RESUMEN
BACKGROUND: Intractable diarrhea (ID) could be defined as a syndrome of severe chronic diarrhea associated with malnutrition not easily resolved by conventional management. AIMS: To provide an overview on etiology and management of ID patients in Italy in the last 12 years. METHODS: The members of Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) enrolled all ID patients seen between January 1, 2011 and December 31, 2022. RESULTS: 69 children were enrolled (49 M, 20 F; median age at ID onset 9.5 days) from 7 tertiary care pediatric centers. Overall 62 patients had genetic diseases; 3 had infantile Inflammatory Bowel Disease and 1 autoimmune enteropathy in absence of genetic mutations; 2 undefined ID. Defects of intestinal immune-related homeostasis caused ID in 29 patients (42 %). CONCLUSION: ID is a rare but challenging problem, although the potential for diagnosis has improved over time. In particular, molecular analysis allowed to identity genetic defects in 90 % of patients and to detect new genetic mutations responsible for ID. Due to both the challenging diagnosis and the treatment for many of these diseases, the close relationship between immune system and digestive tract should require a close collaboration between pediatric immunologists and gastroenterologists, to optimize epidemiologic surveillance and management of ID.
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Diarrea , Enfermedades Inflamatorias del Intestino , Humanos , Recién Nacido , Diarrea/genética , Enfermedades Inflamatorias del Intestino/complicaciones , Intestinos , Italia/epidemiología , Estado Nutricional , Masculino , Femenino , Estudios Multicéntricos como AsuntoRESUMEN
OBJECTIVE: To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. METHODS: We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. RESULTS: The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). CONCLUSIONS: Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.
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Antirreumáticos , Artritis Reumatoide , Biosimilares Farmacéuticos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adalimumab/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Etanercept/uso terapéutico , Etanercept/efectos adversos , Necrosis/inducido químicamente , Necrosis/tratamiento farmacológico , Resultado del Tratamiento , AdultoRESUMEN
BACKGROUND AND AIM: Hypertension (HTN) is common among obese children and adolescents and increases their cardiovascular risk later in adulthood. The aim of the study was to evaluate the prevalence of HTN identified by office blood pressure (BP) measurement and ambulatory BP monitoring (ABPM) in a cohort of obese children and adolescents and its association with anthropometric and glycometabolic indices. METHODS AND RESULTS: Seventy consecutive obese Caucasian children and adolescents aged 7-16 years were enrolled. Patients underwent ABPM, echocardiogram and carotid ultrasonography. Sex- and age-adjusted logistic multivariable analysis models were used to assess the association between HOMA-IR, HOMA-ß, QUICKI with HTN at ABPM. Receiver Operation Curve (ROC) analysis with Youden J statistics was used to identify the optimal HOMA-IR, HOMA-ß and QUICKI cut-off to predict HTN at ABPM. Hypertensive office BP was found in 25.7% of obese patients. ABPM diagnosed HTN in 34.9% of patients: 20.6% of obese patients had masked HTN (MHTN), and 12.7% had white coat HTN (WCH). Hypertensive obese patients (according to ABPM) had higher HOMA-IR and HOMA-ß, and a lower QUICKI than normotensive subjects. HOMA-IR, HOMA-ß and QUICKI predicted HTN at ABPM in obese patients in age- and sex-adjusted logistic multivariable models. Optimal cut-offs to predict HTN at ABPM in obese patients were: HOMA-IR ≥ 3.30, HOMA-ß ≥ 226.7 and QUICKI <0.33, with high sensitivity. CONCLUSIONS: A sequential testing strategy applying office BP and glycometabolic indices can identify hypertensive obese pediatric patients with high diagnostic accuracy and potentially reducing costs. This strategy needs validation in an external and larger cohort.
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Hipertensión , Obesidad Infantil , Humanos , Niño , Adolescente , Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Obesidad Infantil/complicaciones , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/complicaciones , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea , Monitoreo Ambulatorio de la Presión ArterialRESUMEN
In recent years, the spectrum of possible treatments for Intestinal Failure (IF)-Short Bowel Syndrome (SBS) has been enriched by the implementation of GLP-2 analogues. In Italy, teduglutide (Ted), an analogue of GLP-2, was approved in January 2021 by the Italian Regulatory Agency for Drugs (AIFA) for IF-SBS patients ≥1 year old. According to the Agency indications, Ted can now be prescribed by regional reference centers, with costs fully charged to the National Health Service. Following pediatric-use approval in our country and in light of scarce evidence in childhood, the pediatric network for IF of the Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) planned to share management methods of Ted in pediatric IF. The main purpose was to identify the best candidates from a cost-effective perspective. Thus, focusing on available literature and on expert opinions, the present position statement provides consensus-based recommendations on the use of Ted for pediatric gastroenterologists and nutritionists treating children with SBS.
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Gastroenterología , Insuficiencia Intestinal , Síndrome del Intestino Corto , Niño , Fármacos Gastrointestinales/uso terapéutico , Péptido 2 Similar al Glucagón/uso terapéutico , Humanos , Lactante , Péptidos , Síndrome del Intestino Corto/tratamiento farmacológico , Medicina EstatalRESUMEN
INTRODUCTION: The aim of this study was to evaluate the prevalence of antiphospholipid antibodies (aPLs) in infertile women undergoing in vitro fertilization (IVF). METHOD OF STUDY: From January 2012 to December 2017, 520 consecutive clinical records of infertile women undergoing IVF were evaluated. Among them, 100 consecutive clinical records of patients with positive autoantibodies were selected. RESULTS: In 100/520 (19.23%) women, positive auto-antibodies were detected: 35/520 (6.73%) fulfilled classification criteria for a systemic disease. Positive aPLs were observed in 43 women (8.27%): 17/520 (3.27%) fulfilled diagnostic criteria for PAPS/APS, whereas patients with positive aPLs, who fulfilled diagnostic criteria for a systemic autoimmune disease other than APS were 18/520 (3.46%). LA and aCL were the main aPLs detected 53.49% and 44.19% respectively, whereas aB2GPI were found in 25.58%. CONCLUSIONS: we suggest that women with infertility may represent a subpopulation of patients with underhanded systemic autoimmune syndromes in which the main symptoms represented are obstetrical complications. We, therefore, recommend evaluating aPLs in all patients undergoing IVF with the aim of recognizing women at a higher risk of miscarriage or pregnancy morbidity.
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Anticuerpos Antifosfolípidos/sangre , Autoanticuerpos/sangre , Autoinmunidad/inmunología , Fertilización In Vitro , Infertilidad Femenina/sangre , Adulto , Femenino , Humanos , Infertilidad Femenina/inmunología , Infertilidad Femenina/terapia , Persona de Mediana Edad , EmbarazoRESUMEN
In our letter, we comment the paper of Kounis et al., that highlights a poor-known clinical entity determined by systemic use of corticosteroids, the so-called "Kounis syndrome type I". We appreciated and shared the intent of Authors to treat the important issue of high risk of adverse drug reaction in patients with atopic diathesis and we confirm the need to administer corticosteroids with caution in patients suffering from allergic disease.
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Anafilaxia , Corticoesteroides , Humanos , Metilprednisolona , SíndromeRESUMEN
Meningococcal polysaccharide (Men-Ps) vaccine immunogenicity following either primary immunization or revaccination in adults was evaluated. The study population consisted of subjects who have received tetravalent Men-Ps vaccine once (group 1) or at least twice, with a 2-6 dose range (group 2). Human leucocyte antigen (HLA)-typing was performed by polymerase chain reaction and specific immunoglobulin (Ig)G was measured by enzyme-linked immunosorbent assay. Nine months post-immunization, the percentages of individuals with levels of anti-Men-Ps IgG ≥ 2 µg/ml were comparable in both groups, with the exception of anti-Men-PsW135 IgG, which were significantly higher in group 2. The percentage of subjects doubling IgG levels at 9 months was significantly higher in group 1. The high baseline anti-Men-Ps antibody levels negatively influenced the response to revaccination, suggesting a feedback control of specific IgG. The calculated durability of anti-Men-Ps IgG was 2·5-4·5 years, depending on the Men-Ps, following a single vaccine dose. No interference by other vaccinations nor HLA alleles association with immune response were observed. This study confirms that Men-Ps vaccine in adults is immunogenic, even when administered repeatedly, and underlines the vaccine suitability for large-scale adult immunization programmes that the higher costs of conjugate vaccines may limit in developing countries.
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Anticuerpos Antibacterianos/sangre , Inmunoglobulina G/sangre , Meningitis Meningocócica/prevención & control , Vacunas Meningococicas/inmunología , Neisseria meningitidis/inmunología , Polisacáridos Bacterianos/inmunología , Adulto , Anticuerpos Antibacterianos/inmunología , Femenino , Prueba de Histocompatibilidad , Humanos , Inmunización Secundaria , Inmunoglobulina G/inmunología , Masculino , Meningitis Meningocócica/inmunología , Meningitis Meningocócica/microbiología , Personal Militar , Vacunación , Adulto JovenRESUMEN
OBJECTIVE: Fatigue affects the almost totality of Systemic Lupus Erythematous (SLE) patients impairing physical function and leading to a strong reduction of health-related quality of life (HRQoL). Similarly, SLE patients have an increased rate of work loss and work limitations. The aim of our paper was to systematically assess the relationship between fatigue and work disability in SLE. MATERIALS AND METHODS: We performed a systematic review using the terms "fatigue" and "employment", "work disability", "work impairment", "presenteeism" and "absenteeism." RESULTS: 19 studies were identified. Fatigue was involved in the development of work loss. In employed patients, fatigue led to impairment of work productivity and presenteeism with a parallel increase of both direct and indirect health costs. Fatigue also affected parenting and household productivity. CONCLUSIONS: An adequate control of fatigue could improve physical and work performance in SLE patients thus reducing rates of work loss.
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Fatiga , Lupus Eritematoso Sistémico/patología , Bases de Datos Factuales , Empleo , Humanos , Responsabilidad Parental , Calidad de Vida , Rendimiento LaboralRESUMEN
INTRODUCTION: the prevalence of malnutrition in children and its impact on clinical outcomes is underrecognized by clinicians in Italy as well as worldwide. A novel definition of pediatric malnutrition has been recently proposed by a working group of the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), based on the correlation between illness and the use of zscores of anthropometric measurements. AIM: to investigate the prevalence of malnutrition and related nutritional support among hospitalized children in Italy, in a nationwide survey performed in a single day (16/4/2015). METHODS: an open access website (http://nday.biomedia.net) was used to collected data from 73 hospitals and 101 wards in 14 Italian regions (1994 patients). Anonymous information was collected on hospitals' characteristics, patient's anthropometry, admission diagnosis, presence of chronic diseases and use of nutritional support: oral nutritional supplements (ONS), enteral nutrition (EN) or parenteral nutrition (PN). Z-scores of anthropometric measurements, calculated with Epi Info 7.1.5, defined nutritional status: wasting was identified by BMI or Weight-for-Length z-score (<-1 mild, <-2 moderate, <-3 severe), stunting by Height-for-Age Z-score <-2. WHO 2006 and CDC 2000 growth charts were used respectively for children younger and older than 2 years old. RESULTS: 1790 complete records were obtained for hospitalized patients aged 0-20 years, with median age 6.16 (0.1-20 years and 53.3% males). 52.9% were aged 0-6 years and 58.8% of children suffered from chronic diseases. Wasting was detected in 28.7% of the total sample with higher occurrence observed in age ranges 0-6 and 14-20 years, while 17.3% of patients showed stunting; surprisingly almost 27% of them were aged 0-2. A ranking of the admission diagnosis with the highest rate of malnutrition was complied. The prevalence of wasting was significantly (p < 0.005) higher amongst children with chronic diseases (34.1% vs. 27.1%); stunting prevalence tripled in patients with chronic disease (24.5% vs. 8.3%). Only 23.5% of malnourished children (17%, 25.6% and 36.7%, respectively mild, moderate and severe malnutrition) received nutritional support: 11.7% received oral nutrition supplements (ONS, modular or complete), 11.5% enteral nutrition (EN, 6.4% via nasogastric tube, 5.1% via gastrostomy) and 6.8 % received parenteral nutrition (PN); in some patients a combination of two. Nutritional support is more commonly used among stunting patients, 39.5% of children under treatment. CONCLUSION: Malnutrition of any grade was observed in nearly 1/3 and stunting in 17% of the reported hospitalized children, and it is likely to be underrecognized as the nutritional support reached only a small part of the malnourished children.
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Trastornos del Crecimiento/epidemiología , Desnutrición/epidemiología , Encuestas Nutricionales , Adolescente , Niño , Desarrollo Infantil , Niño Hospitalizado , Preescolar , Enfermedad Crónica , Femenino , Gráficos de Crecimiento , Trastornos del Crecimiento/terapia , Humanos , Lactante , Italia/epidemiología , Masculino , Desnutrición/diagnóstico , Desnutrición/terapia , Estado Nutricional , Apoyo Nutricional , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). CASE REPORT: An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. CONCLUSIONS: Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE.
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Dieta Cetogénica/métodos , Nutrición Enteral/métodos , Unidades de Cuidado Intensivo Pediátrico , Estado Epiléptico/dietoterapia , Niño , Humanos , Masculino , Retratamiento , Resultado del TratamientoAsunto(s)
Ácido Ascórbico , Trastornos de la Nutrición del Niño , Niños con Discapacidad , Terapia Nutricional/métodos , Escorbuto , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/sangre , Parálisis Cerebral/complicaciones , Niño , Trastornos de la Nutrición del Niño/diagnóstico , Trastornos de la Nutrición del Niño/etiología , Trastornos de la Nutrición del Niño/fisiopatología , Trastornos de la Nutrición del Niño/terapia , Nutrición Enteral/métodos , Femenino , Alimentos Formulados , Humanos , Masculino , Síndrome de Rett/complicaciones , Escorbuto/diagnóstico , Escorbuto/etiología , Escorbuto/fisiopatología , Escorbuto/terapia , Resultado del Tratamiento , Vitaminas/administración & dosificación , Vitaminas/sangreRESUMEN
We describe the nutritional status of a cohort of celiac disease (CD) children at presentation and during follow-up on gluten-free diet (GFD). Two Italian centers (Rome and Bari) prospectively enrolled 445 biopsy-confirmed CD children, diagnosed between 2009 and 2013. Body Mass Index was used as a measure of nutritional status according to Italian growth charts of Cacciari. The overweight/obese subject was 7.8% at onset and did not significantly increase during follow-up (9.8% at final assessment). The prevalence of overweight/obesity was significantly higher among males than females. Furthermore, overweight/obesity children as compared with those with normal weight were significantly older and had significantly lower levels of tTG antibodies. This study shows that some CD children are obese/overweight at diagnosis; therefore, overweight/obesity can be considered a rare but a possible mode of CD presentation. Thus, CD diagnosis must be considered even in overweight/obese children where this diagnosis can be easily missed.
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Enfermedad Celíaca/etiología , Obesidad/complicaciones , Sobrepeso/complicaciones , Índice de Masa Corporal , Enfermedad Celíaca/fisiopatología , Niño , Preescolar , Femenino , Humanos , Italia/epidemiología , Estudios Longitudinales , Masculino , Estado Nutricional , Obesidad/epidemiología , Sobrepeso/epidemiología , Prevalencia , Estudios Retrospectivos , Factores SexualesRESUMEN
BACKGROUND/OBJECTIVES: Neonatal short bowel syndrome (SBS) follows early intestinal resections that may expose the children to increased intestinal contact with undigested food proteins and to the risk of food allergy. We report three consecutive cases of cow's milk allergy (CMA) in SBS infants. SUBJECTS/METHODS: We reviewed three cases of CMA developed in 37 children with neonatal SBS followed up in the last 10 years. The setting of the survey was the Gastroenterology-Hepatology and Nutrition Unit of the Pediatric Hospital 'Bambino Gesù' in Rome. The diagnosis of CMA was based on the oral food challenge and was supported by the results of the skin prick tests (SPT) and/or the specific immunoglobulin (Ig) E. RESULTS: Two patients had persistent liquid stools and periodic episodes of vomiting when they were fed with an intact milk protein-based formula, that disappeared with extensively hydrolyzed formula and amino-acid-based formulae, respectively. The third patient developed maculo-papular rash, flushing and angioedema, when he was introduced a regular formula. The challenge-confirmed CMA in all patients. Positive specific IgE for milk proteins was documented in all the three patients. Two out of the three patients had positive familial history for allergy and positive SPT. CONCLUSIONS: Our findings suggest that the SBS patients require a careful clinical monitoring of the tolerance for the cow's milk proteins, because CMA could be more frequent than expected. A prospective regular assessment for the potential cow milk sensitization by SPT and specific IgE may clarify the nature of the association and support the clinical surveillance. Multicenter studies are required to better evaluate this comorbidity.
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Hipersensibilidad a la Leche/epidemiología , Síndrome del Intestino Corto/epidemiología , Animales , Bovinos , Comorbilidad , Humanos , Inmunoglobulina E/sangre , Lactante , Fórmulas Infantiles , Recién Nacido , Italia/epidemiología , Masculino , Hipersensibilidad a la Leche/diagnóstico , Hipersensibilidad a la Leche/inmunología , Proteínas de la Leche/inmunología , Pruebas CutáneasRESUMEN
B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients.
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Enfermedades Autoinmunes/diagnóstico por imagen , Enfermedades Autoinmunes/inmunología , Linfocitos B/diagnóstico por imagen , Linfocitos B/inmunología , Inflamación/diagnóstico por imagen , Inflamación/inmunología , Tomografía Computarizada de Emisión/métodos , Animales , Enfermedades Autoinmunes/patología , Rastreo Celular/métodos , Humanos , Inflamación/patología , Radiofármacos/inmunologíaRESUMEN
INTRODUCTION: Acute severe exacerbations of Ulcerative Colitis (UC) represent a medical emergency in children and adults. Intravenous steroids remain the first line therapy for this condition, although the steroid refractoriness is common. Second-line therapy, based on the infliximab or thiopurines should be started if no response to corticosteroids is noted. The use of infliximab in children with acute severe UC, nevertheless, does not avoid the colectomy in all cases. METHODS: We present a case of severe acute UC in a paediatric patient successfully treated with thalidomide following the failed treatment with infliximab and a review of the literature. CONCLUSIONS: This is the first case of a patient presenting with acute severe UC who was treated with thalidomide, with favorable evolution. In our case the use of this drug was able to avoid the colectomy that represent the conventional but very invasive recommended therapeutic option of this condition. Therefore, thalidomide may be considered as rescue therapy in selected and carefully monitored cases of acute severe CU.
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Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Inmunosupresores/uso terapéutico , Talidomida/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Niño , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/patología , Colon/patología , Femenino , Humanos , Infliximab , Radiografía AbdominalRESUMEN
B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasmacells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 Rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients.
RESUMEN
The use of biological agents combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients has strongly improved disease outcome. In this study, the effects of abatacept on the size and function of circulating B and T cells in RA patients not responding to anti-tumour necrosis factor (TNF)-α have been analysed, with the aim of identifying immunological parameters helpful to choosing suitable tailored therapies. We analysed the frequency of peripheral B and T cell subsets, B cell function and T regulatory cell (Treg ) inhibitory function in 20 moderate/severe RA patients, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, primary non-responders to one TNF-α blocking agent, who received abatacept + MTX. Patients were studied before and 6 months after therapy. We found that abatacept therapy significantly reduced disease activity score on 44 joints (DAS)/erythrocyte sedimentation rate (ESR) values without causing severe side effects. The size of the circulating B and T cell compartments in RA patients was not significantly different from healthy donors, but B cell proliferation and plasma cell differentiation was impaired before therapy and restored by abatacept. While Treg cell frequency was normal, its inhibitory function was absent before therapy and was partially recovered 6 months after abatacept. B and Treg cell function is impaired in RA patients not responding to the first anti-TNF-α agent. Abatacept therapy was able to rescue immune function and led to an effective and safe clinical outcome, suggesting that RA patients, in whom anti-TNF-α failed, are immunologically prone to benefit from an agent targeting a different pathway.
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Artritis Reumatoide/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Inmunoconjugados/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Abatacept , Adulto , Anciano , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Subgrupos de Linfocitos B/efectos de los fármacos , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Humanos , Inmunoconjugados/uso terapéutico , Inmunofenotipificación , Recuento de Linfocitos , Persona de Mediana Edad , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
Several scores are currently used to estimate the radiologic progression of patients affected by rheumatoid arthritis. Modified Sharp score, Genant-modified Sharp score and van der Heijde-modified Sharp score are actually the most commonly used scores in randomized controlled trials on biologic drugs actually available in scientific literature. An intensive literature search (EMBASE, PubMed, MEDLINE) was performed in order to identify randomized controlled studies reporting on the efficacy of biologic drugs on radiologic progression in rheumatoid arthritis by means of approved scoring methods such as Sharp score variants. All studies were evaluated for their approach to radiologic outcome, and a global evaluation of trends towards radiologic evaluation was performed. Eighteen studies were identified and analyzed, and data from such randomized controlled trials (RCTs) were reported and described regarding their approach to radiologic outcomes. The use of three different scoring methodologies generated similar but non-comparable data; although a big part of the studies reported good efficacy profiles of several biologic drugs on radiologic progression, data from such studies are not comparable as the three different scoring methods are not convertible from one to another. At present, there is no standardization for the evaluation of radiologic outcomes, thus preventing comparison of results obtained by different drugs. The use of a single, standardized and widely approved scoring method would grant the possibility of comparing such data.