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ACG Case Reports Journal Apr 2024There is a known association between inflammatory bowel disease (IBD) and vasculitis, which can present with mesenteric ischemia or cutaneous manifestations. Infliximab,...
There is a known association between inflammatory bowel disease (IBD) and vasculitis, which can present with mesenteric ischemia or cutaneous manifestations. Infliximab, an anti-tumor necrosis factor (anti-TNF) used to treat IBD, has been implicated as a potential culprit. We present a unique case of a patient with ulcerative colitis who developed isolated celiac artery vasculitis presenting with abdominal pain and ileus after decreasing his dosage of azathioprine. Vasculitis resolved with steroids and increasing azathioprine dosage, while continuing anti-TNF therapy, suggesting that anti-TNF agents are not the only cause of vasculitis in patients with IBD or that thiopurines may be protective.
PubMed: 38638204
DOI: 10.14309/crj.0000000000001335 -
ACG Case Reports Journal Apr 2024Intrahepatic cholestasis of pregnancy is an intrahepatic etiology of acute cholestasis commonly defined by pruritus and increased bile acids, liver transaminases, and,...
Intrahepatic cholestasis of pregnancy is an intrahepatic etiology of acute cholestasis commonly defined by pruritus and increased bile acids, liver transaminases, and, occasionally, bilirubin. Azathioprine is an immunosuppressive agent associated with various forms of hepatoxicity, ranging from transient rises in serum aminotransferase levels, acute cholestatic injury, and chronic hepatic injury. In this report, we present a 20-year-old pregnant woman who presented with cholestatic liver injury due to intrahepatic cholestasis of pregnancy with a clinical picture complicated by increased levels of azathioprine metabolites.
PubMed: 38638198
DOI: 10.14309/crj.0000000000001339 -
Current Allergy and Asthma Reports May 2024Historically, systemic treatments for atopic dermatitis (AD) primarily consisted of immunosuppressive agents such as corticosteroids and Disease Modifying Antirheumatic... (Review)
Review Comparative Study
PURPOSE OF REVIEW
Historically, systemic treatments for atopic dermatitis (AD) primarily consisted of immunosuppressive agents such as corticosteroids and Disease Modifying Antirheumatic Drugs (DMARDS), which provided symptomatic relief but often had long-term adverse effects. Newer treatments have shown significant efficacy with less side effects in clinical trials. This review discusses and compares conventional and newer systemic treatments for AD.
RECENT FINDINGS
Newer medications for AD including dupilumab, tralokinumab, lebrikizumab, and oral JAK inhibitors have been shown to be safe and efficacious. High dose cyclosporine and dupilumab were more effective than methotrexate and azathioprine in improving clinical signs of AD. High-dose upadacitinib was shown in another meta-analysis to be most effective in the measured outcomes but had the highest frequency of adverse events. Targeted biologic treatments are increasingly favored over traditional immunosuppressive treatments of AD. Treatment can be individualized based on potency, adverse side effects, mechanism of action, and administration preference. Ongoing research continues to expand treatment options for AD.
Topics: Dermatitis, Atopic; Humans; Immunosuppressive Agents; Janus Kinase Inhibitors; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Treatment Outcome; Antibodies, Monoclonal; Adrenal Cortex Hormones
PubMed: 38632138
DOI: 10.1007/s11882-024-01145-x -
Journal of Clinical Neurology (Seoul,... May 2024Giant-cell arteritis (GCA) is the most common type of vasculitis in the elderly and is associated with high risks of visual loss and recurrence. Owing to its rarity in...
BACKGROUND AND PURPOSE
Giant-cell arteritis (GCA) is the most common type of vasculitis in the elderly and is associated with high risks of visual loss and recurrence. Owing to its rarity in Asian populations, the current clinical interventions for these patients are not well known. Here we aimed to characterize the current management status of patients with GCA using Korean multicenter data.
METHODS
This retrospective study analyzed medical records of patients with GCA at six Korean university hospitals from February 2009 to November 2022. GCA had originally been diagnosed based on the 1990 American College of Rheumatology (ACR) criteria, and cases were selected for inclusion in this study based on the 2022 ACR/European Alliance of Associations for Rheumatology criteria. We evaluated treatments, follow-up periods, and outcomes (relapse, remission, and adverse drug reactions) in patients with GCA with or without arteritic anterior ischemic optic neuropathy (AAION).
RESULTS
This study analyzed 18 patients with a median age of 75.5 years that included 12 females (66.7%). Seven patients (38.8%) had AAION. All patients initially received prednisolone treatment, while four (22.2%) underwent adjuvant treatment with methotrexate and azathioprine during prednisolone tapering. During the median follow-up of 3.5 months (interquartile range: 2.0-23.2 months), 4 patients (22.2%) had prednisolone-related adverse reactions, 2 (11.1%) relapsed, and 13 (72.3%) dropped out. Nine patients (50.0%) experienced remission, with this being sustained in four (36.4%).
CONCLUSIONS
This study observed high dropout rates and short follow-ups. Adverse effects of prednisolone were common, and relapses occurred in approximately one-tenth of Korean patients with GCA. Thus, optimizing GCA treatment necessitates regular monitoring and long-term follow-up.
PubMed: 38627226
DOI: 10.3988/jcn.2023.0169 -
Neuromuscular Disorders : NMD May 2024Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as...
Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.
Topics: Humans; Myasthenia Gravis; Methotrexate; Female; Mycophenolic Acid; Azathioprine; Immunosuppressive Agents; Male; Middle Aged; Adult; Aged; United Kingdom
PubMed: 38626662
DOI: 10.1016/j.nmd.2024.03.010 -
Rheumatology International Jun 2024Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with... (Comparative Study)
Comparative Study
BACKGROUND/OBJECTIVES
Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with antirheumatic medications, this study aims to analyse and compare ADR reporting for these drugs in the pharmacovigilance datasets of Western Australia (WA) and the United States (US).
METHODS
Therapeutic Goods Administration provided WA pharmacovigilance data of selected antirheumatic drugs to from 1995 to 2015. The proportional reporting ratio (PRR) for WA case reports was compared to corresponding USA pharmacovigilance data by assessing the disproportionality of each ADR. clinically significant or true ADRs were determined using the Evans 2001 criteria (n > 2, chi-square > 4, PRR > 2).
RESULTS
A total of 232 reports were found in WA, mostly on sixty-nine women aged 45 to 69. Methotrexate, leflunomide, azathioprine, sulfasalazine, and infliximab had the highest reported ADRs, related to gastrointestinal disorders. Patients who used biological agents in WA had 2.7 times the likelihood of reporting true ADRs compared to conventional antirheumatic drugs. The ADR rates in the two datasets were comparable over the study period.
CONCLUSIONS
The PRR values of ADRs were consistent between WA and US databases. Methotrexate and infliximab use were commonly associated with ADR reports in WA females, with incidence rates comparable to the US; while patients using biological agents were more likely to report true ADRs than those on conventional antirheumatic drugs in WA.
Topics: Humans; Female; Antirheumatic Agents; Western Australia; Middle Aged; Retrospective Studies; Pharmacovigilance; Aged; Male; Adverse Drug Reaction Reporting Systems; Adult; Drug-Related Side Effects and Adverse Reactions; Databases, Factual; United States; Time Factors; Young Adult
PubMed: 38615313
DOI: 10.1007/s00296-024-05588-3 -
Journal of Community Hospital Internal... 2023Patients with granulomatous disease often have widespread pulmonary and extrapulmonary disease. In the absence of this, a search of the pulmonary, renal, hepatic,...
Patients with granulomatous disease often have widespread pulmonary and extrapulmonary disease. In the absence of this, a search of the pulmonary, renal, hepatic, ocular, and bone marrow is warranted in the setting of hypercalcemia with unexplained elevated 1,25-dihydroxyvitamin D, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). We present a case of hypercalcemia and a decline in renal function in a patient with bone marrow sarcoidosis. A 45-year-old woman was admitted to the hospital after hypercalcemia, acute kidney injury, and pancytopenia were found on a routine outpatient lab. She was discharged after improvement with IV fluids. She had interval worsening of hypercalcemia and was readmitted within a week for pamidronate treatment. Imaging and labs were concerning for sarcoidosis, but bronchoscopy with biopsy was nondiagnostic. Eventual bone marrow biopsy confirmed evidence of granulomas. Her condition improved with prednisone over 3 months and ultimately, azathioprine. Non-parathyroid hormone-mediated hypercalcemia should be thoroughly worked up for a source to rule out malignancy and to diagnose treatable causes such as sarcoidosis. Sarcoidosis may not present in its traditional pulmonary pattern, necessitating further diagnostic measures such as a bone marrow biopsy.
PubMed: 38596540
DOI: 10.55729/2000-9666.1257 -
Journal of Gastroenterology Jun 2024This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world...
BACKGROUND
This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies.
METHODS
A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status.
RESULTS
Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users.
CONCLUSIONS
NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.
Topics: Humans; Pyrophosphatases; Female; Male; Retrospective Studies; Adult; Middle Aged; Mercaptopurine; Genotype; Inflammatory Bowel Diseases; Japan; Azathioprine; Young Adult; Aged; Immunosuppressive Agents; Adolescent; Risk Factors; Codon; Nudix Hydrolases
PubMed: 38589597
DOI: 10.1007/s00535-024-02099-7 -
European Journal of Case Reports in... 2024Most pregnancies in women after a kidney transplant result in a live birth, but kidney functions should be stable for one year before conception. For immunosuppression...
INTRODUCTION
Most pregnancies in women after a kidney transplant result in a live birth, but kidney functions should be stable for one year before conception. For immunosuppression modification occurring before pregnancy, azathioprine is used because it is considered safe for major congenital malformations during pregnancy. However, there may be an association between exposure to azathioprine during pregnancy and the onset of an unusual, early and severe form of intrahepatic cholestasis.
CASE DESCRIPTION
A young patient with a twin pregnancy after a second kidney transplant experienced intrahepatic cholestasis. There was a wide range of differential diagnosis. A battery of tests was requested including autoimmune markers, virology, and imaging. The conclusion that azathioprine was contributing to intrahepatic cholestasis with pregnancy was reached after exclusion of all other differentials.
CONCLUSIONS
Complications of pregnancy after a kidney transplant include hypertension, pre-eclampsia, deterioration of graft function up to rejection, but also unusual side effects of immunosuppression medication.
LEARNING POINTS
A twin pregnancy after a second kidney transplant is rare.In addition to bone marrow suppression and elevation of liver enzymes, azathioprine can contribute to intrahepatic cholestasis of pregnancy.Complications of pregnancy after kidney transplant include hypertension, pre-eclampsia, deterioration of graft function up to rejection, but also unusual side effects of immunosuppression medication.
PubMed: 38584904
DOI: 10.12890/2024_004385 -
Annals of Medicine and Surgery (2012) Apr 2024Dermatomyositis (DM), sometimes referred to as inflammatory and degenerative changes in the skin and muscles, is a rare autoimmune disorder. DM is distinguished by...
INTRODUCTION AND IMPORTANCE
Dermatomyositis (DM), sometimes referred to as inflammatory and degenerative changes in the skin and muscles, is a rare autoimmune disorder. DM is distinguished by myopathic disease, symmetrical proximal muscle weakness, and increased creatine kinase (CK).
CASE PRESENTATION
A 30-year-old-female presented to the department of dermatology with a history of chronic right hand pain spreading to the shoulder, severe tachycardia, and dyspenia that increased during routine tasks like using the bathroom. What makes this case unique is that the CPK developed without doubling, and the final concentration was 207 ng/ml. Other common clinical symptoms include amyopathic/hypomyopathic muscle involvement and DM-specific rash (Gottron's papules, heliotrope rash), and these manifestations were in our patients. Sun protection, topical treatment with corticosteroids and/or calcineurin inhibitors, and systemic medication should be utilized for all individuals with nonvasculopathic disease. In our case, the patient stopped using azathioprine and began taking methotrexate.
CLINICAL DISCUSSION
Sun protection, topical therapy with corticosteroids and/or calcineurin inhibitors, and systemic medication should be utilized in layers for all individuals with nonvasculopathic illnesses. Mycophenolat Mofetil is beneficial in treating refractory illnesses as well as individuals with interstitial lung disease or substantial skin disease.
CONCLUSION
Even if test findings are not conclusive, dermatomyositis should always be considered when muscular weakness manifests. It's important to distinguish the disorder from connective tissue diseases like lupus erythematosus. In fact, to correctly diagnose DM, if there are any doubts, a muscle biopsy is required.
PubMed: 38576947
DOI: 10.1097/MS9.0000000000001682