Health Tips

Gout is a condition characterised by high uric acid level in the blood and inflammatory arthritis that causes extreme joint pain. The high level of uric acid in blood leads to the deposition of urate crystals in joints such as the joint in the first toe, ankle and knee. 

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If you have gout, you may be taking a medication called allopurinol. Allopurinol lowers the high level of uric acid by inhibiting an enzyme in your body called xanthine oxidase. This enzyme is responsible for the conversion of hypoxanthine to xanthine to uric acid. Food that contains high purine is typically restricted in gout patients because purine is the primary source of uric acid in the body. Read more in our previous infographics to find out foods that contain high purine.

Image credit: Memorang

However, purine is also essential for many body functions. Taking allopurinol would not disrupt the vital functions of purine, yet at the same time lowers the uric acid level arises from purine. Due to this unique action of allopurinol, it is widely preferred in the management of gout.

Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

Allopurinol is an effective medication for gout. However, for a small group of allopurinol user, they may develop hypersensitivity (or ‘allergies’ as a layman would call it) towards allopurinol, results in Steven-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN). 

Image credit: Doctoroncall

SJS and TEN are rare and life-threatening reaction towards a medication, usually characterised by painful blisters on the skin. If left untreated, a patient who experienced SJS or TEN can have their upper layer skin sloughed off. 

Image credit: BMJ

Image credit: BMJ

The difference between SJS and TEN is the severity of the disease. In SJS, skin involvement is less than 10% of the body surface, and the death rate among SJS patient is relatively low (1-5%). In contrast, the patient can experience severe skin reactions for more than 30% of the total body surface, and the death rate in TEN is as high as 30%. 

The EuroSCAR study, a European case-control surveillance of severe cutaneous adverse reactions (SCAR), found out that allopurinol was the high-risk medication most frequently associated with SJS or TEN. SJS and TEN caused by allopurinol were noted in 17.4% of 379 patients and 1.9% of 1,505 control subjects. 

Similar findings were noted in many countries. In Malaysia, a study found that 20.8% of 24 cases of both SJS and TEN were due to allopurinol. 

Why?

1. Dose of allopurinol

The EuroSCAR study also found that a daily dose of 200 mg or more of allopurinol was associated with an increased risk for SJS or TEN compared with lower daily doses. 

2. Kidney diseases

It is common to find kidney diseases among gout patients. The declining function of the kidney can lead to reduced excretion of allopurinol as compared to a healthy person, thus leading to accumulation of allopurinol in the body.

3. Genetics

Some people are naturally more prone to develop SJS and TEN when taking allopurinol. In 2005, an association between an allele called HLA-B*5801 and increased risk of allopurinol-related skin reactions in Han Chinese was identified. In other words, having this gene in your body increases your risk of developing skin reactions when taking allopurinol.

4. Taking other medications

The use of diuretics in patients with gout is common because many have other diseases, such as hypertension and heart failure. Taking diuretics alongside with allopurinol can increase the risk of developing SJS/TEN. Besides, taking diuretics may counterintuitively increase the uric acid in the blood. As a result, the gout patient who takes diuretics may need to increase their dose of allopurinol, thereby increasing the risk of developing SJS/TEN.

Image credit: BMJ 

How to prevent?

1. Consult a well-trained doctor or pharmacist when taking allopurinol. They know what to do to reduce the risk of developing SJS/TEN.

2. Reveal your complete medical history and the medications you are taking to the doctor and pharmacist.

3. Follow your doctor and pharmacist’s instructions when taking allopurinol. Do not change the dose without consulting them.

4. Seek medical attention immediately if you notice any skin reactions when taking allopurinol.

References:

1. https://www.rcpe.ac.uk/sites/default/files/foong.pdf

2. https://academic.oup.com/rheumatology/article/57/suppl_1/i35/4762105

3. BMJ Best Practice

4. UpToDate Database

Written by

Ms Joyce Toh