Comparison of magnetic resonance imaging and 99mTechnetium-labelled methylene diphosphonate bone scintigraphy in the initial assessment of chronic non-bacterial osteomyelitis of childhood and adolescents.

OBJECTIVES: To compare sensitivity of bone scintigraphy using 99mTechnetium-labelled methylene diphosphonate (Tc-99m MDP) and magnetic resonance imaging (MRI) in the detection of inflammatory bone lesions in patients with chronic non-bacterial osteomyelitis (CNO). METHODS: Tc-99m MDP bone scintigraphy and MRI were performed in 32 CNO patients at the time of diagnosis and compared regarding their sensitivity in detecting inflammatory lesions in symptomatic regions of the body. RESULTS: Inflammatory lesions could be detected in 40 out of the 54 (74.1%) symptomatic regions by bone scintigraphy and in 53 (98.1%) of these regions by MRI (p<0.001). Sensitivity of MRI compared to bone scintigraphy was superior in detecting lesions in the long bones of the thigh and the lower legs (100% vs. 78.4%, respectively, p<0.05). CONCLUSIONS: Bone scintigraphy does not seem to display the whole extent of the inflammatory process in CNO. Therefore, depending on clinical relevance, MRI rather than planar bone scintigraphy should be considered for the detection of CNO lesions at diagnosis.

Daratumumab therapy for post-HSCT immune-mediated cytopenia: experiences from two pediatric cases and review of literature.

BACKGROUND: Immune-mediated cytopenias (AIC) are challenging complications following allogeneic hematopoietic stem cell transplantation (HSCT). While broad-acting immunosuppressive agents like corticosteroids are often standard of care, several novel therapies which target specific immunological pathways have recently been developed and provide hope for patients with steroid-refractory courses and may limit long-term toxicity. The successful off-label use of the plasma cell depleting anti-CD38 antibody daratumumab was published in several case reports, suggesting efficacy, i.e., in patients with antibody-mediated AIC refractory to previous B cell depletion. We want to share our experience with two children, whom we treated with daratumumab, including one fatal course with uncontrolled disease. Given the absence of substantial data from HSCT registries or prospective trials, we furthermore provide a critical review of the literature on daratumumab treatment of AIC. CASE PRESENTATIONS: Patient 1 (P1), an 11-year-old girl with lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency who developed immune-mediated thrombocytopenia (AIT) from day +58 after HSCT, showed a complete response to daratumumab after the fourth of six total daratumumab doses. She remains transfusion independent for over a year of follow-up. Previously, her thrombocytopenia was refractory to corticosteroids, rituximab, intravenous immunoglobulins (IVIG), eltrombopag, cyclosporine A, and sirolimus. Patient 2 (P2), a 6-year-old boy with CD40 ligand (CD40L) deficiency, developed both AIT and hemolytic anemia (AIHA) after HSCT on days +58 and +83, respectively, and was also treated with daratumumab after being previously refractory to prednisolone, rituximab, and IVIG. Yet, he did neither respond to daratumumab nor the concomitantly administered methyprednisolone pulse, plasmapheresis, and eculizumab and succumbed due to refractory disease. CONCLUSION: Reviewing the literature on the use of daratumumab for refractory AIC post-HSCT, we consider daratumumab a promising agent for this life-threatening disorder: ten of the twelve patients reached transfusion independency in the literature. However, treatment failures are likely to be underreported. Thus, controlled trials are needed to explore the safety and efficacy of daratumumab in this rare post-HSCT complication.

Inflammatory Bowel Disease in Juvenile Idiopathic Arthritis Patients Treated with Biologics.

OBJECTIVE: Evolving inflammatory bowel disease (IBD) is a matter of interest in patients with juvenile idiopathic arthritis (JIA) and might be associated with JIA therapy. METHODS: Data from the German biologics registry (Biologika in der Kinderrheumatologie; BiKeR) from 2001 to 2013 were analyzed. RESULTS: There were 3071 patients with 8389 patient-years (PY) of observation followed. IBD was diagnosed in 11 patients, 8 with Crohn disease and 3 with ulcerative colitis. IBD incidence in patients with JIA was 1.31/1000 PY and higher than published IBD incidences in pediatric populations. Compared with the total BiKeR cohort, patients with IBD more commonly had enthesitis-related arthritis, extended oligoarthritis, psoriatic arthritis, and also rheumatoid factor (RF)-negative polyarthritis. No IBD occurred in patients with systemic JIA or RF-positive polyarthritis. In patients treated with methotrexate (MTX), the IBD incidence was significantly lower compared with patients not treated with MTX. Etanercept (ETN) monotherapy, but not the combination of ETN and MTX, was associated with an increased incidence of IBD. CONCLUSION: Incidence of IBD in patients with JIA is higher than in the population. MTX turned out to be protective, even in combination with ETN.

Molecular survival strategies of the Lyme disease spirochete Borrelia burgdorferi.

Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. The bacterium adopts different strategies for its survival inside the immunocompetent host from the time of infection until dissemination in different parts of body tissues. The success of this spirochete depends on its ability to colonise the host tissues and counteract the host's defence mechanisms. During this process borrelia seems to maintain its vitality to ensure long-term survival in the host. Borrelia's proteins are encoded by plasmid and chromosomal genes. These genes are differentially regulated and expressed by different environmental factors in ticks as well as in the mammalian host during infection. In addition, antigenic diversity enables the spirochete to escape host defence mechanisms and maintain infection. In this review we focus on the differential expression of proteins and genes, and further molecular mechanisms used by borrelia to maintain its survival in the host. In light of these pathogenetic mechanisms, further studies on spirochete host interaction are needed to understand the complex interplay that finally lead to host autoimmunity.

Long-term follow-up of bone mineral density in childhood hypophosphatasia.

OBJECTIVE: Hypophosphatasia (HP; MIM 241510) is an inborn error of bone metabolism, characterized by a genetic defect in the gene of the tissue-non-specific alkaline phosphatase TNSALP. Long-term data on bone mineral density measurements are not available. METHODS: We have analyzed changes of bone mineral density (pQCT and DXA) prospectively during 4years of follow-up in a cohort of 6 patients with childhood HP. RESULTS: At diagnosis hypermineralization of the trabecular bone in the metaphyseal area of long bones in affected children was noted. During 4 years of follow-up a gradual, significant decrease of mineralization was noted in the radial metaphyses. In contrast, BMC by DXA and total body DXA values were stable in comparison to healthy controls. During follow-up a systemic hyperprostaglandinism was documented in the majority of the patients. Non-steroidal anti-inflammatory drug treatment was evaluated by measuring prostaglandin excretion in the urine. CONCLUSIONS: Metaphyseal hypermineralization in childhood HP, which might be a compensation for a mechanically incompetent bony structure, decreased over time. There might be a pathophysiological link to continually elevated systemic prostaglandins.