701
Allopurinol
1,2 1 2,3,4 3 5
2 3 4
1 5
Allopurinol allopuri-
nol allopurinol
Allopurinol ( allopurinol hypersensitivity syndrome,
AHS ) allopurinol AHS 2
AHS 0.4 25-30 54
( 11.1
mg/dL ) allopurinol 24
allopurinol - ( Stevens-Johnson syndrome )
2 Allopurinol
AHS
AHS
Allopurinol
( Hypersensitivity ) ( Corticosteroid )
( Stevens-Johnson Syndrome )
Allopurinol
allopurinol
allopu-
rinol Allopurinol
( Allopurinol hypersensitivity syndrome,
AHS ) allopurinol
AHS 2%
A H S 0 . 4 %
25-30%
( toxic epidermal necrolysis, TEN )
- ( Stevens-Johnson syndrome, SJS )
1
A H S S J S
A H S
A H S allopuri- n o l
SJS
5 4
92 11
( daily protein loses, DPL ) 23.9
( creatinine clearance, CCr ) 97.8 ml/min
( Gr. I cortical echogenicity ) ( diabetic nephropathy, DN ) ( nephrotic syndrome, NS ) 93-94
( s e r u m
creatinine, SCr ) 93 9
( SCr >
1.5 mg/dL ) 94 6
1 6
3.1 mg/dl
( chronic renal insufficiency with acute deterioration )
11.1 mg/dL 6 16 allopurinol 100mg
6 28
9 4 7 1 7
( 38.9 ) ( 201/82 mmHg )
( A )
( B )
( )
( ) ( C )
( 19,100/mm
3) ( Seg: 78% )
( 8% ) ( eosinophil )
A
7%
12%
( Hb 10.5 g/dL ) ( Hct 30.9% )
( BUN/SCr 70/3.2 mg/dL, GOT/GPT 60/89 u/L )
( Nitrite )
- ( SJS )
allopurinol ( 6/16 ) metoclo-
pramide ( 6/24 )
cyproheptadine Unasyn® 3 g
1 2
triamcinolone tetracycline
silver sulfadia-
zine cefazolin 1g 12
4 0 ( 7 20 ) ( BUN/SCr 70/3.2 105/4.2 mg/dL )
m e t h y l -
prednisolone 50 mg ce-
fazoline Unasyn® 3g 12
1 1%
270-400 mg/dL glimepiride
40 mg
Unasyn®
50mg levofloxacin
8 / 1 5 0 m g p r e d -
nisolone
1 2
( 11 mg/dL ) A H S
( )
AHS allopurinol
2%
0.4% AHS
( TEN ) ( sepsis ) ( GOT ) 500 U/L
25-30%
1A H S
AHS allopurinol
BC 10X
( ) ( )
( 300mg )
1 A H S
A H S A H S
( thiazide
diuretics ) allopurinol
1
5 4
A H S
AHS allopurinol
allopurinol (
)
2oxypurinol
( )
AHS ( )
1986 Singer AHS
( ) allpurinol
A H S
3
1993 Arellano 101
A H S
AHS 1
I.
100~400 mg ( 46% 300 mg/day )
( 1 728 days )
57 ( 25-89 )
= 2 1
( 55% ) ( 48% ) ( 22% )
( 16% )
( 60% ) thiazides 38%
II.
( 38.9 ) 95 %
93 %
(Maculopapular) 53 %
(Toxic epidermal necrolysis, TEN) 25 %
(Exfoliative dermatitis) 21 %
(Erythema multiforme, EM) 9 %
(Elevated serum creatinine > 3.5 mg/dl) 83 %
(Eosinophilia, eosin > 500/mm3) 60 %
(Leukocytosis, WBC > 15000/mm3) 40 %
(Hepatomegaly, GOT > 40U/L) 16 %
A H S
1
allopurinol
AHS Singer
Arellano AHS
94 6 16 allo-
purinol 100 mg 7 17
metoclopramide ( 94/06/27- 94/07/17 ) furosemide ( 93/07-94/07/21 ) inda- pamide SR ( 93/08-94/07/21 ) acarbose ( 92/12- 94/07/21 ) glimepiride ( 92/12- ) diltiazem SR ( 94/05- ) nifedipine OROS ( 94/02- )
f u r o s e m i d e i n d a p a m i d e diltiazem nifedipine
-
allopurinol AHS
- allopurinol
3 8 . 9 A H S Naranjo score
4allopurinol
( 7 )
( ) AHS
allopurinol AHS
allopurinol oxy-
Allopurinol 2
CCr (ml/min) Allopurinol (mg)
140 400 daily
120 350 daily
100 300 daily
80 250 daily
60 200 daily
40 150 daily
20 100 daily
10 100 every 2 days
0 100 every 3 days
Allopurinol AHS
Singer JR.19863 Arellano F. 19931
allopurinol
A B
A.
( -
)
B.
purinol
( )
1
AHS
A H S allopurinol
A H S
AHS
A H S
2
- Tripathi
-
67 (
)
( methyl-
prednisolone 160-240 mg )
5
1-14
4.6 -
6
allopurinol
A H S
Khoo 1995-1998
13 AHS 12
1 allopurinol 21
( 4-45 )
-
62% 10 10
9/L 54%
7 9
prednisolone ( 30-60 mg/ ) hydrocor-
tisone ( 400 mg/ ) 3-14
7
A H S
A H S
Arellano 101 AHS
Naranjo score 4
1. +1 0 0
2. +2 -1 0
3. +1 0 0
4. +2 -1 0
5. -1 +2 0
6. -1 +1 0
7. +1 0 0
8. +1 0 0
9. +1 0 0
10. +1 0 0
( 9 ) (1-4 )
(5-8 ) ( 0 )
( 30.3% 9.1% )
1
3 8
allopurinol 4 6 AHS
98% 89%
86% 60%
4 5 %
29% 38 AHS
9 ( 24% )
( 7 )
8
A H S -
cyproheptadine triamcinolone
tetracycline silver sulfadiazine
methylprednisolone 50 mg
Khoo AHS
A H S
( ) AHS
allop- urinol AHS
allopurinol
5 1 H L A - B * 5 8 0 1
allopurinol
15% ( odds ra-
tio ) 580.3 HLA-B*5801
allopurinol
9
( ) allopurinol
Allopurinol
A H S
A H S
A H S
1.Arellano F, Sacristan JA. Allopurinol hypersensitivity syn- drome: a review. Ann Pharmacother 1993; 27: 337-43.
2.Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity.
Description and guidelines for prevention in patients with renal insufficiency. Am J Med 1984; 76: 47-56.
3.Singer JZ, Wallace SL. The allopurinol hypersensitivity syn- drome. Unnecessary morbidity and mortality. Arthritis Rheum 1986; 29: 82-7.
4.Naranjo CA, Busto U, Sellers EM, et al. A method for estimat- ing the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-45.
5.Tripathi A, Ditto AM, Grammer LC, et al. Corticosteroid the- rapy in an additional 13 cases of Stevens-Johnson syndrome: a total series of 67 cases. Allergy Asthma Proc 2000; 21: 101-5.
6.Kakourou T, Klontza D, Soteropoulou F, Kattamis C.
Corticosteroid treatment of erythema multiforme major (Stevens-Johnson syndrome) in children. Eur J Pediatr 1997;
156: 90-3.
7.Khoo BP, Leow YH. A review of inpatients with adverse drug reactions to allopurinol. Singapore Med J 2000; 41: 156-60.
8.Lee SS, Lin HY, Wang SR, Tsai YY. Allopurinol hypersensiti- vity syndrome. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi 1994; 27: 140-7.
9.Hung SL, Chung WH, Liou LB, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA 2005; 102: 4134-9.
Corticosteroid Therapy in Allopurinol
Hypersensitivity Syndrome A Case Report
Der-Chang Wung, Meng-Fu Cheng
1,2, Jeng-Jong Huang
1, Tak-Wah Wong
2,3,4, J. Yu-Yun Lee
3, Yu-Chin Wu
5, and Yea-Huei Kao Yang
Allopurinol, an analogue of hypoxanthine, has been widely used in clinical practice for treatment of hype- ruricemia and gout. Although it is generally well tolerated, a small number of patients may develop a cutaneous rash, especially in the patients with chronic kidney disease. Allopurinol hypersensitivity syndrome (AHS), cha- racterized by skin rash, fever, leukocytosis, eosinophilia, aminotransferase elevation, is an infrequent but life- threatening adverse effect of allopurinol therapy. Because corticosteroid can modify the immunological process which is considered the major mechanism involved in AHS, it is used to treat AHS clinically. However, corticos- teroid therapy may have deleterious effect (e.g., delayed healing of cutaneous lesions, infections, prolonged hos- pital stay). Therefore, the use of corticosteroids for AHS remains controversial. We reported a 54-year-old man who had underlying diabetes mellitus with chronic renal insufficiency, hypertension and hyperlipidemia. Allopurinol 100mg twice a day was initiated one month prior to admission. After taking the drug for 24 days, he developed a generalized mild itchy eruption on the trunk and upper extremities followed by chillness, fever, ocular discomfort and painful oral ulcer over one-week period and was admitted to the hospital. A skin biopsy revealed changes consistent with Stevens-Johnson syndrome. Overall, allopurinol is still the most often prescribed drug for hype- ruricemia in clinical practice. Although the incidence rate of AHS is rare, its mortality rate is high once it happens.
Steroid therapy showed benefits in some case reports, however, it is hard to titrate the dose under considera- tions of increasing infection probability. Therefore, we don't suggest steroid therapy as an initial treatment for all AHS patients. In severe AHS cases, without expected response to supportive care, steroid therapy and close monitoring infection signs are recommened. ( J Intern Med Taiwan 2006; 17: 133-140 )
Institute of Clinical Pharmacy,
1Departments of Internal Medicine,
2Institute of Clinical Medicine,
3
