Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization

The presence of anti-HLA antibodies is an increasing challenge in kidney transplantation. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), has been proposed to complement conventional desensitization therapy. We aimed to describe TCZ plasma trough concentrations and their variability and to investigate the link between TCZ concentration and the evolution of anti-HLA antibodies. Sensitized kidney-transplant candidates treated monthly with TCZ (8 mg/kg) for desensitization were retrospectively included. TCZ concentrations were determined by liquid chromatography-tandem mass spectrometry. Seventy-four TCZ concentrations from 10 patients were analyzed. The TCZ trough concentration ranged from <1.0 to 52.5 mg·L−1, with a median of 25.6 mg·L−1 [25th–75th percentiles: 13.2–35.3 mg·L−1). The inter- and intra-individual coefficients of variation were 55.0% and 33.0%, respectively. The TCZ trough concentration was not related to IL-6 (rho = −0.46, p = 0.792), soluble IL-6R (rho = −0.81, p = 0.65) concentrations or reduction of anti-HLA antibodies (mixed-effects model adjusting, effect of TCZ trough concentration: rho = −0.004, p = 0.26). The individual median TCZ concentration tended to be associated with the number of antibodies, with an initial MFI > 3000 that dropped to <3000 after TCZ treatment (rho = 0.397, p = 0.083). TCZ trough concentrations in kidney-transplant candidates treated for desensitization were highly variable. Further studies on larger cohorts are needed to study the possible link between TCZ concentrations and the reduction of anti-HLA antibodies.

Food-Induced Anaphylaxis among Children Weighing <15 kg: A Single-Center Case Series of the Pediatric Emergency Department

<b><i>Introduction:</i></b> Food-induced anaphylaxis among infants shows an increasing prevalence; however, the prescription of epinephrine auto-injectors (EAIs) for children weighing &#x3c;15 kg is associated with issues of the needle length and the epinephrine dose. Several studies have shown age-related differences in food-induced anaphylaxis, although little is known about the weight-related differences in food-induced anaphylaxis. This study aimed to reveal the incidence, clinical characteristics, and management of food-induced anaphylaxis in children weighing &#x3c;15 kg. <b><i>Methods:</i></b> This chart review included children who visited the pediatric emergency department (ED) of the National Center for Child Health and Development (Tokyo, Japan) from January 2014 to December 2016 and were diagnosed with food-induced anaphylaxis. The severity of anaphylaxis was evaluated using the Sampson Grading Scale. <b><i>Results:</i></b> Of 89,232 ED visits, 444 visits included patients with food-induced anaphylaxis, after excluding cases of food-induced anaphylaxis related to oral desensitization therapy. The incidence was 4.98 per 1,000 visits. More than half of the children (<i>n</i> = 247/444, 55.6%) weighed &#x3c;15 kg. The proportion of grade 3 and higher severity anaphylactic symptoms was 74.5% (184/247) in children weighing &#x3c;15 kg and 79.2% (156/197) in children weighing 15 kg or more. The recurrence rate of food-induced anaphylaxis was 22.3% (55/247) in children weighing &#x3c;15 kg and 48.7% (96/197) in children weighing 15 kg or more. Among the children weighing &#x3c;15 kg, the proportion of those with recurrent food-induced anaphylaxis was 4 times higher in children weighing 10–15 kg than in those weighing &#x3c;10 kg (32.2% [47/146] vs. 7.9% [8/101]). The proportion of patients who were prescribed EAIs before each visit was 25.5% (14/55) in children weighing &#x3c;15 kg with a history of food-induced anaphylaxis. <b><i>Conclusion:</i></b> Food-induced anaphylaxis among children weighing &#x3c;15 kg occurred as frequently and was as severe as that among children weighing 15 kg or more. However, the proportion of patients prescribed EAIs was very low in children weighing &#x3c;15 kg with food-induced anaphylaxis. The potential need for EAIs is suggested among children weighing &#x3c;15 kg, especially among children weighing 10 kg or more but &#x3c;15 kg.

Drug-induced hypersensitivity syndrome following temozolimide for glioblastoma multiforme and the role of desensitization therapy

Introduction Temozolomide is an oral alkylating agent used as first line treatment of glioblastoma multiforme (GBM). It has also been used in the treatment of certain solid tumors such as metastatic melanoma. Commonly reported adverse effects include nausea and vomiting, constipation, headache, fatigue and myelosuppression. Cutaneous hypersensitivity reactions are rare and include an urticarial hypersensitivity reaction, alopecia, and Stevens–Johnson syndrome. To our knowledge, there are minimal reports of temozolomide-induced DRESS syndrome. Case Report We present a 54-year-old man with glioblastoma multiforme who presented with a fever, diarrhea and progressively worsening rash 6 weeks after starting temozolomide. Management & Outcome The patient was diagnosed recurrent DRESS syndrome and restarted on a gradual prednisone taper with resolution over the following weeks. Unfortunately, the patient was unable to be followed long-term due to relocation to a different state. Discussion To our knowledge, there are minimal reports of temozolomide-induced DRESS syndrome. The diagnosis can be life-threatening, which makes management of patients with GBM and no alternative treatment option challenging. The use of de-sensitization therapy to temozolomide has been proposed for the management of severe adverse cutaneous reactions.