Severe Complication of Thiopurine Treatment in a Young Woman with Crohn’s Disease

Voet, Michiel Pj; Calon, Tga; Hendriks, M M C; Schreuder, RM

doi:10.12890/2021_002350

Cited by 3 publications

(1 citation statement)

References 14 publications

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“…The primo-infection of Epstein-Barr virus (EBV) in young patients treated with TP has been associated with an increased risk of HLH (69). There are also some case reports about the relationship between cytomegalovirus (CMV) and HLH or severe primo-infection in patients under thiopurine therapy (70,71). In a recent study, exposure to TP was an independent risk factor for developing serious viral infections, mainly caused by CMV or EBV (72).…”

Section: Viral Infections (Epstein-barr Virus and Cytomegalovirus Serological Status)mentioning

confidence: 99%

Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era?

2021

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Thiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed.

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Section: Viral Infections (Epstein-barr Virus and Cytomegalovirus Serological Status)mentioning

confidence: 99%

Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era?

2021

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Mercaptopurine

2021

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Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations

Ren,

Yong,

Wang

et al. 2023

IDR

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The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients. Methods: Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis. Results: In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes. Conclusion: Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.

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Severe Complication of Thiopurine Treatment in a Young Woman with Crohn’s Disease

Cited by 3 publications

References 14 publications

Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era?

Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era?

Mercaptopurine

Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations

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