RESUMO
Alternatives are urgently needed in patients with CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome (L-HES) requiring high-level steroids or who are unresponsive and/or intolerant to conventional alternative therapies. We report five L-HES patients (44-66â¯years) with cutaneous involvement (nâ¯=â¯5) and persistent eosinophilia (nâ¯=â¯3) despite conventional therapies, who successfully received JAK inhibitors (tofacitinib nâ¯=â¯1, ruxolitinib nâ¯=â¯4). JAKi led to complete clinical remission in the first 3â¯months in all (with prednisone withdrawal in four). Absolute eosinophil counts normalized in cases receiving ruxolitinib, while reduction was partial under tofacitinib. After switch from tofacitinib to ruxolitinib, complete clinical response persisted despite prednisone withdrawal. The clone size remained stable in all patients. After 3-13â¯months of follow-up, no adverse event was reported. Prospective clinical trials are warranted to examine the use of JAKi in L-HES.
Assuntos
Síndrome Hipereosinofílica , Humanos , Prednisona/uso terapêutico , Estudos Prospectivos , Complexo CD3 , Síndrome Hipereosinofílica/tratamento farmacológico , Linfócitos T CD4-PositivosRESUMO
Eosinophils are often considered as the pathologic landmark of chronic rhinosinusitis with nasal polyps (CRSwNP). Many studies emphasize their pivotal role in mucosal remodeling by their innate action via cytotoxic proteins degranulation. Eosinophil nasal recruitment from the bloodstream through endothelium diapedeses requires the intricate action between the nasal epithelium, epithelial cell-activated type 2 innate lymphoid cells, and adaptive immune cells secreting alarmins, cytokines, and specific chemokines. This immune pathway refers to a T-helper 2 (T2)-driven lymphocyte response, often considered as the main inflammatory process in CRSwNP in western countries. The release of T2 cytokines, among which interleukin (IL)-4, IL-5, and IL-13, fundamentally contributes to this immune response. New biologic agents capable of blocking T2 cytokines have been developed in the field of eosinophil-associated diseases, shifting the paradigm of treatment for patients with CRSwNP. The first part of this review describes each step of the eosinophil journey from hematopoietic stem cell maturation to nasal mucosa homing. The different eosinophil activation processes and their inflammatory functions are also described. This is followed by a discussion on currently available biologic therapies in CRSwNP with a specific focus on eosinophilic response. Beyond an eosinophil-blocking strategy, a cluster analysis of specific T2 biomarkers could be required to best predict the response to such biologic therapies in the future.