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Objective: The main aim of this study was to define the best treatment option for multisystem inflammatory syndrome in children (MIS-C) and to analyse the role of anakinra., Methods: This is a multicentre retrospective cohort study. Patients were treated according to the attending physician's decision. The patients were divided into four groups on the basis of the first treatment at time of admittance: (i) IVIG, (ii) IVIG and methylprednisolone (≤2 mg/kg/day), (iii) IVIG with high-dose methylprednisolone (>2 mg/kg/day) and (iv) anakinra with or without IVIG and/or methylprednisolone. Primary outcomes were defined as the presence of at least one of the following features: death, the failure of initial treatment, meaning the need for additional treatment for clinical worsening and cardiac involvement at the end of follow-up., Results: Two hundred thirty-nine patients were recruited. At univariate analysis, persistent heart involvement at discharge was more frequent in those not receiving anakinra as initial treatment (3/21 vs 66/189; P = 0.047). After comparisons between the four treatment regimens, adjusting for the propensity score, we observed that early treatment with anakinra was associated with a lower probability of developing persistent heart disease at the end of follow-up (odds ratio: 0.6; 95% CI: 0.4-1.0)., Conclusion: We report that early treatment with anakinra is safe and very effective in patients with severe MIS-C. In addition, our study suggests that early treatment with anakinra is the most favourable option for patients with a higher risk of developing a severe disease outcome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries.

Brucellosis, a common disease in some areas of the world, beside its typical signs and symptoms, as fever, arthropathy, hepatomegaly and splenomegaly, sometimes can complicate into thrombocytopenia, even in severe forms. The pathogenesis of thrombocytopenia in course of brucellosis is variable, and a main role is played by immunological reactions. Authors describe a case report of an eight years child who presented a severe thrombocytopenia in course of acute brucellosis. The patient responded efficaciously to the antibiotic therapy combined with immunoglobulin intravenous therapy.

Spondylodiscitis is an infection of the intervertebral disk and the adjacent vertebrae, with or without associated epidural or psoas abscesses. It is a serious disease both due to its long-term course and the possible outcomes. It is frequently caused by S. aureus and, in endemic areas, by Mycobacterium tuberculosis and Brucella spp. We describe 9 cases, from October 2004 to August 2005, all spontaneous diseases occurring in adults (mean age 64 years). The site of infection was lumbar in 7, lumbar-sacral in 1 and dorsal in 1. None were associated to sepsis. The causative bacteria were known in 6 cases (1 BK, 1 S. aureus, 4 Brucella) and unknown in 3 cases. In all cases therapy was only medical. Significant circulation in Sicily of both Mycobacterium tuberculosis and Brucella spp. make those microorganisms the most frequent agents of spondylodiscitis.

Auxological and endocrinological complications frequently occur in children with connatal HIV infection. These complications seem to be related both to the infection itself and the antiretroviral therapy. Many children consequently show height-weight and pubertal retardation without any evidence of hormonal deficit. We studied 10 children with connatal HIV infection who were enrolled in this analysis and followed up for 7 years in order to evaluate their height-weight growth, pubertal maturation, bone age progression and hormonal pattern [basal Growth hormone (GH) and GH after Clonidine or Insulin stimulation, Insulin-like Growth Factor 1 (IGF-1), Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), FSH, LH, ACTH and Cortisol, TSH, fT4, T4, T3, Ab-TGO, Leptin]. Three children showed a height lower than 3rd centile during the first two years of their life and in prepubertal age, with recurring improvement in their growth rate. Weight growth was very compromised in one girl, remaining firmly lower than 3rd centile during the follow-up. Three children presented a weight lower than 3rd centile until they were two years old. However, a height growth rate higher than 10th centile was found in nine children throughout the follow-up, while it was pathological in five children. The blood level of Leptin was higher at the beginning of the study: 0.82 - 11.68 ng/l (M+/-DS: 3.29+/-4.15) than at its conclusion: 0.2 - 3 ng/l (M+/-DS: 1.65+/-1.01). There was a statistically significant correlation between leptinemia and the CD4/CD8 count (p: 0.010; r: 0.916) and the CDC classification (p: 0.006; r: 0.937), indicating a strong relationship with the degree of virological and immunological impairment. The authors stress the importance of a careful height-weight growth rate control in HIV-infected children, as it reflects the clinical and virological course of the disease. Adequate control of the infection allows physiological growth in most patients. Moreover, we emphasize the utility of IGFBP-3 and IGF-1 measurements, since they represent growth markers which are more exact and better capable of reproduction than GH.

Geotrichum capitatum, now known as Blastoschizomyces capitatus, can be responsible for several opportunistic infections (systemic infection or localized at lungs, liver, kidney, encephalitis or meningitis) in an immunocompromised host, especially in those patients affected by leukaemia or under immunosuppressive therapies. A 66-year-old woman with polimyosite under steroid and immunosuppressant therapy was hospitalized in ICU for an acute respiratory distress with moderate hypoxaemia and normocapnia. Pulmonary X-ray revealed a bilateral pneumonia. Hypoxaemia became severe 48 hours later and the patient underwent mechanical ventilation and empirical antibiotic therapy. Blood cultures, urine cultures and serological tests were negative, while yeast was identified by Gram's stain of bronchoaspirate. Before identifying the yeasts Fluconazole was added to therapy. At day 5 the clinical conditions remained severe and Candida spp were excluded: so Fluconazole was switched to liposomal Amphotericin B. At day 8 B. capitatus was identified. At day 26 the patient died of refractory respiratory insufficiency. B. capitatus infection is infrequent and its prognosis is severe, with a high mortality rate (>50%). Microbiological diagnosis requires time to characterize the yeast. At present no standard therapy is available although some authors report a good susceptibility to Amphotericin B and Voriconazole (100%), according to NCCLS guidelines.

Aim: In order to study the impact of clinical and diagnostic parameters on the clinical outcome of children with central nervous system tuberculosis (CNS-TB), we retrospectively reviewed all cases of CNS-TB diagnosed over a 32-year period at the Children's Hospital of Palermo, Italy., Methods: Data were collected with regard to the clinical, laboratory and demographic characteristics of patients, as well as the results of radiological investigations and data on clinical outcome. In relation to the date of introduction of new diagnostic methods (indirect as well direct) and to the change of treatment periods, the authors compared the clinical outcome of patients admitted prior and after 1984. They also classified the patients into 3 different stages of illness according to the severity of the disease on admission., Results: We identified 80 patients with CNS-TB. The mean age of the children was 3 years with 54% of patients younger than 5 years. The contact source was documented in 40 patients (50%). The mean duration of symptoms prior to admission was 22 days (range 5 days - 3 months). Mantoux skin test was positive on admission in 50 patients (62%). CSF smear microscopy and culture were positive in 29% and 45% of patients respectively. PCR for Mycobacterium tuberculosis introduced in 1994 was positive in 11 out of 13 tested patients. Determination of CSF gdT lymphocytes composition applied in 7 patients shows a predominance of Vg9/Vd2 T lymphocytes. Fifteen subjects (19%) died; 11 (13%) suffered from permanent sequelae. The died children and those with permanent sequelae were younger than the others (p<0.05). Prior to 1984, none of the patients were identified during early stage of illness and 4 out of 37 patients with stage II illness died. After 1985, 44% of children were in stage I and 2 out of 4 patients with stage III died (p<0.05)., Conclusions: Stage of disease and young age are still the decisive factors in the clinical outcome of children with CNS-TB. The availability of new advanced methods has improved the identification of patients with CNS-TB in stage I and therefore the possibility of an early treatment of such patients.

Aim: To evaluate the clinical characteristics, diagnostic methods and outcome of paediatric pulmonary tuberculosis (PTB) in relation to children's ages when observed., Methods: Children under 15, who had been admitted to the Children's Hospital with PTB were prospectively evaluated. Our sample included patients with a positive tuberculin skin test and signs or symptoms of tuberculosis (TB), including abnormal chest X-rays which suggested PTB. We collected demographic, clinical, radiographic and microbiological data from the patients, in addition to carrying out contact investigations in order to find a source case. All the patients involved in this study were subjected to anti-tuberculosis treatment., Results: Sixty-two patients (44% under 5) were eligible for inclusion in our study. Children with presenting symptoms were younger than asymptomatic patients (p<0.05). A source case was found in 38 patients out of 62 children (62%) and children under 5 were more likely to have a source case than that found with older children (p<0.05). Ghon complex (infiltrate + adenopathy) tended to occur in young children (median age of 3.25, p<0.05). Fourteen children (23%) had clinical specimens which tested positive for Mycobacterium tuberculosis (MT), and 20 (32%) for MT DNA according to a polymerase chain reaction (PCR). Resistant strains to 1 or more anti-tuberculosis drugs were found in 5 children and in 4 adult sources. The patients with minimal or no radiographic change during therapy displayed symptoms for a longer period of time and were infected by a resistant strain (p<0.05)., Conclusion: Improvements in case detection, case management and contact investigations are necessary for controlling paediatric TB, especially in young children. Given that any diagnosis of TB in children is supported by epidemiological and clinical evidence rather than isolating MT, detection of the source case is important in selecting appropriate treatment.

Tuberculosis (TB) kills 2 million people each year in the world, of which 250,000 are children. In Italy, paediatric TB is 3.5% of total cases with a steady trend in the last ten years. Childhood tuberculosis remains a disease of great concern because its occurrence always indicates recent transmission and is a pivotal indicator of effectiveness of TB control efforts. The epidemiological study, including DNA fingerprinting, of 71 children affected by TB - 62 pulmonary, 9 meningitis, 2 renal- shows that the source case is frequently a parent or household member. Sensitivity to anti-tubercular drugs was tested for 18/20 isolates obtained from the children and 21/44 isolates obtained from infection sources with 5 resistant strains in each group. One child was resistant to isoniazid, and one adult source to rifampin. Multi-drug resistance was observed in 8 cases: 4 children and 4 sources. In the children's case, we may use the term primary resistance as the patients have not been previously treated with the drugs. These children's treatment lasted longer, not only because their regimen had been changed, but also because of their delayed clinical-radiological response to the treatment. These data suggest that it would be opportune to re-evaluate current treatment of childhood tuberculosis, encouraging active and integrated cooperation between epidemiologists, infectious disease specialists and paediatricians.