Update in Rheumatology 2010. Brian F Mandell md phd facr facp Professor and Chairman of Medicine Department of Rheumatic and Immunologic Diseases Center for Vasculitis Care and research Cleveland Clinic. Update in Rheumatology. Rheumatoid arthritis Diagnostic guidelines CCP
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Brian F Mandell mdphdfacrfacp
Professor and Chairman of Medicine
Department of Rheumatic and Immunologic Diseases
Center for Vasculitis Care and research
26yo F c/o acute onset of fatigue, with pain and swelling of bilat wrists, MCPs (2,3,5), PIPs (2,3,4,5), and knees 12 days previously. She needed to remove her rings.
10 months post partum, daughter in day care, not breast feeding
PE: Markedly tender synovitis with effusions as above; no oral or skin lesions. Rest of exam is normal.
LABS: ESR 38, CBC, AST, ALT, Creat, UA normal. RF + @ 24.
26yo F c/o acute onset of fatigue, with pain, tenderness and swelling of bilat wrists, MCPs , PIPs, and knees 12 days previously.
ESR 38, CBC, AST, ALT, Creat, UA normal. RF +.
You decide to:
Hep C is a mimic of seropositive RA!!
(ccp = cyclic citrullinated peptide)
because prognosis is hard to predict, current trend:
Treat early and treat aggressively.
Goal is to prevent damage from occurring.
“This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with developing persistent and/or erosive disease, rather than defining the disease by its late-stage features.”
Target population (Who should be tested?): Patients who
1) have at least1 joint with definite clinical synovitis (swelling)
2) with the synovitis not better explained by another disease
Add A–D; a score of 6/10 is needed to classify patient as having definite RA
1 large joint. 0
2-10 large joints 1
1-3 small joints (with or without involvement of large joints) 2
4-10 small joints (with or without involvement of large joints) 3
3-10 joints (at least 1 small joint) 5
B. Serology (at least 1 test result is needed for classification)
Negative RF and negative ACPA 0
Low-positive RF or low-positive ACPA 2
High-positive RF or high-positive ACPA 3
C. Acute-phase reactants (1 test result is needed for classification)
Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
D. Duration of symptoms
6 weeks 0
>6 weeks 1
(initial methotrexatemonotherapyvs its combination with adalimumab)
In Management of Early Active Rheumatoid Arthritis:
Data from the GUEPARD Trial
Rheumatology 2009 Volume 48, Number 11: 1429-1434
Soubrier, M. et al. Rheumatology 2009 48:1429-1434
Type II DM [HR=2]
Rheumatoid Arthritis [HR=2.2]
Peters et al Arthritis and Rheumatism 2009
Now increasing fatigue, swelling and “pain all over”. She describes increased AM stiffness of her back, neck, hands, hips, chest with trouble sleeping, and difficulties with painful “flares” following any physical exertion. ESR is 32, RF is high titre.
Exam: multiple tender, non-swollen joints; mild ulnar deviation with prolif non-tender bilat 2,3 MCPs, normal grip strength; bilateral trochanteric bursitis / gluteal tenderness / costochondral tenderness.
A. INCREASE PREDNISONE TO 10 mg q A M
B. INCREASE MTX 20 mg WEEKLY
C. ADD A TRICYCLIC AND EXERCISE
D. ADD AN ANTI-TNF AGENT
THE MACK TRUCK
1.Widespread pain index (WPI) >7 and Symptom severity score (SS) >5 or WPI 3-6 and SS >9
2. Symptoms present > 3 months
3. No other disorder to explain pain
WPI – listing of 19 different anatomic sites (1 point per site)
SS - (scored in severity in past week)
Waking unrefreshed (0-3)
Cognitive symptoms (0-3)
Wolfe et al. Arth Rheum 62:600-10, 2010
Prior to current therapy, he had several severe attacks/yr causing him to miss work.
Current meds: enalapril 20 mg, colchicine 0.6 daily, and allopurinol 300 mg qd.
BP 126/70. He has a few olecranonnontender movable nodules, a cool tender left 1st MTP joint with overlying nodule. He has no gallop or edema. The examination is otherwise normal.
Lab: normal CBC, AST, glucose and creatinine. urate is 7.2 (normal < 7.8 mg/dl).
BP well controlled at 126/70. He has a few olecranonnontender movable nodules, a tender left 1st MTP joint with overlying nodule. He has no gallop or edema. The examination is otherwise normal.
Lab: normal CBC, AST, lytes, glucose and creatinine. The serum urate level is 7.2 (normal <7.8 mg/dl).
A. Stop colchicine; continue allopurinol 300; naproxen as needed.
B. Stop colchicine and stop allopurinol, use naproxen as needed.
C. Stop colchicine and increase the allopurinol to 400mg daily; use naproxen as needed.
D. Continue colchicine and increase the allopurinol to 400 mg daily; use naproxen as needed.
Urate crystallizes at
a level of ~6.7 mg/dL
( biological hyperuricemia )
Serum urate levels in 1515 men and 1670 women aged ≥30 in Taiwan 1991-1992
Patients may fit the biological definition for hyperuricemia
but be in the “normal “ range
Serum urate, mg/dL
Lin et al. J Rheumatol. 2000;27:1045-1050.
LEVEL of URATE ~8.0mg/dl
IS NOT BIOLOGICALLY “NORMAL”
URATE SATURATES BIOLOGICAL FLUIDS AT A LEVEL > 6.7
BUT: 47% of Pts HadINADEQUATERESPONSE
to 300mg !
IFDOSE ADJUSTED TO ACHIEVE
TARGET [URATE] LEVEL:
< 6 mg / dl
Perez-Ruiz et al Ann Rheum Dis 57:545-49,1998
Sarawate et al Mayo Clin Proc 81:925-34, 2006
Perez-Ruiz F and Liote F. Lowering serum uric acid levels: what is the optimal target for improving clinical outcomes in gout? Arth Rheum 57: 1324-1328, 2007
sUA 6.0 mg/dLGout Flares After Hypouricemic TherapyInfluenced by Post-Treatment Urate Level
Early flares with acute hypouricemia
(when prophylaxis stopped)
fewer flares with
Subjects Requiring Treatment
1 to 8
8 to 16
16 to 24
24 to 32
32 to 40
40 to 48
48 to 52
Weeks of Treatment (allopurinol of febuxostat)
Becker et al NEJM353:2450-61,2005
40 PATIENTS WITH GOUT; STARTED ON ALLOPURINOL, GIVEN COLCHICINE or PLACEBO (20 in each group)
39 WITH 3 MONTH, 22 WITH 6 MO F/UP
Borstad et al Arth Rheum 46:S140, 2002; J Rheumatol 31:2429-32, 2004.
Gradual drop, fewer flares (?)
TransporterThe Hyperuricemia - Metabolic Syndrome Link With a Twist ( in the RAT )
(vs. dextrose to rats)
Nakagawa et al Am J Physiol Renal Physiol 290:F625-31, 2006
Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response
S E Perez-Pozo, J Schold, T Nakagawa, L G Sánchez-Lozada, R J Johnson and J López Lillo. International Journal of Obesity advance online publication 22 December 2009
2 week study, n=74
200g fructose daily
+/- allopurinol 300 mg
In addition to initiation of calcium and vitamin D therapy, which of the following is the most appropriate next step in this patient’s management?
Even with a “normal” bone density, the age and the high dose corticosteroids needed to treat the GCA significantly increases the fracture risk. The addition of bisphosphonate therapy should be strongly considered.
Excess resorption, Oclasts
Reduced Ca absorption
in placebo arm of
BP/steroid OP trials
compared to 1899
from other trials.
at 1 year at specific
Fracture Incidence (%)
Lumbar Spine T-Score
Van Staa TP et al Arth Rheum 48:3224-29, 2003
Question # 9
Question # 9