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Cureus May 2024Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study... (Review)
Review
Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study aims to evaluate the efficacy of using corticosteroids (prednisolone and azathioprine) as a combination therapy in treating AIH. This study aims to synthesize and analyze existing evidence to inform clinical practices concerning the overall clinical efficacy of this treatment approach in managing AIH. A comprehensive search was conducted across multiple online databases and search engines, including PubMed, Google Scholar, ScienceDirect, Medline, and Embase. RevMan 5.4 software was used for meta-analysis, with forest plots created for each outcome. Thirteen studies were included in this systematic review and meta-analysis. The results indicate that the combination of prednisolone and azathioprine for treating AIH leads to less recurrence and better disease control.
PubMed: 38854256
DOI: 10.7759/cureus.60049 -
Sarcoidosis, Vasculitis, and Diffuse... Dec 2023Sarcoidosis is a multisystem chronic inflammatory disease predominantly affecting the lungs. Myositis as a presenting manifestation of sarcoidosis is extremely uncommon...
Sarcoidosis is a multisystem chronic inflammatory disease predominantly affecting the lungs. Myositis as a presenting manifestation of sarcoidosis is extremely uncommon and seldom reported. Here we report a 20-year-old male who presented with bilateral calf pain for six months. On evaluation magnetic resonance imaging showed features of myositis, and muscle biopsy was suggestive of sarcoidosis with granulomatous vasculitis. Positron emission tomography-computed tomography scan revealed involvement of spleen in addition to the muscles. Patient was managed with corticosteroids and azathioprine, and showed good treatment response.
PubMed: 38126505
DOI: 10.36141/svdld.v40i4.14004 -
Journal of Crohn's & Colitis Aug 2023Despite its efficacy, rational guidance for starting/stopping first-line biologic treatment in individual paediatric Crohn's disease [CD] patients is needed. We assessed... (Randomized Controlled Trial)
Randomized Controlled Trial
Serum Immune Profiling in Paediatric Crohn's Disease Demonstrates Stronger Immune Modulation With First-Line Infliximab Than Conventional Therapy and Pre-Treatment Profiles Predict Clinical Response to Both Treatments.
BACKGROUND
Despite its efficacy, rational guidance for starting/stopping first-line biologic treatment in individual paediatric Crohn's disease [CD] patients is needed. We assessed how serum immune profiles before and after first-line infliximab [FL-IFX] or conventional [CONV] induction therapy associate with disease remission at week 52.
METHODS
Pre- [n = 86], and 10-14-week post-treatment [n = 84] sera were collected from patients with moderate-to-severe paediatric CD in the TISKids trial, randomized to FL-IFX [n = 48; five 5-mg/kg infusions over 22 weeks] or CONV [n = 43; exclusive enteral nutrition or oral prednisolone]; both groups received azathioprine maintenance. The relative concentrations of 92 inflammatory proteins were determined with Olink Proteomics; fold changes [FC] with |log2FC| > 0.5 after false discovery rate adjustment were considered significant.
RESULTS
FL-IFX modulated a larger number of inflammatory proteins and induced stronger suppression than CONV; 18/30 proteins modulated by FL-IFX were not regulated by CONV. Hierarchical clustering based on IFX-modulated proteins at baseline revealed two clusters of patients: CD-hi patients had significantly higher concentrations of 23/30 IFX-modulated proteins [including oncostatin-M, TNFSF14, HGF and TGF-α], and higher clinical disease activity, C-reactive protein and blood neutrophils at baseline than CD-lo patients. Only 24% of CD-hi FL-IFX-treated patients maintained remission without escalation at week 52 vs 58% of CD-lo FL-IFX-treated patients. Similarly, 6% of CD-hi CONV-treated patients achieved remission vs 20% of CONV-treated CD-lo patients. Clustering based on immune profiles post-induction therapy did not relate to remission at week 52.
CONCLUSION
FL-IFX leads to stronger reductions and modulates more immune proteins than CONV. Stratification on pre-treatment profiles of IFX-modulated proteins directly relates to maintenance of remission without treatment escalation.
TRIAL REGISTRATION NUMBER
NCT02517684.
Topics: Child; Humans; Infliximab; Crohn Disease; Azathioprine; C-Reactive Protein; Remission Induction; Treatment Outcome; Gastrointestinal Agents
PubMed: 36934327
DOI: 10.1093/ecco-jcc/jjad049 -
Neurology India Jan 2024Infection is an important trigger of myasthenic crisis (MC), and those infections manifest with pneumonia and muscle involvement may result in more frequent MC. We...
Infection is an important trigger of myasthenic crisis (MC), and those infections manifest with pneumonia and muscle involvement may result in more frequent MC. We report two myasthenia gravis (MG) patients with H1N1 infection, and highlight the reasons for deterioration. Two patients with MG had H1N1 infection. The diagnosis of MG was confirmed by neostigmine, repetitive nerve stimulation, and anti-acetylcholine receptor antibody tests. H1N1 was confirmed by nucleic acid detection study, and myositis by creatinine kinase. The patient with pneumonia and myositis had MC needing mechanical ventilation for 10 days, and the other patient without myositis did not have MC. They were treated with oseltamivir 75 mg twice daily for 5 days, and the patients with MC received ceftriaxone intravenously. Both the patients were on prednisolone and azathioprine, and none received prior H1N1 vaccination. The lady with MC with myositis was discharged on day 27 in wheelchair bound state, and the other one patient without myositis or MC was discharged on 6th day with full recovery. These patients highlight the need for evaluation for myositis along with pneumonia in the MG patients with H1N1 infection. Vaccination in MG patients on immunosuppression may be useful.
Topics: Humans; Influenza A Virus, H1N1 Subtype; Myasthenia Gravis; Myositis; Neostigmine; Pneumonia
PubMed: 38443018
DOI: 10.4103/neuroindia.NI_482_19 -
Sarcoidosis, Vasculitis, and Diffuse... Dec 2023Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare multi-system conditions, usually presenting in older age groups. However, younger...
BACKGROUND AND AIM
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare multi-system conditions, usually presenting in older age groups. However, younger individuals are also affected. The average increase of childbearing age and lack of studies in pregnancy necessitates this comprehensive review of data to guide the management of AAV in pregnancy. This systematic review (SR) aimed to summarise the incidence, clinical features, management and maternal and foetal outcomes in female patients with AAV.
METHODS
The protocol was registered on PROSPERO (CRD42023437482). Articles published in Medline, Embase and Cochrane Databases from 1946 until June 2023 were included. Single case reports, reviews and conference abstracts were excluded. Articles meeting inclusion criteria were examined by two authors. Data on demographics, treatment, clinical features, flares during pregnancy and maternal and foetal outcomes were extracted.
RESULTS
Eight studies were included, detailing 82 pregnancies in 64 women. The most common drugs used for remission induction pre-conception were cyclophosphamide, rituximab, prednisolone and azathioprine. Serious maternal complications in pregnancy included progressive tracheal/subglottic stenosis (n=5), renal disease (n=2), preeclampsia (n=10) and miscarriages (n=5). Foetal anomalies were rare (n=5). The mean birth weight was 3.37kgs and mean gestation age was 38.26 weeks. No maternal deaths or vasculitis in newborns were reported. Conclusions: Patients can have positive maternal and foetal outcomes following strong induction therapy, vigorous monitoring and prompt treatment of flares during pregnancy. Serious complications and flares are not associated with worse outcomes for newborns.
PubMed: 38126499
DOI: 10.36141/svdld.v40i4.15094 -
Indian Journal of Gastroenterology :... Feb 2024Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn's disease (CD) and... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn's disease (CD) and ulcerative colitis (UC). Historically, IBD has been primarily reported in western countries, but over the past decades, its prevalence is rapidly increasing, especially in lower and middle-income countries (LMICs) such as India and China and also in Sub-Saharan Africa. The prevalence of IBD in LMICs has been the subject of growing concern due to the impact of access to public healthcare and the burden it places on healthcare resources. The classical thiopurines face significant challenges due to cessation of therapy in approximately half of patients within one year due to side effects or ineffectiveness. In this article, we highlight innovating thiopurine treatment for IBD patients in downregulating side effects and improving efficacy.
Topics: Humans; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Mercaptopurine; Azathioprine; Immunosuppressive Agents; Purines; Sulfhydryl Compounds
PubMed: 38383877
DOI: 10.1007/s12664-024-01529-x -
Frontiers in Neurology 2023Satralizumab, a monoclonal antibody that recognizes interleukin-6 receptors, is known to reduce the relapse rate in neuromyelitis optica spectrum disorder (NMOSD), but...
BACKGROUND
Satralizumab, a monoclonal antibody that recognizes interleukin-6 receptors, is known to reduce the relapse rate in neuromyelitis optica spectrum disorder (NMOSD), but its safety during pregnancy has not been established. We present the case of an NMOSD patient who safely completed pregnancy, parturition, and breastfeeding under satralizumab treatment. Importantly, satralizumab transfer to umbilical cord blood, infant serum, or breast milk was not observed.
CASE PRESENTATION
A 37-year-old Japanese female developed anti-aquaporin 4 antibody-positive NMOSD with left optic neuritis. Despite responding to steroid and azathioprine therapy, she experienced moon face and weight gain and desired the prompt reduction of the steroid dosage. She also wanted to conceive a child with a safe and preferably early pregnancy and parturition. Because pregnancy and parturition after the onset of NMOSD elevate the risk of relapse and miscarriage, treatment with satralizumab was initiated with the patient's consent. She experienced normal parturition and continued with satralizumab, steroid, and azathioprine treatments while breastfeeding without experiencing any relapses. Concentrations of satralizumab in the umbilical cord blood, infant serum, and breast milk were below the detection sensitivity.
CONCLUSION
These findings suggest that satralizumab may be safe and effective for the perinatal management of NMOSD, especially when there are concerns about continuing pregnancy and the risk of relapse after parturition.
PubMed: 38162440
DOI: 10.3389/fneur.2023.1322412 -
Metabolites Oct 2023Tioguanine is metabolised by fewer enzymatic steps compared to azathioprine and mercaptopurine, without generating 6-methylmercaptopurine ribonucleotides. However,...
Tioguanine is metabolised by fewer enzymatic steps compared to azathioprine and mercaptopurine, without generating 6-methylmercaptopurine ribonucleotides. However, thiopurine S-methyl transferase (TPMT) plays a role in early toxicity in all thiopurines. We aimed to describe the hazards and opportunities of tioguanine use in inflammatory bowel disease (IBD) patients with aberrant TPMT metabolism and propose preventative measures to safely prescribe tioguanine in these patients. In this retrospective cohort study, all determined genotypes (2016-2021) were evaluated for aberrant metabolism (i.e., intermediate and poor TPMT metabolisers). Subsequently, all IBD patients on tioguanine with aberrant genotypes were evaluated for tioguanine dosages, adverse drug events, lab abnormalities, treatment duration and effectiveness. genotypes were determined in 485 patients, of whom, 50 (10.3%) and 4 patients (0.8%) were intermediate and poor metabolisers, respectively. Of these patients, 12 intermediate and 4 poor TPMT metabolisers had been prescribed tioguanine in varying doses. In one poor TPMT metaboliser, tioguanine 10 mg/day induced delayed pancytopenia. In general, reduced tioguanine dosages of 5 mg/day for intermediate TPMT metabolisers, and 10 mg two-weekly for poor TPMT metabolisers, resulted in a safe, long-term treatment strategy. Diminished or absent TPMT enzyme activity was related with a pharmacokinetic shift of tioguanine metabolism which is associated with relatively late-occurring myelotoxicity in patients on standard tioguanine dose. However, in strongly reduced dose regimens with strict therapeutic drug and safety monitoring, tioguanine treatment remained a safe and effective option in IBD patients with dysfunctional TPMT.
PubMed: 37887379
DOI: 10.3390/metabo13101054 -
Italian Journal of Dermatology and... Feb 2024Atopic dermatitis (AD) is the most common dermatological diagnosis during pregnancy. Treatment of AD during pregnancy can be challenging, due to the unpredictable course...
Atopic dermatitis (AD) is the most common dermatological diagnosis during pregnancy. Treatment of AD during pregnancy can be challenging, due to the unpredictable course and the fact that the therapy needs to be safe for both the mother and the fetus. Here we present an up-to-date appraisal of the literature on the treatment options available for AD in patients planning pregnancy, during pregnancy, and during breastfeeding. All patients with AD are recommended to supplement any medical treatment with daily applications of emollients. The first step in the medical treatment for AD during pregnancy are topical corticosteroids, and/or topical tacrolimus. If required, UV-light therapy can also be considered. Treatment with systemic therapy during pregnancy should always rely on a careful risk-benefit assessment and be based on shared-decision making between the treating physician and patient. The first-line systemic treatment option is cyclosporine A, whereas azathioprine may be considered in patients already receiving this treatment prior to pregnancy. Systemic glucocorticoids may also be used. Treatment with systemic JAK inhibitors is not recommended, whereas treatment with mycophenolate mofetil and methotrexate is contraindicated. Targeted therapy with dupilumab is not generally recommended, due to lack of experience in human pregnancies, yet some case-reports on their use are emerging. These recommendations are based on the authors appraisal of existing literature and the current recommendation from the European Task Force on Atopic Dermatitis. It is always the responsibility of the treating physician to stay updated on the newest guidelines and literature when treating patients with AD during pregnancy.
Topics: Pregnancy; Female; Humans; Dermatitis, Atopic; Immunosuppressive Agents; Cyclosporine; Methotrexate; Dermatologic Agents; Glucocorticoids
PubMed: 38226937
DOI: 10.23736/S2784-8671.23.07692-2 -
Pharmaceuticals (Basel, Switzerland) Jan 2024The use of azathioprine (AZA) in human medicine dates back to research conducted in 1975 that led to the development of several drugs, including 6-mercaptopurine. In... (Review)
Review
The use of azathioprine (AZA) in human medicine dates back to research conducted in 1975 that led to the development of several drugs, including 6-mercaptopurine. In 1958, it was shown that 6-mercaptopurine decreased the production of antibodies against earlier administered antigens, raising the hypothesis of an immunomodulatory effect. AZA is a prodrug that belongs to the thiopurine group of drugs that behave as purine analogs. After absorption, it is converted into 6-mercaptopurine. Subsequently, it can be degraded through various enzymatic pathways into inactive compounds and biologically active compounds related to the mechanism of action, which has been the subject of study to evaluate a possible antiviral effect. This study aims to examine the metabolism, mechanism of action, and antiviral potential of AZA and its derivatives, exploring AZA impact on antiviral targets and adverse effects through a narrative literature review. Ultimately, the review will provide insights into the antiviral mechanism, present evidence of its in vitro effectiveness against various DNA and RNA viruses, and suggest in vivo studies to further demonstrate its antiviral effects.
PubMed: 38399389
DOI: 10.3390/ph17020174