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The Australasian Journal of Dermatology May 2022Pemphigus encompasses of a group of rare, and often severe, intraepidermal bullous dermatoses that are mediated by autoantibodies that act against adhesion proteins of... (Review)
Review
Pemphigus encompasses of a group of rare, and often severe, intraepidermal bullous dermatoses that are mediated by autoantibodies that act against adhesion proteins of the desmosome. The current international consensus is that the use of intravenous CD20 inhibitors should be first-line in the management of moderate-to-severe cases of pemphigus, however Australia is yet to adopt this. Systemic corticosteroids, combined with conventional corticosteroid-sparing immunosuppressive agents such as azathioprine, mycophenolate mofetil, cyclosporin and methotrexate is still recommended as first-line therapy in Australia despite overwhelming evidence that combining rituximab with a rapid corticosteroid tapering regime is more effective in the treatment of moderate-to-severe pemphigus, and leads to fewer severe adverse effects. We propose a therapeutic approach that echoes the international consensus and recommend that rituximab, an anti-CD20 monoclonal antibody, be listed in the formularies of Australian Public Hospitals and on the Pharmaceutical Benefits Scheme for use in moderate to severe pemphigus.
Topics: Adrenal Cortex Hormones; Australia; Azathioprine; Humans; Immunosuppressive Agents; Pemphigus; Rituximab
PubMed: 35184283
DOI: 10.1111/ajd.13804 -
Medicina (Kaunas, Lithuania) Dec 2022The pharmacological treatment of systemic lupus erythematosus (SLE) aims to decrease disease activity, progression, systemic compromise, and mortality. Among the... (Review)
Review
The pharmacological treatment of systemic lupus erythematosus (SLE) aims to decrease disease activity, progression, systemic compromise, and mortality. Among the pharmacological alternatives, there are chemically synthesized drugs whose efficacy has been evaluated, but which have the potential to generate adverse events that may compromise adherence and response to treatment. Therapy selection and monitoring will depend on patient characteristics and the safety profile of each drug. The aim of this review is to provide a comprehensive understanding of the most important synthetic drugs used in the treatment of SLE, including the current treatment options (mycophenolate mofetil, azathioprine, and cyclophosphamide), review their mechanism of action, efficacy, safety, and, most importantly, provide monitoring parameters that should be considered while the patient is receiving the pharmacotherapy.
Topics: Humans; Lupus Erythematosus, Systemic; Cyclophosphamide; Azathioprine; Mycophenolic Acid; Immunosuppressive Agents
PubMed: 36676680
DOI: 10.3390/medicina59010056 -
Inflammatory Bowel Diseases Mar 2022Several environmental factors have been implicated in the pathogenesis of inflammatory bowel diseases (IBD); however, the evidence for alcohol is sparse, as is its...
Several environmental factors have been implicated in the pathogenesis of inflammatory bowel diseases (IBD); however, the evidence for alcohol is sparse, as is its implications on disease activity and overall management. Here, we examine the available evidence for the effect of alcohol on IBD, including its association with the development of IBD, role in exacerbations, and potential medication interactions. Several mechanisms have been demonstrated to mediate the effects of ethanol in the gastrointestinal tract. Alcohol has been shown to alter the gut microbiome, disrupt intestinal barrier, and increase intestinal permeability, directly and indirectly promoting immune activation. Conversely, specific alcoholic beverages, notably red wine, may have anti-inflammatory properties capable of assisting in disease control and affecting disease monitoring. Nonetheless, most alcohol-mediated effects seem to facilitate intestinal inflammation and consequently impact disease onset, recurrence, and symptom control. Furthermore, alcohol use interferes with the metabolism of several medications leading to increased side effect profiles or even loss of effect. Notably, mesalamine, azathioprine, methotrexate, and biologic medications can all be affected by concomitant alcohol intake via a variety of mechanisms.
Topics: Azathioprine; Ethanol; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Intestines
PubMed: 33988227
DOI: 10.1093/ibd/izab089 -
International Journal of Rheumatic... Jan 2024Azathioprine hypersensitivity can occasionally present as Sweet-like syndrome, a dose-independent side effect characterized by the unanticipated onset of macules,...
INTRODUCTION
Azathioprine hypersensitivity can occasionally present as Sweet-like syndrome, a dose-independent side effect characterized by the unanticipated onset of macules, papules, and pustules.
CASE PRESENTATION
A 35-year-old woman with systemic lupus erythematosus presented with complaints of generalized maculopapular rash, facial swelling, and bilateral lower extremity edema with a duration of 4 days and a 2-day history of constitutional symptoms within 2 weeks of the beginning of azathioprine therapy to treat existing lupus nephritis (class 2/3).
DISCUSSION
Patients who experience azathioprine hypersensitivity syndrome can present with erythema nodosum, small-vessel vasculitis, acute generalized exanthematous pustulosis, Sweet syndrome, and nonspecific dermatosis. The following signs and symptoms are used as criteria to diagnose drug-induced Sweet syndrome: (a) abrupt onset of painful erythematous plaques, (b) histopathological evidence of dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis, (c) temperature higher than 39.7°C, (d) temporal relationship between drug ingestion and clinical presentation, and (e) temporal resolution of lesions after drug withdrawal. Our patient met three out of five criteria and was diagnosed with Sweet-like syndrome.
CONCLUSION
Our case highlights the uncommonly presented azathioprine-induced Sweet-like syndrome that occurs abruptly after the commencement of the offending drug. This diagnosis can be established through basic laboratory workup and skin biopsy findings.
Topics: Female; Humans; Adult; Azathioprine; Sweet Syndrome; Skin; Lupus Erythematosus, Systemic; Erythema Nodosum
PubMed: 37401805
DOI: 10.1111/1756-185X.14817 -
Revue Medicale Suisse Aug 2022Azathioprine keeps an important place in the treatment of inflammatory bowel disease and autoimmune hepatitis. This molecule has a narrow therapeutic margin, associated...
Azathioprine keeps an important place in the treatment of inflammatory bowel disease and autoimmune hepatitis. This molecule has a narrow therapeutic margin, associated with a risk of toxicity, particularly hematological and hepatic. Its complex metabolism is subject to genetic polymorphisms that are reflected in the inter-individual variability observed in the response to treatment and its tolerance profile. Hence, its use requires a good knowledge of this molecule. Treatment is initiated after a preliminary workup, followed by a progressive titration of the dosage while closely monitoring possible toxicities. Monitoring of blood levels of metabolites (including active ones) helps guide personalized dose adjustment.
Topics: Azathioprine; Gastroenterology; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases
PubMed: 36047549
DOI: 10.53738/REVMED.2022.18.793.1588 -
BMC Gastroenterology Jul 2023Thiopurines continue to play an important role in the treatment of inflammatory bowel disease (IBD). It is well known that thiopurines can cause several adverse...
BACKGROUND
Thiopurines continue to play an important role in the treatment of inflammatory bowel disease (IBD). It is well known that thiopurines can cause several adverse reactions. Especially, hematopoietic toxicity may lead to severe agranulocytosis. In a previous prospective study, we investigated the relationship between inosine triphosphate pyrophosphatase (ITPA) c.94c > a polymorphism, 6-thioguanine nucleotide (6-TGN) concentration and toxicity.
METHODS
To clarify the cause of thiopurine toxicity, we analysed nucleoside disphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphisms, i.e., R139C, V18I, and V19_V19insGV, and measured 6-mercaptopurines and 6-methylmercaptopurines (6-MMP) using the archived blood samples collected from 49 IBD patients for our previous study.
RESULTS
The ITPA c.94c > a polymorphism was detected in 19 patients (38.7%, all heterozygous). The R139C polymorphism was found in 10 patients (20.4%, 1 homozygous, 9 heterozygous), V18_V19insGV in 7 patients (14.3%, all heterozygous), and V18I in 2 patients (4.08%, all heterozygous). Although R139C was more strongly associated with leukopenia than c.94c > a, there were no significant correlations with 6-TGN and 6-MMP levels, as for c.94c > a. The leukopenia incidence rates for each gene polymorphism were 0% in those with all wild-type genes, 21.4% for c.94c > a only, 42.9% for NUDT15 polymorphism (s) only, and 80.0% for both polymorphisms.
CONCLUSIONS
All cases of leukopenia were associated with ITPA c.94c > a and/or polymorphism of NUDT15 and the risk of developing leukopenia was synergistically increased by ITPA and NUDT15 gene polymorphism. However, there was no association between the level of azathioprine metabolites and these polymorphisms.
Topics: Humans; Azathioprine; East Asian People; Inflammatory Bowel Diseases; Leukopenia; Mercaptopurine; Pyrophosphatases
PubMed: 37454061
DOI: 10.1186/s12876-023-02881-6 -
Zeitschrift Fur Gastroenterologie Dec 2014Thiopurines (azathioprine and 6-mercaptopurine) are the most frequently used drugs in the treatment of patients with Crohn's disease. In current guidelines published by... (Review)
Review
Thiopurines (azathioprine and 6-mercaptopurine) are the most frequently used drugs in the treatment of patients with Crohn's disease. In current guidelines published by the German Society of Gastroenterology, Nutritional and Metabolic Diseases (DGVS) in 2014 and by the European Crohn´s and Colitis Organisation (ECCO) in 2010 different indications have been suggested. However, efficacy of azathioprine has been substantially questioned by recent publications in adults as well as in children examining the efficacy of early initiation of this treatment. These articles were published after release of the aforementioned guidelines. Therefore, in this survey recently published data are discussed on the background of our knowledge on the efficacy of azathioprine and 6-mercaptopurine developed in many years, and suggestions for the future use of these substances in the treatment of patients with Crohn's disease will be provided.
Topics: Azathioprine; Crohn Disease; Dose-Response Relationship, Drug; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Practice Guidelines as Topic; Treatment Outcome
PubMed: 25474282
DOI: 10.1055/s-0034-1385650 -
Contact Dermatitis Nov 2023Parthenium dermatitis is the commonest form of plant dermatitis in India, caused by the plant Parthenium hysterophorus. Systemic immunosuppressives are commonly employed... (Meta-Analysis)
Meta-Analysis Review
Parthenium dermatitis is the commonest form of plant dermatitis in India, caused by the plant Parthenium hysterophorus. Systemic immunosuppressives are commonly employed in its treatment. However, there is a relative lack of comparative head-to-head trials. This study was done to assess the relative efficacy and safety of systemic treatments in Parthenium dermatitis. We systematically reviewed all the published studies investigating the safety and efficacy of systemic treatments for Parthenium dermatitis in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and clinical trial registries. Treatment benefit data were tabulated based on outcome measures of scoring systems. The quality of evidence for each outcome was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria for meta-analysis. The pooled Standardized mean difference (SMD) for case series and comparative studies based on clinical severity score (CSS) for azathioprine was 4.007 (95% CI (Confidence interval): 3.141, 4.873) and 0.746 (95% CI: 0.139, 1.352), respectively. About 88.8% (95% CI: 76.8%, 100.8%, p = 0.076) of the patients had excellent or a good response to azathioprine. Our meta-analysis shows that azathioprine has the highest level of evidence in the treatment of Parthenium dermatitis.
Topics: Humans; Azathioprine; Dermatitis, Allergic Contact; Immunosuppressive Agents; Asteraceae; India
PubMed: 37634936
DOI: 10.1111/cod.14406 -
Acta Dermatovenerologica Croatica : ADC Aug 2023Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly...
Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly in flexural areas (1,2). This helps us to differentiate it from PV of Neumann, which is a more extensive and refractory disease, more alike to a pemphigus vulgaris outbreak with blisters which turn into vegetating plaques (3). We report the clinical presentation, course, and therapeutic response in a patient diagnosed with PV of Hallopeau from its early stage during a 3-year follow up. A 62-year-old man, non-smoker, presented at our clinic in July 2018 with hemorrhagic-serous crusts and fissures on the vermilion of the lower lip (Figure 1, a) and two merged circinate, sharply demarcated plaques on the right side of the groin (Figure 1, b). Plaque margins were elevated, with hypertrophic granulation tissue studded with pustules. Mucosal and cutaneous lesions persisted 6 and 4 weeks, respectively. The rest of the mucosa and skin were unaffected; the general state was good. The patient's family history for skin diseases was negative. The medical history included hypertension, atherosclerosis and hypercholesterolemia, hiatus hernia, and recent surgery (3 months prior) of an aortic abdominal aneurysm with reconstruction and synthetic graft placement. He was taking antihypertensives (fixed combination of 3 drugs, among them the ACE-inhibitor perindopril) with well-regulated blood pressure, statins, a pump-proton inhibitor, and acetylsalicylic acid. Differential blood count revealed eosinophilia. Histopathology finding showed acanthosis, suprabasal clefting with a suprabasilar bulla and acantholysis, prominent eosinophilic intraepidermal spongiosis, and heavy dermal infiltration of eosinophils and lymphocytes (Figure 2, a and b). The diagnosis of pemphigus was confirmed by direct immunofluorescence (DIF), which detected C3 deposits on the surface of keratinocytes throughout the epidermis of perilesional skin. Circulating pemphigus antibodies were detected by indirect IF. Only Dsg 3 antibodies were detected using an ELISA assay (233.23 RU/mL). After establishing the diagnosis of PV of Hallopeau, treatment with prednisolone 0.75 mg/kg/day orally in combination with adjuvant immunosuppression (azathioprine 100 mg daily) was started. Appropriate topical therapy with local steroids and antiseptic was applied. The steroid dose was titrated and gradually tapered down to the minimum required to control the disease - 10 mg. One-year remission was achieved. Azathioprine was withdrawn in October 2019 and since then the patient experienced a flare-up twice. The control of pemphigus flare-ups was achieved by a low dose of steroids (30 mg prednisolone orally). It remains debatable whether surgical trauma and radiology procedures such as angiographies (4) well as ACE-inhibitor drugs (5) triggered or aggravated the pemphigus. Early recognition and correct diagnosis of this rare type of pemphigus allows us to treat and control the disease successfully with lower doses of steroids, reducing complications to the minimum.
Topics: Male; Humans; Middle Aged; Pemphigus; Azathioprine; Skin; Eosinophilia; Blister; Prednisolone; Steroids
PubMed: 37843091
DOI: No ID Found -
Taiwanese Journal of Obstetrics &... Sep 2023Azathioprine, a prodrug of 6-mercaptopurine (6-MP), is used in the treatment of inflammatory bowel disease and may be continued during pregnancy. Acute cholestatic liver... (Review)
Review
OBJECTIVE
Azathioprine, a prodrug of 6-mercaptopurine (6-MP), is used in the treatment of inflammatory bowel disease and may be continued during pregnancy. Acute cholestatic liver injury has been reported to occur with azathioprine. We aimed to examine azathioprine related cholestasis effect on pregnancy complications and outcome.
CASE REPORT
We present a unique case of 6-MP-induced severe intrahepatic cholestasis of pregnancy (ICP) that required meticulous combined therapy including plasma exchange. The symptoms resolved following 6-MP withdrawal. A literature review revealed 11 pregnancies complicated by early-induced severe ICP among women treated with azathioprine or 6-MP.
CONCLUSION
We recommend weekly bile acid level tests for pregnant women treated with azathioprine or 6-MP, beginning early in the second trimester of pregnancy, and the prompt discontinuation of treatment upon establishment of an ICP diagnosis.
Topics: Pregnancy; Female; Humans; Azathioprine; Mercaptopurine; Cholestasis, Intrahepatic; Pregnancy Complications
PubMed: 37679010
DOI: 10.1016/j.tjog.2023.07.023