An Unusual Presentaton of Tuberculosis with Septic Shock and Immune Reconstitution Inflammatory Syndrome in an Immunocompetent Patient

Tuberculosis presenting as septic shock is a rare entity especially in an immunocompetent patient. It has been reported in only 1% of patients with septic shock. Tuberculosis associated immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening of the current condition or the development of new lesions in patients who are on anti-tuberculosis treatment. In non-HIV patients with tuberculosis, the incidence of IRIS is only about 2.4%. We report a 29 year old immunocompetant female who presented with septic shock and on continued evaluation she tested positive for mycobacterium tuberculosis by Genexpert (sensitive to rifampicin) done in BAL fluid. All possible causes for immunodeficiency were ruled out. She was started on Anti-Tuberculosis therapy (ATT) and a month later, patient deteriorated clinically with high spiking temperatures and troublesome constitutional symptoms. Contrast-enhanced computed tomography (CECT) abdomen and chest revealed new onset multiple enlarged necrotic mediastinal, para aortic and hilar lymph nodes. After extensive evaluation including autoimmune profile, fungal culture, viral serology, Positron emission tomography (PET) scan, bone marrow analysis and ruling out all other possible causes for fever, IRIS was suspected and patient was started on steroids along with ATT. There was a drastic improvement in her symptoms within a week. She completed her course of ATT and steroids were gradually tapered. At 2 years of follow up, the patient is doing well.

Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 [PIMS-TS] in a Patient Receiving Infliximab Therapy for Inflammatory Bowel Disease

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 [PIMS-TS] is a newly described condition. It has a spectrum of presentations proposed to occur as part of a post-infectious immune response. We report the first case of PIMS-TS in a child on established anti-tumour necrosis factor alpha [anti-TNFα] therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6 weeks of daily fever with mucocutaneous, gastrointestinal, renal, and haematological involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia [up to 691 µ/L; normal 15–80 µg/L], C-reactive protein [CRP] [ >100mg/L for >10 days, normal 0–5 mg/L], erythrocyte sedimentation rate [ESR] consistently >100mm/h [normal 0–15 mm/h], raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase [LDH], anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin [PUO] were negative. The condition was refractory to treatment with intravenous immunoglobulin [IVIG] but improved within 24 h of high-dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow-up. Polymerase chain reaction [PCR] and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock, or organ failure. Accepting the wide spectrum of PIMS-TS presentations, it is possible that previous anti-TNFα therapy may have attenuated the disease course. Given the uncertainty around therapeutic strategies for PIMS-TS, this case supports the need for further investigation into continuing infliximab as a treatment option for the condition.

An ontogenetic switch drives the positive and negative selection of B cells

Developing B cells can be positively or negatively selected by self-antigens, but the mechanisms that determine these outcomes are incompletely understood. Here, we show that a B cell intrinsic switch between positive and negative selection during ontogeny is determined by a change from Lin28b to let-7 gene expression. Ectopic expression of a Lin28b transgene in murine B cells restored the positive selection of autoreactive B-1 B cells by self-antigen in adult bone marrow. Analysis of antigen-specific immature B cells in early and late ontogeny identified Lin28b-dependent genes associated with B-1 B cell development, including Arid3a and Bhleh41, and Lin28b-independent effects are associated with the presence or absence of self-antigen. These findings identify cell intrinsic and extrinsic determinants of B cell fate during ontogeny and reconcile lineage and selection theories of B cell development. They explain how changes in the balance of positive and negative selection may be able to adapt to meet the immunological needs of an individual during its lifetime.

A Rare Case of Hemophagocytic Lymphohistiocytosis in an Adult with Diffuse Large B-Cell Lymphoma

A 71-year-old Indian female presented with a 3-month history of weight loss and fatigue. Further review confirmed a histological diagnosis of diffuse large B-cell lymphoma. Although bone marrow analysis did not reveal hemophagocytosis, she had some clinical and laboratory pointers to hemophagocytic lymphohistiocytosis (HLH). Her clinical state deteriorated rapidly with development of acute respiratory distress syndrome, diffuse alveolar hemorrhage, and subsequently death.

Philadelphia-negatív krónikus myeloproliferativ neoplasia regiszter magyarországi létrehozása

Introduction: The establishment and operation of disease registry can be used to collect data on epidemiology cases. In addition, the registry can help to work out medical and health economical and political decisions for longer term. Aim: The aim of the authors was to collect and analyse data of patients with Philadelphia negative neoplasia in Hungary and draw conclusions about the basic types and features of the relevant disease. Method: An online electronic data collection system has been established, based on the permission of the Regional and Institutional Committee of Science and Research Ethics obtained in April 8, 2013. Data collection has been initiated by hematology centres in Hungary. In addition to collection of the epidemiology data, blood and bone marrow analysis data have been collected. Also, based on cardiovascular medical factors, risk stratification has been carried out. Finally, the authors have investigated the method and practice for patient treatment in Hungary. Results: Data of 901 patients from 15 Hungarian haematology centres have been recorded up to the date of June 30, 2015. After clarification of the data, 426 polycythaemia vera, 350 essential thrombocythaemia and 82 myelofibrosis cases were used for analysis. Conclusions: An online registry has been established which helps to clarify and analyse the basic features of certain medical cases and their treatment in Hungary. Including additional medical centres could help to improve the accuracy of medical analysis. Orv. Hetil., 2016, 157(3), 98–103.

Early switch to nilotinib in a case of non-optimal response to imatinib

We report a case of excellent response to nilotinib in a 22 years old man with chronic myeloid leukemia in suboptimal response to imatinib. After diagnosis he started cytoreductive therapy with cytarabine and hydroxyurea, then he begun therapy with imatinib 400 mg/day. After 3 months of treatment, he obtained a complete hematologic response (CHR) and a minor cytogenetic response (minor CyR). At 6 months CHR was confirmed, but bone marrow analysis showed increasing number of Ph+ cells (minimal CyR) and non significant reduction of BCR-ABL levels. According to ELN (European LeukemiaNet) guidelines, this is considered a suboptimal response. Clonal evolution, kinase domain mutations and reduced drug intake were excluded, thus we decided to early switch to nilotinib at 400 mg/BID. After 3 months of treatment we obtained a complete cytogenetic response (CCyR) and a strong reduction of BCR-ABL transcript, almost reaching a major molecular response (MMR).