Search

A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed. Four hundred and seventy five patients were enrolled; ANA and CAN were prescribed in 421 and 105 treatment courses, respectively. During a mean follow-up of 24.39 ± 27.04 months, 89 adverse events (AE) were recorded; 13 (14.61%) were classified as serious AE (sAE). The overall estimated rate of AE and sAE was 8.4 per 100 patients/year. Safety concerns were more frequent among patients aged ≥ 65 years compared with patients < 16 years (p = 0.002). No differences were detected in the frequency of safety concerns between monotherapy and combination therapy with immunosuppressants (p = 0.055), but a significant difference was observed when injection site reactions were excluded from AE (p = 0.01). No differences were identified in relation to gender (p = 0.462), different lines of biologic therapy (p = 0.775), and different dosages (p = 0.70 ANA; p = 0.39 CAN). The overall drug retention rate was significantly different according to the occurrence of safety concerns (p value < 0.0001); distinguishing between ANA and CAN, significance was maintained only for ANA (p < 0.0001 ANA; p > 0.05 CAN). Treatment duration was the only variable associated with onset of AE (OR = 0.399 [C.I. 0.250–0.638], p = 0.0001). ANA and CAN have shown an excellent safety profile; the risk for AE and sAE tends to decrease over time from the start of IL-1 inhibition.

Introduction: Erythema nodosum (EN)is the most common panniculitis in childhood. The lesions of EN are localized at the lower limbs, in particular in the pretibial region, while upper limbs and trunk are rarely involved. Erythema nodosum can be associated with general symptoms such as fever, weakness, and severe pain, but skin lesions resolve without skin damage. Objectives: To describe five cases of Erythema nodosum in childhood Methods: R.G. f. 3 years old came to our department for a two week history of fever (up to 38 °C) and skin lesions. Physical examination revealed pharyngeal hyperemia and multiple erythematous nodules on the extensor surface of the lower extremities. Laboratory tests showed an elevation of ESR(35 mm/h) and CRP, (1,06 mg/dL) and high levels of Chlamydia Pneumoniae IgM.Throat swab was negative for group A beta-hemolytic Streptococcus (GAS) and her chest X-ray was negative. So antibiotic therapy was prescribed and symptomatology improved. A.N. m. 8 years old was hospitalized for fever up to 39 °C and skin lesions in the lower limbs. Patient suffered from recurrent abdominal pain and diarrhea. Physical examination revealed abdominal pain and erythematous and painful nodules in pretibial region of both lower limbs. Blood tests showed increase of ESR (40 mm/h) and CRP (1,3 mg/dL). Blood examinations for celiac disease were negative. Fecal calprotectin was high (500 mg/kg). Abdomen ultrasound revealed terminal ileum bowel wall thickening. Crohn’s Disease (CD)was suspected and confirmed with an endoscopy including biopsies. A.N. f. 5 years old was admitted to our department for fever (38 °C) and skin lesions that started two weeks ago. The patient also had 1 month history of cough. Physical examination revealed: pharyngeal hyperemia, cervical and axillary lymphadenopathy and skin lesions suggestive of erythema nodosum on the extensor parts of both lower limbs. Inflammatory tests were increased (ERS 28 mm/h, CRP 1,5 mg/dL). Her chest X-ray was negative. Mantoux test was positive with an induration of 15 millimeters (mm) after 48 hours and 18 mm after 72 hours, also a Quantiferon test was positive. L.B. f. 12 years old had an history of fever, headache, fatigue, joint pain and skin lesions.The objective examination revealed: malar rash, arthritis of the right knee, erythematous nodules on the extensor surface of the lower limbs. Blood tests showed anemia (Hb,5 g/dL), thrombocytopenia (PLT 75.000/mm3), ERS increased (30 mm/h) positive ANA, antiDNA. Systemic Lupus Erythematous was diagnosed according to ACR criteria I.L. f. 8 months old had a two months history of recurrent fever and skin lesions. On admission the patient was febrile (TC 38 °C). Physical examination revealed pharyngeal hyperemia, splenomegaly and erythematous nodules on the extensor surface of the lower limbs.Inflammatory tests were increased (ERS 33 mm/h, CRP 2 mg/dL). Antibodies anti CMV, EBV, Chlamydia and Mycoplasma Pneumoniae were negative. Biopsy of a lesion showed a condition compatible with panarteritis nodosa. Results: EN is a skin inflammatory reaction. EN could be associated with infectious diseases (GAS, Chlamydia Pneumoniae, Mycoplasma Pneumoniae, Epstein-Barr virus, Mycobacterium Tuberculosis), drugs, inflammatory bowel diseases, rheumatologic diseases, malignant tumor. Conclusion: The presented cases show that erythema nodosum can be secondary to different diseases.In the diagnostic process associated symptomatology and laboratory tests should be considered to diagnose the disease and to start specific treatment

A 17-year-old female patient affected by systemic lupus erythematosus (SLE) (who had been taking 300 mg/die of hydroxychloroquine for 3 years), Graves' disease (treated with 10 mg/die of tapazole), and celiac disease came to our attention for urticarial vasculitis. She had been taking prednisone (25 mg/die) for 3 days, and her blood tests showed high levels of Mycoplasma pneumoniae IgM and IgG antibodies. The association between urticaria and M. pneumoniae infections can be present in up to 7% of the cases and, to the best of our knowledge, only two reports of urticarial vasculitis and M. pneumoniae in adults are available in the literature. Urticarial vasculitis can also be a rare cutaneous manifestation of SLE (affecting 2% of the patients), and our case is the first in the literature describing the coexistence of M. pneumoniae infection, SLE, and urticarial vasculitis in a pediatric patient, a case that rises an important differential diagnosis issue about the origin of urticarial vasculitis: SLE reactivation or urticarial vasculitis due to M. pneumoniae infection?

Background: Data from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN). Methods: In 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment. Results: 1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child's illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis. Conclusions: Around half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity.

Item does not contain fulltext The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed.

Objectives: To investigate whether the functional variant Q63R of the cannabinoid 2 (CB2) receptor is associated with susceptibility to oligo/poly-articular juvenile idiopathic arthritis (JIA) and with its clinical features. Method: A total of 171 Italian children with oligoarticular/rheumatoid factor negative poly-articular JIA and 600 healthy controls were enrolled in the study and genotyped. Results: A significant difference in genotype distribution of the CB2 Q63R variant (CNR2 rs35761398) between oligo/poly-articular JIA patients and controls was found (p = 0.001). The R63 variant was associated with increased rates of relapse (p = 0.0001). Conclusions: This study indicates that the CB2 receptor contributes to susceptibility to oligo/polyarticular JIA and to the severity of its clinical course.

Acute Rheumatic fever is still a challenge for physicians, it is often not diagnosed at onset and adequately treated.

Lameness is a symptom very common in childhood, it depends on inflammatory, neoplastic, infective, orthopedic diseases.

Type 1 diabetes mellitus may be associated with many autoimmune diseases with the common autoimmune pathogenesis. We describe the case of a girl suffering from Type 1 diabetes mellitus and autoimmune Hashimoto's thyroiditis since the childhood and, due to the onset of Juvenile Idiopathic Arthritis during adolescence, for three years practiced therapy with an anti-TNF drug, etanercept . Currently her inflammatory markers are normal, arthritis is inactive and diabetes is well controlled. During the treatment with anti-TNF drug we observed a significative reduction of insulin dose, probably due to an increased tissue sensitivity secondary to the suppression of the activity of TNF-alpha. Several clinical trials that have evaluated the effect of immunomodulatory agents in diabetic patients, especially in those with recent onset of disease, were already performed but further studies of longer duration on a larger population are needed to assess the role of biologic drugs and immunotherapy in this group of patients.

Item does not contain fulltext OBJECTIVE: To evaluate the response to treatment of autoinflammatory diseases from an international registry and an up-to-date literature review. METHODS: The response to treatment was studied in a web-based registry in which clinical information on anonymised patients with autoinflammatory diseases was collected retrospectively as part of the Eurofever initiative. Participating hospitals included paediatric rheumatology centres of the Paediatric Rheumatology International Trial Organisation network and adult centres with a specific interest in autoinflammatory diseases. The following diseases were included: familial Mediterranean fever (FMF), cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF)-receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), pyogenic arthritis pustulosis acne (PAPA) syndrome, deficiency of interleukin-1 receptor antagonist (DIRA), NLRP12-related periodic fever and periodic fever aphthosis pharyngitis adenitis (PFAPA) syndrome. Cases were independently validated by experts for each disease. A literature search regarding treatment of the abovementioned diseases was also performed using Medline and Embase. RESULTS: 22 months from the beginning of the enrolment, complete information on 496 validated patients was available. Data from the registry in combination with evidence from the literature confirmed that colchicine is the treatment of choice for FMF and IL-1 blockade for DIRA and CAPS. Corticosteroids on demand probably represent a valid therapeutic strategy for PFAPA, but also for MKD and TRAPS. Patients with poorly controlled MKD, TRAPS, PAPA or FMF may benefit from IL-1 blockade; anti-TNF treatment may represent a possible valuable alternative. CONCLUSIONS: In the absence of high-grade evidence, these results could serve as a basis for therapeutic guidelines and to identify candidate drugs for future therapeutic trials.

EULAR/PRINTO/PRES Objectives To validate the previously proposed classification criteria for Henoch-Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA).Methods Step 1: retrospective/prospective webdata collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis

Skin ulcers are a dangerous and uncommon complication of vasculitis. We describe the case of a teenager suffering from Systemic Lupus Erythematosus with digital ulcer resistant to conventional therapy, treated successfully with Hyperbaric Oxygen Therapy. The application of hyperbaric oxygen, which is used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. Further studies are needed to evaluate its role as primary therapy for this group of patients.

Objective To validate and promulgate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile systemic lupus erythematosus (SLE). Methods In 2001, a preliminary consensus-derived core set of measures for evaluating the response to therapy in juvenile SLE was established. In the present study, the core set was validated through an evidence-based, large-scale data collection process that led to the enrollment of 557 patients from 39 different countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, agreement in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. Results The following clinical measures were found to be feasible and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician's global assessment of disease activity, 2) global disease activity measure, 3) 24-hour proteinuria, 4) parent's global assessment of the patient's overall well-being, and 5) health-related quality of life assessment. Conclusion The members of PRINTO propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a patient with juvenile SLE has responded adequately to therapy.

Growth in height was studied in 58 patients with juvenile rheumatoid arthritis (JRA) followed for 4.9 +/- (SD) 2.8 years, who had never received steroids. Height measurements were converted to Height Z Scores. Height Z scores at first and at last visit were respectively 0.7 +/- 1 and 0.7 +/- 0.9 (NS) in pauciarticular, 0 +/- 1.6 and -0.55 +/- 1.6 (p = 0.045) in systemic, 0.29 +/- 0.8 and -0.4 +/- 1 (p = 0.0001) in polyarticular JRA patients. In systemic and polyarticular patients a significant negative relation was found between the duration of disease and the delta Height Z score (p = 0.0008) as well as between the sum of the periods of active disease and the delta Height Z score (p = 0.0001). The patients with functional class = 1 lost 0.01 +/- 0.19 Height Z score per year while those with functional classor = 2 lost 0.16 +/- 0.13 Height Z score per year (p = 0.005). The loss of Height Z score in systemic and polyarticular subjects observed during pubertal age (-0.71 +/- 0.67 Height Z score) was significantly (p = 0.02) greater than in those observed before puberty (-0.1 +/- 0.72). The longer duration of disease, the higher degree of functional joint involvement, and the age of puberty appear to be risk factors for height growth impairment in systemic and polyarticular JRA.

The deterioration rate of creatinine clearance (CCr) was studied in 40 children with chronic renal failure (CRF) on conservative treatment followed up for at least 1 year (range 1-12). The deterioration rate of CCr was significantly (p less than 0.01) higher in glomerulopathies (G) than in hypoplasias (H) and in vascular nephropathies (VN) and significantly (p less than 0.01) higher in hereditary nephropathies (HN) than in VN. The differences in the deterioration rate of CCr between H and HN and between H and VN were not explainable on the basis of the different age at diagnosis or of the different prevalence of hypertension. These data indicate that the primary renal disease is important in determining the progression of CRF.

Serum HBsAg positivity prevalence was studied on 98 children affected by various nephropathies or obstructive uropathies and on a control group of 71 children, consecutively admitted into the same clinical ward, suffering from other than hepatic or renal diseases. No significant difference was found between the group of children with non-glomeruiar nephropathies or obstructive uropathies and the control group. The prevalence of HBsAg positivity was significantly higher in male children with membranous glomerulopathy and in those with lipoid nephrosis than in the control group. All HBsAg positive children with glomerulopathies were chronic carriers of the hepatitis B virus. However, though left undemonstrated, there still lies a probable pathogenetic relationship between the hepatitis B virus infection and membranous glomerulopathy. The authors hypothesize that an impaired immune response in male children with lipoid nephrosis may account for both the hepatitis B virus infection and the development of the glomerular disease.

S-JIA has the worst long-term prognosis compared to other types of JIA. Corticosteroids, methotrexate and anti - tumor necrosis factor (TNF) are the most commonly used drugs for it. Recently, newer biologic agents targeting IL-1 and IL-6 have proven their effectiveness in treating s-JIA and in minimizing corticosteroid exposure.