Search PubMed⌕ Search

Biomedical subjects

C E Grattan

Publications and source records attributed to C E Grattan.

At least 19 recordsLinked to original sources
PubMed2001

Basophils in chronic urticaria.

Blood basophils are reduced in chronic urticaria and respond less well to immunologic stimuli. Active recruitment of basophils from peripheral blood into lesional skin may be important in wheal pathogenesis.

Antibodies, Anti-Idiotypic↗
PubMed2000

Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria.

BACKGROUND: Histamine-releasing activity (HRA) is detectable in up to 50% of patients with chronic ordinary urticaria. OBJECTIVES: To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria. METHODS: Thirty patients with severe unremitting disease, responding poorly to antihistamines and showing a positive autologous serum skin test (ASST) as a marker of HRA, were randomized to 4 mg kg-1 daily of cyclosporin (Sandimmun, n = 20) or placebo (n = 10) for 4 weeks. Non-responders were offered open-label cyclosporin for 4 weeks. All were followed for up to 20 weeks or until clinical relapse; all took cetirizine 20 mg daily throughout the study. The primary measure of efficacy was a daily urticaria activity score (UAS) of weal numbers and itch (maximum score 42 per week). A positive response was defined as a reduction to < 25% of baseline weekly UAS and relapse as a return to > 75%. The effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment. RESULTS: Twenty-nine patients (19 active, 10 controls) completed the randomized trial medication. Eight of 19 on active treatment but none on placebo had responded at 4 weeks (P < 0.05). Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks. Mean reduction in UAS between weeks 0 and 4 was 12.7 (95% confidence interval, CI 6.6-18.8) for active and 2.3 (95% CI - 3.3-7.9) for placebo (P = 0.005). Seventeen non-responders (seven randomized to active and 10 to placebo) chose open-label cyclosporin and 11 responded after 4 weeks. Six of the eight randomized active drug responders relapsed within 6 weeks. Of the 19 responders to randomized and open-label cyclosporin, five (26%) had not relapsed by the study end-point. Mean in vitro serum HRA fell from 36% (95% CI 22-49%) to 5% (95% CI 1-8%) after cyclosporin treatment (n = 11, P < 0.0001). The ASST response to post-treatment serum was also reduced (P < 0.05). CONCLUSIONS: This study shows that cyclosporin is effective for chronic urticaria and provides further evidence for a role of histamine-releasing autoantibodies in the pathogenesis of this chronic 'idiopathic' disease.

Adult↗
PubMed1999

The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria.

One-third of patients with chronic idiopathic urticaria (CIU) have circulating functional autoantibodies against the high affinity IgE receptor FcepsilonRI, or IgE. The intradermal injection of autologous serum causes a weal and flare reaction in many patients with CIU, and this reaction forms the basis of the autologous serum skin test (ASST). We have determined the parameters of the ASST which define the optimal sensitivity and specificity for the identification of patients with autoantibodies. Two physicians (R.A. S. and C.E.H.G.) performed ASSTs in a total of 155 patients with CIU, 40 healthy control subjects, 15 patients with dermographism, nine with cholinergic urticaria and 10 with atopic eczema. Patients were classified as having functional autoantibodies by demonstrating in vitro serum-evoked histamine release from the basophils of two healthy donors. There were significant differences (P < 0.001) in the mean weal diameter, weal volume, weal redness and flare area of the intradermal serum-induced cutaneous responses at 30 min between patients with CIU with autoantibodies and either those without autoantibodies or control subjects. The optimum combined sensitivity and specificity of the ASST was obtained if a positive test was defined as a red serum-induced weal with a diameter of >/= 1.5 mm than the saline-induced response at 30 min. For R.A.S. and C.E.H.G., the ASST sensitivity was 65% and 71% and specificity was 81% and 78%, respectively. Using these criteria, the following subjects had positive ASSTs: none of 15 dermographics, none of 10 atopics, one of nine cholinergics and one of 40 controls.

Autoantibodies↗
PubMed1998

Cutaneous vasculitis in a defined population--clinical and epidemiological associations.

OBJECTIVE: To examine the value of the American College of Rheumatology (ACR) 1990 criteria for Henoch-Schönlein purpura (HSP) and hypersensitivity vasculitis (HSV) and the Chapel Hill Consensus Conference (CHCC) definition of cutaneous leukocytoclastic angiitis (CLA) in the classification of cutaneous vasculitis and to estimate the annual incidence of biopsy proven cutaneous vasculitis in a well defined population. METHODS: ACR criteria for HSP and HSV and the CHCC definition for CLA and HSP were applied to an unselected cohort of 84 patients with biopsy proven cutaneous vasculitis attending a single district hospital in the United Kingdom between January 1990 and December 1994. RESULTS: Thirty-seven patients fulfilled ACR criteria for HSV, of whom 27 also fulfilled the ACR criteria for HSP. Thirty-two patients met the CHCC definition for CLA and 7 the CHCC definition for HSP. The overall annual incidence of cutaneous vasculitis was 38.6/million (95% CI 30.6-48.1), and for CLA 15.4/million (95% CI 10.6-21.8). CONCLUSION: The ACR 1990 criteria for HSP and HSV overlap; the CHCC definitions for CLA and HSP provide clearer distinction. Cutaneous vasculitis is as common as systemic vasculitis.

Antibodies, Antinuclear↗
PubMed1997

Flow cytometric analysis of basophil numbers in chronic urticaria: basopenia is related to serum histamine releasing activity.

BACKGROUND: 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 flow 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-Fc epsilonRI 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 flow 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. CONCLUSION: Basopenia in chronic idiopathic urticaria is associated with serum basophil histamine 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.

Adolescent↗
PubMed1993

Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria.

BACKGROUND: Most urticarias are induced by vasoactive mediators such as histamine released from mast cells. Although mast cells are activated by allergens through cross-linking of cell-surface--bound IgE, this mechanism does not appear to explain most cases of chronic urticaria, which, when allergic, infectious, drug-induced, or physical causes cannot be identified, are classified as idiopathic. METHODS: We recruited 26 patients with chronic idiopathic urticaria, in whom intradermal injection of autologous serum caused a wheal-and-flare response. Serum from four patients that induced marked histamine release from basophils from a donor with very low serum IgE levels was studied with respect to the IgE dependence of the histamine release, the activity of the IgG fractions, and the neutralizing effect of a recombinant preparation of the soluble extracellular domain of the alpha subunit of the high-affinity IgE receptor (sFc epsilon RI alpha). RESULTS: The histamine-releasing activity of the serum was abolished by passive sensitization of basophils with myeloma IgE, enhanced after dissociation of IgE by treatment with lactic acid, and induced by IgG fractions from the serum of all four patients. Preincubation of the serum and isolated IgG with sFc epsilon RI alpha resulted in almost complete neutralization. CONCLUSIONS: Histamine-releasing IgG autoantibodies against the alpha subunit of the high-affinity IgE receptor are present in the circulation of some patients with chronic urticaria. Autoantibody-induced cross-linking of IgE receptors may be an important mechanism in the pathogenesis of chronic urticaria and other diseases mediated by mast cells.

Adult↗
PubMed1992

Plasmapheresis for severe, unremitting, chronic urticaria.

Histamine-releasing autoantibodies have been identified in chronic idiopathic urticaria. 8 patients with severe disease and histamine-releasing activity in their sera underwent plasmapheresis. Symptoms were abolished for 2 months in 1 patient and for 3 weeks in another, 2 showed almost complete resolution of symptoms, 2 had temporary relief, and the other 2 showed little change. Further investigation in 4 of the patients showed significantly reduced skin-test responses to fresh post-exchange autologous sera after plasmapheresis compared with stored pre-exchange sera, but the response to intradermal histamine remained unchanged. Blood cellular histamine increased as in-vitro serum histamine-releasing activity fell after plasmapheresis. These results favour a pathogenetic role for histamine-releasing autoantibodies in patients with chronic urticaria.

Adult↗
PubMed1992

Oral papillary plasmacytosis resembling candidosis without demonstrable fungus in lesional tissue.

Two cases with exuberant papillary and nodular hyperplasia of the hard and soft palates are described. Both were elderly edentulous men with bilateral angular stomatitis. The papillary hyperplasia extended as far as the epiglottis and was associated with swelling and fissuring of the upper lip in patient 1. In patient 2, the palatal change extended to the maxillary gingiva and was associated with smooth plaques and fissuring of the dorsal tongue. Histology of both cases showed a dense polyclonal plasma-cell infiltrate with overlying epithelial hyperplasia, parakeratinization and neutrophil micro-abscesses suggesting Candida infection but fungal elements could not be demonstrated. Patient 1 also showed defective cellular immunity to Candida antigen which was reversed by treatment with ketoconazole and levamisole, antedating clinical improvement.

Aged↗
PubMed1991

Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria.

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 greater than 100 kD in nine of nine patients. There was no response in 10 healthy controls of five patients with symptomatic dermographism. Fourteen chronic urticaria sera elicited histamine release greater than 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 greater than 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 +/- 4.4), P less than 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.

Adult↗
PubMed1991

Histamine-releasing autoantibodies in chronic urticaria.

Circulating histamine-releasing factors have been identified in the serum and plasma of chronic-urticaria patients by in vivo skin testing and in vitro histamine release from heterologous mixed leukocytes. Quantitative mast cell studies of serum skin test biopsies and electron microscopy indicate that the serum factors release histamine by mast cell degranulation. Peripheral blood basophils and total cellular blood histamine are reduced in chronic-urticaria patients suggesting that the circulating serum factors cause sustained degranulation. Histamine-releasing activity has been identified by skin testing in ultrafiltered serum fractions less than 30 kDa and greater than 100 kDa. In vitro histamine-releasing activity was confined to ultrafiltered serum fractions greater than 100 kDa and was present in IgG purified from some chronic-urticaria sera by protein G affinity chromatography. The dose-response relationship and kinetics of histamine release in vitro were similar to those of anti-human IgE. 'Desensitisation' of basophils by prior incubation with anti-IgE in the absence of calcium and competitive inhibition studies with myeloma IgE serum indicated that histamine-releasing autoantibodies in chronic-urticaria sera and purified IgG have the properties of anti-IgE. Plasma exchange in 4 patients with active chronic urticaria refractory to antihistamine therapy showing in vivo and in vitro histamine-releasing activity was followed by temporary remission of disease activity in 2 of them. It is possible that chronic urticaria is an autoimmune disease.

Animals↗
PubMed1991

Comparison of topical PUVA with UVA for chronic vesicular hand eczema.

Topical PUVA was compared with UVA for the treatment of chronic vesicular hand eczema in a double-blind randomized within-patient trial. Twelve of 15 patients completed 8 weeks' treatment and were followed up for 8 weeks. Both sides improved over the 8-week treatment period (p less than 0.05) and both remained substantially better objectively and subjectively at 8 weeks' follow-up. There was no statistical difference between assessments of the treated hands at any stage. Nine of the patients who completed the study answered a questionnaire up to 18 months later. In 4, eczema was healed, 3 were better on the PUVA-treated hand and 1 on the UVA-treated hand. It is possible that UVA alone is beneficial for chronic hand eczema.

Adult↗
PubMed1991

Antiphospholipid syndrome and cutaneous vasoocclusive disorders.

The antiphospholipid syndrome (characterized by the presence of circulating lupus anticoagulants or anticardiolipin antibodies) was first recognized in patients with systemic lupus erythematosus (SLE), but the syndrome can also exist in the absence of SLE. The clinical features include arterial or venous thrombosis, recurrent abortion, neurological problems, and various cutaneous disorders including thrombophlebitis, livedo reticularis, atrophie blanche, leg ulcers, and gangrene. In some cases, antiphospholipid antibodies may play a role with other recognized syndromes characterized by vascular occlusion, such as Sneddon's syndrome (livedo reticularis with cerebrovascular occlusion) and Degos' disease.

Antiphospholipid Syndrome↗
PubMed1990

The pathology of the autologous serum skin test response in chronic urticaria resembles IgE-mediated late-phase reactions.

The wheal-and-flare response to intradermal autologous serum in chronic urticaria offers a model for study of the pathogenesis of the disorder. Serial biopsies of autologous serum induced wheals were performed in 5 chronic urticaria patients to assess the evolution of the cellular inflammatory response and to look for evidence of mast cell degranulation. Perivascular neutrophils and eosinophils were seen as early as 30 min, becoming more intense and diffuse over 2 h. T lymphocyte numbers were increased by 2 h, CD4+ cells outnumbering CD8+ cells at 24 h. By 48 h, the neutrophils were clearing, but eosinophils and lymphocytes persisted. The histology of compound 48/80-induced wheals was similar to serum-induced wheals, but there was little or no response to physiological saline (0.16 M). Stainable mast cells were reduced in compound 48/80- and serum-induced wheals when compared to saline skin tests. Mast cell granules appeared swollen and had lost their characteristic lamellar substructure on electron microscopy of a serum-induced wheal biopsied at 10 min. Eosinophil degranulation was also observed at 2 h. The resemblance of the inflammation to the late phase of IgE-mediated immediate hypersensitivity reactions in atopics supports the concept that a circulating factor causes mast cell degranulation in chronic urticaria and may be important in the pathogenesis of the disorder.

Aged↗