Arthritis in the Arthritis in the ElderlyElderly

Gerald F. Falasca, M.D.

Johnson City, TN

March 2013March 2013

“All the Pearls in 50 Minutes”

GOALS

• Practical advice

• Up to date on mgt

• Hone diagnostic skills

DISEASESTo Be Touched On

• Sjogren’s

• PMR

• DJD

• RA

• Gout

CASE 1

• A 70 year old woman presents with widespread pain, stiffness and fatigue. She recently started keeping a water bottle at her bedside. Physical exam is remarkable for slight synovitis of hands & wrists, and presence of all fibromyalgia tender points.

CASE 1 – cont’d.

• Sed rate is 30 mm/hr but CRP is normal CRP at 0.7 mg/dl (nl 0 - 1.0 mg/dl)

• C4 ↑ at 36 mg/dl.

• RF, CCP & ANA are negative.

CASE 1 – cont’d.

What is the most likely diagnosis?

A. Polymyalgia rheumatica

B. Rheumatoid arthritis

C. Fibromyalgia

D. Primary Sjogren syndrome

E. Paraneoplastic syndrome

Causes of Pain All Over in the Elderly

• Polymyalgia rheumatica• Statins• Fibromyalgia• Depression• Sjogren’s• Rheumatoid• Lupus• Osteoarthritis

Primary Sjogren’s

• Dry eyes, dry mouth

• Fatigue

• Pain all over

• No idea what is wrong with them

• You probably have some in your practice

Sjogren’s - History

• Use of eye drops?

• Can you eat crackers w/o water?

• Keep water on night table?

• Physical Exam: Nothing specific!– Sometimes small joint puffiness– Peripheral neuropathy

Sjogren’s - Lab

• SSA / SSB – insensitive

• ESR often up

• CRP high normal

Sjogren’s - TX

• Hydroxychloroquine

• Low-dose prednisone

• Methotrexate

• Rituximab

• Fibromyalgia treatments (for symptoms)

Polymyalgia Rheumatica

• 10-15% go on to GCA• Respond well to treatment

• In other words, this is a potentially serious disease that is treatable.

PMR

• Pain all over; sudden onset.• Age > 50 (usually >70!)• Weight loss• Shoulder limitation of motion

(periarthritis)• Proximal muscle tenderness• Sed rate > 50 mm/hr• Anemia

PREDNISONE in ELDERLY

• ↓K+, ↑glucose

• DEXA

• Calcium + Vit D

• T/C bisphosphonate

• Eye exams: cataracts & pressure

Amer. College of Rheum.

• Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis 2010

• Arthritis Care & Research, Vol. 62, No. 11, November 2010, pp 1515–1526

• DOI 10.1002/acr.20295

GOUT

The risk factors for gout were known to the

ancients.

Risk Factors for Gout

• Obesity, metabolic syndrome

• Ethanol

• Diuretics

• Fructose ingestion

• Excessive purine ingestion

Ben Franklin (1706 -1790)

"Be temperate in wine, in eating, girls, and sloth, or the Gout will seize you and plague you…"

-- Franklin

Drugs Associated with Hyperuricemia

• Diuretics (loop and thiazide types)

• Low-dose aspirin

• Ethanol

Hyperuricemia & Gout

Serum Uric Acid (mg/dl)

Annual Incidence of Gout (%)

< 7.0 0.1

7.0 – 8.9 0.5

> 9.0 4.9

This is chronic refractory

gout!

Amer. College of Rheum.

• Guidelines for Management of Gout. Part 1 & 2

• Arthritis Care & Research, Vol. 64, No. 10, October 2012, pp 1431–1461

• DOI 10.1002/acr.21773

The Three Phases of Gout Treatment

• Treat acute attack

• Prevent new attacks

• Reduce uric acid level (sometimes)

Phase 1 - Termination

• NSAID

• Colchcine

• Intra-articular steroids

• Systemic steroids

• IL-1 inhibitor (off-label use)

NSAIDs

• Treatment of choice in otherwise healthy (elderly?) patient.

• Avoid in renal insufficiency and in peptic ulcer disease.

• Avoid salicylates (these cause swings in serum uric acid).

Intra-Articular Steroids

• One or a few joints.

• Make sure infection not present.

Oral Colchicine

• 1.2 mg followed by 0.6 mg 2 hrs later.

• Loading dose same in renal insufficiency.

• Maintenance (preventive) dose 0.6 mg qd or bid.

• 0.3 mg 2-3 times per week in dialysis patients (preventive).

Systemic Steroids

• Polyarticular attacks or fever.

• Longstanding attacks (>3-5 days).

• Need divided doses.

• Taper over 7-10 days.

• Start prophylactic agent (colchicine) as soon as possible.

Adjunctive Measures

• Rest

• Ice

• Elevation

• Analgesics

• Anti-motility agents (if using colchicine or indomethacin)

• Continue hypouricemic agent if patient has been taking it.

Phase 2 - Preventive Therapy

• Colchicine or NSAID.• Always use when beginning a

hypouricemic drug.• Continue several weeks to years

(depending on tophi, serum uric acid).

• Always use before surgery in previously gouty patient.

Phase 3 - Hypouricemic Therapy

• Not every patient needs it.

• May not need it in:– Very elderly– Non-compliant– Infrequent attacks and no tophi

• May exacerbate attacks early on

Goals of Hypouricemic Treatment

• Aim for serum uric acid under 6, preferably near 5 for some chronic gouty patients.

• But remember:– allopurinol toxicity more likely with

higher dose.– More likely with renal insufficiency.

Hypouricemic Agents

• Allopurinol

• Febuxostat

• Probenecid

• Losartan (off-label)

• Vitamin C (off-label)

• Pegloticase

Major Toxicities of Allopurinol

• Increased gout attacks early on (use prophylaxis)

• Rash (may be severe)

• Stevens-Johnson syndrome

• Vasculitis

• Hepatitis

• Renal failure (interstitial nephritis)

• Bone marrow suppression

Allopurinol Hypersensitivity Syndrome

• Fever• Rash• Renal Failure

• Hepatic injury• Leukocytosis• Eosinophilia (the

tipoff!)

• May be fatal. Hard to treat.

• Serious reactions to allopurinol reported

in 1 of 260 patients. Arthritis Rheum 29:82, 1986

Febuxostat

• Non-xanthine inhibitor of XO and XD.

• Better tolerated than allopurinol.

• Lower uric acid levels than allopurinol (53% vs. 21% met target of 6.0 mg/dl).

• Better dissolution of tophi.

Tophus ReductionMean Reduction in Tophus Area

Becker MA. N Engl J Med. 2005 Dec 8;353(23):2450-61. Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

Group % Area Reduction P Value

Feb 80 mg 83 P = .08 (NS)

Feb 120 mg 66 P = 0.16 (NS)

Allop 300mg 50

Febuxostat vs. AllopurinolPercentage of Patients Achieving Serum

Uric Acid < 6 mg/dl

Study 1: Allopurinol dosed at 300 mg/d for ClCr ≥ 60 ml/min or 200 mg/d for 30 ≤ ClCr ≤ 59 ml/min.

Febuxostat: Best Use

• Allopurinol failures

• Renal insufficiency

• Tophaceous gout

Allopurinol & Febuxostat Drug Interactions

• Life threatening interaction with azathioprine, 6-mercaptopurine.– Reduce dose of purine analogue by

approximately 2/3.

• Theophylline

• Other interactions also

Gout vs. Pseudogout

• Gout– hallux, ankle, knee, hand– younger, male

• Pseudogout– knee, wrist, ankle– older, female

• Almost any joint can be affected by either disease!

CPPD Deposition

• Wrist: triangular ligament

• Pelvis: symphysis pubis

• Knee: menisci

• Also: annulus fibrosis, articular capsules, bursae, ligaments, tendons

Clinical Associations with Psuedogout

• Aging• Previous joint

surgery• Previous joint

trauma• Familial types• Gout• Amyloidosis

• Hyperpara• Hemochromatosis• Hypomagnesemia• Familial hypocalciuric

hypercalcemia• Hypophosphatasia• Wilson’s disease• Ochronosis

Pseudo-DJD Pattern of CPPD

• 50% of CPPD patients.

• Wrists, MCPs, elbows, shoulders, knees. Note difference from usual DJD pattern.

• Heberden’s or Bouchard’s frequently found.

• May be acute or chronic.

Treatment of Acute Psuedogout

• Aspiration (more important than in gout!)

• Rest

• Intra-articular steroids

• NSAIDs

• Systemic steroids

• Colchicine?

• IL-1 Inhibitors?

Pseudogout Prevention

• Colchicine

• NSAID

• Magnesium?

• There’s no allopurinol for pseudogout (unfortunately).

The Basic (Non-Acidic) Calcium Phosphates

• Hydroxyapatite

• Calcium carbonate

• Octacalcium phosphate

• Tricalcium phosphate (whitlockite)

• Hydroxyapatite is non-birefringent.

Syndromes Associated with Hydroxyapatite

• Acute monoarthritis (pseudopseudogout)

• Acute calcific tendinitis, bursitis

• Scleroderma, dermatomyositis

• Heterotopic calcification

• Milwaukee shoulder

• Crowned Dens Synd.

Acute Apatite Monoarthritis

(Pseudopseudogout)• Is usually a peri-arthritis.

• Intense inflammation (looks septic)

• Synovial fluid often non-inflammatory.

• Often causes podagra (especially in younger women).

• Look for the telltale calcifications on radiographs.

CROWNED DENS SYNDROME

Crowned Dens Synd

• Headache

• Pain with head rotation

• Shoulder myalgias

• Very elevated sed rate

RHEUMATOIDARTHRITIS

In the Elderly

Rheumatoid

• Even in the elderly, completely new paradigm of treatment.

• Dual goals:– Symptom improvement– Prevention of structural damage

Rheumatoid

• “Small joint polyarthritis with morning stiffness”

• MCPs, wrists, MTPs

• ESR, CRP may or may not be up.

• RF or anti-CCP pos 70%

RA in the Elderly

• M:F ratio more nearly equal

• More shoulder involvement

• May overlap with polymyalgia rheumatoica

Initial Tx of RA

• Low dose prednisone (actually a good DMARD!)

• Methotrexate – safer than we expected in 1987!– Lung toxicity is possible– Follow liver enzymes– Added infection risk is relatively low

(2-3%).

What We Try to Prevent

The New Paradigm

• Is it likely that the patient will have destructive or debilitating disease in the long-term?

• If so, begin one or more DMARDs (often MTX).

• If inadequate response after 3 months, add or switch DMARDs, often includes a TNFI.

Anti-CCP

• CCP = cyclic citrullinated peptides• RA synovium overproduces CCP• RA patients THEN make

ANTIBODIES to CCP• 70% sensitive, 90% specific• Anti-CCP is often present years

before RA manifests itself.

Goals of the New Criteria

• Identify persons with “early arthritis” who are at high risk of erosive or debilitating disease.

• Allow for earlier disease modifying treatment.

• But…the criteria are not simple!

2010 ACR/EULAR CRITERIA FOR CLASSIFICATION OF RHEUMATOID ARTHRITIS

Arthritis & Rheumatism 62(9): 2569–2581, 2010.

Lab Eval of Polyarthritis

• Rheum factor• Anti-CCP• ANA• C4• Lyme• CBC• Chem-12

• SSA, SSB• Anti-RNP

Methotrexate

• Standard of care for RA.• dihydrofolate reductase inhibitor.• Best initial treatment for most patients.• Avoid in pre-existing liver disease, renal

disease and in drinkers.• Main risk: pulmonary toxicity• Higher doses being used, espec. Sub Q.• 1/3 of patients will have little or no

radiographic progression on MTX alone.

Methotrexate (cont’d)

• Always give only once a week, but dose may be split in two parts, and given 12 hours apart.

• Most persons should receive supplemental folate 1 mg/d.

• Follow liver enzymes (with albumin), CBC, creatinine monthly initially.

Methotrexate - Side Effects

• Nausea, diarrhea• Stomatitis• Alopecia• Rash• Infections• MTX

pneumonitis

• Hepatitis• Cirrhosis• Pulm. fibrosis• Pancytopenia• Lymphoma?

• Don’t use if creatinine > 2.0!

TNF Inhibitors

• Potent inhibitors of inflammation

• Have revolutionized the treatment of RA since 1998.

• They retard erosions

• Act quickly

• Two approaches: monoclonal Ab vs. soluble receptor

• $$$$

Side Effects of TNF Inhibitors

• Rashes, especially inject. site rxns.• Infections.• Reactivation of tuberculosis.• Demyelinating disease, optic neuritis,

seizures.• Pancytopenia.• Congestive heart failure (effect may last

for months).• Malignancy (espec. lymphoma)

Prednisone

• Low dose prednisone: 7.5 mg/d

• Reduces number of erosions at two years in early RA (22% vs. 46%).

• N Engl J Med 1995 Jul 20;333(3):142-6.

Remission: The New Standard?

• Durable remissions are achievable with combination therapy.

• Definition of remission important however!

• Remission depends heavily on treating early (first year of disease)

• New trials may report the remission rate as the primary outcome measure

RA Take Home Messages

• The treatment paradigm has changed in the past 10-15 years.

• Aggressive treatment changes long-term outcome.

• The earlier treatment is started, the better.

• There are new tools to help us make an earlier diagnosis.

Osteoarthritis

• Everyone gets a little

• Minor degenerative changes on xray often meaningless

• Knee, 1st CMC, DIPs, hip, back

• Usually localized– Exception: Erosive or inflammatory

OA.

Nonpharmacologic Therapy for Patients with OA

Amer. Coll. Of Rheumatology

• Patient education Self-management programs (e.g., Arthritis Foundation Self-Management Program) Personalized social support through telephone contact Weight loss (if overweight) Aerobic exercise programs Physical therapy Range-of-motion exercises Muscle-strengthening exercises Assistive devices for ambulationPatellar tapingAppropriate footwear Lateral-wedged insoles (for genu varum) BracingOccupational therapyJoint protection and energy conservation Assistive devices for activities of daily living

http://www.rheumatology.org/practice/clinical/guidelines/oa-mgmt.asp

Pharmacologic Therapy for Patients with OA

Amer. Coll. Of Rheumatology

• Acetaminophen• COX-2-specific inhibitor• Nonselective NSAID [plus misoprostol or a

proton pump inhibitor if at ↑GI risk]• Non-acetylated salicylate• Other pure analgesics: Tramadol

• Opioids • Intraarticular glucocorticoids, hyaluronan

• Topical    Capsaicin    Methylsalicylate

http://www.rheumatology.org/practice/clinical/guidelines/oa-mgmt.asp

OA of the Knee

• Most sensitive and specific finding on physical exam:

• CREPITUS!CREPITUS!

• Sometimes knee pain is coming from the hip

OA of Knee

• Glucosamine: mixed data

• Corticosteroid injection

• Viscosupplementation

• Quadriceps exercises

• Neoprene sleeve

• Hinged brace

OA of the Hip Joint

• Mimicked by low back pain!

• Most common cause of trochanteric bursitis is low back pain too!

• Hip pain usually radiates to groin, not to the “hip”.

Hip OA

• Injections don’t last long and are not practical.

• Hip replacement is a good operation.

1st CMC Osteoarthritis

• Brace off-the-shelf

• Brace custom molded

• Surgery

• Liniment

NSAIDsToxicity in Elderly

• Peptic ulcer disease

• Hypertension

• Congestive heart failure

• CNS changes

• Intestinal ulceration

GI Less Toxic NSAIDs

• Celecoxib

• Salsalate

• Meloxicam

• Nabumetone

• Etodolac

Risk Factors for UGI EventsAmer. Coll. Of Rheumatology

• Age >=65• Comorbid medical conditions• Oral glucocorticoids• History of peptic ulcer disease• History of upper gastrointestinal

bleeding • Anticoagulants

http://www.rheumatology.org/practice/clinical/guidelines/oa-mgmt.asp

RISK FACTORS FOR ULCERS

• NSAID Use• Age > 64• Prior event• CHF• Ethanol• Warfarin• Concomitant corticosteroid, low

dose aspirin, bisphosphonate, SSRI

• H. pylori

Ann Rheum Dis. 2007 March; 66(3): 417–418.

PREVALENCE OF NSAID ULCERS BY AGE

PREVENTION OF NSAID ULCERS

Arch Intern Med. 2002 Jan 8;162(2):169-75

NSAID ULCER PROPHYLAXIS

• H2 blockers NOT recommended for prophylaxis

• PPI or misoprostol recommended• PPI doesn’t seem to reduce

celecoxib ulcer complications further.

• Low dose aspirin ELIMINATES any benefit of celecoxib.

Amer. Coll. Of Gastro. 2009

• Patients with hx PUD should be tested for H. pylori prior to NSAID or ASA use.

Amer. Coll. Gastro. Guide. 2009

GI RISK

CV

RISK*

High Mod Low

High No NSAID, no COX-2

Naproxen + (PPI or MIS)

Naproxen + (PPI or MIS)

Low COX-2 + (PPI or MIS)

COX-2 or (NSAID + (PPI or MIS))

NSAID alone

*High CV risk defined as those needing aspirin therapy.

Prophylactic Regimens

• Misoprostol 200 mcg QID

• Lansoprazole 15 or 30 mg/d

• Esomeprazole 20 or 40 mg/d

CV Risk - Celecoxib

• 33 months Abs %RR

• Placebo 6/676 0.9% 1.0

• 200 mg BID 18/683 2.6%2.6

• 400 mg BID 23/669 3.4%3.4

N Engl J Med. 2006;355(9):873.