V Messia

Genetic prothrombotic factors in children with otogenic lateral sinus thrombosis: five case reports.

Lateral sinus thrombosis (LST) is an uncommon, but life-threatening complication of both acute and chronic otitis media. There is some evidence that acquired or hereditary prothrombotic disorders are risk factors for LST. The aim of this work was to evaluate the role of thrombotic screening, anticoagulant therapy or prophylaxis in patients with either acute or chronic otitis media and LST. The medical records of five children hospitalized at Pediatric Hospital Bambino Gesù of Rome because of acute or chronic otitis media complicated by mastoiditis and LST were reviewed. All children underwent laboratory workup for hypercoagulability. All the five children were found to be heterozygote for the C677T MTHFR mutation and a child presented also heterozygosity for factor V Leiden mutation. They have been successfully treated with anticoagulant therapy without sequels. Children with acute or chronic otitis media may have a prothrombotic tendency that becomes clinically evident because of the inflammatory state. Patients with a family and/or personal history of thrombosis and/or thrombophilic conditions need anticoagulant prophylaxis also in the absence of clear signs of LST. Treatment with low molecular weight is successful in patients with LST.

Anakinra in Systemic Juvenile Idiopathic Arthritis: A Single-center Experience.

Objective. To assess anakinra as a therapy for systemic juvenile idiopathic arthritis (sJIA) in a single-center series. Methods. We reviewed 25 patients with sJIA treated with anakinra for at least 6 months. The primary outcome was the number of patients who achieved clinically inactive disease at 6 months, according to preliminary criteria for inactive disease and clinical remission of JIA. Results. Among 25 patients evaluated, 14 (56%) met the criteria for inactive disease at 6 months and were classified as responders. For each individual patient, we compared the dose administered with the ideal dose of anakinra and we found that there was no relation with response. We also compared demographic characteristics and clinical and laboratory features at baseline in responders and non-responders: no differences were observed in relation with the number of active joints before starting anakinra or concomitant glucocorticoids treatment. The only variable significantly associated with response was the time from disease onset to receiving anakinra, with earlier treatment being associated with a better outcome. Conclusion. Anakinra is associated with rapid attainment of inactive disease in a significant portion of patients. We found that only the earlier treatment is associated with better outcome. However, formal studies on early treatment and on the pathophysiology and response to treatments, including anakinra, of early- and late-onset sJIA are needed to optimize the management of this challenging disease.

Whole-Body MRI versus bone scintigraphy: which is the best diagnostic tool in patients with chronic recurrent multifocal osteomyelitis (CRMO)?

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder of unknown etiology with a wide range of clinical manifestations. Since CRMO is a systemic disorder that can affect multiple skeletal sites, whole-body imaging techniques (whole body bone scintigraphy -WBBS- or whole body magnetic risonance -WBMRI-) provide major contribution to the initial diagnostic approach, as well as during follow-up.

Anakinra in a Cohort of Children with Chronic Nonbacterial Osteomyelitis

Objective. To report efficacy and safety in patients with chronic nonbacterial osteomyelitis (CNO) unresponsive to nonsteroidal antiinflammatory drugs (NSAID) and bisphosphonates and/or glucocorticoids treated with anakinra. Methods. Nine patients (6 females) with refractory CNO were treated with anakinra for at least 6 months. We recorded, at baseline and after 6 months of treatment, clinical and laboratory features, and number and distribution of bone lesions detected by 99mTc-MDP bone scintigraphy. Disease activity was evaluated using a physician’s global assessment (PGA). Results. At baseline, 9/9 patients had mild to severe PGA. After 6 months of treatment, in 5 patients the PGA score was graded from none to minimal. At baseline, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated in 8 out of 9 patients. After 6 months, 5/9 patients had normalized CRP and ESR and in all except 1, CRP and ESR decreased. Before starting anakinra, a total of 77 bone lesions were detected by bone scintigraphy. After 6 months of treatment of the 77 lesions, 42 had resolved and 35 were stable. In 7/9 patients, 20 new lesions appeared during treatment; 2 of these 7 patients were symptomatic. At the last followup visit (median 1.7 yrs, range 0.8–2.8), 6/9 patients maintained a PGA graded as none to minimal. Conclusion. Anakinra is a possible therapeutic alternative in patients with refractory CNO. The practical significance of clinically silent bone lesions detected by bone scintigraphy remains to be established.

Chronic recurrent multifocal osteomyelitis (CRMO): typical patterns of bone involvement on MRI with particular emphasis on Whole Body MRI (WBMRI)

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder of unknown ethiology. The clinical manifestations of CRMO are highly variable. One to 20 sites can be affected at one time. Since CNO is a systemic disorder that can affect multiple skeletal sites, whole-body imaging techniques (Tc-99 bone scintigraphy or MRI) provide major contribution to the initial diagnostic approach, as well as during follow-up.

P02-016 - A novel PSMB8 mutation causing candle syndrome

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly described autoinflammatory disease, which had been recently reported in 9 patients. It is characterized by onset during the first year of life of recurrent fevers, purpuric skin lesions, arthralgia, progressive lipodystrophy, hypochromic or normocytic anemia, delayed physical development and increased levels of acute phase reactants.

Predictors of Flare Following Etanercept Withdrawal in Patients with Rheumatoid Factor–negative Juvenile Idiopathic Arthritis Who Reached Remission while Taking Medication

Objective. To evaluate the rate of flare after etanercept (ETN) withdrawal in patients with juvenile idiopathic arthritis (JIA) who attained clinical remission while taking medication, and to identify predictors of flare. Methods. Patients were included with oligo- (oJIA) and rheumatoid factor–negative polyarticular JIA (pJIA) who received a first course of ETN for at least 18 months, maintained clinically inactive disease (CID) for at least 6 months during treatment, and were followed for 12 months after ETN withdrawal. Demographic and clinical features were collected at onset, at baseline (initiation of ETN), and at time of disease flare. Results. After ETN withdrawal, 66 of the 110 patients enrolled (60%) flared with arthritis (of whom 7 flared with concurrent anterior uveitis; none with uveitis alone). The median time to flare was 4.3 months (interquartile range 2.5–6.4) with no evident differences between oJIA and pJIA. The number and type of joints involved at baseline and characteristics of ETN treatment/discontinuation were not associated with flare. Patients who flared were more frequently males (p = 0.034), positive for antinuclear antibody (ANA; p = 0.047), and had higher values of C-reactive protein (CRP; p = 0.012) at baseline. These variables remained significantly associated with flare in a multivariate logistic analysis, a model accounting for only 14% of the variability of the occurrence of the flare. Conclusion. Our results show that a significant proportion of patients with JIA who maintain CID for at least 6 months experience a relapse after ETN withdrawal. Male sex, presence of ANA, and elevated CRP at baseline were associated with higher risk of flare.

Inflammatory Cytokine response in a cohort of patients carrying novel NLRP12 variants

The NLRP12 related autoinflammatory disorder (NLRP12-RD) is a rare autosomal dominant disease, caused by mutations in the NLRP12 gene, a member of NLRs family involved in negative regulation of NF-kB pro-inflammatory pathways. At present, few cases have been reported, although novel NLRP12 variants have recently been described.

Cronic non-bacterial osteomyelitis (CNO) in a cohort of pediatric patients: clinical, biological and radiological response to treatment with Anakinra

Chronic nonbacterial osteomyelitis (CNO) is the most common autoinflammatory bone disorder in childhood (1). Diagnostic information is provided by TC-99 bone scintigraphy (BS) and/or whole body MRI. Non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, bisphosphonates and tumour necrosis factor inhibitors have been used until now with variable response (2).

Single center experience in Next Generation Sequencing for genetic diagnosis of Autoinflammatory Disorders (AIDs)

Autoinflammatory disorders (AIDs) represent an expanding group of complex diseases characterized by periodic or chronic systemic inflammations. Mutations in more than 15 geneshave been associated with autoinflammatory recessive or dominant syndromes. Next Generation Sequencing (NGS) has emerged in the last year as new diagnostic tool in this field.