Is allopurinol an advantage in treating gout?

*It is only for medical professionals to read for reference.
This side effect must be careful! Allopurinol (Allopurinol) has been the first-line uric acid-lowering treatment for patients with gout and hyperuricemia worldwide since the 1960s
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But looking up the relevant literature [1-11], one has to think of a word: daunting! One of the cases is even more impressive.
Let’s take a look at what happened.
Brief medical history The patient, female, 79 years old
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She was admitted to the hospital on December 4 of the same year due to a rash all over the body for 4 months, which worsened by half a month
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After taking allopurinol 4 months ago, there was a rash with fever all over the body (the rash after 29 days of taking the drug) was admitted to the hospital for the first time, and was discharged after treatment with methylprednisolone, calcium supplementation, and anti-allergic treatment (during the first hospitalization) The rash repeated 4 times due to the rapid reduction of hormones)
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After being discharged from the hospital, no more standardized hormone therapy was performed.
Because the rash recurred and worsened half a month ago, he went to see the doctor again
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Past history: The patient has a history of gout, hypertension, coronary heart disease, and atrial fibrillation
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▌ The whole body was swollen, face, neck, trunk, limbs diffuse erythema, maculopapular rash, patches with chaff-like desquamation, and glove-like desquamation of the skin on both hands
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Blood WBC6.
9X109/L, neutral 0.
79, eosinophilic 0.
001, Hb74g/L, PLT173X109/L, normal blood and liver function, electrolytes, and immunoglobulins, blood glucose 6.
17mmol/L, BUN18.
20mmol/L, Cr196μmol/L, UA644mmol/L
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▌ After treatment, he was admitted to the hospital by intravenous infusion of methylprednisolone 30mg/d, with a weekly dose reduction of 1/6~1/10, gradually transitioning to oral methylprednisolone 16mg/d, and then a reduction of 2mg every two weeks
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During the regular medication period, the patient had perineal and oral mucosal erosions and ulcers; repeated pain in the right upper abdomen
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Abdominal ultrasound showed acute cholecystitis and fluid in the abdominal cavity; the patient had repeated lung infections, fast-ventricular atrial fibrillation, and elevated fasting blood glucose
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Therefore, he was given treatments such as blood sugar control, cardiotonic, diuretic, and anti-infection, and he had undergone hemodialysis once
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After treatment, although the patient’s rash gradually improved (except for the 3 exacerbations of local skin rashes, the hormones were reduced according to the original plan), but on February 13 of the following year, the cough worsened, and he developed acute respiratory acidosis, rapid ventricular fibrillation, and blood pressure.
Decline, blood BUN and Cr increase, coma, and died on February 19, with a total course of 196 days
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The original sin or allopurinol The initial onset of this patient was a severe drug eruption caused by gout taking allopurinol
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From morbidity to death, intermediate drug eruption has experienced improvement-relapse-recovery-relapse, repeated many times.
Among them, there is a factor of too fast hormone reduction, but even if the hormone is gradually reduced as required, it can only reduce the recurrence rate of drug eruption.
, And can not completely avoid recurrence 100%, this case belongs to this case
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In this case, the drug eruption treatment improved, but still resulted in death.
It seems that the death has nothing to do with the drug eruption
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The final direct cause of death was related to secondary infection, impaired renal function, and the patient's primary coronary heart disease and atrial fibrillation
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However, it must be noted that the primary cause is severe drug eruption caused by allopurinol.
It is to treat this drug eruption that hormone therapy has to be used repeatedly
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Repeated use of a large amount of hormone therapy before and after will inevitably lead to a decline in the body's immunity, and eventually secondary infections
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In addition, the patient himself was older (79 years old), and had a history of basic hypertension, coronary heart disease, and atrial fibrillation, which eventually led to death
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In recent years, studies have found that genetic testing can effectively avoid the occurrence of adverse reactions of allopurinol and the determination of drugs that cause adverse drug reactions (detailed below)
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However, it is a pity that this patient did not have a genetic test from the beginning to the end! Since the allopurinol drug eruption is so serious, let's take a good look at how to diagnose and treat it! How to use allopurinol well? These 5 points must be vigilant! 1.
Allopurinol drug eruption has the following characteristics: ①Most of the patients are middle-aged and elderly; ②The incubation period of first contact is long, and the incubation period of re-contact is short; 7 times; ④It is more common with fever and liver and kidney damage
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Liver damage accounts for 63.
2%-69.
2%, and kidney damage accounts for 52.
6%-65.
4%
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Foreign literature reported that liver and kidney damage accounted for 40%-69% and 45%-54% respectively; ⑤Measles-like rashes are the most common type, and the same patient can have a change of rash types or two types of rashes at the same time; ⑥Severe illness and mortality It is as high as 19.
2%-23.
1%, and 15% has been reported abroad; ⑦The severity of renal damage is related to the severity of drug eruption and prognosis
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2.
Allopurinol drug eruption hormone therapy is effective.
Hormone therapy is effective, but it is not advisable to reduce the dose quickly
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It should be emphasized that the hormone reduction must be slow, especially for elderly patients, start to reduce the dose by 1/6~1/10 every week to the equivalent of 20mg prednisone, and then slow down
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3.
The daunting allopurinol first look at the report of adverse reactions of allopurinol found in the author's rough investigation of the literature: ①Wu Hongxuan and others reported 1 case in the "Clinical Analysis of 21 Cases of Allopurinol-induced Drug Hypersensitivity Syndrome" Death cases
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② Gan Jiecheng and others reported 4 deaths in "47 Cases of Allopurinol Drug Eruption Clinical and Prognostic Analysis"
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③ Huang Yubin and others reported 42 deaths in "Analysis of 381 Cases of Adverse Reactions to Allopurinol"
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④Chen Xiaohong et al.
reported 38 deaths in "Analysis and Discussion of Adverse Reactions of Allopurinol"
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⑤ Wang Xiaoliu and others reported 2 deaths in "Clinical Analysis of 13 Cases of Severe Drug Eruption Caused by Allopurinol"
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⑥ Fan Jiaojiao and others reported a death case in "Clinical Analysis of 50 Cases of Severe Drug Eruption in Elderly Hospitalized Patients"
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⑦Tang Li et al.
reported "A death from exfoliative dermatitis caused by allopurinol tablets"
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⑧ Liu Yanxiang and others reported "Analysis of 1 Case of Exfoliative Dermatitis Caused by Allopurinol"
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⑨ Xiang Danli et al.
reported "Analysis of a death case of severe drug eruption combined with malignant histiocytosis caused by allopurinol
.
"
⑩ Yao Jiachen and others reported "A death case of bullous epidermal atrophic drug eruption caused by allopurinol
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"
⑪Wei Chunyan and others reported "A death case of toxic epidermal necrolysis caused by allopurinol"
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There are many more, so I won't list them one by one
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What do you think after reading these reports? Will it be "daunted"? How to prevent the adverse reactions of allopurinol? 4.
Prevention of adverse reactions of allopurinol (1) Patients who are not suitable to use allopurinol must not use the drug ①This drug should not be used in patients with acute attacks of gouty arthritis, so as not to aggravate the symptoms of arthritis
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② Allopurinol is not recommended for the treatment of asymptomatic hyperuricemia
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Because the incidence of severe skin adverse reactions (SCAR) is significantly increased when allopurinol is used to treat asymptomatic hyperuricemia, and the prognosis is worse, especially in patients with chronic kidney disease (CKD) or cardiovascular disease
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③ Use with caution in patients with liver and kidney dysfunction
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Because the drug has a long half-life (14-28h), the original drug and its metabolite oxypurinol are excreted by the kidneys, and have certain hepatotoxicity.
Therefore, it should be used with caution in patients with liver and kidney insufficiency and the elderly.
Reduce the dose
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During medication, liver and kidney function and blood picture should be checked regularly
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Emphasize: Avoid use in CKD patients
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CKD is one of the common complications of gout patients
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US Health and Nutrition Survey data show that 71% of gout patients have CKD
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In a large study of 901 SCAR cases, 48% of SCAR patients had CKD
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Because renal function is difficult to improve in most cases, for CKD patients, an effective way to avoid SCAR is to avoid using allopurinol as much as possible
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④ Those who are HLA-B*5801 allele positive are not used
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Studies have shown that HLA-B*5801 alleles are associated with adverse reactions of allopurinol
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Therefore, it is recommended to perform HLA-B*5801 allele testing before medication
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Although genetic factors cannot be changed, genetic testing can be used to screen people who need to take allopurinol for treatment, which can help reduce the occurrence of such adverse reactions
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Those with positive results should avoid allopurinol
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(2) Low-dose medication The drug must start with a small dose, gradually increase to an effective dose to maintain normal uric acid levels, and then gradually reduce the dose to the minimum effective dose to maintain treatment
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(3) Strengthen the publicity and education of relevant knowledge of pharmacy for doctors and patients.
Clinical pharmacy personnel shall provide necessary guidance and publicity and education of relevant pharmacy knowledge for patients and doctors
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If SCAR occurs, the first solution is to stop allopurinol; if skin rash or itching occurs during medication, seek medical treatment in time, especially if these reactions occur within a few weeks to several months after starting allopurinol treatment Internally or after increasing the dose of allopurinol
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(4) Pay attention to drug interactions ① Aspirin and other salicylic acid drugs can increase the concentration of uric acid and reduce the efficacy of the drug, and should be avoided in combination
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②Combined use with thiazide diuretics can cause renal failure and cause allergic reactions
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③Combination with ampicillin can increase the incidence of rash
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④ Combination with cyclophosphamide can significantly increase the suppression of bone marrow
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⑤Combination with drugs that acidify urine can increase the possibility of kidney stones
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⑥ When combined with dicoumarin anticoagulants, the efficacy of anticoagulants can be enhanced, and attention should be paid to adjusting the dosage of anticoagulants
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⑦The drug is a xanthine oxidase inhibitor, which can inhibit the metabolism of theophylline, reduce theophylline clearance rate, prolong the half-life, and increase the blood concentration to cause theophylline poisoning
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Therefore, if the drug is used in combination with theophylline, the blood concentration of theophylline should be tested and the dosage of theophylline should be adjusted in time
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5.
Treatment of adverse reactions of allopurinol Once adverse reactions occur, allopurinol should be discontinued as soon as possible
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Glucocorticoids can slow down the progression of allopurinol skin adverse reactions.
Oral glucocorticoids should be used as the main treatment, and should be used in sufficient quantities as soon as possible.
The reduction should be slow to avoid recurrence of the disease.
In severe cases, intravenous dexamethasone and hydrocortisone can be given.
Glucocorticoids such as sodium pine succinate
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Wounds such as skin and mucous membranes should be carefully taken care of to prevent concurrent infections, and antibacterial drugs should be selected for those who have been co-infected
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And strengthen the observation of vital signs, regular blood routine and liver and kidney function examinations, in order to detect and prevent serious complications as soon as possible
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For severely ill patients, attention should also be paid to electrolyte balance
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If necessary, treatments such as immunoglobulin, cyclosporine, anti-tumor necrosis factor or acetylcysteine, and even plasma exchange can also be given
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However, due to the lack of large-scale controlled studies, these treatments are still controversial
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References: [1] Wu Hongxuan.
Clinical analysis of 21 cases of drug hypersensitivity syndrome caused by allopurinol[J].
Practical Clinical Medicine, 2008, 9 (12): 65-66.
[2] Gan Jicheng, Zhuang Xuan, Yao Zhirong, et al.
Clinical and prognostic analysis of 47 cases of allopurinol drug eruption[J].
Dermatology and Venereal Diseases, 2007,29(3):6-7.
[3]Huang Yubin.
Analysis of 381 cases of allopurinol adverse reactions[J] ].
Chinese Drug Application and Monitoring, 2005, 2 (1): 32-34.
[4] Chen Xiaohong, Zhao Zhigang, Wei Lirong.
Literature analysis and discussion of adverse reactions of allopurinol[J].
Practical Medicines and Clinics, 2010, 13 (2): 149-151.
[5] Wang Xiaoliu, Li Rui, Dong Dan, et al.
Clinical analysis of 13 cases of severe drug eruption caused by allopurinol[J].
China Modern Medicine Application, 2010, 4(15): 158- 159.
[6] Fan Jiaojiao, Cao Yan, Zhang Anping.
Clinical analysis of 50 cases of severe drug eruption in elderly hospitalized patients[J]).
Journal of Diagnosis and Treatment of Dermatovenereology, 2021, 28(3): 202-205.
[7] Tang Li, Zhu Hao.
A death case from exfoliative dermatitis caused by allopurinol tablets[J].
Chinese Journal of Hospital Pharmacy, 2013, 33(1): 82-84.
[8] Liu Yanxiang, Ma E, Liang Wu.
Allopurinol Analysis of 1 case of death caused by exfoliative dermatitis[J].
Chinese Pharmacovigilance, 2006, 3(1): 47-48.
[9] Xiang Danli, Zhang Lin.
Allopurinol-induced severe drug eruption with malignant histiocytosis 1 Case death analysis[J].
West China Medicine, 2000, 15(1): 108-108.
[10] Yao Jiachen, Xue Peihua.
A death case of bullous epidermal atrophic drug eruption caused by allopurinol[J].
Pharmaceutical Care and Research, 2005, 5 (1): 53,76.
[11] Wei Chunyan, Xu Wei.
1 case of death from toxic epidermal necrolysis caused by allopurinol[J].
Journal of Pharmaceutical Epidemiology, 2015, 24 (3) : 189-190.