Lisa Maddox, MD 2/22/12

ORTHO-RHEUM ROUNDS

Mr. T (no, the other Mr. T)

46 y/o RHD AA male professional furniture

mover for ~ 30 years Decreased hand strength and pain for ~ 3 years Concerned about not being able to continue to move furniture due to pain and weakness (concern for possible injury to himself or co-workers) Also, intermittent pain in the right instep

Mr. T continued
Originally evaluated by his PCP and was

referred to NRH based on his Xray. Initially seen in MSK outpatient clinic, diagnosed with an inflammatory arthritis
Office Xrays showed moderate to marked erosive

changes in the osseous structures of the wrists, distal radius, ulna carpal bones and metacarpal bases, right hand > left hand

Treated at that time with Dose Pack, Feldene

and referred to Rheumatology

Mr. T continued
PMH:
HTN

Medications:
IB or Naprosyn prn

Allergies:
NKDA

Social History:
Denies EtOH 16 pack year history (quit 1 year ago)

Mr. T Fam Hx
No FH of gout 2 healthy brothers Mother:
DM Spine disease Arthritis in hands and fingers

Father: unsure of history, possible stroke and

HTN

Mr. T, ROS
Stiffness in the mornings
Could not quantify time OTC NSAIDS do help some

Occasional nonproductive cough Denied any back pain Appetite normal

Lost ~ 15 pounds in 2 months

Denied fevers, chills, sweats, h/o infections, tick bite exposure, psoriasis, podagra, infectious diarrhea, or chlamydia exposure

Mr T. Physical Exam
Healthy appearing muscular male in NAD Neck, Heart, Lungs, Abdomen and Skin were

unremarkable Extremities:
Pain and swelling in his bilateral hands, wrists and

MCP joints. Dorsal subluxation, warmth, tenderness and dorsal wrist swelling Separation of his fingernails from the plate Clubbing of the fingernails

Mr. T, Physical Exam continued

Mild tenderness over his right instep. Functional range of motion in all joints + evidence of fingernail and toenail fungal

infection

Mr. T, right wrist 2007

Mr. T, January 2012

Mr. T, January 2012

Mr. T, January 2012

Mr. T, January 2012

Labs
WNL except:

ALT: 62 HCT: 36 RF: 113 Anticitrullinated protein antibody (ACPA ) or Anti Cyclic Citrullinated Peptide (Anti-CCP) antibody: > 250
19 Units or less: Negative 20-39 Units: Weak positive 40-59 Units: Moderate positive 60 Units or Greater: Strong positive

Uric Acid: elevated

Diagnosis and Treatment

Diagnosis
Rheumatoid Arthritis Possible superimposed gout

Treatment
Methotrexate Obtain Hepatitis screening to R/O Viral hepatitis prior to starting Methotrexate Anti-TNF Therapy PPD prior to TNF therapy Allopurinol

RA Classic manifestations

OA vs. RA joint distribution

(A) RA and (B) OA. RA = almost all synovial joints in the body. OA has a much more limited distribution. Importantly, RA, rarely if ever, involves the DIP joints, but OA commonly does.

RA hand deformities
A: Pt with early RA. No joint deformities, but the soft tissue synovial swelling around the 3rd and 5th PIP joints is easily seen.

B: A patient with advanced RA with severe joint deformities including subluxation at the MCP joints and swan-neck deformities (hyperextension at the PIP joints).

Progressive destruction of an MCP joint by RA

Sequential radiographs of the same 2nd MCP joint. A: The joint is normal 1 year prior to the development of RA. B: 6 months following the onset RA, there is a bony erosion adjacent to the joint and joint space narrowing. C: After 3 years of disease, diffuse loss of articular cartilage has led to marked joint space narrowing.

Keys to Optimize Outcome

Treatment Options for RA

Medication DMARDs BRMs Passive treatments Cold/heat Compression and elevation Massage TENS Acupuncture Orthosis

Surgery Synovectomy Arthrodesis Tendon reconstruction

BRM, Biologic response

modifier; DMARD, diseasemodifying antirheumatic drug; TENS, transcutaneous electrical nerve stimulation.

Exercise, Equipment, and Education Treatment Options in Rheumatoid Arthritis

Exercise, Equipment, and Education Treatment Options in Rheumatoid Arthritis Exercises LE strengthening Walking Whole-body physical activity Jogging in water Combined LE strengthening, flexibility, and mobility Aerobic exercises LE range of motion, mobility, or flexibility Manual therapy with exercises

Equipment Adaptive for ADL Assistive for ambulation Appropriate footwear or insoles Education Self-management Weight loss (if obese) Activity management or joint protection Social support Stress management/relaxation ADL, activities of daily living; LE, Lower extremity.

Old ACR criteria

The previous criteria (revised 1987)
Provided the benchmark in defining RA Helped discriminate patients with established RA

from those with a combination of other rheumatologic diagnoses. Was somewhat limited because they did not identify patients who would benefit from early effective intervention

1987 ACR Criteria

Criterion
1. Morning stiffness 2. Arthritis of 3 or more joint areas

Definition
Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a physician. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints At least 1 area swollen (as defined above) in a wrist, MCP, or PIP joint Simultaneous involvement of the same joint areas (as defined in 2) on both sides fo the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry) Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxtaarticular regions, observed by a physician Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in <5% of normal control subjects Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs, which must include erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify)

3. Arthritis of hand joints 4. Symmetric arthritis

5. Rheumatoid nodules

6. Serum rheumatoid factor

7. Radiographic changes

Misc
Smoking increases the risk of RA 20-40 fold In pre-RA, anti-citrullinated protein

antibodies and other auto-antibodies like RFs can appear more than 10 years before clinical arthritis. Rheumatoid synovium has many characteristics of locally invasive malignancy
But never becomes completely unresponsive to

anti-inflammatory and anti-proliferative factors

In 2010, things changed a bit

New (2010) Criteria Goals

Prevent a chronic, erosive disease state (as exemplified by the 1987 criteria) by early

treatment Set of rules to be applied to newly presenting patients with undifferentiated synovitis that would
1) identify the subset at high risk of chronicity and

erosive damage; 2) be used as a basis for initiating disease- modifying therapy; 3) not exclude the capture of patients later in the disease course.

The New ACR/EULAR classification

Helps identify patients with a relatively short

duration of symptoms Helps those that may benefit from entry into clinical trials of promising new agents By initiating these new medications, may halt the development of the disease that currently fulfills the 1987 ACR criteria.

Who can the criteria be applied to?

The classification criteria can be applied to:
any patient or otherwise healthy individual, as

long as 2 mandatory requirements are met:

First, there must be evidence of currently active clinical synovitis (i.e., swelling) in at least 1 joint Second, the observed synovitis is not better explained by another diagnosis

The New Classification Criteria

Jointly published by the American College of Rheumatology (ACR) and the European League

Against Rheumatism (EULAR) Uses a point value between 0 and 10. 6 is unequivocally classified as an RA patient
provided he has synovitis in at least one joint and

given that there is no other diagnosis better explaining the synovitis.

Addresses 4 areas: Joint involvement,

Serological Parameters, Acute phase reactants and arthritis duration

2010 Classification Tree Criteria for Rheumatoid Arthritis (RA)

Joint Involvement
Joint involvement refers to any swollen or

tender joint on examination, which may be confirmed by imaging evidence of synovitis. DIP joints, 1st CMC joints, and 1st MTP joints are excluded from assessment because they are commonly found in OA.

Whats in a joint?
Small joints
MCP PIP thumb IP 2nd-5th MTP Wrist

Large joints
Elbows Hips knees

Joint Involvement and scoring

Type of Joint 1 large joint 2-10 joints 1-3 small joints (+ or large joints) 4-10 small joints (+ or large joints) > 10 joints (w/ at least 1 small joint) 1 joint must be a small joint; the other joints can include any combo of large and additional small joints, as well as other joints not specifically listed elsewhere (e.g., TMJ, AC SCJ, etc) Points applied 0 points 1 point 2 points 3 points 5 points

Serologic
Serology criteria:
at least 1 test result is needed for classification i.e., Anti-Citrullinated Peptide Antibodies or Rheumatoid Factor

Serologic
Neg test Low positive High Positive ULN > ULN ULN X 3 > ULN X 3

Serologic Marker Negative RF and negative ACPA Low-positive RF or low-positive ACPA High-positive RF and/or high-positive ACPA ULN = upper limit of normal RF = rheumatoid Factor ACPA = anticitrullinated protein antibody

Points 0 points 2 points 3 points

What is CCP
The cyclic citrullinated peptide antibody (CCP) test is an assay that detects the presence of

citrulline antibodies in the blood.

These autoantibodies are proteins produced by the

immune system in response to a perceived threat from citrulline. Citrulline is an unusual amino acid produced when the amino acid arginine is altered There is speculation that the conversion of arginine to citrulline may play a role in the autoimmune inflammatory process seen in the joints of those with RA

Why CCP/ACPA?
2nd generation CCP antibody testing:
sensitivity of 80% and a specificity of 98% for RA

Robust Rheumatoid Arthritis

Cohort of patients that had:
robust personality Practically infinite capacity for work Substantial subcutaneous nodules (often the

reason for the referral) High titer on the Rose test

Robust Rheumatoid Arthritis

ROM was unaffected and unguarded Joints were at sometime painful, but rarely had

to stop working Shoulder joints affected in all patients Subcutaneous nodules at the elbows and the fingers in 3 patients
Pathology confirmed RA histology

Function:
Decreased grip strength

Most were on maintenance Gold Therapy

Robust Rheumatoid Arthritis

Psychologically the Robust patient scored

more closely to normals, with regard to:

exploitation of disease-induced dependence
Neuroticism Robust RA scores normal, in contrast to most RA patients who tended to have higher scores

Robust Rheumatoid Arthritis

Robust type rheumatoid arthritis represents a

special reaction to the disease of a strong body supported by a tough mind, but is in no other way a separate clinical entity.

Robust Rheumatoid Arthritis

They had the prognostically unfavorable symptoms of subcutaneous nodules and a high

titer of the Rose test However the were robust, felt well and worked normally. Additional sthentic (i.e., strong, vigorous, or active) properties included:
Athletic build, good grip strength, high pain threshold

in the finger joints, mental stolidity and independence

Raised question of possibility of mental attitude on disease and disability

Outcome Measures and Treatment Efficacy

counts of the number of tender and swollen

joints; patient and physician global assessment of disease activity; pain assessment using a visual analogue scale; a validated measure of disability; and an acute phase reactant (e.g., erythrocyte sedimentation rate or C-reactive protein).

Commonly Used Outcome Measures For The Rheumatic Diseases

Treatment to Target Schema

Treatment to Target
Recommendations

Treating rheumatoid arthritis to target: recommendations of an international task force http://ard.bmj.com/content/69/4/631.short

Treatment to Target
Treatment of RA must be based on a shared decision

between the patient and the rheumatologist The primary goal of treating the patient with RA is to maximize long-term health-related quality of life through control of symptoms, prevention of structural damage and normalization of function and social participation Abrogation of inflammation is the most important way to achieve these goals Treatment to target by measuring disease activity and adjusting therapy accordingly optimizes outcomes in RA

Medication Options
NSAIDS Glucocorticoids DMARDS Biological DMARDS

Medication Options - DMARDS

Conventional (synthetic) DMARDs:
methotrexate sulfasalazine gold no longer commonly used antimalarials

leflunomide
azathioprine penicillamine

minocycline.

Biological DMARDS
Biological DMARDs:
Biological therapies have had a significant impact

on the treatment of patients with RA. It is now clear that proinflammatory cytokines, most notably tumor necrosis factor- (TNF- ) and interleukin-1, play a central role in the pathophysiology of RA

Biological DMARDS
Anti TNF
Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) Interleukin-1 (anakinra)

Block T-cell co-stimulation

Abatacept (Orencia)

Target B-cells
Rituximab (Rituxan)

References

Aletaha, D., et al.:2010 Rheumatoid Arthritis Classification Criteria, Arthritis & Rheumatism Vol. 62, No. 9, September 2010, pp 25692581 http://www.rheumatology.org/practice/clinical/classification/ra/ratree_2010.asp Schur, PH, et al.: Pathogenesis of rheumatoid arthritis; www.uptodate.com De Haas, WH, et al: Rheumatoid arthritis of the robust reaction type.; Annals of Rheum Disease. 1974 January; 33(1): 8185. Atzeni, F, et: Anti-cyclic citrullinated peptide antibodies in primary Sjgren syndrome may be associated with non-erosive synovitis.; http://arthritisresearch.com/content/10/3/R51, Arthritis Research & Therapy 2008, 10:R51 Vossenaar, ER: Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis.; Arthritis Research and Ther 2004, 6:107-111 (DOI 10.1186/ar1184). Braddom, Physical Medicine and Rehabilitation 3rd Edition Current Rheumatology Diagnosis & Treatment, 2nd edition