zithromax and Lymphohistiocytosis--Hemophagocytic

The optimal dose regimen of ruxolitinib (RUX) in children with hemophagocytic lymphohistiocytosis (HLH) remains to be determined. The aim was to develop and verify a population pharmacokinetic (PPK) model, and then provide references for the optimization of dose regimen of RUX in children with HLH.. A total of 189 RUX concentrations from 32 children were included. The PPK model was established using the nonlinear mixed-effects model approach. Predictive performance and stability of the final PPK model were evaluated. The exposure of RUX in different clinical scenarios was simulated through Monte Carlo simulations.. For the first time, a PPK model of RUX in children with HLH was developed and evaluated. The coadministration with TZS and/or AZM were found to reduce the clearance of RUX in children. These findings could provide new insights for the precise treatment of RUX in children with HLH.

Topics: Azithromycin; Child; Drug Interactions; Humans; Lymphohistiocytosis, Hemophagocytic; Models, Biological; Nitriles; Pyrimidines

Topics: Aged; Atovaquone; Azithromycin; Babesiosis; Biopsy; Combined Modality Therapy; Exchange Transfusion, Whole Blood; Female; Humans; Induction Chemotherapy; Lymphohistiocytosis, Hemophagocytic; Spleen

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Age Factors; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Bromhexine; Coronavirus Infections; COVID-19; Cytokines; Expectorants; Humans; Hydroxychloroquine; Hypertension; Inflammation; Interferon beta-1a; Interleukin-1; Interleukin-12; Interleukin-6; Lymphohistiocytosis, Hemophagocytic; Obesity; Pandemics; Pneumonia, Viral; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Risk Factors; Smoking; Tumor Necrosis Factor-alpha

Novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in Wuhan, China. Since then, COVID-19 has become a pandemic affecting more than 4.1 million people worldwide. Patients with COVID-19 have a wide spectrum of manifestations, one being cytokine release syndrome (CRS) and its fatal correlate, secondary hemophagocytic lymphohistiocytosis (sHLH). Anti-cytokine therapy such as tocilizumab, an IL-6 receptor antagonist, is a potential treatment for COVID-19; however, data regarding the efficacy of this anti-IL-6 therapy are currently lacking. We report two cases of patients who received a diagnosis of COVID-19 complicated by CRS and were treated with tocilizumab. Both patients progressed to sHLH despite treatment with tocilizumab, and one developed viral myocarditis, challenging the safety and clinical usefulness of tocilizumab in the treatment of COVID-19-induced CRS. These cases highlight the need for clinical trials to determine optimal patient selection and timing for the use of tocilizumab during this disease process.

Topics: Adult; Aged; Anti-Infective Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Azithromycin; Betacoronavirus; C-Reactive Protein; Clinical Deterioration; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Fatal Outcome; Female; Humans; Hydroxychloroquine; Hypoxia; Lymphohistiocytosis, Hemophagocytic; Male; Myocarditis; Pandemics; Pneumonia, Viral; Respiration, Artificial; SARS-CoV-2; Shock, Septic

Topics: Adult; Atovaquone; Azithromycin; Babesia; Babesiosis; Cyclosporine; Dexamethasone; Humans; Immunocompetence; Lymphohistiocytosis, Hemophagocytic; Male; Treatment Outcome

To analyze the clinical manifestations and intervention against fulminant scrub typhus-associated hemophagocytic syndrome.. The medical records for the onset time of hemophagocytic syndrome, the clinical course, the chest radiographic findings, laboratory data, antibiotic therapy, clinical outcome and its prognosis were retrospectively reviewed.. (1) Four patients were diagnosed as scrub typhus based on clinical manifestations only, while 15 patients met the criteria of laboratory diagnosis. All 19 patients with scrub typhus had hemophagocytic syndrome. Eschar lesion was identified in 12 patients, 7 patients were described as an ulcer. A seasonal pattern (78.9% from June through September in 15 patients) was observed. Clinical misdiagnosis was common (all 19 cases). There were 9 patients with admitting diagnosis of scrub typhus, 10 patients were not diagnosed as scrub typhus after admission. In 5 cases within 3 days after admission diagnosis was corrected as scrub typhus. Until discharge from the hospital, 5 cases were not diagnosed with scrub typhus. In this study, the length of time from the illness onset (beginning of fever) to the occurrence of clinical symptoms was (9 ± 4) days. (2) All 19 patients had changed AST levels (149 ± 37) U/L, albumin levels (23 ± 4) g/L, C-reactive protein levels (103 ± 51) mg/L, and platelet count (48 ± 41) × 10⁹/L; bone marrow aspiration revealed in 16 patients marked hemophagocytosis. Weil-Felix agglutination test revealed positive results in 6 of 15 cases. Diagnostic IFA results were positive for 14 patients; 19 patients had interstitial pneumonitis and 17 patients had pleural effusion. (3) Five cases with failure to diagnose the disease had ineffective antibiotics treatment (imipenem or β-lactam-based regimens). These patients did not receive appropriate treatment with antibiotics against scrub typhus. Fourteen patients with admitting diagnosis of scrub typhus were successfully treated with appropriate antibiotics, 8 cases with chloramphenicol, 3 cases with azithromycin, and in 3 patients (2 cases of azithromycin and one case of erythromycin), therapy was then switched to chloramphenicol. Four patients were treated with methylprednisolone and 10 patients with dexamethasone. (4) During their hospitalization, the clinical course in five cases with failure to diagnose the disease rapidly developed and progressed to the life-threatening MODS, four of five cases died. However, the course in 14 patients were relieved and did not progress to MODS.. The diagnosis of scrub typhus was frequently delayed, the early course of scrub typhus could be associated with hemophagocytic syndrome. Serious complications of MODS generally occur without antibiotic treatment. Scrub typhus-associated hemophagocytic syndrome should be taken into consideration among patients with acute systemic febrile illness, significant increases in levels of CRP, hypoalbuminemia, thrombocytopenia, splenomegaly, pneumonitis with pleural effusion, especially those with suspected exposure history. It was not easily recognized without careful observation and was present for a few days in each patient.

Topics: Anti-Bacterial Agents; Azithromycin; C-Reactive Protein; Clinical Laboratory Techniques; Diagnosis, Differential; Erythromycin; Humans; Imipenem; Lymphohistiocytosis, Hemophagocytic; Pneumonia; Retrospective Studies; Scrub Typhus