QuestionSBA
QuestionChoice
This may be considered if the patient has very poor renal function and is not able to take either non-steroidal anti-inflammatory drugs or colchicine. Blood glucose monitoring should be done whilst on prednisolone, especially since the patient is diabetic, as it usually causes elevated glucose levels in the evening or nighttime
32210
c
Prednisolone
QuestionChoice
This patient likely has an acute attack of crystal arthropathy. Septic arthritis should be ruled out, especially in a diabetic patient who may be immunocompromised. Joint aspiration should be considered for diagnosis. Colchicine would be suitable in a patient with chronic kidney disease, and renal adjustment considered if eGFR 10-50, below which it would be contraindicated
32208
a
Colchicine
QuestionChoice
This would not be appropriate in a patient with chronic kidney disease as it may worsen renal function. Creatinine clearance should be calculated first. Proton pump inhibitor therapy should also be considered if initiating treatment with non-steroidal anti-inflammatory drugs
32209
b
Naproxen
QuestionChoice
This would not be appropriate in a patient with chronic kidney disease as it may worsen renal function. Creatinine clearance should be calculated first. Proton pump inhibitor therapy should also be considered if initiating treatment with non-steroidal anti-inflammatory drugs
32211
d
Allopurinol
QuestionChoice
This would be a second-line agent for urate lowering therapy if allopurinol is contraindicated, not tolerated or unable to achieve target serum uric acid
32212
e
Febuxostat
QuestionComment
As this patient has a high temperature, wouldn't you be concerned about septic arthritis?
7970
User
subscriber
Myotonia NICU
QuestionComment
Surely this question should be about next step in management i.e. performing joint aspiration to rule out septic arthritis rather than going straight to gout treatment?
22241
User
subscriber
Anterior Myotonia
QuestionComment
Why is the WCC raised

28618
QuestionComment
crystals are DAMPS -> activates innate immune response
59730
User
subscriber
Rohan
User
subscriber
Epidermis Haemophilus
Concept
Chapter
# Summary

Gout is a type of arthritis caused by the accumulation of monosodium urate crystals in and around the joints. It presents acutely with rapid onset of severe pain, swelling and redness of affected joints, with the first metatarsophalangeal joints the most commonly affected. Chronic untreated gout may lead to tophi which are hard nodules made up of monosodium urate crystals that deposit in soft tissues. Gout may be diagnosed clinically, with supportive investigations including a serum urate and synovial fluid analysis looking for monosodium urate crystals. Management of acute gout is with NSAIDs, colchicine or a short course of oral steroids. Urate-lowering therapy with allopurinol or febuxostat should be considered to reduce the risk of further gout flares. 

# Definition

Gout is a form of arthritis that occurs when monosodium urate crystals deposit in joints. This causes both acute inflammation (gout flares) and in the longer-term, a chronic gouty arthritis with tophi (hard deposits of monosodium urate crystals in soft tissues).

# Epidemiology

- Gout is the most common inflammatory arthritis and prevalence is increasing with time (currently 2.5%)
- Hyperuricaemia (high urate) is the main risk factor (although most patients with a high urate do not develop gout, and some patients develop gout with a normal urate)
- Factors that contribute to this include:
- Older age - typically patients are above the age of 40
- Male sex (post-menopausal women are also at increased risk)
- Comorbidities including chronic kidney disease (CKD), diabetes, osteoarthritis, hypertension
- Excess alcohol consumption
- Dietary excess of meat, seafood and sugary drinks
- Overweight or obesity
- Medications such as thiazide diuretics and ciclosporin
- Family history of hyperuricaemia and gout
- Genetic disorders associated with hyperuricaemia such as Lesch-Nyhan or glycogen storage disorders
- Organ transplant recipients
- Acute attacks may be triggered by stressors including:
- Trauma and surgery
- Intercurrent illness
- Alcohol excess
- Sudden excess of protein in the diet
- Chemotherapy (due to cell breakdown)
- Urate-lowering medications can cause a flare (as crystals are shed into the joint space)

# Signs and Symptoms

Overlapping clinical syndromes are caused by the deposition of monosodium urate crystals in different tissues:

**Acute gout** 

- Commonly presents with a monoarthritis
- Pain is severe and rapid in onset, reaching a peak within 24 hours 
- Affected joints become swollen, erythematous and tender
- The first metatarsophalangeal (MTP) joint is the most commonly affected (70% of first attacks)
- Other common sites include the knees, ankles, midtarsal joints, wrists, elbows and small joints of the hands
- Systemic features such as fever and malaise may be seen
- Patients may be tachycardic due to pain

**Tophaceous gout**

- Patients will usually have a history of longstanding recurrent acute gout
- However in atypical cases patients may present with tophi without previous flares
- Tophi are firm white nodules of sodium monosulphate crystals under the skin
- They commonly occur on extensor surfaces of joints such as knees or elbows, the Achilles tendons, backs of hands and feet and on the helices of the ears
- Usually they are painless however they can become infected, inflamed or ulcerated
- They may discharge white material onto the skin surface
- Chronic gouty arthritis may present with tender and stiff joints with reduced range of motion

# Differential Diagnosis

- **Septic arthritis** must be ruled out in patients who are systemically unwell with an acute monoarthritis - urgent synovial fluid analysis is needed if this is suspected
- **Pseudogout** typically affects the knee and wrists rather than the MTP joint; synovial fluid analysis shows calcium pyrophosphate crystals
- **Cellulitis** causes erythema, pain and swelling of the skin rather than the joint - patients may be systemically unwell
- **Trauma** should be asked about in the history as this may cause similar symptoms of pain, difficulty mobilising and swelling
- **Other inflammatory arthritides** such as rheumatoid arthritis may mimic chronic gouty arthritis

# Investigations

**Bedside tests:**

- **Joint aspiration** is the gold standard diagnostic investigation 
- Needle-shaped monosodium urate crystals with negative birefringence are seen in gout
- Synovial fluid should also be sent for gram stain and culture to rule out septic arthritis
- Tophi can be biopsied to look for these crystals

**Blood tests:**

- **Serum uric acid** should be measured in all patients with suspected gout
- A serum urate of 360 micromol/L or more confirms the diagnosis
- Levels may be falsely low in an acute attack and so should be repeated 2-4 weeks after the flare has resolved
- Levels are used to guide urate-lowering therapy if this is initiated as prophylaxis
- **Screening for risk factors** should be considered:
- Fasting glucose or HbA1c for diabetes
- Renal function and urine albumin:creatinine ratio for CKD
- Lipids for hypercholesterolaemia
- **Inflammatory markers** with FBC and CRP should be checked if septic arthritis is suspected
- **Liver function tests** are needed prior to starting febuxostat
- Patients from Han Chinese, Thai and Korean backgrounds should be screened for **HLA-B5801** prior to starting allopurinol (as this increases the risk of severe cutaneous adverse reactions if present)

**Imaging tests:**

- These may be useful to assess chronic disease or where the diagnosis of acute gout is uncertain
- X-rays in chronic disease show punched-out periarticular erosions, areas of sclerosis and tophi
- Ultrasound may show joint effusions, tophi, synovial thickening and erosions

# Management 

**Acute gout flares** 

There are three first-line options for treatment of a gout flare:

- NSAIDs e.g. naproxen
- Give at maximum dose
- Continue until 1-2 days after resolution of symptoms
- Consider giving with a PPI for gastric protection
- Avoid in heart failure, patients at high risk of gastrointestinal bleeding and severe renal failure
- Colchicine
- Dosing is 500 mcg 2-4 times per day
- Continue until pain resolves
- Dose-dependent side effects include diarrhoea, nausea and vomiting
- Oral corticosteroids
- e.g. prednisolone 30mg once a day for 3-5 days
- Useful in patients with contraindications to both NSAIDs and colchicine
- An injection of intramuscular, intravenous or intra-articular steroids can also be considered
- Alongside this, consider other analgesia (e.g. paracetamol) and other non-pharmacological pain relief such as ice packs
- A combination of the above may be tried if a single agent is ineffective
- Patients should be advised to keep the affected joint cool and exposed and to rest and elevate the affected limb
- Patients already on urate lowering treatment should continue this throughout the acute flare

## Prevention

Patients should be followed up 4-6 weeks after an acute episode of gout to think about preventative strategies and assess for risk factors (also see Investigations). 

Optimisation of risk factors may include:

- Reducing alcohol consumption
- Maintaining a balanced diet and healthy weight
- Investigate and treat for comorbidities such as hypertension or CKD
- Review medications and consider switching medications such as thiazides that cause hyperuricaemia
- Where possible, switch antihypertensive medications to losartan or amlodipine, which have modest urate-lowering effects 
- Initiating urate-lowering therapy (see below)

Most patients can be managed in primary care, however the following should prompt referral to or discussion with specialist services:

- Patients with complications of gout
- Atypical presentations (e.g. aged under 30) or uncertain diagnosis
- Pregnant patients
- Stage 3b to 5 CKD
- Organ transplant recipients
- Those at risk of adverse effects with standard medical treatment, or if treatment is ineffective or not tolerated

Indications for **urate-lowering therapy** include:

- Multiple or troublesome gout flares
- Chronic gouty arthritis or tophi
- Patients taking diuretics
- CKD stage 3 to 5

**Starting and monitoring urate-lowering therapy (ULT):**

- ULT should be started at least 2-4 weeks after an acute flare if possible as medications can precipitate further attacks
- Colchicine should be given whilst starting ULT to reduce the risk of a flare (NSAIDs or steroids are second-line)
- Doses should be uptitrated with monthly monitoring of serum urate levels, aiming for a target of 360 micromol/L
- A target urate level of 300 micromol/L may be helpful in patients with tophi or chronic arthritis due to gout, or those who continue to have flares despite ULT
- First-line options are either allopurinol or febuxostat which are both xanthine oxidase inhibitors (so reduce uric acid production)
- Allopurinol is preferred in patients with significant cardiovascular disease
- Second line options include uricosuric medications (e.g. probenecid) - these can promote stone formation so should be avoided if there is nephrolithiasis

# Complications

- Chronic gouty arthritis and permanent joint damage
- Tophi, which may become inflamed or infected
- Nephrolithiasis due to uric acid precipitation - these are responsible for 8% of renal calculi and are radiolucent
- Chronic urate nephropathy - urate deposition in the renal interstitium causes inflammation and fibrosis
- Both allopurinol and febuxostat can cause rashes, which in rare cases may be severe (e.g. Stevens Johnson syndrome or toxic epidermal necrolysis)
- Increased risk of cardiovascular disease and mortality

# NICE Guidelines

[NICE CKS - Gout](https://cks.nice.org.uk/topics/gout/)

[NICE - Gout: diagnosis and management](https://www.nice.org.uk/guidance/ng219/)

# References

[Patient UK - Gout](https://patient.info/doctor/gout-pro)

[Radiopaedia - Gout](https://radiopaedia.org/articles/gout?lang=gb)
151
420
Gout
Topic
54
Rheumatology
Video
Concept
420
Gout
335
dh9LRhf
images/videos/rheumatology.png
Quesmed Tutorial: Rheumatology
Video
Concept
420
Gout
614
ZMAGtgf
images/videos/cardiology.png
Quesmed Tutorial: General Practice
Video
Concept
420
Gout
153
S3HYFUo
images/videos/rheumatology.png
Gout 
Colchicine
6442
Colchicine can be used for gout in chronic kidney disease, but doses must be reduced for an eGFR of 10-50 to avoid toxicity, with close monitoring
A 70-year-old man is admitted with sudden onset right ankle pain and swelling for 1 day, the third episode this year. His medical history includes type 2 diabetes and chronic kidney disease, likely from diabetic nephropathy.


On examination, his right ankle is erythematous, warm, and tender, with full range of movement.




Observations: Temperature 38.1°C, pulse 90, BP 110/70, respiratory rate 18, SpO<sub>2</sub> 100% on room air



Initial blood tests are as follows:

||||
|--------------|:-------:|---------------|
|Haemoglobin|142 g/L|(M) 130 - 170, (F) 115 - 155|
|White Cell Count|16.1x10<sup>9</sup>/L|3.0 - 10.0|
|Neutrophils|5.5x10<sup>9</sup>/L|2.0 - 7.5|
|Platelets|210x10<sup>9</sup>/L|150 - 400|
|Sodium|137 mmol/L|135 - 145|
|Potassium|4 mmol/L|3.5 - 5.3|
|Chloride|102 mmol/L|95 - 106|
|Urea|8 mmol/L|2.5 - 7.8|
|Creatinine|151 µmol/L|60 - 120|
|eGFR|60 mL/min/1.73m<sup>2</sup>|> 60|





X-ray of the right ankle showed no acute fractures or bony erosions.



Which of the following is the next most appropriate treatment?
a