Search

Objectives: Auto-inflammatory Diseases (AIDs) are agroup of diseases with a strong genetic component, inducing an inappropriate activation of innate immunity.The patients with pediatric onset will face the transitionalcare (TC) from a pediatrician to an adult care setting, during the critical phase of the adolescence. That implies arisk of failure and drop out, due to the different approach ofpediatrician compared to the adult doctor. To describe themodel of TC for AIDs from a paediatric to adult centre of twohospitals in Rome, and to pointing out the different stepsemerged from specific experiences. Methods: In November 2020, a Board of paediatriciansand internists discussed their experience to identify “hot topics” for a successful management of TC. Results: The Board agreed on the optimal time for thetransition (12-18 years). Specific elements to be consideredare the reached level of emotional and intellectual matu-rity, and the clinical stability of the disease. Conclusions: The TC of patients with chronic AIDs, re-quires a strong cooperation to define the adequate follow-up, and to guarantee the compliance to the treatment. Thismodel allows us to investigate AIDs complex cases requiring a long period of observations.

A longliving patient with MPS type I is herein depicted.

Fabry disease (FD) is a genetic disease included in the group of lysosomal storage disorders, caused by X-linked deficiency of the enzyme alpha-galactosidase A. The aim of this study was to evaluate different aspects related to the quality of life (QoL) of a multicentre cohort of Italian patients with FD. An observational survey was conducted to measure health-related quality of life (HR-QoL) in FD patients using the CAPI (Computer-Assisted Personal Interview) method: 106 patients (mostly women) responded to the questionnaire. Geographically, 53.7% of patients lived in northern Italy, 18.9% in central Italy and 27.4% in southern Italy or the Islands. All data were collected through a five-dimensional EuroQoL questionnaire referring to functional aspects (mobility, personal care, routine activities) and perception of physical/mental well-being (pain or discomfort, anxiety or depression). A descriptive analysis of responses was performed; FD patients were compared in terms of QoL with subjects suffering from other chronic diseases, such as Crohn’s disease, chronic hepatitis, cirrhosis and multiple sclerosis. Difficulty in normal daily activities was reported by 47.2% of FD patients. About one third of subjects also had mobility difficulties. Feelings of loneliness and isolation were reported by 33.3% of those being 60–69 years old. Anxiety was equally reported in both oldest and youngest patients (66.7%), while depression, relational problems, fear of other people’s judgement increased along with age, reaching 66.7% in the over-70-years group. Male patients were largely troubled about the risk of physical disability, particularly those aged 60 years or over. Furthermore, FD patients had a poorer QoL than people suffering from other chronic inflammatory disorders. Our study upholds that FD patients have a poor QoL, as already known, negatively impacting psychic well-being and social activities. Our survey has also found a worse QoL in FD patients compared with other se

Alpha-mannosidosis is a rare lysosomal storage disorder that generally presents in early childhood. It is a progressive, highly heterogeneous disease that is difficult to recognize, and a diagnosis is usually reached after referrals to multiple specialists. It is important to understand the challenges faced by patients and their caregiver up to and after a diagnosis of alpha-mannosidosis. In this report, we describe the process of alpha-mannosidosis diagnosis and treatment from the caregivers’ and physicians’ perspectives. For the caregivers’ perspective, the mothers of two patients with alpha-mannosidosis (‘Adele’ aged 35 years and ‘Amedeo’ aged 40 years) were interviewed in their homes in Italy, and anonymized transcripts were used to describe their experiences. Adele lived in a large city with access to hospitals and specialized centers and was diagnosed with alpha-mannosidosis before 3 years of age. Amedeo was from a small village and was diagnosed when he was 10–11 years old. In both cases, their mothers sought help from pediatricians and other specialists for recurrent infections and delayed speech and motor development in the first years of their lives, but diagnosis was delayed. Although the diagnostic pathway was concerning and frustrating for her mother, Adele was able to live at home and receive multidisciplinary care and psychosocial support locally, but the transition from pediatric to adult services was difficult. She is currently waiting for access to enzyme replacement therapy. Amedeo had to travel widely and frequently to receive a diagnosis and access supportive treatment. The cumulative morbidity resulting from the delays and poor access to care necessitated long-term residential care. From the physicians’ perspective, greater awareness of alpha-mannosidosis is required among healthcare professionals and more support is needed for patients and caregivers, particularly those living in rural areas or small centers.

Background: 2D speckle tracking echocardiography (2DSTE) is superior to standard echocardiography in the assessment of subtle right ventricle (RV) systolic dysfunction. In this study we aimed to: 1) test the hypothesis that 2DSTE may unveil subtle RV systolic dysfunction in patients with Fabry disease; 2) investigate whether the physiologic difference between the 3-segment (RV-FWS) and the 6-segment (RV-GLS) RV strain (∆RV strain) is preserved in Fabry patients. Methods and results: Standard echocardiography and 2DSTE were performed in 49 Fabry patients and 49 age- and sex-matched healthy controls. Fabry patients were divided in two groups according to the presence/absence of left ventricular hypertrophy (LVH+: left ventricular wall thickness > 12 mm, 49% of total Fabry patients). RV systolic function assessed by standard echocardiography was normal in the majority of Fabry patients (92%) while RV-GLS and RV-FWS were impaired in about 40%. RV-GLS and RV-FWS were significantly worse in patients LVH+ vs LVH- and vs controls (RV-GLS: LVH+ vs LVH-: −18.4 ± −4.3% vs −23.8 ± −3.1% p<0.001; LVH+ vs controls: −18.4 ± −4.3% vs −23.9 ± −2.8% p<0.001; RV-FWS: LVH+ vs LVH-: −21.8 ± −5.3% vs −26.7 ± −3.8% p = 0.002, LVH+ vs controls −21.8 ± −5.3% vs −26.8 ± −3.9% p<0.001). No difference was found between LVH- patients and controls in both RV-GLS (p = 0.65) and RV-FWS (p = 0.79). ∆RV strain was similar among the groups. Conclusions: In Fabry cardiomyopathy impaired RV-GLS and RV-FWS is a common finding, while RV strain is preserved in Fabry patients without overt cardiac involvement. The physiologic difference between RV-FWS and RV-GLS is maintained in Fabry patients, regardless of the presence of cardiomyopathy.

Aims: In Fabry cardiomyopathy, left ventricular outflow tract obstruction mimicking hypertrophic cardiomyopathy is a very rare finding, with few cases reported and successfully treated with cardiac surgery. In our population of patients with Fabry disease and severe left ventricular hypertrophy (LVH) at the time of diagnosis, we observed an evolution towards a midventricular obstructive phenotype. Methods and results: We present a case series of three classically affected Fabry male patients with significant diagnostic delay and severe cardiac involvement (maximal wall thickness >20 mm) at first evaluation. All patients developed midventricular obstructive form over time despite prompt initiation and optimal compliance to enzyme replacement therapy. The extension and distribution of the LVH, involving the papillary muscles, was the main mechanism of obstruction, unlike the asymmetric septal basal hypertrophy and the mitral valve abnormalities commonly seen as substrate of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. Conclusions: Fabry cardiomyopathy can evolve over time towards a midventricular obstructive form due to massive LVH in classically affected men with significant diagnostic delay and severe LVH before enzyme replacement therapy initiation. This newly described cardiac phenotype could represent an adverse outcome of the disease.

Aims: Right ventricular hypertrophy (RVH) is a common finding in Anderson–Fabry disease (AFD), but the prognostic role of right ventricular (RV) involvement has never been assessed. The aim of our study was to evaluate the prognostic significance of RVH and RV systolic function in AFD. Methods and results: Forty-five AFD patients (56% male patients) with extensive baseline evaluation, including assessment of RVH and RV systolic function, were followed-up for an average of 51.2 ± 11.4 months. RV systolic function was assessed by standard and tissue Doppler echocardiography. Cardiovascular events were defined as new-onset atrial fibrillation (AF), sustained ventricular arrhythmias, heart failure, or pacemaker/implantable cardioverter defibrillator implantation; renal events were defined as progression to dialysis and/or renal transplantation or significant worsening of glomerular filtration rate; and cerebrovascular events were defined as transient ischaemic attack or stroke. Fourteen patients (31.1%) presented RVH, while RV systolic function was normal in all cases. During the follow-up period, 13 patients (28.8%, 11 male) experienced 18 major events, including two deaths. Cardiovascular events occurred in eight patients (17.7%). The most common event was pacemaker/implantable cardioverter defibrillator implantation (six patients, 13.3%), followed by AF (three cases, 6.6%). Only one case of worsening New York Heart Association class (from II to III and IV) was observed. Ischaemic stroke occurred in three cases (6.6%). Renal events were recorded in three patients (6.6%). At univariate analysis, several variables were associated with the occurrence of events, including RVH (HR: 7.09, 95% CI: 2.17 to 23.14, P = 0.001) and indexes of RV systolic function (tricuspid annular plane systolic excursion HR: 0.77, 95% CI: 0.62 to 0.96, P = 0.02; and RV tissue Doppler systolic velocity HR: 0.76, 95% CI: 0.61 to 0.93, P = 0.01). At mul

Hepatic involvement in familial Mediterranean fever (FMF) ranges from a nonspecific increase in liver enzymes to cryptogenic cirrhosis, and the liver is mostly involved in patients bearing the M694V MEFV mutation in homozygosis. A 44-year-old Jewish woman with FMF developed nonalcoholic steatohepatitis during colchicine treatment (2,5 mg per day), confirmed by both elastography and liver biopsy. Therefore, combined therapy with the interleukin-1 (IL-1) blocking agent canakinumab (150 mg every four weeks) and colchicine (at a reduced dose of 1.5 mg per day) was started. Three months later, transaminases became normal, and after further six months, there was a marked improvement of liver fibrosis. IL-1 blockade has the power to halt or mitigate liver involvement in FMF patients. However, further experience is required to assess its therapeutic potential in the most severe patients with the hepatic disease who are partially responsive to long-term prophylaxis with colchicine.

Objective. Familial Mediterranean fever (FMF) is an autosomal recessive disease due to a MEFV gene mutation. Since Helicobacter pylori infection has been described to increase the severity and frequency of FMF attacks, we evaluate if overgrowth of small intestinal bacterial (SIBO), associated with a release of bacterial products, can affect the response to colchicine in FMF patients poorly responsive to colchicine. Methods. We revised our Periodic Fever Centre database to detect FMF patients who were poorly responsive to colchicine, without a well-defined cause of drug resistance. They were evaluated for SIBO presence, then treated with decontamination therapy. Results. Among 223 FMF patients, 49 subjects show colchicine resistance, and no other known causes of colchicine unresponsiveness has been found in 25 patients. All 25 patients underwent glucose breath test; 20 (80%) of them were positive, thus affected by SIBO. After a successful decontamination treatment, 11 patients (55%) did not show FMF attacks during the following three months (p<0.01), while 9 of them revealed a significant reduction of the number of attacks compared to three months before (p<0.01). Conclusion. The SIBO eradication improves laboratory and clinical features of FMF patients. Thus, patients with unresponsiveness to colchicine treatment should be investigated for SIBO.

Objective: To identify a set of variables that could discriminate patients with adult-onset PFAPA syndrome from subjects with fever of unknown origin (FUO). Methods: We enrolled 74 adults diagnosed with PFAPA syndrome according to the currently used pediatric diagnostic criteria and 62 additional patients with FUO. After having collected clinical and laboratory data from both groups, monovariate and multivariate analysis was performed in order to identify the variables associated with PFAPA diagnosis. Odds ratio (OR) values, their statistical significance and corresponding 95% confidence interval (CI) were evaluated for each diagnostic factor both at the monovariate and multivariate analysis. Diagnostic accuracy was evaluated by the area under receiver operating characteristic curve, while the leave-one-out cross-validation procedure was used to ensure that the model maintains the same diagnostic power when applied to new data Results: According to the multivariate analysis, the clinical variables that discriminated PFAPA patients were: fever episodes associated with cervical lymphadenitis (OR=92; p<0.0001), fever attacks associated with erythematous pharyngitis (OR=231; p<0.0001), increased inflammatory markers during fever attacks (OR=588; p=0.001) and the lack of clinical and laboratory signs of inflammation between flares (OR=1202; p<0.0001). These variables were considered for a diagnostic model which accounted for their OR values. The diagnostic accuracy of the proposed set of criteria corresponded to an area under receiver operating characteristic curve of 0.978 (95% CI 0.958-0.998), with a model sensitivity and specificity equal to 93.4% (95% CI 87.5%-96.5%) and 91.7% (95% CI 82.8%-96.7%), respectively. Conclusions: We have provided herein a set of clinical diagnostic criteria for adult-onset PFAPA syndrome. Our criteria represent an easy-to-use diagnostic tool aimed at identifying PFAPA patients among subjects with FUO with a high predictive potent

Malnutrition is a major complication of inflammatory bowel disease (IBD). This mini review is focusing on main determinants of malnutrition in IBD, the most important components of malnutrition, including lean mass loss and sarcopenia, as an emerging problem. Each one of these components needs to be well considered in a correct nutritional evaluation of an IBD patient in order to build a correct multidisciplinary approach. The review is then focusing on possible instrumental and clinical armamentarium for the nutritional evaluation.

The familial Mediterranean fever (FMF) is the primarily described and most prevalent autoinflammatory disease known in the world. FMF was so named by Heller, because of its high prevalence in the Mediterranean population. Indeed, it was previously denominated as benign paroxysmal peritonitis by Siegal, a New York allergist of Jewish origin, whereas it has been described as Maladie periodique by French authors.

Pulmonary-renal syndromes (PRS) are characterized by the simultaneous presence of diffuse alveolar hemorrhage and acute glomerulonephritis. The most common causes of PRS are ANCA-associated vasculitides, Goodpasture's syndrome and systemic lupus erythematosus. The clinical picture of PRS includes hemoptysis (not always present), acute-onset anemia and renal abnormalities ranging from isolated urinary abnormalities to rapidly progressive glomerulonephritis. The severity of the pulmonary involvement determines the mortality risk as well as the need for mechanical ventilation in intensive care. The diagnosis of PRS is based upon clinical, serological, radiological and histological findings. Immunosuppressive therapy, along with an adequate support therapy (especially aimed at avoiding microbial infection), needs to be started promptly and effectively to reduce both the mortality risk and long-term complications such as end-stage renal disease.