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BACKGROUND AND PURPOSE: Patients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischaemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported. METHODS: In this cohort study, patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands were included. The frequency and recurrence rates of neurological manifestations before and after initiation of tumor necrosis factor α (TNF-α) inhibiting therapy were analyzed. RESULTS: Twenty-nine patients were included with a median age at presentation of 5 years (interquartile range 1-17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. Transient ischaemic attack (TIA)/ischaemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischaemic strokes occurred in 12 patients, one after initiation of TNF-α inhibiting therapy and one whilst switching between TNF-α inhibitors. None was large-vessel occlusion stroke. Two hemorrhagic strokes occurred: one aneurysmatic subarachnoid hemorrhage and one spontaneous intracerebral hemorrhage. Most neurological symptoms, including cranial nerve deficits, vertigo, ataxia and seizures, were caused by TIAs/ischaemic strokes and seldom recurred after initiation of TNF-α inhibiting therapy. CONCLUSIONS: Neurological manifestations, especially TIA/ischaemic stroke, are common in patients with ADA2 deficiency and frequently are the presenting symptom. Because it is a treatable cause of young stroke, for which antiplatelet and anticoagulant therapy are considered contraindicated, awareness amongst neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small-vessel ischaemic stroke without an identified cause should be considered.
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Isquemia Encefálica , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Preescolar , Accidente Cerebrovascular/etiología , Ataque Isquémico Transitorio/complicaciones , Adenosina Desaminasa/genética , Estudios de Cohortes , Péptidos y Proteínas de Señalización Intercelular/genética , Isquemia Encefálica/complicaciones , Factor de Necrosis Tumoral alfa , Accidente Cerebrovascular Isquémico/complicaciones , FenotipoRESUMEN
BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is associated with NLRP3 pathogenic variants, mostly located in the NACHT (neuronal apoptosis inhibitor protein, MHC class 2 transcription activator, incompatibility locus protein from Podospora anserina, telomerase-associated protein) domain. Cold-induced urticarial rash is among the main clinical features. However, this study identified a series of 14 patients with pathogenic variants of the Y861 residue (p.Tyr861) of the LRR domain of NLRP3 and minimal prevalence of cold-induced urticarial rash. OBJECTIVES: This study aimed to address a possible genotype/phenotype correlation for patients with CAPS and to investigate at the cellular levels the impact of the Y861C substitution (p.Tyr861Cys) on NLRP3 activation. METHODS: Clinical features of 14 patients with CAPS and heterozygous substitution at position 861 in the LRR domain of NLRP3 were compared to clinical features of 48 patients with CAPS and pathogenic variants outside the LRR domain of NLRP3. IL-1ß secretion by PBMCs and purified monocytes from patients and healthy donors was evaluated following LPS and monosodium urate crystal stimulation. RESULTS: Patients with substitution at position 861 of NLRP3 demonstrated a higher prevalence of sensorineural hearing loss while being less prone to skin urticarial. In contrast to patients with classical CAPS, cells from patients with a pathogenic variant at position 861 required an activation signal to secrete IL-1ß but produced more IL-1ß during the early and late phase of secretion than cells from healthy donors. CONCLUSIONS: Pathogenic variants of Y861 of NLRP3 drive a boost-dependent oversecretion of IL-1ß associated with an atypical CAPS phenotype.
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Síndromes Periódicos Asociados a Criopirina , Exantema , Urticaria , Humanos , Síndromes Periódicos Asociados a Criopirina/genética , Exantema/complicaciones , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Fenotipo , Urticaria/genéticaRESUMEN
Here, we describe an adult female with severe fasciitis and skin necrosis who carried a private, predicted deleterious missense mutation in OTULIN in heterozygosity. OTULIN is a cellular regulator of deubiquitination that has been shown to play a key role in intrinsic immunity against staphylococcal α-toxin. The patient was treated with broad-spectrum antibiotics, and multiple surgical explorations were conducted without clinical response. Since autoinflammation was the predominant clinical feature, TNF inhibition was started with a good clinical response. We show that excessive inflammation in OTULIN haploinsufficiency can be effectively treated by TNF inhibition.
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Fascitis , Haploinsuficiencia , Femenino , Humanos , Inflamación/genética , Necrosis , UbiquitinaciónRESUMEN
Deficiency of adenosine deaminase-2 (DADA2) is an autosomal recessive autoinflammatory disease with an extremely variable disease presentation. This paper provides a comprehensive overview of the Dutch DADA2 cohort. We performed a retrospective cohort study in 29 ADA2-deficient patients from 23 families with a median age at inclusion of 26 years. All patients had biallelic pathogenic variants in the ADA2 gene. The most common clinical findings included cutaneous involvement (79.3%), (hepato)splenomegaly (70.8%) and recurrent infections (58.6%). Stroke was observed in 41.4% of the patients. The main laboratory abnormalities were hypogammaglobulinemia and various cytopenias. Patients presented most often with a mixed phenotype involving vasculopathy, immunodeficiency and hematologic manifestations (62.1%). In this cohort, malignancies were reported in eight patients (27.6%), of whom five presented with a hematologic malignancy and two with a basal cell carcinoma. Four patients developed hemophagocytic lymphohistiocytosis (HLH) or an HLH-like episode, of whom three passed away during or shortly after the occurrence of HLH. TNF-inhibitors (TNFi) were effective in treating vasculopathy-associated symptoms and preventing stroke, but were hardly effective in the treatment of hematologic manifestations. Three patients underwent hematopoietic cell transplantation and two of them are doing well with complete resolution of DADA2-related symptoms. The overall mortality in this cohort was 17.2%. In conclusion, this cohort describes the clinical, genetic and laboratory findings of 29 Dutch DADA2 patients. We describe the occurrence of HLH as a life-threatening disease complication and report a relatively high incidence of malignancies and mortality.
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Linfohistiocitosis Hemofagocítica , Accidente Cerebrovascular , Humanos , Adulto , Adenosina Desaminasa/genética , Estudios de Seguimiento , Estudios Retrospectivos , Péptidos y Proteínas de Señalización Intercelular/genética , Mutación/genéticaRESUMEN
BACKGROUND: Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis. Most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. OBJECTIVES: To conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. METHODS: The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of 3 rounds. In the first two rounds, online list of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. RESULTS: Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate, and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side-effect, and preferred the use of biologics over conventional treatment. The role of interleukin-1 and interleukin-6 blocking agents was considered important in the treatment of AOSD. CONCLUSIONS: In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline.
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BACKGROUND: [18F]FDG-PET/CT is one of the most important diagnostic techniques in the work-up of patients with fever of unknown origin (FUO)/inflammation of unknown origin (IUO). Little is known on how to optimize the diagnostic value of [18F]FDG-PET/CT in patients with FUO/IUO. METHODS: Retrospective study in all patients who underwent [18F]FDG-PET/CT during the work-up of FUO/IUO in a tertiary expert center between 2005 and 2014. Data were extracted from medical records. RESULTS: One hundred and four patients were identified, of whom 68 had a final diagnosis (65.4%). Mainly infections (30.8%) and non-infectious inflammatory diseases (30.8%). [18F]FDG-PET/CT contributed to the final diagnosis in 47 of the 68 patients (69.1%). In 21 patients [18F]FDG-PET/CT did not help making a diagnosis. In ten of these patients [18F]FDG-PET/CT was performed while body temperature, CRP and ESR were normal or unknown. Sixteen of 104 patients underwent repeated [18F]FDG-PET/CT. The second scan contributed to the final diagnosis in five of these patients. In two of these patients, the first scan retrospectively was truly non-contributory. In both patients the first [18F]FDG-PET/CT was made while CRP/ESR was low and fever was not present or not measured. A third or fourth scan never contributed to the final diagnosis when the second one did not. CONCLUSIONS: [18F]FDG-PET/CT contributed to the final diagnosis in 45.2% of patients, but never contributed when both inflammatory parameters and body temperature were normal. Repeating [18F]FDG-PET/CT should only be done in patients with a non-contributory [18F]FDG-PET/CT when new symptoms or signs appear, or when the first scan was made in absence of fever or elevated inflammatory parameters.
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Fiebre de Origen Desconocido/diagnóstico por imagen , Fluorodesoxiglucosa F18/química , Inflamación/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , TemperaturaRESUMEN
More than 50 years after the first definition of fever of unknown origin (FUO), it still remains a diagnostic challenge. Evaluation starts with the identification of potential diagnostic clues (PDCs), which should guide further investigations. In the absence of PDCs a standardised diagnostic protocol should be followed with PET-CT as the imaging technique of first choice. Even with a standardised protocol, in a large proportion of patients from western countries the cause for FUO cannot be identified. The treatment of FUO is guided by the final diagnosis, but when no cause is found, antipyretic drugs can be prescribed. Corticosteroids should be avoided in the absence of a diagnosis, especially at an early stage. The prognosis of FUO is determined by the underlying cause. The majority of patients with unexplained FUO will eventually show spontaneous remission of fever. We describe the definition, diagnostic workup, causes and treatment of FUO.
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Fiebre de Origen Desconocido/diagnóstico , Fiebre de Origen Desconocido/tratamiento farmacológico , Fiebre de Origen Desconocido/etiología , HumanosRESUMEN
BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostic challenges that often require an extensive work-up. When first-line tests do not provide any or only misleading clues, second-line investigations such as specialized imaging techniques are often warranted. OBJECTIVES: To provide an overview of the diagnostic value of imaging techniques that are commonly used in patients with FUO/IUO. SOURCES: MEDLINE database was searched to identify the most relevant studies, trials, reviews, or meta-analyses until 31 March 2023. CONTENT: The most important types of second-line imaging tests for FUO and IUO are outlined, including [67Ga]-citrate single-photon emission computed tomography/computed tomography (CT), labelled leukocyte imaging, [18F]-fluorodeoxyglucose positron emission tomography CT ([18F]-FDG-PET), and whole-body magnetic resonance imaging. This review summarizes the diagnostic yield, extends on potential future imaging techniques (pathogen-specific bacterial imaging and [18F]-FDG-PET/magnetic resonance imaging), discusses cost-effectiveness, highlights practical implications and pitfalls, and addresses future perspectives. Where applicable, we provide additional data specifically for the infection subgroup. IMPLICATIONS: Although many imaging examinations are proven to be useful in FUO and IUO, [18F]-FDG-PET/CT is the preferred second-line test when available as it provides a high diagnostic yield in a presumably cost-effective way.
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Fiebre de Origen Desconocido , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Imagen por Resonancia Magnética , Imagen de Cuerpo Entero , Inflamación/diagnóstico , Fiebre de Origen Desconocido/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodosRESUMEN
With a growing emphasis on value-based reimbursement, developing quality indicators for infectious diseases has gained attention. Quality indicators for fever of unknown origin and inflammation of unknown origin are lacking. An assembled group of international experts developed 12 quality measures for these conditions, which could be validated with additional study.
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Background: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are syndromes commonly used as medical diagnoses. Since the existing literature has a mixture of diagnostic approaches, developing consensus-based recommendations would be helpful for clinicians, researchers, and patients. Methods: A modified Delphi process was performed from October 2022 to July 2023, involving 4 rounds of online surveys and 2 live video conferences. The panel comprised international experts recruited based on peer-reviewed published publications and studies. Results: Among 50 invited experts, 26 (52.0%) agreed to participate. Twenty-three panelists completed round 1 of the survey, 21 completed rounds 2 and 3, 20 completed round 4, and 7 participated in round 5 live video discussions. Of the participants, 18 (78.3%) were academic-based clinicians and researchers, 5 (21.7%) practiced in a community-based hospital, and 6 (26.1%) were female. Consensus was reached on 5 themes: (1) incorporating epidemiologic factors, such as geographic location and travel history; (2) updated criteria for classifying FUO or IUO; (3) initial evaluation approaches; (4) a classification system for diagnoses; and (5) recommendations for judicious limitation of empiric therapies. Experts strongly disagreed with using 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography as part of the diagnostic criteria for FUO. There were mixed opinions about the importance of the temperature measurement site, the 3-week minimum illness criterion, the need for a standard definition of relapsing fevers, and the use of similar evaluation strategies for FUO and IUO. Conclusions: These Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research.
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BACKGROUND: Patients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up. METHODS: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models. RESULTS: A total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25-39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36-0.95]; I2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05-0.58]; I2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23-3.38]; I2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16-10.69]; I2 0 %). CONCLUSION: Based on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach.
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Fiebre de Origen Desconocido , Inflamación , Fiebre de Origen Desconocido/etiología , Humanos , Inflamación/diagnóstico , Diagnóstico DiferencialRESUMEN
Prolonged fever of 38.3°C or higher for at least 3 weeks' duration has been termed fever of unknown origin if unexplained after preliminary investigations. Initially codified in 1961, classification with subgroups was revised in 1991. Additional changes to the definition were proposed in 1997, recommending a set of standardized initial investigations. Advances in diagnosis and management and diagnostic testing over the last 3 decades have prompted a needed update to the definition and approaches. While a 3-week fever duration remains part of the criteria, a lower temperature threshold of 38°C and revised minimum testing criteria will assist clinicians and their patients, setting a solid foundation for future research.
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Fiebre de Origen Desconocido/diagnóstico , Fiebre de Origen Desconocido/patología , Fiebre de Origen Desconocido/clasificación , HumanosRESUMEN
Mevalonate kinase deficiency (MKD) is characterized by recurrent fevers and flares of systemic inflammation, caused by biallelic loss-of-function mutations in MVK. The underlying disease mechanisms and triggers of inflammatory flares are poorly understood because of the lack of in vivo models. We describe genetically modified mice bearing the hypomorphic mutation p.Val377Ile (the commonest variant in patients with MKD) and amorphic, frameshift mutations in Mvk. Compound heterozygous mice recapitulated the characteristic biochemical phenotype of MKD, with increased plasma mevalonic acid and clear buildup of unprenylated GTPases in PBMCs, splenocytes, and bone marrow. The inflammatory response to LPS was enhanced in compound heterozygous mice and treatment with the NLRP3 inflammasome inhibitor MCC950 prevented the elevation of circulating IL-1ß, thus identifying a potential inflammasome target for future therapeutic approaches. Furthermore, lines of mice with a range of deficiencies in mevalonate kinase and abnormal prenylation mirrored the genotype-phenotype relationship in human MKD. Importantly, these mice allowed the determination of a threshold level of residual enzyme activity, below which protein prenylation is impaired. Elevated temperature dramatically but reversibly exacerbated the deficit in the mevalonate pathway and the defective prenylation in vitro and in vivo, highlighting increased body temperature as a likely trigger of inflammatory flares.
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Deficiencia de Mevalonato Quinasa , Animales , Temperatura Corporal , Fiebre , GTP Fosfohidrolasas/genética , Humanos , Inflamasomas/genética , Inflamasomas/metabolismo , Lipopolisacáridos/metabolismo , Deficiencia de Mevalonato Quinasa/tratamiento farmacológico , Deficiencia de Mevalonato Quinasa/genética , Deficiencia de Mevalonato Quinasa/metabolismo , Ácido Mevalónico/metabolismo , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Prenilación de ProteínaRESUMEN
Background: COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown. Patients and methods: CORONavirus and Ischemic Stroke (CORONIS) is a multicentre prospective cohort study investigating the prevalence, risk factors and long-term incidence of (silent) cerebral ischemia, and the long-term functional outcome among patients with COVID-19. We aim to include 200 adult patients hospitalized with COVID-19 without symptomatic ischemic stroke to investigate the prevalence of silent cerebral ischemia compared with 60 (matched) controls with MRI. In addition, we will identify potential risk factors and/or causes of cerebral ischemia in COVID-19 patients with (n = 70) or without symptomatic stroke (n = 200) by means of blood sampling, cardiac workup and brain MRI. We will measure functional outcome and cognitive function after 3 and 12 months with standardized questionnaires in all patients with COVID-19. Finally, the long-term incidence of (new) silent cerebral ischemia in patients with COVID-19 will be assessed with follow up MRI (n = 120). Summary: The CORONIS study is designed to add further insight into the prevalence, long-term incidence and risk factors of cerebral ischemia, and the long-term functional outcome in hospitalized adult patients with COVID-19.
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In 30-50% of patients with fever of unknown origin (IUO) no explanation for the fever can be found. Prognosis and effects of empirical treatment of these patients are largely unknown.With this retrospective, questionnaire based corort study in all unexplained FUO patients in an expert center between 2003 and 2014 we studied mortality and outcome.In 131 of 274 FUO patients, FUO remained unexplained. Ninety-nine of them responded to the long-term follow up questionnaire. Adter a median duration of follow-up of 60 months, spontaneous remission of fever occured in 47.3%. Empirical treatment was effective in 66.7% of patients. Mortality was 6.9%. The cause of death was considered not to be related to the febrile disease in five out of six patients. Ten out of 99 responders reported to have received a final explanation for FUO after evaluation in the expertise center, but this diagnosis could not be confirmed in six cases and was considered to be an unlikely explanation for FUO in four out of six cases.We conclude that mortality in unexplained FUO is low en mostly unrelated to the febrile disease. Spontaneous resolution of fever is common. Empirical treatment prescribed by an expert physician is often effective, but should be avoided untill all diagnostic possibilities have been exhaused.
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Fiebre de Origen Desconocido/tratamiento farmacológico , Fiebre de Origen Desconocido/mortalidad , Pronóstico , Resultado del Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fiebre de Origen Desconocido/epidemiología , Fiebre de Origen Desconocido/etiología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Remisión Espontánea , Estudios Retrospectivos , Encuestas y Cuestionarios/normas , Análisis de SupervivenciaRESUMEN
Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3°C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory investigations. The differential diagnosis of FUO can be subdivided in four categories: infections, malignancies, noninfectious inflammatory diseases, and miscellaneous causes. In most cases of FUO, there is an uncommon presentation of a common disease. FDG-PET/CT is a sensitive diagnostic technique for the evaluation of FUO by facilitating anatomical localization of focally increased FDG uptake, thereby guiding further diagnostic tests to achieve a final diagnosis. FDG-PET/CT should become a routine procedure in the workup of FUO when diagnostic clues are absent. FDG-PET/CT appears to be a cost-effective routine imaging technique in FUO by avoiding unnecessary investigations and reducing the duration of hospitalization.
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Fiebre de Origen Desconocido/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Factores de Edad , Proteína C-Reactiva/metabolismo , Análisis Costo-Beneficio , Fiebre de Origen Desconocido/metabolismo , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/economíaRESUMEN
BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is a rare disease. Knowledge on the quality of life (QoL) and the disease's societal impact is limited. Canakinumab is used in increasing frequency for the treatment of CAPS. METHODS: Observational study in Dutch CAPS patients. Patients completed questionnaires regarding treatment with canakinumab at baseline and retrospectively. Quality of life was assessed using the EQ-5D-5L in adults and CHQ-PF50 in children. Impact on work and school was assessed. Caregivers' quality of life was assessed using the CarerQol. RESULTS: Mean quality of life scores during treatment with canakinumab were 0.769 (EQ-5D-5L), 51.1 (CHQ-P) and 57-1 (CHQ-M). Most patients experienced problems on the pain/discomfort dimension. Higher disease activity and the presence of complications negatively influenced QoL. Half of the patients with a paid job reported absenteeism from work due to CAPS, for an average of 8.7 days in a 4-week period. All schoolgoing patients (N = 5) reported absence from school due to CAPS, for an average of 2.9 days. Caregivers reported gaining a lot fulfillment from providing care for their family members. CONCLUSION: QoL during treatment is lower than in the general Dutch population. CAPS leads to productivity loss and absenteeism from school, and impacts the quality of life in informal caregivers.
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Anticuerpos Monoclonales/uso terapéutico , Síndromes Periódicos Asociados a Criopirina/tratamiento farmacológico , Síndromes Periódicos Asociados a Criopirina/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
In patients undergoing solid organ transplantation, the presence of an interleukin-1 (IL-1) driven disease may require the addition of IL-1 inhibiting drugs to the standard immunosuppressive regimen to protect against inflammation and negative graft outcome. Three patients undergoing renal transplantation were treated perioperatively with the interleukin-1 receptor antagonist anakinra. Kidney function increased rapidly in all three and the only complications seen were minor infections. In vitro studies report associations between serum and urinary levels of IL-1ß and IL-1 receptor antagonist and negative graft outcome, and studies in animals and two small human trials illustrate a possible protective effect of anti-IL-1 therapy after solid organ transplantation. Peri- and postoperative use of anakinra is safe and effective in patients undergoing renal transplantation.