Mesalazine allergy and an attempt at desensitization therapy in patients with inflammatory bowel disease

Abstract

Mesalazine is a key drug used for remission induction and maintenance therapy in inflammatory bowel disease (IBD). We sometimes encounter patients who develop allergic reactions to the drug and inevitably discontinue treatment. Of 692 patients who received mesalazine for IBD between 2014 and March 2020, 33 diagnosed with mesalazine allergy (43 episodes) were included, and their clinical manifestations were evaluated. For ten patients undergoing desensitization therapy, therapeutic outcomes were evaluated. The incidence of mesalazine allergy was 4.8%. The time from the start of oral medication to allergy onset was 10 ± 5 days for the first allergic attack and 2 ± 1 days for the second and subsequent allergic attacks. The observed clinical symptoms included fever (93%), diarrhea (26%), abdominal pain (23%), and bloody stool (12%). Drug-induced lymphocyte stimulation test was performed in 85% of the patients (28/33), and the sensitivity was 51%. Desensitization therapy with a time-dependent mesalazine granule formulation was successful in nine of the ten patients (90%), allowing them to receive 2000 mg or more of the drug. Fever was a common allergic symptom, and its presence appeared to be useful for distinguishing mesalazine allergy from exacerbation of the primary disease. Desensitization therapy was useful in patients with mesalazine allergy.

Retrospective investigation of mesalamine intolerance in patients with ulcerative colitis

“…Although the number of cases was limited, the success rate was not affected by the results of DLST or desensitization therapy. A recent report also showed that the success rate of the desensitization treatment was not related to the results of DLST, which was similar to the course of this study.‍ ( 36 )…”

“…Hepatotoxicity,‍ ( 26 , 27 ) pancreatitis,‍ ( 28 , 29 ) interstitial nephritis,‍ ( 30 , 31 ) pneumonia,‍ ( 32 ) and pericarditis‍ ( 12 , 33 ) have been reported as rare but serious symptoms of mesalamine intolerance. The frequency of these side effects does not increase with increasing mesalamine dose,‍ ( 34 ) but these symptoms are always dose-dependent and have been reported to resolve with decreasing dose.‍ ( 35 ) The frequency of fever (85.7%), a typical symptom of 5-ASA intolerance, observed in this study was comparable to that reported in recent years (93.0%).‍ ( 36 ) In addition, the clinical course of the cases in this study was similar to previous reports in that symptoms appeared within 2 weeks and serum CRP levels were high.‍ ( 25 , 36 )…”

“…As there are also a certain number of false-negative cases that also exist in clinical practice,‍ ( 22 ) the diagnosis of allergy should be based on the evaluation of the clinical course. The timing of DLST is also important, and it has also been reported that the time from the onset of allergic symptoms to blood collection is significantly longer in patients with mesalamine DLST-positive than in patients with DLST-negative.‍ ( 36 ) When an allergic hypersensitivity reaction occurs, memory T cells proliferate unevenly, and regulatory T cells are strongly activated. As DLST is based on the response of memory T cells, the test can be falsely negative in this situation.…”

Drug-induced hypersensitivity syndrome with lupus manifestations due to mesalazine in a patient with ulcerative colitis

“…Several reports have pointed to varied adverse drug reactions associated with 5-ASA-containing compounds, the most frequent being fever and gastrointestinal reactions with an incidence of approximately 5%. The mechanism behind these is thought to be a drug-induced hypersensitivity syndrome, with desensitisation therapy successful in up to 90% of cases, according to a recent study 1. Much rarer adverse effects include pericarditis, eosinophilic pneumonia, pancreatitis, interstitial nephritis and hepatotoxicity 2–4.…”

Analysis of clinical characteristics of mesalazine-induced cardiotoxicity

“…5-ASA, also termed mesalazine, is often associated with fever, diarrhea, abdominalgia, and hematochezia ( Matsumoto and Mashima, 2020 ). However, cardiotoxicity has been reported as a rare but potentially fatal adverse reaction ( Kristensen et al, 1990 ).…”