Chronic Urticaria in Children: an Update on Diagnosis and Treatment.

PURPOSE OF REVIEW: Both adults and children are frequently affected by symptoms of itchy urticarial lesions that cause considerable distress and impact nearly all their daily activities. A comprehensive history is critical to identify the etiology in patients who have chronic spontaneous urticaria (CSU) (those with symptoms for > 6 weeks) and is more important than extensive laboratory serum tests. Unfortunately, most of the current treatment guidelines have been based on data from adult studies since there is rare data on children. These treatment algorithms have been subsequently used to extrapolate treatments for children. RECENT FINDINGS: Current treatment regiments do not achieve complete success in all patients, neither adults nor children. As the pathophysiology of chronic urticaria slowly becomes defined, novel therapies are being tested which target these individual molecular pathways to treat those that continue to experience symptoms. Future studies are required to establish the natural history, risks/benefits and efficacy of current medications, and biologics used to treat CSU in children.

Hydrogen sulfide is an endogenous potentiator of T cell activation.

H(2)S is an endogenous signaling molecule that may act via protein sulfhydrylation to regulate various physiological functions. H(2)S is also a byproduct of dietary sulfate metabolism by gut bacteria. Inflammatory bowel diseases such as ulcerative colitis are associated with an increase in the colonization of the intestine by sulfate reducing bacteria along with an increase in H(2)S production. Consistent with its increased production, H(2)S is implicated as a mediator of ulcerative colitis both in its genesis or maintenance. As T cells are well established mediators of inflammatory bowel disease, we investigated the effect of H(2)S exposure on T cell activation. Using primary mouse T lymphocytes (CD3+), OT-II CD4+ T cells, and the human Jurkat T cell line, we show that physiological levels of H(2)S potentiate TCR-induced activation. Nanomolar levels of H(2)S (50-500 nM) enhance T cell activation assessed by CD69 expression, interleukin-2 expression, and CD25 levels. Exposure of T cells to H(2)S dose-dependently enhances TCR-stimulated proliferation with a maximum at 300 nM (30% increase, p < 0.01). Furthermore, activation increases the capacity of T cells to make H(2)S via increased expression of cystathionine γ-lyase and cystathionine ß-synthase. Disrupting this response by silencing these H(2)S producing enzymes impairs T cell activation, and proliferation and can be rescued by the addition of 300 nM H(2)S. Thus, H(2)S represents a novel autocrine immunomodulatory molecule in T cells.