A monogenic autoinflammatory disease with fatal vasculitis: deficiency of adenosine deaminase 2

Purpose of review To recap the expanding clinical spectrum, genotype-phenotype associations and treatment options in the light of recently published articles regarding the deficiency of adenosine deaminase 2 (DADA2). Recent findings Whole-exome sequencing enabled novel clinical phenotypes associated withADA2mutations. Since its discovery, the phenotypic spectrum of DADA2 has substantially expanded to cover Diamond-Blackfan anaemia, cytopenia and immunodeficiency syndromes. In addition to elevated TNF alpha levels, increased levels of interferon-stimulated genes were also detected in patients with DADA2. Given the absence of clinical trials until now, no standard treatment strategy exists for DADA2. Currently, anti-TNF alpha agents are the mainstay of treatment, based on the data both from the initial two reports and from subsequent studies. However, it is still unclear how to manage asymptomatic patients withADA2mutation and/or with absent ADA2 activity and what is the optimal duration of anti-TNF therapy. Among a total of 206 DADA2 patients described so far, the overall mortality was found as 8.3%. Biallelic homozygous G47R mutations were mostly associated with a vascular phenotype, whereas patients with homozygous R169Q mutations seem to display a mixed clinical phenotype including vascular, haematological and immunological manifestations. HSCT should be reserved as a curative treatment option for DADA2 patients unresponsive to the anti-TNF therapy, as it carries a significant morbidity

Childhood Rheumatic Diseases and COVID-19 Pandemic: An Intriguing Linkage and a New Horizon

As it is known, we are all in a pandemic situation due to a novel coronavirus, officially named "Severe Acute Respiratory Syndrome Coronavirus 2" and the disease caused by the virus named "Coronavirus disease-2019". The virus seems to has propensity to infect older male individuals with underlying disease. The clinical features were on a large scale that varies from being an asymptomatic carrier to acute respiratory distress syndrome and multiorgan dysfunction. Fever, dry cough and fatigue are the most common symptoms. Not only, the disease seems to be rare and have a milder course in pediatric age but also respiratory failure, multiorgan dysfunction, and death are extremely rare. Although several comorbidities such as hypertension, diabetes and cardiovascular diseases are defined as a risk factor for developing the acute respiratory syndrome and need for intensive care; immune-compromised situations such as rheumatic disease which require immunosuppressive treatment strikingly are not found to be a risk factor for more severe disease course. However, there is a lack of data regarding the effects of "Coronavirus disease-2019" on pediatric patients with rheumatic diseases. Additionally, there are three controversial circumstances that patients with rheumatic diseases are believed to be more likely to have viral infections like "Severe Acute Respiratory Syndrome Coronavirus 2", on the other hand, antirheumatic drugs may have a protective and therapeutic role in Coronavirus disease-2019 and children are more unlikely to have serious disease course. Therefore, we aimed to have a contributor role for explaining this conundrum and present a bird's eye view regarding this equivocal issue in this review

Autoinflammatory Diseases in Childhood

Autoinflammatory diseases are characterized by recurrent fevers and clinical findings of impaired natural immunity and can involve various organ systems. The concept of autoinflammatory disease emerged after the definition of familial Mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome. This new disease group was considered to differ from the standard concept of autoimmune diseases, which is relatively better known in terms of basic features, such as defects in innate immunity and the absence of antibodies. A better understanding has been achieved regarding the genetic and pathogenetic mechanisms of this relatively new disease group over the past 20 years since they were first diagnosed, which have led to some changes in the concept of autoinflammatory diseases. The recent definition classifies autoinflammatory disease to be a wide range of diseases with different clinical features, mainly accompanied by changes in innate immune and rarely in humoral immunity. The spectrum of autoinflammatory diseases is rapidly expanding owing to recent developments in molecular sciences and genetics. This review article discusses the clinical features, classification criteria, treatment options, and long-term prognosis of periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome, and other common autoinflammatory diseases in the light of current literature

Effects of sense and functionality changes in the hands on activity and participation in patients with juvenile scleroderma

Objective

Biologics in juvenile idiopathic arthritis-main advantages and major challenges: A narrative review

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The disease is divided in different subtypes based on main clinical features and disease course. Emergence of biological agents targeting specific pro-inflammatory cytokines responsible for the disease pathogenesis represents the revolution in the JIA treatment. Discovery and widespread usage of biological agents have led to significant improvement in JIA patients' treatment, with evidently increased functionality and decreased disease sequel. Increased risk of infections remains the main discussion topic for years. Despite the slightly increased frequency of upper respiratory tract infections reported in some studies, the general safety of drugs is acceptable with rare reports of severe adverse effects (SAEs). Tuberculosis (TBC) represents the important threat in regions with increased TBC prevalence. Therefore, routine screening for TBC should not be neglected when prescribing and during the follow-up of biological treatment. Malignancy represents a hypothetical complication that sometimes causes hesitations for physicians and patients in its prescription and usage. On the other hand, current reports from the literature do not support the increased risk for malignancy among JIA patients treated with biological agents. A multidisciplinary approach including a pediatric rheumatologist and an infectious disease specialist is mandatory in the follow-up of JIA patients. Although the efficacy and safety of biological agents have been proven in different studies, there is still a need for long-term, multicentric evaluation providing relevant data

A recently explored aspect of the iceberg named COVID-19: multisystem inflammatory syndrome in children (MIS-C)

Humanity has recently gained a novel foe named coronavirus disease 2019. Although data so far mostly suggest that children are more likely to have a favorable disease course, new concerns have been raised because of recently reported pediatric cases with hyperinflammatory conditions resembling Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Because the increasing evidence suggests that this recent hyperinflammatory condition emerged in the coronavirus disease 2019 era is a distinct clinical picture, the Centers for Disease Control and Prevention named this novel disease multisystem inflammatory syndrome in children. Even if this novel disease is rare, it seems to be highly fatal. Therefore, it is urgent to understand the pathogenesis of the disease to be able to establish the appropriate treatment regimes. Concerns regarding the diagnostic process and the management of the disease have been raised even among pediatricians. Therefore, we aimed to clarify this newly occurring enigma based on the current literature and our clinical insights

Pediatric Behcet's Disease

Behcet's Disease (BD) is a systemic vasculitis firstly described as a disorder causing aphthous lesion in oral and genital mucosae and uveitis. The disease has an extremely unique distribution characterized by the highest incidence in communities living along the historical Silk road. Although our understanding of the etiopathogenesis of BD has expanded over time, there are still lots of unidentified points in the underlying mechanisms of the disease. The accepted opinion in the light of the current knowledge is that various identified and/or unidentified infectious and/or environmental triggers can take a role as a trigger in individuals with genetic susceptibility. Although the disease usually develops in young adulthood, it is reported that about 15-20% of all Behcet's patients develop in childhood. Pediatric BD differs from adult BD not only with the age of onset but also in the frequency and distribution of clinical findings, disease severity and outcome. While gastrointestinal system involvement, neurological findings, arthralgia and positive family history are more common in children, genital lesions and vascular lesions are more common in adult patients. In addition, a better disease outcome with lower severity score and activity index has been reported in children. The diagnosis of the disease is made according to clinical findings. It can be challenging to diagnose the disease due to the absence of a specific diagnostic test, and the long time interval from the first finding of the disease to the full-blown disease phenotype in pediatric cases. Therefore, many classification criteria have been proposed so far. The widely accepted ones are proposed by the International Study Group. The new sets of classification criteria which is the only one for pediatric BD were also developed for pediatric cases by the PEDBD group. The primary goal for the treatment is preventing the organ damages by suppressing the ongoing inflammation and forestalling the disease flares. The treatment of the BD can be onerous due to its multisystemic nature and a multidisciplinary approach is essential for the management of the patients. In this review article, the definition, clinical findings, epidemiology, etiopathogenesis, and treatment will be discussed