Pamela S. Morales

Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis.

To report the clinical, radiological, and immunological association of demyelinating disorders with anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis.

Higher latitude and lower solar radiation influence on anaphylaxis in Chilean children

Recent studies suggest an association between higher latitude, a proxy of vitamin D (VD) status, and allergic diseases. Chile provides an ideal setting to study this association due to its latitude span and high rates of VD deficiency in southern regions. The aim of this study is to explore the associations of latitude and solar radiation with anaphylaxis admission rates.

Overlapping demyelinating syndromes and anti-NMDA receptor encephalitis

To report the clinical, radiological, and immunological association of demyelinating disorders with anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis.

Severe Spinal Neurofibromatosis in a Child

A 13-year-old boy with neurofibromatosis type 1 (NF-1) was referred for evaluation of a 5-month history of gait disturbance, frequent falls, muscle weakness, and lumbosacral pain. Physical examination revealed emaciation, diffuse muscle atrophy, multiple freckles, cafe-au-lait spots, and subcutaneous nodules (Figure 1, A). No xyphoscoliosis was observed. Neurologic examination showed spastic tetraparesis, hyperreflexia, clonus, and extensor plantar reflex. Urodynamic studies showed mild urinary retention that was asymptomatic. Magnetic resonance imaging (MRI) of the spine showed an intradural mass measuring 3.2 1.4 cm at the level of C2-C4 vertebrae with secondary compression of the spinal cord (Figure 1, B). Spinal cord was crescentshaped at this level and reduced to 2 mm in diameter with abnormal T2-weighted hyperintensity, consistent with a compressive myelopathy (Figure 2; available at www.jpeds. com). In addition, MRI showed innumerable large paraspinal and lumbosacral plexus nerve sheath tumors, compatible with neurofibromas (Figure 1, C). The patient underwent decompressive laminectomy of the C2-C4 segments with partial tumor ressection, which resulted in complete resolution of his spastic tetraparesis and pain at 6 months of follow-up. Other tumors were deemed unresectable. Spinal neurofibromas are found in up to 38% of NF-1 patients but are symptomatic in less than 2% of patients. Severe symmetric involvement affecting the entire spine is extremely uncommon. Even rarer are symptomatic spinal neurofibromas

Incidence and risk factors of food allergy after umbilical cord blood transplantation in children

New-onset food allergy (FA) after transplantation has been reported after solid organ transplantation, especially in tacrolimus-treated liver transplant recipients, and in some cases of allogeneic bone marrow transplantation (BMT) from foodallergic donors. The development of FA after umbilical cord blood transplantation (UCBT) is a rare event with unclear pathogenesis, considering that the donor has a mostly naive immune system. Few reports have documented IgE-mediated FA after UCBT. Therefore, the true incidence and risk factors of post-UCBT FA remain unclear. We report 3 cases of IgE-mediated FA developed after unrelated UCBT from a series of 92 children treated at our institution between 1996 and 2015. Seventy-one patients (77%) were transplanted for malignancy and 21 (23%) for nonmalignant diseases. Thirty-eight patients (37%) were excluded from the analysis because of missing information, death, or engraftment failure within 100 days after UCBT; the remaining 54 subjects were enrolled. Patient 1 is a 10-year-old girl with no prior FA history, who received an unrelated UCBT for acute lymphoblastic leukemia (ALL) in third central nervous system remission. Conditioning included treosulfan, fludarabine, and thiotepa. Graft-versus-host disease (GVHD) prophylaxis was done with cyclosporine and mycophenolate mofetil. One month after UCBT she presented cutaneous and gastrointestinal GVHD requiring treatment with prednisone and tacrolimus, with good response and gradual taper. Three months after UCBT she developed food-induced anaphylaxis. Five minutes after egg ingestion she developed oral and pharyngeal itching, vomiting, and abdominal pain, without hives or angioedema. Subsequently, she developed immediate hypersensitivity reactions to milk, nuts, and lentils. Laboratory examinations confirmed IgE-mediated FA (Table I). She was prescribed complete avoidance of offending foods, which she did until leukemia relapse-related death at 18-month followup. Patient 2 is a 13-year-old girl with M2 acute myeloid leukemia. She previously had seasonal allergic rhinitis but no FA. Family history was notable for exercise-induced anaphylaxis in a brother. After bone marrow relapse she received an unrelated UCBT on second remission. Conditioning regimen included cyclophosphamide, fludarabine, and total body irradiation. Prevention of GVHD was done with cyclosporine and mycophenolate mofetil, but she developed cutaneous and gastrointestinal GVHD treated with tacrolimus achieving remission. Three months after UCBT she developed anaphylaxis twice within 30 minutes of eating egg (hives, stridor, abdominal pain, diarrhea, and dizziness). Specific IgE to egg white was 3.5 kU/L, egg yolk 0.98 kU/L. Twelve months after UCBT she reported complete tolerance to egg, confirmed by oral food challenge. Thirteen years later, specific IgE to egg resulted negative. Patient 3 is a 3-year-old boy, with no prior FA history, treated with intensive chemotherapy for very high risk ALL, receiving an unrelated UCBT in first remission. Conditioning regimen included cyclophosphamide, fludarabine, and total body irradiation. Despite GVHD prevention with mycophenolate mofetil and cyclosporine, he developed cutaneous and gastrointestinal GVHD, after which prednisone was added. After 3.5 months from UCBT, he developed sudden-onset vomiting, abdominal pain, and diarrhea within 30 minutes of eating egg. Specific IgE to egg resulted at 3.33 kU/L. He was prescribed egg avoidance, but 9 months after UCBT, the mother reported that the child had achieved complete tolerance to egg, confirmed by oral food challenge. Three years later, specific IgE to egg decreased to 0.49 kU/L, with continued tolerance. We report IgE-mediated FA after UCBT in 3 of 54 children who survived at least 100 days after transplant, revealing an incidence of 5.6%. This rate is lower than that reported in Japanese children surviving more than 1 year after UCBT (14.2%), but similar to Japanese adults surviving at least 30 days after UCBT (6.6%). Including our patients, 12 cases of IgEmediated FA after UCBT have been documented (Table I). In all cases, FA onset occurred at 3 months after UCBT. Resolution of FA in these patients appears to be common 1 to 2 years after UCBT, revealing that this is mostly a transient phenomenon. The pathogenesis of post-UCBT FA is yet unclear. Unlike BMT, the atopic status and family history of UCBT donors are usually unknown because most cords proceed from cord blood banks. However, because cord blood-derived hematopoietic stem cells carry a mostly naive immune system, allogeneic transfer of IgE-mediated allergy is unlikely. Studies have shown that T-cell responses at birth have a nearly universal Th2 skewing that balances with Th1 over time. Thus, it is plausible to speculate that acquisition of post-UCBT FA and, subsequently, the acquisition of tolerance follow a similar progression as infants who develop FA. GVHD, a Th2-skewed immune reconstitution, and use of tacrolimus after UCBT appear to be important risk factors of IgE-mediated FA in this population. As shown in Table I, 75% of post-UCBT FA patients had GVHD, which frequently increases intestinal permeability and inflammation. This would favor the passage of food allergens from the intestinal lumen and stimulate a developing immune system, increasing the risk of sensitization and new-onset FA. In our series, 3 of 37 subjects

Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis: Anti-NMDAR Encephalitis

To report the clinical, radiological, and immunological association of demyelinating disorders with anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis.