases of RA

Mode of OnsetMode of Onset

Monoarticular 21%

Oligoarticular 44%

Polyarticular 35%

Monoarticular 21%

Oligoarticular 44%

Polyarticular 35%

Site of OnsetSite of Onset

Joint Involvement

MCP, PIP

Wrist

Knees

Shoulders

Ankles

Feet

Elbows

Hips

Joint Involvement

MCP, PIP

Wrist

Knees

Shoulders

Ankles

Feet

Elbows

Hips

Mean % of Patients

91

78

64

65

50

43

38

17

Mean % of Patients

91

78

64

65

50

43

38

17

Course of DiseaseCourse of Disease

Clinical remission 10%

Intermittent 15 - 20%

Progressive 70 - 75%

Clinical remission 10%

Intermittent 15 - 20%

Progressive 70 - 75%

Extra-articular Manifestations of


Extra-articular Manifestations of


Sceritis

Secondary Sjögren’s SyndromeSecondary Sjögren’s Syndrome

SICCA

Pleuritis/ Pericarditis

Ro/La positive

Hypergammaglobulinemia

SICCA

Pleuritis/ Pericarditis

Ro/La positive

Hypergammaglobulinemia

VasculitisVasculitis

Digital vasculitis

Cutaneous ulceration

Peripheral neuropathy

Mononeuritis multiplex

Digital vasculitis

Cutaneous ulceration

Peripheral neuropathy

Mononeuritis multiplex

Pulmonary InvolvementPulmonary Involvement

Pleural Disease

Interstitial fibrosis

Nodules

Pneumonitis

Pleural Disease

Interstitial fibrosis

Nodules

Pneumonitis

Cardiac InvolvementCardiac Involvement

Pericarditis

Myositis

Endocardial Inflammation

Conduction Defects

Pericarditis

Myositis

Endocardial Inflammation

Conduction Defects

Articular Manifestations: Synovial Fluid Analysis

Articular Manifestations: Synovial Fluid Analysis

Straw colored to slightly cloudy

WBC 5000 – 25,000/ mm3

Rheumatoid Factor

Elevated protein

Decreased glucose

Straw colored to slightly cloudy

WBC 5000 – 25,000/ mm3

Rheumatoid Factor

Elevated protein

Decreased glucose

Laboratory PresentationLaboratory Presentation

Leukocytosis

Eosinophilia

Thrombocytosis

Mild Anemia

ESR > 30 mm/hr

Normal renal and hepatic function

Negative ANA

Rheumatoid Factor

Leukocytosis

Eosinophilia

Thrombocytosis

Mild Anemia

ESR > 30 mm/hr

Normal renal and hepatic function

Negative ANA

Rheumatoid Factor

Anti-Cyclic Citrullinated Peptide(CCP) Antibodies

Anti-Cyclic Citrullinated Peptide(CCP) Antibodies

High diagnostic specificity (>98%) and sensitivity

Presence in 65% of early RA, with the same specificity

Prognosis value linked to the most erosive forms

High diagnostic specificity (>98%) and sensitivity

Presence in 65% of early RA, with the same specificity

Prognosis value linked to the most erosive forms

Differential DiagnosisDifferential Diagnosis

Seronegative polyarthritis

Psoriatic Arthritis

Reiter’s Syndrome

Chondrocalcinosis

Gout

Behcet’s Syndrome

Seronegative polyarthritis

Psoriatic Arthritis

Reiter’s Syndrome

Chondrocalcinosis

Gout

Behcet’s Syndrome

Infectious Arthritis

Thyroid Disease

Malignancies

Polymyalgia Rheumatica

Hemochromatosis

Infectious Arthritis

Thyroid Disease

Malignancies

Polymyalgia Rheumatica

Hemochromatosis

Baseline EvaluationBaseline Evaluation

43 yo AAF came to PMD, reports 4 mo. h/o bilateral wrist and knee pain.

Occasional swelling in wrists and “knuckles”

No PMH

Takes tylenol for pain w/o relief

BASELINE EVALUATION:

Important questions

43 yo AAF came to PMD, reports 4 mo. h/o bilateral wrist and knee pain.

Occasional swelling in wrists and “knuckles”

No PMH

Takes tylenol for pain w/o relief

BASELINE EVALUATION:

Important questions

Baseline Evaluation of Patients Baseline Evaluation of Patients

Subjective/History

Degree of joint pain/swelling symmetry? # joints involved?

Presence/Duration of morning stiffness

Presence of fatigue

Limitation of function

H/o SICCA symptoms? Recent GI/GU infection? Sexual Activity?

Subjective/History

Degree of joint pain/swelling symmetry? # joints involved?

Presence/Duration of morning stiffness

Presence of fatigue

Limitation of function

H/o SICCA symptoms? Recent GI/GU infection? Sexual Activity?

Baseline Evaluation of PatientsBaseline Evaluation of Patients

Physical Exam

Essential Assessments

Physical Exam

Essential Assessments


Physical Examination

Documentation of actively inflamed joints

Documentation of mechanical joint problems: loss of motion, crepitus, instability, deformity

Documentation of extra-articular manifestations

Optho, cardiac, pulmonary, rash, LAD

Physical Examination

Documentation of actively inflamed joints

Documentation of mechanical joint problems: loss of motion, crepitus, instability, deformity

Documentation of extra-articular manifestations

Optho, cardiac, pulmonary, rash, LAD


LABS/STUDIES LABS/STUDIES


Laboratory

ESR /C-reactive protein

Rheumatoid factor/Anti-CCP Ab

ANA, Subserologies?

Complete blood cell count

Renal function and electrolytes

Hepatic panel

Urinalysis

Synovial fluid analysis

Consider: HIV, Uric Acid

Laboratory

ESR /C-reactive protein

Rheumatoid factor/Anti-CCP Ab

ANA, Subserologies?

Complete blood cell count

Renal function and electrolytes

Hepatic panel

Urinalysis

Synovial fluid analysis

Consider: HIV, Uric Acid


Radiography

Wrist and hands

Feet

Other symptomatic joints

Radiography

Wrist and hands

Feet

Other symptomatic joints

Rheumatoid Arthritis: Classification of Function

Rheumatoid Arthritis: Classification of Function

Class I: No Limitations

Class II: Adequate for Normal Activities Despite Joint Discomfort or

Limitation of Movement

Class III: Inadequate for Most Self-Care and Occupational Activities

Class IV: Largely or Wholly Unable to Manage Self-Care: Restricted to Bed or Chair

Class I: No Limitations

Class II: Adequate for Normal Activities Despite Joint Discomfort or

Limitation of Movement

Class III: Inadequate for Most Self-Care and Occupational Activities

Class IV: Largely or Wholly Unable to Manage Self-Care: Restricted to Bed or Chair

Felson DT, et al. Arthritis Rheum. 1995;38:727–735; Felson DT, et al. Arthritis Rheum. 1998;41:1564–1570.Felson DT, et al. Arthritis Rheum. 1995;38:727–735; Felson DT, et al. Arthritis Rheum. 1998;41:1564–1570.

ACR20/50/70/90 Response CriteriaACR20/50/70/90 Response Criteria

A 20%, 50%, or 70% or 90% improvement in:

Swollen joint count, AND

Tender joint count, AND

At least three of the following:

Patient’s global assessment of disease activity

Physician’s global assessment of disease activity

Patient’s assessment of pain

Acute-phase reactants (ESR or CRP)

Patient’s assessment of disability (HAQ)

A 20%, 50%, or 70% or 90% improvement in:

Swollen joint count, AND

Tender joint count, AND

At least three of the following:

Patient’s global assessment of disease activity

Physician’s global assessment of disease activity

Patient’s assessment of pain

Acute-phase reactants (ESR or CRP)

Patient’s assessment of disability (HAQ)

Health Assessment Questionnaire (HAQ)Health Assessment Questionnaire (HAQ)

Widely accepted, validated, rheumatology-specific instrument to assess physical function in RA

Gold standard

20 questions covering 8 activities

Dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, activities of daily living

Widely accepted, validated, rheumatology-specific instrument to assess physical function in RA

Gold standard

20 questions covering 8 activities

Dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, activities of daily living

Buchbinder R et al. Arthritis Rheum. 1995;38:1568-1580. Sullivan FM et al. Ann Rheum Dis. 1987;46:598-600.

OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials

Disease Activity Score 28 (DAS28)Disease Activity Score 28 (DAS28)

DAS28 = 0.56 • (t28) + 0.28 • (sw28) + 0.70 • Ln(ESR) + .014•GHDAS28 = 0.56 • (t28) + 0.28 • (sw28) + 0.70 • Ln(ESR) + .014•GH

DAS28 = Simplified disease activity score

Prevoo ML, et al. Arthritis Rheum. 1995;38:44–48.

DAS28 = Simplified disease activity score

Prevoo ML, et al. Arthritis Rheum. 1995;38:44–48.

Assessment of Improvement or ResponseAssessment of Improvement or Response

t28 = number of tender joints among 28 joints

sw28 = number of swollen joints among 28 joints

ESR = erythrocyte sedimentation rate (mm/hour)

GH = general health status using a 100-mm visual analog scale (VAS)

t28 = number of tender joints among 28 joints

sw28 = number of swollen joints among 28 joints

ESR = erythrocyte sedimentation rate (mm/hour)

GH = general health status using a 100-mm visual analog scale (VAS)

High disease activity 5.1, low disease activity 3.2, remission 2.6High disease activity 5.1, low disease activity 3.2, remission 2.6

Sharp Scores of Radiographic ProgressionSharp Scores of Radiographic Progression

Erosion scores 17 joints of each hand/wrist 6 joints of each forefoot Scale: 0–5; Total score: 0–230

Joint space narrowing (JSN) scores 16 joints of each hand/wrist 5 joints of each forefoot Scale: 0–4; Total score: 0–168

Total Sharp score Add erosion and JSN scores Total score: 0–398

Erosion scores 17 joints of each hand/wrist 6 joints of each forefoot Scale: 0–5; Total score: 0–230

Joint space narrowing (JSN) scores 16 joints of each hand/wrist 5 joints of each forefoot Scale: 0–4; Total score: 0–168

Total Sharp score Add erosion and JSN scores Total score: 0–398

Sharp JT, et al. Arthritis Rheum.1985;28:1326–1335van der Heijde DM, et al. J Rheumatol. 1995;22:1792–1796.Sharp JT, et al. Arthritis Rheum.1985;28:1326–1335van der Heijde DM, et al. J Rheumatol. 1995;22:1792–1796.

Prognostic Markers in RAPrognostic Markers in RA

Early Markers

Generalized onset with numerous joints involved

Systemic involvement including fatigue, fever, weight loss, morning stiffness

Elevated CRP or ESR

Positive test for rheumatoid factor/Anti-CCP

Early erosions, JSN

HLA-DR4 genetic marker

Early Markers

Generalized onset with numerous joints involved

Systemic involvement including fatigue, fever, weight loss, morning stiffness

Elevated CRP or ESR

Positive test for rheumatoid factor/Anti-CCP

Early erosions, JSN

HLA-DR4 genetic marker


Later Markers

Involvement of more joints

Increased morning stiffness

Rheumatoid factor 1:160 or greater

Anemia and thrombocytosis

Later Markers

Involvement of more joints

Increased morning stiffness

Rheumatoid factor 1:160 or greater

Anemia and thrombocytosis


Definitive Markers

Subcutaneous nodules

Detection of erosions on x-ray

Definitive Markers

Subcutaneous nodules

Detection of erosions on x-ray

The Importance of Early DiagnosisThe Importance of Early Diagnosis

RA is progressive, not benign

Structural damage and disability occurs within first two to three years of disease

Slower progression of disease is linked to early treatment with DMARDs, Biologic Agents

RA is progressive, not benign

Structural damage and disability occurs within first two to three years of disease

Slower progression of disease is linked to early treatment with DMARDs, Biologic Agents

RA Progression RA Progression

Adapted from Kirwan JR. J Rheumatol. 2001;28:881–886.Adapted from Kirwan JR. J Rheumatol. 2001;28:881–886.

Sev

erit

y (a

rbit

rary

un

its)

Sev

erit

y (a

rbit

rary

un

its)

00

Duration of Disease (years)Duration of Disease (years)

55 1010 1515 2020 2525 3030

Inflammation

Disability

Radiographs

Inflammation

Disability

Radiographs

I.6I.6

Joint Erosions Occur Early in RAJoint Erosions Occur Early in RA

0

10

20

30

0 1 2 3

0

10

20

30

0 1 2 3

Up to 93% of patients with<2 years of RA may have radiographic abnormalities

Erosions can bedetected by MRI within 4 months of RA onset

Rate of progression is significantly more rapid in the first year than in the second and third years

Up to 93% of patients with<2 years of RA may have radiographic abnormalities

Erosions can bedetected by MRI within 4 months of RA onset

Rate of progression is significantly more rapid in the first year than in the second and third years

Hand

MTP

All

Fuchs HA et al. J Rheumatol. 1989;16:585-591.McQueen FM et al. Ann Rheum Dis. 1998;57:350-356.van der Heijde DM et al. J Rheumatol. 1995;22:1792-1796.

Year

Max

imu

m %

Jo

ints

Aff

ecte

d

Ch

ang

e in

Med

ian

S

har

p S

core

Ch

ang

e in

Med

ian

S

har

p S

core

00

22

44

66

88

1010

1212

1414

00 66 1212 1818 2424

Time (months)Time (months)

*Patients were treated with chloroquine or azathioprine.Lard LR, et al. Am J Med. 2001;111:446–451. *Patients were treated with chloroquine or azathioprine.Lard LR, et al. Am J Med. 2001;111:446–451.

Treatment: The Earlier the BetterTreatment: The Earlier the BetterTreatment: The Earlier the BetterTreatment: The Earlier the Better

Delayed Treatment*(median treatment lag time = 123 days; n = 109)

Early Treatment* (median treatment lag time = 15 days; n = 97)

Delayed Treatment*(median treatment lag time = 123 days; n = 109)

Early Treatment* (median treatment lag time = 15 days; n = 97)

I.16I.16

The Goals of TreatmentThe Goals of Treatment

Eliminate synovitis and disease activity

Improve symptoms

Prevent joint damage

Prevent or reduce disability

Prevent or reduce other adverse outcomes

Eliminate synovitis and disease activity

Improve symptoms

Prevent joint damage

Prevent or reduce disability

Prevent or reduce other adverse outcomes

Adapted from Wolfe F et al. J Rheumatol. 2001;28:1423.

Current Treatment OptionsCurrent Treatment Options

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Corticosteroids

Disease Modifying Anti-rheumatic Drugs (DMARDs)

Biologic Agents

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Corticosteroids

Disease Modifying Anti-rheumatic Drugs (DMARDs)

Biologic Agents

Potential Toxicity of NSAIDsPotential Toxicity of NSAIDs COX-1

Gastrointestinal toxicity

Platelet dysfunction

COX-1 and COX-2

Decreased renal blood flow

Hepatic dysfunction

CNS toxicity: dizziness, tinnitus, confusion, anxiety

Hypersensitivity

COX-2

Increased risk of cardiovascular disease

Increased risk of thrombosis

COX-1

Gastrointestinal toxicity

Platelet dysfunction

COX-1 and COX-2

Decreased renal blood flow

Hepatic dysfunction

CNS toxicity: dizziness, tinnitus, confusion, anxiety

Hypersensitivity

COX-2

Increased risk of cardiovascular disease

Increased risk of thrombosis

Traditional DMARDsTraditional DMARDs

Methotrexate (MTX)

Hydroxychloroquine

Leflunomide

Sulfasalazine

Methotrexate (MTX)

Hydroxychloroquine

Leflunomide

Sulfasalazine

Cyclosporine

Parenteral/oral gold

Azathioprine

D-penicillamine

Minocycline*

Cyclosporine

Parenteral/oral gold

Azathioprine

D-penicillamine

Minocycline*

* Not approved by the FDA for the treatment of RA.ACR guidelines for the management of rheumatoid arthritis. Arthritis Rheum. 2002;46:328-346.

Methotrexate - DosageMethotrexate - Dosage

Initiation : 7.5 mg once weekly

Maximum : 25 mg once weekly

Route: po, SQ

Initiation : 7.5 mg once weekly

Maximum : 25 mg once weekly

Route: po, SQ

Methotrexate - Potential ToxicityMethotrexate - Potential Toxicity

• Stomatitis

• Alopecia

• Pulmonary

• Hepatic- check LFTS q 6 weeks then q 3 mo when on stable dose

• Stomatitis

• Alopecia

• Pulmonary

• Hepatic- check LFTS q 6 weeks then q 3 mo when on stable dose

• Hematologic

• Teratogenic

• ?Carcinogenic

• Hematologic

• Teratogenic

• ?Carcinogenic

Leflunamide - AravaLeflunamide - Arava

Can be given with loading dose 100mg qd x 3 days, then 10-20mg po qd

Monitor CBC, LFTs

Teratogenic

Cholestyramine is given if rapid removal is necessary

Can be given with loading dose 100mg qd x 3 days, then 10-20mg po qd

Monitor CBC, LFTs

Teratogenic

Cholestyramine is given if rapid removal is necessary

AntimalarialsAntimalarials

Hydroxychloroquine - plaquenil

Initiation: 400 – 600 mg qd

Maintenance: 200 mg qd

Chloroquine

Initiation: 500 mg qd

Maintenance 250 mg qd

Potential Toxicities: GI, Retinopathy

Hydroxychloroquine - plaquenil

Initiation: 400 – 600 mg qd

Maintenance: 200 mg qd

Chloroquine

Initiation: 500 mg qd

Maintenance 250 mg qd

Potential Toxicities: GI, Retinopathy

SulfasalazineSulfasalazine

Dosage 2 – 3 gm qd in 2 – 3 divided

doses

Potential toxicity Hematologic

Monitor CBC q2 weeks the first 3 months of therapy

HepaticMonitor hepatic function monthly

Dosage 2 – 3 gm qd in 2 – 3 divided

doses

Potential toxicity Hematologic

Monitor CBC q2 weeks the first 3 months of therapy

HepaticMonitor hepatic function monthly

Adapted with permission from Choy EH, Panayi GS. N Engl J Med. 2001;344:907–916.Adapted with permission from Choy EH, Panayi GS. N Engl J Med. 2001;344:907–916.

Inhibition of CytokinesInhibition of Cytokines

Activation ofanti-inflammatory pathways

Activation ofanti-inflammatory pathways

Anti-inflammatorycytokine

Anti-inflammatorycytokineSuppression ofinflammatorycytokines

Suppression ofinflammatorycytokines

Neutralization of cytokinesNeutralization of cytokines

Soluble receptorSoluble receptor

Monoclonal antibodyMonoclonal antibody

No signalNo signal

Receptor blockadeReceptor blockade

Monoclonal antibodyMonoclonal antibody

Receptor antagonistReceptor antagonist

No signalNo signal

Inflammatory cytokine Inflammatory cytokine

Normal interactionNormal interaction

Cytokine receptorCytokine receptor

Inflammatory signalInflammatory signal

TNF Blocking Therapies TNF Blocking Therapies

*Some patients not taking concomitant MTX may derive additional benefit fromincreasing the dosing frequency of adalimumab to 40 mg every week*Some patients not taking concomitant MTX may derive additional benefit fromincreasing the dosing frequency of adalimumab to 40 mg every week

Etanercept Infliximab Adalimumab

Characteristic (ENBREL) (REMICADE (HUMIRA™)

Class sTNFR TNF MAb TNF MAb

Construct Recombinant Chimeric MAb Recombinant

fusion protein human MAb

Half-life 4 days 8–10 days 10–20 days

Binding target TNF/LT TNF TNF

Administration 50 mg 3–10 mg/kg 40 mg

SC IV with MTX SC

Once weekly Every 4–8 weeks Every other week*

Etanercept Infliximab Adalimumab

Characteristic (ENBREL) (REMICADE (HUMIRA™)

Class sTNFR TNF MAb TNF MAb

Construct Recombinant Chimeric MAb Recombinant

fusion protein human MAb

Half-life 4 days 8–10 days 10–20 days

Binding target TNF/LT TNF TNF

Administration 50 mg 3–10 mg/kg 40 mg

SC IV with MTX SC

Once weekly Every 4–8 weeks Every other week*

Rituximab (chimeric murine-human anti CD20 Ab)

in combination with methotrexate is indicated to reduce signs and symptoms in adult patients with moderately- to severely- active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Salama AD and Pusey CD (2006) Drug Insight: rituximab in renal disease and transplantationNat Clin Pract Neprol 2: 221–230 doi:10.1038/ncpneph0133

Figure 2 B-cell functions are inhibited following cell depletion by rituximab

Abatacept – CTLA-4Ig

Establish diagnosis of RA early

Initiate therapyPCP

Periodically assess disease activity

RHEUMATOLOGIST

Adequate response Inadequate response

Change/add DMARDs

MTX naïve Suboptimal MTX response

MTX Othermonotherapy

Combination Combination Othermonotherapy

Biologics

Monotherapy Combination

Multiple DMARD failure

Symptomatic and/or structural joint damage

ACR Treatment AlgorithmACR Treatment Algorithm

Adapted from ACR guidelines for the management of rheumatoid arthritis. Arthritis Rheum. 2002;46:328-346. 84

Questions

Case report

Questions

Case report

Case ReportCase Report

57-year-old man was admitted to a hospital affiliated with dyspnea and dry cough lasting 2 weeks.

He had previously been diagnosed with rheumatoid arthritis, manifested by painful swelling of the joints 2 years prior to admission.

The patient was being treated with prednisone and gold.

Patient with diffuse pulmonary rheumatoid nodules and interstitial fibrosis throughout both lungs, is described.

The patient, with articular symptoms and seropositivity, exhibited a rapid clinical course and died of respiratory failure 3 months after the appearance of dyspnea.

57-year-old man was admitted to a hospital affiliated with dyspnea and dry cough lasting 2 weeks.

He had previously been diagnosed with rheumatoid arthritis, manifested by painful swelling of the joints 2 years prior to admission.

The patient was being treated with prednisone and gold.

Patient with diffuse pulmonary rheumatoid nodules and interstitial fibrosis throughout both lungs, is described.

The patient, with articular symptoms and seropositivity, exhibited a rapid clinical course and died of respiratory failure 3 months after the appearance of dyspnea.

Chest radiography indicated interstitial pneumonitis with bilateral diffuse peripheral shadows.

At autopsy, numerous rheumatoid nodules and interstitial fibrosis had destroyed both lungs, such that no residual normal pulmonary tissue remained.

It is believed that this was an extremely rare case exhibiting large numbers of rheumatoid nodules throughout the lungs.

Findings with this patient indicate that, in patients with rheumatoid arthritis, clinical interstitial pneumonitis confirmed radiographically does not exclude the existence of rheumatoid lung nodules.

Chest radiography indicated interstitial pneumonitis with bilateral diffuse peripheral shadows.

At autopsy, numerous rheumatoid nodules and interstitial fibrosis had destroyed both lungs, such that no residual normal pulmonary tissue remained.

It is believed that this was an extremely rare case exhibiting large numbers of rheumatoid nodules throughout the lungs.

Findings with this patient indicate that, in patients with rheumatoid arthritis, clinical interstitial pneumonitis confirmed radiographically does not exclude the existence of rheumatoid lung nodules.

Case Report

Documents

Transcript of Case Report