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Neurology(R) Neuroimmunology &... Nov 2023Autoimmune encephalitis (AE) refers to a heterogenous group of inflammatory CNS diseases. Subgroups with specified neural autoantibodies are more homogeneous in...
BACKGROUND AND OBJECTIVES
Autoimmune encephalitis (AE) refers to a heterogenous group of inflammatory CNS diseases. Subgroups with specified neural autoantibodies are more homogeneous in presentation, trigger factors, outcome, and response to therapy. However, a considerable fraction of patients has AE features but does not harbor detectable autoantibodies and is referred to as antibody-negative AE. Our aim was to describe clinical features, trigger factors, treatments, and outcome of a cohort of comprehensively tested antibody-negative AE patients.
METHODS
This retrospective monocentric study recruited adult patients whose serum and/or CSF was sent to our tertiary center for neural antibody testing between 2011 and 2020, who entered the diagnostic algorithm as possible antibody-negative AE and had the following: (1) probable antibody-negative AE, definite antibody-negative acute disseminated encephalomyelitis (ADEM), or definite autoimmune limbic encephalitis (LE) according to diagnostic criteria; (2) available data on MRI of the brain, CSF, and EEG; and (3) stored serum and/or CSF samples. These samples were reanalyzed using a comprehensive combination of cell-based and tissue-based assays.
RESULTS
Of 2,250 patients tested, 33 (1.5%) were classified as possible antibody-negative AE. Of these, 5 were found to have antibodies by comprehensive testing, 5 fulfilled the criteria of probable AE (3F:2M, median age 67, range 42-67), 4 of definite autoimmune LE (2F:2M, median age 45.5, range 27-60 years), one of definite antibody-negative ADEM, 2 of Hashimoto encephalopathy, one had no samples available for additional testing, and 15 had no further categorization. Of 10 probable/definite AE/LE/ADEM, one had a malignancy and none of them received an alternative diagnosis until the end of follow-up (median 18 months). In total, 80% (8/10) of patients received immunotherapy including corticosteroids, and 6/10 (60%) patients received rituximab, azathioprine, cyclophosphamide, plasma exchange, or IV immunoglobulins. Five (50%) patients improved, one (10%) stabilized, one (10%) worsened, and 3 (30%) died. All deaths were considered to be related to encephalitis. We did not observe differences of immunotherapy-treated patients in likelihood of improvement with or without nonsteroidal immunotherapy (with 2/6, without 1/2).
DISCUSSION
Antibody-negative AE should be diagnosed only after comprehensive testing. Diagnostic effort is important because many patients benefit from immunotherapy and some have malignancies.
Topics: Adult; Humans; Aged; Middle Aged; Retrospective Studies; Encephalitis; Autoantibodies; Neoplasms; Autoimmune Diseases of the Nervous System
PubMed: 37879962
DOI: 10.1212/NXI.0000000000200170 -
BMJ Open Respiratory Research Feb 2024Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.
DESIGN
Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.
DATA SYNTHESIS
The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.
RESULTS
A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DL (95% CI 2.05 to 6.79, I=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.
CONCLUSIONS
There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.
PROSPERO REGISTRATION NUMBER
CRD42023423223.
Topics: Humans; Azathioprine; Immunosuppressive Agents; Lung Diseases, Interstitial; Lung; Mycophenolic Acid; Enzyme Inhibitors; Observational Studies as Topic
PubMed: 38413120
DOI: 10.1136/bmjresp-2023-002163 -
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 -
Cureus Aug 2023Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated destruction of hepatocytes, leading to inflammation and fibrosis. In recent years,... (Review)
Review
Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated destruction of hepatocytes, leading to inflammation and fibrosis. In recent years, significant advances have been made in understanding the pathogenesis, epidemiology, diagnosis, and treatment of AIH. This comprehensive narrative review aims to provide an up-to-date overview of these advances. The review begins by outlining the historical background of AIH, dating back to its initial recognition in the 1940s, and highlights the evolution of diagnostic criteria and classification based on autoantibody profiles. The epidemiology of AIH is explored, discussing its varying prevalence across different regions and the role of genetic predisposition, viral infections, and drug exposure as risk factors. Furthermore, the review delves into the pathogenesis of AIH, focusing on the dysregulated immune response, involvement of T cells, and potential contribution of the gut microbiome. Clinical presentation, diagnostic criteria, and liver biopsy as crucial tools for diagnosis are also discussed. Regarding management, the review provides an in-depth analysis of the standard first-line treatments involving glucocorticoids and azathioprine, as well as alternative therapies for non-responsive cases. Additionally, emerging second and third-line treatment options are examined. In conclusion, this narrative review highlights the complexity of AIH and underscores the importance of early diagnosis and individualized treatment approaches to improve patient outcomes. Further research and clinical trials are needed to optimize AIH management and ensure a better long-term prognosis for affected individuals.
PubMed: 37622052
DOI: 10.7759/cureus.43973 -
Biomedical Reports Feb 2024Autoimmune pancreatitis (AIP) is a rare disease. There are two distinct types of AIP: AIP type 1 (AIP-1), a pancreatic manifestation of a multi-organ disease linked to... (Review)
Review
Autoimmune pancreatitis (AIP) is a rare disease. There are two distinct types of AIP: AIP type 1 (AIP-1), a pancreatic manifestation of a multi-organ disease linked to immunoglobulin (Ig)G4, and AIP type 2 (AIP-2), a pancreas-specific disease unrelated to IgG4. The usual course of treatment for AIP is oral corticosteroid medication. Rituximab has also been recommended for recurrent AIP-1 in order to initiate remission and provide ongoing treatment. Immunomodulators such as azathioprine are used to keep certain patients in remission. Evaluation also takes into account a number of pharmacological alternatives, including biologic drugs like anti-tumor necrosis factor therapy, a safe and efficient second-line treatment for AIP-2 relapse or steroid dependence. Corticosteroids and immunosuppressants, which are poorly tolerated due to considerable side effects, are being replaced by other biologic drugs, which may offer a beneficial therapeutic alternative.
PubMed: 38259589
DOI: 10.3892/br.2023.1714 -
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 -
Revista Espanola de Enfermedades... Jun 2024We report the case of a 58-year-old male patient presenting with clinical and laboratory findings indicative of acute hepatitis. Abdominal ultrasound excluded biliary...
We report the case of a 58-year-old male patient presenting with clinical and laboratory findings indicative of acute hepatitis. Abdominal ultrasound excluded biliary tract abnormalities. Two weeks prior, the patient had contracted COVID-19. Viral hepatitis was ruled out, and the presence of autoantibodies was confirmed. Liver biopsy findings were consistent with autoimmune hepatitis and grade 1 fibrosis. Initial treatment with budesonide was ineffective, leading to a switch to prednisone, with maintenance therapy comprising prednisone and azathioprine. COVID-19 infection may act as a trigger for the development of autoimmune hepatitis.
PubMed: 38832588
DOI: 10.17235/reed.2024.10532/2024 -
Medicina 2024Autoimmune hepatitis (AIH) is a rare, chronic, inflammatory, and necrotic liver disease characterized by the presence of autoantibodies. Its etiology is unknown. It... (Review)
Review
Autoimmune hepatitis (AIH) is a rare, chronic, inflammatory, and necrotic liver disease characterized by the presence of autoantibodies. Its etiology is unknown. It affects 1 in 200 000 people annually in the US and occurs predominantly in women. Its presentation varies from asymptomatic forms to cirrhosis and acute liver failure and its diagnosis is based on the measurement of autoantibodies, such as antinuclear autoantibodies (ANA), anti-smooth muscle antibodies (ASMA) and anti-liver and kidney microsomal antibodies (anti-LKM). 1). 10% of HAIs do not present antibodies, being called seronegative HAI, requiring a liver biopsy for diagnosis. To date the evidence remains limited and different societies have issued suggestions and recommendations. For this reason, we believe it is relevant to carry out a bibliographic review on the subject, capturing in this document the important information for the understanding and management of this pathology.
Topics: Humans; Hepatitis, Autoimmune; Autoantibodies; Female; Biopsy; Male
PubMed: 38907968
DOI: No ID Found -
ARP Rheumatology 2023To characterise the idiopathic inflammatory myopathies (IIM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/myositis) and the patients in its cohort.
AIMS
To characterise the idiopathic inflammatory myopathies (IIM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/myositis) and the patients in its cohort.
METHODS
Reuma.pt is a web-based system with standardised patient files gathered in a registry. This was a multicentre open cohort study, including patients registered in Reuma.pt/myositis up to January 2022.
RESULTS
Reuma.pt/myositis was designed to record all relevant data in clinical practice and includes disease-specific diagnosis and classification criteria, clinical manifestations, immunological data, and disease activity scores. Two hundred eighty patients were included, 71.4% female, 89.4% Caucasian, with a median age at diagnosis and disease duration of 48.9 (33.6-59.3) and 5.3 (3.0-9.8) years. Patients were classified as having definite (N=57/118, 48.3%), likely (N=23/118, 19.5%), or possible (N=2/118, 1.7%) IIM by 2017 EULAR/ACR criteria. The most common disease subtypes were dermatomyositis (DM, N=122/280, 43.6%), polymyositis (N=59/280, 21.1%), and myositis in overlap syndromes (N=41/280, 14.6%). The most common symptoms were proximal muscle weakness (N=180/215, 83.7%) and arthralgia (N=127/249, 52.9%), and the most common clinical signs were Gottron's sign (N=75/184, 40.8%) and heliotrope rash (N=101/252, 40.1%). Organ involvement included lung (N=78/230, 33.9%) and heart (N=11/229, 4.8%) involvements. Most patients expressed myositis-specific (MSA, N=158/242, 65.3%) or myositis-associated (MAA, 112/242, 46.3%) antibodies. The most frequent were anti-SSA/SSB (N=70/231, 30.3%), anti-Jo1 (N=56/236, 23.7%), and anti-Mi2 (N=31/212, 14.6%). Most patients had a myopathic pattern on electromyogram (N=101/138, 73.2%), muscle oedema in magnetic resonance (N=33/62, 53.2%), and high CK (N=154/200, 55.0%) and aldolase levels (N=74/135, 54.8%). Cancer was found in 11/127 patients (8.7%), most commonly breast cancer (N=3/11, 27.3%). Most patients with cancer-associated myositis had DM (N=8/11, 72.7%) and expressed MSA (N=6/11) and/or MAA (N=3/11). The most used drugs were glucocorticoids (N=201/280, 71.8%), methotrexate (N=117/280, 41.8%), hydroxychloroquine (N=87/280, 31.1%), azathioprine (N=85/280, 30.4%), and mycophenolate mofetil (N=56/280, 20.0%). At the last follow-up, there was a median MMT8 of 150 (142-150), modified DAS skin of 0 (0-1), global VAS of 10 (0-50) mm, and HAQ of 0.125 (0.000-1.125).
CONCLUSIONS
Reuma.pt/myositis adequately captures the main features of inflammatory myopathies' patients, depicting, in this first report, a heterogeneous population with frequent muscle, joint, skin, and lung involvements.
PubMed: 37728117
DOI: No ID Found