Pathogenic
RIPK1
variants have been described as the cause of two different inborn errors of immunity. Biallelic
loss-of-function
variants cause the recessively inherited RIPK1 deficiency, while ...monoallelic variants impairing the caspase-8-mediated RIPK1 cleavage provoke a novel autoinflammatory disease (AID) called cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome. The aim of this study was to characterize the pathogenicity of two novel RIPK1 variants located at the cleavage site of caspase-8 detected in patients with dominantly-inherited, early-onset undefined AID.
RIPK1
genotyping was performed by Sanger and next-generation sequencing. Clinical and analytical data were collected from medical charts, and in silico and in vitro assays were performed to evaluate the functional consequences. Genetic analyses identified two novel heterozygous
RIPK1
variants at the caspase-8 cleavage site (p.Leu321Arg and p.Asp324Gly), which displayed a perfect intrafamilial phenotype-genotype segregation following a dominant inheritance pattern. Structural analyses suggested that these variants disrupt the normal RIPK1 structure, probably making it less accessible to and/or less cleavable by caspase-8.
In vitro
experiments confirmed that the p.Leu321Arg and p.Asp324Gly RIPK1 variants were resistant to caspase-8-mediated cleavage and induced a constitutive activation of necroptotic pathway in a similar manner that previously characterized RIPK1 variants causing CRIA syndrome. All these results strongly supported the pathogenicity of the two novel RIPK1 variants and the diagnosis of CRIA syndrome in all enrolled patients. Moreover, the evidences here collected expand the phenotypic and genetic diversity of this recently described AID, and provide interesting data about effectiveness of treatments that may benefit future patients.
Juvenile dermatomyositis is the most common idiopathic inflammatory myopathy in childhood. Nailfold capillaroscopy plays an important role in its assessment, being useful for diagnosis and follow-up. ...It is well documented that the morphological changes of nailfold capillaries reflect microvascular alterations presented in connective tissue diseases, including juvenile dermatomyositis. Several studies reported that the extent of microangiopathy detected by nailfold capillaroscopy examination offers a good correlation with disease activity and severity in juvenile dermatomyositis. The aim of this study was to assess the associations between distinct nailfold capillaries abnormalities and juvenile dermatomyositis clinical forms.
Nailfold capillaroscopy is a simple, non-invasive and low-cost method, that is extremely important in the assessment of adults and children with definite or suspected connective tissue diseases. ...Peripheral microvascular changes found in nailfold capillaroscopy examination can provide useful information in differential diagnosis and therapy monitoring in majority of connective tissue diseases. Although in adult rheumatology this method has had an incredibly growing interest in the last decades, studies in paediatric population are fewer and generally, the capillaroscopic data used in children are extrapolated from adults. The normal capillaroscopic pattern in the paediatric population has some differences which must be known when performing nailfold capillaroscopy in children.
•Pediatric patients on immunosuppressive drugs had mild COVID-19.•Risk of flare related to SARS CoV-2 exposure in rheumatic disease patients was similar to baseline.•Seroprevalence survey identified ...high asymptomatic infection rate.
Bruton’s agammaglobulinemia is a rare X-linked humoral immunodeficiency manifesting with recurrent bacterial infections early in life. Klinefelter’s syndrome caused by an additional X chromosome is ...the most common sex chromosome disorder. A previously unreported association of these two conditions is described here.
Juvenile idiopathic arthritis is the most frequent rheumatic disease in pediatrics. Immunosuppressive drugs, either conventional or biologic, used for its treatment, pose higher infectious risks. A ...short literature review is presented. Even though still safe while being on immunosuppressive drugs, vaccination is advisable to be completed for tuberculosis, hepatitis B, measles, varicella and pneumococcus before such treatment is used. As these vaccines are expensive and at times not available on market, they should all be offered by the national health insurance system to JIA patients.
ETANERCEPT WITHDRAWAL IN JIA Farkas, Oana-Maria; Cochino, Alexis-Virgil; Covaci, Sigrid
Revista română de reumatologie,
06/2017, Letnik:
26, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic disease in children. The use of biologic therapy has improved prognosis and quality of life for these patients. Remission is more ...easily achieved and pediatric rheumatologists started to question if, when and how this expensive and potentially dangerous treatment might be withdrawn. To date, few studies have addressed these questions and results are divergent, more research being needed. As the latest Romanian protocol for biologic therapy in JIA includes it, and because Etanercept is the most prescribed biologic drug in our country, we propose an Etanercept treatment withdrawal protocol for JIA patients in remission.
BENIGN JOINT HYPERMOBILITY SYNDROME Covaci, Sigrid; Farkas, Oana-Maria; Cochino, Alexis-Virgil
Revista română de reumatologie,
03/2017, Letnik:
26, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Musculoskeletal pain is the most common cause of presentation in rheumatology service. Most frequent causes of joint pain are noninflammatory conditions, with benign joint hypermobility syndrome ...(BJHS) being one of them. BJHS is not an actual disease but an inherited variation of normal. Some clinical features of this syndrome can lead to confusion with Juvenile Idiopathic Arthritis (JIA) and therefore to unjustified treatment, which makes its recognition mandatory. A case of BJHS in a 11-year-old girl is presented; the patient was initially diagnosed as JIA and received immunosuppressive treatment for 2 years.
Pediatric Systemic Lupus Erythematosus (pSLE) is a complex autoimmune disease with onset of symptoms before 18 years of age, accounting for 18-20% of all SLE cases. Although the American College of ...Rheumatology (ACR) classification criteria and the SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for adults with SLE are commonly applied to pSLE, its clinical onset is different. Renal and neurological involvement tend to be more common and more severe in pediatric population as compared to adults, being therefore major determinants of prognosis and mortality. Renal biopsy should be performed as early as possible in every case of pSLE with signs and symptoms of renal impairment.
PARRY ROMBERG SYNDROME Cochino, Alexis-Virgil; Covaci, Sigrid; Farkas, Oana-Maria
Revista română de reumatologie,
12/2016, Letnik:
25, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Parry-Romberg syndrome, which is also known as progressive facial hemiatrophy, is a variant of localized scleroderma. This is a rare condition (OMIM # 141300), characterized by a progressive but ...self-limited atrophy of the skin and subcutaneous tissue on one side of the face. We present the case of a 9 year old boy with a typical presentation of hemifacial atrophy, with Borrelia burgdorferi infection without any changes of the nervous system.
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