“Urticaria is a mast cell derived disease which is characterized by short lived itchy wheals, angioedema or bothâ€. It can either present as acute urticaria with onset of symptoms and disease duration of less than 6 weeks or chronic urticaria where disease duration is equal or more than 6 weeks. Onset of chronic urticaria can be spontaneous or induced. It affects 10-30% of population once or more in a lifetime. According to EAACI guidelines, first line symptomatic treatment for the management of urticaria is 2nd generation non sedating antihistaminics. If standard dosing is not effective, it is recommended to hike the dose upto 4 times. Few patients of urticaria tend to be more severely affected, and does not even respond to 4 fold increased dosage of antihistaminics. In these antihistamine refractory urticaria, other modalities used are Omalizumab, cyclosporine, azathioprine, methotrexate and phototherapy, plasmapheresis and corticosteroids, IVIG. There is enough evidence to say that chronic urticaria is characterized by a systemic pro- inflammatory state. There are two major mechanisms described for the pathogenesis of chronic urticaria. One mechanism involves dysregulation in intracellular signaling pathways in the mast cells and basophils which causes defects in trafficking or function of these cells. The second mechanism is decribed by the development of circulating antibodies against FcεRI or IgE on both mast cells and basophils. IL-9 was initially considered a Th2-cytokine but now it is said to be a product of Th9 specialized subset of CD4+ T helper cells. IL-9 is a pleiotropic cytokine. It has both direct and indirect effects on various cell types. IL-9 is a potent growth factor which promots the proliferation as well as differentiation of mast cells. Patients with CSU patients showed markedly increased numbers of Th9 cells in peripheral blood, though levels were not as high as seen in acute urticaria. It indicates a high expression of IL-9 in peripheral blood because of the positive correlation between Th9 and IL-9. Study by Feng et al suggested that IL-9 and IL-10 contribute to the pathogenesis of Chronic Spontaneous Urticaria via activation of the JAK/STAT signalling pathway. Recent studies have suggested a vital role for apolipoproteins in the pathogenesis of various inflammatory diseases. ApoA-IV is known to have an inhibitory effect on basophil histamine release, which indicates that it could be a potential therapeutic target for allergic diseases. It is an endogenous antiâ€inflammatory protein which potently represses effector cell functions in eosinophils. Therefore, ApoAâ€IV if applied exogenously may characterize a fresh pharmacological approach for the treatment of allergic inflammation and other eosinophil driven disorders. A possible role for complement in pathogenesis of chronic urticaria is supported by lack of enhancement of serum pathogenic IgG if the serum is scarce in the second or fifth components of complement. Hence an anaphylatoxic complement fragment, most likely C5a, was considered to mediate the direct activation of basophils and mast cells. Kikuchi et al confirmed that cross- linking of the IgE receptor α subunit by pathogenic IgG in patients with CU leads to release of histamine, which is augmented by complement, and they verified that C5a is responsible for that augmentation.
The proposed study aims to identify biomarkers by correlating their levels with disease activity and response to treatment. It could be useful to predict the future evolution and response to treatment or to monitor the activity of CSU and the efficacy of treatment. |