Genetic variants found in paediatric oncology patients with severe chemotherapy-induced toxicity: A case series.

Paediatric oncology patients who develop severe chemotherapy-induced toxicity that requires dose reduction, delay or termination of treatment are at risk of decreased treatment efficacy. Previous research has provided evidence that genetic variants in TPMT, NUDT15, UGT1A1 and DPYD are associated with toxicity of anticancer drugs. This led to pharmacogenetic guidelines that are integrated into clinical practice in paediatric oncology. Recently, novel genetic variants have been associated with a higher risk of developing chemotherapy-induced toxicity. In this case series, we selected 21 novel variants and genotyped these in nine patients with excessive chemotherapy-induced toxicity using whole exome sequencing or micro-array data. We observed that six out of nine patients carried at least one variant that, according to recent studies, potentially increased the risk of developing methotrexate- or vincristine-induced toxicity. As patient-derived genetic data are becoming widely accessible in paediatric oncology, these variants could potentially enter clinical practice to mitigate chemotherapy-induced toxicity.

T-cell response to viral antigens in adults and children with common variable immunodeficiency and specific antibody deficiency.

Several T cell abnormalities have been described in common variable immunodeficiency (CVID), a B cell disorder of mainly unknown origin. A subset of CVID patients suffers from frequent reactivations of herpes viruses. We studied T cell function in CVID [and in a subset of paediatric patients with specific antibody deficiency (SAD)] by measuring T cell proliferation and cytokine production in response to herpes virus-antigens in paediatric CVID patients (n=9) and paediatric SAD patients (n=5), in adult CVID patients (n=14) and in healthy controls. Paediatric CVID patients, but not SAD patients, displayed moderately increased CD8+ T cell proliferation in response to cytomegalovirus, human herpes virus type 6B (HHV6-B) and herpes simplex virus compared to controls. CD8+ T cell responses in adult CVID patients tended to be increased in response to cytomegalovirus and herpes simplex virus. In response to stimulation with herpes virus antigens, the proinflammatory cytokines interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and interferon inducible protein (IP)-10 were produced. Overall, no major differences were detected in cytokine production upon stimulation between patients and controls, although higher IL-10 and IL-12 production was detected in paediatric patients. In conclusion, cellular immunity against herpes virus antigens appears undisturbed in CVID patients, although defects in subpopulations of CVID patients cannot be excluded.

[Complaints of back pain in childhood: find curable causes]. / Rugpijnklachten op de kinderleeftijd: behandelbare oorzaken opsporen.

Three children, a 13-year-old boy and a 3-year-old and 6-year-old girl, were presented to the hospital with back pain, caused by Scheuermann's disease, spondylodiscitis and sickle cell disease, respectively. The boy with Scheuermann's disease received exercise therapy, the spondylodiscitis was treated with antibiotic therapy and the girl with sickle cell disease was given hyperhydration and folic acid. Although back pain is a common problem in children and teenagers, it is infrequently reported in the clinic. In contrast to back pain in adults, the same complaint in childhood is more often caused by a serious disorder which should be treated. Various causes of back pain in children can be distinguished: mechanical problems, infections of the lumbar spine, neoplasia, inflammation, and other causes, such as sickle cell disease. A child or adolescent presenting to the clinic with complaints of back pain deserves a careful detailed evaluation of the history, appropriate physical examination and additional investigation. Alarm symptoms are an increase in back pain, age below 4 years, pain during the night, restriction in function, systemic complaints or neurological deficits.

Congenital staphylococcal scalded skin syndrome in a premature infant.

UNLABELLED: A case of congenital staphylococcal scalded skin syndrome (SSSS) with fatal outcome in a premature infant is reported. An intrauterine infection with Staphylococcus aureus was probably the cause for the fulminant course of the disease. Despite adequate antibiotic treatment, the infant died within 24 h after birth because of respiratory failure. CONCLUSION: Although rare, infection may occur in the perinatal period and SSSS may present within the first 24 h of life. In this situation, early administering of appropriate antibiotics is essential.

[Serious invasive pneumococcal disease in young children: the importance of vaccination]. / Ernstige pneumokokkeninfecties bij jonge kinderen: het belang van vaccinatie.

In three children with fever, two girls aged 8 and almost 10 months and one boy aged 5 months, invasive pneumococcal disease was present. The youngest girl presented with pneumococcal sepsis which was complicated by haemolytic uraemic syndrome--she recovered--and the boy developed fulminant fatal pneumococcal sepsis/meningitis. The oldest girl was admitted for pneumococcal cellulitis and recovered. More than 80% of the cases of childhood invasive pneumococcal disease occur in children less than 2 years of age. However, the long available 23-valent pneumococcal polysaccharide vaccine is not effective in this age group. Recently, a 7-valent pneumococcal conjugate vaccine was registered in the Netherlands. This conjugate vaccine is effective in protecting infants and children from invasive pneumococcal disease. The Health Council of the Netherlands has recommended inclusion of the conjugate vaccine in the standard vaccine schedule. In the absence of a universal vaccination, the 7-valent pneumococcal conjugate vaccine is recommended for children at high risk of invasive disease.