Urticaria: new molecular insights and treatments. The Parkes Weber Lecture 1991.
Chronic urticaria remains one of the major unsolved clinical problems in dermatology. My group has employed an integrated experimental approach in order to shed light on the pathophysiology and treatment of this group of disorders. Using delayed pressure urticaria as a model, evidence has emerged of the role of eosinophil major basic protein (MBP) and of interleukin-6 (IL-6) as important molecular mediators, possibly explaining the poor response to H1 antihistamines. Our recent work in chronic idiopathic urticaria has led to identification of a circulating greater than 100 kD factor which causes wealing following intradermal injection and which releases histamine from normal leukocytes in vitro. Further characterisation confirmed that this skin and histamine releasing reactivity is due mainly to an IgG anti-IgE autoantibody. That this autoantibody is functionally significant is supported not only by its ability to release histamine and cause local wealing, but also by the results of removal by plasmapheresis which we have shown to cause clinical improvement in seven out of eight patients with severe unremitting chronic urticaria. It is concluded that chronic 'idiopathic' urticaria is an autoimmune disease due, in most patients, to a functionally significant IgG anti-IgE autoantibody. Immunotherapy offers the best long-term prospects of relief in severe unremitting cases.
Greaves
M W
MW
St John's Institute of Dermatology, St Thomas's Hospital, London.
D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D001798:Blood Proteins / Q000502:physiology; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis; D015777:Eicosanoids / Q000032:analysis; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000502:physiology; D005122:Exudates and Transudates / Q000737:chemistry; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015850:Interleukin-6 / Q000502:physiology; D010956:Plasmapheresis; D012260:Ribonucleases; D012867:Skin / Q000737:chemistry / Q000473:pathology; D012882:Skin Tests; D014581:Urticaria / Q000276:immunology / Q000503:physiopathology / Q000628:therapy
D001323:Autoantibodies; D001798:Blood Proteins; D016207:Cytokines; D015777:Eicosanoids; D047091:Eosinophil Granule Proteins; D007074:Immunoglobulin G; D015850:Interleukin-6; D007073:Immunoglobulin E; D012260:Ribonucleases