"Refractory gout in the elderly" is complicated and tricky.

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 Introduction: "Refractory gout in the elderly" is complicated and tricky? The main points of diagnosis and treatment are clear.

Mr.
Chen is 68 years old this year.
He found elevated uric acid when he was in his 30s.
He has not paid attention to it, has not standardized treatment, and has not controlled his diet.

14 years ago, the first right first metatarsophalangeal joint pain occurred suddenly, and the pain was severe, accompanied by local redness, swelling, heat pain, and limited mobility.
After taking analgesics, the symptoms could be relieved slightly, but the diet was a little careless and repeated attacks , Did not take uric acid lowering drugs.
Later, joint swelling and pain occurred more and more frequently, and gradually spread to the hands, knees, and ankle joints of both feet.
Eight years ago, tophi gradually appeared on the left foot, auricle, and fingers, as well as multiple joints in the hands.
Deformed.

After taking uric acid-lowering drugs intermittently, the blood uric acid is still as high as 650umol/L.
Two weeks ago, he suffered severe pain in his left foot and left bowl joint after eating seafood and was unable to walk.
He was admitted to the hospital for treatment and was diagnosed with elderly refractory gout.

 The patient has a history of hypertension for 10 years, usually has good blood pressure control, and has a history of diabetes for 6 years.
He has oral metformin and glimepiride, and his blood sugar can be controlled.

Analysis of this case has the following characteristics: 1.
Elderly male (over 65 years old); 2.
Multiple joint involvement, bone destruction and deformation; 3.
Multiple tophi; 4.
Long history of gout and not standardized treatment; 5.
Poor control of blood uric acid; 6.
Many complications (diabetes, hypertension).

In line with the diagnosis of refractory gout in the elderly.

  With the development of my country’s economy and changes in diet, the incidence of gout caused by hyperuricemia has been increasing, and it has become a common disease threatening the health of middle-aged and elderly people.
However, gout in the elderly is mostly "refractory to treatment".
"Gout", like the patients in the above cases, often coexists with multiple diseases and involves multiple joints.
The treatment is very difficult and brings great pain to the patients.

To this end, the author refers to the literature and summarizes the elderly refractory gout and its related diagnosis and treatment strategies for readers.

 What is "refractory gout in the elderly"? Guidelines for the first time in my country give the definition "Chinese Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout (2019)" for the first time proposes the definition of refractory gout (meet any one of the following): ➤Single or combined use of conventional uric acid lowering drugs in sufficient quantity and full course of treatment , But the blood uric acid is still ≥360umol/L; ➤Received standardized treatment, but the gout attacks are still ≥2 times/year; ➤There are multiple or progressive tophis.

 We define gout in the elderly over the age of 65 as elderly gout.
According to the time of first onset, elderly gout can be divided into two types: ➤Patients with gout attacks in the middle and young ages enter the elderly stage; ➤New onset in the elderly Gout, that is, the first attack of gout over the age of 65.

Elderly patients with gout that meet the above-mentioned refractory gout manifestations are senile refractory gout.

 What is so special about "senile refractory gout"? 1.
Long medical history, poor efficacy of drugs, most of the elderly refractory gout is the onset of young and middle-aged, gouty arthritis recurrent attacks and poor efficacy of conventional analgesics.

2.
The coexistence of multiple diseases affects the metabolism of uric acid.
For example, in elderly gout patients with basic kidney disease, the renal excretion capacity decreases and the excretion of uric acid decreases, or the use of uric acid lowering drugs due to abnormal liver and kidney function is contraindicated, making it difficult for patients to control blood uric acid to reach the standard.
.

3.
Elderly patients have a relatively shallow understanding of the personal management of gout, and often only pay attention to the control of acute gout symptoms, but do not pay attention to the importance of long-term control of blood uric acid levels.
The uric acid-lowering treatment is not timely and the compliance is poor.

4.
Due to the coexistence of multiple diseases, the elderly use multiple drugs.
Some drugs affect the pharmacokinetics of uric acid-lowering drugs and affect the efficacy of uric acid-lowering drugs.

For example, antihypertensive drugs (such as hydrochlorothiazide, β-receptor blockers) and pyrazinamide for the treatment of tuberculosis have the adverse effect of increasing blood uric acid at the same time, which can increase the risk of secondary hyperuricemia and gout.

5.
Poor drug tolerance may cause analgesics and uric acid lowering to damage important organs and affect the treatment of gout.  The treatment strategy of "senile refractory gout" 1.
Basic treatment ➤ Diet control: Eat less high-purine foods (such as animal offal), reduce the intake of meat and seafood (sea fish, shells, etc.
), but do not overemphasize low Purine diet; avoid drinking beer, sugary soda, and increase the intake of dairy products and vegetables.

➤Encourage drinking more water to ensure a urine output of more than 2000 ml/d, but elderly patients with heart disease should be alert to the possibility of inducing acute heart failure.

 2.
Prevention of tophus ulcer infections Gout patients with tophus ulcers rarely have infections, but elderly people have low nutrition and resistance and are prone to serious infections.

When tophi is ruptured and infected, it is important to keep the ruptured area clean and take care of it.

  3.
The treatment of gout in the remission period is mainly to control the level of blood uric acid, and "continuously reaching the standard" of uric acid is the key to the treatment of refractory gout.

"Continuously reaching the standard" contains two meanings of "continuing" and "reaching the standard": ➤Continuous: refers to the continuous reduction of uric acid.
The treatment course takes several years, decades or even life.
The longer the course of the disease, the more tophus in the body, and the duration of the reduction of uric acid may be The longer.

➤Meeting the standard: "reaching the blood uric acid control standard", usually for patients with tophi, blood uric acid should be strictly controlled below 300umol/L to ensure the slow dissolution of tophi; for patients without tophi, blood uric acid is also It should be controlled below 360umol/L to avoid repeated attacks of gouty arthritis.

For patients with refractory gout, the control of uric acid should be stricter, and it is recommended to keep it below 240umol/L.

In addition, because elderly patients with gout have more complications, it is necessary to pay close attention to the influence of drugs on the treatment of other diseases during the use of uric acid-lowering drugs.

The main measure for blood uric acid to continue to reach the standard is drug treatment.
The following drugs are commonly used in clinical practice: The conventional dose of allopurinol is 300 mg/d or even less in clinical practice.
However, most studies show that the long-term low-dose difference Purinol is not effective in lowering uric acid and cannot reduce the occurrence of fatal hypersensitivity syndrome.

The highest dose of allopurinol can reach (800～900) mg/d.

Studies have shown that high doses of allopurinol can increase the efficacy without significantly increasing the side effects.
Therefore, for elderly patients with refractory gout, you can consider increasing the dose of allopurinol appropriately, provided that the The guidelines require genetic testing to avoid severe skin rashes.
In addition, elderly people with kidney and liver damage should use medication with caution.

The conventional dose of benzbromarone is 50mg/d, the effective rate of lowering uric acid is 93.
7%, the tophi dissolves faster, the curative effect is stronger, and the curative effect on patients with renal insufficiency is the same as that of normal patients, suitable for elderly patients.

However, benzbromarone is forbidden when the blood creatinine level is greater than 356umol/L or the endogenous creatinine clearance rate is less than 20ml/min.

Febuxostat, as a new type of drug that inhibits the production of uric acid, can significantly reduce the blood uric acid level.
It is excreted through multiple channels and has high renal safety.
However, elderly patients with gout often have renal insufficiency.
Therefore, it is recommended to use febuxostat as refractory to the elderly.
The drug of choice for patients with gout, but febuxostat lacks evidence when the endogenous creatinine clearance rate is less than 30ml/min and should be used with caution.

As a new drug that promotes the decomposition of uric acid, Precash can effectively reduce blood uric acid and dissolve tophi.
It can be used for elderly patients with refractory gout who have failed traditional uric acid-lowering treatments.

Alkalizing urine medicine keeps the urine pH at 6.
2 to 6.
8, which is conducive to the dissolution and excretion of urate crystals.

There are two kinds of drugs commonly used clinically to alkalize urine, namely sodium bicarbonate and sodium potassium hydrogen citrate granules.

Sodium bicarbonate is a traditional medicine that alkalizes urine.
However, due to its high sodium content, long-term use can easily cause water and sodium retention and increased blood pressure.
It is not suitable for elderly patients with poor cardiac function or high blood pressure.
It is recommended Using potassium citrate to alkalize urine is safer.

Combination therapy is for patients with ineffective or poor efficacy of a single drug.
If there are no contraindications or intolerances, the combination therapy can be considered.
The drugs that inhibit uric acid production and the drugs that promote uric acid excretion are combined to make blood uric acid reach the standard as soon as possible, such as allopurinol.
The uric acid-lowering effect of adding benzbromarone was significantly better than that of allopurinol or benzbromarone alone; the effect of benzbromarone plus febuxostat was significantly greater than that of febuxostat alone. Appropriate selection of drugs that have both uric acid-lowering effects.
In addition, there are clinically some drugs that also have uric acid-lowering effects.
For example, losartan and fenofibrate can reduce blood pressure and triglycerides while promoting uric acid excretion; While torvastatin lowers blood cholesterol levels, it can also reduce blood uric acid by inhibiting uric acid synthesis; sulfonylureas can promote the excretion of uric acid, and thiazolidinediones may reduce blood uric acid levels by reducing insulin resistance.
SGLT-2 inhibitors such as dapagliflozin and canagliflozin can lower blood uric acid levels.

For elderly patients with high blood pressure, hyperlipidemia, or diabetes, these drugs can be considered to kill two birds with one stone.

Note: In the early stage of uric acid lowering treatment, acute attacks of gout must be prevented.
Small doses of colchicine or non-steroidal anti-inflammatory drugs (NSAIDs) can be taken orally.
When using, attention should be paid to adverse reactions such as gastrointestinal, cardiovascular, and kidney injury.
There are contraindications.
For patients who are ineffective or ineffective, low-dose prednisone or prednisolone is recommended.
For those with poor systemic treatment effects, consider intra-articular injection of short-acting glucocorticoids (limited to only involving 1-2 large joints) to avoid short-term Repeated use; HUA patients without a history of gout attacks are not recommended to use drugs to prevent gout attacks when receiving uric acid-lowering treatment, but they should be informed of the risk of inducing gout attacks.

4.
The choice of medication during the acute attack of gout is mainly effective analgesia.

Commonly used anti-inflammatory and analgesics include: colchicine, NSAIDs, glucocorticoids, IL-1B receptor inhibitors (such as Linazep) and so on.

Analgesic drugs can be used alone.
Depending on the severity of the pain, a combination of drugs can be used if necessary: ​​colchicine plus NSAIDs or colchicine plus oral hormones; or intra-articular injection of hormones plus oral hormones or colchicine .

➤Colchicine: the first dose is 1.
0mg, then 0.
5mg after 1 hour, 0.
5mg after 12 hours, 1-3 times/d, the course of treatment does not exceed 14 days; patients with chronic renal insufficiency should be based on the glomerular filtration rate Adjust the dose, eGFR 35-59ml/min, the maximum daily dose of 0.
5mg, eGFR 10-34ml/min, the maximum daily dose of 0.
5mg, once every other day, eGFR<10ml/min should be forbidden; hepatic insufficiency transaminase increased 2.
5 times Disabled when above. ➤NSAIDs: including diclofenac sodium, ibuprofen, celecoxib, etoricoxib, etc.
, used when colchicine is ineffective, and special attention should be paid to the gastrointestinal, cardiovascular, liver, and kidney problems when using gout in the elderly In response, it should be used with caution or forbidden for chronic diseases such as coronary heart disease and chronic renal insufficiency (eGFR<50ml/min); it is also forbidden when the transaminase of liver insufficiency rises more than 2.
5 times.

➤Glucocorticoid: Oral prednisone is suitable for patients with colchicine, NSAIDs treatment ineffective or limited use, or patients with cardiovascular and cerebrovascular diseases, renal insufficiency, 0.
5mg/kg/d, continuous 5-10 days, directly Discontinue the drug; or 0.
5mg/kg/d, use for 2-5 days, gradually reduce the dose, stop the drug for 7-10 days; advocate local treatment when combined with liver insufficiency.

➤IL-1 receptor antagonist: Linazep is suitable for refractory acute gout that is ineffective in NSAIDs, colchicine or glucocorticoid treatment, or when the patient is contraindicated with the above drugs.

5.
Pay attention to the treatment of elderly refractory gout comorbidities.
Elderly refractory gout patients often have three highs (hyperglycemia, hypertension and hyperlipidemia) or liver and kidney dysfunction, cardiovascular and cerebrovascular diseases, etc.
, so emphasize the difficulty Treatment of comorbidities in patients with curative gout, and the improvement of comorbidities can help control hyperuricemia and relieve gout symptoms.

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Clinical diagnosis and treatment strategies for refractory gout in the elderly.
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Clinical treatment of 30 cases of refractory gout[J].
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Continuous treatment of blood uric acid in refractory Significance in gout[J].
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