Gout.pdf doctor Maher Mohammed yasseen tala

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1. •
• Crystal Arthropathies-Gout
• Dr.MahirAl-Talah
• M.B.Ch.BF.I.B.M.S.(Med.)

2. •Goutis the most common inflammatory arthritis in men and in older
women.
•It is resulting from deposition of monosodium urate (MSU) monohydrate
crystals in and around the tissues of joints causing attacks of acute
inflammatory arthritis.
•Gout is associated with hyperuricemia, which is defined as a serum urate
level greater than 6.8 mg/dL.
•Although hyperuricaemiais a strong risk factor for gout, only a minority of
hyperuricaemicindividuals actualydevelop gout.
•The risk of developing gout increases with ageand with serum uric acid
(SUA) levels.

3. •Typically, the disease presents as an acute and episodic monoarthritis
affecting the lower extremities but can become recurrent, chronic, and
deforming, affecting multiple joints.
•Tophiare a pathognomonicfeature of gout resulting from accumulation
of urate crystals in soft tissues or joints.
•The prevalence of gout is approximately 1%–2%, with a greater than 5:1
malepreponderance.

4. •Gout has become progressively more common over recent years in affluent
societies due to the;
•1-Increased prevalence of obesityand metabolic syndrome, of which
hyperuricaemiais an integral component.
•2-Increased use of certain medications such as diuretics,and the increasing
frequency of risk factors for hyperuricemia including hypertension, renal
disease and cardiovascular disease.
•3-High alcohol intake (predominantly beer, which contains guanosine),
generalisedosteoarthritis(OA) and a diet such as offal, seafood, red
meat and fructose, or low in vitamin C.

5. •Lead poisoning may cause gout (saturnine gout).
•The association between OA and gout is thought to be due to a reduction
in levels of proteoglycan and other inhibitors of crystal formation in
osteoarthritic cartilage, predisposing to crystal formation.
•Severe hyperuricaemiacan also occur in patients with haematologicaland
other cancers who are undergoing chemotherapy due to increased purine
turnover (tumourlysis syndrome).
•Men are three to five times more likely to have gout than women, but the
sex disparity decreases with age due to loss of the uricosuriceffect of
estrogen after menopause.

6. •About one-third of the body uric acid pool is derived from dietary sources
and two-thirds from endogenous purine metabolism .
•The concentration of uric acid in body fluids depends on the balance
between endogenous synthesis and elimination by the kidneys (two-thirds)
and gut (one-third).
•Purine nucleotide synthesis and degradation are regulated by a network of
enzyme pathways, but xanthine oxidase plays a pivotal role in catalysingthe
conversion of hypoxanthine to xanthine and xanthine to uric acid.

7. The main causes of hyperuricaemiaand
gout

8. •Clinical Features
•Gout has three stages: asymptomatic hyperuricemia, acute intermittent
gout, and chronic gout.
•Acute Gouty Attacks The classic picture of acute gout is rapid development
of an inflammatory arthritis involving one or occasionally two joints.
•This clinical picture can be easily confused with that of septic arthritis or
bacterial cellulitis, because many patients can mount an intense systemic
inflammatory response with fever, chills, and elevated inflammatory
markers.

9. •The classical presentation is with an acute monoarthritis, which affects
the first MTP joint in over 50% of cases. Other common sites are the
ankle, midfoot, knee, small joints of hands, wrist and elbow.
•The axial skeleton and large proximal joints are rarely involved. Typical
features include:
❖Rapid onset, reaching maximum severity in 2–6 hours, worse in the
early morning
❖Severe pain, often described as the ‘worst pain ever’
❖Extreme tenderness, so the patient is unable to wear a sock or to let
bedding rest on the joint
❖Marked swelling with overlying red, shiny skin
❖Self-limitingover 5–14 days, with complete resolution.

10. •The most commonly involved joints are the first metatarsophalangeal joint
(podagra), followed by the joints of the ankle, midfoot, and knee.
•During the attack, the joint shows signs of marked synovitis, swelling and
erythema.
•There may be accompanying fever, malaise and even delirium, especially if
a large joint such as the knee is involved.

11. •As the attack subsides, pruritus and desquamation of overlying skin are
common.
•Acute attacks may also manifest as bursitis, or tenosynovitis.
•Sometimes an acute attack will be followed by further attacks in other joints a
few days later (cluster attacks), the first possibly acting as a trigger.
•Simultaneous polyarticular attacks are unusual.
•Some people never have a second episode and in others several years may
elapse before a second attack occurs.

12. •Chronic gout
•This phase, called chronic gout (also referred to as chronic tophaceousgout or
chronic advanced gout), typically develops 10 or more years after the onset of
acute attacks.
•Transition to the chronic phase occurs if hyperuricemia is inadequately
treated.
•Patients with repeated attacks may progress to chronic gout, with chronic
pain, joint damage, deformity and functional impairment.
•Patients with uncontrolled hyperuricaemiawho suffer multiple attacks of
acute gout may also progress to chronic gout.

13. •The pathognomonicfeature of chronic gout is the tophus, a palpable
collection of MSU crystals in soft tissue or joints.
•These have a predilection for the extensor surfaces of fingers, hands, forearm,
elbows, achillestendons and some times the helix of the ear.
•Tophi have a white color ,differentiating them from rheumatoid nodules.
•Tophi can ulcerate, discharging white gritty material, become infected or
induce a local inflammatory response, with erythema and pus in the absence
of secondary infection.

14. •They are usually a feature of long-standing gout, but can sometimes develop
within 12 months in patients with chronic renal failure.
•Occasionally, tophi may develop in the absence of previous acute attacks,
especially in patients on thiazide therapywho have coexisting OA.
•In addition to causing musculoskeletal disease, chronic hyperuricaemiamay
be complicated by renal stone formation and, if severe, renal impairment
due to the development of interstitial nephritis as a result of urate
deposition in the kidney.
•Infiltration of tophi into boneis thought to be the driving mechanism for
bone erosion and joint damage in gout.

15. •Diagnosis
•The typical presentation of acute gouty arthritis in a characteristic joint
distribution is strongly suggestive of the diagnosis, particularly if history of
similar attacks that completely resolved is reported.
•However, detection of MSU crystals in the synovial fluid, bursa or tophus
remains the diagnostic “gold standard.” Arthrocentesis is not only important
to confirm clinical suspicion but also to rule out septic arthritis or other
crystalline arthropathies.
•MSU crystals can also be demonstrated in tophus aspiration

16. During acute attacks, intracellular, strongly negative birefringent,
needle-shaped MSU crystals are typically identified by polarized
compensated microscopy.
Polarized microscopy image of
strongly negative birefringent
monosodium urate crystals

17. •Septic arthritis can coexist with urate crystals in the synovial fluid; Gram stain
and culture should be performed and are necessary to exclude septic arthritis.
•Serum uric acid is not a diagnostically reliable test during acute flares since
serum urate level may be normal or even low.
•Laboratory testing may reveal leukocytosis and elevated inflammatory
markers, both of which are nonspecific.
•Between attacks, MSU crystals can often be demonstrated in previously
inflamed joints, providing support to the diagnosis.

18. •Investigations
•The diagnosis of gout can be confirmed by the identification of urate crystals
in the aspirate from a joint, bursa or tophus.
•In acute gout, the synovial fluid may be turbid due to an elevated neutrophil
count.
•In chronic gout, the appearance is more variable, but occasionally the fluid
appears white due to the presence of urate crystals.
•Between attacks, aspiration of an asymptomatic first MTP joint or knee may
still reveal crystals.

19. •A biochemical screen, including renal function, uric acid, glucose and lipid
profile, should be performed because of the association with metabolic
syndrome.
•Hyperuricaemia is usually present in gout, but levels may be normal during
an attack because serum urate falls during inflammation.
•Acute gout is characterised by an elevated ESR and CRP and with a
neutrophilia, all of which return to normal as the attack subsides.

20. •Tophaceous gout may be accompanied by a modest but chronic elevation in
ESR and CRP.
•X-rays are usually normal in acute gout, but well-demarcated erosions may be
seen in patients with chronic or tophaceous gout .
•Tophi may also be visible on X-rays as soft tissue swellings.
•In late disease, destructive changes may occur that are similar to those in
other forms of advanced inflammatory arthritis.

21. Erosive arthritis in chronic gout. Punched-out (‘Lulworth Cove’) erosions (arrows) in
association with a destructive arthritis affecting the first metatarsophalangeal joint.

22. •Treatment
•Management strategies should focus on treating acute attacks, long
term management of hyperuricemia, patient education, and
lifestyle modification.
•Management of Acute Gouty Attack
•Oral colchicine given in doses of 0.5 mg 2–4 times daily is the
treatment of first choice in acute gout.
•It works by inhibiting the inflammation, which reduces IL-1β
production by macrophages.
•The most common adverse effects are nausea, vomiting and
diarrhoea.

23. •Oral NSAIDs are also effective, but are used less commonly since many
patients affected by acute gout have coexisting cardiovascular,
cerebrovascular or chronic kidney disease.
•Oral prednisolone (15–20 mg daily for 2–3 days) or intramuscular
methylprednisolone (80–120 mg daily) are highly effective and are a good
choice in older patients where there is an increased risk of toxicity with
colchicine and NSAID.

24. •IL-1 inhibition with anakinra or canakinumab is effective but both
treatments are expensive and so are seldom given.
•Local ice packs can also be used for symptomatic relief.
•Patients with recurrent episodes can keep a supply of an NSAID, colchicine
or prednisolone and take it as soon as the first symptoms occur, continuing
until the attack resolves.
•Joint aspiration can give pain relief, particularly if a large joint is affected,
and may be combined with an intra-articular glucocorticoid injection if the
diagnosis is clear and infection can be excluded.

25. •Prophylaxis Patients who have had a single attack of gout do not
necessarily need to be given urate-lowering therapy, but it should be
offered to individuals who have more than one acute attack within 12
months and those with complications such as tophi or erosions .
•The long-term therapeutic aim is to prevent attacks occurring by
bringing SUA below the level at which monosodium urate
monohydrate crystals form.

26. •Allopurinol is the drug of first choice. It inhibits xanthine oxidase, which
reduces the conversion of hypoxanthine and xanthine to uric acid.
•The recommended starting dose is 100 mg daily, or 50 mg in older patients
and in renal impairment.
•The dose of allopurinol should be increased by 100 mg every 4 weeks (50 mg
in older patients and those with renal impairment) until the target uric acid
level is achieved, side-effects occur or the maximum recommended dose is
reached (900 mg/day).

27. •Acute flares of gout often follow initiation of urate-lowering therapy.
•The patient should be warned about this and told to continue therapy, even if
an attack occurs.
•The risk of flares can be reduced by prophylaxis with oral colchicine (0.5–1
mg daily) or an NSAID for the first few months.
•Alternatively, patients can be given a supply of colchicine, an NSAID or
prednisolone to be taken at the first sign of an acute attack.
•In the longer term, annual monitoring of uric acid levels is recommended.
•In most patients, urate-lowering therapy needs to be continued indefinitely.

28. •Febuxostat also inhibits xanthine oxidase. It is typically used in patients with
an inadequate response to allopurinol and when allopurinol is contraindicated
or causes adverse effects.
•Febuxostat undergoes hepatic metabolism and no dose adjustment is
required for renal impairment.
•It is more effective than allopurinol, but commonly provokes acute attacks
when therapy is initiated.
•Prophylaxis against acute attacks should be given on initiating therapy, as
described for allopurinol.

29. •Uricosuric drugs, such as probenecid, sulfenpyrazone and benzbromarone,
lower urate levels but are seldom used in routine clinical practice.
•They are contraindicated in urate over-producers and those with renal
impairment or urolithiasis and require patients to maintain a high fluid intake
to avoid uric acid crystallisation in the renal tubules.
•Pegloticase is a biologic treatment comprised of the enzyme uricase
conjugated to monomethoxypolyethylene glycol.
•It breaks down uric acid and is indicated for the treatment of tophaceous gout
resistant to standard therapy and is administered as an intravenous infusion
every 2 weeks for up to 6 months.

30. •It is highly effective at controlling hyperuricaemia and can cause regression of
tophi.
•The main adverse effects are infusion reactions (which can be treated with
antihistamines or glucocorticoids) and flares of gout during the first 3 months
of therapy.
•A limiting factor for longer-term treatment is the development of antibodies
to pegloticase, which occur in a high proportion of cases and are associated
with an impaired therapeutic response.

31. •Lifestyle measures are as important as drug therapy in treatment of gout.
•Patients should be advised to lose weight if appropriate and reduce excessive
alcohol intake, especialy beer.
•Several antihypertensive drugs, including thiazides, β-adrenoceptor
antagonists (β-blockers) and angiotensin converting enzyme (ACE) inhibitors,
increase uric acid levels, whereas losartan has a uricosuric effect and should
be substituted for other drugs if possible.
• Patients should avoid large amounts of seafood and offal, which have a high
purine content, but a highly restrictive diet is not necessary.

32. Calcium pyrophosphate deposition (CPPD) disease
•Calcium pyrophosphate deposition (CPPD) disease encompasses a
range of clinical presentations. Crystals can deposit in articular
cartilage, synovium, entheses, tendons and ligaments – both axial
and peripheral skeletal sites.
•The acute form of CPPD disease is acute calcium pyro phosphate
(CPP) crystal arthritis (‘pseudogout’).
•Acute CPP crystal arthritis is rare under the age of 55 years, but
occurs in 10%–15% of people between 65 and 75 years and 30%–60%
of those over 85 years old.
• It typically involves the knee, wrist, ankle, shoulder and hip.
•Acute CPP inflammation can also affect axial skeletal structures.

33. ➢Risk factors for CPPD disease
➢Commen
➢Older age
➢Osteoarthritis
➢Hyperparathyroidism (both primary and secondary)
➢Hypovitaminosis-D (by causing secondary hyperparathyroidism)
➢Rare
➢Familial factors
➢Haemochromatosis
➢Hypophosphatasia
➢Hypomagnesaemia
➢Hypoparathyroidism
➢Wilson’s disease

34. •Clinical features
•The typical acute CPP crystal arthritis presentation is with a swollen tender
joint that is warm and erythematous with a large effusion.
•Fever is common and the patient may appear confused and ill.
•The knee is most commonly affected, followed by the wrist, shoulder, ankle
and elbow.
•Trigger factors include trauma, intercurrent illness, dehydration and surgery.

35. •Chronic CPP crystal arthritis can mimic RA, though joint involvement patterns
are generally different (in chronic CPP crystal arthritis: wrists, MCP joints 2
and 3, ankles, shoulders).
•Affected joints usually show features of OA, with varying degrees of synovitis.
•Effusion and synovial thickening are usually most apparent at knees and
wrists.
•Wrist involvement may result in carpal tunnel syndrome.

36. •Investigations
•The pivotal investigation in diagnosing acute CPP crystal arthritis is joint
aspiration, followed by examination of synovial fluid using compensated
polarised microscopy to demonstrate CPP crystals.
•The aspirated fluid is often turbid and may be uniformly blood-stained,
reflecting the severity of inflammation.
•Since sepsis and acute CPP crystal arthritis can coexist, Gram stain and
culture of the fluid should be performed to exclude sepsis, even if CPP
crystals are identified in synovial fluid.

37. •Management
•In acute CPP crystal arthritis, ice packs, joint elevation and joint aspiration
provides symptomatic relief.
•Once infection is excluded, intra-articular glucocorticoid can be injected.
•NSAIDs and colchicine (0.5–2 mg daily) are helpful, but must be used with
caution in older patients.
•Chronic CPP crystal arthritis can respond to low-dose oral glucocorticoids,
methotrexate and hydroxychloroquine.