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Myocarditis
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
COVID-19 is less frequent in children, with a milder course. More severe disease is now reported in a minority of children. They appear to have a cytokine storm, reflected clinically by HF, pneumonia, GI, neurological and renal features, associated with elevated CRP levels, ferritin and cytokines (IL-1, TNFα and IL-6) and many require intensive care support. It is interesting that some of these children met the biological criteria for macrophage-activation syndrome (MAS) highlighting the role of macrophages. This is now called a systemic inflammatory syndrome mimicking Kawasaki disease (KD), temporally associated with SARS-CoV-2 infection (Kawa-COVID-19).18 No EMB or autopsy findings are reported and, thankfully, all survive.
Immunosuppressants, rheumatic and gastrointestinal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Ciclosporin, a fungal macrolide, may be considered as an adjunct to methotrexate in resistant JIA. It is used specifically in the treatment of macrophage activation syndrome in systemic JIA [44]. Dosages of 3–5 mg/kg/day are frequently employed. Ciclosporin may be effective in juvenile dermatomyositis resistant to first-line therapy [45]. Blood pressure is monitored weekly for 4 weeks and monthly thereafter. Full blood count and renal profile is monitored monthly. Twelve hour trough blood levels are monitored at 1 week then monthly (range 95–205 mcg/ml, although in rheumatology practice, levels significantly below this range are frequently sufficient to achieve an adequate effect). Some centres monitor trough levels 4–6 monthly when a patient is established on a stable low dose of ciclosporin. Adverse effects include impaired renal function (increased risk with concomitant administration of NSAIDs), hypertension, hepatic toxicity, tremor, gingival hyperplasia and hypertrichosis.
Bispecific CAR T-cells for B-cell Malignancies
Published in Expert Opinion on Biological Therapy, 2022
In a phase 1 study, 17 patients with R/R B-ALL and 22 patients with R/R large B-cell lymphoma (LBCL) received CD19-22BB.zCAR infusion in a 3 + 3 dose escalation followed by a dose expansion phase (Tables 2 and 3) [21]. The bispecific CAR comprised a single cistron encoding the anti-CD19 murine FMC63 single-chain variable fragment (scFv) and fully human anti-CD22 m971 scFv. CRS was reported in 76% of patients, with two patients having grade 3 or higher. Thirty-seven percent of patients had neurotoxicity, four patients with grade 3 or higher. Two patients with grade ≥3 neurotoxicity also had macrophage activation syndrome. All adverse effects resolved with treatment. In LBCL, the best ORR and CRR at any time were 62% and 29%, respectively, and the median OSS and PFS were 22.5 and 3.2 months, respectively. On the other hand, 82% patients with B-ALL achieved CR and three achieved PR at 28 days while median OS and PFS were 11.8 and 5.8 months, respectively. In patients who relapsed, CD19 expression was low or absent but they continued to express CD22. The likely cause of CD22+ relapse could be due to a lower cytokine production by CD22 targeting versus CD19.
Hemophagocytic lymph histiocytosis (HLH): etiologies, pathogenesis, treatment, and outcomes in critically ill patients: a review article and literature to review
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Mohsin Mirza, Maryam Zafar, Joseph Nahas, Wafa Arshad, Anum Abbas, Abubakar Tauseef
An uncontrolled immune response spearheaded by disordered cytotoxic cell activity precipitating cytokine and macrophage over-activation also known as Macrophage activation syndrome (MAS). It’s the forefront of the frequent multiple organ damage induced by hemophagocytic lymph histiocytosis [1,6]. In the literature, while genetic mutations are identified as a cause of primary HLH, it is suggested that genetic mutation variants that are yet to be discovered may form the basis of secondary HLH as well [1]. Secondary HLH in the critically ill, which is the primary subject of this review, is identified mostly in the adult population as primary HLH often presents in childhood [6,13]. Secondary HLH is attributed mostly to triggers such as infection, malignancy, autoimmune disease, immunodeficiency, and drug reaction [4,6]. Infections are most commonly identified as causative factors of secondary HLH in the critically ill in both pediatric and adult population, followed by malignancy; Among infectious etiologies, viral infections are most frequently identified with Epstein Barr Virus and cytomegalovirus being the most common of the viruses identified [4,6,7]. Children are more likely to experience the HLH associated manifestation of a primary EBV infection [4]. An EBV reactivation presenting as HLH can occur in older patients with T cell lymphoma or in solid organ transplant recipients [4].
Aggressive natural killer cell leukemia: diagnosis, treatment recommendations, and emerging therapies
Published in Expert Review of Hematology, 2021
Yumeng Zhang, Dasom Lee, Quinto Gesiotto, Lubomir Sokol
The incidence of ANKL is highest in East Asia [3] and lowest in Europe and North America [9]. It mainly affects young adults, with the exception of ANKL deriving from chronic active EBV infection, which is frequently observed in children and adolescent patients [7]. Both males and females are equally affected. Patients often present with B symptoms, such as high fevers, hepatosplenomegaly, jaundice, lymphadenopathy, and less frequently with malignant ascites. The central nervous system and gastrointestinal tract are commonly involved with malignant cells [3,10,11]. Based on retrospective cohorts, the CNS positive rate was between 5–10% [11–13]. However, if CNS involvement is left untreated, the outcome is usually fatal. Unlike the more common indolent T-cell large granular lymphocytic leukemia, ANKL is not associated with rheumatologic disease. Laboratory evaluation has shown that cytopenias and coagulopathy related to disseminated intravascular coagulopathy (DIC) often require patients to undergo transfusion support. Many patients also develop macrophage activation syndrome (MAS) either at the time of diagnosis or during the disease course [14]. Neoplastic NK cells release a large number of cytokines, causing uncontrolled activation of normal lymphocytes, NK cells, and macrophages, which results in the development of MAS.