Osteoarthritis
- degeneration of cartilage (with structural and functional failure of synovial joints) - most common type of joint disease - oligoarticular - females: hands and knees- males: hips Morphology- bone eburnation- narrowed joint space- subchondral sclerosis- cysts- osteophytes Clinical course- pain that worsens with use- morning stiffness- crepitus- Heberden nodes (bone swellings in the DIP)
Rheumatoid arthritis
- chronic inflammatory disorder of autoimmune origin that principally attacks the joints producing synovitis - F:M = 3:1 - positive for: rheumatoid factor, anti-CCP (citrullinated peptides) antibodies - HLA-DR1 association Joint- symmetric arthritis principally affecting small joints of the hand/feet- fibrous/bony ankylosisSkin- rheumatoid subcutaneous nodules (also in lungs & other organs) which resemble necrotizing granulomas Clinical course:- begins with malaise, fatigue, musculoskeletal pain- symmetrical joint involvement- metacarpophalangeal and PIP joints, wrists, ankles, elbows, knees, upper spine (lumbosacral region & hips spared!)- swollen, warm, painful joints- stiff in the morning- decreased range of motion evolving to complete ankylosis- swan-neck deformity, boutonnière deformity- Baker cyst (herniation of the synovium) Therapy: TNF-Antagonists
Juvenile idiopathic arthritis
Differences to rheumathoid arthritis:1. Oligoarthritis is more common 2. systemic disease is more frequent 3. large joints are affected more often than small joints 4. rheumatoid nodules and rheumatoid factor are absent 5. antinuclear antibody (ANA) seropositivity is common
Seronegative Spondyloarthropathies
Unified by:- Absence of rheumatoid factor- Association with HLA-B27 - Pathologic changes in the ligamentous attachments rather than synovium- Involvement of sacroiliac joints Ankylosing Spondylitis- destruction of articular cartilage and bony ankylosis, especially of the sacroiliac joint Reactive Arthritis- Triad of arthritis, non-gonococcal urethritis/cervicitis, and conjunctivitis- prior infection: urethritis (Chlamydia) or diarrhea (Shigella, Salmonella, Campylobacter, Yersinia)- asymmetric pattern- ankles, knees, feet Psoriatic Arthritis- affects peripheral and axial joints and enthesis- distal interphalangeal joints (RA: proximal)- asymmetric- 'pencil in cup' deformity
Infective Arthritis
Suppurative Arthritis- involves a single joint- most commonly the knee (< hip < shoulder, axial joints in drug users)- H. influenza arthritis < 2 year olds- S. aureus in older children/adults- Gonococcus during late adolescence/young adulthood- Salmonella in individuals with sickle cell diseases Mycobacterial Arthritis- monoarticular- granulomas with central caseous necrosis Lyme Arthritis- Borrelia burgdoferi (transmitted by ticks)- knee joint Viral Arthritis- HIV, influenza, echovirus, parvovirus B19, EBV, hepatitis B and C viruses- acute symptoms
Gout
- transient attacks of acute arthritis initiated by crystallization of monosodium urate with and around joints - 90% primary - 10% secondary: increased nucleuc acid turnover (leukemia), chronic renal disease, congenital (Lesch-Nyhan syndrome, HGPRT deficiency) - inflammation is triggered by the precipitation of MSU crystals into the joints, which result in the production of cytokines that recruit leukocytes - low temperatures favor precipitation Clinical course- more common in men, patients with obesity, metabolic syndrom, excess alcohol intake, renal failure- 50% occur in the first metatarsophalangeal joint
Calcium Pyrophosphate Crystal Deposition Disease (CPPD, Pseudo-Gout, Chondrocalcinosis)
- sexes and race equally affected - crystals first develop in the articular cartilage, menisci, and intervertebral discs - as the deposits enlage they may rupture and seed the joint Histology- oval blue-purple aggregates- rhomboid- positively birefringent
Osteogenesis imperfecta
- deficiencies in the synthesis of type I collagen- impacts bone, joints, eyes (blue sclerae), ears (hearing loss), skin, teeth Subtype 1- compatible with survival- autosomal dominant- decreased snythesis of a-chain Subtype 2- perinatal lethal- autosomal recessive Subtype 3- progressive, deforming Subtype 4- compatible with survival- autosomal dominant
Osteopetrosis
= marble bone disease, Albers-Schönberg disease - reduced bone resorption and skeletal sclerosis due to impaired function of osteoclasts- mutation in carbonic anhydrase (CA2) which prevents acidification of the osteoclast resorption pit Morphology- Erlenmeyer flask deformity- spongiosa filling the medullary cavity, leaving no room for hematopoietic marrow (--> anaemia, extramedullary hematopoiesis)- small neural foramina, which compress exiting nerves (--> cranial nerve deficity like deafness, facial paralysis) - Severe infantile osteopetrosis: autosomal recessive- mild autosomal dominant form Therapy: hematopoietic stem cell transplantation (osteoclasts are derived from hematopoietic precursors)
Achondroplasia
- autosomal dominant- retarded cartilage growth, dwarfism - gain-of-function mutation in the FGF receptor 3 (FGF-mediated activation of FGFR3 normally inhibits endochondral growth) - shortened extremities, trunk of normal length, enlarged head
Osteopenia
- decreased bone mass 1-2.5 standard deviations below the mean
Osteoporosis
- bone mass at least 2.5 standard deviations below the mean (young adults) - Age-related changes- Reduced physical activity (resistance exercises such as weight training stimulate bone remodeling)- Genetic factors- Calcium deficiency, increased PTH concentrations, reduced vitamin D levels- Hormonal influences- Steroids - Osteoporosis cannot be detected in radiographs until 30-40% of the bone mass is lost and blood levels of calcium/phosphorus/alkaline phosphatase are not diagnostic--> dual-energy x-ray absorptiometry Therapy:- exercise, calcium & vitamin D intake- biphosphonates (reduce osteoclast activity)- denosumab (anti-RANKL antibody)
Paget Disease (Osteitis Deformans)
- increased, but disordered bone mass - usually begins in late adult hood (average age of diagnosis: 70 years), mostly in England, whites Three sequential phases1. Osteolytic stage2. Mixed osteoclastic-osteoblastic stage3. Osteosclerotic stage - alkaline phosphatase ↑ (osteoblast-isoenzyme) - increased risk for tumor development
