​Kembara Xtra - Medicine - Gout

​Kembara Xtra - Medicine - Gout 
A chronic tophaceous joint that is accompanied by pain, nodule growth, and cutaneous compromise can develop from an inflammatory arthritis that causes an acutely red, hot, and swollen joint.
Acute and chronic arthritis, tophi, urate nephropathy, and uric acid nephrolithiasis are all conditions caused by the deposition of monosodium urate (MSU) crystals in joints and soft tissues.
The long limb, foot, ankle, and knee are most commonly affected.
The first metatarsophalangeal joint (podagra) involvement is distinctive.
● Gout flares can affect the elbows, wrists, and hands, but patients with severe, poorly controlled gout are more likely to experience upper limb involvement.
It occasionally involves the axial skeleton.
Flares typically have one articulation. Polyarticular flares can be accompanied by severe systemic symptoms such delirium, fever, and chills.
Hyperuricemia (serum uric acid level >6.8 mg/dL) is associated with gout.

Gout has a higher frequency in men than in women, with an incidence of between 0.6 and 2.9 per 1,000 person years.
Prevalence
Adult prevalence ranges from 0.68 to 3.9%.

Pathophysiology and Etiology 
Four stages of pathophysiology

 Formation of MSU crystals (Changes in uric acid solubility induced by local temperature reduction, trauma, or acidosis may precipitate out of solution and collect as crystals in joints and soft tissues). Development of hyperuricemia (from uric acid overproduction and/or renal underexcretion).
Clinical manifestation of acute inflammatory reactions to accumulated crystals that cause gout flares
Advanced disease's clinical appearance is characterized by tophi and joint degeneration. 

Genetics: For individuals of Asian ancestry, consider genotyping for the HLA-B*5801 mutation.
Inherited enzyme defects linked to overproduction of uric acid include hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficiency and phosphoribosyl pyrophosphate (PRPP) deficiency (Lesch-Nyhan syndrome).

Risk Elements 

Age >40 years, male gender, and excessive dietary purine intake (beer, red meat, seafood, sugar-sweetened beverages).
Obesity/Metabolic Syndrome (BMI > 30) 
Heart failure that is congestive

CKD, or chronic kidney disease
Smoking, hypertension, dyslipidemia, and dehydration (which has effects akin to those of diuretics)
Diabetes is a condition.
Drugs that increase urate include thiazide diuretics, loop diuretics (less risky than thiazides), niacin, and aspirin.
Transplant-associated gout can develop in immunosuppressed solid organ transplant recipients on calcineurin inhibitors (cyclosporine and tacrolimus) and low dosage prednisolone because these drugs raise uric acid levels.

 Hyperuricemia resulting from chemotherapy, hemolysis, or the syndrome of fast cell turnover/tumor lysis

Prevention 
Avoid purine-rich foods like red meat and shellfish in your diet. Reduce your alcohol (beer and liquor) usage.
Keep up your fluid intake to prevent dehydration.

Accompanying Conditions 

non-traumatic joint ailments, metabolic syndrome, obesity (BMI >30), renal disease, and other diseases

Gout's typical initial appearance is diagnosed as follows (2): - Lower limb and monoarticular arthritis are common early in the course of the disease. Gout flares can occur in the joints or periarticular tissues (e.g., bursae, tendons, and entheses), while upper extremity and polyarticular presentations are typically seen in chronic cases. - Gout flares can occur in the joints or periarticular tissues (e.g., bursae, tendons, and entheses).
– The joint may be sensitive to the touch, heated, swollen, and erythematous. Stabbing, gnawing, searing, or throbbing are all possible adjectives to characterize the agony.
– Use of the affected areas is severely restricted, walking is challenging, and anxiety of even light physical contact pervades.
– Patients are frequently startled out of sleep because they are sensitive to contact with clothing or bed linens. - There is a sudden onset of severe pain, which frequently worsens over the course of 12 to 24 hours.
– Infection, injuries, dehydration, or excessive alcohol or purine ingestion may cause acute episodes.
- There may be a fever.
- Tophi, or subcutaneous or intraosseous nodules, may appear following numerous recurring bouts.
Rarely, chronic occurrences of uric acid renal stones might cause pain with urine.
Chronic gout symptoms include: - Subcutaneous tophi in the finger pads, tendon, olecranon bursae, joints, and ears. Tophi can ulcerate with thick/white discharge and underlying infections, but they are typically not sensitive. Tophi are stiff and rigid, come in different sizes, and can become intensely irritated.

clinical assessment 

 Check the range of motion (ROM) and pain in the suspected joint(s).
Tophi can be seen on the Achilles tendon, in the ear's helix, above the olecranon process, or in the afflicted joints.

Multiple Diagnoses 
Septic arthritis, cellulitis, osteoarthritis, rheumatoid arthritis and bursitis, traumatic arthritis, hemarthrosis, calcium pyrophosphate deposition illness (formerly known as "pseudogout"), 

Diagnostic compound score for patients presenting with monarthritis in primary care settings based on laboratory findings - First metatarsophalangeal joint involvement - Male sex - Previous patient-reported arthritis attack - Onset within 1 day - Joint redness
- High blood pressure or heart disease
High blood urate concentration Score 4 ruled out gout in 97% of cases; score >8 ruled in gout in 80% of cases.
Initial acute gout attack: CBC (WBC may be increased), ESR/CRP, and Uric acid (may be normal or low).
Gram stain and culture to rule out infection; urate crystals (negatively birefringent under polarized microscopy); cell count (WBC typically 2,000 to 5,000 cells/mm3;
Radiographs/plain x-rays are normal early in the disease but can reveal periarticular erosions with periosteum overgrowth in chronic gout. 24-hour urine to screen for uric acid overproduction (>800 mg/24 hr) in patients with beginning before the age of 25 or with a history of urolithiasis.
Ultrasonography can reveal intra-articular or intrabursal tophi, a snowstorm appearance, and a twofold contour sign (indicating MSU crystal formation on the surface of hyaline articular cartilage).
Urate deposition at articular or periarticular sites can be seen with dual-energy CT (DECT) imaging.

Management 

support services such as cold packs, rest, help with movement, and sufficient nutrition and water

Medication Immediate care
- Pharmacologic therapy should start within 12 to 24 hours of the onset of an acute gout attack and continue for 1 to 2 days after the event has abated.
- Treatment to decrease uric acid shouldn't be stopped during an acute gout attack.
- Mild to moderate gout intensity (6 or less on a scale of 1 to 10 for visual analog pain), especially when only one or a few minor joints or one to two large joints are affected. an NSAID
500 mg of naproxen each day
Indomethacin: 50 to 150 mg/day (usually less well tolerated than other drugs); Meloxicam: 7.5 to 15 mg/day. Ibuprofen: 800 mg every eight hours; Diclofenac: 75 mg twice daily.
- Corticosteroids administered intravenously, orally, intramuscularly, orally
 Think about using corticosteroids intra-articularly.
In patients with acute gout flares who cannot tolerate NSAIDs or have contraindications to NSAIDs and colchicine, such as CKD, corticosteroids may be helpful.
NSAIDs may be used with intra-articular corticosteroid, oral steroid, or colchicine when monotherapy is ineffective for treating acute flares.
Oral corticosteroids: 15 to 20 mg to 35 mg per day for five days, depending on the dose. 
If you are unable to take oral drugs, consider the following intraarticular, intramuscular, or intravenous preparations: colchicine, dexamethasone, and triamcinolone acetonide.
Used for gout bouts whose onset was 36 hours before the start of treatment Start with a loading dose of 1.0–1.2 mg, then follow with 0.5–0.6 mg. 0.5 to 0.6 mg every 8 hours with a maximum of 6 mg per course and a minimum of 3 days between courses should be resumed an hour later, after 12 hours. - Inhibitors of interleukin 1 (IL-1)
 Reserved for patients with unacceptable side effects or conditions that make first-line anti-inflammatory medication inappropriate.
Canakinumab 150 mg SQ X1 (Watch for side effects, including life-threatening infections.)
Anakinra 100 mg SQ once a day for five days if you have severe gout (7 on a 10-point pain scale, >4 joints, >1 region of arthritis, or >3 big joints). Initial combination therapy is a possibility and involves taking the following medications in their full doses: Colchicine as well as NSAIDs
Colchicine and corticosteroids given orally
Intra-articular steroids: If pharmacologic monotherapy is ineffective for a patient, add a second medication.
Treatment that is ongoing - urea-lowering medication for:
 Radiographic gout damage or fewer than one annual attack
 Urolithiasis or CKD stage 2 or worse: Treat to a serum uric acid level of 6 mg/dL (may need 5 mg/dL to alleviate symptoms).
- Urate-lowering medications can be used during an acute attack as long as effective anti-inflammatory prophylaxis, such as:  NSAIDs at low doses: naproxen 250 mg PO BID
If NSAIDs and colchicine are prohibited or ineffective, use low-dose colchicine (0.5 to 0.6 mg once or twice day).
 Low-dose prednisone at 10 mg/day for a minimum of 6 months or 3 months after the serum urate target is reached 
Agents that lower urea such as Allopurinol, a xanthine oxidase inhibitor, do not decrease the frequency of acute attacks.
Start at a maximum of 100 mg per day (50 mg per day in stages 4 or 5 of CKD).
Titrate dose up to maximum level every two to five weeks.
 Check serum uric acid levels and renal function every year following the first for three months.
 Keep an eye out for symptoms of eosinophilia, pruritus, rash, increased hepatic transaminases, and allopurinol hypersensitivity syndrome (AHS). Testing for the HLA-B*5801 allele in people of Korean, Chinese, or Thai descent should be done.
Selective Xanthine Oxidase Inhibitor Febuxostat: Start at 40 mg/day and titrate to 80 mg/day.
Probenecid is a uricosuric drug.
If xanthine oxidase inhibitor is not recommended, an alternative is available.
 Can be administered in addition to febuxostat or allopurinol if serum urate goal is not met. Increased risk of urolithiasis with this medication. Start with 250 mg BID and titrate to 2,000 mg/day. Not advised if CrCl 50 or if history of urolithiasis.

Furthermore Treated

Other therapies
 Consider Losartan for people with hypertension as it has uricosuric characteristics.
Fenofibrate has uricosuric qualities as well and may help with lipid problems.

Surgical Techniques 

The removal of large tophi that are infected or obstructing joint motion may require surgery.

Alternative Therapies 
It has been demonstrated that taking vitamin C (>500 mg daily) lowers serum uric acid levels.


Patient Follow-Up Monitoring
Serum uric acid measurements every two to five weeks (q2–5wk) when urate-lowering therapy is titrated to the desired effect CBC, renal function, liver function tests, and urinalysis are routinely monitored.

Diet
Avoid: - Organ meats with a high purine content, such as sweetbreads, liver, and kidney; - meals or beverages sweetened with high-fructose corn syrup (limit fructose to less than 1 g/kg/day). - Alcohol abuse (more than two drinks per day for men and more than one drink per day for women).
Limit: - Servings of naturally sweetened fruit juices - Beef, lamb, pig, and seafood with a high purine content, such as sardines and shellfish.
- Desserts, beverages with added sugar, and sugar
- Table salt, which is found in sauces and gravies - All patients should consume between one and two units of alcohol per day, preferably beer
Encourage: - A daily coffee intake of more than four cups decreased the risk of gout by 57%.
- Dietary fiber, folate, vitamin C, and dairy products all reduced the risk of developing gout. - Eating cherries may help prevent gout.

Dietary and lifestyle changes; discussion of the etiology of gout and the fact that an effective urate-lowering medicine is frequently required for treatment.

Gout may typically be successfully controlled with the right care and lifestyle changes.

Complications include kidney stones, uric acid nephropathy, and inflammatory arthritis with joint damage.

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