Early anakinra treatment improves cardiac outcome of multisystem inflammatory syndrome in children, regardless of disease severity.

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.

Case Report: An early-onset inflammatory colitis due to a variant in TNFAIP3 causing A20 haploinsufficiency.

Autoinflammatory diseases (AID) are a heterogeneous group of inherited conditions caused by abnormal activation of systems mediating innate immunity. Recent literature focuses on A20 Haploinsufficiency, an autoinflammatory disease with a phenotype resembling Behçet disease (BD). It is caused by loss-of-function mutations in TNFAIP3 gene that result in the activation of a pro-inflammatory pathway. In this case report we describe a one-year-old baby who came to our attention for hematochezia appeared at three months of age which was considered an expression of early-onset colitis. The following appearance of cutaneous inflammation Behçet-like and the positive family history concurred with the diagnosis of an autoinflammatory disease. Extended genetic tests in the patient allowed to identify a heterozygous variant in TNFAIP3 [NM_006290.4:c.460G > T, p.(Glu154Ter)], not previously described and not present in the GnomAD database. As a consequence the diagnosis A20 Haploinsufficiency was established and the appropriate management was started. The same TNFAIP3 variant was also found in her father who had suffered from recurrent oral aphthosis, vitiligo and thyroiditis since childhood. In conclusion, we described a young patient with a novel heterozygous mutation in TNFAIP3 who developed BD-like symptoms. We proposed that loss-of-function variants in TNFAIP3 may be associated with a very early-onset intestinal BD phenotype.

Reduced levels of circulating progenitor cells in juvenile idiopathic arthritis are counteracted by anti TNF-α therapy.

BACKGROUND: Endothelial progenitor cells (EPC) promote angiogenesis and vascular repair. Though reduced EPC levels have been shown in rheumatoid arthritis, no study has so far evaluated EPCs in children with juvenile idiopathic arthritis (JIA). We aimed to study circulating EPCs in children with JIA, their relation to disease activity, and effects of anti TNF-α treatment. METHODS: Circulating EPCs were quantified by flow cytometry based on CD34, CD133 and KDR expression in peripheral blood of 22 patients with oligoarticular JIA and 29 age-matched controls. EPCs were re-assessed in children with methotrexate-resistant oligo-extended JIA before and up to 12 month after initiation of anti-TNF-alpha therapy. Plasma concentrations of inflammatory and EPC-regulating factors were measured using a multiplex array. Confocal immunofluorescence was used to demonstrate EPCs in synovial tissues. RESULTS: Children with active JIA showed a significant reduction of relative and absolute counts of circulating progenitor cells and EPCs compared to age-matched healthy controls. CD34(+) cell levels were modestly and inversely correlated to disease activity. A strong inverse correlation was found between serum TNF-α and EPC levels. In 8 patients treated with anti TNF-α agents, the number of EPCs rose to values similar to healthy controls. CD34(+)KDR(+) EPCs were found in the synovial tissue of JIA children, but not in control. CONCLUSIONS: Children with JIA have reduced levels of the vasculoprotective and proangiogenic EPCs. While EPCs may contribute to synovial tissue remodelling, EPC pauperization may indicate an excess cardiovascular risk if projected later in life.

Intraosseous angioma: a rare cause of a rib mass in childhood.

Rib tumors are uncommon and represent 5% to 10% of all bony tumors. Regarding the benign rib lesions, costal angioma is very rare in childhood. We report a case of a rare angioma of a rib complicated by bone erosion in a young boy.

A child with dermatomyositis and a suspicious lymphadenopathy.

Dermatomyositis (DM) in adults is frequently associated with cancer. In contrast, juvenile DM (JDM) is predominantly idiopathic and rarely reported with occult neoplasm. We describe a patient who presented with DM that was found to be a paraneoplastic manifestation of nasopharyngeal carcinoma. Although rare, paraneoplastic JDM must be suspected in the presence of unusual features such as elevated inflammatory markers or lymphadenopathy. Accurate clinical assessment including appropriate biopsies is needed before starting glucocorticoid therapy.