BL.2.8: Crystal Arthritis, Sponyloarthropathies Flashcards
Review normal uric acid metabolism and identify secondary causes of hyperuricemia.
Urate Produced + Urate Absorbed by the GI tract = Urate Excreted + Urate Loss by the GI tract.A 24h urinary excretion of uric acid >750 mg on a regular diet suggests an overproduction of uric acid where a value <750 mg/24h would imply underexcretion of uric acid. The majority of patients (90%) with primary gout are underexcretors of uric acid.Primary gout: underexcretion of uric acidSecondary causes: overproduction? Unconfirmed.
Describe the general clinical and synovial fluid analysis features of gout including crystal morphology and birefringence.
Gout includes:Gouty arthritis: recurrent attacks of severe acute or chronic articular and periarticular inflammation.Tophi: aggregated deposits of MSU occurring in joints, bones, and soft tissue.Gouty nephropathy: renal interstitial, glomerular, and/or tubular deposition of MSU crystals.Uric acid nephrolithiasis (kidney stones).The intracellular crystals in PMNs are needle-shaped and negatively birefringent (yellow when parallel to the axis of the red compensator) on polarizing microscopy. The synovial fluid is inflammatory (typically 20,000-100,000 leukocytes/mm3 ) with a predominance of neutrophils. Hematological evaluation may show an elevated ESR, mild neutrophil leukocytosis, and possibly reactive thrombocytosis.
What are the 2 important enzymes that are altered in the gout?
Increase in PRPP leads to increased formation of uric acidHGPRT: deficiency- causes Lesch-Nyhan syndrome
Contrast the differences in the pathophysiology of gout and pseudogout.
Gout: MTP joint most affected, Pseudo: knee most affectedDifferent synovial fluid compositionSource of gout: purines.Source of Calcium Pyrophosphate Dihidrate Deposition Disease (CPDD = pseudogout): nucleoside triphosphatesUnlike MSU crystals, CPDD crystals do not form in synovial fluid by spontaneous precipitation of supersaturated solutions. CPDD crystals are released into synovial fluids by a “shedding phenomenon” or “enzymatic strip mining” of pre-formed crystals in the cartilage matrix.Similar inflammatory response in both.
Discuss the treatments for acute crystal-related arthritis and chronic symptomatic hyperuricemia.
Lifestyle and nutritional modifications including weight loss, reduction of dietary intake of foods high in purines such as meats and shellfish, and limitation of alcohol consumption can improve hyperuricemia.The acute gouty attack can be effectively treated with anti-inflammatory medications such as nonsteroidal anti-inflammatories (NSAIDs), colchicines, or corticosteroids.For chronic treatment of symptomatic hyperuricemia, the following anti-hyperuricemic medications are effective in reducing serum uric acid levels below supersaturation levels: a uricosuric such as probenecid is used to enhance renal excretion of uric acid if the patient is an under-excretor; a xanthine oxidase inhibitor such as allopurinol is used to decrease uric acid production if the patient is an over-producer of uric acid. New therapies for hyperuricemia and gout include febuxostat (a more selective xanthine oxidase inhibitor); and intravenous PEGylated-uricase (pegloticase).
Describe the clinical, laboratory, and x-ray features of Ankylosing Spondylitis, including any extra-articular manifestations.
All patients have inflammatory back pain characterized by: 1) Insidious onset of pain lasting > 3 months 2) Prolonged morning stiffness (> 30-60 minutes) 3) Improvement of pain with exercise 4) No neurologic sequelaePhysical examination of back shows: 1) SI joint tenderness 2) Global loss of spine range of motion 3) Late in disease course may find back deformities and reduced chest expansion.Approximately 25% of AS patients have peripheral arthritis usually of hips and shoulders (i.e. joints close to spine).Extra-articular findings: acute anterior uveitis, osteoporosis, microscopic colitis, pulmonary apical fibrosis, CVD, cauda equina syndrome, amyloidosisLabs: Elevated sedimentation rate (ESR); negative rheumatoid factor (RF), negative ANA (serologically negative)Radiographs show sacroiliitis characterized by bone erosion and sclerosis (+/- bony fusion) in 100% of patients with AS by age 45.Over 66% of AS patients develop radiographic spondylitis with thin, marginal syndesmophytes. Only 10% develop complete spinal fusion (bamboo spine).Peripheral joint radiographs can show inflammatory hip disease which can lead to bony fusion (20-25%).
Discuss the epidemiology and genetics of the seronegative spondyloarthropathies.
Ank. Spond.: Affects males > females 7:3, onset 16 - 40, Caucasians more than other racial groups.Reactive Arthritis: Affects males > females (5-10:1 ratio),Onset occurs from childhood to age 40-50.Caucasians affected more than other racial groups.The relationship between the major histocompatibility antigen HLA-B27 and ankylosing spondylitis is the strongest of all associations between class I HLA and disease. Over 90% of Caucasian AS patients are HLA-B27 positive.
Explain the theories of the pathogenesis of the seronegative spondyloarthropathies.
Since not all persons who possess HLA-B27 develop a spondyloarthropathy, it’s thought that agenetically susceptible individual develops the disease when exposed to an environmental trigger.Bacteria such as salmonella, shigella, yersinia, campylobacter, and chlamydia induce reactive arthritis in 20% of B27 positive individuals. The trigger for ankylosing spondylitis is unknown although normal bowel bacteria has been proposed.Possible mechanisms:Molecular mimicry: B27 and infectious agent have shared epitopes –> cross reactivityArthritogenic peptide: B27 presents pathogenic peptide in a unique way, causes cross reactive, joint specific troubleB27 Heavy Chain: B27 misfolds heavy chains into homodimers which clogs ER, causing ER stress response, creates autoreactive Th17 cells
Discuss the treatment of the seronegative spondyloarthropathies as it relates to the pathogenesis.
Back exercises, sleep with small/no pillow, no smoking, NSAIDs, steroid injections, sulfasalazine, tetracycline, antibiotics, anti-TNF therapies.
Describe the general clinical and synovial fluid analysis features of calcium pyrophosphate dihyrate deposition disease (CPDD), including crystal morphology and birefringence.
CPDD is a type of arthritis associated with the release of calcium pyrophosphate dihydrate (CPPD) crystals into the joint space and chondrocalcinosis (calcified joint cartilage). Pseudogout is the term used to describe an acute episodic arthritis due to CPPD crystals. Pseudogout attacks are characterized by a sudden onset of severe pain, swelling, warmth, and redness of usually a large joint, most often the knee, and less frequently the wrist and ankle. Unlike gout, the first MTP is rarely involved.CPPD crystals are rhomboid-shaped and positively birefringent (blue when parallel to the axis of the red compensator) on polarizing microscopy. The synovial fluid is inflammatory (typically 2,000- 80,000 leukocytes/mm3) with a predominance of neutrophils. Peripheral blood WBC and ESR may be increased during acute attacks. Serum calcium, phosphorus, and iron studies are helpful in searching for associated metabolic causes of CPDD.
What are the four stages of the gout?
Asymptomatic Hyperurecemia: elevated serum uric acid levelAcute gouty arthritis: painful joint gout attackIntercritical gout: asymptomatic period between gout attacksChronic tophacious gout: soft tissue deposition of MSU crystals
Which joints are involved in ankylosing spondylitis?Reactive arthritis?Rheumatoid arthritis?Gout?Osteoarthritis?
AS: Spine, SI, hips, shoulders, no nodules.ankylosing spondylitis frequently affects synchondroses which are areas of cartilaginous union with bone. This includes manubriosternal joint, costovertebral joints, and pubic ramis.Reactive Arthritis: knees, ankles, hips, no nodules (no RF)Rheumatoid Arthritis: small joints, symmetrical distribution, synovitis, can get nodules (+ RF)Gout: MTP (Big toe), ankle, midfoot, small joints of hands, wrist (note, peripheral, cold)OA: DIPs, PIPs, 1st metacarpal at base of thumb, knees, weight baring joints, spine, hips, great toe
What are some key clinical features of ankylosing spondylitis?
EnthesisitisSacroilitisHLA-B27Other stuff, of course, but these are pretty important
What is the common genetic component shared by Rheumatoid arthritis patients?Ankylosing spondylitis?
RA: HLA- DR4, the shared epitope”Class 2 MHC
