Arthritis

Arthritis

DegenerativeImmune-mediated Crystal-induced Infectious

(Septic)

Osteoarthritis -Rheumatoid arthritis-Seronegative spondyloarthropathies

-Gout-Pseudogout

A diagram of a normal joint

Chondrocytes synthesize type II collagen & proteoglycans…important for frictionless movement

Check https://en.wikipedia.org/wiki/Synovial_joint for references

Osteoarthritis (= “Degenerative joint disease”)The most common type of joint disease

*Defect in chondrocytes response to biochemicaland mechanical stresses resulting in breakdown of thematrix

*Most cases: with aging= primary or idiopathic osteoarthritis…usually oligoarticular (few joints)

*5% occur in younger individuals due to:joint deformity, a previous joint injury, or anunderlying systemic disease such as diabetes,ochronosis, hemochromatosis, or marked obesity…= secondary osteoarthritis

-Knees & hands more in females-Hips more in males

Clefting & fissuring of articular cartilage

*The prevalence of OA increases exponentiallybeyond the age of 50, and about 40% of peopleolder than 70 are affected

Elsevier. Kumar et al. Robbins basic pathology 9th…modified

*Pathogenesis:(1) chondrocyte injury, related to genetic and biochemical factors(2) early OA, in which chondrocytes proliferate and secrete inflammatory mediators, collagens, proteoglycans, and proteases…degradation exceeds synthesis and inflammation is induced(3) late OA, in which repetitive injury andchronic inflammation lead to chondrocyte drop out, marked loss of cartilage, and extensive subchondral bone changes

*Important mediators:-TGF-β (which induces matrix metalloproteinases)-TNF -Prostaglandins -Nitric oxide…all have been implicated

Bone eburnation (polished ivory appearance of the exposed bone (because cartilage is lost due to friction)

*Small fractures through the articulating bone are

common, and the fracture gaps allow synovial fluid to be

forced into the subchondral regions. The loculated fluid

collection increases in size, forming fibrous-walled cysts.

Elsevier. Kumar et al. Robbins basic pathology 9th…modified

These dislodged pieces of

cartilage form loose bodies called:

joint mice

= bone spurs(the bony outgrowths at the margins of the articular surface)

Remember the subchondral bone sclerosis that occurs

Check http://medical-dictionary.thefreedictionary.com/osteoarthritis for references...modified

Check http://www.en.rheumatologie.usz.ch/expert-knowledge/Pages/osteoarthritis.aspx for references

*Clinical course:

-Insidious, patients with primary disease are usually asymptomatic until they are in their 50s

-Deep, achy pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement

-Spinal roots compression by osteophytes may occur with radicular pain, muscle spasm, atrophy and neurological deficits

-The joints commonly involved include the hips, knees, lower lumbar and cervical vertebrae, proximal and distal interphalangeal joints of the fingers, first carpometacarpal joints, and first tarsometatarsal joints

-Heberden nodes, prominent osteophytes at the distal interphalangeal joints, are common in women (but not men)

-The wrists, elbows, and shoulders are usually spared

-With time, joint deformity can occur, but unlike rheumatoid arthritis, fusion (ankylosis) does not take place

-Therapy includes management of pain, activity modification and, for severe cases, arthroplasty.

Rheumatoid arthritis (RA)

…may affect many tissues and organs but principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis

*RA often progresses to destruction of the articularcartilage and ankylosis of the joints

…may involve skin, heart, blood vessels and lungs…so it can resemble other systemic autoimmune diseases

*The prevalence in the United States is approximately 1% *The disease peaks in the second to fourth decades *Three times more common in women than men

*Genetic predisposition and environmental factors

*Pathogenesis:Cytokine-mediated inflammation, predominantly secreted by CD4+ T-cells + antibodies against self antigens:

The most important cytokine here

*Important mediators:

Pannus is the aggregation of lymphocytes, plasma cells, macrophages, neutrophils…etc+ the hypertrophic synovium

Marked synovial hyperplasia with underlying dense chronic inflammation

Lymphoid follicles, some with germinal centers

Elsevier. Kumar et al. Robbins basic pathology 9th…modified…(A, Modified with permission from Feldmann M: Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol 2:364, 2002.)

Elsevier. Kumar et al. Robbins basic pathology 9th...modified

Rheumatoid arthritis (RA), more about pathogenesis

• Many patients (70%) produce antibodies against cyclic citrullinated peptides (CCPs)

…These antibodies are a diagnostic marker for the disease and may be involved in tissue injury

• 50% of the risk of developing RA is related to genetic factors

…HLA-DRB1 locus and polymorphism in PTPN22 gene

• Environmental insults such as smoking and infections may induce the citrullination of some self proteins, creating new epitopes that trigger autoimmune reactions

• Certain microbial antigens may induce the autoimmune response

Rheumatoid arthritis (RA), clinical notes• Symmetric polyarticular arthritis, principally affecting the small joints

of the hands and feet, ankles, knees, wrists, elbows, and shoulders

• Most often, the proximal interphalangeal and metacarpophalangeal joints are affected, but distal interphalangeal joints are spared

• Axial involvement, when it occurs, is limited to the upper cervical spine

• Hip joint involvement is extremely uncommon

• Vasculitis, pericarditis & pleuritis can occur, also uveitis, keratoconjunctivitis & interstitial lung disease

• Rheumatoid subcutaneous nodules…in 25% of patients

…along the extensor surface of the forearm or other areas

subjected to mechanical pressure

…rarely, they can form in the lungs, spleen, heart, aorta,

and other viscera

*Ligaments, tendons & joint capsules are also affected and destroyed…this may lead to deformities such as:-radial deviation of the wrist-ulnar deviation of the fingers-flexion-hyperextension abnormalities of the fingers (swan-neck deformity, boutonnière deformity)

Felty’s syndrome (rare) = RA + neutropenia + splenomegaly

Rheumatoid arthritis (RA), clinical notes…cont’d

• There also may be constitutional symptoms such as weakness, malaise, and low-grade fever

• Aching and stiffness of the joints, particularly in the morning

• As the disease advances, the joints become enlarged, motion is limited, and in time ankylosis may appear

• Vasculitic involvement of the extremities may give rise to Raynaud phenomenon & chronic leg ulcers

• In most patients, it pursues a chronic, remitting relapsing course

• RA is an important cause of reactive amyloidosis, which develops in 5% to 10% of these patients, particularly those with long-standing severe disease

Gout

*1% of the population*Males more*Recurrent episodes of acute arthritis …sometimes accompanied by the formation of large crystalline aggregates called tophi…eventual permanent joint deformity

*Although an elevated level of uric acid is an essential component of gout, not all such persons develop gout, and genetic and environmental factors also contribute to its pathogenesis

*Uric acid is an end product of purine metabolism

Elsevier. Kumar et al. Robbins basic pathology 9th

-Long, slender, needle-shaped monosodium urate crystals-Negatively birefringent on polarized microscopy

*Acute Gouty arthritis: neutrophils engulfing the urate crystals and deposition of uriate crystals in synovium…then solubilization (remission of the attack)

*

tophus

Tophus: aggregate of dissolved urate crystals is surrounded by reactive fibroblasts, mononuclear inflammatory cells, and giant cells

Remember also: urate stones &Gouty nephropathy

Elsevier. Kumar et al. Robbins basic pathology 9th…modified

Gout, more clinical notes• Usually no symptoms before the age of 30

• Asymptomatic hyperuricemia appears around puberty in males and after menopause in women. After a long interval of years, acute arthritis appears

• Risk factors for the disease include obesity, excess alcohol intake, consumption of purine-rich foods, diabetes, and renal failure

• Acute Gouty arthritis appears in the form of sudden onset, excruciating joint pain associated with localized erythema, and warmth; constitutional symptoms are uncommon, except possibly mild fever

…most are monoarticular and mostly 1st metatarsophalangeal joint

…other joints: instep, ankle, heel, or wrist

• After the remission of acute gouty attack: asymptomatic intercritical period

• Most will have recurrent attacks after the first one

• With recurrence, more joints are involved and without therapy: chronic tophaceous disease after many years

• About 20% of persons with chronic gout die of renal failure

Pseudogout “Chondrocalcinosis” -Rhomboid calcium pyrophosphate crystals-Positively birefringent on polarized microscopy

…typically first occurs in persons 50 years of age or older…no gender or race predilection…the knees, followed by the wrists, elbows, shoulders, and ankles, are most commonly affected

Elsevier. Kumar et al. Robbins and Cotran pathologic basis of diseases 9th

Seronegative Spondyloarthropathies

…characterized by the following:

1- Pathologic changes that begin in the ligamentous attachments to

bone rather than in the synovium

2- Involvement of the sacroiliac joints (sacroiliitis), with or without

arthritis in other peripheral joints

3- Absence of rheumatoid factor (hence the designation seronegative)

4- Association with HLA-B27

Seronegative Spondyloarthropathies, include:

• Ankylosing spondylitis…the prototype

• Reiter syndrome

• Psoriatic arthritis

• Spondylitis associated with inflammatory bowel diseases

• Reactive arthropathies after infections (e.g., with Yersinia, Shigella, Salmonella, Helicobacter, or Campylobacter)

They are distinguished from one another by the particular peripheral joints involved, as well as on the basis of associated extraskeletal manifestations (for example, urethritis, conjunctivitis, and uveitis are characteristic of Reiter syndrome)