Allergic Reactions to 6-Mercaptopurine During Treatment of Inflammatory Bowel Disease

Abstract

Hypersensitivity reactions to 6-mercaptopurine (6-MP) or azathioprine occur during the treatment of inflammatory bowel disease (IBD), raising significant diagnostic and therapeutic challenges. Charts of 591 patient with IBD treated with 6-MP in a single center were retrospectively reviewed. All allergic reactions were recorded along with results of rechallenge, desensitization, and subsequent course of IBD. Sixteen (2.7%) allergic reactions to 6-MP were noted, with fever being the most common (14 cases). Nine of these were rechallenged with 6-MP with recurrence of the same symptoms. Azathioprine was tried in six patients and in five the same symptoms recurred. Four patients underwent successful desensitization to either 6-MP or azathioprine; all four plus another patient who tolerated direct switch to azathioprine entered long-term remission. Among the remaining 11, 5 required surgery, 2 are well on methotrexate, and 4 have chronic symptoms while being treated with other medications. If an allergic reaction to 6-MP occurs during the treatment of IBD, direct switching to azathioprine is probably not justified. Instead, desensitization to either 6-MP or azathioprine should be attempted. Patients who can tolerate these medications after previous allergic reactions have improved outcomes compared with patients who resort to other forms of treatment.

Mercaptopurine treatment should be considered in azathioprine intolerant patients with inflammatory bowel disease

“…Also, a majority of patients with arthralgia and ⁄ or myalgia during AZA treatment tolerated a shift to MP, while only a minority of patients with other types of idiosyncratic reactions like flu-like symptoms, fever and rash did so. It has been described that de-sensitization techniques can be used with good results in these types of idiosyncratic reactions, [21][22][23] but in this study, the de-sensitization technique was used in only a few patients and with variable results. This study has some limitations due to its retrospective nature.…”

“…AEs to AZA or MP occur in 9-34% of patients and often necessitate dose reduction or discontinuation of the administered drug. [17][18][19][20] Different approaches to the management of patients with thiopurine intolerance have been proposed, including the use of de-sensitization techniques [21][22][23] and switch to another thiopurine drug. It has been postulated that some early idiosyncratic reactions, such as digestive intolerance, pancreatitis, cholestasis and flu-like symptoms during AZA therapy, might be due to the nitro-imidazole moiety found in AZA, which is released to produce MP.…”

A Nurse-Driven Outpatient Clinic for Thiopurine-Treated Inflammatory Bowel Disease Patients Reduces Physician Visits and Increases Follow-Up Efficiency

“…The percentage of leucopenia varies depending on its definition, but it has been reported to be as high as 11%. (de Jong, D. J., et al 2003) Type B adverse events, including fever, pancreatitis, rash, and arthralgia (Korelitz et al, 1999), occur in 2% of the patients and appear more often at the beginning of the treatment. Pancreatitis is one of the most frequent idiosyncratic reactions (1.4%-5%) and generally appears in the first 3-4 weeks (Weersma et al, 2004); it is usually mild and improves after discontinuation of the drug.…”

Adverse events of thiopurine immunomodulators in patients with inflammatory bowel disease

“…27 Drug doses used in the patients who developed pancreatitis were lower than in the rest of toxicities (less than 1.5 mg/kg of AZA and less than 1 mg/kg of MP) and the time of appearance of the symptoms was less than 1 month in most of the cases, which seems to be related to allergic or idiosyncratic nature, coinciding with previously published articles. 5,6,8,14,[26][27][28] Finally, gastrointestinal intolerance was observed in 4% of the patients and although they had no clinical severity, it resulted in a significant percentage of drug suspension. In these cases, however, various strategies are described to prevent this adverse event without directly rejecting the thiopurine option.…”