Aim of this study was to investigate the activation of the IFNγ pathway in the affected liver and in the blood of patients with secondary hemophagocytic lymphohistiocytosis (sHLH). To this purpose, ...the mRNA expression levels of IFNG and IFNγ-inducible genes as well as Tyrosine (701)-phosphorylated signal transducer and activator of transcription 1 (STAT1) protein levels were evaluated in the liver and in peripheral blood mononuclear cells (PBMCs) of three patients with sHLH with predominant liver involvement. The mRNA expression levels of IFNG and IFNγ-inducible genes were markedly higher in patient livers compared to control livers and to one disease control liver. Conversely, slight differences in the expression levels of Type I IFN-inducible genes and other classical inflammatory cytokine genes were found. Further supporting the activation of the IFNγ pathway, higher protein levels of phosphorylated and total STAT1 were detected in patient livers compared to control livers. When the expression of the same genes analysed in liver tissues was evaluated in PBMCs collected from 2 out of 3 patients before the liver biopsy, we found that mRNA levels of IFNγ-inducible genes were markedly increased. Accordingly, high circulating levels of IFNγ-inducible CXCL9 were observed in patients. Altogether, these data demonstrate the selective and marked up-regulation of the IFNγ pathway in the liver tissue and blood of patients with active sHLH. Finally, we show that measurement of circulating CXCL9 levels and evaluation of IFNγ-inducible gene expression levels in PBMCs may represent a new valid tool to better identify patients with suspected HLH with predominant liver involvement.
Juvenile osteoperiostites (JOP) are a group of inflammatory bone diseases whose differential diagnosis is often difficult. The main conditions are acute osteomyelitis (AOM), chronic non-bacterial ...osteomyelitis (CNO) and the Goldbloom syndrome (GS). The study was aimed to develop an algorithm to enable an early diagnosis of JOP. Clinical records of patients with AOM, CNO and GS, followed at our Center over the past 10 years, were reviewed. Twelve additional patients with GS were selected from PubMed/MEDLINE literature search. Data collected included demographics, clinical manifestations, laboratory and instrumental investigations at disease onset. The association between categorical variables was investigated, and the segmentation of patients with different diagnoses was analyzed through a classification tree model (CTREE package) in order to build up a diagnostic algorithm. Ninety-two patients (33 CNO, 44 AOM, 15 GS) entered the study. Among 30 variables considered at onset, nine (age at onset, fever, weight loss, symmetry, focality, functional limitation, anemia, elevated ESR, CRP) resulted statistically significant in differentiating the three clinical entities from each other and were chosen to build up a decisional tree. Three variables, symmetry of bone involvement, presence of fever and age at disease onset, resulted significant to discriminate each of the three diseases from the others. The performance of the diagnostic algorithm was validated by comparing the diagnoses provided by the model with the real diagnoses and showed 85.9% accuracy.
Conclusion
: We propose a diagnostic algorithm, based on simple clinical data, which can help guide a prompt and appropriate diagnosis of JOP.
What is Known:
• Juvenile osteoperiostitis (JOP) are a group of inflammatory bone diseases followed by various pediatric specialists.
• The distinction between these conditions is not easy as clinical and laboratory features often overlap.
What is New:
• We propose a diagnostic algorithm, based on clinical data of real patients, with high degree accuracy.
• This instrument can help guide the prompt and appropriate diagnosis of JOP.
To evaluate the efficacy of levofolinic acid (LVF) administered 48 h before methotrexate (MTX) in reducing gastrointestinal side effects without interference with drug efficacy.
A prospective ...observational study was performed including patients with Juvenile Idiopathic Arthritis (JIA) reporting significant gastrointestinal discomfort after MTX despite taking a dose of LVF 48 h after MTX. Patients with anticipatory symptoms were excluded. A LVF supplemental dose was added 48 h before MTX and patients were followed every 3-4 months. At each visit data on gastrointestinal symptoms, disease activity (JADAS, ESR, CRP values) and treatment changes were collected. Friedman test for repeated measures analyzed differences between these variables over time.
Twenty-one patients were recruited and followed for at least 12 months. All patients received MTX subcutaneously (mean 9.54 mg/m2) and LVF 48 h before and after MTX (mean 6.5 mg/dose), 7 received a biological agent too. Complete remission of gastrointestinal side effects was reported in 61.9% of study patients at first visit (T1) and increased over time (85.7%, 95.2%, 85.7% and 100% at T2, T3, T4, T5, respectively). MTX efficacy was maintained as showed by significant reduction of JADAS and CRP (p = 0.006 and 0.008) from T1 to T4 and it was withdrawn for remission in 7/21.
LVF given 48 h before MTX significantly reduced gastrointestinal side effects and did not reduce drug's efficacy. Our results suggest that this strategy may improve compliance and quality of life in patients with JIA and other rheumatic diseases treated with MTX.
Multisystem Inflammatory Syndrome in Children (MIS-C) is a known severe condition affecting children previously exposed to SARS-CoV-2. The aim of our study was to describe the early cardiac ...abnormalities in patients with MIS-C, evaluated by speckle tracking echocardiography (STE) and cardiac MRI (CMR). Clinical, laboratory and microbiological data were measured for all patients. All children underwent standard transthoracic echocardiography, STE with analysis of left ventricle global longitudinal strain (GLS). Seventeen (75%) of the children were evaluated with CMR. Twenty-three patients (13M, 10F) were recruited, mean age was 8.1 ± 4 years. Cardiovascular symptoms were present in 10 (43.5%). Nine children (39.1%) shared Kawasaki Disease-like symptoms. Four patients (17.4%) needed ICU admission. In-hospital survival was 100%. TnI was elevated in 15 (65.2%) and BNP in 20 (86.9%) patients. The median time to STE evaluation was 8 days and to CMR was 18 days after fever onset. Mean LVEF was 59 ± 10%. Coronary dilation was observed in six (26.1%) patients. STE showed a reduced mean LVGLS (−17 ± 4.3%). LGE with a non-ischemic pattern was evident in six out of seventeen patients (35.2%). The elevation of myocardial necrosis markers, the reduction of LVGLS and the presence of LGE on CMR in about a quarter of MIS-C patients supports the hypothesis of a post-viral immune-mediated myocarditis-like pathogenesis.
Background Limited joint mobility (LJM), previously known as cheiroarthropathy, refers to the presence of reduced extension at the finger joints in people with diabetes and may be associated with ...scleroderma-like syndromes such as diabetic sclerodactyly. While scleroderma-like syndromes and LJM have been observed in patients with long-term diabetes and associated complications, the coexistence of diabetes with Juvenile systemic sclerosis (jSSc) is rarely described. Case presentation We describe the case of a 14-year-old boy with long-lasting type 1 diabetes (T1D) and suspected LJM associated with Raynaud phenomenon, sclerodactyly and tapering of the fingertips. A comprehensive work-up showed positive autoantibodies (ANA, anti-Ro-52, anti-Mi-2b), abnormal nailfold capillaroscopy with a scleroderma pattern, interstitial lung disease and cardiac involvement. The overall clinical picture was consistent with the diagnosis of jSSc. Conclusions LJM can be the initial sign of underlying systemic sclerosis. Nailfold capillaroscopy may help differentiate jSSc from classical LJM in pediatric patients with T1D and finger contractures or skin induration of no clear origin. This case report provides a starting point for a novel hypothesis regarding the pathogenesis of jSSc. The association between T1D and jSSc may be more than a coincidence and could suggest a relationship between glucose metabolism, fibrosis and microangiopathy. Keywords: Limited joint mobility, Cheiroarthropathy, Sclerodactyly, Nailfold capillaroscopy, Microangiopathy, Dipeptidyl peptidase-4
Currently, monoarticular Juvenile Idiopathic Arthritis (monoJIA) is included in the ILAR classification as oligoarticular subtype although various aspects, from clinical practice, suggest it as a ...separate entity.
To describe the clinical characteristics of persistent monoJIA.
Patients with oligoJIA and with at least two years follow-up entered the study. Those with monoarticular onset and persistent monoarticular course were compared with those with oligoJIA. Variables considered were: sex, age at onset, presence of benign joint hypermobility (BJH), ANA, uveitis, therapy and outcome. Patients who had not undergone clinical follow-up for more than 12 months were contacted by structured telephone interview.
Of 347 patients with oligoJIA, 196 with monoarticular onset entered the study and 118 (60.2%), identified as persistent monoJIA, were compared with 229 oligoJIA. The mean follow-up was 11.4 years. The switch from monoarticular onset to oligoarticular course of 78 patients (38.8%) occurred by the first three years from onset. In comparison with oligoJIA, the most significant features of monoJIA were later age at onset (6.1 vs. 4.7 years), lower female prevalence (70.3 vs. 83.4%), higher frequency of BJH (61.9 vs. 46.3%), lower frequency of uveitis (14.4 vs. 34.1%) and ANA+ (68.6 vs. 89.5%) and better long-term outcome.
MonoJIA, defined as persistent arthritis of unknown origin of a single joint for at least three years, seems to be a separate clinical entity from oligoJIA. This evidence may be taken into consideration for its possible inclusion into the new classification criteria for JIA and open new therapeutic perspectives.
Background: Eligibility criteria for blood donation require hemoglobin levels of ≥12.5 g/dL for women and ≥13.5 g/dL for men, and a platelet count of ≥180 × 109/L. Screening methods before donation ...should ensure high accuracy, precision, and ease in operation. We assessed the performance, precision, and repeatability of the Horiba Micros ES 60 (Horiba) compared to the Beckman Coulter DXH 800. Methods: Performance was compared by testing samples for each of the 11 devices across 6 sites in the Transfusion Service of Friuli Venezia Giulia Region, Italy. We measured precision by calculating the coefficient of variation (CV), concordance with ρ-Pearson’s correlation coefficient, and accuracy with F-tests. The intra-assay agreement was examined in the 11 devices, and repeatability was performed by using CV and the Kruskal−Wallis test. Results: The precision of Horiba was acceptable. Overall, ρ-Pearson’s coefficients indicated a strong correlation and positive relationship between all variables. The Bland−Altman plots showed that most of the differences lay within the limits of agreement. All CV were below the reference threshold for all the parameters. Finally, the Kruskal−Wallis test reported non-significant statistical differences for all parameters, except platelet count (p < 0.000). Conclusions: Horiba is adequate for routine pre-donation screening. The intra-assay agreement further demonstrates the accuracy of the device.
Multisystem inflammatory syndrome in children (MIS-C) is a serious condition triggered by SARS-COV-2 infection, characterized by persistent fever, multiorgan dysfunction, and increased inflammatory ...markers. It requires hospitalization and prompt treatment, with nearly 60% of the cases needing intensive care and 2% fatality rate. A wide spectrum of clinical characteristics and therapeutic approaches has been reported in MIS-C. We describe a series of four patients with MIS-C, defined according to the current case definitions, with a self-limiting course and no need for immunomodulatory treatment ("self-limiting MIS-C"). Few data about self-limiting MIS-C are available to date and no information on medium- and long-term outcome of this subset of patients has been reported. Although limited in size, our experience provides new insights into the MIS-C syndrome, highlighting an underestimated aspect of the disease that may have significant therapeutic implications.
Macrophage activation syndrome (MAS) is a rare, potentially life-threatening, condition triggered by infections or flares in rheumatologic and neoplastic diseases. The mainstay of treatment includes ...high dose corticosteroids, intravenous immunoglobulins and immunosuppressive drugs although, more recently, a more targeted approach, based on the use of selective cytokines inhibitors, has been reported. We present the case of a two-year-old boy with 1-month history of high degree fever associated with limping gait, cervical lymphadenopathy and skin rash. Laboratory tests showed elevation of inflammatory markers and ferritin. By exclusion criteria, systemic onset Juvenile Idiopathic Arthritis (sJIA) was diagnosed and steroid therapy started. A couple of weeks later, fever relapsed and laboratory tests were consistent with MAS. He was promptly treated with high doses intravenous methylprednisolone pulses and oral cyclosporin A. One day later, he developed an acute myocarditis and a systemic capillary leak syndrome needing intensive care. Intravenous Immunoglobulin and subcutaneous IL-1-antagonists Anakinra were added. On day 4, after an episode of cardiac arrest, venous-arterial extracorporeal membrane oxygenation (VA-ECMO) was started. Considering the severe refractory clinical picture, we tried high dose intravenous Anakinra (HDIV-ANA, 2 mg/Kg q6h). This treatment brought immediate benefit: serial echocardiography showed progressive resolution of myocarditis, VA-ECMO was gradually decreased and definitively weaned off in 6 days and MAS laboratory markers improved. Our case underscores the importance of an early aggressive treatment in refractory life-threatening sJIA-related MAS and adds evidence on safety and efficacy of HDIV-ANA particularly in acute myocarditis needing VA-ECMO support.
Kidney involvement has been poorly investigated in SARS-CoV-2 Multisystem Inflammatory Syndrome in Children (MIS-C). To analyze the spectrum of renal involvement in MIS-C, we performed a ...single-center retrospective observational study including all MIS-C patients diagnosed at our Pediatric Department between April 2020 and May 2022. Demographic, clinical, pediatric intensive care unit (PICU) admission’s need and laboratory data were collected at onset and after 6 months. Among 55 MIS-C patients enrolled in the study, kidney involvement was present in 20 (36.4%): 13 with acute kidney injury (AKI) and 7 with isolated tubular dysfunction (TD). In eight patients, concomitant AKI and TD was present (AKI-TD). AKI patients needed higher levels of intensive care (PICU: 61.5%, p < 0.001; inotropes: 46.2%, p = 0.002; second-line immuno-therapy: 53.8%, p < 0.001) and showed lower levels of HCO3- (p = 0.012), higher inflammatory markers neutrophils (p = 0.092), PCT (p = 0.04), IL-6 (p = 0.007) as compared to no-AKI. TD markers showed that isolated TD presented higher levels of HCO3- and lower inflammatory markers than AKI-TD. Our results indicate a combination of both pre-renal and inflammatory damage in the pathogenesis of kidney injury in MIS-C syndrome. We highlight, for the first time, the presence of tubular involvement in MIS-C, providing new insights in the evaluation of kidney involvement and its management in this condition.
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