Acute hepatitis in a child heterozygous for the I259V MEFV gene variant.

Familial Mediterranean Fever (FMF) is a systemic auto-inflammatory disease characterized by recurrent episodes of fever accompanied by synovial, serosal and/or cutaneous inflammation. Liver involvement has been described mainly in patients with paired FMF gene mutations, i.e. involving both alleles, and rarely in patients heterozygous for FMF mutations. These patients may present with acute or chronic hepatitis, with or without liver failure. Non-alcoholic hepatitis, mild hyperbilirubinemia, and elevation of liver enzymes of unknown etiology should also raise suspicion of FMF. Patients with FMF and liver involvement usually respond to colchicine medication. The mutation I259V (c.775A MEFV gene has not been reported in FMF patients with liver involvement. Furthermore, among several MEFV gene variants, it has been reported so far in only one heterozygous FMF patient of Turkish ancestry presenting with abdominal pain without any hepatic complication. Herein, the second case of a FMF patient heterozygous for the above mentioned mutation is discussed. It is a male child with FMF clinical phenotype which presented two consecutively episodes of acute hepatitis during fever attacks, that spontaneously resolved. Therapeutic trial with colchicine was successful, since no other fever attacks and acute hepatitis episodes were noticed.

Whole-body magnetic resonance imaging findings and patterns of chronic nonbacterial osteomyelitis in a series of Greek pediatric patients.

Background: Chronic nonbacterial osteomyelitis (CNO) is a pediatric autoinflammatory disorder presenting with sterile inflammatory bone lesions. Whole-body MRI (WBMRI) has most recently emerged for disease assessment, but data are limited. Purpose: The purpose is to evaluate the imaging findings and patterns of CNO on WBMRI in a series of Greek pediatric patients. Material and Methods: Whole-body magnetic resonance imaging studies of all children with documented CNO, performed in a single tertiary center, were retrospectively reviewed. WBMRI included coronal T1 and short-tau inversion recovery (STIR), whole spine sagittal STIR, and ankle/foot sagittal STIR images. High signal intensity lesions on STIR images corresponding to bone marrow edema were recorded. The SPSS v.20 statistical package was used for descriptive statistics. Results: Twenty children were included (mean age: 12, range: 6-16 years) with 1-31 lesions (mean: 11.8) on WBMRI. Two children had unifocal disease localized at the clavicle, three paucifocal (1-4 lesions), and 15 multifocal bone involvement. All but two children presented with ankle pain and exhibited lesions at the bones of the ankle joint (90%) followed by the knee (50%) and pelvis (10%). The tibia was the most frequently affected bone (70%) followed by calcaneus (60%), fibula (50%), femur (45%), talus, and metatarsals (45%). No lesions in the cervical, thoracic, lumbar spine, and mandible were documented. Only small sacral lesions were seen in 25% of patients with the extensive peripheral disease. Bilateral metaphyseal and epiphyseal involvement with transphyseal extension were common, but the periosteal reaction and well-defined lesion margins were rare. Conclusion: Frequent involvement of the foot and ankle and paucity of substantial spinal involvement were seen in Greek pediatric patients with CNO.

Age-related differences of bone mass, geometry, and strength in treatment-naïve postmenopausal women. A tibia pQCT study.

Most studies addressing the effects of aging on bone strength have focused mainly on (areal) bone mineral densities and bone mineral content (BMC) and less on bone geometry. We assessed age-related differences of bone mass (grams of bone mineral), geometry, and derived strength in 219 treatment-naïve postmenopausal women using peripheral quantitative computed tomography of the load-bearing tibia. Subjects were separated in 3 age groups: A=48-59yr (N=80), B=60-69yr (N=84), C=70-80yr (N=55). Three slices were obtained for each individual, at the 4% (trabecular), 14% (subcortical and cortical), and 38% (cortical bone) of tibia length sites. Trabecular, subcortical, and cortical BMC (mg per 1-mm slice), volumetric bone mineral densities (mg/cm(3)), bone cross-sectional areas (mm(2)), periosteal (PERI_C, mm) and endosteal circumference (ENDO_C, mm), mean cortical thickness (CRT_THK, mm), and Stress Strain Indexes (SSIs, mm(3)) were studied. Trabecular and cortical BMC and volumetric densities were significantly lower in the elder subjects (group C) compared with younger subjects (groups A and B), p<0.0005. Cortical area and CRT_THK were significantly lower in group C (vs A and B, p<0.0005), whereas total cross-sectional area was higher in group C compared with A and B. ENDO_C was significantly higher in older subjects (group C vs A and B, p<0.0005), whereas PERI_C did not differ significantly between the age groups. SSIs were significantly lower in older subjects at the 14% site (group C vs A, p<0.0005 and C vs B, p<0.005), and at the 38% site (group C vs group A, p<0.01). Our results indicate that age-induced differences on bone strength entail significant alterations not only of bone mass, but also of bone geometry.

Live attenuated MMR/V booster vaccines in children with rheumatic diseases on immunosuppressive therapy are safe: Multicenter, retrospective data collection.

PURPOSE: To collect retrospective data of patients with Juvenile Idiopathic Arthritis (JIA) and other rheumatic diseases who received live attenuated booster measles-mumps-rubella (MMR) or measles-mumps-rubella-varicella (MMR/V) during treatment with immunosuppressive therapy. RESULTS: Data from 13 pediatric rheumatology centers in 10 countries, including 234 patients, were collected. Mean age at diagnosis was 5 ± 2.7 years, 67% were girls. Among them, 211 (90.2%) had JIA and 110 (47%) were in remission on medication. Disease activity was low in 37%, high in 8%, and moderate in 8%. One hundred-twenty-four received MMR/V booster while on methotrexate (MTX); 3 reported local mild adverse events (AE). Among 62 on MTX + biologics and 9 patients who received a combination of 2 disease modifying antirheumatic drugs (DMARDs), 9 reported mild AE. Among 39 on biologics, 1 reported fever one day after booster vaccination. No vaccine-related infection of measles, rubella, mumps or varicella was reported, none of the patients developed disease flare, including those with high disease activity. CONCLUSIONS: In this retrospective study, live-attenuated MMR/V booster vaccines were safe for children with rheumatic diseases, on immunosuppressive therapies. This strengthens the Paediatric Rheumatology European Society (PReS) recommendation that vaccination with live attenuated vaccines in patients on immunosuppressive therapies can be considered individually, weighing the benefit of vaccination against the risk of inducing infection through vaccination. These data provide the basis for a prospective data collection study, planned by the PReS vaccination study group.

Murine Typhus Mimicking Kawasaki Disease in a Preadolescent Girl.

We report the case of an 11-year-old preadolescent girl presenting with prolonged fever, lymphadenitis, nonpurulent conjunctivitis, a generalized maculopapular rash, erythematous lips and edema of hands/feet. Although major diagnostic criteria for Kawasaki disease were met, local epidemiologic data suggested a possible vector-borne etiology. Treatment with doxycycline was initiated, and defervescence occurred. Laboratory investigation confirmed the diagnosis of Rickettsia typhi infection.

Meningitis registry of hospitalized cases in children: epidemiological patterns of acute bacterial meningitis throughout a 32-year period.

BACKGROUND: Bacterial meningitis remains a source of substantial morbidity and mortality in childhood. During the last decades gradual changes have been observed in the epidemiology of bacterial meningitis, related to the introduction of new polysaccharide and conjugate vaccines. The study presents an overview of the epidemiological patterns of acute bacterial meningitis in a tertiary children 's hospital during a 32-year period, using information from a disease registry. Moreover, it discusses the contribution of communicable disease registries in the study of acute infectious diseases. METHODS: In the early 1970s a Meningitis Registry (MR) was created for patients admitted with meningitis in Aghia Sofia Children's Hospital in Athens. The MR includes demographic, clinical and laboratory data as well as treatment, complications and outcome of the patients. In 2000 a database was created and the collected data were entered, analyzed and presented in three chronological periods: A (1974-1984), B (1985-1994) and C (1995-2005). RESULTS: Of the 2,477 cases of bacterial meningitis registered in total, 1,146 cases (46.3%) were classified as "probable" and 1,331 (53.7%) as "confirmed" bacterial meningitis. The estimated mean annual Incidence Rate (IR) was 16.9/100,000 for bacterial meningitis, 8.9/100,000 for Neisseria meningitidis, 1.3/100,000 for Streptococcus pneumoniae, 2.5/100,000 for Haemophilus influenzae type b (Hib) before vaccination and 0.4/100,000 for Hib after vaccination. Neisseria meningitis constituted the leading cause of childhood bacterial meningitis for all periods and in all age groups. Hib was the second most common cause of bacterial meningitis before the introduction of Hib conjugate vaccine, in periods A and B. The incidence of bacterial meningitis due to Streptococcus pneumoniae was stable. The long-term epidemiological pattern of Neisseria meningitidis appears in cycles of approximately 10 years, confirmed by a significant rise of IR in period C. The Case Fatality Rate (CFR) from all causes was 3.8%, while higher CFR were estimated for Streptococcus pneumoniae (7.5%, RR=2.1, 95% CI 1.2-3.7) and Neisseria meningitidis (4.8%, RR=1.7, 95% CI 1.1-2.5) compared to other pathogens. Moreover, overall CFR varied significantly among the three time periods (p = 0.0015), and was estimated to be higher in period C. CONCLUSION: By using the MR we were able to delineate long-term changes in the epidemiology of bacterial meningitis. Thus the MR proved to be a useful tool in the study and the prevention of communicable diseases in correlation with prevention strategies, such as vaccinations.

Radiographic and MR Imaging Findings of the Spine after Bisphosphonate Treatment, in a Child with Idiopathic Juvenile Osteoporosis.

Bisphosphonates are employed with increasing frequency in various pediatric disorders, mainly associated with osteoporosis. After cessation of bisphosphonate treatment in children, skeletal radiologic changes have been documented including dense metaphyseal lines of the long bones and "bone in bone" appearance of the vertebrae. However, the evolution of these radiographic changes has not been fully explored. We describe the MR imaging appearance of the spine that, to our knowledge, has not been previously addressed in a child with idiopathic juvenile osteoporosis who had received bisphosphonates and emphasize the evolution of the radiographic findings of the spine and pelvis over a four-year period.

Amyloid arthropathy associated with multiple myeloma: a systematic analysis of 101 reported cases.

OBJECTIVE: Amyloid deposition in multiple myeloma (MM) may lead to an arthropathy resembling rheumatoid arthritis (RA). Since a systematic description of its natural history is lacking, we have performed a systematic analysis of all published cases. METHODS: Literature review featuring backward and forward database searches and direct inspection of reference lists. Inclusion criteria were as follows: publication between 1931 and 2012, diagnosis of multiple myeloma, and demonstration of light chain amyloid (AL) in any organ or in synovial fluid, arthritis, or synovitis. RESULTS: Overall, 101 cases were identified. Median age was 59 years and the male-to-female ratio was 1:1. A systemic manifestation of MM was reported in 88 cases. In 53 of these, characteristic physical findings (carpal tunnel syndrome, macroglossia, shoulder pad, and soft tissue swelling/masses) were present. Arthritis manifested before the diagnosis of MM in 63 cases, with 33 cases initially misdiagnosed as RA. There were 72 cases of poly-, 17 of oligo-, and three of monoarthritis. The shoulder joint was most commonly affected, followed by knees and small hand joints. Median synovial fluid leukocyte count was 2460 cells/mm(3), and was normal in seven cases. Synovial histopathology often featured mild synovitis without plasma cell infiltration. Imaging revealed articular or periarticular inflammation in many cases and bone lesions near 22% of affected joints. Treatments varied but led to some improvement in the majority of cases. CONCLUSIONS: These results solidify previous experience that MM arthropathy tends to feature a symmetric RF-negative nonerosive polyarthritis. However, the results also highlight the diversity of its presentations and stress the importance of arthropathy as a potentially under-recognized presenting manifestation of MM.

Postoperative spinal infection mimicking systemic vasculitis with titanium-spinal implants.

BACKGROUND: Secondary systemic vasculitis after posterior spinal fusion surgery is rare. It is usually related to over-reaction of immune-system, to genetic factors, toxicity, infection or metal allergies. CASE DESCRIPTION: A 14 year-old girl with a history of extended posterior spinal fusion due to idiopathic scoliosis presented to our department with diffuse erythema and nephritis (macroscopic hemuresis and proteinuria) 5 months post surgery. The surgical trauma had no signs of inflammation or infection. The blood markers ESR and CRP were increased. Skin tests were positive for nickel allergy, which is a content of titanium alloy. The patient received corticosteroids systematically (hydrocortisone 10 mg) for 6 months, leading to total recess of skin and systemic reaction. However, a palpable mass close to the surgical wound raised the suspicion of a late infection. The patient had a second surgery consisting of surgical debridement and one stage revision of posterior spinal instrumentation. Intraoperative cultures were positive to Staphylococcus aureus. Intravenous antibiotics were administered. The patient is now free of symptoms 24 months post revision surgery without any signs of recurrence of either vasculitis or infection. LITERATURE REVIEW: Systemic vasculitis after spinal surgery is exceptionally rare. Causative factors are broad and sometimes controversial. In general, it is associated with allergy to metal ions. This is usually addressed with metal on metal total hip bearings. In spinal surgery, titanium implants are considered to be inert and only few reports have presented cases with systemic vasculitides. Therefore, other etiologies of immune over-reaction should always be considered, such as drug toxicity, infection, or genetic predisposition. PURPOSES AND CLINICAL RELEVANCE: Our purpose was to highlight the difficulties during the diagnostic work-up for systemic vasculitis and management in cases of posterior spinal surgery.