Chronic spontaneous urticaria: from the hunt for causes and pathogenesis to the identification of different endotypes.

Summary: The hunt for the causes and pathogenic mechanisms involved in chronic spontaneous urticaria (CSU) has engaged clinicians and scientists for decades. Although not all aspects of the disease are defined, our knowledge has now improved to the point that we can consider CSU as an umbrella clinical phenotype under which several different endotypes probably exist. The present article will briefly summarize the fascinating history of the progress in our knowledge of this disease.

Report of consensus panel 2 from the 11th international workshop on Waldenström's macroglobulinemia on the management of relapsed or refractory WM patients.

The consensus panel 2 (CP2) of the 11th International Workshop on Waldenström's macroglobulinemia (IWWM-11) has reviewed and incorporated current data to update the recommendations for treatment approaches in patients with relapsed or refractory WM (RRWM). The key recommendations from IWWM-11 CP2 include: (1) Chemoimmunotherapy (CIT) and/or a covalent Bruton tyrosine kinase (cBTKi) strategies are important options; their use should reflect the prior upfront strategy and are subject to their availability. (2) In selecting treatment, biological age, co-morbidities and fitness are important; nature of relapse, disease phenotype and WM-related complications, patient preferences and hematopoietic reserve are also critical factors while the composition of the BM disease and mutational status (MYD88, CXCR4, TP53) should also be noted. (3) The trigger for initiating treatment in RRWM should utilize knowledge of patients' prior disease characteristics to avoid unnecessary delays. (4) Risk factors for cBTKi related toxicities (cardiovascular dysfunction, bleeding risk and concurrent medication) should be addressed when choosing cBTKi. Mutational status (MYD88, CXCR4) may influence the cBTKi efficacy, and the role of TP53 disruptions requires further study) in the event of cBTKi failure dose intensity could be up titrated subject to toxicities. Options after BTKi failure include CIT with a non-cross-reactive regimen to one previously used CIT, addition of anti-CD20 antibody to BTKi, switching to a newer cBTKi or non-covalent BTKi, proteasome inhibitors, BCL-2 inhibitors, and new anti-CD20 combinations are additional options. Clinical trial participation should be encouraged for all patients with RRWM.

35 years of autologous serum skin test in chronic spontaneous urticaria: what we know and what we do not know.

Summary: The autologous serum skin test (ASST) has been used in patients with chronic spontaneous urticaria (CSU) as a means to detect an autoreactivity state for thirty-five years now. Nonetheless, several aspects of this old diagnostic test are still insufficiently defined. Particularly, the nature of the factor(s) responsible for the appearance of the wheal-and-flare skin reaction is still poorly characterized. This article will review our current knowledge about the clinical significance of the ASST and the factors possibly associated with the occurrence of the skin reaction following the intradermal administration of autologous serum that are known so far.