Dr. Mariam Hanna, MD @PedsAllergyDoc:
Dr Begin - Reviewing Omalizumab’s mechanism of action: 1) Formation of Allergen-specific blocking complexes. 2) Decrease in free allergen-specific IgE. 3) Disarming/dissociation of IgE from its receptor.
Proposed mechanism for Chronic Spontaneous Urticaria (CSU):
1) Autoimmune urticaria - anti IgE and to receptor
2) Autoallergic urticaria - IgE against self
Dr. Ellis @DrAnneEllis: Ligelizumab is a new "Hyper-Xolair" - much higher affinity for IgE antibody - showing promise for the management of chronic spontaneous urticaria (CSU).
Chronic Urticaria Treatment Options (click to enlarge the image).
Starting off the morning with Dr. Franks Siebenhaar from Charite, Germany- the role of PAF in itch of urticaria.
Chronic Urticaria is chronic - 20% of patients have hives for more than 20 years. Chronic urticaria is associated with a low QOL.
CSU in children - if symptoms are severe, it predicts it will be long lasting.
Goal of management for CSU: "Treat the disease until it is gone".
Treatment algorithm for CSU in international guidelines - 2nd generation antihistamines first and foremost - then double the dose, then quadruple the dose, then omalizumab.
Response to antihistamines indeed is dose dependent. 4 fold updosing has clearly been shown to more effective than licensed doses.
Siebenhaar: Mast cells are immunologic bombs.
Platelet Activating Factor (PAF) Increases vascular permeability - can cause a wheal and flare reaction similar to histamine. PAF induces itch just like other neuropeptides. Importantly, however, PAF does not release histamine from skin mast cells. Yet we still see a wheal and flare reaction. So it's independent. PAF levels have been shown to be elevated in chronic spontaneous urticaria (CSU).
Rupatadine is designed to inhibit both histamine and PAF. Has proven in vivo anti histamine as well as anti PAF activities. Siebenhaar: Rupatadine is also clearly efficacious in the treatment of cold induced urticaria. Histamine causes itch. PAF causes itch and burning sensation. Recent study in Japan show clear benefit of itch reduction with rupatadine regardless of the reason for their itchy skin. Siebenhaar: PAF should be considered a target for treatment of urticaria.
No clinically relevant drug interactions have been observed for any second generation antihistamines.