Objective. Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID), is a severe, early-onset autoinflammatory disease characterized by an urticaria-like rash, arthritis/ arthropathy, variable neurologic involvement, and dysmorphic features, which usually respond to interleukin-1 blockade. CINCA/NOMID has been associated with dominant Mendelian inherited NLRP3 mutations. However, conventional sequencing analyses detect true disease-causing mutations in only ϳ55-60% of patients, which suggests the presence of genetic heterogeneity. We undertook the current study to assess the presence of somatic, nongermline NLRP3 mutations in a sporadic case of CINCA/NOMID.Methods. Clinical data, laboratory results, and information on treatment outcomes were gathered through direct interviews. Exhaustive genetic studies, including Sanger method sequencing, subcloning, restriction fragment length polymorphism assay, and pyrosequencing, were performed.Results. The patient's CINCA/NOMID was diagnosed based on clinical features (early onset of the disease, urticaria-like rash, knee arthropathy, and dysmorphic features). The patient has exhibited a successful response to anakinra within the last 28 months. Analysis of NLRP3 identified a novel heterozygous variant (p.D303H) that was detected in ϳ30-38% of circulating leukocytes. The absence of this variant in healthy controls and in the patient's parents suggested a de novo true disease-causing mutation. Additional analyses showed that this novel mutation was present in both leukocyte subpopulations and epithelial cells.Conclusion. Our findings identify the novel p.D303H NLRP3 variant in a Spanish patient with CINCA/NOMID as a new disease-causing mutation, which was detected as a somatic, nongermline mutation in hematopoietic and nonhematopoietic cell lineages. Our data provide new insight into the role of low-level mosaicism in NLRP3 as the pathophysiologic mechanism underlying cryopyrin-associated periodic syndrome.

To develop recommendations on the transition from pediatric care to adult care in patients with chronic inflammatory rheumatic diseases with childhood onset based. Recommendations were generated following nominal group methodology and Delphi technique. A panel of 16 experts was established. A systematic literature review (on transitional care) and a narrative review were performed and presented to the panel in the first panel meeting to be discussed. A first draft of recommendations was generated and circulated. Focal groups with adolescents, young adults and parents were organized. In a second meeting, the focus group results along with the input from invited psychologist were used to establish definitive recommendations. Then, a Delphi process (two rounds) was carried out. A group of 72 pediatric and adult rheumatologists took part. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70 % voted ≥7. The level of evidence and grade or recommendation was assessed using the Oxford center for evidence-based medicine levels of evidence. Transition care was defined as a purposeful, planned process that addresses the medical, psychosocial and educational/vocational needs of adolescents and young adults with chronic inflammatory rheumatic diseases with childhood onset as they move from child-centered to adult-oriented healthcare systems. The consensus covers: transition needs, barriers and facilitators, transitional issues (objectives, participants, content, phases, timing, plans, documentation and responsibilities), physicians' and other health professionals' knowledge and skill requirements, models/programs, and strategies and guideline for implementation. Preliminary recommendations and agreement grade are shown in the Table (first Delphi round). These recommendations are intended to provide health professionals, patients, families and other stakeholders with a consensus on the transition process from pediatric to adult care.

Background Primary pyomyositis is a rare condition in children that should be included in the differential diagnosis of musculoskeletal infections. Objectives To describe the clinical features of pyomyositis as well as its diagnostic and therapeutic approach. Methods A descriptive and retrospective study was performed by reviewing medical records of patients admitted to our hospital from January 1996 to July 2013 with a diagnosis of primary pyomyositis. Results A total of 25 patients (16 men, 9 women) aged between one month and 14 years (median age 2 years) were registered. Two peaks of incidence have been found in the months of July and October. The most frequent clinical manifestations were the presence of local pain (24 patients), fever (18 patients), local swelling (9 patients) and skin rash (7 patients). Predisposing factors in 8 patients (1 strenuous exercise, 4 trauma, 3 intramuscular injections) were found. The primary site was pelvic muscles or lower extremities (20 patients). In laboratory results, we found the presence of leukocytosis, with an average value of 12,936±5.753/uL leukocytes, total neutrophils 4.659/uL ±7.350), ESR of 55±28 mm) and PCR 8±6 mg/dL). CPK was normal in 5 out of 6 patients who were requested. Laboratory results were positive for Staphylococcus aureus (7 patients), Salmonella no tiphy (1 patient) and Bacteroides fragillis (1 patient). Ultrasound suggested the diagnosis in 11 cases and magnetic resonance imaging support the diagnosis in all cases. All patients received intravenous antibiotic therapy (mean duration 11 days) followed by oral antibiotic therapy (mean duration 23 days). 9 patients suffered complications as abscess formation, 3 need abscess aspiration and one of them required surgical drainage. None of our patients had residual functional limitations. Conclusions It is important to have a high index of suspicion for pyomyositis in patients with fever and musculoskeletal pain at an early stage in order to initiate start appropriate antibiotic treatment against Staphylococcus aureus. Although ESR and ultrasound may be useful, it is necessary to complement with magnetic resonance imaging in order to support the diagnosis in all cases. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4467

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Background This study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in pediatric patients with rheumatic and musculoskeletal diseases (RMD) and identify the risk factors associated with symptomatic or severe disease defined as hospital admission, intensive care admission or death. Methods An observational longitudinal study was conducted during the first year of the SARS-CoV-2 pandemic (March 2020–March 2021). All pediatric patients attended at the rheumatology outpatient clinics of six tertiary referral hospitals in Madrid, Spain, with a diagnosis of RMD and COVID-19 were included. Main outcomes were symptomatic disease and hospital admission. The covariates were sociodemographic and clinical characteristics and treatment regimens. We ran a multivariable logistic regression model to assess associated factors for outcomes. Results The study population included 77 pediatric patients. Mean age was 11.88 (4.04) years Of these, 30 patients (38.96%) were asymptomatic, 41 (53.25%) had a mild-moderate COVID-19 and 6 patients (7.79%) required hospital admission. The median length of hospital admission was 5 (2–20) days, one patient required intensive care and there were no deaths. Previous comorbidities increased the risk for symptomatic disease and hospital admission. Compared with outpatients, the factor independently associated with hospital admission was previous use of glucocorticoids (OR 3.51; p = 0.00). No statistically significant risk factors for symptomatic COVID-19 were found in the final model. Conclusion No differences in COVID-19 outcomes according to childhood-onset rheumatic disease types were found. Results suggest that associated comorbidities and treatment with glucocorticoids increase the risk of hospital admission.

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BackgroundDeficiency of the interleukin (IL)−36 receptor antagonist (DITRA) is an autosomal recessive autoinflammatory syndrome caused by mutations in the IL36RN gene. Clinical manifestations of DITRA include recurrent episodes of generalised skin postulation, fever, systemic inflammation and leukocytosis. An uniformly effective treatment for DITRA has not yet been identified.ObjectivesWe present a case of a 5 year old patient with DITRA with prolonged response with tumour necrosis factor alfa inhibition with adalimumab.MethodsA five-year-old came to our dermatology clinic after worsening of a previous diagnosed plaque psoriasis, with an erythematous scaly dermatitis that extended throughout the trunk. Treatment with acitretin and cyclosporin were not effective and patient developed in few weeks a generalised erythroderma with pustules covering almost every part of his body, including palms and soles. He was admitted for the onset of fever and irritability due to painful rubbing of the skin. Family history of recurrent fevers or psoriasis were not revealed. Parents were not consanguineous.Complete blood count showed leukocytosis with neutrophilia and thrombocytosis, with an erythrocyte sedimentation rate (ESR) of 6 mm/hr and a C-reactive protein (CRP) of 8,4 mg/dl. Biochemistry panel revealed a mild elevation of liver enzymes without other abnormalities. Antinuclear antibody (ANA) and rheumatoid factor were negative with normal serum immunoglobulin and complement. Blood culture grew E. Coli, S. Maltophila and S. epidermidis. Skin biopsy showed acanthosis and papillomatosis with perivascular polymorphous inflammatory cells. Genetic analyses showed a homozygous mutation in the IL36RN gene (pSer113Leu). No mutations were detected in IL1RN and CARD 14 genes.ResultsTreatment was initiated with intravenous methylprednisolone 2 mg/kg/day and subcutaneous anakinra 2 mg/kg/day. Cefotaxime and co-trimoxazole were added until blood cultures were negative. Although skins lesions improved during the following days and patient was finally discharged, symptoms reappeared when decreasing the steroid dose. Three months later adalimumab and methotrexate were started, allowing the patient to end treatment with corticoids without evidence of activity of the disease.Abstract AB1087 – Figure 1ConclusionsAfter incomplete response with anakinra, inhibition of tumour necrosis factor alfa resulted in a prolonged response in our patient with deficiency of the interleukin (IL)−36 receptor antagonist (DITRA).Disclosure of InterestNone declared

The role of patient adherence in improving the efficacy of any treatment is widely accepted, as well as its impact in optimizing the use of healthcare resources and associated costs. Adherence is particularly affected in chronic conditions, such as rheumatoid arthritis (RA), requiring long-term therapies and a commitment of the patient to manage his/her disease. Methotrexate (MTX) is one of the mainstays of treatment for several immunemediated inflammatory joint and skin diseases, especially RA. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised a great interest to overcome the limitations of oral MTX. For addressing this issue, new optimized self-injection systems have been developed to improve the ease of use of SC MTX. Increasing evidence shows how patients tend to opt for autoinjectors over prefilled syringes or conventional syringes in terms of easiness of use, preference and satisfaction, regardless of whether the treatment is a biologic or MTX. Additionally, positive views and beliefs of patients about treatment may contribute to increasing expectations of effectiveness and treatment adherence. Similarly, the implementation of prefilled pens in clinical practice might be a way to facilitate and simplify the self-injection of SC MTX delivery, optimizing adherence and treatment outcomes as a consequence. This article aimed to review the available literature data on the use of MTX autoinjectors and their impact on treatment adherence and patients' perceptions.