Term
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Definition
• Disease state arising from the deposition of monosodium urate crystals in assorted tissues, with accompanying inflammatory and/or degenerative consequences
– In joints -> inflammatory arthritis
– In soft tissue -> tophi
– In kidneys -> nephrolithiasis, nephropathy
• Most common inflammatory arthritis in men >40 |
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Term
| normal uric acid metabolism |
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Definition
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Term
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Definition
• Serum uric acid >6.8 mg/dL
• Caused by uric acid overproduction and/or under excretion |
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Definition
• 10% of cases
• 24 hour urinalysis >1000 mg/d
• Causes
– Genetic • Glucose-6-phosphatase deficiency (glycogen storage disease type I) • Hypoxanthineguanine phosphoribosyltransferase deficiency (HGPRT) • PRPP-synthetase superactivity
other causes: – Excessive purine intake
– Ethanol
– Drugs: nicotinic acid, warfarin, chemotherapy (tumor lysis)
– Obesity
– Malignancies (myeloproliferative, lymphoproliferative)
– Psoriasis
– Hemolytic anemia
– Tissue destruction (hypoxia, ischemia, trauma) |
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Term
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Definition
• 90% of cases
• <500 mg/d excretion
• Causes
– Genetic (polycystic kidney disease, etc.) – Decreased GFR
– Organic acidosis
– Lead nephropathy
– Drugs |
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Term
| drugs that affect uric acid |
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Definition
• Cyclosporin
– Reduced GFR
– Reduces urate secretion
• Aspirin
– Low dose (eg. 81 mg): inhibits urate secretion
– High dose (>3g): decreases tubular reabsorption
• Diuretics
– Volume depletion -> increased reabsorption
– Thiazides interfere with secretion |
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Term
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Definition
• Hyperuricemia present in 5-10% of adult men
• 80% of hyperuricemic patients do not develop gout |
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Term
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Definition
• Hyperuricemia is associated with hypertension, renal disease, metabolic syndrome, cardiovascular disease
• Studies are beginning to suggest that uric acid is an independent risk factor for these conditions and may be involved in their pathogenesis
–An elevated uric acid level consistently predicts the development of hypertension.
– An elevated uric acid level is observed in 25–60% of patients with untreated essential hypertension and in nearly 90% of adolescents with essential hypertension of recent onset.
– Raising the uric acid level in rodents results in hypertension with the clinical, hemodynamic, and histologic characteristics of hypertension.
– Reducing the uric acid level with xanthine oxidase inhibitors lowers blood pressure in adolescents with hypertension of recent onset
• However, currently not sufficient evidence to support treatment of asymptomatic hyperuricemia |
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Term
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Definition
• Most common inflammatory arthritis in men>40
• Total prevalence ~3%; 6-9% if >80
• U.S. incidence may be rising (>2 fold) |
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Term
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Definition
• Asymptomatic hyperuricemia
• Acute gout flares
• Chronic(tophaceous) gout |
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Term
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Definition
• 4th-6th decade (men); later in women
• Sudden onset, rapid escalation
• 1st MTP
– 50%haveasfirstattack – 90%willhaveeventually
• Other lower extremity joints
• Systemic symptoms
• Extra-articular (bursitis, tenosynovitis)
• Triggered by: trauma, surgery, sepsis, overindulgence (alcohol, purine-rich foods), drugs |
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Term
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Definition
• Chronic destructive arthritis
• Flares become polyarticular, additive, ascending
• Can be mistaken for rheumatoid arthritis |
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Term
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Definition
tophaceous gout
So here's an example of tophi in gout. Personally, I've never tophi in the ears, but I do know that it's a common site of them. These are examples of tophi, but more so you'll see tophus on extensor surfaces or surfaces that have pressure points. Here's an example of an olecranon process tophi. And here you see multiple tophi in gout throughout the hands.
-can present similarly to rheumatoid nodules on olecranon but different radiologic and ultrasound properties |
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Term
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Definition
In this radiograph, which is a little bit zoomed out, but there are some definitive features that we see in patients with gout. One of the main findings here is this lytic or overhanging edge, overhanging bony erosion, which forms this lytic lesion. You can clearly see the sharp jagged edge of bone hanging over the edge. You can see that there is destruction in the joint spaces.
And on the image to the right, what we're identifying here is potentially the formation of different tophus through deposition of uric acid. But you can see that there's many erosions, there's many subchondral cysts, there's evidence of erosions here. There's evidence of joint space narrowing and destruction. And these little jagged edges that come above the edge, which I'm trying to point out here, are these overhanging lytic lesions, which are really important to identify in gout and kind of clue you in on to the diagnosis, in conjunction with the physical exam and clinical picture. |
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Term
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Definition
Arthrocentesis
• Can be performed even if not in acute attack
• Inflammatory joint fluid, sometimes septic appearing |
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Term
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Definition
Asymptomatic hyperuricemia -> no treatment
Acute gout -> antiinflammatory preventative
Chronic gout -> uric acid lowering therapy |
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Term
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Definition
• NSAIDs
• Steroids
– Intraarticular – Oral/IV
• Anakinra
• Colchicine
– Never IV
– Used prophylactically in intercritical periods
– Toxicities: diarrhea (common), neuromyopathy, bone marrow suppression, hematologic abnormalities
– Not dialyzable |
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Term
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Definition
• Adjust offending medications (ex. diuretics)
• Weight loss
• Dietary adjustments
– Less meat, seafood
– Less alcohol (particularly beer)
– Less fructose containing soft drinks
• Purine rich foods
– Beer, other alcoholic beverages.
– Anchovies, sardines in oil, fish roes, herring
– Yeast
– Organ meat (liver, kidneys, sweetbreads)
– Meat extracts, consomme, gravies
– Mushrooms, spinach, asparagus, cauliflower, legumes (dried beans, peas) less associated with gout |
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Term
| Indications for Uric Acid Lowering Medication |
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Definition
• Tophaceous gout
• Erosive gout
• Unacceptably frequent attacks(>3-4/year)
• Nephrolithiasis
• Serum uric acid > 12 with other risk factors for gout or nephrolithiasis
• Goals: lower serum urate<6.0(<5.0 if tophi)
• Should not be initiated during an acute flare |
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Term
| Treating Under Secretion of uric acid: Uricosurics |
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Definition
• SuppressURAT1->decreasestubular reabsorption
• Probenecid
• (sulfinpyrazone,benzbromarone)
• Others:losartan,fenofibrate
• Limitations:
– Require adequate GFR
– Increases risk of uric acid stone formation/ urinary crystallization
– Numerous drug-drug interactions (ampicillin, salicylates, indomethacin, heparin, etc.) |
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Term
| Treating overproduction of uric acid |
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Definition
So treating the over-producers. There are many ways, but we have a class of medication known as xanthine oxidase inhibitors. These include allopurinol and febuxostat. And then there's another class of medication called uric oxidase. And an example of that is rasburicase, or Pegloticase is the trade name. Xanthine oxidase inhibitors stop xanthine oxidase, which prevents hypozanthine from becoming xanthine, which further stops xanthine from becoming uric acid.
So both of these pathways are inhibited, leading to less uric acid in general. The uric oxidase works by taking the uric acid and converting it into allantoin, which then is inert and does not cause gout or inflammation. So these medications are rare, they're infusions. They're often not used because they're extremely, extremely expensive. And they need to be used often in a hospital setting by infusion. |
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Term
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Definition
• Purine analog of xanthine
• Competitive xanthine oxidase inhibitor
• Active metabolite = oxypurinol
• Potentiates azathioprine and warfarin
• Side effects:
– Rash/toxic epidermolysis/Stevens Johnson syndrome
– GI intolerance/liver enzyme elevation – Cytopenia |
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Term
| Allopurinol Hypersensitivity Syndrome |
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Definition
• Idiosyncratic; usually develops within first 3 months of initiation
• Fever, rash, hepatitis, interstitial nephritis, myocarditis, rhabdomyolysis, eosinophilia
• Incidence ~0.4%, mortality 25% |
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Term
| Other Urate Lowering Therapies |
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Definition
• Febuxostat
– Non-purine selective xanthine oxidase inhibitor
– Hepatically metabolized -> ?safer in renal insufficiency
– Side effects: transaminitis
• Uricase
– Converts uric acid to allantoin
– Prevents/manages tumor lysis syndrome – Infusion reactions; anti-uricase antibodies |
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Term
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Definition
• Calciumpyrophosphatedepositiondisease – Pseudogout
– Also pseudo-septic, pseudo-RA, pseudo-OA
• Associatedwithaging
• Alsoassociatedwith
– Hemochromatosis
– Hyperparathyroidism
– Hypomagnesemia/hypophosphatemia – Gout
– Trauma
– Hypothyroidism |
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Term
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Definition
• Acute inflammatory attacks
• Asymptomatic in between
• Flares involve large joints: knees, shoulders, wrists, ankles
• Also can involve MCPs
• May take longer to reach peak intensity, longer to subside than gout
• Not due to uric acid |
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Term
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Definition
• Jointaspiration
– Crystals more rhomboid
– Weakly positive birefringence |
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Term
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Definition
So if you look at this X-ray here on the left immediately, it's not abundantly really clear what's going on in terms of CPPD or really what this X-ray is trying to elucidate. So what's important to remember is, you really have to look at the whole X-ray. And that means looking at not just the DIPs, the PIPs, that MCPs and the wrist bones, but you also have to look at the wrist itself which includes this area I'm circling. And let me circle it in red. It's called the TFCC, the triangular fibrocartilage complex, which is a cartilaginous structure located on the ulnar aspect of the wrist that cushions and supports the small carpal bones of the wrist.
This cartilage in CPPD gets deposition of calcium. It gets calcified-- calcifications. So you can see what should be opaque or translucent-- you can actually see these kind of white calcium dots, which represent deposition of chondrocalcinosis.
So the point of this slide is, look at the whole X-ray. Don't forget to look at the wrist. Don't forget to look at subtle aspects, especially in CPPD, of the TFCC and evaluate that area for any calcifications or abnormal chondrocalcinosis.
On the knee it's a little bit more easy to depict. We talked about in gout how the ultrasound may reveal, on ultrasound, a thick line above and below the cartilage. Well, what you see in CPPD, which you can see on the ultrasound, but as well as the radiograph, is that this calcification, this thick, irregular white line that you see, actually happens in-between the cartilage, not on top of it or not below it. But the calcification is actually happening in-between if. And if I erase it you'll see that you can clearly see that white line. That is definitive CPPD-- or, what most-likely is definitive-- where the gold standard is aspirating and looking at crystals. But if any rheumatologist saw this X-ray, probably 10 out of 10 will tell you that this patient has CPPD. |
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Term
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Definition
CPPD arthritis again has a predilection-- we don't know why-- to the second and third MCPs. So again, if you get OA in a joint that's not supposed to get OA, raise your clinical suspicion. Again, just to highlight the second and third MCPs here. And a lot of times you'll get a squaring of the MCP, but that's not really depicted that well here.
What is depicted a little bit better is these kind of calcifications in the TFCC I was mentioning. And, you know, just to kind of mention, it's quite subtle. It's not just staring you in the face. So you really can see where the black arrow is, that subtle calcification. And that's enough, a lot of times, to lead you towards a diagnosis or to point you in the direction of a correct treatment. |
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Term
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Definition
Here is an example of CPPD arthritis. Some of the other things you can see on this X-ray is the periarticular osteopenia. But you can see the abnormal calcifictous deposition here. And you can see this kind of squaring of the metacarpal phalangeal.
And as you see these with time, you'll be able to recognize the nuances. For example, if you see this fifth finger you can see that it's not really squared off, and it has its normal curvature. So these are just kind of nuances which will help guide you with the diagnosis. But again, commonly tested, the only definitive way of proving CPPD is joint aspiration, evaluating the fluid under a microscope.
But in the real world you don't always have the ability to do that. And, for example, in this patient-- you know, if it was just pain of the MCPs second and third, it doesn't look like there's much fluid that would be able to be aspirated anyway. So you might just be putting the patient through a lot of pain and you're not going to get any fluid in this type of joint. |
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Term
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Definition
• NSAIDs
• Steroids
• ?Colchicine
• Treat associated disorders (hemachromatosis, hyperparathyroidism) |
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Term
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Definition
• Lyme disease was named in 1977 when arthritis was observed in a cluster of children in and around Lyme, CT
• Conditions suggested that this was an infectious disease probably transmitted by an arthropod
• Further investigation revealed that Lyme disease is caused by the bacterium
– Borrelia burgdorferi |
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Term
| Three Stages of Lyme Disease |
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Definition
• Localized rash – erythema chronicum migrans
• Dissemination to multiple organ systems
• Chronic disseminated stage often with arthritic symptoms |
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Term
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Definition
• Signsofearlydisseminatedinfectionusually occur days to weeks after the appearance of a solitary erythema migrans lesion
• Neurologic–Bell’sPalsy
• Musculoskeletalmanifestationsmayinclude migratory joint and muscle pains
• Intermittent swelling and pain of one or more joints in late disseminated disease |
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Term
| Chronic Disseminated Lyme |
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Definition
• Chronic arthritis
• Chronic axonal polyneuropathy
• Lyme disease morbidity may be severe, chronic, and disabling.
• Rarely, if ever, fatal |
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Term
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Definition
• Diagnosedclinically,confirmedserologically.
• Oftenappropriatetotreatpatientswithearly disease solely on the basis of objective signs and a known exposure.
• CDCrecommendstestinginitiallywitha sensitive first test, ELISA or an IFA test
– Followed by testing with the more specific Western immunoblot (WB) test to corroborate equivocal or positive results obtained with the first test. |
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Term
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Definition
• Single dose doxycycline shortly after tick bite.
• If Lyme disease proven, give course doxycycline or amoxicillin
• For neurologic disease, IV Ceftriaxone is required |
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