Library

Notes: Urticaria has diverse clinical presentations and causes. The implication of classifying urticaria primarily by clinical presentation rather than aetiology is that management can be focused on specific clinical problems without extensive investigations. Management pathways may involve nonpharmacological measures and drug interventions, which can be grouped into first-, second- and third-line therapies. Stronger, but potentially more risky, second- and third-line approaches may be justified for patients who do not respond to first-line therapy with antihistamines even though it may not be possible to define a specific aetiology, such as autoimmune urticaria, with confidence.

Notes: The relationship of aspirin sensitivity to urticaria is complex. Aspirin sensitivity can cause acute urticaria in some individuals, aggravate pre-existing chronic urticaria in others or, rarely, act as a cofactor with food or exercise to provoke anaphylaxis. Individuals who react with urticaria appear to come from a different population to those who react with asthma, although there is some overlap. Aspirin-sensitive chronic urticaria patients may also react adversely to some food additives. The pharmacological mechanisms of aspirin-sensitive urticaria are not fully understood but probably involve diversion of arachidonic acid metabolism from prostaglandin to cysteinyl leukotriene formation leading to direct effects on blood vessels and delayed mast cell degranulation with release of histamine. Cross-reactivity amongst all nonsteroidal drugs is common in aspirin-aggravated chronic urticaria but appears not to occur with selective cyclo-oxygenase 2 inhibitors.

Notes: Background The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis.Methods Manual basophil counts using a toluidine blue stain and automated 5-part differentials (Coulter® Gen. S™) were performed at 4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7.Results There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophil were higher in healthy controls than chronic urticaria (43.4/µL (2.1) vs. 4.4 (0.8), P 〈 0.001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P 〈 0.001) but increased in chronic urticaria (8.9 (1.9), P 〈 0.001). Loratadine did not influence them. UAS fell on treatment (3.3 (0.4) baseline, 1.4 (0.5) on loratadine and 0.5 (0.2) on prednisolone with loratadine, P 〈 0.001). There was a negative linear correlation between basophil numbers and UAS in untreated chronic urticaria patients (P = 0.001, Spearman rank correlation). Manual and automated basophil counts showed poor agreement. Lymphocyte numbers were lower in chronic urticaria than healthy controls. Neutrophils increased whereas lymphocytes and eosinophils decreased in all subjects on prednisolone. They were unaffected by loratadine.Conclusion The results are consistent with the hypothesis that circulating basophils may be recruited from blood into urticarial weals during disease activity. Automated counts are not suitable for assessing basophil numbers in chronic urticaria. The relevance of reduced lymphocyte numbers in chronic urticaria needs to be explored.

Notes: Background and Objective Peripheral blood basophils are reduced in some chronic urticaria patients when counted with granule stains. Approximately 30% of patients with severe chronic urticaria have functional autoantibodies which release histamine from healthy donor basophils in vitro but the relationship between basophil numbers in vivo and serum histamine releasing activity has not been studied.Objective To determine the relationship between basophil numbers and serum basophil histamine releasing activity and to assess whether basophils are present, but undetectable, in peripheral blood with granule stains by using a new Row cytometric method based on surface immunophenotype.Methods Basophils were counted manually by a chamber method using a granule stain and by flow cytometry using dual staining with anti-IgE and anti-FceRI in 25 chronic idiopathic urticaria patients and 25 healthy controls. Serum histamine releasing activity was assessed on healthy donor basophils in vitro and by the weal response to autologous serum skin testing in vivo (patients only).Results Basophils were significantly reduced in chronic urticaria by manual counting and How cytometry. A subgroup of seven patients with in vitro histamine releasing activity showed a marked reduction or absence of basophils by both methods. There were no obvious distinguishing clinical characteristics between these patients and the others; six of them showed positive autologous serum skin-test responses. On comparing the two methods, the manual basophil counts were generally lower than flow cytometric counts. Agreement over the full range of values was not strong and therefore counts obtained by the two methods are not directly interchangeable.Conclusions Basopenia in chronic idiopathic urticaria is associated with serum basophil bistamine releasing activity in a subgroup of patients. The lack of granule and surface immunophenotype staining suggests a reduction in numbers rather than an inability to detect circulating degranulated cells by conventional counting methods.

Notes: Circulating histamine releasing factor(s) have been demonstrated previously in chronic urticaria by an immediate weal-and-flare response to intradermal autologous serum injection. We have studied 25 chronic urticaria patients by in vivo skin testing with autologous sera and an in vitro histamine release assay using mixed leukocytes of healthy donors, to define the nature and functional properties of the serum factor(s). Twenty showed a weal response to autologous serum (mean ± s.e.m., 37.3±6.8 mm3). Weal formation was confined to ultrafiltered serum fractions 〉 100 kD in nine of nine patients. There was no response in 10 healthy controls or five patients with symptomatic dermographism. Fourteen chronic urticaria sera elicited histamine release 〉 10% (mean ± s.e.m., 44-3%± 6 7) above basal levels from leukocytes of at least one of seven healthy donors. This in vitro response was also confined to ultrafiltered serum fractions 〉 100 kD in seven of seven sera and was present in IgG fractions of six of seven chronic urticaria sera that showed histamine releasing activity. Functional studies indicated that this histamine releasing autoantibody had the properties of anti-IgE: chronic urticaria sera ‘desensitized’ basophil leukocytes to subsequent challenge with other chronic urticaria sera and to goat anti-human IgE antibody; human myeloma IgE inhibited histamine release from leukocytes in response to chronic urticaria sera; removal of surface-bound IgE by lactic acid “stripping” reduced histamine release in response to chronic urticaria sera and anti-IgE and subsequent passive sensitization with IgE myeloma serum partially restored it, Stainable peripheral blood basophils/mm3 in chronic urticaria patients were significantly reduced (mean ± s.e.m., 7.9 ± 2 0) when compared to healthy controls (39.6 ± 44), P 〈 0.001. These results suggest that histamine releasing autoantibodies are important in the pathogenesis of chronic urticaria by stimulating or facilitating degranulation of basophils and cutaneous mast cells through cross-linking cell surface IgE receptors.