Rheumatoid Arthritis

Systemic disease Primarily Presents as Arthritis Other Organs can be involved Etiology not clear probably Multifactor involved

Epidemiology
Can affect ant age
Peak 30-55 Women affected 2-3 times > men Worldwide affect 1% Annual incidence about 30/100,000

population Prevalence in women > 65 years old 5%

Joint and surrounding

Basic Changes
Chronic synovial inflammation
Joint infiltration by inflammatory cells

Inflammation mechanism
Increasing the production of

proinflammatory cytokines Increasing cell migration by activating cellular adhesion molecules Increasing tissue destruction by matrixdegrading proteinases

Constitutional symptoms and signs of systemic rheumatoid arthritis

Fatigue
Weight loss Myalgia Excessive sweating Low-grade fevers

Morning stiffness
Lymphadenopathy

Laboratory features of rheumatoid arthritis

Anemia Eosinophilia Thrombocytosis Increased levels of alkaline phosphatase, aspartate amino-transferase, and glutamyltransferase Decreased albumin and prealbumin Elevated erythrocyte sedimentation rate Elevated C-reactive protein

RF
Rheumatoid factors are antibodies directed

against the Fc portion of IgG RF-positive patients with RA may experience more aggressive and erosive joint disease and extraarticular manifestations than those who are RFnegative

RF positive conditions
Condition Frequency of RF, percent

Aging (>age 60)

Infection Bacterial endocarditis* Hepatitis B or hepatitis C* Tuberculosis Syphilis* Parasitic diseases Leprosy* Viral infection*

5 to 25

25 to 50 20 to 75 8 Up to 13 20 to 90 5 to 58 15 to 65

RF positive Pulmonary disease

Frequency of RF, percent

Frequency of RF, percent

Sarcoidosis Interstitial pulmonary fibrosis Silicosis

Asbestosis

3 to 33 10 to 50 30 to 50
30

Other diseases RF positive

Primary biliary cirrhosis

45 to 70

Malignancy

5 to 25

After multiple immunizations

10 to 15

Anti-cyclic citrullinated peptide (CCP) antibodies

are as sensitive as, and more specific than,

IgM rheumatoid factors may predict the eventual development into RA when found in undifferentiated arthritis are a marker of erosive disease in RA may be detected in healthy individuals years before onset of clinical RA

Diagnosis
Typical clinical presentation
RF presence /absence does not make or

exclude diagnosis but positive RF :more extrarticular manifestations and more severe Exclude other diseases that may mimic RA

History taking and Exam in RA

Discussing main points Joint pain localized Duration since onset Past similar history Swelling? Stiffness ? Joint affected small (hands), large Skin rash DD of arthritis GI symptoms DD of arthritis Fever Eye symptoms Urinary symptoms Back pain Family history Document swelling , deformities, and functional disability

Early RA ,symmetrical synovitis of MCPs,PIPs,no deformity

Early RA with soft tissue swelling,involving PIPs Joints

Active severe RA,synovitis Subluxation and of MCPs,RA nodules

Swan neck and Boutonniere

Longstanding RA,ulnar deviation,nodules,m.atrophy

RA patient with CTS

Rupture tendon in RA patient

MTPs joints affected in RA feet MCPs in hands

Soft tissue swelling around MCP PIP joints,osteoporosis

RA:deformity,subluxation osteoporosis,erosions(MCP)

Distal IP joints erosions /destruction psoriatic arthritis,

Ulna styloid erosion

Erosion of

th 5

MTP

MTP joints with erosions,subluxation,osteopenia

Bone uptake in RA,carpal bones,MCPs and PIPs

Deferential Diagnosis
Viral syndromes
Post Streptococcal/other infections Psoriatic arthritis,reactive arthritis, and

other systemic rheumatological diseases Crystal arthropathy Septic arthritis, and may coexist

Viral
Parvo Virus (B19)mimic RA last from

months to years Hepatitis C ,also RF positive Hepatitis B Rubella Other viruses

Bacterial infections(reactive0
Post streptoccocal
Endocarditis Lyme disease

Psoriatic arthritis
Can be like RA and difficult to

differentiate But you may see Asymmetrical,affect DIP joints while RA usually symmetrical.and does not affect DIPs Skin changes of psoriasis Can affect SI joint and cause low back pain,while RA more likely to affect Cervical spine dactylitis ,enthesiopathy in psoriatic

Subcutaneous nodules in RA
Look for Nodules Over Olecranon

,Achilles,Occiput and pressure areas RF positive More extrarticular manifestations My worsen with treatment (methotrexate) Surgery for very large nodules But can be seen in other Rheumatic diseases (SLE,MCTD)

Subcutaneous nodules

SYSTEMIC FEATURES

Lung nodules in RA

ILD ,Cavitation TB,abscess,fungi,tumor,Nodule

Major ocular manifestations

Keratoconjunctivitis sicca
Scleritis:painful and serious Episcleritis Uveitis

Episcleritis,Superficial but cause irritation

Scleromalacia :potential serious complications/perforation

Scleromalacia perforance

Marginal corneal disease,and perforation

Vasculitis affecting small terminal arterioles

Vasculitis and gangrene

Signs of spinal cord damage

Severe neck pain radiating to Occiput
Tingling or numbness in fingers and feet Motor weakness Urinary bladder dysfunction Jumping legs

Normal

Normal

Posterior displacement of odontoid process,normal preodontoid space <3mm

Treatment Goals
Control symptoms Prevent Progression Preserve Function

Minimize side effects of treatment

Treat early to prevent joint damage and

disability Combination therapy works better Educate patient about disease and medications

NSAIDS
Symptomatic relieve
Be aware of side effects:GI toxicity,Fluid

retention,hypertension,renal impairment,hepatic injury Use one your familiar with COX2 ,less GI toxicity but not 100% GI safe ,other side effects may be more common,not cardio protective consider add ASA if patient has CVS risks

Steroids
Very effective ,fast action,used both as

local as intra-articular injection or systematic. 1-Induction therapy, and to treat flares 2- bridging therapy till other DMARDS start to act Treat RA vasculitis with DMARDS Local injection (into joints or soft tissue)

Steroids side effects ,many

Osteonecrosis
Osteoporosis Hypertension,accelerated atherosclerosis Hyperglycemia Wt gain, Fluid retention,Cushenoid

features Adrenal suppression Skin thinning,easy bruising,acne like rash

Hydroxychroloquine
For mild disease and as part of multi drug

therapy Usual dose 200mg bid po Very safe Delayed onset of action :within 3 months Retinopathy is rare and only if dosage of > 6mg/kg is used Eye exam q6months to screen for retinopathy

Methotrexate
Antimetabolite when treating cancer
Inhibition of inflammation in RA by

increasing intracellular adenosine and inhibit cells that participate in inflammation Main DMARD for RA Used alone or in combination Safe if used and monitored appropriately

Methotrexate continue
Usual starting dose 7.5-10mg given as

single weekly dose,average dose 1517.5mg,may need 20-25mg Po absorption is less when dose is higher than 15mg ,better if given SQ Onset of action about 4 weeks Always give folate supplement to reduce adverse effects including stomatitis,hair loss,bone marrow suppression

MTX side effects continue..

Hepatic toxicity monitor liver

transaminases and albumin q 2 months Hypersensitivity peumonitis :stop MTX in case of unexplained cough or SOB Bone marrow suppression Teratogenic

Other medications
Leflunmide: effective as single or in

combination 10-20mg qd,may cause diarrhea,heaptotoxic Sulfsalazine :slow acting,helps in combination therapy, cause myelosuppression,rare heaptotoxicity Azathioprine :cause myelosuppresion,hepatotoxicity

New agents
1-To Block TNF like infliximab, etanercept 2-Block IL1 3-Block IL 6 4-Block Co-stimulatory signal

New biological agents

Effective as single or combined
Expensive Injection only Side effects:local and systemic reaction to

injection or infusion,opportunistic infection and sepsis,(test all for PPD),may trigger autoimmune antibodies.

Juvenile Rheumatoid Arthritis

Syndrome of several type of arthritis Most common chronic disease in children Incidence 6-19/100,000 and prevalence 113.4/100.000 Etiology :unknown ,evidence of altered immunity but exact mechanism and cause no clear

ACR 1977 Criteria for JRA

Onset < 16 years of age
Persistent arthritis > 6 weeks Types:

Pauciarticular :< 5 joints Polyarticular :> 4 joints Systemic : Fever and rash

Systemic onset JRA

Typical:< 5 Y old child with daily spiking fever often in the evenings associated with transient macular salmon-pink rash,nonpruritic,over trunk and extremities.Rash appear with fever and subside when fever subside.Temp will go back to normal or bellow normal in between episodes. Arthritis onset may be delayed,typically symmetrical polyarthritis with wrists and ankles most commonly affected

Other features of systemic JRA

Pericarditis
Pleuritis Generalized lymphadenopathy Hepato-spleenomegaly Uveitis is uncommon

Elevated acute phase reactants

:ESR,CRP,WBC,Plts RF and ANA typically negative

Deferential Diagnosis
Includes Infections and febrile illnesses Leukemia/lymphoma Other tumors of children Other connective tissue diseases Reaction to drugs

Polyarticular
Affect 5 or > joints, 2 main subtypes
1-RF positive usually > 8 years old,more

girls,more erosive and aggressive disease resemble adult RF+ RA,remission is rare Uveitis is uncommon but often develop pulmonary disease,keratitis,vasculitis and Sjogren syndrome 2-RF negative ,less systemic features,less aggressive arthritis,ANA+ 50%. Uveitis is

Pauciarticular JRA
Early onset type:age 1-5,more girls,often

ANA+,highest risk of eye involvement 3050%,80% of whom has minimal or no symptoms Late onset:affects more boys,50% HLA+,affect large joints,spine,likely to have tendonitis,enthesitis,eye involvement less than early onset type

Irregular pupil due synechiae between the lens and iris Also hypopyon is seen

Systemic JRA rash

JRA affect growth,leg length

2nd toe is short ,2nd MT bone on X-ray

JRA affecting PIPs , MCPs and wrist joints

Treatment
NSAIDS
Steroids:systemic and intra-articular DMARDS:Methotrexate,Azathioprine,

TNF blocking