Crohn's Disease with Mesalazine Allergy that Was Difficult to Differentiate from Comorbid Ulcerative Colitis

Tsuboi, Rumiko; Matsumoto, Satohiro; Matsuda, Hiroyuki; Mashima, Hirosato

doi:10.2169/internalmedicine.1607-18

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…Therefore, the patient may be judged to be steroid-dependent, which may result in overtreatment or a delayed diagnosis of mesalazine allergy 19 . In addition, we previously experienced a case of mesalazine allergy that was difficult to diagnose because of adalimumab 20 . Although DLST detects type IV allergy associated with T-lymphocytes, adalimumab also inhibits T-lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

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

Matsumoto

Mashima

2020

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 99%

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

Matsumoto

Mashima

2020

Sci Rep

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“…DLST detects type IV allergies associated with T lymphocytes, but adalimumab also suppresses T lymphocytes. Therefore, adalimumab may have masked mesalamine allergy and alleviated symptoms.‍ ( 40 ) In this study, since there were only four cases of concomitant use of steroids and all had positive DLST results, concomitant use of steroids is thought to have no effect on the DLST results. In the present study, seven patients were treated with desensitization therapy.…”

Section: Discussionmentioning

confidence: 74%

“…As DLST is based on the response of memory T cells, the test can be falsely negative in this situation. Therefore, DLST should be performed after the allergic reaction is in remission or after 4 weeks.‍ ( 37 , 38 ) The combination of steroids‍ ( 39 ) or adalimumab‍ ( 40 ) has been reported to prevent accurate results from DLST for mesalamine allergy. DLST detects type IV allergies associated with T lymphocytes, but adalimumab also suppresses T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Retrospective investigation of mesalamine intolerance in patients with ulcerative colitis

Minagawa

Uchiyama

Takagi

et al. 2022

J. Clin. Biochem. Nutr.

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Mesalamine is a key drug in the treatment of ulcerative colitis (UC) for both induction and maintenance therapy. On the other hand, it is known that there are some cases of mesalamine intolerance that are difficult to distinguish from symptoms due to aggravation of UC. The aim of this study is to investigate the clinical characteristic of mesalamine intolerance in UC. A retrospective, observational study was conducted. We enrolled 31 patients who were diagnosed as mesalamine intolerance between April 2015 to March 2020. We examined clinical features, time to onset, drug types of mesalamine, DLST positive rate, colonoscopy findings, disease activity, and clinical course after diagnosis. The average dose of mesalamine was 3.69 g and DLST-positive was 57.1%. Within the first 2 weeks from the start of mesalamine, 51.6% showed symptoms of intolerance. The serum CRP level was relatively high at ≥10.0 mg/dl in 53.6% of the cases. There was no difference in clinical background, symptoms, or laboratory findings between patients with DLST-positive and negative. In this study, we clarified the clinical characteristics of mesalamine intolerant patients, and found no difference in the clinical background or success rate of desensitization therapy between positive and negative DLST cases.

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“…Previous reports about mesalamine allergy were studies or case reports mostly concerning UC, [25][26][27] and few reports compared the incidence rate of mesalamine allergy between CD and UC. 28 Most of these cases experienced these symptoms at the active phase of UC, that is, after the initial administration of high-dose mesalamine. Interestingly, all patients with UC experiencing mesalamine allergy in the Tohoku cohort had left-sided colitis or total colitis, with no proctitis type.…”

Section: Discussionmentioning

confidence: 99%

Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease

Suzuki

Kakuta

Naito

et al. 2021

Inflammatory Bowel Diseases

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Background Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called “mesalamine allergy,” which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. Methods Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. Results In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn’s disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). Conclusions Mesalamine allergy was more common in ulcerative colitis than in Crohn’s disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.

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Crohn's Disease with Mesalazine Allergy that Was Difficult to Differentiate from Comorbid Ulcerative Colitis

Cited by 4 publications

References 9 publications

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

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

Retrospective investigation of mesalamine intolerance in patients with ulcerative colitis

Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease

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