Allopurinol-induced granulomatous hepatitis

Espiritu, Carmelita R.; Alalu, Jaime; Glueckauf, Lewis G.; Lubin, Jack

doi:10.1007/bf01073035

Cited by 29 publications

(2 citation statements)

References 9 publications

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“…A liver biopsy specimen revealed normal hepatic tissue with no granulomas. COMMENT Like the two previous patients with allopurinol-induced granulomatous hepatitis, our patient had fever, malaise, abnormal liver function, and noncaseating granulomas on liver biopsy specimen.5 6 Unlike these patients, our patient also had cholangitis and pericholangitis on liver biopsy specimen, lymphopenia, and substantial weight loss. These symptoms and findings were not present before the patient started taking the drug, and they disappeared when the drug therapy was discontinued, suggesting druginduced hypersensitivity.…”

Section: Report Of a Casesupporting

confidence: 51%

Allopurinol-Induced Granulomatous Hepatitis With Cholangitis and a Sarcoid-like Reaction

Swank¹

1978

Arch Intern Med

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Section: Report Of a Casesupporting

confidence: 51%

Allopurinol-Induced Granulomatous Hepatitis With Cholangitis and a Sarcoid-like Reaction

Swank¹

1978

Arch Intern Med

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“…Allopurinol, a xanthine oxidase inhibitor, is currently a firstline drug for the treatment of gout and hyperuricemia (Braden et al, 1994). Although generally well tolerated, allopurinol is associated with severe cutaneous adverse reactions (SCARs) that include drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrosis (TEN) (Espiritu et al, 1976;Braden et al, 1994;Ramasamy et al, 2013). We first reported a strong association between the HLA-B*58:01 allele and allopurinol-induced SCAR in Han Chinese, and this association was further validated in different populations (Hung et al, 2005;Kaniwa et al, 2008;Lonjou et al, 2008;Tassaneeyakul et al, 2009;Phillips and Mallal, 2010;Kang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Oxypurinol-Specific T Cells Possess Preferential TCR Clonotypes and Express Granulysin in Allopurinol-Induced Severe Cutaneous Adverse Reactions

Chung

Pan

Chu³

et al. 2015

Journal of Investigative Dermatology

112

114

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Allopurinol, a first-line drug for treating gout and hyperuricemia, is one of the leading causes of severe cutaneous adverse reactions (SCARs). To investigate the molecular mechanism of allopurinol-induced SCAR, we enrolled 21 patients (13 Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and 8 drug reaction with eosinophilia and systemic symptoms (DRESS)), 11 tolerant controls, and 23 healthy donors. We performed in vitro T-cell activation assays by culturing peripheral blood mononuclear cells (PBMCs) with allopurinol, oxypurinol, or febuxostat and measuring the expression of granulysin and IFN-γ in the supernatants of cultures. TCR repertoire was investigated by next-generation sequencing. Oxypurinol stimulation resulted in a significant increase in granulysin in the cultures of blood samples from SCAR patients (n=14) but not tolerant controls (n=11) or healthy donors (n=23). Oxypurinol induced T-cell response in a concentration- and time-dependent manner, whereas allopurinol or febuxostat did not. T cells from patients with allopurinol-SCAR showed no crossreactivity with febuxostat. Preferential TCR-V-β usage and clonal expansion of specific CDR3 (third complementarity-determining region) were found in the blister cells from skin lesions (n=8) and oxypurinol-activated T-cell cultures (n=4) from patients with allopurinol-SCAR. These data suggest that, in addition to HLA-B*58:01, clonotype-specific T cells expressing granulysin upon oxypurinol induction participate in the pathogenesis of allopurinol-induced SCAR.

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