Ten-month follow-up of patients with covid-19 temporally related multi-system inflammatory syndrome in children: the experience of the children hospital of Palermo

Background: In Sicily, the first wave of COVID-19 showed a low epidemic impact in paediatric population, while the second and the third waves had a higher impact on clinical presentation of COVID-19 in children and a significantly higher severe outcome in patients with multisystem inflammatory syndrome in children (MIS-C), with a frequent life-threatening progression. Methods: We describe a cohort of 22 Sicilian children (11 M; 11 F; age: 1.4-14 years), presenting with clinical features compatible with MIS-C. Patients with negative swab had a history of recent personal or parental infection. Results: The following diagnostic criteria were detected: fever (100%); cheilitis and/or pharyngeal hyperaemia (86%); latero-cervical lymphadenitis (82%); rash (73%); abdominal pain and/or vomiting and/or diarrhoea (64%); conjunctivitis (64%); hands and feet oedema (18%). 59% showed cardiac involvement (6 pericardial effusion; 8 mitral valve insufficiency; 4 insufficiency of two valves; 3 coronary artery lesions (CAL)). In all the patients, treatment was started within 72 h after the admission, with intravenous immunoglobulins (IVIG) (2 g/Kg/dose), methylprednisolone (2 mg/Kg/day in 73% of patients; 30 mg/Kg/day for 3 days, followed by 2 mg/Kg/day in 27% of patients). Two patients were treated with enoxaparin. Two patients with shock, were additionally treated with vasoactive drugs, albumin, diuretics. Cardiac involvement evolved into the complete resolution of lesions in most of the patients. All the patients were included in a follow-up, to investigate on clinical outcome and resolution of organ involvement. Cardiac valve insufficiency persisted only in 18% of children, CAL persisted only in 33% of children with coronary involvement, however without the evolution into aneurisms. Conclusions: The preferred treatment strategy was more aggressive at the diagnosis of MIS-C, to block the cytokine cascade. Most of our patients, in fact, received a first-line treatment with IVIG and steroids. This approach could explain the favourable prognosis, the rapid restoring of cardiac function also in patients with MAS or shock, and the good outcome during the 10 months follow-up in all the patients

MIS-C and co-infection with P. vivax and P. falciparum in a child: a clinical conundrum

Background The ongoing Coronavirus Disease 2019 (COVID-19) epidemic represents an unprecedented global health challenge. Many COVID-19 symptoms are similar to symptoms that can occur in other infections. Malaria should always be considered in patients with SARS-CoV-2 infection returning from endemic areas. Case presentation We present the first case of multisystem inflammatory syndrome (MIS-C) and Plasmodium vivax-falciparum and SARS-CoV2 coinfection in children. Despite clearance of parassitaemia and a negative COVID-19 nasopharyngeal PCR, the patient's clinical conditions worsened. The World Health Organization (WHO) criteria were used to make the diagnosis of MIS-C. Treatment with intravenous immunoglobulins and methylprednisolone was effective. Conclusions This case emphasizes the importance of considering malaria diagnosis in patients returning from endemic areas, even in the COVID 19 era. Malaria and SARS-CoV2 co-infection may increase the risk of MIS-C, for which early detection is critical for proper management

Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy

IntroductionImmunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response. MethodsTo better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.Results and discussionStratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56bright, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor

Proceedings of the 24th Paediatric Rheumatology European Society Congress: Part three

From Springer Nature via Jisc Publications Router.Publication status: PublishedHistory: collection 2017-09, epub 2017-09-0

CASO CLINICO: CARCINOMA TIROIDEO ASSOCIATO A IPERTIROIDISMO IN ETÀ PEDIATRICA: UNA RARA ASSOCIAZIONE

PRESENTAZIONE DEL CASO, STORIA CLINICA E SINTOMATOLOGIA R, 8 anni, sesso femminile. Nulla di rilevante all’anamnesi fisiologica e patologica remota. Bimba in sovrappeso (BMI 24,65 Kg/m2). Familiarità per neoplasia tiroidea (zia materna), tiroidite di Hashimoto e per neoplasie di altri organi. Un mese prima, tonsillite essudativa trattata con terapia antibiotica; simultaneamente comparsa di tumefazione laterocervicale dx non dolente; insorgenza di dolore e progressivo incremento del volume della tumefazione per veniva condotta in PS; all’EO: aspetto non sofferente, tumefazione laterocervicale di consistenza parenchimatosa dura, mobile nei piani sopra e sottostanti; linfoadenopatie multiple in sede laterocervicale bilateralmente;non epatosplenomegalia; all’ecografia del collo, formazioni ovalariformi disomogeneamente iperecogene, riccamente vascolarizzate (d.max 3x2cm); si disponeva ricovero c/o altra UO. IPOTESI DIAGNOSTICHE Linfoadenopatia reattiva-linfoma-patologia tiroidea (tiroidite? neoplasia?). INDAGINI DI I E II LIVELLO Nel sospetto di linfoadenopatia reattiva venivano eseguiti emocromo, indici di flogosi, tampone per SBEA, TAS, Ig per Bartonella, EBV, CMV, Mycoplasma, Adenovirus; si praticava terapia con claritromicina ed ibuprofene per 10 giorni; dato il persistere della sintomatologia e la negatività degli esami precedentemente citati, nel sospetto di malattia linfomatosa si eseguiva TAC-collo con evidenza di formazioni solide iperdense a livello della giugulare esterna (36x23 mm) e in regione paratiroidea bilateralmente (dmax 30 mm); linfoadenopatie laterocervicali diffuse, trachea improntata a dx e presenza di nodulo tiroideo nel lobo dx di circa 6 mm; immagine confermata dall’ecografia dove il nodulo appariva isoecogeno con orletto ipoecogeno. Venivano dunque eseguiti esami di funzionalità tiroidea con riscontro di TSH inferiore ai limiti di norma (0,041mg/dl), FT3-FT4 nei limiti, tireoglobulina elevata (7000ng/L), aumento di abTg (214Iu/ml). Calcitonina e anticorpi anti recettore-TSH nella norma. Si procedeva a esecuzione di biopsia linfonodale. Dopo asportazione linfonodale, riduzione della tireoglobulina (5000ng/L) DIAGNOSI ED EVENTUALE TERAPIA Alla luce dei valori di TSH quasi soppressi, seppur senza sintomatologia da ipertiroidismo, si iniziava terapia con metimazolo. All’esame istologico diagnosi di carcinoma tiroideo papillare; per volontà genitoriale, R. veniva condotta c/o Altro centro per il prosieguo della stadiazione ed intervento di tireodectomia. Segnaliamo questo caso per la rarità d’incidenza di carcinoma tiroideo in età pediatrica (incidenza: 0,5 casi/100000/anno) e per la necessità di considerarlo nella diagnosi differenziale di linfoadenopatia. L’associazione tra tiroidite e carcinoma tiroideo risulta essere frequente, è invece molto rara l’associazione con ipertiroidismo. Nel caso riportato, data la familiarità per neoplasie tiroidee potrebbe essere utile eseguire indagine genetica per gene BRAF

Interleukin-6 Is a Promising Marker of COVID-19 in Children: A Case Series of 2 Brothers with Severe COVID-19 Pneumonia

BACKGROUND To date, Coronavirus disease 2019 (COVID-19) remains a global health concern, with fatalities mostly in older age groups with underlying medical conditions, while children are less likely to manifest severe symptoms. CASE REPORT We describe the clinical cases of 2 brothers admitted to our Children's Hospital for persistent fever and cough during the COVID-19 pandemic. Case 1. A 1.5-year-old boy had fever, expiratory dyspnea, desaturation, oxygen saturation 94-96% with O2, and bilateral hissing and crackling rales. His interleukin-6 level in the acute phase of the disease was 100.41 and at the resolution it was 46.2 pg/ml. Treatment with amoxicillin plus clavulanic acid, methylprednisolone, and O2 allowed progressive improvement of clinical conditions and laboratory data. Case 2. A 3-month-old toddler was admitted to our hospital for fever, cough, and tachypnea, which started 2 days before hospitalization. He had fever, cough, conjunctivitis, mucous rhinorrhea, and 99% oxygen saturation on room air. Thorax auscultation showed whistles and buzzes. He had a positive molecular test result from a COVID-19 swab. Interleukin-6 levels during all the phases of the disease were <6.25 pg/ml. The chest X-ray was normal. Treatment with azithromycin and methylprednisolone was followed by progressive improvement of clinical conditions. CONCLUSIONS These cases support the strong correlation between interleukin-6 levels and severe clinical manifestations such as COVID-19 pneumonia, and this marker predicts a more severe clinical outcome in children. Testing serum levels of interleukin-6 in children with COVID-19 could be useful to better understand the outcome of lung damage

The Koolen-de Vries syndrome: A phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype