Severe Life-Threatening Diarrhea Caused by Azathioprine but Not by 6-Mercaptopurine

Marbet, Urs A.; Schmid, I.

doi:10.1159/000051882

Cited by 16 publications

(3 citation statements)

References 18 publications

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“…Side effects can be reduced by administering 6-MP instead of Az. 27 Dose-dependent side effects include leukopenia, thrombocytopenia and hepatitis. Az was used at dosages of 2–3 mg/kg to treat acute renal allograft rejection 28 (for more details, see Supplementary Tables 1 and 2 ).…”

Section: Immunosuppressive Drug Classesmentioning

confidence: 99%

Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches

et al. 2016

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Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.

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Section: Immunosuppressive Drug Classesmentioning

confidence: 99%

Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches

et al. 2016

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“…Association of high 6-TGN with gut sensitivity has been reported elsewhere, for IBD patients, and diarrhea has long been an often severe complication for IBD patients receiving AZA (32). However, some IBD cases appear to be intolerant to AZA but not 6-mercaptopurine (31), suggesting that a proportion of gut sensitivity cases may be caused by the imidazole moiety of AZA (33). Thus, withdrawal or reduction of AZA, or swapping to 6mercaptopurine, may be especially relevant for patients with IBD with diarrhea and other gut sensitivities.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Azathioprine: An Old and Wronged Immunosuppressant

Chocair

Neves²,

Mohrbacher³

et al. 2022

Front. Immunol.

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Mycophenolate rapidly substituted azathioprine (AZA) in transplant immunosuppression regimens since the 1990s, when early clinical trials indicated better outcomes, although opposite results were also observed. However, none of these trials used the well-established optimization methods for AZA dosing, namely, thiopurine methyltransferase pharmacogenetics combined with monitoring of the thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP). Resistance to optimize AZA therapy remains today in transplant therapy, despite the fact that thiopurine metabolite testing is being used by other medical disciplines with evident improvement in clinical results. In a previous analysis, we found that active 6-TGN metabolites were not detectable in about 30% of kidney transplant patients under continuous use of apparently adequate azathioprine dosage, which demonstrates the need to monitor these metabolites for therapeutic optimization. Two of four case studies presented here exemplifies this fact. On the other hand, some patients have toxic 6-TGN levels with a theoretically appropriate dose, as seen in the other two case studies in this presentation, constituting one more important reason to monitor the AZA dose administered by its metabolites. This analysis is not intended to prove the superiority of one immunosuppressant over another, but to draw attention to a fact: there are thousands of patients around the world receiving an inadequate dose of azathioprine and, therefore, with inappropriate immunosuppression. This report is also intended to draw attention, to clinicians using thiopurines, that allopurinol co-therapy with AZA is a useful therapeutic pathway for those patients who do not adequately form active thioguanine metabolites.

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“…2 Because of gastrointestinal manifestation, especially in the case of chronic inflammatory colitis it is mistaken for active illness. 4,15,16 But it can also mimic aggravation of disease in rheumatoid arthritis, vasculitis, or even neurologic illnesses such as myasthenia gravis. 3,[17][18][19][20] An allergic reaction to AZA cannot be predicted.…”

Section: Discussionmentioning

confidence: 99%

Azathioprine-Associated Hypersensitivity Reaction in a Patient With Churg Strauss Vasculitis

Lehmann¹,

Schöelmerich²,

Haerle³

2010

JCR: Journal of Clinical Rheumatology

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A zathioprine (AZA) has been used since the beginnings of immunosuppressive therapy in organ transplantation, and later, to treat various autoimmune diseases. We report a case of a patient with an AZA-induced hypersensitivity reaction, a rare but potentially harmful side effect. CASEA 59-year-old male patient presented with elevated systemic inflammatory markers, blood eosinophilia of 53%, clinical and laboratory signs of myositis, bilateral pulmonary infiltrates, and peripheral polyneuropathy with rapid onset and progression. He had been suffering from asthma and chronic rhinitis for years. Antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, and antisynthetase-antibodies were negative, and complement levels were found to be within the normal range. Sarcoidosis, hematologic disorders, malignant, and allergic causes were excluded. A clinical diagnosis of a Churg Strauss vasculitis was made. After prednisone pulse and intravenous cyclophosphamide therapy, the patient improved rapidly, eosinophils returned within the normal range, pulmonary infiltrates vanished, and the polyneuropathy remained stable. After remission induction, a maintenance therapy with AZA was initiated with the patient, and the dose tapered to 200 mg/d. Initially, the drug was well tolerated. However, after 2 weeks of AZA treatment, the patient was presented to our emergency department with an acute onset of fever of up to 39°C, nausea, vomiting, and diarrhea. Laboratory tests showed an elevated C-reactive protein concentration of 74 mg/L, and a normal white blood count with relative neutrophilia of 92% and lymphopenia of 1.5%. Level of eosinophils was not elevated (0.7%). Liver function tests were normal. Urine analysis, chest x-ray, and abdominal ultrasound revealed no bacterial focus. AZA was stopped, and the patient was discharged with antibiotic treatment, as he refused to be admitted to the hospital. The patient recovered completely within a couple of days, and blood tests showed inflammatory markers and differential blood count within the normal range; therefore, AZA treatment was resumed about 3 weeks later. After 1 dose of AZA (50 mg), he developed the same symptoms and laboratory changes as those seen before. AZA hypersensitivity was now suspected, and the medication was stopped. Without any antibiotic treatment, the patient again recovered within days. C-reactive protein and differential blood count returned within the normal range. Immunosuppressive therapy was then switched to methotrexate without any sign of relapse of the apparent Churg Strauss vasculitis.

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Severe Life-Threatening Diarrhea Caused by Azathioprine but Not by 6-Mercaptopurine

Cited by 16 publications

References 18 publications

Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches

Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches

Case Report: Azathioprine: An Old and Wronged Immunosuppressant

Azathioprine-Associated Hypersensitivity Reaction in a Patient With Churg Strauss Vasculitis

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