Objectives: Recurrent respiratory infections (RRI) are a common problem mainly in pre-school age,... more Objectives: Recurrent respiratory infections (RRI) are a common problem mainly in pre-school age, due to the presence of unfavourable environmental conditions, including early socialization, as well as the immaturity and inexperience of the immune system. The relation between atopy and RRI has been evaluated in several studies, but the results were not conclusive. This study sought to determine the impact of atopy, the immunological and clinical profile in 297 Italian children with RRI, younger than 6 years. Methods: All children were assessed for blood leukocyte count, serum immunoglobulin level, IgG subclasses, lymphocytic subpopulations, total and specific IgE levels for common food and inhalant allergens. Results: A total of 218 children (73.4%) provided a positive family history of atopic disorders. Atopy was found in 150 out of 297 children (50.5%). Early onset (<1 year) of RRI symptoms occurred more frequently in atopic children that in non atopic ones (58.9% vs 44%, p=0.02). A higher percentage of the male children (61.6%) got sick, as compared with the percentage of female children (38.4%), and the male children were more frequently atopic (67.3% vs 55.8%, p=0.03). Thirty-nine out of 297 children (13.2%) were diagnosed as having immunological disorders (IgA deficiency, IgG2 deficiency and transient hypogammaglobulinemia). Conclusions: Our results provide evidence that, in our population, atopy is a frequent condition and it's likely to be a favouring factor for RRI, while the presence of an underlying immunological disease is relatively uncommon and immune defects are mostly mild.
The patient was a 21-year-old boy affected by X-linked chronic granulomatous disease (CGD-OMIM nu... more The patient was a 21-year-old boy affected by X-linked chronic granulomatous disease (CGD-OMIM number 3064000), with a mutation in the gene encoding gp91 phox (deletion of a single G in position 767, with loss of gp91 phox and no residual NADPH oxidase activity), diagnosed at the age of 2, because of a positive family history for CGD. He had recurrent skin abscesses, lymphadenitis, bacterial pneumonia, and lung aspergillosis with probable brain dissemination. His parents compliance was poor and they had discontinued all therapies for a number of years without notice. The patient was referred to our hospital for the first time at the age of 10 because of a multifocal pneumonia with isolation of Aspergillus fumigatus in multiple sputum cultures. He was successfully treated with intravenous conventional amphotericin B and then a prophylactic regimen with trimethoprim–sulfamethoxazole, itraconazole and interferon gamma was prescribed. At the age of 13, the patient presented another brain focus, which resolved under a treatment with liposomal amphotericin B followed by oral itraconazole. His parents admitted once again their poor compliance with prophylactic treatment. When he was 21, the patient was hospitalised because of a large popliteal abscess in the right leg (Fig. 1) and a large area of parenchymal consolidation in the right lung. Right leg magnetic resonance imaging (MRI) excluded bone damage on multiple scans and a brain MRI did not reveal any new damage, but only traces of the old parenchymal lesions. Aspergillus spp. was isolated from a sputum sample and Aspergillus nidulans was isolated in repeated popliteal abscess cultures. An in vitro antifungal susceptibility test of the A. nidulans isolate was performed with Etest (AB-Biodisk, Solna, Sweden). The minimum inhibitory concentrations resulted in the following: itraconazole 0.12 lg ml, voriconazole 0.094 lg ml, amphotericin B 0.19 lg ml. Histological examination showed granulation tissue with abscesses, a granuloma of giant plurinucleated cells and the presence of septate hyphae compatible with the morphology of the isolated A. nidulans. The presence of precipitating antibodies against somatic and metabolic A. fumigatus antigens (Microgen Bioproducts, Camberley, UK; Bio-Rad, Marnes-la Coquette, France) agreed with the isolation of Aspergillus in culture. On the contrary, no galactomannan antigen was detected using Platelia Aspergillus (Bio-Rad) in repeated serum samples. The level of total serum IgE was 8910 kIU l and anti A. fumigatus IgE Correspondence: Prof. Maria Cristina Pietrogrande, Department of Pediatrics, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Via Commenda 9, Milan 20122, Italy. Tel.: +39 2 5503 2496. Fax: +39 2 5032 0210. E-mail: mariacristina.pietrogrande@unimi.it
A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ioniz... more A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ionizing radiation is highly desirable. We designed a study to evaluate lung changes using magnetic resonance imaging (MRI), and to investigate the relationships among severity and extent of pulmonary abnormalities and clinical, microbiological and functional data in children and young adults with AT. Fifteen AT patients (age, 11.3 years; range, 6-31) underwent 3.0-T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified Helbich score. Although only 8 patients (53 %) had recurrent/chronic respiratory symptoms, MRI identified lung abnormalities in all. Bronchiectasis, peribronchial thickening, mucous plugging, and collapse/consolidation were present in 60 %, 87 %, 67 %, and 13 % of cases, respectively, with no difference between subjects with or without respiratory symptoms. No difference in changes of specific scores was found between the two groups, but the total MRI score was higher in patients with respiratory symptoms (6.5 versus 5, respectively; p = 0.02). Total or specific MRI scores were not associated with patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; age. Of all scores, only mucous plugging subscore appeared significantly related to FEV1 (r = 0.7, p = 0.04) and FEF25-75% (r = 0.9, p = 0.001). MRI scores from patients with positive (n = 5) or negative (n = 10) sputum culture were not significantly different. MRI is valuable in the assessment of extent and severity of pulmonary changes in children and adults with AT. It represents an helpful tool for the longitudinal evaluation of patients and may be also used as an outcome surrogate to track the effects of medications.
... Publication date: 2010. Citation: Sindrome da iper-IgE: una patologia sistemica con important... more ... Publication date: 2010. Citation: Sindrome da iper-IgE: una patologia sistemica con importanti implicazioni odontostomatologiche / L. Esposito, B. Colangelo, P. Pavesi, RM Dellepiane, G. Farronato, MC Pietrogrande. - In: Il Dentista Moderno. - ISSN 1827-3726. - 28:4(2010), pp. ...
IntroductionThe primary aim of this study is to investigate the evolution of the clinical and lab... more IntroductionThe primary aim of this study is to investigate the evolution of the clinical and laboratory characteristics during the time in a longitudinal cohort of pediatric-onset and adult-onset Common Variable Immunodeficiency (CVID) patients in order to identify early predictive features of the disease and immune dysregulation complications.MethodsThis is a retrospective-prospective monocentric longitudinal study spanning from 1984 to the end of 2021. The data of pediatric-onset vs. adult-onset patients have been compared for immunological features and for infectious and non-infectious complications assessed at diagnosis and follow-up.ResultsSeventy-three CVID patients have been enrolled, with a mean of 10.0 years (SD ± 8.17) of prospective follow-up. At diagnosis, infections were observed in 89.0% of patients and immune dysregulation in 42.5% of patients. At diagnosis, 38.6% of pediatric-onset and 20.7% of adult-onset patients presented with only infections. Polyclonal lymphoid...
The Job Syndrome or Autosomal Dominant Hyper Immunoglobulin E Syndrome (AD-HIES, LOF-STAT3 gene) ... more The Job Syndrome or Autosomal Dominant Hyper Immunoglobulin E Syndrome (AD-HIES, LOF-STAT3 gene) is a very rare inborn error of immunity disorder with multi-organ involvement and long-life post-infective damages. Longitudinal registries are of main importance to improve knowledge on natural history and management of these rare disorders. This study aims to describe the natural history of 30 Italian patients recorded in the IPINet registry with AD-HIES, with a cumulative observational-time of 721.1 patient-years. Age at disease onset was < 12 months in the 66.7% of patients, but the mean time of diagnostic delay was 13.7 years. At diagnosis skin involvement was present in 93.3% of patients (eczema 80.8%, abscess 66.7%). At the follow up eczema was still present in 63.3% and abscess in 56.7%. Respiratory complications such as bronchiectasis and pneumatoceles were present at diagnosis in the 46.7% and 43.3% respectively. Antimicrobial prophylaxis resulted in decrease of pneumonia fr...
La malattia di Kawasaki e una vasculite acuta sistemica che colpisce i vasi di medio calibro, tip... more La malattia di Kawasaki e una vasculite acuta sistemica che colpisce i vasi di medio calibro, tipica dell’eta pe-diatrica e soprattutto dei bambini di eta inferiore ai 5 anni, la cui complicanza principale e rappresentata dallo sviluppo di aneurismi coronarici. La diagnosi e essenzialmente clinica e la terapia si basa sulla somministrazione di immunoglobuline per via endovenosa (IVIG). Questo lavoro ha lo scopo di descrivere la malattia di Kawasaki in una popolazione di 60 pazienti e valutare i principali fattori di rischio per lo sviluppo del danno coronarico. La malattia si e presentata in forma tipica nel 77% dei pazienti, in forma incompleta nel 18%, in forma atipica nel 5%. Nel 77% dei pazienti si e ottenuta la remissione dopo un solo ciclo di IVIG e nella maggior parte dei casi (81%) le IVIG sono state somministrate entro 10 giorni dall’esordio della malattia. La compromissione coronari-ca e stata riscontrata nel 55% dei pazienti, ma solo il 21% di questi (12% di tutti i pazie...
Background and purposeAtaxia‐telangiectasia (A‐T) is a rare neurodegenerative disease, due to A‐T... more Background and purposeAtaxia‐telangiectasia (A‐T) is a rare neurodegenerative disease, due to A‐T mutated (ATM) gene mutations, which typically presents with signs of progressive neurological dysfunction, cerebellar ataxia and uncoordinated movements. A‐T severely affects patients’ quality of life. Successful treatment options are still not available. The aim of this multicenter study, performed with a blind evaluation procedure, was to define the minimal effective dosage of oral betamethasone, thus preventing the occurrence of side effects.MethodsNine A‐T patients were enrolled to receive betamethasone at increasing dosages of 0.001, 0.005 and 0.01 mg/kg/day. Neurological assessment and the evaluation of quality of life were performed through the Scale for the Assessment and Rating of Ataxia and the Italian version of the Childhood Health Assessment Questionnaire (CHAQ) at each time‐point. The drug safety profile was evaluated. Patients were categorized as responders, partial respo...
Objectives: Recurrent respiratory infections (RRI) are a common problem mainly in pre-school age,... more Objectives: Recurrent respiratory infections (RRI) are a common problem mainly in pre-school age, due to the presence of unfavourable environmental conditions, including early socialization, as well as the immaturity and inexperience of the immune system. The relation between atopy and RRI has been evaluated in several studies, but the results were not conclusive. This study sought to determine the impact of atopy, the immunological and clinical profile in 297 Italian children with RRI, younger than 6 years. Methods: All children were assessed for blood leukocyte count, serum immunoglobulin level, IgG subclasses, lymphocytic subpopulations, total and specific IgE levels for common food and inhalant allergens. Results: A total of 218 children (73.4%) provided a positive family history of atopic disorders. Atopy was found in 150 out of 297 children (50.5%). Early onset (<1 year) of RRI symptoms occurred more frequently in atopic children that in non atopic ones (58.9% vs 44%, p=0.02). A higher percentage of the male children (61.6%) got sick, as compared with the percentage of female children (38.4%), and the male children were more frequently atopic (67.3% vs 55.8%, p=0.03). Thirty-nine out of 297 children (13.2%) were diagnosed as having immunological disorders (IgA deficiency, IgG2 deficiency and transient hypogammaglobulinemia). Conclusions: Our results provide evidence that, in our population, atopy is a frequent condition and it's likely to be a favouring factor for RRI, while the presence of an underlying immunological disease is relatively uncommon and immune defects are mostly mild.
The patient was a 21-year-old boy affected by X-linked chronic granulomatous disease (CGD-OMIM nu... more The patient was a 21-year-old boy affected by X-linked chronic granulomatous disease (CGD-OMIM number 3064000), with a mutation in the gene encoding gp91 phox (deletion of a single G in position 767, with loss of gp91 phox and no residual NADPH oxidase activity), diagnosed at the age of 2, because of a positive family history for CGD. He had recurrent skin abscesses, lymphadenitis, bacterial pneumonia, and lung aspergillosis with probable brain dissemination. His parents compliance was poor and they had discontinued all therapies for a number of years without notice. The patient was referred to our hospital for the first time at the age of 10 because of a multifocal pneumonia with isolation of Aspergillus fumigatus in multiple sputum cultures. He was successfully treated with intravenous conventional amphotericin B and then a prophylactic regimen with trimethoprim–sulfamethoxazole, itraconazole and interferon gamma was prescribed. At the age of 13, the patient presented another brain focus, which resolved under a treatment with liposomal amphotericin B followed by oral itraconazole. His parents admitted once again their poor compliance with prophylactic treatment. When he was 21, the patient was hospitalised because of a large popliteal abscess in the right leg (Fig. 1) and a large area of parenchymal consolidation in the right lung. Right leg magnetic resonance imaging (MRI) excluded bone damage on multiple scans and a brain MRI did not reveal any new damage, but only traces of the old parenchymal lesions. Aspergillus spp. was isolated from a sputum sample and Aspergillus nidulans was isolated in repeated popliteal abscess cultures. An in vitro antifungal susceptibility test of the A. nidulans isolate was performed with Etest (AB-Biodisk, Solna, Sweden). The minimum inhibitory concentrations resulted in the following: itraconazole 0.12 lg ml, voriconazole 0.094 lg ml, amphotericin B 0.19 lg ml. Histological examination showed granulation tissue with abscesses, a granuloma of giant plurinucleated cells and the presence of septate hyphae compatible with the morphology of the isolated A. nidulans. The presence of precipitating antibodies against somatic and metabolic A. fumigatus antigens (Microgen Bioproducts, Camberley, UK; Bio-Rad, Marnes-la Coquette, France) agreed with the isolation of Aspergillus in culture. On the contrary, no galactomannan antigen was detected using Platelia Aspergillus (Bio-Rad) in repeated serum samples. The level of total serum IgE was 8910 kIU l and anti A. fumigatus IgE Correspondence: Prof. Maria Cristina Pietrogrande, Department of Pediatrics, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Via Commenda 9, Milan 20122, Italy. Tel.: +39 2 5503 2496. Fax: +39 2 5032 0210. E-mail: mariacristina.pietrogrande@unimi.it
A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ioniz... more A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ionizing radiation is highly desirable. We designed a study to evaluate lung changes using magnetic resonance imaging (MRI), and to investigate the relationships among severity and extent of pulmonary abnormalities and clinical, microbiological and functional data in children and young adults with AT. Fifteen AT patients (age, 11.3 years; range, 6-31) underwent 3.0-T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified Helbich score. Although only 8 patients (53 %) had recurrent/chronic respiratory symptoms, MRI identified lung abnormalities in all. Bronchiectasis, peribronchial thickening, mucous plugging, and collapse/consolidation were present in 60 %, 87 %, 67 %, and 13 % of cases, respectively, with no difference between subjects with or without respiratory symptoms. No difference in changes of specific scores was found between the two groups, but the total MRI score was higher in patients with respiratory symptoms (6.5 versus 5, respectively; p = 0.02). Total or specific MRI scores were not associated with patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; age. Of all scores, only mucous plugging subscore appeared significantly related to FEV1 (r = 0.7, p = 0.04) and FEF25-75% (r = 0.9, p = 0.001). MRI scores from patients with positive (n = 5) or negative (n = 10) sputum culture were not significantly different. MRI is valuable in the assessment of extent and severity of pulmonary changes in children and adults with AT. It represents an helpful tool for the longitudinal evaluation of patients and may be also used as an outcome surrogate to track the effects of medications.
... Publication date: 2010. Citation: Sindrome da iper-IgE: una patologia sistemica con important... more ... Publication date: 2010. Citation: Sindrome da iper-IgE: una patologia sistemica con importanti implicazioni odontostomatologiche / L. Esposito, B. Colangelo, P. Pavesi, RM Dellepiane, G. Farronato, MC Pietrogrande. - In: Il Dentista Moderno. - ISSN 1827-3726. - 28:4(2010), pp. ...
IntroductionThe primary aim of this study is to investigate the evolution of the clinical and lab... more IntroductionThe primary aim of this study is to investigate the evolution of the clinical and laboratory characteristics during the time in a longitudinal cohort of pediatric-onset and adult-onset Common Variable Immunodeficiency (CVID) patients in order to identify early predictive features of the disease and immune dysregulation complications.MethodsThis is a retrospective-prospective monocentric longitudinal study spanning from 1984 to the end of 2021. The data of pediatric-onset vs. adult-onset patients have been compared for immunological features and for infectious and non-infectious complications assessed at diagnosis and follow-up.ResultsSeventy-three CVID patients have been enrolled, with a mean of 10.0 years (SD ± 8.17) of prospective follow-up. At diagnosis, infections were observed in 89.0% of patients and immune dysregulation in 42.5% of patients. At diagnosis, 38.6% of pediatric-onset and 20.7% of adult-onset patients presented with only infections. Polyclonal lymphoid...
The Job Syndrome or Autosomal Dominant Hyper Immunoglobulin E Syndrome (AD-HIES, LOF-STAT3 gene) ... more The Job Syndrome or Autosomal Dominant Hyper Immunoglobulin E Syndrome (AD-HIES, LOF-STAT3 gene) is a very rare inborn error of immunity disorder with multi-organ involvement and long-life post-infective damages. Longitudinal registries are of main importance to improve knowledge on natural history and management of these rare disorders. This study aims to describe the natural history of 30 Italian patients recorded in the IPINet registry with AD-HIES, with a cumulative observational-time of 721.1 patient-years. Age at disease onset was < 12 months in the 66.7% of patients, but the mean time of diagnostic delay was 13.7 years. At diagnosis skin involvement was present in 93.3% of patients (eczema 80.8%, abscess 66.7%). At the follow up eczema was still present in 63.3% and abscess in 56.7%. Respiratory complications such as bronchiectasis and pneumatoceles were present at diagnosis in the 46.7% and 43.3% respectively. Antimicrobial prophylaxis resulted in decrease of pneumonia fr...
La malattia di Kawasaki e una vasculite acuta sistemica che colpisce i vasi di medio calibro, tip... more La malattia di Kawasaki e una vasculite acuta sistemica che colpisce i vasi di medio calibro, tipica dell’eta pe-diatrica e soprattutto dei bambini di eta inferiore ai 5 anni, la cui complicanza principale e rappresentata dallo sviluppo di aneurismi coronarici. La diagnosi e essenzialmente clinica e la terapia si basa sulla somministrazione di immunoglobuline per via endovenosa (IVIG). Questo lavoro ha lo scopo di descrivere la malattia di Kawasaki in una popolazione di 60 pazienti e valutare i principali fattori di rischio per lo sviluppo del danno coronarico. La malattia si e presentata in forma tipica nel 77% dei pazienti, in forma incompleta nel 18%, in forma atipica nel 5%. Nel 77% dei pazienti si e ottenuta la remissione dopo un solo ciclo di IVIG e nella maggior parte dei casi (81%) le IVIG sono state somministrate entro 10 giorni dall’esordio della malattia. La compromissione coronari-ca e stata riscontrata nel 55% dei pazienti, ma solo il 21% di questi (12% di tutti i pazie...
Background and purposeAtaxia‐telangiectasia (A‐T) is a rare neurodegenerative disease, due to A‐T... more Background and purposeAtaxia‐telangiectasia (A‐T) is a rare neurodegenerative disease, due to A‐T mutated (ATM) gene mutations, which typically presents with signs of progressive neurological dysfunction, cerebellar ataxia and uncoordinated movements. A‐T severely affects patients’ quality of life. Successful treatment options are still not available. The aim of this multicenter study, performed with a blind evaluation procedure, was to define the minimal effective dosage of oral betamethasone, thus preventing the occurrence of side effects.MethodsNine A‐T patients were enrolled to receive betamethasone at increasing dosages of 0.001, 0.005 and 0.01 mg/kg/day. Neurological assessment and the evaluation of quality of life were performed through the Scale for the Assessment and Rating of Ataxia and the Italian version of the Childhood Health Assessment Questionnaire (CHAQ) at each time‐point. The drug safety profile was evaluated. Patients were categorized as responders, partial respo...
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