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While most countries provide safe and effective influenza vaccines for at-risk groups, influenza vaccine coverage among children with rheumatic diseases remains uncertain. This study investigated influenza vaccination rates in children with juvenile idiopathic arthritis (JIA) during the 2019-2020 season and assessed the knowledge and attitudes of caregivers of children with JIA regarding influenza vaccination. The secondary aims were to identify barriers to vaccination and explore strategies to improve vaccination rates. A multi-centre, cross-sectional anonymous survey was conducted in 7 countries during the 2019-2020 influenza season to assess the uptake history of influenza vaccination. Among 287 participants, only 87 (30%) children with JIA received the influenza vaccine during the 2019-2020 season. Children who were more likely to be vaccinated were those with systemic juvenile idiopathic arthritis (sJIA), a history of previous vaccination and those aware of the vaccination recommendations. Conversely, children who previously experienced adverse vaccine-related events reported the lowest uptake. The primary reason for non-vaccination was lack of awareness about the necessity of influenza vaccination. Conclusion: Despite variations among countries, the uptake of influenza vaccines remains low in children with JIA. Improving awareness among families about the importance of influenza vaccination may increase vaccination rates in children with rheumatic diseases. What is Known: ⢠Rheumatic children are at increased risk for influenza infection due to immunosuppressive therapy and immune dysregulation. ⢠Influenza vaccine is formally recommended to children with rheumatic diseases. What is New: ⢠This multicentre study showed that influenza vaccine uptake rates remain suboptimal among children with Juvenile Idiopathic Arthritis despite formal recommendations. ⢠Factors like previous experience with vaccination and information provided by medical professionals via different ways play essential roles in increasing vaccination rates and can contribute to improved health outcomes for these vulnerable children.
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Artritis Juvenil , Vacunas contra la Influenza , Gripe Humana , Humanos , Estudios Transversales , Vacunas contra la Influenza/administración & dosificación , Masculino , Femenino , Niño , Gripe Humana/prevención & control , Preescolar , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Vacunación/estadística & datos numéricos , Cobertura de Vacunación/estadística & datos numéricosRESUMEN
OBJECTIVE: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. METHODS: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. RESULTS: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. CONCLUSION: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes.
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Enfermedades Autoinmunes del Sistema Nervioso , Malformaciones del Sistema Nervioso , Reumatología , Enfermedades de la Piel , Eritema Nudoso , Dedos/anomalías , Humanos , Calidad de VidaRESUMEN
Camptodactyly and clinodactyly are most commonly considered just cosmetic defects, but they can pose a major diagnostic and therapeutic challenge, mainly because of their apparently similar clinical presentation. For years, experts have been arguing over definitions, descriptions, and therapeutic approaches to these deformities, with some favoring surgical approach, some advocating conservative treatment, while others are prone to use a combination of the aforementioned approaches. This article provides an overview of the current literature on two different entities, with emphasis on differences in clinical presentation and treatment modalities. This may improve the understanding and recognition of these deformities in children, and help the attending physician select the most appropriate therapy for the individual patient.
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Tratamiento Conservador , Niño , HumanosRESUMEN
BACKGROUND: The last two decades brought new treatment options and high quality guidelines into the paediatric rheumatologic practice. Nevertheless, a number of patients still present a diagnostic and therapeutic challenge due to combination of vague symptoms and unresponsiveness to available treatment modalities. CASE PRESENTATION: We report a case of sixteen years old girl suffering from polyarticular type of juvenile idiopathic arthritis refractory to multiple treatment options. She first presented at the age of 4 with swelling and contractures of both knees. Her symptoms were initially unresponsive to nonsteroidal anti-inflammatory drugs and progressed despite treatment with intraarticular and systemic glucocorticoids and methotrexate. Throughout the years, she received several biologics together with continuous administration of nonsteroidal anti-inflammatory drugs and disease modifying anti-rheumatic drugs as well as intraarticular and systemic glucocorticoids in disease flares. However, none of this options provided a permanent remission, so various other modalities, as well as other possible diagnoses were constantly being considered. Eventually she became dependent on a daily dose of systemic glucocorticoids. In 2018, the treatment with Janus kinase inhibitor tofacitinib was initiated, which led to gradual amelioration of musculoskeletal symptoms, improvement of inflammatory markers and overall well-being, as well as to the weaning of systemic glucocorticoids. As the swelling of the wrists subsided for the first time in many years, Madelung's deformity was noticed, first clinically, and later radiographically as well. Genetic analysis revealed short-stature homeobox gene deficiency and confirmed the diagnosis of Leri Weill syndrome. CONCLUSIONS: This case report emphasizes the need for reporting refractory, complicated cases from everyday clinical practice in order to build-up the overall knowledge and share experience which is complementary to available guidelines. Individual reports of difficult to treat cases, especially when additional diagnoses are involved, can be helpful for physicians treating patients with common rheumatological diseases such as juvenile idiopathic arthritis.
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Antirreumáticos , Artritis Juvenil , Osteocondrodisplasias , Adolescente , Antirreumáticos/uso terapéutico , Artritis Juvenil/diagnóstico , Artritis Juvenil/tratamiento farmacológico , Niño , Femenino , Trastornos del Crecimiento , Humanos , Metotrexato/uso terapéuticoRESUMEN
Type I interferons (IFN) are a class of inducible and protective cytokines best known for immune defence against viruses and intracellular bacteria. Inappropriate stimulation or defective negative regulation of type I IFN expression however can lead to persistent type I IFN activity with detrimental effects. This is particularly relevant for a class of monogenic autoinflammatory diseases ("type I interferonopathies"), along with many other complex rheumatic diseases such as systemic lupus erythematosus (SLE), dermatomyositis (DM), systemic sclerosis (SSc), rheumatoid arthritis (RA) and Sjögren's syndrome (SS). Direct detection of type I interferon protein in biologic samples has proved challenging, thus indirect methods are often used to infer the presence of type I IFN via quantification of antiviral activity and/or induced expression of IFN-responsive genes. While some of these methods have been used to inform clinical care, none have proven feasible for everyday clinical practice. However, with new technologies emerging, this may soon change. This review provides a brief summary of the available methods to gauge the presence of type I IFN and their application for the improved understanding, diagnosis and monitoring of type I interferonopathies and other rheumatic diseases.
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Artritis Reumatoide , Interferón Tipo I , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Síndrome de Sjögren , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Humanos , Interferón Tipo I/sangre , Interferón Tipo I/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Enfermedades Reumáticas/sangre , Enfermedades Reumáticas/inmunología , Síndrome de Sjögren/sangre , Síndrome de Sjögren/inmunologíaRESUMEN
BACKGROUND: Osteoid osteoma is a painful benign skeletal tumour of unknown aetiology. Most often it occurs in the long bones of extremities and responds well to nonsteroidal anti-inflammatory medications. However, unusual localization and atypical presentation of this tumour might present a diagnostic challenge, especially if symptoms mimic that indicative of juvenile spondyloarthritis. CASE PRESENTATION: A misdiagnosed ten-and-a-half-year-old girl with osteoid osteoma involving the distal phalanx of a little finger is presented. Her initial symptoms were pain and swelling of the little finger resembling dactylitis, while various imaging modalities showed signs of tenosynovitis, indicating a possible development of juvenile spondyloarthritis. Several trials of different non-steroid anti-inflammatory drugs gave no satisfactory results and ultrasound guided triamcinolone-hexacetonide injection provided only a short relief. Finally, almost three years after initial presentation, persistent clinical symptoms warranted repeated imaging that raised suspicion of an osteoid osteoma. Directed treatment with surgical intervention led to almost immediate and complete resolution of her symptoms. CONCLUSIONS: Osteoid osteoma should be suspected in case of a tender swelling of a digit in children and adolescents, regardless of initial imaging findings and clinical presentation. Early diagnosis and treatment of this benign condition can have a substantial impact on quality of life of patients and their families and protect them from many unnecessary diagnostic procedures and treatment.
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Artritis Juvenil/diagnóstico , Neoplasias Óseas/diagnóstico , Osteoma Osteoide/diagnóstico , Dolor/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Niño , Diagnóstico Diferencial , Errores Diagnósticos , Femenino , Falanges de los Dedos de la Mano/diagnóstico por imagen , Falanges de los Dedos de la Mano/patología , Falanges de los Dedos de la Mano/cirugía , Humanos , Imagen por Resonancia Magnética , Osteoma Osteoide/complicaciones , Osteoma Osteoide/patología , Osteoma Osteoide/cirugía , Dolor/etiología , Resultado del TratamientoRESUMEN
OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children, with heterogeneous clinical features. Although therapeutic options are wide and in the majority of children symptoms improve with the combination of non-steroidal anti-inflammatory and disease-modifying drugs, there are a number of patients who do not respond to conventional therapy and who do not meet the criteria for systemic biologics, namely anti TNF-alpha. Those patients are potential candidates for intraarticular therapy with biologics and in this report we present the results of intra-articular infliximab treatment in a series of patients diagnosed with oligoarticular subtype of JIA. METHODS: Twenty patients (30 joints) were treated with intraarticular infliximab and monitored by power Doppler musculoskeletal ultrasound according to the OMERACT and Juvenile Arthritis Disease Activity Score (JADAS 10) before intraarticular application and during the follow-up period of 18 months (0, 1, 12, 18 months). RESULTS: The results showed statistically significant improvement in PD-MSUS measures and JADAS in both B mode and power Doppler mode scores (p<0.001, p<0.001, respectively) in patients treated with i.a. infliximab with persistent response in fifteen patients. The JADAS score, as well as the ultrasound scores, were significantly reduced during the follow-up period. CONCLUSIONS: This study showed promising results, good safety and potential for the clinical benefit of intraarticular infliximab treatment in a selected group of patients with oligoarticular subtype of JIA.
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Antirreumáticos/administración & dosificación , Artritis Juvenil/tratamiento farmacológico , Infliximab/administración & dosificación , Sistema Musculoesquelético/diagnóstico por imagen , Artritis Juvenil/diagnóstico por imagen , Artritis Juvenil/mortalidad , Femenino , Humanos , Inyecciones Intraarticulares , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad , UltrasonografíaRESUMEN
The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Croatian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability and construct validity (convergent and discriminant validity). A total of 100 JIA patients (7% systemic, 38% oligoarticular, 19% RF negative polyarthritis, 36% other categories) and 100 healthy children, were enrolled in the paediatric rheumatology centres of the Clinical Hospital Center Sestre Milosrdnice and Childen's Hospital Srebrnjak in Zagreb. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed satisfactory psychometric performances. In conclusion, the Croatian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.
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Artritis Juvenil/diagnóstico , Evaluación de la Discapacidad , Medición de Resultados Informados por el Paciente , Reumatología/métodos , Adolescente , Edad de Inicio , Artritis Juvenil/fisiopatología , Artritis Juvenil/psicología , Artritis Juvenil/terapia , Estudios de Casos y Controles , Niño , Preescolar , Croacia , Características Culturales , Femenino , Estado de Salud , Humanos , Masculino , Padres/psicología , Pacientes/psicología , Valor Predictivo de las Pruebas , Pronóstico , Psicometría , Calidad de Vida , Reproducibilidad de los Resultados , TraducciónRESUMEN
Juvenile spondyloartrhritis is a group of multifactorial diseases in which a disturbed interplay occurs between the immune system and environmental factors on a predisposing genetic background, which leads to inflammation and structural damage of the target tissue. First symptoms of jSpA rarely involve the spine, while asymmetrical oligoarthritis of lower extremities, dactylitis, and peripheral enthesitis are much more common. There are many classification criteria for jSpA, but the majority of pediatric rheumatologists currently use the International League Against Rheumatism (ILAR) criteria according to which most patients with jSpA are classified into the enthesitis-related arthritis group of juvenile idiopathic arthritis. To meet these criteria, a patient should have arthritis and/or enthesitis, with two or more symptoms such as sacroiliac joint tenderness and/or inflammatory back pain, HLAB27 genotype, HLA B27 genotype-associated disease in a first- or second-degree relative, uveitis, and male sex with eight or more years of age. Therefore, diagnosis is most oft en made only based on clinical examination and medical history. Anti- nuclear antibodies (ANA), rheumatoid factor (RF), and HLA testing with B27, B7, and DR4 alleles are preferred. Since subclinical gut inflammation is present in many patients, it is recommended to check fecal calprotectin levels. In patients with signs of peripheral enthesitis it is warranted to perform power Doppler musculoskeletal ultrasound (PDUS), and in patients with signs of axial involvement radiographic and contrast-enhanced magnetic resonance imaging. Most patients are treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy, while in refractory cases with peripheral disease synthetic disease- modifying antirheumatic drugs (DMARDs), such as sulfasalazine, are used. In patients with axial involvement, biological DMARDs such as adalimumab, infliximab, and etanercept are obligatory. Although a number of studies gave us a good insight into the disease pathogenesis, the response to treatment and prognosis are still difficult to predict.
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Artritis Juvenil/diagnóstico , Artritis Juvenil/terapia , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/terapia , Artritis Juvenil/etiología , Niño , Humanos , Espondilitis Anquilosante/etiologíaRESUMEN
Microarray gene expression analysis is high-throughput method in which many different sized DNA molecules are attached to solid surface in designated spots. These molecules are used for the discovery of specific RNA molecules isolated from various biological samples of interest. Core principle of this method is hybridization of complementary nucleotides (A-T and G-C), which leads to creation of double stranded nucleic acids. Gene expression differences in two groups of samples are discovered and quantificated by comparison of signal intensity values in microarray spots. Systemic analysis of data gathered in microarray gene expression measurement is performed by various bioinformatic methods such as group analysis, annotation analysis as well as network and pathway analysis. Expression comparison of all genes in different cells of the same individual or same cells of different individuals provides an insight into the mechanism responsible for development of a certain condition or disease.
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Perfilación de la Expresión Génica/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Investigación Genética , Pruebas Genéticas , HumanosRESUMEN
Spondyloarthritis or spondyloarthropathy (SpA) is a multifactorial disease in which a disturbed interplay occurs between the immune system and environmental factors on a predisposing genetic background, which leads to inflammation and structural damage of target tissue. Many recent researches on development of SpA showed important role of innate and adaptive immunity as well as of prominent bone tissue remodeling which leads to osteoproliferation and ankylosis. It is believed that possible sites of inflammation in SpA are entheses, sinovium and gut. Current knowledge on inflammation and tissue destruction leads to conclusion that SpA is disease characterized by disorders on different levels. Disorder on the first level is disturbed pathogen recognition and immune response activation, on second level disturbed inflammatory cells migration and on third level disturbed immune response regulation. As follows, disease progress depends on range of disturbances: disease course can be short, as in reactive arthritis, or long-lasting with substantial structural damage, as in ankylosing spondylitis. Unfortunately, there are still no confident markers of disease progression, so at the mere beginning disease is often described as undifferentiated.
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Espondiloartritis/inmunología , Espondiloartritis/patología , Artritis Reactiva , Biomarcadores , Humanos , InflamaciónRESUMEN
In addition to the long-established association of HLA-B27 antigen and spondyloarthritis, several studies have shown a similar association with HLA-B7 antigen. But since the whole MHC region carries less than half of the risk for the development of the disease, the main goal of many recently performed researches, which implemented various high-throughput methods, was to discover the influence of genes outside the MHC region on disease development. The results showed that genes closely linked to spondyloarthritis participate in antigen processing and coding of various cytokines. This can lead to the conclusion that diseases from the spondyloarthritis group are polygenic, affected by both autoinflammatory and autoimmune mechanisms.
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Predisposición Genética a la Enfermedad , Espondiloartritis/genética , HumanosRESUMEN
INTRODUCTION: Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes. AIM: A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period. METHODS AND MATERIALS: Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes. RESULTS: During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet-Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0-31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0-141.0) months. The median follow-up duration in the cohort was 3.0 (1.0-7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation. CONCLUSION: This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD.
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Hematopoietic stem cell transplantation (HSCT) has become an effective therapeutic option for the treatment of severe cases of autoimmune diseases (AD). Hematopoietic stem cells (HSC) can be collected from the patient (autologous), identical twin (syngenic) or HLA identical donor (allogenous). In allogenous transplantation autoagressive immunological effector cells are substituted with non-autoagressive cells of the donor. Possible graft versus host reaction (GVHD) makes this type of transplantation less attractive. On the other hand, autologous transplantation can induce the >>resetting<< of immunological clock without any fear of GVHD, but it requires previous conditioning. As an alternative option, transplantation ofmesenchymal stem cells (MSS) was developed. MSS has a strong immunosuppressive effect, while it doesn't require previous conditioning, nor does it induce GVHD. Due to the treatment related mortality, these therapeutic option should remain reserved for the most severe cases of AD. Nevertheless, they present a great opportunity for these patients, and even a chance for full recovery.
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Enfermedades Autoinmunes/terapia , Trasplante de Células Madre Hematopoyéticas , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante Autólogo , Trasplante HomólogoRESUMEN
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children, and one of the major causes of short-term or long-term disability, and impairment of quality of life in childhood. Without early and adequate treatment the disease will progress and result with irreparable joint damage. The choice of therapy depends on the JIA subtype, disease activity index, prognostic factors, and prooven efficacy and probable side-effects of the drugs. The goal of modern JIA therapy is the achievement of complete disease remission, and not only the improvement of symptoms and temporarily inflammation control. The implementation of biologics significantly altered therapeutic approach to children with resistant JIA. We present Croatian guidelines on biologic drugs for the treatment of patients with JIA.
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Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Niño , Humanos , Inducción de RemisiónRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is one of the leading causes of end-stage renal disease. In spite of the recent tremendous progress in the understanding of ADPKD pathogenesis, the molecular mechanisms of the disease remain incompletely understood. Considering emerging new targeted therapies for ADPKD, it has become crucial to disclose easily measurable and widely available biomarkers for identifying patients with future rapid disease progression. This review encompasses all the research with a shared goal of identifying promising serum or urine biomarkers for predicting ADPKD progression or response to therapy. The rate of the ADPKD progress varies significantly between patients. The phenotypic variability is only partly explained by the underlying genetic lesion diversity. Considering significant decline in kidney function in ADPKD is not usually evident until at least 50% of the parenchyma has been destroyed, conventional kidney function measures, such as glomerular filtration rate (GFR), are not suitable for monitoring disease progression in ADPKD, particularly in its early stages. Since polycystic kidney enlargement usually precedes the decline in GFR, height-adjusted total kidney volume (ht-TKV) has been accepted as an early biomarker for assessing disease severity in ADPKD patients. However, since measuring ht-TKV is time-consuming and observer-dependent, the identification of a sensitive and quickly measurable biomarker is of a great interest for everyday clinical practice. Throughout the last decade, due to development of proteomic and metabolomic techniques and the enlightenment of multiple molecular pathways involved in the ADPKD pathogenesis, a number of urine and serum protein biomarkers have been investigated in ADPKD patients, some of which seem worth of further exploring. These include copeptin, angiotensinogen, monocyte chemoattractant protein 1, kidney injury molecule-1 and urine-to-plasma urea ratio among many others. The aim of the current review is to provide an overview of all of the published evidence on potentially clinically valuable serum and urine biomarkers that could be used for predicting disease progression or response to therapy in patients with ADPKD. Hopefully, this review will encourage future longitudinal prospective clinical studies evaluating proposed biomarkers as prognostic tools to improve management and outcome of ADPKD patients in everyday clinical practice.
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Cystinuria is a rare genetic disorder inherited by an autosomal recessive pattern which affects the transmembrane transporter for the base amino acid cystine. It has a general prevalence of 1 in 7000 with demographic variations. Patients with cystinuria have excessive urinary excretion of cystine, which can lead to the formation of stones. Up to 70% of patients will develop chronic kidney disease that can progress even to end-stage renal disease. Symptoms usually start in the first two decades of life with a typical presentation consisting of flank pain and renal colic, usually accompanied by urinary tract infection and deterioration of kidney function. Men are typically affected twice as often as women and have a more severe clinical course. Diagnosis is made by spectrophotometric analysis of the stones that are collected after spontaneous expulsion or medical intervention. Genetic testing is not mandatory but is recommended in uncertain cases or as a part of genetic counseling. Treatment consists of diet modification, alkalization of urine, and thiol-based therapies if other measures fail to prevent stone formation. In pregnancy, cystinuria with the formation of cystine stones represents a therapeutic challenge and requires a multidisciplinary approach consisting of an uro-nephrology team and a gynecologist. We present the case of a 34-year-old woman with cystinuria on whom the diagnosis was made by analysis of the expulsed stone. While her previous pregnancies were without complications, her third pregnancy was accompanied by frequent urinary tract infections, acute worsening of kidney function, and urological interventions during pregnancy due to the formation of new stones. Despite the complicated course, the pregnancy was successfully carried to term with the delivery of a healthy female child.
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Introduction: Genetic kidney diseases are underdiagnosed; namely, from 7% to 40% of patients suffering from chronic kidney disease (CKD) can carry a pathogenic variant, depending on population characteristics. Hereditary tubulointerstitial kidney diseases, including autosomal dominant tubulointerstitial kidney diseases (ADTKD), are even more challenging to diagnose. ADTKD is a rare form of genetic kidney disease resulting from pathogenic variants in the MUC1, UMOD, HNF1B, REN, SEC61A1, and DNAJB11 genes. There is no typical clinical or histopathological sign of ADTKD, it is characterized by progressive CKD, an autosomal dominant inheritance pattern, and tubular atrophy with interstitial fibrosis on kidney biopsy. There is no significant proteinuria, and the urinary sediment is bland. The patients usually do not have severe arterial hypertension. There can be a history of early gout, especially when compared to the UMOD gene variants. Children can have enuresis due to a loss of renal concentration. On ultrasound, the kidneys can appear normal or small in size. Renal cysts are not pathognomonic for any of the named diseases. End-stage renal disease (ESRD) develops at the average age of 45, but this can be very variable. Family history that suggests autosomal dominant inheritance and CKD fulfilling the aforementioned characteristics of tubulointerstitial kidney disease should raise suspicion of ADTKD. In the setting of a negative family history for CKD, clinical suspicion should be raised based on clinical characteristics, including early onset of hyperuricemia or gout and compatible histology on the kidney biopsy. Contrary to the aforementioned characteristics of ADTKD, in the case of HNF1B-related disease, there is a more complex clinical presentation with extrarenal manifestations of the disease (diabetes mellitus, hypomagnesemia, neurologic and psychiatric disturbances, etc.). The diagnosis of ADTKD is based on a positive family history and a detection of the pathogenic variant in one of the genes in an affected individual. Aim: The aim of our study is to present two case reports of ADTKD with different characteristics (slowly progressive CKD vs. complex clinical presentation with an extrarenal manifestation of the disease) with a literature review. Methods: A 34-year-old patient with CKD and a positive family history of CKD in whom kidney biopsy showed nonspecific chronic changes, with only genetic analysis confirming the diagnosis of MUC1-related ADTKD. Our second case is of a 17-year-old patient with an unremarkable family history who was initially referred to genetic counseling due to cognitive and motor impairment with long-lasting epilepsy. Extensive workup revealed increased serum creatinine levels with no proteinuria and bland urinary sediment, along with hypomagnesemia. His genetic analysis revealed 17q12 deletion syndrome, causing the loss of one copy of the HNF1B gene, the AATF, and the LHX1 gene. Conclusion: Autosomal dominant tubulointerstitial kidney diseases are challenging to diagnose due to a lack of typical clinical or histopathological signs as well as an uncharacteristic and versatile clinical presentation. Increased clinical awareness is crucial for the detection of these diseases.
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Introduction: As the global pandemic continues, new complications of COVID-19 in pediatric population have turned up, one of them being hemolytic uremic syndrome (HUS), a complement-mediated thrombotic microangiopathy (CM-TMA) characterized by triad of thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI). With both multisystem inflammatory syndrome in children (MIS-C) and HUS sharing complement dysregulation as one of the key factors, the aim of this case report is to highlight differences between these two conditions and also emphasize the importance of complement blockade as a treatment modality. Case report: We describe a 21-month-old toddler who initially presented with fever and confirmed COVID-19. His condition quickly deteriorated and he developed oliguria, accompanied with diarrhea, vomiting and oral intake intolerance. HUS was suspected, supported with compelling laboratory findings, including decreased platelets count and C3 levels, elevated LDH, urea, serum creatinine and sC5b-9 and presence of schistocytes in peripheral blood, negative fecal Shiga toxin and normal ADAMTS13 metalloprotease activity. The patient was given C5 complement blocker Ravulizumab and started to display rapid improvement. Conclusion: Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.
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OBJECTIVE: The COVID-19 pandemic has affected patient care in general. We aimed to analyze the impact of the pandemic on pediatric rheumatology practice. METHODS: An online survey including 22 questions was created by the representatives of the Emerging RheumatoloGists and rEsearchers (EMERGE) group of the Pediatric Rheumatology European Society (PReS) on SurveyMonkey. The descriptive analysis of the responses was performed on SurveyMonkey. RESULTS: Overall, 469 pediatric rheumatologists (F/M: 2.9) from 70 countries completed the survey. The practice of drug prescription is not affected by the pandemic, according to 65.3 % of the respondents, while 24.3 % and 16.5 % are prescribing biologic drugs and corticosteroids less often, respectively. Over 40 % of the respondents have seen an increased number of patients with vasculitis or chilblains during the pandemic. One-third of the respondents stated no adjustments in their clinical practice after 2.5 years of COVID-19 pandemic. The rest indicated implementing various changes, with an emphasis on incorporating telemedicine. Telemedicine constitutes ≥10 % of the clinical practice for one-third of the participants. Nonetheless, 35.5 % agree that there are still delays in patient care due to the pandemic. However, most (â¼90 %) think our practice is returning to the pre-pandemic routine. CONCLUSION: The findings of our study indicate a significant alteration in pediatric rheumatology practice due to the pandemic. This includes increased caution when prescribing anti-rheumatic drugs, a transition towards telemedicine utilization, delays in routine care, and a rise in COVID-19-related inflammatory conditions. It is imperative to address these aspects in order to improve patient care in pediatric rheumatology.