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Modern Rheumatology Sep 2020Relapsing polychondritis (RP) is a rare auto-immune disease that causes progressive destruction of cartilaginous structures. Most cases of pediatric-onset RP were... (Review)
Review
Relapsing polychondritis (RP) is a rare auto-immune disease that causes progressive destruction of cartilaginous structures. Most cases of pediatric-onset RP were published as a single case report or hand-full case series although the prevalence of RP is unknown. This review aimed to describe the characteristics of pediatric-onset RP in order to provide a comparison between childhood and adulthood features of the disease and to review the experiences of biological agents used in children with RP. In children, the diagnosis of RP is either delayed or overlooked due to low incidence and variability in clinical features. Treatment of RP is challenging due to the recurrent episodic nature of the disease. Different immunosuppressive medications, including steroid and steroid-sparing disease-modifying antirheumatic drugs (DMARDs), such as methotrexate or azathioprine, are used to treat RP. There is no rigorous clinical research to support the use of new therapeutic modalities, including biological agents. It is challenging to protocolize the treatment of pediatric-onset RP due to the rarity of the disease. Corticosteroids are the primary form of therapy. However, DMARDs and biological agents may have a role in treating patients with sustained or refractory disease.
Topics: Adolescent; Adrenal Cortex Hormones; Antirheumatic Agents; Azathioprine; Child; Delayed Diagnosis; Humans; Methotrexate; Polychondritis, Relapsing
PubMed: 31858851
DOI: 10.1080/14397595.2019.1707995 -
Journal of Hepatology Apr 2019Autoimmune hepatitis is a corticosteroid-responsive liver disease arising consequent to immunogenetic and environmental risk factors. The clinical course reflects... (Review)
Review
Autoimmune hepatitis is a corticosteroid-responsive liver disease arising consequent to immunogenetic and environmental risk factors. The clinical course reflects relapsing and remitting, hepatocyte targeted immunologic damage, which is countered by reparative responses to cell injury. Appropriate and timely immunosuppressive therapy drives the disease into remission, albeit with inevitable side effects. Many challenges faced in the clinic reflect practice that must capture a heterogeneous disease presentation, course, and treatment response, as well as treatment tolerability. In this Grand Round we appraise the evidence supporting current treatment approaches, address the impact of autoimmune liver disease 'crossover or overlap' presentations, explore important clinical correlates to immune-serological classifiers, and discuss the factors influencing choice of alternative therapy in difficult-to-treat situations.
Topics: Adolescent; Adult; Anti-Inflammatory Agents; Azathioprine; Clinical Decision-Making; Complementary Therapies; Drug Tolerance; Female; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Male; Precision Medicine; Prednisolone; Recurrence; Risk Factors; Treatment Outcome; Young Adult
PubMed: 30465775
DOI: 10.1016/j.jhep.2018.11.006 -
Dermatologic Therapy Jan 2021Azathioprine, a purine synthesis inhibitor is widely used as an effective immunosuppressant in several immune mediated diseases, usually in a dose of 2 to 2.5 mg/kg per... (Review)
Review
Azathioprine, a purine synthesis inhibitor is widely used as an effective immunosuppressant in several immune mediated diseases, usually in a dose of 2 to 2.5 mg/kg per day. The pulse dose of azathioprine is an unique once weekly dosing regimen, which has been used as an alternative to daily dose regimen in some immune mediated dermatologic disorders. In this review, we looked at a specific dosing regimen, "weekly azathioprine pulse" with respect to its efficacy and safety in the treatment of dermatologic diseases. We performed a literature search for studies on azathioprine weekly pulse in dermatology in various scientific databases using keywords "azathioprine-pulse", "dermatology", "weekly azathioprine", and so on. Dosing regimens, indications, efficacy, monitoring, and side effect profile as described in these studies were recorded. Evidence level of the regimens used in various indications was also calculated. We could find six published studies using azathioprine weekly pulse, of which three were randomized comparative clinical trials. Azathioprine pulse was administered in a dose of 300 mg (6 tablets of 50 mg each) every week in all the studies. It has been found to be effective in management of contact dermatitis due to parthenium (IB), chronic plaque psoriasis (IIB), and alopecia areata (IB). Adverse effect profile was found to be almost similar to daily azathioprine. Weekly azathioprine pulse, therefore, appears to be an effective and safe alternative to daily azathioprine in the management of immune mediated disorders in dermatology. Although studies are limited, this regimen seems promising and further studies are warranted.
Topics: Azathioprine; Humans; Immunosuppressive Agents; Psoriasis
PubMed: 33166048
DOI: 10.1111/dth.14513 -
Interdisciplinary Sciences,... Jun 2016Thiopurine methyltransferase (TPMT) is a cytoplasmic transmethylase present in both prokaryotes and eukaryotes. In humans, it shows its presence in almost all of the... (Review)
Review
Thiopurine methyltransferase (TPMT) is a cytoplasmic transmethylase present in both prokaryotes and eukaryotes. In humans, it shows its presence in almost all of the tissues, predominantly in liver and kidney. TPMT is one of the important metabolic enzymes of phase II metabolic pathway and catalyzes methylation of thiopurine drugs such as azathioprine, 6-thioguanine and 6-mercaptopurine, which are used to treat patients with neoplasia and autoimmune disease as well as transplant recipients. In this sense, TPMT acts as shield against toxic effect of these drugs. Pharmacogenomic studies revealed that genetic polymorphism in TPMT is responsible for variable and, in some cases, adverse drug reaction. Those human groups who carry variants of TPMT (i.e., [Formula: see text], [Formula: see text], [Formula: see text]) are at high risk, because they are unable to metabolize thiopurine drugs thus becoming a weakness of patients against these drugs. Keeping in the mind the importance of TPMT, this review discusses the existence and distribution of various TPMT variants throughout different ethnic groups and risk of adverse drug reactions to them, and how they can avoid this risk of side effects. The review also highlighted factors responsible for variable reactions of TPMT, how this TPMT polymorphism can be considered in drug designing process to avoid toxic effects, designing precautions against them and more importantly designing personalized medicine.
Topics: Animals; Azathioprine; Drug Design; Humans; Mercaptopurine; Methyltransferases; Polymorphism, Genetic; Thioguanine
PubMed: 26297310
DOI: 10.1007/s12539-015-0111-1 -
International Journal of Molecular... Nov 2022Azathioprine (AZA) is a pharmacologic immunosuppressive agent administrated in various conditions such as autoimmune disease or to prevent the rejection of organ...
Azathioprine (AZA) is a pharmacologic immunosuppressive agent administrated in various conditions such as autoimmune disease or to prevent the rejection of organ transplantation. The mechanism of action is based on its biologically active metabolite 6-mercaptopurine (6-MP), which is converted, among others, into thioguanine nucleotides capable of incorporating into replicating DNA, which may act as a strong UV chromophore and trigger DNA oxidation. The interaction between azathioprine and DNA, before and after exposure to solar simulator radiation, was investigated using UV-vis spectrometry and differential pulse voltammetry at a glassy carbon electrode. The results indicated that the interaction of AZA with UV radiation was pH-dependent and occurred with the formation of several metabolites, which induced oxidative damage in DNA, and the formation of DNA-metabolite adducts. Moreover, the viability assays obtained for the L929 cell culture showed that both azathioprine and degraded azathioprine induced a decrease in cell proliferation.
Topics: Azathioprine; Photolysis; Mercaptopurine; DNA; Immunosuppressive Agents; DNA Adducts
PubMed: 36430909
DOI: 10.3390/ijms232214438 -
Current Rheumatology Reports Oct 2023Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies. (Review)
Review
PURPOSE OF REVIEW
Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies.
RECENT FINDINGS
Recently performed clinical trials and observational cohort studies underscore the high frequency of relapses of kidney disease, following initial response, in patients with proliferative and/or membranous lupus nephritis. Analysis of hard disease outcomes such as progression to chronic kidney disease or end-stage kidney disease, coupled with histological findings from repeat kidney biopsy studies, have drawn attention to the importance of renal function preservation that should be pursued as early as lupus nephritis is diagnosed. In this respect, non-randomized and randomized evidence have suggested a number of factors associated with reduced risk of renal flares such as attaining a very low level of proteinuria (< 700-800 mg/24 h by 12 months), using mycophenolate over azathioprine, adding belimumab to standard therapy, maintaining immunosuppressive/biological treatment for at least 3 to 5 years, and using hydroxychloroquine. Other factors that warrant further clarification include serological activity and the use of repeat kidney biopsy to guide the intensity and duration of treatment in selected cases. The results from ongoing innovative studies integrating kidney histological and clinical outcomes, together with an expanding spectrum of therapies in lupus nephritis, are expected to facilitate individual medical care and long-term disease and patient prognosis.
Topics: Humans; Lupus Nephritis; Immunosuppressive Agents; Azathioprine; Kidney; Risk Factors
PubMed: 37452914
DOI: 10.1007/s11926-023-01109-6 -
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 -
Saudi Journal of Gastroenterology :... 2022Methotrexate is an antineoplastic agent that is also used at lower doses for anti-inflammatory properties. Along with thiopurines (azathioprine and 6-mercaptopurine), it... (Review)
Review
Methotrexate is an antineoplastic agent that is also used at lower doses for anti-inflammatory properties. Along with thiopurines (azathioprine and 6-mercaptopurine), it has historically been an important part of pharmacological treatment for patients with inflammatory bowel disease. Despite an increase in therapeutic options, these immunomodulators continue to play important roles in the management of inflammatory bowel disease, used either as a monotherapy in mild to moderate cases or in combination with monoclonal antibodies to prevent immunogenicity and maintain efficacy. In light of data linking the use of thiopurines with the risk of malignancies, methotrexate has regained attention as a potential alternative. In this article, we review data on the pharmacology, safety, and efficacy of methotrexate and discuss options for the positioning of methotrexate alone, or in combination, in therapeutic algorithms for Crohn's disease and ulcerative colitis.
Topics: Azathioprine; Colitis, Ulcerative; Gastroenterologists; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Methotrexate
PubMed: 35042318
DOI: 10.4103/sjg.sjg_496_21 -
Revista Espanola de Enfermedades... May 2021Chronic diarrhea is a common symptom seen in the Gastroenterology clinic. Occasionally, the diagnosis is a real challenge as there are multiple entities with unremitting...
Chronic diarrhea is a common symptom seen in the Gastroenterology clinic. Occasionally, the diagnosis is a real challenge as there are multiple entities with unremitting diarrhea as a symptom. Herein, we present a patient affected with intractable diarrhea who was transferred to our department. After many laboratory, endoscopy and radiological tests, she was diagnosed with autoimmune enteropathy (AE) and achieved clinical remission with corticosteroids and azathioprine.
Topics: Azathioprine; Diarrhea; Female; Humans; Polyendocrinopathies, Autoimmune
PubMed: 33256418
DOI: 10.17235/reed.2020.7218/2020 -
Dermatologic Therapy Sep 2022Most patients with atopic dermatitis (AD) have a good response to topical treatment. However, some need systemic therapy in order to satisfactorily control the disease.... (Review)
Review
Most patients with atopic dermatitis (AD) have a good response to topical treatment. However, some need systemic therapy in order to satisfactorily control the disease. Azathioprine is an accessible drug for patients in many countries, including underdeveloped countries, and therefore it is used by many dermatologists in moderate and severe AD. It is important to have a deep knowledge and understanding about this drug since it is an alternative therapy as a steroid-sparing agent and an affordable one. However, when it comes to systemic therapy for AD, it is not always clear its indications and it is necessary to have a closer follow-up of the patient. In this paper, we describe thoroughly its indications in AD, the mechanism of action of the drug, as well as the interactions, adverse effects, adequate monitoring, and precautions in special population that must be considered when prescribing azathioprine. This review will help dermatologists prescribe it safely to all patients who require it.
Topics: Azathioprine; Dermatitis, Atopic; Drug-Related Side Effects and Adverse Reactions; Humans; Immunosuppressive Agents
PubMed: 35751547
DOI: 10.1111/dth.15665