Rolando Cimaz

In this systematic review we analyzed the published articles related to the predictive value for flare of subclinical synovitis assessed by ultrasound (US) in juvenile idiopathic arthritis (JIA). Medline, Embase and Cochrane databases were searched from 1990 to 2020 by two authors, using PICO methodology. The study is built and reported according to PRISMA guidelines. Searches identified four articles comprising a total of 187 JIA patients in clinical remission from at least 3 months. Two of the articles found US subclinical signs of synovitis to be predictive for flare, with a five times higher risk (with Power Doppler signal as an important feature), while in the other two baseline US abnormalities did not predict a clinical flare. The articles differed for protocols, definitions, and length of follow-up. US has an expanding role in pediatric rheumatology, with interest-ing applications especially during the follow-up, potentially identifying subclinical inflammatory signs predictive of flare. However, the few studies available do not allow definite conclusions at this time.

(1) Background: The link between periodontal disease and rheumatoid arthritis (RA) is now widely reported. Several studies suggest the role of Porphyromonas gingivalis (P. gingivalis) in the pathophysiology of RA and some observations highlight the improvement of the disease activity induced by therapies against P. gingivalis. We have very little data on the prevalence of P. gingivalis carriage in patients with juvenile idiopathic arthritis (JIA) and its possible involvement in the pathophysiology of inflammatory joint diseases in children. (2) Methods: The specific IgG responses against P. gingivalis and Prevotella intermedia (P. intermedia) were determined in a cohort of 101 patients with JIA and 19 patients with other autoimmune diseases (inflammatory bowel disease and type 1 diabetes). (3) Results: Specific anti-P. gingivalis and anti-P. intermedia IgG titers were higher in JIA group than in control groups. These differences were mainly observed in the oligoarthritis group. The same pattern was observed in enthesitis-related arthritis (ERA). (4) Conclusions: Children with oligoarticular and ERA subsets had higher IgG titers to P. gingivalis and P. intermedia. These results suggest involvement of an oral dysbiosis in the occurrence of JIA in these subgroups.

Background: Chronic recurrent multifocal osteomyelitis (CRMO) is a bone inflammatory disorder characterized by osteolytic, usually multiple, symmetric lesions. Diagnosis is one of exclusion, and no standardized therapies are available. Presumed deregulation of the interleukin (IL)‐1β axis, as observed in 2 monogenic autoinflammatory conditions such as Majeed syndrome (LPIN2 mutations) and deficiency of IL‐1 receptor antagonist (IL1RN mutations) with CRMO‐like bone involvement, suggests the blockade of IL‐1 as potentially useful also in this condition, even if scarce data are available.Case presentation: We report the case of a 13‐year‐old girl affected by a multidrug‐resistant and pyoderma gangrenosum‐complicated CRMO treated with canakinumab, a human monoclonal antibody targeting IL‐1β.Conclusion: In this young patient pyoderma gangrenosum and CRMO showed a rapid and satisfactory response to canakinumab, although over time a decreased efficacy in controlling bone disease was observed.

Arthritis is a common condition that any pediatrician may have to deal with

Osteoporosis may affect young individuals, albeit infrequently. In childhood, bone mass increases, reaching its peak between the second and third decades; then, after a period of stability, it gradually declines. Several conditions, including genetic disorders, chronic diseases, and some medications, can have an impact on bone homeostasis. Diagnosis in young patients is based on the criteria defined by the International Society for Clinical Densitometry (ISCD), published in 2013. High risk factors should be identified and monitored. Often simple interventions aimed to eliminate the underlying cause, to minimize the negative bone effects linked to drugs, or to increase calcium and vitamin D intake can protect bone mass. However, in selected cases, pharmacological treatment should be considered. Bisphosphonates remain the main therapeutic agent for children with significant skeletal fragility and are also useful in a large number of other bone conditions. Denosumab, an anti-RANKL antibody, could become a potential alternative treatment. Clinical trials to evaluate the long-term effects and safety of denosumab in children are ongoing.

Editorial: Pathogenesis, Clinical Findings, and Treatment Advances in Kawasaki Disease

The term septic arthritis refers to an infection of the synovial space. This is an infrequent condition in healthy children, but it should be considered a medical emergency potentially leading to irreversible articular damage. Therefore, prompt diagnosis and antimicrobial treatment play a crucial role in improving the prognosis. Although septic arthritis is the most common cause of acute arthritis, many other diseases may mimic a similar clinical picture, constituting a diagnostic challenge for the clinician who first approaches the patient. Herein we analyze the main features of septic arthritis, offering an overview of the main conditions involved in the differential diagnosis and suggesting a diagnostic workup plan.

Introduction IgA vasculitis nephritis (IgAVN) is almost the only cause of morbidity and mortality among children suffering from this most common childhood-vasculitis. Several histological classifications are used in the analysis of renal biopsy findings in IgAVN, but it remains unknown which one is the best predictor of severity and disease outcome. Objectives The aim was to compare the four most commonly used histologic classifications for IgAVN and to establish which variables of each histological classification have the strongest association with unfavorable outcome. Methods The cross-sectional study included 69 patients with IgAVN (diagnosed by EULAR/PRES/PRINTO criteria) and available renal biopsy specimens for analysis using the four histological classifications for IgAVN (the International Study of Kidney Disease in Children (ISKDC) classification, the Oxford classification, the Haas histologic classification of IgA nephropathy and the modified semi-quantitative classification (SQC), developed by Koskela et al.). The clinical outcome was defined through four categories, graded according to the modified classification of Counahan (physical examination, hematuria, proteinuria, urine albumin-to-creatinine ratio, hypertension and eGFR). The linear relationships between outcome and histological classifications were analysed using ordinal regressions using the first-order of polynomial orthogonal contrasts. Results The SQC classification proved to be the best, reducing the deviation (of the model-predicted outcome value from the observed value) by 9.5% (χ21=13,89, pConclusion This study showed that the SQC classification has the strongest association with the IgAVN severity and outcome. Although crescents on renal biopsy were considered the most important outcome indicators, our study suggests that tubulointerstitial changes could be more important as predictors of poor outcome. Interstitial and renal tubules changes should be further explored in order to have better predictive values of IgAVN outcome and to be incorporated into existing or new classifications, on the basis of which guidelines for the treatment of patients would be developed. SUPPORT: Croatian Science Foundation project IP-2019-04-8822.

Since the coronavirus disease 2019 (COVID-19) outbreak started, children have been considered marginally involved compared to adults, with a quite significant percentage of asymptomatic carriers. Very recently, an overwhelming inflammatory activation, which shares clinical similarities with Kawasaki disease (KD), has been described in children exposed to COVID-19. We report three KD-like cases that occurred during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a highly affected area of Northern Italy. The clinical presentation was characterized by the presence of unremitting fever, diarrhea and elevated inflammatory markers. Case #1 and Case #2 occurred one week apart and shared other clinical features: laboratory tests confirmed COVID-19 exposure and high inflammatory activation with myocardial involvement. Case #3 followed a more typical pattern for KD. Interestingly, this patient showed lower levels of procalcitonin, C-reactive protein, D-dimers, and ferritin compared to the other two cases, whereas platelet count was higher. We hypothesize that SARS-CoV-2 might act in children as a trigger, either inducing a classical KD phenotype or causing a systemic inflammatory response leading to a severe KD-like phenotype, eventually characterized by myocardial impairment. We think that bringing these cases and their differences to the attention of the rheumatology community during the COVID-19 pandemic will be beneficial in order to highlight the importance of early diagnosis and to increase awareness of this new phenomenon.