179 research outputs found
Severe congenital neutropenia due to G6PC3 deficiency: early and delayed phenotype in two patients with two novel mutations
No full textSevere Congenital Neutropenia type 4 (SCN4, OMIM 612541) is a rare autosomal recessive disease due to mutations in the G6PC3 gene. The phenotype comprises neutropenia of variable severity and other anomalies including congenital heart defects, prominent superficial veins, uro-genital anomalies, facial dysmorphism, growth and developmental delay and intermittent thrombocytopenia. In some patients, SCN represents the only manifestation of the disease. Variable findings have been reported at bone marrow examination ranging from a maturation arrest at the myelocyte/promyelocyte stage (either in a hypocellular or hypercellular context) to myelokathexis. Here we report two patients harbouring two novel mutations in the G6PC3 gene, including the first Italian patient even described. Both the patients share profound neutropenia with severe infections early in life; in one case non-hematopoietic stigmata of the syndrome, including evident facial dysmorphism and vascular anomalies, appeared gradually over time, prominently in the second decade. Therefore, G6PC3 defects should be considered in any case of congenital, unexplained neutropenia regardless of the clinical phenotype. Both patients are on G-CSF treatment with no evidence of malignant evolution. Even if G6PC3 deficiency seems not to have a propensity towards malignancy, a careful evaluation is warranted
Effectiveness and Safety of Real-Time Transthoracic Ultrasound-Guided Thoracentesis
No full textPurpose: The purpose of the present study was to specifically evaluate the effectiveness and safety of real-time ultrasound-guided thoracentesis in a case series of pleural effusion. Patients and methods: An observational prospective study was conducted. From February 2018 to December 2019, a total of 361 consecutive real-time transthoracic ultrasound (TUS)-guided thoracentesis were performed in the Unit of Diagnostic and Interventional Ultrasound of the Research Hospital “Fondazione Casa Sollievo della Sofferenza” of San Giovanni Rotondo, Foggia, Italy. The primary indication for thoracentesis was therapeutic in all the cases (i.e., evacuation of persistent small/moderate pleural effusions to avoid super-infection; drainage of symptomatic moderate/massive effusions). For completeness, further diagnostic investigations (including chemical, microbiological, and cytological analysis) were conducted. All the procedures were performed by two internists with more than 30 years of experience in interventional ultrasound using a multifrequency convex probe (3–8 MHz). For pleural effusions with a depth of 2–3 cm measured at the level of the costo-phrenic sinus was employed a dedicated holed convex-array probe (5 MHz). Results: In all the cases, the attempts at thoracentesis were successful, allowing the achievement of the therapeutic purpose of the procedure (i.e., the complete drying of the pleural space or the withdrawal of fluid till a “safe” quantity [a mean of 1.5 L, max 2 L] producing relief from symptoms) regardless of the initial extent of the pleural effusion. There were only 3 cases of pneumothorax, for a prevalence rate of complications in this population of 0.83%. No statistical difference was recorded in the rate of pneumothorax according to the initial amount of pleural fluid in the effusion (p = 0.12). All the pleural effusions classified as transudates showed an anechoic TUS appearance. Only the exudative effusions showed a complex nonseptated or a hyperechoic TUS appearance. However, an anechoic TUS pattern was not unequivocally associated with transudates. Some chronic transudates have been classified as exudates by Light’s criteria, showing also a complex nonseptated TUS appearance. The cytological examination of the drained fluid allowed the detection of neoplastic cells in 15.89% cases. On the other hand, the microbiological examination of effusions yielded negative results in all the cases. Conclusions: Real-time TUS-guided thoracentesis is a therapeutically effective and safe procedure, despite the diagnostic yield of the cytological or microbiological examinations on the collected liquid being very low. Future blinded randomized studies are required to definitely clarify the actual benefit of the real-time TUS-guided procedure over percussion-guided and other ultrasound-based procedures
A multicenter, real-world experience with recombinant FXIII for the treatment of patients with FXIII deficiency: from pharmacokinetics to clinical practice. The Italian FXIII Study
No full textBackground: Congenital factor XIII (FXIII) deficiency is a rare coagulation disorder characterized by muscular or mucocutaneous bleeding with life-threatening intracranial hemorrhages (ICHs), especially in cases with severe disease. The best treatment is the use of prophylactic plasma-derived or recombinant FXIII (rFXIII). Few data on the use of rFXIII in the real-world scenario are available. The main goal of this study was to assess the efficacy and safety of catridecacog (NovoThirteen®) in a population of patients with FXIII deficiency. Other objectives were to compare the different pharmacokinetic (PK) profiles of each patient and to use them to create a tailored prophylaxis regimen. Materials and methods: We collected and analyzed all pharmacokinetic and clinical data in our registry of the patients with congenital FXIII deficiency treated with rFXIII at eleven Italian hemophilia centers. Data were collected from January 2019 to December 2020. Results: Overall, data on 20 patients with FXIII deficiency were collected, 16 of whom presented with severe disease. Pharmacokinetics was assessed in 18 cases before starting prophylaxis. Prophylaxis was subsequently started in these patients using a wide range of dosages (25.0-80.0 IU/kg; mean 33.8 IU/kg) and infusion intervals (3.0-8.0 weeks). During a mean follow up of 47 months, two minor bleeds and one ICH in a severe patient who had remained under on-demand treatment were reported. Discussion: Efficacy and safety of rFXIII were proven in all patients. The dosage and infusion timing for the treated patients sometimes differed to those reported in the MENTOR pivotal studies, thus underlying the importance of tailored management in a real-world scenario
Congenital Hypopigmentary Disorders with Multiorgan Impairment: A Case Report and an Overview on Gray Hair Syndromes
No full textThe term congenital hypopigmentary disorders refers to a wide group of heterogeneous hereditary diseases, clinically characterized by inborn pigmentary defects of the iris, hair, and/or skin. They include Gray Hair Syndromes (GHSs), a rare group of autosomal recessive genodermatosis hallmarked by inborn silvery gray hair. GHSs encompass Griscelli, Chediak–Higashi, Elejalde, and Cross syndromes, which are all characterized by a broad spectrum of severe multisystem disorders, including neurological, ocular, skeletal, and immune system impairment. In this manuscript, we describe in detail the clinical, trichoscopic, and genetic features of a rare case of Griscelli syndrome; moreover, we provide an overview of all the GHSs known to date. Our report highlights how an accurate clinical examination with noninvasive methods, like trichoscopy, may play a crucial rule in diagnosis of rare and potentially lethal genetic syndromes such as Griscelli syndrome, in which timely diagnosis and therapy may modify the clinical course, quality of life, and likelihood of survival
Role of antithyroid autoimmunity as a predictive biomarker of chronic immune thrombocytopenia
No full textImmune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia. Pediatric ITP patients are prone to develop autoantibodies such as antithyroglobulin (TG) and antithyroperoxidase (TPO), even in the absence of clinical signs of autoimmune disease. The aim of this multicenter retrospective study was to evaluate (1) the prevalence of positivity of antithyroid antibodies (TPO and TG) in a large cohort of pediatric patients with chronic ITP; (2) the role of autoimmune thyroiditis as a prognostic factor for chronicity of ITP
Case Report: Severe Rhabdomyolysis and Multiorgan Failure After ChAdOx1 nCoV-19 Vaccination
No full textBackground: Severe skeletal muscle damage has been recently reported in patients with
SARS-CoV-2 infection and as a rare vaccination complication.
Case summary: On Apr 28, 2021 a 68-year-old man who was previously healthy
presented with an extremely severe rhabdomyolysis that occurred nine days following the
first dose of SARS-CoV-2 ChAdOx1 nCov-19 vaccination. He had no risk factors, and
denied any further assumption of drugs except for fermented red rice, and berberine
supplement. The clinical scenario was complicated by a multi organ failure involving bone
marrow, liver, lung, and kidney. For the rapid increase of the inflammatory markers, a
cytokine storm was suspected and multi-target biologic immunosuppressive therapy was
started, consisting of steroids, anakinra, and eculizumab, which was initially successful
resulting in close to normal values of creatine phosphokinase after 17 days of treatment.
Unfortunately, 48 days after the vaccination an accelerated phase of deterioration,
characterized by severe multi-lineage cytopenia, untreatable hypotensive shock,
hypoglycemia, and dramatic increase of procalcitonin (PCT), led to patient death.
Conclusion: Physicians should be aware that severe and fatal rhabdomyolysis may occur
after SARS-CoV2 vaccine administration
ROLE OF ANTITHYROID AUTOIMMUNITY AS A PREDICTIVE BIOMARKER OF CHRONIC IMMUNE THROMBOCYTOPENIA
No full textBackground:Immunethrombocytopenia(ITP)isanacquiredimmune-mediateddisordercharac-terizedbyisolatedthrombocytopenia.PediatricITPpatientsarepronetodevelopautoantibod-iessuchasantithyroglobulin(TG)andantithyroperoxidase(TPO),evenintheabsenceofclinicalsignsofautoimmunedisease.Theaimofthismulticenterretrospectivestudywastoevaluate(1)theprevalenceofpositivityofantithyroidantibodies(TPOandTG)inalargecohortofpediatricpatientswithchronicITP;(2)theroleofautoimmunethyroiditisasaprognosticfactorforchronic-ityofITP.Procedure:Forthisretrospectivestudy,wecollecteddatafrompatientsdiagnosedasaffectedbychronicITPbetween2011and2014insixcentersbelongingtotheItalianAssociationofPediatricHaematologyandOncology(AIEOP).Results:Fromtheanalysisofdata,wefoundasignificantlyhigherprevalenceofantithyroidanti-bodiesinchildrenwithchronicITP(11.6%)thaninthepediatricpopulation(1.2%–1.3%).Nocorrelationhasbeenfoundbetweentheplateletcountandtheprevalenceofpositiveantithy-roidantibodiesatanydetectiontimeofthestudy.Conclusions:The results of our study demonstrated that (1) the prevalence of positivity forantithyroidantibodies(anti-TPOandanti-TG)inpediatricpatientswithchronicITPresultsissig-nificantlyhigherthaninthepediatricpopulation;(2)autoimmunethyroiditisdoesnotseemtoplayaroleasaprognosticfactorforchronicityofITPinpediatricpatient
Long term outcome of eight patients with type 1 Leukocyte Adhesion Deficiency (LAD-1): Not only infections, but high risk of autoimmune complications
No full textLeukocyte Adhesion Deficiency type 1 (LAD-1) is a rare primary immunodeficiency due to mutations in the gene encoding for the common β-chain of the β2 integrin family (CD18). Herein, we describe clinical manifestations and long-term complications of eight LAD-1 patients. Four LAD-1 patients were treated with hematopoietic stem cell transplantation (HSCT), while the remaining four, including two with moderate LAD-1 deficiency, received continuous antibiotic prophylaxis. Untreated patients presented numerous infections and autoimmune manifestations. In particular, two of them developed renal and intestinal autoimmune diseases, despite the expression of Beta-2 integrin was partially conserved. Other two LAD-1 patients developed type 1 diabetes and autoimmune cytopenia after HSCT, suggesting that HSCT is effective for preventing infections in LAD-1, but does not prevent the risk of the autoimmune complications
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