UNASSIGNED: To report a case of a female patient with hemophagocytic lymphohistiocytosis (HLH) and to systematically review the available cases of the association between HLH and inflammatory bowel disease (IBD).
UNASSIGNED: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), Biblioteca Regional de Medicina, Latin American and Caribbean Health Sciences Literature, Cochrane Library for Systematic Reviews and Opengrey.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually.
UNASSIGNED: The search strategy retrieved 223 references. In the final analysis, 28 references were included, with the report of 35 cases. The most common clinical finding was fever, 57% of patients had a cytomegalovirus infection and 30 patients were on thiopurines previously to HLH diagnosis. Most patients were treated with steroids and antiviral therapy. All-cause mortality was 22%.
UNASSIGNED: These findings suggest that there might be a connection of HLH to IBD, opportunistic viral infections and the use of thiopurines. Due to the severity of such disease, the clinical suspicion is paramount to early diagnosis and therapy.

Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels and anti-drug antibodies, is a promising strategy that can be used to optimize inflammatory bowel disease therapeutics. It is based on the premise that there is a relationship between drug exposure and outcomes, and that considerable inter-individual variability exists in how patients metabolize the drug (pharmacokinetics) and the magnitude and duration of response to therapy (pharmacodynamics). Therefore, the American Gastroenterological Association has prioritized clinical guidelines on the role of TDM in the management of inflammatory bowel disease. To inform these clinical guidelines, this technical review was developed in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework for interventional and prognostic studies, and focused on the application of TDM for biologic therapy, specifically anti-tumor necrosis factor-α agents, and for thiopurines. Focused questions address the benefits and risks of a strategy of reactive TDM (in patients with active inflammatory bowel disease) to guide treatment changes compared with empiric treatment changes, and the benefits and risks of a strategy of routine proactive TDM (during routine clinical care in patients with quiescent disease) compared with no routine TDM. Additionally, the review addresses the benefits and risks of routine measurement of thiopurine methyltransferase enzyme activity or genotype before starting thiopurine therapy compared with empiric weight-based dosing and explores the performance of different trough drug concentrations for anti-tumor necrosis factor agents and thiopurines to inform clinical decision making when applying TDM in a reactive setting. Due to a paucity of data, this review does not address the role of TDM for more recently approved biologic agents, such as vedolizumab or ustekinumab.

BACKGROUND: Immunosuppression is a risk factor for carcinogenesis. Thiopurines specifically contribute to this. As thiopurines are used more aggressively in the treatment of IBD, it is likely that we will see more thiopurine-related malignancy.
OBJECTIVE: To review the literature, exploring how immunosuppression, thiopurines specifically, might cause cancer and which malignancies occur in practice, placing specific emphasis on IBD cohorts.
METHODS: Search terms included \'malignancy\' \'cancer\' \'azathioprine\' \'mercaptopurine\' \'tioguanine (thioguanine)\' \'thiopurine\' and \'inflammatory bowel disease\' \'Crohn\'s disease\' \'ulcerative colitis\'. We also searched for specific cancers (lymphoma, colorectal cancer, skin cancer, cervical cancer) and reviewed the reference lists of the articles detected.
RESULTS: Immunosuppression is associated with an increased risk of cancer. Thiopurines are associated with specific additional risks. In IBD cohorts, very few thiopurine-related malignancies have been reported. However, studies suggest a relative risk of 4-5 for lymphoma. This still translates into a low actual risk, (one extra lymphoma in every 300-1400 years of thiopurine treatment).
CONCLUSIONS: Whilst we must be aware of this risk and counsel our patients appropriately, thiopurines remain a mainstay of IBD therapy. We present practical advice aimed at minimizing our patients\' risk of developing malignancy, whilst optimizing the benefits that thiopurines can provide.