You are on page 1of 40

L21

Infectious Arthritis

Infectious Arthritis
 Infectious arthritis – the synovial inflammatory
reaction caused by invasion of the joint space by
various microorganisms
 Acute (septic) arthritis – monoarticular arthritis of the
large synovial joints caused by pyogenic bacteria
invading via the hematogenous route
 Gonococcal arthritis – caused by hematogenous spread of N.
gonorrhea to the joints in patients ages 18-35 with gonorrhea
 Non-gonococcal arthritis – commonly caused by S. aureus as
the most rapidly destructive form of joint disease, destroying
the cartilage within days of onset in children < 5 years and
adults > 64 years
 Predisposing factors in adults: prosthetic joint, rheumatoid arthritis,
malignancy, diabetes
 Chronic arthritis – caused by slowly progressive
organisms that are difficult to eradicate

Non-gonococcal Arthritis
 Source of invasion:
 Hematogenous seeding (55%) of the synovium during bacteremia
due to high vascularization of the synovial membrane (which lacks a
basement membrane)
 Sources of bacteremia: cutaneous, respiratory, or urinary infections;
invasive procedures; intravenous catheters, IV drug use
 Direct inoculation (through surgery, trauma, or animal bites)
 Contiguous source (e.g., osteomyelitis)
 Infants < 1 year: the metaphyseal blood vessels transverse the
epiphyseal growth plate, providing a channel for infections from
bone to joint space
 In older children, infection of the bone can break the outer cortex
and cause secondary septic arthritis
 Microorganisms: S. aureus (50%) in adults and children;
Streptococcus spp. (20%) in adults and children; Gram-negative
bacilli (13%) (e.g., P. aeruginosa, E. coli) in IV drug users, young
children, and immunocompromised

Non-gonococcal Arthritis
 Pathogenesis: After adhesion and colonization of the joint space,
bacteria rapidly proliferate and activate an acute inflammatory
response, stimulating the release of pro-inflammatory from synovial
cells and, subsequently, metalloproteinases and proteolytic enzymes
from neutrophils → rapid degradation of the articular cartilage (and
damage of the joint even after clearance)
 Risk factors: elderly, underlying joints disease, diabetes, skin infection
 Symptoms: fever; malaise; warmth, redness, and severe pain with
swelling at the joint (e.g., knee)
 Diagnosis:
 Positive blood cultures (50%) with elevated erythrocyte sedimentation rate
(ESR) and C-reactive protein (CRP) levels
 Positive synovial fluid (90%) aspirated from the joint with elevated WBC
and discoloration
 CT / MRI for distinguishing joint effusions (and greater ability to image the
soft tissue with MRI)
 Treatment: antibiotics, joint drainage, joint mobilization
 Only 50% of patients with acute non-gonococcal arthritis fully recover

Gonococcal Arthritis  Possible pathogenesis: deposition of circulating gonococcal Ag/Ig complexes  Risk factors: virulence of N.g. wrist. generally resolving spontaneously (30-40%)  Forms:  Tenosynovitis and dermatitis:  Tenosynovitis – asymmetric inflammation of the synovial sheath that surrounds the tendon is rare in other forms of septic arthritis. gonorrhea. female.. complement deficiency. disappearing within a few days  Purulent arthritis – polyarticular inflammation of the joints (e. low socioeconomic / educational status  Symptoms: polyarticular asymmetric migratory arthralgias in the upper extremity (e. knees. wrist. ankle. or vesicular lesions on an erythematous base on the extremities or the trunk in which the centers necrotize or hemorrhage (but are painless and nonpruritic).. elbow). gonorrhea on Thayer-Martin agar (requiring both blood and synovial samples since synovial fluid only allows 50 growth) . menstruation / pregnancy. delay of diagnosis.. hands)  Dermatitis – tiny maculopapular. pustular. generating pain with selling and limited ROM of the afflicted joint (e.g. elbow). ankles. SLE. toes. wrists.g. generating redness and swelling with associated pain and limited ROM (and an elevated WBC count that is lower than non-gonococcal arthritis)  Diagnosis: Gram-staining of gram-negative diplococcic and culture of N.

knees) in men ages > 50. peripherally located osseous erosion. immunocompromised. poor and homeless. and gradual diminution of the joint space (as opposed to joint narrowing)  Acid-fast stain (10-20%) of M. prisoners.Tuberculosis Arthritis  Epidemiology: increasing due to expansion of the HIV pandemic and increased antituberculous drug resistance  Pathogenesis:  Secondary direct invasion from adjacent tuberculous osteomyelitis  Hematogenous dissemination from a primary focus in the lungs or lymph nodes  Risk factors: elderly. tuberculosis and culture (80%) of synovial fluid  Open biopsy technique positive for typical caseous granulomas (94%)  Treatment prevents complete joint obliteration with fibrous ankylosis . alcoholics. anorexia  Diagnosis:  Radiograph: Phemister triad of periarticular osteoporosis. night sweats. weight loss. hip. reactivation due to surgical and joint/bone trauma  Symptoms: chronic monoarthritis of the large and medium weight-bearing joints (e.g.. generating chronic progressive low- grade joint pain and swelling (without warmth or erythema) and progressive loss of ROM  Possible fever.

and development of multiple erythema migrans lesions (e..g. beginning as a red macule that expands uniformly with central clearing to produce a “bull’s eye” (that is associated with flu-like symptoms)  Early disseminated infection (weeks after onset): debilitating fatigue.Lyme Arthritis  Lyme disease – caused by infection with spirochete B. and periarticular pain  Accompanied myopericarditis (1-3%) and meningitis (10%)  Late disease (months after onset): Lyme arthritis of the joints and encephalomyelitis in untreated patients  Lyme arthritis – self-limited monoarticular or oligoarticular arthritis of < 5 large joints (e.g. joint. burgdorferi transmitted through deer ticks  Phases:  Early localized infection: skin lesion erythema migrans (80-90%) within 1 month of the tick bite.. appearing ill. knee) in which the joints are warm with large effusions and limited pain . trunk) with migratory muscle.

Lyme Arthritis  Diagnosis:  Nonspecific:  Elevated WBC count predominated by neutrophils  Depending on the chronicity. burgdorferi (through molecular mimicry) . burgdorferi antibodies (through ELISA or indirect immunofluorescence followed by confirmation from Western blot)  Treatment:  “Antibiotic-refractory” lyme arthritis – persistent joint inflammation and proliferative synovitis unresponsive to further antimicrobials. causing synovial pannus that leads to destruction of articular cartilage and permanent deformities  Possible cause: T cell cross-reaction to HLA-DR molecules bound to surface protein A of B. synovial biopsy present with only mononuclear cell infiltrates or pannus development in more advanced cases  Silver stains may reveal low numbers of organisms near the blood vessels (25%)  Specific: detection of B.

ankle) with morning stiffness and fusiform swelling (and no erythema).g. alphaviruses. antiviral drugs . knees. HPV  Symptoms: self-limited symmetrical small-joint involvement of the periphery (e.Viral Arthritis  Causes: parvovirus B19. mumps. varicella-zoster. progressively resolving (and non-destructive)  Diagnosis (based on symptomology and serology): review of non-rheumatic symptoms and medical history  PCR-based examination of synovial material (which may be inconclusive)  Treatment: NSAIDs (with possible steroids or INF). HIV. Epstein-Barr. hepatitis A-C. hands. rubella. wrists.. HTLV-1.

L22 Osteoporosis .

Osteoporosis  Osteopenia – decreased bone mass (with 1 to 2.5 STDEV below mean peak bone mass)  Osteoporosis – localized (through disuse) or generalized (due to a metabolic bone disease) osteopenia characterized by porous bones and a reduced bone mass that significantly increases the risk of fracture (with atleast -2.5 STDEV below mean peak bone mass)  Signified by the presence of an atraumatic or vertebral compression  Typically refers to senile and postmenopausal forms .

Pathogenesis  Peak bone mass is achieved during young adulthood (with its magnitude receiving influence from hereditary factors. physical activity. muscle strength.7% per year) . diet. and hormonal state)  Once maximal skeletal mass is reached. a small deficit in bone formation accrues with every resorption and formation cycle (average 0.

growth factors) lose their biologic activity over time. and compensatory osteoblastic activity cannot keep pace . generating an overall diminished capacity to make bone  Postmenopausal (Type I) osteoporosis – hormonal influences after menopause cause yearly reductions in bone mass ( < 2% of cortical bone and < 9% of cancellous bone).. thereby increasing RANKL levels and decreasing OPG expression.Pathogenesis  Senile (Type II) osteoporosis – age-related changes in bone cells and matrix strongly impact bone metabolism  Low-turnover form: Osteoblasts in the elderly have reduced proliferative and biosynthetic potential and proteins bound to the extracellular matrix (e. causing postmenopausal women to suffer more osteoporotic fractures than men of similar age  Strongly influenced by estrogen deficiency (in which estrogen replacement can protect against bone loss)  High-turnover form: Decreased estrogen levels (through increased stimulation of inflammatory cytokines by monocytes and bone marrow cells) stimulate osteoclast recruitment and activity.g.

and RANK play key roles (as regulators of osteoclasts)  MHC locus (through the effects of inflammation on calcium metabolism) and estrogen receptor gene  Variants of Vitamin D receptor and LRP5 as risk factors  Calcium nutritional state of the body: The insufficient intake of dietary calcium in girls during periods of rapid bone growth ultimately stunts peak bone mass.Pathogenesis  Reduced physical activity increases the rate of bone loss since mechanical forces stimulate normal bone remodeling (in which the type of exercise and associated load magnitude plays an important role)  Genetic factors (60-80% of bone density variation):  Genome-wide association studies (GWAS) – conclude RANKL. OPG. increasing the risk of osteoporosis .

Morphology  Postmenopausal osteoporosis – increased osteoclast activity affects bones with increased surface areas (e. systems . thinned.  Senile osteoporosis – thinning of both the trabecular bone of the cortex by subperiosteal and the medulla (bottom) and endosteal resorption with the cortical bone (top) are widening of the haversian markedly thinned. leading to progressive microfractures → vertebral collapse In advanced osteoporosis.. and lose their interconnection.g. cancellous compartment of the vertebral bodies)  Effect: The trabecular plates become perforated.

contributing to significant loss of height and spinal curvature deformities  Complications of femoral neck. bisphosphonates) that bind to bone and inhibit osteoclasts .Clinical Presentation  Vertebral fractures commonly in the thoracic and lumbar regions: painful.g. and alkaline phosphatase are not diagnostic  Specialized imaging techniques for the measurement of bone density: Dual-energy X-ray Absorptiometry (DEXA) / Quantitative CT  Prevention and treatment: exercise. phosphorus. pelvis. relative calcium and Vitamin D intake. pharmacologic agents (e. pneumonia  Remains asymptomatic until advancement of skeletal fragility:  Cannot be reliably detected from x-rays until 30-40% of bone mass is lost  Blood levels of calcium.. and spine fractures: pulmonary embolism.

L23 Osteoarthritis .

pubic)  Cavitated joints – synovial joints with a wide space that allows for a wide range of motion between the ends of bones formed via endochondral ossification  Fibrous capsule – strengthens the joint with reinforcement by ligaments and muscles  Synovial membrane – the boundary of the joint space that is anchored to the underlying capsule.Joints  Joints allow movement while providing mechanical stability  Solid joints (synarthroses) – nonsynovial joints that lack a joint space. allowing for the exchange of nutrients and wastes between the blood and synovial fluids  Type A synoviocytes – specialized macrophages  Type B synoviocytes – fibroblast-like cells that synthesize hyaluronic acid and various proteins  Synovial fluid – a plasma filtrate containing hyaluronic acid that acts as a lubricant and provides nutrition for the articular hyaline cartilage . and lacks a basement membrane. providing structural integrity while allowing only minimal movement  Fibrous synarthroses: cranial sutures and the bonds between the roots of teeth/jawbones  Cartilaginous synarthroses: the symphyses (e. appearing smooth (except near the osseous insertion where it possesses numerous villous folds)..g. manubriosternalis.

10% Type II collagen. chondrocytes  Collagen fibers grant resistance to tensile stresses and transmit vertical loads  Water and proteoglycans grant resistance to compression and limit friction  Chondrocytes synthesize and enzymatically digest the matrix. proteoglycans. secreting degradative enzymes in inactive forms and enriching the matrix with enzyme inhibitors  Diseases that destroy articular cartilage (by IL-1/TNF) activate the catabolic enzymes and decrease the production of inhibitors in order to accelerate matrix breakdown  Articular cartilage – contributes to frictionless movement of the joint with resistance to tension and compression .Joints  Hyaline cartilage – a unique connective tissue suited for shock absorption and wear-resistance. 8%. and lymphatic drainage  Composition: 70% water. innervation. lacking a blood supply.

Synovial Joint .

activity modification. and arthroplasty .g. diabetes. appearing asymptomatic until age 50  Primary (idiopathic) osteoarthritis – oligoarticular OA that appears insidiously without an apparent initiating cause (by aging)  Secondary osteoarthritis (5%) – OA in younger individuals arising from previous joint injuries. knees. a congenital developmental deformity of the joints. proximal and distal IP joints)  Heberden nodes – prominent osteophytes at the DIP joints  No effective means to prevent or halt progression of primary OA  Therapy includes pain management. or a systemic disease (e. obesity)  Symptoms: deep and achy pain that worsens with use. lower lumbar and cervical vertebrae.g. morning stiffness..Osteoarthritis  Osteoarthritis (OA) – most common degenerative joint disease characterized by the degeneration of articular cartilage resulting in structural and functional failure of the synovial joints (due to chondrocyte-induced breakdown of the matrix). limited ROM → joint deformity without fusion  Involvement of 1+ joints (e. hips..

g. TNF. and extensive subchondral bone changes  Extracellular components: Degradation of type II collagen by matrix metalloproteinases and proteoglycans during disease progression  Increased counts of cytokines and diffusible factors (e. loss of cartilage. and proteases. prostaglandins. leading to chondrocyte drop out. NO  Environmental and genetic influences: Aging and biomechanical stress  Genetically heterogeneous: Risk is associated with the additive effect of multiple genes .Pathogenesis  Phases of chondrocytic changes:  Chondrocyte injury due to genetic and biochemical factors  Early OA: proliferation of chondrocytes and secretion of inflammatory mediators. acting to remodel the matrix and initiate secondary inflammatory changes in the synovium and subchondral bone  Late OA: repetitive injury and chronic inflammation. proteoglycans. collagens.. TGF-β).

generating a granular soft articular surface  In the later stage.Morphology  In the early stages during chondrocyte proliferation.  The horizontally-arranged type II collagen fibers in the superficial zone are cleaved into fissures and clefts at the articular surface. tumbling into the joint to form lose bodies (or joint mice)  The newly exposed subchondral plate becomes the new articular surface. the chondrocytes cluster as the water content increases and proteoglycan concentration decreases. the chondrocytes die and the thick portions of the cartilage are sloughed. and friction with the opposing surface smooths and burnishes the exposed bone. gradually ossifying) . creating gaps that allow synovial fluid into the subchondral regions to form fibrous walled cysts  Mushroom-shaped osteophytes (or bony outgrowths) develop at the margins of the articular surface (which are capped by fibrocartilage and hyaline cartilage. polishing it during bone eburnation  Small fractures develop through the articulating bone.

L24 Crystal-induced Arthritis .

talcum. calcium pyrophosphate dehydrate → pseudogout. basic calcium phosphate  Exogenous crystals: corticosteroid ester crystals.Crystal-induced Arthritis  Crystals produce disease by triggering a cytokine-mediated cascade that destroys cartilage  Endogenous crystals: monosodium urate → gout. polyethylene. methyl methacrylate  Gout / gouty arthritis – marked by transient attacks of acute arthritis caused by crystallization of monosodium urate within and around the joints  Primary (90%) – increased uric acid biosynthesis (manifesting as gout) due to unknown causes  Secondary – increased uric acid (and urinary excretion) due to a dominant/known underlying disease .

Uric Acid  Hyperuricemia ( > 6. obesity. lead toxicity . degrading into uric acid instead  Excretion: uric acid is filtered from circulation by the glomerulus and resorbed by the proximal tubule of the kidneys  Contributing factors for gout: age of the patient and associated duration of hyperuricemia.. thiazides). heavy alcohol consumption. drugs that reduce the excretion of urate (e. genetic predisposition.g.8 g/dL of plasma urate levels) is not sufficient for the development of gout (since elevated uric acid can result from overproduction or reduced excretion of uric acid)  Uric acid – the final product of purine catabolism (by xanthine oxidase)  De novo pathway: purine nucleotides are synthesized from nonpurine precursors  Salvage pathways: purine nucleotides are synthesized from free purine bases from dietary sources or recycled purine nucleotides  Possible cause of primary gout: deficiency of HGPRT inhibits the recycling of purine metabolites.

resulting in the production of cytokines that recruit leukocytes  Macrophages phagocytose MSU and subsequently produce cytokines (e. promoting the accumulation of neutrophils and macrophages at the joint (pro-inflammatory)  Newly recruited leukocytes release cytokines. free radicals. proteases. IL-1).Gout – Pathogenesis  Inflammation is triggered by the precipitation of monosodium urate (MSU) crystals in the joints. and arachidonic acid metabolites to ultimately recruit more leukocytes and damage the joint  The cascades trigger acute arthritis (which spontaneously regresses)  Modulated solubility of MSU in the joint:  Synovial fluid is a poor solvent for MSU (compared to plasma)  Lower temperatures of the peripheral joints favor precipitation .g..

ligaments/tendons. softer tissue. forming tophi  Tophi – large aggregates of urate crystals with associated inflammation in the synovial membranes and periarticular tissue. compromising the function of the joints  Simultaneous development of urate nephropathy  Phases of development: ① Asymptomatic hyperuricemia → ② Acute arthritis → ③ Asymptomatic intercritical period → ④ Chronic tophaceous arthritis → ⑤ Tophi in various sites → ⑥ Gouty nephropathy . appearing in articular cartilage. kidneys  Severe damage to the cartilage develops.Gout – Pathogenesis  Repeated episodes of acute arthritis eventually leads to chronic tophaceous arthritis.

slender. and macrophages  Chronic tophaceous arthritis: encrusting of MSU at the articular surface. fibrotic. forming visible deposits in the synovium  Synovium: hyperplastic.Gout – Morphology  Acute arthritis: dense neutrophilic infiltrate in the synovium and synovial fluid with clusters of MSU crystals within the cytoplasm of the neutrophils  Crystals: long. forming a pannus that destroys the underlying cartilage and leads to juxta-articular bone erosions  Pannus – membrane of granulation tissue  Fibrous or bony ankylosis (or union) can develop to hinder joint function . and thickened with inflammatory cells. plasma cells. containing scattered lymphocytes. needle-shaped with negative birefringent (or polarity)  Synovium: edematous and congested.

fingers. wrists.. it may last for days to weeks but will gradually resolve (before recurring polyarticularly at shorter intervals without therapy)  Chronic tophaceous gout develops years after the initial acute attack. knees. progressing to chronic gouty nephropathy (in which 20% die of renal failure)  Treatment acts to stop or prevent acute attacks and mobilize tophaceous deposits . progressing to a severely crippling disease  Radiograph: juxta-articular bone erosion (due to osteoclastic bone resorption and joint space loss)  Renal manifestations: renal colic associated with the passage of gravel and stones. ankles.g.Gout – Clinical Presentation  Acute arthritis presents with sudden onset of excruciating joint pain (and associated localized hyperemia and warmth)  First presentations are monoarticular (with 50% occurring at the 1st metatarsophalangeal joint) and progress to other locations (e. elbows)  If untreated.

hypothyroidism) .g. occurring in patients > 50 years (which becomes more prevalent with increasing age)  Possible cause: degradation of cartilage proteoglycans (that normally inhibit mineralization). allowing crystallization around chondrocytes  Types:  Sporadic (idiopathic)  Hereditary – autosomal dominant germline mutations in the pyrophosphate channel that cause the development of crystals early in life  Secondary – associated with various disorders (e. ochonosis.CPPD Disease  Calcium pyrophosphate crystal deposition (CPPD) disease (or pseudogout) – accumulation of crystals that stimulates inflammation at the joints. previous joint damage. hyperparathyroidism.. diabetes. hemochromatosis. hypomagnesemia.

enlarging and rupturing the joint  Seeding allows for phagocytosis by macrophages. appearing as blue- purple oval clusters (that are weakly polarized)  Symptoms: asymptomatic → acute. elbows. menisci. shoulders. and IV discs. triggering pro- inflammatory cascades  The crystals form chalky white. or chronic arthritis  Joint involvement may involve 1+ joints for several days to weeks at the wrists.CPPD Disease  Crystals first develop in the articular matrix. and ankles (with 50% of patients suffering from significant joint damage)  Treatment: none (with supportive therapy) . subacute. crumbly deposits.

L25 Rheumatoid Arthritis .

Rheumatoid Arthritis  Rheumatoid arthritis – a chronic systemic inflammatory autoimmune disorder that produces a non-suppurative proliferative and inflammatory synovitis. progressing to destructions of the articular cartilage and ankylosis of the joints  Epidemiology: affects mostly women ages 20-50  Risk factors:  Genetic susceptibility (50%): HLA-DRB1 / PTPNN2  Environmental arthritogen-activation of T and B cells: certain environmental influences promote citrullination of self-proteins. creating new epitopes that trigger autoimmune reactions  Citrullinated peptides (CCPs) – post-translational modification of arginine residues to citrulline .

g.Pathogenesis  Initiation of autoimmune responses by CD4+ TH cells + arthritogenic agents (e. producing cytokines that stimulate tissue injury  TNF from macrophages stimulate synovial cells to secrete proteases.. synovial fluid. microbial or self- antigen). and synovial membranes  Act as a marker for disease (but can be seronegative)  Manifests as a symmetric arthritis of the small joints of the hand and feet . destroying hyaline cartilage  Rheumatoid factors – Fc portion of autologous IgM / IgG that generates immune complexes of autoantibodies in the sera.

Morphology  Initially. granulation tissues. inflammatory cells. Increased vascularity due to angiogenesis 4. plasma cells. developing delicate and bulbous fronds  Pannus – a mass of edematous synovium. allowing the synovium to penetrate into the bone and cause periarticular erosions and subchondral cysts . the synovium becomes grossly edematous. Fibrinopurulent exudate on the synovial and joint surfaces 5. APCs 3. and hyperplastic. thickened. Dense inflammatory infiltrates of CD4+ TH cells. Synovial cell hyperplasia and proliferation 2. ossifying and resulting in fusion of the bones as a bony ankylosis  Characteristics: 1. B cells. Osteoclastic activity in the underlying bone. the pannus bridges the apposing bones to form a fibrous ankylosis. and fibroblasts that grows over the articular cartilage and causes erosion  After destruction of the cartilage.

occiput. round-to-oval nodules that arise in regions of the skin subjected to pressure (e. cutaneous ulcers. ulcers. and gangrene  Leukocytoclastic vasculitis produces purpura.Morphology  Rheumatoid subcutaneous nodules – severe cutaneous lesions characterized by firm. elbows. lumbosacral area)  Microscopically resemble necrotizing granulomas with a central zone of fibrinoid necrosis surrounded by a rim of activated macrophages and lymphocytes  Affected individuals with severe RA are at-risk of developing vasculitis:  Acute necrotizing vasculitis involves small and large arteries and can evolve into chronic fibrosing processes (with involvement in the pleura and pericardium)  Obstruction of the small arteries by obliterating endarteritis can lead to peripheral neuropathy.g. ulnar aspect of the forearm. and nail be infections . nontender..

IL-1) before involving the joints (in a symmetrical patterns progressing from smaller to larger joints)  The affected joints are swollen. fatigue. poor mucin clot formation.Clinical Presentation  Symptoms of malaise. causing herniation of the synovium  Multisystem involvement for definitive diagnosis:  Characteristic radiographic findings: joint effusions and juxta-articular osteopenia with erosions and narrowing of the joint space and loss of cartilage  Sterile. warm. painful..g. and inclusion-bearing neutrophils  Presence of rheumatoid factor and anti-CCP antibody (80%) . turbid synovial fluid with decreased viscosity. and stiff following inactivity and progressively enlarge (which decreases ROM until complete ankylosis)  Swan-neck/boutonniere deformity – characteristic radial deviation of the wrist and ulnar deviation / flexion-hyperextension of the fingers → no stability and minimal ROM  Baker’s cyst – large synovial cyst of the posterior knee that develops with increasing intra-articular pressure. and generalized MSK pain develop slowly and insidiously through cytokine-mediation (e. TNF.

opportunistic infections (in patients who receive longterm immunosuppressive agents) .g. methotrexate). synthetic and biologic disease-modifying drugs (e.. TNF antagonists  Biologic agents that interfere with T and B cell lymphocyte responses  Longterm complications: systemic amyloidosis (5-10%).Clinical Presentation  Treatment is aimed at relieving pain and inflammation while slowing/stopping joint destruction: corticosteroids.

IL-17. TNF. and IFN-γ released by TH cells)  Risk factors: HLA / PTPN22 variants  Compared to RA: more common oligoarthritis. more frequent systemic disease.Juvenile Idiopathic Arthritis  Juvenile idiopathic arthritis (JIA) – a heterogeneous group of disorders of unknown cause that present with arthritis before age 16 (due to cytokine-mediated inflammation by IL-1. affliction of larger joints. absence of rheumatoid nodules and rheumatoid factor. presence of antinuclear antibody (ANA) seropositivity  Subclassifications are based on clinical and laboratory variables  Treatment is aimed at relieving pain and inflammation while slowing/stopping joint destruction: IL-6 receptor antibody in systemic form .