Neurology and the histiocytoses: a case of Rosai-Dorfman-Destombes disease

The histiocytoses are a group of rare disorders characterised by the accumulation of neoplastic or non-neoplastic activated histiocytes in various tissues. Phenotypes vary widely from cutaneous lesions or lymphadenopathy that regress spontaneously to disseminated disease with poor prognosis. Neurological symptoms can be a presenting feature or appear during the course of disease. We present a challenging diagnostic and management case of Rosai-Dorfman-Destombes disease in a 48-year-old woman with a relapsing, partially steroid-responsive syndrome comprising patchy, non-length-dependent radiculoneuropathy with diffuse pachymeningitis and widespread systemic disease, and recent dramatic response to novel mitogen-activated kinase pathway inhibition. We discuss the clinical characteristics, diagnosis, recent breakthroughs in pathogenesis and emerging treatment options for Rosai-Dorfman disease and for the histiocytoses with neurological sequelae, including Langerhans cell histiocytosis and Erdheim-Chester disease

Development of DNA vaccines for patients following stem cell transplantation

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Development of DNA vaccines for patients following stem cell transplantation

For intracellular tumour or infectious disease antigens, induction of a cytotoxic lymphocyte (CTL) response is desirable.  To optimise induction of CTL, a modified DNA fusion vaccine has been developed: the C-terminal domain of FrC was removed to delete competitive epitopes.  Epitope presentation was then enhanced by re-positioning the peptide sequence of interest to the C-terminus of the remaining FrC domain.  We have previously shown in murine models that this vaccine (pDOM.peptide) successfully induced CTLs specific for a chosen tumour peptide.  In order to test the operation of this design in the clinic, an epitope from human cytomegalovirus, NLVPMVATV was chosen.  We have previously shown in mice that the DNA vaccine p.DOM-NLVPMVATV can induce CTL specific for the naturally processed peptide.  As part of a phase I clinical trail we have now safely vaccinated 3 stem cell transplant donors.  Cellular and humoral immune responses were monitored following vaccination and the results are presented. Finally, to gain more insight into the ability of the new vaccine design to induce significant levels of specific CTL, I have developed the DNA vaccine pDOM-GILGFVFTL.  This vaccine induced CTLs specific for the epitope which is immunodominant in the response of HLA-A0201 individuals to Influenza A virus.  These CTLs could lyse cells infected with influenza virus and showed some efficacy in protecting mice from challenge with a lethal dose of influenza A virus.</p

Vaccine-induced immune thrombotic thrombocytopenia (VITT) - a novel clinico-pathological entity with heterogeneous clinical presentations

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel entity that emerged in March 2021 following reports of unusual thrombosis after ChAdOx1 nCoV-19, (AstraZeneca) vaccination. Following the recognition of this syndrome, multiple consensus guidelines have been released to risk stratify patients presenting with possible symptoms after ChAdOx1 nCoV-19 vaccination. All guidelines rapidly identify VITT in patients with the complete triad of thrombocytopenia, thrombosis and elevated D-dimers after ChAdOx1 nCoV-19 vaccination. However, with earlier recognition of the associated symptoms, the clinical manifestations are likely to be more heterogeneous and represent an evolving spectrum of disease. In this setting, current guidelines may lack the sensitivity to detect early cases of VITT and risk missed or delayed diagnoses. The broad clinical phenotype and challenges associated with diagnosis of VITT are highlighted in our present case series of four patients with confirmed VITT. Dependent on the guidance used, each patient could have been classified as a low probability of VITT at presentation. The present study highlights the issues associated with the recognition of VITT, the limitations of current guidance and the need for heightened clinical vigilance as our understanding of the pathophysiology of this novel condition evolves