Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients

Lupus ◽  
2004 ◽  
Vol 13 (5) ◽  
pp. 391-397 ◽  
Author(s):  
P I Sidiropoulos ◽  
D T Boumpas
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Lessons Learned ◽  
Systemic Lupus

scholarly journals Fever of Multiple Possible Origins

2021 ◽  
Vol 16 (2) ◽  
pp. 43-48
Author(s):  
David Spillane ◽  
Jeffrey Wiseman
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Inflammatory Markers ◽  
Bone Marrow Aspirate ◽  
Final Diagnosis ◽  
Lessons Learned ◽  
Prise En Charge ◽  
Systemic Lupus ◽  
Lupus Érythémateux Systémique ◽  
La Modification

A 60-year-old man presented with 1 week of fever despite broad-spectrum antibiotics for presumed pyelonephritis based on extended spectrum bacteriuria, recent bladder catheterization, and a negative search for other infections. He developed a maculopapular truncal rash, and pancytopenia with persistent fevers and worsening inflammatory markers despite modifying then stopping antibiotics. The non-specific clinical features at presentation and absence of hemophagocytosis on the initial bone marrow aspirate confounded multiple subspecialists and delayed the final diagnosis of hemophagocytic lymphohistiocytosis (HLH). Once this syndrome was elucidated, he responded well to dexamethasone and etoposide. An underlying diagnosis of systemic lupus erythematosus with aortic vasculitis was made, which in combination with pyelonephritis likely precipitated HLH. We summarize current concepts, pitfalls, and lessons learned in the diagnosis and management of HLH. RésuméUn homme de 60 ans se présente à l’hôpital à la suite d’une semaine de fièvre malgré la prise d’antibiotiques à large spectre pour traiter une pyélonéphrite soupçonnée, fondée sur une bactériurie à spectre étendu, un cathétérisme vésical récent et une recherche infructueuse d’autres infections. Il a développé une éruption cutanée maculopapulaire sur le tronc et une pancytopénie accompagnée d’une fièvre persistante et d’une augmentation des marqueurs de l’inflammation malgré la modification, puis l’arrêt des antibiotiques. Les manifestations cliniques non spécifiques à la présentation et l’absence d’hémophagocytose lors de la ponction médullaire initiale ont confondu de multiples surspécialistes et retardé le diagnostic définitif de lymphohistiocytose hémophagocytaire (LHH). Une fois que ce syndrome a été élucidé, le patient a bien répondu au traitement par la dexaméthasone et l’étoposide. Un diagnostic sous-jacent de lupus érythémateux systémique accompagné d’une vascularite de l’aorte a été posé qui, combiné à la pyélonéphrite, a probablement précipité la LHH. Nous résumons les concepts actuels, les pièges et les leçons apprises dans le diagnostic et la prise en charge de la LHH.

scholarly journals Developing novel drugs for systemic lupus erythematosus. Lessons learned from the belimumab trials

2012 ◽  
Vol 3 (3) ◽  
pp. 209-222
Author(s):  
Cristina Pamfil ◽  
Antonis Fanouriakis ◽  
Dimitrios T Boumpas
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Standard Of Care ◽  
Lessons Learned ◽  
Phase Iii ◽  
Systemic Lupus ◽  
Novel Therapy ◽  
Key Factor ◽  
B Cell Homeostasis

Systemic lupus erythematosus is the prototypic autoimmune disease with a broad range of clinical manifestations and a complex pathogenesis. B-cells hold a central role in its pathogenesis, not only as autoantibody producing cells, but also by producing other inflammatory mediators and by presenting autoantigens to autoreactive T cells. BlyS, a soluble ligand of the TNF cytokine family, is a key factor affecting B-cell homeostasis and survival and its blockade ameliorated the disease in animal models and preclinical studies of SLE. Following an unsuccessful phase II trial of belimumab, a monoclonal antibody targeting BlyS, two large phase III studies in patients with mild-to-moderate disease, BLISS-52 and BLISS-76, met their primary endpoints showing better efficacy of the drug over standard of care alone. To this end, development of a novel more sensitive responder index and improvements in study designs were crucial. As a result, belimumab became the first drug to get approval for the treatment of SLE after more than 50 years. In this paper we discuss the rationale, development, indications, lessons learned, pitfalls and challenges for this novel therapy and point-out to additional issues that need to be addressed in the future.http://dx.doi.org/10.7175/rhc.v3i3.206

scholarly journals Cerebral Microstructure Analysis by Diffusion-Based MRI in Systemic Lupus Erythematosus: Lessons Learned and Research Directions

2021 ◽  
Vol 12 (1) ◽  
pp. 70
Author(s):  
Ettore Silvagni ◽  
Alessandra Bortoluzzi ◽  
Massimo Borrelli ◽  
Andrea Bianchi ◽  
Enrico Fainardi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Diffusion Tensor ◽  
Lessons Learned ◽  
Quantitative Mri ◽  
Microstructure Analysis ◽  
Future Research ◽  
Water Molecules ◽  
Systemic Lupus ◽  
Research Perspectives

Diffusion-based magnetic resonance imaging (MRI) studies, namely diffusion-weighted imaging (DWI) and diffusion-tensor imaging (DTI), have been performed in the context of systemic lupus erythematosus (SLE), either with or without neuropsychiatric (NP) involvement, to deepen cerebral microstructure alterations. These techniques permit the measurement of the variations in random movement of water molecules in tissues, enabling their microarchitecture analysis. While DWI is recommended as part of the initial MRI assessment of SLE patients suspected for NP involvement, DTI is not routinely part of the instrumental evaluation for clinical purposes, and it has been mainly used for research. DWI and DTI studies revealed less restricted movement of water molecules inside cerebral white matter (WM), expression of a global loss of WM density, occurring in the context of SLE, prevalently, but not exclusively, in case of NP involvement. More advanced studies have combined DTI with other quantitative MRI techniques, to further characterize disease pathogenesis, while brain connectomes analysis revealed structural WM network disruption. In this narrative review, the authors provide a summary of the evidence regarding cerebral microstructure analysis by DWI and DTI studies in SLE, focusing on lessons learned and future research perspectives.

scholarly journals Developing novel drugs for systemic lupus erythematosus. Lessons learned from the belimumab trials

2012 ◽  
Vol 3 (3) ◽  
pp. 209
Author(s):  
Cristina Pamfil ◽  
Antonis Fanouriakis ◽  
Dimitrios T Boumpas
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Standard Of Care ◽  
Lessons Learned ◽  
Phase Iii ◽  
Systemic Lupus ◽  
Novel Therapy ◽  
Key Factor ◽  
B Cell Homeostasis

Systemic lupus erythematosus is the prototypic autoimmune disease with a broad range of clinical manifestations and a complex pathogenesis. B-cells hold a central role in its pathogenesis, not only as autoantibody producing cells, but also by producing other inflammatory mediators and by presenting autoantigens to autoreactive T cells. BlyS, a soluble ligand of the TNF cytokine family, is a key factor affecting B-cell homeostasis and survival and its blockade ameliorated the disease in animal models and preclinical studies of SLE. Following an unsuccessful phase II trial of belimumab, a monoclonal antibody targeting BlyS, two large phase III studies in patients with mild-to-moderate disease, BLISS-52 and BLISS-76, met their primary endpoints showing better efficacy of the drug over standard of care alone. To this end, development of a novel more sensitive responder index and improvements in study designs were crucial. As a result, belimumab became the first drug to get approval for the treatment of SLE after more than 50 years. In this paper we discuss the rationale, development, indications, lessons learned, pitfalls and challenges for this novel therapy and point-out to additional issues that need to be addressed in the future.http://dx.doi.org/10.7175/rhc.v3i3.206

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