Transcript Rheumatoid Arthritis

Rheumatoid
Arthritis
Chris Gordon, M.D.
• I don't deserve this award, but I
have arthritis and I don't deserve
that either.
– Jack Benny (1894 - 1974)
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History
Mrs. B is a 66 year old Caucasian woman who was treated with Celebrex for joint
pain. Ten days after starting therapy she developed a diffuse, pruritic, erythematous
rash and was admitted to the hospital. Dermatology consult and skin biopsy were
obtained. Pathology was consistent with a drug eruption. The rash improved with
intravenous steriods. On hospital day #3 she complained of dyspnea. A chest x-ray
showed a new large left pleural effusion.
Past Medical History
"Arthritis" since the age of 13; treated only with intermittent NSAIDS and steroids.
Right-sided empyema one year ago treated with prolonged antibiotics and chest
tube drainage.
History of coronary artery disease (CAD), non-insulin dependent diabetes mellitus
(NIDDM), chronic obstructive pulmonary disease (COPD), depression, diverticulitis
Medications
Cardizem, Pepcid, Premarin, Remeron, Darvocet
Social History
She worked as a typist but quit because of arthritis when she was in her 20's. She
smoked 1-2 packs of cigarettes a day for 40 years.
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Review of Systems
Diffuse joint pain and stiffness, worse in the morning, lasting all day, denies
joint swelling or warmth. She is able to do all of her activities of daily living.
Denies constitutional symptoms
Mild sicca symptoms, no history of sinusitis or otitis
Denies prior history of rash, photosensitivity, alopecia, oral ulcers,
Raynauds, paresthesias, myalgias, weakness
Physical Examination
The patient was frail, somewhat anxious and confused.
BP 130/60, pulse 70, afebrile.
HEENT - no alopecia, conjunctivae were clear, no nasal or oral ulcers.
Lungs - decreased breath sounds at left base, no crackles or wheezes;
surgical scar over right posterior chest. Cardiac and abdominal exams
were unremarkable. Neurological exam was nonfocal. The skin showed
diffuse erythematous macules over her trunk and extremities.
• Musculoskeletal exam was notable for the following:
cervical spine - mildly diminished range of motion
shoulders, elbows - full range of motion without synovitis,
tenderness, or deformity
MCPs - synovial thickening with minimal tenderness, slight ulnar
deviation, subluxations of the IPJs
PIPs - no synovitis, deformities, or tenderness
DIPs - Heberden nodes
hips, knees, ankles - full range of motion without synovitis,
deformities or tenderness
feet - hallux valgus, no synovitis
• Laboratory Studies
• Hematocrit 37.5%; WBC 6,800; platelets 674,00; ESR 35;
electrolytes normal; BUN 25; creatinine 0.9; glucose 193; calcium
9.1; albumin 2.7; total protein 5.6; liver function tests normal; uric
acid 5.5 urinalysis negative for blood or protein. ABG on room air:
pH 7.42 pCO2 35 p02 61, 93% saturation
• Clinical Course and Radiology Studies
• Chest x-ray one year prior to admission showed clear
lung fields following drainage of the empyema.
• Chest x-ray taken on hospital day #3 shows a large left
pleural effusion.
• On hospital day #3 thoracentesis produced 540cc of
turbid fluid: WBC 2025, 6% neutrophils, 42%
lymphocytes, 52%; reactive mesothelial cells; LDH
9638; glucose 133; total protein 4.6
• On hospital day #4, the left pleural effusion rapidly reaccumulated, requiring a repeat thoracentesis WBC
1346,; LDH 7579; glucose 139; total protein 4.7; pH 7.1
• Pleural fluid showed no malignancy on cytology; a
negative AFB and fungal smear; a negative Grams stain
and routine culture.
• The patients dyspnea improved after the thoracentesis.
She remained clinically stable with minimal joint pain
throughout her hospitalization.
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On hospital day #5, a chest CT scan showed a 2.0 x 1.5 cm lung mass at the right
posterior base with right hydropneumothorax and a left pleural effusion. Multiple lung
nodules were present in both lung fields.
(click on image for larger view)
A CT-guided transthoracic needle biopsy was performed on both the right lower and
upper lung masses. Biopsy results were non-diagnostic showing only necrotic debris
and inflammatory cells.
On hospital day #12, thoracoscopic biopsy of the left lower lung mass was
performed.
A Rheumatology consult was obtained.
• Differential Diagnosis of Exudative Pleural Effusion
1.[ ]Infection (parapneumonic, tuberculosis, fungi)
2.[ ]Malignancy (bronchogenic, metastatic)
3.[ ]Pulmonary Embolism
4.[ ]Gastrointestinal disease
5.[ ]Rheumatic Conditions (rheumatoid arthritis, systemic lupus
erythematosus)
• Differential Diagnosis of Pulmonary Nodules
1.[ ]Infection (tuberculosis, fungi, pyogenic abscess)
2.[ ]Malignancy (bronchogenic, lymphoproliferative, metastatic)
3.[ ]Benign tumors
4.[ ]Arteriovenous malformations
5.[ ]Rheumatic conditions (rheumatoid arthritis, Wegeners
granulomatosis, Churg-Strauss, sarcoidosis, amyloidosis)
• Pathology Results
• The gross pathologic examination revealed
multiple small yellowish nodular lesions. Most of
the lung showed interstitial fibrosis and chronic
inflammation. There were several areas of
necrosis of varying size. There were no areas of
palisading cells. Special stains for mycotic and
acid fast organisms were negative.
• The final pathologic reading described changes
most consistent with Wegener's granulomatosis,
but the possibility of a rheumatoid nodule could
not be excluded.
• Additional Diagnostic Studies
• Rheumatoid factor was highly positive at a
titer of 1:1280.
• Anti-neutrophilic antibodies were negative.
• CT scan of the sinuses was normal.
• Hand x-rays showed erosions most
consistent with rheumatoid arthritis.
• Case Discussion
• Summary:
Mrs. B is a 66 year old smoker with a long history of
"arthritis" and an empyema one year ago, who
presented with a new exudative pleural effusion and
multiple lung nodules. Although the pathology of the
lung nodule showed features suggesting Wegeners
granulomatosis (necrotizing vasculitis, giant cells,
disorganized cellular infiltrate), she lacked clinical
evidence to support this diagnosis. The most likely
cause of her illness was seropositive, erosive
rheumatoid arthritis complicated by pulmonary
rheumatoid nodules, bronchopleural fistulae, and
recurrent pleural effusions.
• Conclusions
• There were several unusual features of this case: the
patient was a woman without nodular disease, the
pleural effusions were bilateral with a normal glucose
and many mesothelial cells, and the pathology was not
classic for a pulmonary rheumatoid nodule. However,
she lacked clinical evidence of other diagnoses, and in
fact, had a very high titer rheumatoid factor as well as
classic findings of erosive RA on hand x-rays. This case
illustrates the importance of viewing RA as a systemic
disease, not simply a problem of joints
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Most common inflammatory arthritis
Affects 0.8% worldwide
Usually begins between ages 30 and 50
US incidence 25 per 100,000 in men and
54 per 100,000 in women1
• 250,000 hospitalizations and 9 million
visits annually2
• 20-30% disabled within 3 years if
untreated3
Etiology
• Not fully understood
• Genetic and environmental factors
• 30% concordance rate in monozygotic
twins
• 80% of Caucasians with RA express HLADR1 or -DR4 subtypes
• Specific arthrogenic peptides to be
presented to CD4+ T cells?4
Pathophysiology
• Triggering incident (auto-immune vs infection)
• Proliferation of synovial macrophages and
fibroblasts leading to lymphocyte and
endothelial cell proliferation
• Small vessel occlusion leading to ischemia,
neovascularization, inflammation
• Irregular growth of inflamed tissue (Pannus
formation)
• Destruction of cartilage and bone and systemic
complications
Risk Factors
Positive6,7
• Female
• Smoking
• Age
• Family history
• Silicate exposure
• Caffeine ?
Negative8
• High vitamin D intake
• Tea consumption
• OCP use
Signs / Symptoms
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Primarily a clinical diagnosis
Morning stiffness > 45 minutes
Anorexia
Weakness
Fatigue
Low grade fever
Pain, stiffness, tenderness, swelling, bogginess
in multiple joints (wrist, PIP, MCP)
• Muscle atrophy
• Joints held in slight flexion
ACR Criteria9
Differential Diagnosis
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Connective tissue diseases
Fibromyalgia
Hemochromatosis
Infectious endocarditis
Polyarticular gout
Polymyalgia rheumatica
Seronegative spondyloarthropathies
Reactive arthritis
Diagnostic Tests
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CRP
ESR
Rheumatoid factor
CBC
Anticyclic citrullinated peptide antibody
ANA
Complement levels
Immunoglobulins
Joint aspiration
Urinalysis
RF and anti-CCP
• RF
• Specificity 80%
• Negative in 30% early
in disease
• Repeat 6-12 months
• + in SLE,
scleroderma,
infection, cancer,
Sjogrens
• Anti-CCP
• Correlates well with
disease progression
• Specificity 90%
• Increased sensitivity
when used with RF
Treatment
• Joint destruction begins within weeks of
symptoms
• Early treatment decreases rate of joint
destruction14
• Refer to specialist within 3 months
• NSAIDS
• Glucocorticoids
• DMARDs
Goals of Care
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Preservation function
Preservation of quality of life
Minimize pain and inflammation
Protect joints
Control of systemic complications
NSAIDs2
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Used initially for symptom control
Don’t alter disease progression
Should not be used alone
Twice as likely to have NSAID
complication then patients with OA
Glucocorticoids
• Highly effective in relieving symptoms
• Slow joint damage
• Doses as low as Prednisone 10 mg daily
effective
• Minimize dose to avoid side effects
• Vitamin D and Calcium supplements
• Often used as bridging therapy with DMARDs
• Joint injection useful if single joint inflamed
DMARDs
• Consider for all patients
• Combinations can be more effective than
single drugs
• Contraception for women
• Comorbidities, experience and severity
guide selection
• Sulfasalazine or Hydroxychloroquin
usually initiated
• MTX or combination if severe
Algorithm8
Leflunomide
• Arava
• Dose: 10 – 20 mg daily
• Competitive inhibitor of an intracellular
enzyme needed for de novo pyrimidine
synthesis by activated lymphocytes19
• Slows progression of joint damage
• Prevented new erosions in 80% of
patients over two years22
TNF Antagonists
• Etanercept (Enbrel)->long-term effects
comparable to MTX,
• Infliximab (Remicade)->patients with
poorer MTX reponse had better
outcomes17
• Adalimumab (Humira)->long-term effects
are comparable with MTX in some
studies, rapid effects within 2 weeks23
• Increased risk of infection, TB reactivation
Adjunctive
• + Evidence
• Therapeutic fasting
• Dietary supplementation
of essential fatty acids
• Journaling have shown
benefit26
• Spa therapies27
• Exercise28
• Patient education29
• Multi-disciplinary
approach to patient
care30
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No evidence
Herbal medications31
Acupuncture26
Splinting32
Complications
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Anemia
Cancer
Pericarditis, myocarditis, AV block
C-spine Dz / Tenosynovitis tranverse ligament
Episcleritis
Ulnar deviation MCP, boutonniere deformity, swan neck
deformity
Rheumatoid nodules
Lung nodules
Vasculitis
Increased infections
Boutonniere Deformity
Swan Neck Deformity
Rheumatoid Nodules
The End!