Arthritis

AARTHRITIS AND AANALGESICS

GOUTY GOUTY ARTHRITIS ARTHRITIS

Gouty arthritis

A systemic disease caused by deposition of uric acid crystals in the joint and body tissues

ETIOLOGY

Primary Innate defect of purine metabolism or uric acid

excretion HYPERURICEMIA

Overproduction (10%, >800mg/dL) Impaired renal clearance (90%, <600mg/dL) HGPRT (Hypoxanthine Guanine

phosphoribosyltransferase) deficiency PRPP (Phosphoribosyl – 1 pyrophosphate) excess

ETILOGY

Secondary Hematological causes CRF Drug – induced

ASA and Salicylates (<2g/day) Cytotoxic drugs Diuretics (except spironolactone) Ethambutol and Nicotinic acid Cyclosporine, INH, L – dopa Ethanol

Miscellaneous disorders

INCIDENCE

Higher in men (95%)

Onset is at 47 y/o

Marked by >7mg/dL serum uric acid

Genetic predisposition (10 – 60%)

Risk factors Obesity Heavy alcoholics

Gouty arthritis

ASSESSMENT FINDINGS1. Severe pain in the involved joints, initially the big toe2. Swelling and inflammation of the joint3. TOPHI- yellowish-whitish, irregular deposits in the skin that break open and reveal a gritty appearance4. PODAGRA-big toe

Gouty arthritis

ASSESSMENT FINDINGS

5. Fever, malaise

6. Body weakness and headache

7. Renal stones

Gouty arthritis

DIAGNOSTIC TEST

Elevated levels of uric acid in the blood

(+) monosodium urate crystals

Dramatic response to colchicine

INOSINIC ACID

HYPOXANTHINE

XANTHINE

URIC ACID

XANTHINE

OXIDASE

XANTHINE

OXIDASE

ALLANTOIN URATE OXIDASE

METABOLISM PATHWAYMETABOLISM PATHWAY

PATHOPHYSIOLOGY

MONOSODIUM URATE CRYSTALS INFLAMMATION

TOPHICOMPLICATIONS

•ACUTE TUBULAR OBSTRUCTION•UROLITHIASIS•CHRONIC URATE NEPHROPATHY

ACUTE GOUTY ARTHRITIS

Differentials Pseudogout (Ca pyrophosphate dihydrate crystals) Septic arthritis

TREATMENT 1. Colchicine Initiate within 12 – 36 hrs after attack DOC for ACUTE attack

MOA: impairs leukocyte migration and disrupts urate deposition and subsequent inflammation

- S/E: GI toxicity, BM toxicity

THERAPY FOR ACUTE GOUT

COLCHICINE PO

1mg 0.5 q 2hrs relief/ GIT discomfort Total : 8mg

IV NEVER GIVEN IM OR

SQ!

2. Indomethacin

as effective as colchicine but less GI toxicity

S/E: GI ulcer and bleeding

headache and dizziness (unique)

other NSAIDs are also effective

3. Corticosteroids

- for resistant patients

THERAPY FOR ACUTE GOUT

CORTICOSTEROIDS Intra – articular injections (Methylprednisolone

acetate) Systemic corticosteroid therapy

C/I NSAIDS, colchicine Oral prednisone IM corticotropin IM Triamcinolone acetonide IV methylprednisolone

Taper dose!

Prophylactic Therapy/Chronic gout

1. Allopurinol (Zyloprim)- xanthine analog- xanthine oxidase inhibitor- major metabolite: oxypurinol- indicated for patients with renal failure, leukemias-S/E: rash, leucopenia, GI toxicity,acute gouty attack with initiation

2. Uricosurics

- probenecid, sulfinpyrazone

- inh. renal tubular reabsorption of uric acid

- maintain adequate urine flow, alkalinize urine with NaHCO3

-S/E: GI irritation, rash, acute gout,

renal stones

Gout

Gout

NONDRUG Avoid purines! Control weight Avoid alcohol

Goodbye meat, organ meats,

seafood, beans, peas,

asparagus…

CHRONIC TOPACEOUS GOUT

May remain undetected and untreated for years

Development of tophi in pinna of external ear

Allopurinol and probenecid

OSTEOARTHRITISOSTEOARTHRITIS

DEFINITION and ETIOLOGY

OSTEOARTHRITIS (OA) “Degenerative Joint Disease” Chronic cartilage degeneration Most common form of arthritis >55 y/o, M = F, F> M if > 55y/o

AGING tendon, ligament, muscle strength chondrocytes proteoglycan production

AGING tendon, ligament, muscle strength chondrocytes proteoglycan production

CHONDROCYTES healing and remodelling cartilage matrix degeneration proteoglycans

CHONDROCYTES healing and remodelling cartilage matrix degeneration proteoglycans

IL – 1 andProinflammatory cytokines IL – 1 andProinflammatory cytokines

PAIN Osteophytes

SynovitisBursitis

Tendonitis

PAIN Osteophytes

SynovitisBursitis

Tendonitis

RISK FACTORSAdvanced ageFemale gender Muscle weaknessObesityJoint traumaHeredityCongenital defectsRepetitive stress

SIGNS AND SYMPTOMS

Deep, localized joint pain with rest or immobility

Lasts < 30 minutes

Mild inflammation

Crepitus upon joint movement

DIAGNOSIS

Physical examination Joint tenderness, diminished motion range,

crepitus, abnormalities in joint shape

Radiography Narrowing of joint space (+) Osteophytes

TREATMENT

NONDRUG Weight reduction Aerobic exercises and physical therapy Devices Avoid prolonged standing, kneeling, and

squatting Thermal therapy

Pharmacologic:

1. Acetaminophen

- first-line drug for pain in OA

- dose: 325-650 mg 4x daily

S/E: hepatotoxicity

2. NSAIDS

3. Capsaicin

- extract of red peppers

- MOA: release and depletion of substance P from nerve fibers

-S/E: burning at site of application

4. Glucosamine and chondroitin dietary supplements- shown to alleviate pain, slows down loss of cartilage5. Corticosteroids- systemic steroids not recommended- intraarticular steroids for local inflammation

6. Hyaluronate injection (Na hyaluronate, hylan G-F 20)

- reported to decrease pain

7. Narcotic analgesics

- for unresponsive patients and those with contraindications to acetaminophen or NSAIDs

RHEUMATOIDRHEUMATOIDARTHRITISARTHRITIS

PATHOPHYSIOLOGYTNF -

a

TNF - a

IL - 1IL - 1

IL - 6IL - 6GFGF

INFLAMMED

SYNOVIUM

INFLAMMED

SYNOVIUM

PANNUSPANNUS

PROTEOLYTIC ENZYMES

CARTILAGE DEGRADATION

CARTILAGE DEGRADATION

BONE DEMINERALIZATION

BONE DEMINERALIZATION

OSTEOCLAST ACTIVATION

PROGNOSIS

High RF titer

Elevated ESR

> 20 joints

Early age onset

Extra – articular involvement

Rheumatoid arthritis

A type of chronic systemic inflammatory arthritis and connective tissue disorder affecting more women (ages 35-45) than men

TREATMENT : NONDRUG

Joint protection

Exercises

Rest

PT and OT

Support groups

First-line

1. Methotrexate

- MOA: DHF reductase inhibitor; inhibits cytokine production and purine synthesis

- relatively rapid onset (2 to 3 weeks)

- S/E: GI (stomatitis, nausea, vomiting, diarrhea),

hematologic (leukopenia, thrombocytopenia),

pulmonary (fibrosis, pneumonitis),

hepatic (elevated enzymes, cirrhosis)

Teratogenic

leucovorin

2. Leflunomide (Arava)

- inhibits pyrimidine synthesis

- S/E: liver toxicity, teratogenic

3. Hydroxychloroquine

Inhibit NA synthesis

- S/E: diarrhea, blurring of vision, rash

4. Sulfasalazine

- S/E: rash, leukopenia

Less frequently used

1. Gold preparations

- aurothioglucose (suspension in oil), gold sodium thiomalate (aqueous solution)- IM

- auranofin- oral but less effective than IM

Taken up by macrophages,supressing phagocytosis,then lysosomal activity

S/E: GI (nausea, vomiting, diarrhea),

derma (rash, stomatitis), renal (proteinuria),

hematologic (anemia, leukopenia)

dimercaprol

2. Azathioprine

- purine analog converted to 6-mercaptopurine which inhibits DNA and RNA synthesis

-S/E: bone marrow suppression, hepatotoxicity, oncogenic

3. PenicillamineAnalog of AA cysteine-S/E: rash, metallic taste, hypogeusia (blunting of taste),stomatitis, proteinuria4. Cyclosporine- decreases production of cytokines- S/E: hypertension, hyperglycemia, nephrotoxicity, tremor, GI intolerance, hirsutism, gingival hyperplasia

Biologic agents

1. Etanercept (Enbrel)

- TNF receptor; binds to and inactivates TNF

2. Infliximab (Remicade)

- anti-TNF antibody

- combination with MTX is superior than MTX alone

- S/E: infections

3. Adalimumab (Humira)

- anti-TNF antibody

- S/E: local injection site reaction, infection

4. Anakinra (Kineret)

- IL-1 receptor antagonist

Treatment1.NSAIDSAnalgesic and anti-inflammatory but does not slow disease progression2.Disease-modifying anti-rheumatic drugs (DMARDs)Started within the first 3 months of symptom onset

Treatment1.NSAIDSAnalgesic and anti-inflammatory but does not slow disease progression2.Disease-modifying anti-rheumatic drugs (DMARDs)Started within the first 3 months of symptom onset

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