13 results on '"Kronbichler, Andreas"'
Search Results
2. Refractory lupus nephritis: When, why and how to treat.
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Kronbichler, Andreas, Brezina, Biljana, Gauckler, Philipp, Quintana, Luis F., and Jayne, David R.W.
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LUPUS nephritis , *CHRONIC kidney failure , *STEM cell transplantation , *THERAPEUTICS - Abstract
Refractory lupus nephritis indicates an inadequate response to lupus nephritis therapy. It implies persisting or worsening disease activity despite therapy, but the definition is complicated by the parameters of response, proteinuria and renal function, that do not discriminate clearly between activity and irreversible damage. Understanding the causes of refractory disease and developing treatment strategies is important because these patients are more likely to develop poor outcomes, especially end stage renal disease. This review explores current concepts and definitions of refractory disease and summarises treatment approaches that have been used in observational cohort studies and case series. We highlight the importance of optimising adherence to the prescribed immunosuppressive and supportive measures and avoidance of diagnostic delay. Treatment options include higher dose glucocorticoid, switching between cyclophosphamide and mycophenolate acid derivates, or addition of rituximab, the latter potentially in combination with belimumab. Less evidence supports extracorporeal treatment (plasma exchange or immunoadsorption), calcineurin inhibitors (cyclosporine A or tacrolimus), intravenous immunoglobulin and stem cell transplantation. Improvements in understanding what refractory disease is and how definitions can be integrated into treatment pathways has the potential to enhance lupus nephritis outcomes. [ABSTRACT FROM AUTHOR]
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- 2019
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3. Cardiovascular involvement in systemic rheumatic diseases: An integrated view for the treating physicians.
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Lee, Kwang Seob, Kronbichler, Andreas, Eisenhut, Michael, Lee, Keum Hwa, and Shin, Jae Il
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RHEUMATISM treatment , *PHYSICIANS , *CARDIOVASCULAR diseases , *AUTOIMMUNE diseases , *ATHEROSCLEROSIS - Abstract
Systemic autoimmune diseases can affect various kinds of organs including the kidney, the skin, soft tissue and the bone. Among others, cardiovascular involvement in rheumatic diseases has been shown to affect myocardium, pericardium, cardiac vessels, conduction system and valves, eventually leading to increased mortality. In general, underlying chronic inflammation leads to premature atherosclerosis, but also other manifestations such as arrhythmia and heart failure may have a ‘silent’ progress. Traditional cardiovascular risk factors play a secondary role, while disease-specific factors (i.e. disease duration, severity, antibody positivity, persistent disease activity) can directly influence the cardiovascular system. Therefore, early diagnosis is critical to optimize management and to control inflammatory activity and recent data suggest that risk factors (i.e. hypercholesterolemia and hypertension) need intensive treatment as well. With the advent of immunosuppressive agents, most rheumatic diseases are well controlled on treatment, but information related to their cardioprotective efficacy is not well-defined. In this review, we focus on cardiovascular involvement in rheumatic diseases and highlight current evidence which should be of help for the treating physicians. Moreover, cardiotoxicity of immunosuppressive drugs is a rare issue and such potential adverse events will be briefly discussed. [ABSTRACT FROM AUTHOR]
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- 2018
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4. Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review.
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Lee, Keum Hwa, Kronbichler, Andreas, Park, David Duck-Young, Park, YoungMin, Moon, Hanwool, Kim, Hyungdo, Choi, Jun Hyug, Choi, YoungSeo, Shim, Songjoo, Lyu, Il Suk, Yun, Byung Hwan, Han, Yeonseung, Lee, Donghee, Lee, Sang Yoon, Yoo, Byung Hun, Lee, Kyung Hwan, Kim, Tai Lim, Kim, Heonki, Shim, Joo Sung, and Nam, Wonseok
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NEUTROPHILS , *AUTOIMMUNE disease treatment , *INTERLEUKIN-8 , *SYSTEMIC lupus erythematosus , *THERAPEUTIC use of immunoglobulins , *THERAPEUTICS - Abstract
Neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membranes of activated neutrophils. NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. Studies suggest that an imbalance between “NETosis,” which is a process by which NETs are formed, and NET degradation may be associated with autoimmune diseases. Neutrophils, interleukin-8, ANCA and other inflammatory molecules are considered to play a key role in NET formation. Prolonged exposure to NETs-related cascades is associated with autoimmunity and increases the chance of systemic organ damage. In this review, we discuss the roles of various inflammatory molecules in relation to NETs. We also describe the role of NETs in the pathogenesis of autoimmune diseases and discuss the possibility of using targeted therapies directed to NETs and associated molecules to treat autoimmune diseases. [ABSTRACT FROM AUTHOR]
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- 2017
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5. Rituximab for immunologic renal disease: What the nephrologist needs to know.
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Kronbichler, Andreas, Windpessl, Martin, Pieringer, Herwig, and Jayne, David R.W.
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RITUXIMAB , *KIDNEY disease treatments , *NEPHROLOGISTS , *MEDICATION safety , *DRUG side effects - Abstract
Rituximab (RTX), a chimeric, monoclonal anti-CD20 antibody, is increasingly used in immune-mediated renal diseases. While licensed in the induction treatment of ANCA-associated vasculitis, it represents one of the most commonly prescribed off-label drugs. Much of the information regarding its safety has been drawn from experience in hematology and rheumatology. Ample evidence illustrates the safety of RTX, however, rare but serious adverse events have emerged that include progressive multifocal leucoencephalopathy and hepatitis B reactivation. Moderate to severe hypogammaglobulinemia and late-onset neutropenia following RTX therapy confer an increased infectious risk and factors predicting these side effects (i.e. a genetic basis) need to be identified. Nephrologists initiating RTX need to bear in mind that long-term risks and optimal dosing for many renal indications remain unclear. Special considerations must be given when RTX is used in women of childbearing age. We summarize practical aspects concerning the use of RTX. This review will provide nephrologists with information to guide their use of RTX alerting them to safety risks and the need for patient counselling. [ABSTRACT FROM AUTHOR]
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- 2017
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6. Efficacy of plasma exchange and immunoadsorption in systemic lupus erythematosus and antiphospholipid syndrome: A systematic review.
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Kronbichler, Andreas, Brezina, Biljana, Quintana, Luis F., and Jayne, David R.W.
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SYSTEMIC lupus erythematosus treatment , *PLASMA exchange (Therapeutics) , *SYSTEMIC lupus erythematosus , *PREGNANCY complications , *IMMUNOADSORPTION , *SYSTEMATIC reviews , *COMPLEMENT (Immunology) , *PATIENTS - Abstract
Extracorporeal treatments have been used since the 1970s in the management of systemic lupus erythematosus (SLE). A randomised controlled trial comparing the efficacy of standard of care (SOC) combined with plasma exchange against SOC alone in patients with lupus nephritis revealed no difference in terms of renal outcome. Subsequently, initial expectations have been dampened and further experience with plasma exchange is mainly limited to observational studies and single case reports. Beneficial effects have been reported in patients with refractory disease course or in pregnancy with prior complications due to SLE and antiphospholipid syndrome. A more specific form of extracorporeal treatment, immunoadsorption (IAS), has emerged as a valuable option in the treatment of SLE. In line with the plasma exchange experience, IAS seems to have beneficial effects in patients with refractory disease, contraindications to standard immunosuppression or during pregnancy. The mechanism IAS relates to autoantibody removal but for plasma exchange removal of activated complement components, coagulation factors, cytokines and microparticles may also be relevant. Both treatment forms have good safety profiles although reactions to blood product replacement in plasma exchange and procedure related complications such as bleeding or catheter-related infections have occurred. There is a need to more clearly define the clinical utility of plasma exchange and IAS in refractory lupus and APS subgroups. [ABSTRACT FROM AUTHOR]
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- 2016
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7. The COVID-19 pandemic and ANCA-associated vasculitis – reports from the EUVAS meeting and EUVAS education forum.
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Kronbichler, Andreas, Geetha, Duvuru, Smith, Rona M., Egan, Allyson C., Bajema, Ingeborg M., Schönermarck, Ulf, Mahr, Alfred, Anders, Hans-Joachim, Bruchfeld, Annette, Cid, Maria C., and Jayne, David R.W.
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COVID-19 pandemic , *COVID-19 , *ANTINEUTROPHIL cytoplasmic antibodies , *SOCIAL distancing - Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20–25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19+ B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19+ B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses ("booster") of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19. • A high proportion of patients with ANCA-associated vasculitis and COVID-19 have a severe disease course with an excess fatality rate. • Antibody response to COVID-19 vaccination is impaired in most patients receiving immunosuppression , and absent in most patients with a recent dose of rituximab. • Antibodies should be regularly monitored, and booster doses may be considered in those with low antibody titres , as neutralisation titres are per se reduced against emerging variants of concern and protection against COVID-19 directly relates to the level of antibody titres. • Patients should continue social distancing measures and vaccination of close contacts is of importance. [ABSTRACT FROM AUTHOR]
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- 2021
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8. Seven recommendations to rescue the patients and reduce the mortality from COVID-19 infection: An immunological point of view.
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Kronbichler, Andreas, Effenberger, Maria, Eisenhut, Michael, Lee, Keum Hwa, and Shin, Jae Il
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COVID-19 , *CYTOKINE release syndrome , *MORTALITY , *INFECTION - Abstract
Now COVID-19 is causing a severe public health emergency and the mortality is rapidly increasing all over the world. In the current pandemic era, although there have been many efforts to diagnose a number of patients with symptoms or close contacts, there is no definite guideline for the initial therapeutic approach for them and therefore, many patients have been dying due to a hyperinflammatory immunological reaction labeled as "cytokine storm". Severe patients are hospitalized and the treatment is done, though they have not been established yet. Currently, however, no treatment is provided for those who are isolated at home or shelter until they get severe symptoms, which will increase the harms to the patients. In this review, we discuss some important points dedicated to the management of patients with COVID-19, which should help reducing morbidity and mortality. In this era, we suggest 7 recommendations to rescue the patients and to reduce the morbidity and mortality due to COVID-19 based on the immunological point of view. [ABSTRACT FROM AUTHOR]
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- 2020
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9. Clinical associations of renal involvement in ANCA-associated vasculitis.
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Kronbichler, Andreas, Shin, Jae Il, Lee, Keum Hwa, Nakagomi, Daiki, Quintana, Luis F., Busch, Martin, Craven, Anthea, Luqmani, Raashid A., Merkel, Peter A., Mayer, Gert, Jayne, David R.W., and Watts, Richard A.
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GRANULOMATOSIS with polyangiitis , *PULMONARY fibrosis , *POLYARTERITIS nodosa , *NASAL polyps , *SERUM albumin , *AGE factors in disease , *GASTROINTESTINAL hemorrhage - Abstract
Renal involvement in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is associated with significant morbidity and higher mortality rates. This study examined clinical manifestations associated with renal involvement in ANCA-associated vasculitis within a large, international cross-sectional cohort. Univariate and multivariate analyses were performed to identify clinical factors associated with renal disease, which was defined as i) a serum-creatinine >30% above normal and a fall in creatinine-clearance >25%; or ii) haematuria attributable to active vasculitis. The study cohort include 1230 patients from 31 countries; 723 (58.8%) presented with renal involvement: microscopic polyangiitis (82.2%), granulomatosis with polyangiitis (58.6%), and eosinophilic granulomatosis with polyangiitis (26.4%). The following clinical and laboratory factors were more common among patients with renal disease: age (OR 1.01, 95% CI 1.01–1.02), fever (OR 1.97, 95% CI 1.35–2.88), fatigue (OR 1.55, 95% CI 1.14–2.10), weight loss (OR 1.62, 95% CI 1.23–2.12), polyarthritis (OR 1.39, 95% CI 1.02–1.89), petechiae/purpura (OR 1.47, 95% CI 1.06–2.05), pulmonary haemorrhage (OR 5.23, 95% CI 1.39–19.63), gastrointestinal symptoms (OR 2.19, 95% CI 1.34–3.58), seizures (OR 3.42, 95% CI 1.26–9.30), lower serum albumin (OR 2.42, 95% CI 1.64–3.57), higher CRP (OR 2.06, 95% CI 1.04–4.06), low serum C3 at baseline (OR 3.86, 95% CI 1.30–11.53), myeloperoxidase- (OR 7.97, 95% CI 2.74–23.20) and proteinase 3-ANCA (OR 3.40, 95% CI 1.22–9.50). The following clinical factors were less common among patients with renal disease: mononeuritis multiplex (OR 0.63, 95% CI 0.41–0.98), proptosis/exophthalmos (OR 0.19, 95% CI 0.06–0.59), nasal polyps (OR 0.32, 95% CI 0.19–0.55), septal defect/perforation (OR 0.29, 95% CI 0.14–0.60), respiratory distress/pulmonary fibrosis/asthma (OR 0.08, 95% CI 0.04–0.19), and wheeze/obstructive airway disease (OR 0.29, 95% CI 0.16–0.52). In this large international study, several clinical and laboratory factors were identified as associated with renal involvement in ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]
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- 2020
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10. Induction and maintenance treatment of inflammatory bowel disease: A comprehensive review.
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Jeong, Dong Yeon, Kim, Seung, Son, Min Ji, Son, Chei Yun, Kim, Jong Yeob, Kronbichler, Andreas, Lee, Keum Hwa, and Shin, Jae Il
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INFLAMMATORY bowel disease treatment , *CROHN'S disease , *INFLAMMATORY bowel diseases , *ULCERATIVE colitis , *THERAPEUTICS - Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) are the two major types of inflammatory bowel disease (IBD). We conducted a comprehensive review of meta-analyses to summarize the reported effectiveness of different drugs for IBD. We performed a literature search and a total of 110 meta-analyses from 66 articles were summarized and re-analyzed (62 in UC and 48 in CD). In summary, 5-ASA was more effective than placebo in both induction and maintenance treatment of UC, but there were conflicting results on the effect of 5-ASA on the induction treatment or relapse of CD. The use of immunomodulatory agents in the induction or maintenance phase of UC and CD using immunomodulators appeared to be more effective than placebo, but the results were impacted by small number of patients, discordant results with the largest study and risk of biases. Anti-TNF-α and anti-integrin therapeutic antibodies in both, induction and maintenance, showed a better efficacy than placebo in a large proportion of patients analyzed. Other agents, such as probiotics, antibiotics, omega-3, were shown to be more effective than placebo, but the same issues arose as stated above with the use of immunomodulatory agents. In conclusion, we performed a comprehensive review of meta-analysis on comparative efficacy of pharmacotherapy used in the management of IBD. Our review will augment our understanding of the treatment of UC and CD by providing a guideline for interpreting the statistically significant findings and discusses the optimal choice for IBD treatment. • This is a comprehensive review which analyzed an immense amount of meta-analyses on pharmacotherapies for UC and CD. • Our review will augment understanding of the comparative effectiveness of pharmacologic treatment of IBD. [ABSTRACT FROM AUTHOR]
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- 2019
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11. Genetic variation and systemic lupus erythematosus: A field synopsis and systematic meta-analysis.
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Jeong, Dong Yeon, Lee, Sang Woo, Park, Young Ha, Choi, Ji Hoon, Kwon, Young Wook, Moon, Gabin, Eisenhut, Michael, Kronbichler, Andreas, and Shin, Jae Il
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SYSTEMIC lupus erythematosus , *IMMUNOLOGICAL tolerance , *GENETIC polymorphisms , *MOLECULAR immunology , *META-analysis , *GENETICS - Abstract
Systemic lupus erythematosus (SLE) is a multi-systemic severe autoimmune disease which results from the irreversible loss of self-tolerance and impaired molecular responses, especially an altered interferon signature. We synthesized all meta-analyses reporting a genetic association of SLE, and further investigated their validity to discover false positive results under Bayesian methods. We executed a PubMed search to extract the respective results regarding gene polymorphisms of SLE, published until June 30th 2017 and selected a single result per genetic variant among duplicates. Among 133 significant genotype comparisons, 45 (34%) were found noteworthy under both false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). From the meta-analysis of genome-wide association studies (GWAS), we could confirm that all significant comparisons were noteworthy under both Bayesian approaches. Both approaches may be advantageous for determining whether the reported associations are genuine, especially for interpreting results from observational studies instead of GWAS whose significance was determined in a more strict manner. When determining results from GWAS with a p -value ranging between 0.05 and 5 × 10 −8 , other statistical approaches, rather than single standard significance may be beneficial. Taking into account these considerations, a proportion of meta-analyses claimed statistical significance, but these results need to be interpreted with caution. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome.
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Danlos, François-Xavier, Rossi, Giovanni Maria, Blockmans, Daniel, Emmi, Giacomo, Kronbichler, Andreas, Durupt, Stéphane, Maynard, Claire, Luca, Luminita, Garrouste, Cyril, Lioger, Bertrand, Mourot-Cottet, Rachel, Dhote, Robin, Arlet, Jean-Benoit, Hanslik, Thomas, Rouvier, Philippe, Ebbo, Mikael, Puéchal, Xavier, Nochy, Dominique, Carlotti, Agnès, and Mouthon, Luc
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VASCULITIS , *ANTINEUTROPHIL cytoplasmic antibodies , *IMMUNOGLOBULIN G , *EOSINOPHILIC granuloma , *TUBULOINTERSTITIAL nephritis & uveitis syndrome - Abstract
Objective Atypical manifestations have been described in patients with ANCA-associated vasculitides (AAV), such as pachymeningitis, orbital mass or chronic periaortitis. Because these manifestations have been associated to the spectrum of IgG4-related disease (IgG4-RD), we hypothesized that both diseases could overlap. Methods We conducted a European retrospective multicenter observational study including patients fulfilling ACR and Chapel Hill criteria for AAV and IgG4-RD Comprehensive Diagnostic Criteria. Results Eighteen patients were included (median age 55.5 years, 13 men). AAV and IgG4-RD were diagnosed concomitantly in 13/18 (72%) patients; AAV preceded IgG4-RD in 3/18 (17%) while IgG4-RD preceded AAV in 2/18 (11%). AAV diagnoses included granulomatosis with polyangiitis in 14 (78%), microscopic polyangiitis in 3 (17%), and eosinophilic granulomatosis with polyangiitis in one case. IgG4-RD diagnosis included definite IgG4-RD in 5 (28%) cases, probable IgG4-RD in 5 (28%) and possible IgG4-RD in 8 (44%). IgG4-RD manifestations were chronic periaortitis in 9/18 (50%) patients, orbital mass and tubulointerstitial nephritis in 4 (22%) cases, prevertebral fibrosis in 3 (17%), pachymeningitis and autoimmune pancreatitis in 2 (11%) cases. Patients required median number of 2 (range 0–4) lines of immunosuppressants in combination with glucocorticoids. During the follow-up (median 49,8 months, range 17,25–108 months), AAV manifestations relapsed in 10/18 (56%) cases and IgG4-RD lesions in 5/18 (28%). When used, mainly for relapses, rituximab showed response in all cases. Conclusion AAV and IgG4-RD may overlap. Clinicians should consider that atypical manifestations during AAV could be related to IgG4-RD rather than to refractory granulomatous or vasculitic lesions. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review.
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Park, Jae Hyon, Lee, Keum Hwa, Jeon, Bokyoung, Ochs, Hans D., Lee, Joon Suk, Gee, Heon Yung, Seo, Seeun, Geum, Dongil, Piccirillo, Ciriaco A., Eisenhut, Michael, van der Vliet, Hans J., Lee, Jiwon M., Kronbichler, Andreas, Ko, Younhee, and Shin, Jae Il
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AUTOIMMUNE hemolytic anemia , *INTESTINAL diseases , *META-analysis , *GENETIC mutation , *SEPTIC shock , *SYNDROMES - Abstract
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder characterized by early onset fatal multi-system autoimmunity due to loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor which is crucial for the development, maturation, and maintenance of CD4+ regulatory T (T-reg) cells. Various autoimmune phenomena such as enteropathy, endocrinopathies, cytopenias, renal disease, and skin manifestations are characteristic findings in patients affected by IPEX syndrome. In this systematic review, we focus on both clinical and demographic characteristics of IPEX patients, highlighting possible genotype-phenotype correlations and address prognostic factors for disease outcome. We performed a literature search to systematically investigate the case reports of IPEX which were published before August 7th, 2017. A total of 75 articles (195 patients) were identified. All IPEX patients included had FOXP3 mutations which were most frequently located in the forkhead domain (n = 68, 34.9%) followed by the leucine-zipper domain (n = 30, 15.4%) and repressor domain (n = 36, 18.4%). Clinical manifestations were as follows: enteropathy (n = 191, 97.9%), skin manifestations (n = 121, 62.1%), endocrinopathy (n = 104, 53.3%), hematologic abnormalities (n = 75, 38.5%), infections (n = 78, 40.0%), other immune-related complications (n = 43, 22.1%), and renal involvement (n = 32, 16.4%). Enteropathic presentations (P = 0.017), eczema (P = 0.030), autoimmune hemolytic anemia (P = 0.022) and food allergy (P = 0.009) were associated with better survival, while thrombocytopenia (P = 0.034), septic shock (P = 0.045) and mutations affecting the repressor domain (P = 0.021), intron 7 (P = 0.033) or poly A sequence (P = 0.025) were associated with increased risk of death. Immunosuppressive therapy alone was significantly associated with increased cumulative survival compared to patients who received no treatment (P = 0.041). We report the most comprehensive summary of demographic and clinical profiles derived from a total of 195 IPEX patients with deleterious mutations in FOXP3. Analysis of our findings provides new insights into genotype/phenotype correlations, and clinical and genetic factors associated with increased risk of death and response to treatment strategies. [ABSTRACT FROM AUTHOR]
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- 2020
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