arthritis in the elderly gerald f. falasca, m.d. johnson city, tn march 2013 “all the pearls in 50...

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.