1 RA in 2016 It’s not what it Used to Be! Richard S. Pope MPAS, PA-C Dept of Rheumatology Western CT Health Network Danbury, CT 06810 Or is it? RA throughout history Modern disease or Ancient? Archaeological investigations have turned up evidence of injuries, degenerative disease, infections, and tumors in ancient skeletons, but no signs of rheumatoid arthritis. "It isn’t clear how old rheumatoid arthritis is," says Nortin Hadler, MD, a professor of rheumatology and microbiology/immunology at the University of North Carolina at Chapel Hill. "The more you look for it in history, the less you find it.“ The first confirmed cases of RA were probably in the late 1800s Current Hypothesis of Rheumatoid Arthritis • RA is not a disease of recent origin, and was both present and problematic hundreds, possibly thousands of years ago, potentially with a geographic distribution distinct from its current profile. • RA occurs as a response to an environmental stimulus or stimuli experienced by genetically susceptible individuals. • The identities and origins of these stimuli or inciting events are still incompletely known, although tantalizing clues have emerged. • Distinct environmental triggers may be important in subsets of patients with RA. For example, smoking may be a more important risk factor in RA patients who carry an MHC allele that encodes the shared-epitope and who have autoantibodies to citrulline-containing proteins. Thus, the historical analysis of RA needs to incorporate the likely possibility that what we currently define as RA is more than one disease. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119866/ Historical perspective on the etiology of Rheumatoid Arthritis Hand Clin. 2011 Feb; 27(1): 1–10.
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RA in 2016
It’s not what it Used to Be!
Richard S. Pope MPAS, PA-C Dept of Rheumatology
Western CT Health Network Danbury, CT 06810
Or is it?
RA throughout history Modern disease or Ancient?
Archaeological investigations have turned up evidence of injuries, degenerative disease, infections, and tumors in ancient skeletons, but no signs of rheumatoid arthritis. "It isn’t clear how old rheumatoid arthritis is," says Nortin Hadler, MD, a professor of rheumatology and microbiology/immunology at the University of North Carolina at Chapel Hill. "The more you look for it in history, the less you find it.“ The first confirmed cases of RA were probably in the late 1800s
Current Hypothesis of Rheumatoid Arthritis
• RA is not a disease of recent origin, and was both present and problematic hundreds, possibly thousands of years ago, potentially with a geographic distribution distinct from its current profile.
• RA occurs as a response to an environmental stimulus or stimuli experienced by genetically susceptible individuals.
• The identities and origins of these stimuli or inciting events are still incompletely known, although tantalizing clues have emerged.
• Distinct environmental triggers may be important in subsets of patients with RA. For example, smoking may be a more important risk factor in RA patients who carry an MHC allele that encodes the shared-epitope and who have autoantibodies to citrulline-containing proteins.
Thus, the historical analysis of RA needs to incorporate the likely possibility that what
we currently define as RA is more than one disease.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119866/ Historical perspective on the etiology of Rheumatoid Arthritis Hand Clin. 2011 Feb; 27(1): 1–10.
• 23 year old Hispanic female diffuse arthralgias and swelling
• HPI:2 months of gradual onset of mild wrist arthralgias, followed by tingling and weakness of her fingers and dropping things. 1 month later she was waking up with hand swelling, particularly in the wrists bilaterally. She had AM stiffness lasting 30-45 minutes. Then in the last two weeks she had bilateral ankle swelling (L>R). When she kneels it hurts severely and feels like her “knees will explode”. She took two weeks of doxycycline given to her by the Americares clinic. No tick bite history, no rash, no flu lke syndrome. Denied fevers, chills, weight loss. Denies alopecia, rash, photosensitivity, pleurisy, oral or genital ulcers. No change in bowel habits.
Case 2
• FMHx: - for autoimmune disease
• SH: engaged, dental assistant and home health care assistant, past smoker, history of social alcohol use.
• Allergies: NKA
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Case 2
• Physical Exam: + Tinel sign bilaterally, + tender/swollen joints in several PIP and MCP joints bilaterally, tender wrists, and elbows tender and unable to fully extend. 10/18 tenderpoints +.
Case 2
• Anti-CCP
• RF
• Lyme and tick panel
• Parvovirus B-19
• HIV ½
• HLA B-27
• ESR
• CBC
• + 20.9 (up to 20.0)
• RF – 8.6 IU/ml (<=11.9)
• negative
• IgG, IgM negative
• negative
• negative
• 32 (uln is 20)
• CBC – HgB 11.5 – plt ct 414
– MCI normal
Case 2
Before x-rays are taken in a female
Of child bearing years always take a
What test?
Serum pregnancy test
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Foot and hand X-rays
Normal
The truths about x-rays in RA
• Early in disease, x-rays are not diagnostic
– Support the physical findings of soft tissue swelling and joint effusion.
• Later, help determine extent of cartilage destruction and bone erosion, especially when monitoring impact of Rx with DMARDs, biologic response modifiers or small molecule targeted RA meds.
If you ordered X-rays and they were not
normal what would be the description of
Rheumatoid hands with advanced disease?
Rheumatoid
Mouse bite erosions Ulnar deviation or drift MCP and PIP involvement Periarticular osteopenia Symmetrical narrowing (No excess bone)
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What is the sensitivity specificity of RF?
Which of the following is True Regarding the RF autoantibodies
1. RF tests are diagnostic of RA?
2. Only 80-85% of RA patients are ever positive for RF?
3. RF should be serially monitored as a marker for disease activity?
Which of the following is True Regarding the RF autoantibodies
1. RF tests are diagnostic of RA?
2. Only 80-85% of RA patients are ever positive for RF?
3. RF should be serially monitored as a marker for disease activity?
The diagnosis is clinical with support from lab and x-rays
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The truths about Rheumatoid Factor
• <50% of pts are positive within the first 6 months
• Only 80-85% of pts are ever positive
• Not specific for RA: chronic infections, active TB, cirrhosis, malignancies, other rheumatic diseases
• High titer in early RA worse prognosis
• Once positive, not necessary to check again
Lindqvist E, et al. Ann Rheum Dis. 2005;64(2):196-201. Erhardt CC, et al. Ann Rheum Dis. 1989;48(1):7-13.
Wolfe F, et al. Arthritis Rheum. 2003;48(6):1530-1541.
• Antibodies against CCPS: Fibrinogen, enolase, collage II, vimentin and others
• May be seen earlier than RF
• Similar or higher sensitivity for RA than RF – Found in up to 40% of patients who are RF negative
– Not all RA pts are anti-CCP +
• Higher specificity for RA than RF: close to 90-99%
• Predictive of poor prognosis (erosions, joint damage)
Schellekens GA, et al. Arthritis Rheum. 2000;43(1):155-163. Lee DM, et al. Ann Rheum Dis. 2003;62(9):870-874.
Jansen LMA, et al. J Rheumatol. 2002;29(10):2074-2076. Nielen MMJ, et al. Arthritis Rheum. 2004;50(2):380-386.
Vallbracht I, et al. Ann Rheum Dis. 2004;63(9):1079-1084. van Gaalen FA, et al. Ann Rheum Dis. 2005;64(10):1510-1512.
Acute Phase Reactants
Erythrocyte Sedimentation Rate
Male = age/2
Female= (age + 10)/2
Causes of elevated ESR
Infection
CTD
Malignancy
Pregnancy
Anemia
Obesity
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Acute Phase Reactants
C-Reactive Protein
Male=age/50
Female=age/50 + 0.6
Rises and falls more quickly than ESR
Making the Diagnosis
• Does your patient have:
Swollen or tender joints
• Either >1 large or ≥1 small joint of the hands or feet, or
• Positive squeeze test (pain when gently squeezing across the MCP/MTP joints)
Symptoms lasting ≥6 weeks
• If patient has swollen joints or a positive squeeze test as above for ≥6 weeks, refer to a rheumatologist for provisional RA
• If the patient does not meet these criteria but has at least 1 swollen or tender joint and a positive RF or anti-CCP test, he or she should be referred to a rheumatologist
2. Environmental - smoking, bacteria in the microbiome of the mouth, lung, gut (periodontal disease)
3. Initiation of disease – unknown
4. Perpetuation of disease - both innate immune response and adaptive immune response are involved. This creates options for Rx at different levels and thus different drugs developed with separate MOAs.
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What is the patient’s prognosis?
• High + RF and high + CCP show a worse prognosis over time
• The key is to treat the patient aggressively to shut down the disease.
Case 3 New Milford CT
• 60 year old Caucasian male referred sudden onset of bilateral hand pain and knee pain with no observed swelling. 3 separate occasions over the prior 3 weeks he described shaking chills and the 3rd episode he took his temp and it was 101º F. He described fullness and stiffness in his hands which is now lasting 1-2 hrs and improves as the day wears on. Tick bite documented by MD over this right hip. Tick panel xs 2 was negative and six weeks apart. – Then developed an abrupt onset of left followed by right wrist swelling
and swelling behind the left knee.
Case 3 New Milford CT
• ROS: No anorexia, no weight loss or gain, no history of Raynaud’s, malar rash, alopecia, muscle weakness or other autoimmune symptoms. Not sleeping well due to the pain, no history of anxiety, depression.
• Social History: recently retired, social ETOH intake, Married does not smoke and never smoked
Platelets 410,000 (ULN 400,000) WBC 12.1 (has been on prednisone) Chem. profile BS-noon-fasting 135, Creatiinine Anti-CCP > 300 RF 17.6 (negative is < 11.9) HLA B-27 negative Hep B and C negative
• X-rays of both hands – for erosions or symmetrical narrowing
Would you expect the x-ray to
Show erosions?
Case 3 New Milford CT
With the shaking chill xs 3 we were concerned about a septic event
We ordered a transthoracic echocardiogram Results – for valvular lesion were negative
Treatment: What would you do for treatment for this patient
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Case 2 How to improve patient outcomes
Primary care
• Provisional diagnosis
• Early referral to rheumatologist
• Monitor for disease progression, medication toxicities and co-morbidities
Rheumatologist
• Confirm diagnosis
• Initiate early and aggressive DMARD Rx
• Monitor for disease progression, medication toxicities, and comorbidities
Collaboration
RA: Initial Management
• Symptomatic relief while waiting for rheumatology referral
– NSAIDs (short term)
• Assess CV, renal, GI bleed, CHF risk
• Consider GI protectives (PPI, H2RA, misoprostol)
• Preference to COX-2 selective when possible
– Acetaminophen ≤4 g/d
• Screen for other OTC acetaminophen sources to avoid toxicity
– Systemic corticosteroids
• Short term only
• 10 mg/d prednisone (or equivalent) or less
– Simple opioid analgesia as “rescue”
Combe B, et al. Ann Rheum Dis. 2007;66(1):34-35. CV, cardiovascular; GI, gastrointestinal; PPI, proton pump inhibitor; H2RA, H2 receptor antagonists; OTC, over the counter
Steroids
• Generally use only low doses for RA (prednisone ≤10 mg/day)
• Intra-articular steroids might reduce a flare
• Use steroids as a bridge with DMARDs while waiting for DMARDs to work
• Should not be used as solo therapy
van Everdingen AA, et al. Ann Intern Med. 2002;136(1):1-12. Kirwan JR. N Engl J Med. 1995;333(3):142-146.
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What Are DMARDs?
• Disease-modifying antirheumatic drugs
– Alter natural course of disease
– Decrease RA severity, disability, and mortality
– Lower rates of RA complications
– Control of inflammation may decrease cardiac and malignancy risks
– Declining rates of lower-extremity orthopedic surgical procedures in recent years
Weisman M. Ann Rheum Dis. 2002;61(4):287-289. Wolfe F, et al. J Rheumatol. 2001;28(6):1423-1430.
Weiss RJ, et al. Ann Rheum Dis. 2006(3);65:335-341. Pap G, et al. Curr Opin Rheumatol. 2001;13(3):214-218.
Hakala M, et al. J Rheumatol. 1994;21(8):1432-1437. Weinblatt ME. Ann Rheum Dis. 2003;62 Suppl 2:ii94-96.
“Window of Opportunity” in RA
Years of Disease
Rad
iog
rap
hic
Sco
re
(Dis
ease P
rog
ressio
n)
DMARDs are associated with a decrease in radiographic progression
Lard LR, et al. Am J Med. 2001;111(6):446-451. Weisman M. Ann Rheum Dis. 2002;61(4):287-289.
Avery RK. Rheum Dis Clin North Am. 1999 Aug;25(3):567-584. Chalmers A, et al. J Rheumatol. 1994;21(7):1203-1206.
Harpaz R, et al. MMWR Recomm Rep. 2008;57(RR-5):1-30. Herpes zoster (shingles) vaccine guidelines for immunocompromised patients. American College of Rheumatology web site.
Avery RK. Rheum Dis Clin North Am. 1999 Aug;25(3):567-584. Chalmers A, et al. J Rheumatol. 1994;21(7):1203-1206.
Harpaz R, et al. MMWR Recomm Rep. 2008;57(RR-5):1-30. Herpes zoster (shingles) vaccine guidelines for immunocompromised patients. American College of Rheumatology web site.
2. Soft- tissue swelling or fluid in at least 3 joint areas simultaneously
3. At least one area swollen in a wrist, MCP, or PIP joint*
4. Symmetric arthritis*
5. Rheumatoid nodules
6. Abnormal amounts of serum rheumatoid factor
7. Erosions or bony decalcification on radiographs of the hand and wrist
* For classification purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfied at least 4 or these 7 criteria. Criteria 1 through 4 must have been present for at least 6 weeks.