Javed Sheikh

Purpose of review Hypereosinophilic syndromes (HESs) are disorders characterized by sustained blood or tissue hypereosinophilia or both with subsequent damage to various organs due to eosinophilic infiltration and release of mediators. HES are now recognized to include varied eosinophilic disorders for some of which there are recent insights into their pathogenesis and targeted treatment. Recent findings Studies have helped delineate two subtypes of HES: the myeloproliferative variants of HES and the lymphocytic variants of HES. Many, but not all, myeloproliferative-HES patients have interstitial deletions on chromosome 4q12 that lead to fusion of the FIP1-like 1 and platelet-derived growth factor receptor α genes, with the fusion product encoding a protein that has constitutive tyrosine kinase activity. Lymphocytic-HES is a primary lymphoid disorder characterized by nonmalignant expansion of a T-cell population able to produce eosinophilopoietic cytokines, with the T-cell population being identified by flow cytometry or reverse transcriptase-PCR for T-cell receptor usage or both. Other HES subtypes are of uncertain causes and are included in recent diagnostic algorithms for the spectrum of HES. Summary The contemporary definition of the hypereosinophilic syndromes encompasses a range of eosinophilic disorders characterized by chronic blood hypereosinophilia often with eosinophil-mediated damage to various organs.

Eighty to 90% of patients with chronic urticaria have no specific external cause for their disease, which is therefore labeled 'chronic idiopathic urticaria'. We now know, however, that as many as 30-50% of patients have evidence of an autoantibody to the high-affinity receptor for IgE (FcepsilonRI), which may be pathogenic. The exact prevalence and role of these autoantibodies is still under investigation. The frequency of autoantibodies to FcepsilonRI in chronic urticaria has been estimated at 30-50%, but extensive epidemiological studies have not been done. Recent work has confirmed that autoantibodies to FcepsilonRI can be functional, meaning that they can cause histamine release from basophils in vitro. Evidence increasingly suggests that such autoantibodies are also functional in vivo, but conclusive evidence is still lacking. Approximately 50% of cases of urticaria still have no known cause, but recent studies have demonstrated that some of these patients may have intrinsic abnormalities of basophils or mast cells. The recent evidence that is discussed in this review helps to clarify the role of autoantibodies in some cases of urticaria, but also points towards other non-autoimmune mechanisms that might be pathogenic. Further investigation in these areas will help us to understand the cause of urticaria in cases that are still classified as 'idiopathic'.