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Allopurinol hypersensitivity syndrome in patients with hematological malignancies: characteristics and clinical outcomes

  • Min, Hong Ki (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lee, Boin (Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kwok, Seung-Ki (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Ju, Ji Hyeon (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Wan-Uk (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Park, Young Min (Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Park, Sung-Hwan (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2014.05.21
  • Accepted : 2014.07.28
  • Published : 2015.07.01

Abstract

Background/Aims: Allopurinol is a urate-lowering agent that is commonly used to prevent chemotherapy-related hyperuricemia. Allopurinol hypersensitivity syndrome (AHS) is a disorder involving multiple organs, which may be accompanied by cutaneous adverse reactions. We identified the characteristics and clinical outcomes of chemotherapy-associated AHS in patients with hematological malignancies. Methods: This retrospective single-center study included 26 AHS patients (11 with and 15 without hematological malignancies) admitted to Seoul St. Mary's Hospital. AHS was defined using the criteria of Singer and Wallace. Comparisons were made using the Mann-Whitney U test and Fisher exact test as appropriate. Results: In patients with a hematological malignancy and AHS, statistically significant differences were observed in terms of younger age at onset; shorter duration of exposure; higher starting and maintenance doses of allopurinol; lower incidence of eosinophilia, leukocytosis, and underlying renal insufficiency; and more frequent occurrence of fever compared to AHS patients without a hematological malignancy. Two AHS patients with a hematological malignancy were examined for human leukocyte antigen (HLA)-B typing, but neither patient harbored the $HLA-B^*5801$ allele. All of the patients ceased allopurinol treatment, with most patients making a full recovery. Two patients in the study died; however, these deaths were unrelated to AHS. One patient developed serious sequelae of AHS that required hemodialysis. Conclusions: Physicians who prescribe allopurinol for the prevention of chemotherapy-related hyperuricemia should be aware of the unique risk of AHS, even in patients with hematological malignancies who do not have known risk factors for AHS. Novel urate-lowering agents should be considered alternative treatments.

Keywords

Acknowledgement

Supported by : Ministry of Health and Welfare

References

  1. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012;64:1431-1446. https://doi.org/10.1002/acr.21772
  2. Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 2006;47:51-59. https://doi.org/10.1053/j.ajkd.2005.10.006
  3. Gaffo AL, Saag KG. Drug treatment of hyperuricemia to prevent cardiovascular outcomes: are we there yet? Am J Cardiovasc Drugs 2012;12:1-6. https://doi.org/10.2165/11594580-000000000-00000
  4. Lang PG Jr. Severe hypersensitivity reactions to allopurinol. South Med J 1979;72:1361-1368. https://doi.org/10.1097/00007611-197911000-00004
  5. Singer JZ, Wallace SL. The allopurinol hypersensitivity syndrome: unnecessary morbidity and mortality. Arthritis Rheum 1986;29:82-87. https://doi.org/10.1002/art.1780290111
  6. Marotti M. Severe cutaneous adverse reactions (SCAR) syndromes. Rev Assoc Med Bras 2012;58:276-278. https://doi.org/10.1016/S0104-4230(12)70193-8
  7. Halevy S, Ghislain PD, Mockenhaupt M, et al. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol 2008;58:25-32. https://doi.org/10.1016/j.jaad.2007.08.036
  8. Mockenhaupt M, Viboud C, Dunant A, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs: the EuroSCAR-study. J Invest Dermatol 2008;128:35-44. https://doi.org/10.1038/sj.jid.5701033
  9. Baumann MA, Frick JC, Holoye PY. The tumor lysis syndrome. JAMA 1983;250:615. https://doi.org/10.1001/jama.1983.03340050027019
  10. Cohen LF, Balow JE, Magrath IT, Poplack DG, Ziegler JL. Acute tumor lysis syndrome: a review of 37 patients with Burkitt’s lymphoma. Am J Med 1980;68:486-491. https://doi.org/10.1016/0002-9343(80)90286-7
  11. Burghi G, Berrutti D, Manzanares W. Tumor lysis syn-drome in intensive therapy: diagnostic and therapeutic encare. Med Intensiva 2011;35:170-178. https://doi.org/10.1016/j.medin.2010.07.014
  12. Wilson FP, Berns JS. Onco-nephrology: tumor lysis syndrome. Clin J Am Soc Nephrol 2012;7:1730-1739. https://doi.org/10.2215/CJN.03150312
  13. Nicoll D, Lu CM, Pignone M, McPhee SJ. Pocket Guide to Diagnostic Tests. 6th ed. Stamford: McGraw-Hill, 2012.
  14. Yue TF, Gutman AB. Effect of allopurinol (4-hydroxypyrazolo-(3,4-d)pyrimidine) on serum and urinary uric acid in primary and secondary gout. Am J Med 1964;37:885-898. https://doi.org/10.1016/0002-9343(64)90131-7
  15. Edwards NL. The role of hyperuricemia and gout in kidney and cardiovascular disease. Cleve Clin J Med 2008;75 Suppl 5:S13-S16.
  16. Goncalves JP, Oliveira A, Severo M, Santos AC, Lopes C. Cross-sectional and longitudinal associations between serum uric acid and metabolic syndrome. Endocrine 2012;41:450-457. https://doi.org/10.1007/s12020-012-9629-8
  17. Johnson RJ, Kang DH, Feig D, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003;41:1183-1190. https://doi.org/10.1161/01.HYP.0000069700.62727.C5
  18. Kantor GL. Toxic epidermal necrolysis, azotemia, and death after allopurinol therapy. JAMA 1970;212:478-479. https://doi.org/10.1001/jama.1970.03170160066019
  19. Ramasamy SN, Korb-Wells CS, Kannangara DR, et al. Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012. Drug Saf 2013;36:953-980. https://doi.org/10.1007/s40264-013-0084-0
  20. Hung SI, 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 U S A 2005;102:4134-4139. https://doi.org/10.1073/pnas.0409500102
  21. Tassaneeyakul W, Jantararoungtong T, Chen P, et al. Strong association between HLA-B*5801 and allopurinol- induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics 2009;19:704-709. https://doi.org/10.1097/FPC.0b013e328330a3b8
  22. Jung JW, Song WJ, Kim YS, et al. HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency. Nephrol Dial Transplant 2011;26:3567-3572. https://doi.org/10.1093/ndt/gfr060
  23. Somkrua R, Eickman EE, Saokaew S, Lohitnavy M, Chaiyakunapruk N. Association of HLA-B*5801 allele and allopurinol- induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. BMC Med Genet 2011;12:118. https://doi.org/10.1186/1471-2350-12-118
  24. Kaniwa N, Saito Y, Aihara M, et al. HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics 2008;9:1617-1622. https://doi.org/10.2217/14622416.9.11.1617
  25. Gibson SE, Luo J, Sathanoori M, Liao J, Surti U, Swerdlow SH. Whole-genome single nucleotide polymorphism array analysis is complementary to classical cytogenetic analysis in the evaluation of lymphoid proliferations. Am J Clin Pathol 2014;141:247-255. https://doi.org/10.1309/AJCPRHGHT28DUWLA
  26. Kang HR, Jee YK, Kim YS, et al. Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics 2011;21:303-307. https://doi.org/10.1097/FPC.0b013e32834282b8
  27. Rice KL, Lin X, Wolniak K, et al. Analysis of genomic aberrations and gene expression profiling identifies novel lesions and pathways in myeloproliferative neoplasms. Blood Cancer J 2011;1:e40. https://doi.org/10.1038/bcj.2011.39
  28. Cluzeau T, Moreilhon C, Mounier N, et al. Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine. Blood Cancer J 2013;3:e155. https://doi.org/10.1038/bcj.2013.52
  29. McInnes GT, Lawson DH, Jick H. Acute adverse reactions attributed to allopurinol in hospitalised patients. Ann Rheum Dis 1981;40:245-249. https://doi.org/10.1136/ard.40.3.245
  30. Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum 2012;64:2529-2536. https://doi.org/10.1002/art.34488
  31. Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer 2004;100:228-237. https://doi.org/10.1002/cncr.11882
  32. Aubock J, Fritsch P. Asymptomatic hyperuricaemia and allopurinol induced toxic epidermal necrolysis. Br Med J (Clin Res Ed) 1985;290:1969-1970. https://doi.org/10.1136/bmj.290.6486.1969
  33. Kim SC, Newcomb C, Margolis D, Roy J, Hennessy S. Severe cutaneous reactions requiring hospitalization in allopurinol initiators: a population-based cohort study. Arthritis Care Res (Hoboken) 2013;65:578-584. https://doi.org/10.1002/acr.21817
  34. Calogiuri G, Nettis E, Di Leo E, Foti C, Ferrannini A, Butani L. Allopurinol hypersensitivity reactions: desensitization strategies and new therapeutic alternative molecules. Inflamm Allergy Drug Targets 2013;12:19-28. https://doi.org/10.2174/1871528111312010004
  35. Yu KH. Febuxostat: a novel non-purine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in gout. Recent Pat Inflamm Allergy Drug Discov 2007;1:69-75. https://doi.org/10.2174/187221307779815020
  36. Chohan S. Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions. J Rheumatol 2011;38:1957-1959. https://doi.org/10.3899/jrheum.110092
  37. Feng X, Dong K, Pham D, Pence S, Inciardi J, Bhutada NS. Efficacy and cost of single-dose rasburicase in prevention and treatment of adult tumour lysis syndrome: a meta-analysis. J Clin Pharm Ther 2013;38:301-308. https://doi.org/10.1111/jcpt.12061
  38. Mockenhaupt M. The current understanding of Stevens-Johnson syndrome and toxic epidermal necrolysis. Expert Rev Clin Immunol 2011;7:803-813; quiz 814-815. https://doi.org/10.1586/eci.11.66
  39. Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR Study. J Am Acad Dermatol 2008;58:33-40. https://doi.org/10.1016/j.jaad.2007.08.039
  40. Alejandria MM, Lansang MA, Dans LF, Mantaring JB 3rd. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev 2013;9:CD001090.

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