Adverse Effects Of Azathioprine Research Articles

Anagen Effluvium due to Azathioprine in a Patient With Normal Thiopurine S-Methyltransferase Levels: A Case Report Using Videodermoscopic Analysis

Introduction: Anagen effluvium (AE) is caused by impaired mitotic activity of matrix cells in the hair follicles. It presents with sudden loss of hair and myelosuppression. The diagnosis is based on the clinical history, trichoscopy, and trichogram. We herein report a case in which videodermoscopy revealed new trichoscopic features of AE caused by azathioprine in a patient with normal thiopurine S-methyltransferase (TPMT) levels. Case presentation: A 20-year-old woman presented with sudden loss of hair following treatment with oral azathioprine. Evaluation of the TPMT were within normal limits both in genotype and phenotype levels. Hair pull test was positive. Trichoscopy revealed yellow dots and multiple black dots, empty yellow dots, dark lines, upright regrowing hairs, and circle hairs. Azathioprine was stopped, and minoxidil 5% and oral multivitamin were started. Posttreatment trichoscopic analysis revealed terminal hairs and upright regrowing hairs. Discussion: AE is characterized by abrupt loss of anagen hairs due to impaired metabolic activity. Trichoscopy in AE shows coudability hairs, black dots, exclamation mark hairs, multiple broken shafts, and regrowing hairs. Empty yellow dots, yellow dots with black dots, pigtail hairs, and dark lines were additional features in this study. Conclusion: Trichoscopy assists in the accurate diagnosis of AE. Adverse effects of azathioprine can be observed even with normal TPMT levels. Weekly monitoring is therefore of prime importance.

Adverse Events in NMOSD Therapy.

Neuromyelitis optica spectrum disorders (NMOSD) are rare neurologic autoimmune diseases that have a poor prognosis if left untreated. For many years, generic oral immunosuppressants and repurposed monoclonal antibodies that target the interleukin-6 pathway or B cells were the mainstays of drug treatment. Recently, these drug treatments have been complemented by new biologics developed and approved specifically for NMOSD. In principle, all of these drugs are effective, but treatment recommendations that take this into account are still pending. Instead, the choice of a drug may depend on other criteria such as drug safety or tolerability. In this review, we summarise current knowledge on the adverse effects of azathioprine, mycophenolate mofetil, rituximab, tocilizumab, eculizumab, satralizumab, and inebilizumab in NMOSD. Infections, cytopenias, and infusion-related reactions are most common, but the data are as heterogeneous as the manifestations are diverse. Nevertheless, knowledge of safety issues may facilitate treatment choices for individual patients.

Second-line therapy with mycophenolate mofetil in patients with autoimmune hepatitis who were intolerant or failed to respond to standard treatment

Although standard treatment for autoimmune hepatitis (AIH) comprises prednisolone (PSL) and azathioprine (AZA), some patients are intolerant to or do not respond to PSL and/or AZA. The clinical practice guidelines of AIH in Europe and North America recommend mycophenolate mofetil (MMF) as second-line treatment in these patients. We administered MMF as second-line therapy to 7 patients with AIH (male/female 1/6, age range 27-79 years) who were intolerant to or failed to respond to standard treatment. At the commencement of MMF, the median ALT value was 84U/L (28-254U/L), and the PSL dose was 15.0mg/day (0-45mg/day). In terms of adverse effects of PSL, diabetes mellitus was observed in 4 patients (insulin injection in 2) and femoral head necrolysis in 2. Adverse effects of AZA were present in 2, and 5 patients were not treated with AZA. At 24 weeks of MMF treatment, the median ALT and daily PSL dose were decreased to 16U/L (6-41U/L) and 7.0mg, respectively. Blood sugar control improved, and insulin injection was discontinued in both the patients. While intractable diarrhea developed in 1 patient with cirrhosis, no adverse effect was observed in other 6 patients. In conclusion, MMF appeared effective and safe in at least non-cirrhotic patients with AIH who were intolerant or failed to respond to standard treatment with PSL and AZA in Japanese clinical practice.

TPMT Genotype and Adverse Effects of Azathioprine among Jordanian Group.

Inflammatory Bowel Disease (IBD) is a common disease affecting many patients. This disease is treated by azathioprine and TPMT genetic polymorphism affecting the patient's tolerance. The aim of this study is to investigate the importance of TMPT genotyping in reducing the incidence of adverse effects of azathioprine. One hundred and forty-one IBD patients were followed for azathioprine Adverse Drug Reaction (ADR). Patients were genotyped for TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C. The frequency of Azathioprine adverse effect was about 35.5%. An association between TPMT genotypes 1/3A and 3B/3B and azathioprine related bone marrow suppression was found (P value ≤ 0.05). The findings suggest that there was a significant association between TPMT genotypes 1/3A and 3B/3B and azathioprine related bone marrow suppression.

P577 Adverse effects of azathioprine in patients with inflammatory bowel disease (IBD)

P577 Adverse effects of azathioprine in patients with inflammatory bowel disease (IBD)

Differences in the adverse effects of azathioprine between inflammatory bowel disease and autoimmune hepatitis in Korean patients.

Azathioprine (AZA) has been widely used in the therapy of inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). However, studies evaluating the adverse effects of AZA in these two diseases are lacking. The aim of this study was to compare the adverse effects of AZA in Korean IBD and AIH patients. Patients with IBD or AIH who were treated with AZA at Keimyung University Dongsan Medical Center (Daegu, Korea) between January 2002 and March 2011 were enrolled. Their medical records were reviewed retrospectively in terms of clinical characteristics and adverse effects of AZA. A total of 139 IBD patients and 55 AIH patients were finally enrolled. Thirty IBD patients (21.6%) and eight AIH patients (14.5%) experienced adverse effects of AZA. In particular, the prevalence of leukopenia was significantly higher in the IBD group than in the AIH group (p=0.026). T474C mutation was observed in three of 10 patients who were assessed for thiopurine methyltransferase (TPMT) genotype. IBD patients are at increased risk for the adverse effects of AZA compared with AIH patients, of which leukopenia was the most commonly observed. Therefore, IBD patients receiving AZA therapy should be carefully monitored.

Y a-t-il intérêt à doser les métabolites de l’azathioprine chez les malades ayant une maladie inflammatoire chronique de l’intestin?

The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population. We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1year. Each patient had a dosage of azathioprine metabolites. We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients. Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule.

Azathioprine induced hepatitis in patients with inflammatory bowel disease

I welcome Salem and colleagues recent article on Azathioprine induced cholestatic hepatitis [1]. Azathioprine is an immunosuppressant used in the management of a number of clinical conditions. Concerns at time of commencing azathioprine are related to bone marrow suppression, consequently the TPMT levels are checked to ensure appropriate dosing regimen. However, azathioprine induced hepatitis is a rare but serious problem, which manifests either as a problem associated with chronic use and a gradual derangement of liver function tests or more concerning an acute severe hepatitis occurring within weeks of commencing treatment. This latter presentation is well reported in the literature and demonstrated to occur in patients on azathioprine for a number of different clinical conditions. In our institution over the last 4 years there have been two patients with inflammatory bowel disease that developed severe hepatitis following commencement of azathioprine. In both cases, patients developed upper abdominal pain, nausea and felt generally unwell. Both patients denied taking other medications or herbal remedies at this time. The bloods tests demonstrated a negative liver screen (including viral hepatitis screen, immunoglobulins, ferritin, urinary copper, caeuroplasmin, liver autoantibodies). Both patients’ had a normal amylase and deranged liver function tests; with marked rise in bilirubin of [100 lmol/l, and associated transaminitis. Both these patients had normal TPMT levels ([25 pmol/h/mg), hence neither were heterozygote or homozygote for TPMT deficiency. The Naranjo ADR probability scale was applied to these cases, which determined that hepatitis was probably due to the azathioprine in both cases (Naranjo probability score of 5 in each case). Following worsening of liver function tests, the azathioprine was stopped in both cases; this lead to a complete resolution of abnormal liver biochemistry over a period of 4 and 6 weeks, respectively. Upon reviewing the literature regarding azathioprine induced hepatitis, TPMT deficiency was not recognized in a number of cases [2–4]. To date fortunately there have not been any deaths related to azathioprine induced hepatitis. In all published cases, liver function tests improve upon cessation of azathioprine. Currently there is no test available to identify which patients will develop severe azathioprine associated hepatitis. Therefore, it is our practice to monitor all patients commencing on azathioprine and we have a shared care protocol with the general practitioners. This involves full blood counts, renal and liver function tests being checked at weeks 2, 4 and 6 weeks following commencement of azathioprine. We recommend a similar pathways exist for all other specialties commencing patients on azathioprine to enable early detection of this rare but serious adverse effect of azathioprine. With reference to the article by Salem et al. [1], it is important to note that acute azathioprine associated hepatitis occurs in patients with normal TPMT as well as those with TPMT deficiency. Secondly, frequent and regular blood tests at commencement of therapy currently are the only way to determine if a patient is developing an acute hepatitis. R. Srirajaskanthan (&) D. Valliani University Hospital Lewisham, London, UK e-mail: r.srirajaskanthan@nhs.net

W1197 Effectiveness and Adverse Effects of Azathioprine in Inflammatory Bowel Disease: 5-Year Follow-up Study

W1197 Effectiveness and Adverse Effects of Azathioprine in Inflammatory Bowel Disease: 5-Year Follow-up Study

An Audit of Tolerability and Adverse Effects of Azathioprine and 6-Mercaptopurine in Patients with IBD

An Audit of Tolerability and Adverse Effects of Azathioprine and 6-Mercaptopurine in Patients with IBD

Thiopurine Methyltransferase (TPMT) Activity and Adverse Effects of Azathioprine in Inflammatory Bowel Disease: Long-Term Follow-Up Study of 394 Patients

Thiopurine Methyltransferase (TPMT) Activity and Adverse Effects of Azathioprine in Inflammatory Bowel Disease: Long-Term Follow-Up Study of 394 Patients

Glutathione-S-transferase genotypes and the adverse effects of azathioprine in young patients with inflammatory bowel disease

Adverse drug reactions to azathioprine, the prodrug of 6-mercaptopurine, occur in 15%-38% of patients and the majority are not explained by thiopurine-S-methyltransferase (TPMT) deficiency. Azathioprine is known to induce glutathione depletion and consumption of glutathione is greater in cells with high glutathione-S-transferase (GST) activity compared with those with low activity; moreover, some reports indicate that GST might play a direct role in the reaction of glutathione with azathioprine. The association between polymorphisms of GST-M1, GST-P1, GST-T1, and TPMT genes and the adverse effects of azathioprine was therefore investigated. Seventy patients with inflammatory bowel disease (IBD), treated with azathioprine, were enrolled and clinical data were retrospectively determined. TPMT and GST genotyping were performed by polymerase chain reaction (PCR) assays on DNA extracted from blood samples. Fifteen patients developed adverse effects (21.4%); there was a significant underrepresentation of the GST-M1 null genotype among patients developing adverse drug reactions to azathioprine (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.037-0.72, P = 0.0072) compared with patients who did not develop adverse effects. Patients heterozygous for TPMT mutations presented a marginally significant increased probability of developing adverse effects (OR = 6.38, 95% CI = 0.66-84.1, P = 0.062). Moreover, among the 55 patients who did not develop adverse effects, there was a significant underrepresentation of the GST-M1 null genotype among patients who displayed lymphopenia as compared with those that did not display this effect of azathioprine (OR = 0.15, 95% CI = 0.013-1.08, P = 0.032). Patients with IBD with a wildtype GST-M1 genotype present increased probability of developing adverse effects and increased incidence of lymphopenia during azathioprine treatment.

Thiopurine Methyltransferase (TPMT) Activity and Adverse Effects of Azathioprine in Inflammatory Bowel Disease: Long-Term Follow-Up Study of 394 Patients

To prospectively evaluate whether a relationship between thiopurine methyltransferase (TPMT) activity and incidence of adverse effects (especially myelotoxicity) exists, in a long-term follow-up study of a large group of patients with inflammatory bowel disease treated with azathioprine. TPMT activity in red blood cells (RBC) was measured by a radiochemical method in 394 consecutive patients with Crohn's disease (238) or ulcerative colitis (156) starting treatment with azathioprine. The relationship among several variables and TPMT values was assessed, and the correlation between such levels and the incidence of adverse effects was evaluated. Mean TPMT value was 18.6 +/- 4 U/mL RBCs (range 9.4-33.7). No patient had low levels (<5), 7.1% had intermediate levels (5-13.7), and 92.9% had high levels (>13.8). Differences (P < 0.001) were demonstrated in TPMT activity depending on the type of inflammatory bowel disease, but not on the remaining variables (including treatment with 5-aminosalycilates). Adverse effects were reported in 74 patients (18.8%), the most frequent being gastrointestinal intolerance (9.1%) and myelotoxicity (4.3%). No patient having adverse effects had low TPMT levels. However, mean TPMT activity was lower in those with adverse effects (16.6 +/- 3 vs 19.1 +/- 4 U/mL, P < 0.001). Moreover, the probability of suffering myelotoxicity in the high TPMT group was only 3.5%, compared with 14.3% in the TPMT intermediate group (95% CI = 1.37-14.9; OR = 4.5). The strategy of determining TPMT activity in all patients prior to initiating treatment with azathioprine could help to minimize the risk of myelotoxicity, as patients with intermediate TPMT activity had fourfold more risk than high TPMT activity patients.

Genetic Testing in Crohn Disease

Inflammatory bowel disease (IBD), with its two subforms of Crohn disease and ulcerative colitis, is a polygenic disease that manifests due to environmental trigger factors on the background of a complex genetic predisposition. The first risk gene underlying susceptibility to Crohn disease has been identified as CARD15 (located on chromosome 16q12, encoding NOD2). Three single nucleotide polymorphisms in the leucine rich region (LRR) of this gene are strongly and independently associated with Crohn disease susceptibility and explain up to 20% of the total genetic predisposition for Crohn disease. These variants have been consistently replicated as associated with a particular sub-phenotype characterized by small bowel (ileum) involvement and early age at onset. Presently, genetic testing for the CARD15 variants has only a modest relevance in clinical practice. The most attractive use of genetic testing is for the prediction of response to therapy. Most therapies only show efficacy in subgroups of patients and no clinical parameters are available to distinguish, prior to therapy, whether the patients will be responders or non-responders, or if the patients will experience adverse effects. The pharmacogenetic basis of toxicity is well known for azathioprine: several thiopurine methyltransferase (TPMT) polymorphisms that are associated with reduced activity of this thiopurine drug metabolizing enzyme result in cytotoxic and immunosuppressive adverse effects of azathioprine. Genetic screening, which has found its way into routine clinical diagnostics, allows the identification of the patients who will not tolerate a standard dose of the drug. The extensive search for genetic predictors of response to the anti-tumor necrosis factor treatment with infliximab, which results in a remission rate of 30-40%, has, however, failed to identify a variation associated with a differential response.

Adverse effects of azathioprine

Adverse effects of azathioprine

Chromosomal Abnormalities in the Offspring of a Renal Transplant Recipient.

Meeting Abstracts1 May 1970Chromosomal Abnormalities in the Offspring of a Renal Transplant Recipient.Daniel E. Leb, M.D., F.A.C.P., Bob S. Kanovitz, M.D., Bernard Weisskopf, M.D.Daniel E. Leb, M.D., F.A.C.P.Search for more papers by this author, Bob S. Kanovitz, M.D.Search for more papers by this author, Bernard Weisskopf, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-805_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo date only five successful pregnancies in renal allograft recipients have been reported. Data on the adverse effects of azathioprine and prednisone on the fetus in the allograft situation is sketchy.Eighteen months before delivery, this 26-year-old white woman received a cadaver kidney transplant after being on hemodialysis. The patient was found to have an entirely normal response to pregnancy. Renal clearance of creatinine increased as would be expected. Late in pregnancy edema, hypertension, and proteinuria developed, suggesting that preeclampsia could occur in the allograft.Immunosuppression continued throughout pregnancy. Azathioprine dosage was reduced from 150 mg/day to 100 mg/day and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Louisville, Ky. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 805-806KeywordsChromosomesCreatinineEdemaFetusesHypertensionPreeclampsiaPregnancyProteinuriaRenal transplantationResearch design ePublished: 1 December 2008 Issue Published: 1 May 1970 PDF downloadLoading ...