case report 39-year-old white male, diagnosed with rf+ rheumatoid arthritis at the age of 17,...
TRANSCRIPT
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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
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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Rheumatoid Arthritis
Julie Schwartzman, MD
Rheumatoid Arthritis
Julie Schwartzman, MD
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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
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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
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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
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Mode of OnsetMode of Onset
Monoarticular 21%
Oligoarticular 44%
Polyarticular 35%
Monoarticular 21%
Oligoarticular 44%
Polyarticular 35%
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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
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Course of DiseaseCourse of Disease
Clinical remission 10%
Intermittent 15 - 20%
Progressive 70 - 75%
Clinical remission 10%
Intermittent 15 - 20%
Progressive 70 - 75%
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Extra-articular Manifestations of
Rheumatoid Arthritis
Extra-articular Manifestations of
Rheumatoid Arthritis
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Sceritis
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Secondary Sjögren’s SyndromeSecondary Sjögren’s Syndrome
SICCA
Pleuritis/ Pericarditis
Ro/La positive
Hypergammaglobulinemia
SICCA
Pleuritis/ Pericarditis
Ro/La positive
Hypergammaglobulinemia
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VasculitisVasculitis
Digital vasculitis
Cutaneous ulceration
Peripheral neuropathy
Mononeuritis multiplex
Digital vasculitis
Cutaneous ulceration
Peripheral neuropathy
Mononeuritis multiplex
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Pulmonary InvolvementPulmonary Involvement
Pleural Disease
Interstitial fibrosis
Nodules
Pneumonitis
Pleural Disease
Interstitial fibrosis
Nodules
Pneumonitis
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Cardiac InvolvementCardiac Involvement
Pericarditis
Myositis
Endocardial Inflammation
Conduction Defects
Pericarditis
Myositis
Endocardial Inflammation
Conduction Defects
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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
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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
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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
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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
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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
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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?
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Baseline Evaluation of PatientsBaseline Evaluation of Patients
Physical Exam
Essential Assessments
Physical Exam
Essential Assessments
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Baseline Evaluation of PatientsBaseline Evaluation of Patients
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
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Baseline Evaluation of PatientsBaseline Evaluation of Patients
LABS/STUDIES LABS/STUDIES
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Baseline Evaluation of PatientsBaseline Evaluation of Patients
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
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Baseline Evaluation of PatientsBaseline Evaluation of Patients
Radiography
Wrist and hands
Feet
Other symptomatic joints
Radiography
Wrist and hands
Feet
Other symptomatic joints
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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
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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)
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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
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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
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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.
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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
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Prognostic Markers in RAPrognostic Markers in RA
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
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Prognostic Markers in RAPrognostic Markers in RA
Definitive Markers
Subcutaneous nodules
Detection of erosions on x-ray
Definitive Markers
Subcutaneous nodules
Detection of erosions on x-ray
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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
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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
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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
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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
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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.
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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
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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
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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.
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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
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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
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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
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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
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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
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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
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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*
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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.
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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
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Abatacept – CTLA-4Ig
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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
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Questions
Case report
Questions
Case report
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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.
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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.