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Biomedical subjects

M W Greaves

Publications and source records attributed to M W Greaves.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

The extent and nature of disability in different urticarial conditions.

Chronic forms of urticaria are common, often adversely impacting on quality of life. No formal studies have assessed the extent and nature of disability in different types of urticaria. The Dermatology Life Quality Index (DLQI) is a simple and validated 10-item questionnaire designed to measure and compare disability in different skin conditions. In this study, we aimed to assess the disability in different urticarial groups using the DLQI, allowing comparison with previously published DLQI scores in common skin diseases. The DLQI was administered to 170 consecutive patients attending a specialist urticaria clinic over a 4-month period. Consistent with previous studies using the DLQI, mean scores were not influenced by gender or age. Patients with chronic idiopathic urticaria without a concurrent physical urticaria (n = 47) suffered moderate quality of life impairment (mean +/- SD DLQI 25 +/- 24%). In comparison, patients with chronic idiopathic urticaria with concurrent delayed pressure urticaria (DPU) (n = 26) suffered significantly higher quality of life impairment (mean +/- SD DLQI 43 +/- 23%, 95% confidence interval for difference 7-29%). Disability in this group was greatest in the dimensions of work/study, symptoms/feelings and leisure. Subjects with another form of physical urticaria, cholinergic urticaria, also endured high levels of disability (n = 9, mean +/- SD DLQI 50 +/- 34%). From our urticaria study group, we have shown that subjects with DPU and cholinergic urticaria endure the most quality of life impairment. The mean DLQI scores demonstrated in these groups are comparable with those previously seen in severe atopic dermatitis out-patients (60%) and higher than those seen in out-patients with psoriasis (29.7%), acne (24.3%) and vitiligo (16.1%).

Activities of Daily Living↗
PubMed1999

Human leucocyte antigen class II associations in chronic idiopathic urticaria.

The major histocompatibility complex (MHC) acts as a marker for self during T-cell ontogeny and is associated with the pathogenesis of many autoimmune diseases. Recent investigations have shown about 30% of patients with chronic idiopathic urticaria (CIU) have IgG autoantibodies against the high-affinity IgE receptor, FcepsilonRI, or IgE. A link between MHC class II alleles and CIU has not been reported previously. DNA was extracted from blood of 100 Caucasian patients with CIU, and the MHC class II type determined using the polymerase chain reaction with sequence-specific primers, testing for DRB and DQB1 alleles. The frequency of alleles in CIU patients was compared with that found in 603 controls. Further human leucocyte antigen (HLA) typing on patient subsets, classified by the patients' responses to intradermal injection of autologous serum and their serum-induced histamine release from basophil leucocytes of healthy donors, was undertaken. HLA DRB1*04 (DR4) and its associated allele, DQB1*0302 (DQ8), are raised in CIU patients compared with a control population (P = 2 x 10-5 and P = 2 x 10-4, respectively). HLA DRB1*15 (DR15) and its associated allele, DQB1*06 (DQ6), are significantly less frequently associated with CIU. The HLA DRB1*04 association is particularly strong (corrected P = 3.6 x 10-6) for patients whose serum has in vivo and in vitro histamine-releasing activity. HLA class II typing is consistent with the concept that CIU is a heterogeneous disease, and supports an autoimmune pathogenesis in a subset of patients.

Adolescent↗
PubMed1999

Suppressed alloantigen presentation, increased TNF-alpha, IL-1, IL-1Ra, IL-10, and modulation of TNF-R in UV-irradiated human skin.

Cytokines induced in skin by ultraviolet radiation cause local and systemic immunosuppression. Tumor necrosis factor alpha, interleukin-1, and interleukin-10 are key mediators in the mouse, but less is known about cytokine synthesis and function in ultraviolet-irradiated human skin. We exposed human skin to 3 minimal erythema doses of solar-simulated radiation and raised suction blisters at intervals to 72 h. Alloantigen presentation was suppressed in a mixed epidermal cell-lymphocyte reaction by 69% from 4 to 15 h post-solar-simulated radiation, but recovered to control values by 24 h. Tumor necrosis factor alpha was raised at 4 h after solar-simulated radiation, reached a maximum 8-fold increase at 15 h, then rapidly declined to control values. Interleukin-1alpha and interleukin-1beta were first increased at 15 h, and remained raised to 72 h, although interleukin-1beta declined from its 15 h maximum. Interleukin-10 increased a maximum 2-fold between 15 and 24 h, coincident with recovery of mixed epidermal cell-lymphocyte reaction responses and downregulation of tumor necrosis factor alpha and interleukin-1beta. Solar-simulated radiation differentially affected soluble tumor necrosis factor alpha receptors; soluble tumor necrosis factor-RI was suppressed 33% at 8-15 h whereas soluble tumor necrosis factor-RII increased 2-fold from 15 to 48 h. Interleukin-1 receptor antagonist was raised at all times post-irradiation. Interleukin-12 was not detectable in control or irradiated skin. These kinetics suggest the tumor necrosis factor alpha network has primary importance in ultraviolet-damaged human skin. The small increase in interleukin-10 implies that 3 minimal erythema doses of solar-simulated radiation is the threshold dose for its induction and local, rather than systemic, functions for interleukin-10 in immunosuppression and regulation of other cytokines.

Adolescent↗
PubMed1998

Anti-Fc(episilon)RI auto antibodies and basophil histamine releasability in chronic idiopathic urticaria.

BACKGROUND: Circulating functional autoantibodies to the high-affinity IgE receptor (Fc(epsilon)RI) or to IgE have been found in approximately one third of patients with chronic idiopathic urticaria (CIU). OBJECTIVE: We sought to compare basophil histamine release and basophil numbers in patients with CIU with and without autoantibodies. METHODS: Basophil histamine release to the anti-Fc(epsilon)RI mAb 22E7, anti-IgE, and formyl-methionyl-leucyl-phenylalanine (fMLP); basophil numbers; and total cellular histamine were measured in 26 patients with CIU and 18 healthy control subjects. Twelve patients were classified as having functional anti-Fc(epsilon)RI and/or anti-IgE autoantibodies on the basis of their serum-evoked histamine release from the basophils of 2 healthy donors. RESULTS: 22E7 and anti-IgE, but not fMLP, released less histamine from basophils of patients with CIU than from those of control subjects. Mean+/-SEM maximum histamine release to 22E7 from basophils of control subjects and patients with CIU with and without autoantibodies was 38.5%+/-5.0%, 17.9%+/-6.0% (P =.01), and 1.0%+/-0.3% (P <.0001), respectively. Similar results were obtained with anti-IgE, which is dependent on and cross-links cell bound IgE, and 22E7, which directly cross-links the IgE receptor. The mean+/-SEM basophil counts for control subjects and patients with CIU without and with autoantibodies were 52+/-7, 34+/-9 (P =.04), and 5+/-1 (P <.0001) x 10(6) cells/L, respectively, and similar changes were found in measurements of total cellular histamine. CONCLUSION: Patients with autoantibodies have both markedly reduced basophil numbers and basophil histamine release to factors acting through Fc(epsilon)RI, which indicates either a residual pool of functionally distinct basophils or may be a consequence of desensitization of the Fc(epsilon)RI pathway.

Adult↗
PubMed1998

Intravenous immunoglobulin in autoimmune chronic urticaria.

Histamine releasing autoantibodies play a central role in the pathogenesis of chronic urticaria (CU) in approximately 30% of affected patients. We investigated the therapeutic effect of high-dose intravenous immunoglobulin (IVIG) on disease activity in patients with severe CU of autoimmune aetiology. Autoimmune urticaria was diagnosed by the development of a weal-and-flare reaction to the intradermal injection of autologous serum and by serum-induced histamine release from the basophil leucocytes of healthy donors in vitro. Ten patients with severe, autoimmune CU, poorly responsive to conventional treatment, were treated with IVIG 0.4 g/kg per day for 5 days. The outcome on cutaneous wealing and itch was monitored using urticaria activity scores, visual analogue scales and autologous intradermal serum tests. Clinical benefit was noted in nine of 10 patients: three patients continue in prolonged complete remissions (3 years follow-up), two had temporary complete remissions, and symptoms in four patients improved subsequent to treatment. There was significant improvement in the urticaria activity scores and visual analogue scores at 2 (P < 0.01) and 6 weeks (P < 0.01) post-IVIG compared with the baseline values (Wilcoxon matched pairs). The diminution in urticarial activity in the majority of patients corresponded with a reduced weal-and-flare response to the intradermal injection of autologous post-treatment serum compared with the pretreatment serum. Minor side-effects were common, but there were no serious or long-term adverse effects. IVIG represents a novel therapeutic option in selected patients with recalcitrant CU associated with histamine releasing autoantibodies.

Adult↗
PubMed1998

The intradermal effects of the H3 receptor agonist R alpha methylhistamine in human skin.

We have investigated the possible existence of the H3 histamine receptor in human skin with the highly selective ligands R alpha methylhistamine (RAMHA) (H3 agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H1 antagonist terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare responses that were approximately 10- and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine (P < 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histamine-induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H3 receptors on cutaneous endothelial or mast cells.

Adult↗
PubMed1998

Pemphigus vulgaris in pregnancy with favourable foetal prognosis.

Pemphigus vulgaris is an immunobullous disease affecting the skin and mucous membranes most commonly during the fifth and sixth decades of life. Its occurrence in pregnancy is rare. We now report two severe cases of the disorder presenting during pregnancy and discuss its potential effects on the foetus and its management in pregnancy.

Adult↗
PubMed1998

Not all chronic urticaria is "idiopathic"!

The aetiology of chronic urticaria in the majority of patients is elusive. The cause of physical urticarias (dermographism, delayed pressure urticaria, cold urticaria) is unknown. We have identified a subset of chronic "idiopathic" urticaria patients, representing approximately 30% of the total in which the disease is caused by the presence of IgG autoantibodies against the high affinity IgE receptor (FcepsilonRIalpha). This functional autoantibody stimulates normal (albeit vicarious) activation of mast cells and basophils via FcepsilonRI, causing whealing and angioedema. Anti-FcepsilonRI-positive patients are recognized by a combination of autologous serum skin testing and evoked histamine release from basophils of normal human donors. Autoantibody-positive and -negative patients are clinically indistinguishable and are treated routinely by combinations of H1 and occasionally H2-antihistamines in both cases. However, severely affected patients who are anti-FcepsilonRI-positive can also be treated by non-specific immunotherapy (plasma pheresis, intravenous immunoglobulin, cyclosporin.

Autoantibodies↗
PubMed1997

The impact of chronic urticaria on the quality of life.

The impact of chronic urticaria (CU) on the quality of life is undocumented. We assessed quality of life in patients with CU, including patients with associated delayed pressure urticaria (DPU). One hundred and forty-two out-patients completed self-administered questionnaires: a disease-specific, purpose designed questionnaire, and the Nottingham health profile (NHP). Many patients reported problems attributable to their skin condition in facets of everyday life including home management, personal care, recreation and social interaction, mobility, emotional factors, sleep, rest and work. The NHP part I scores showed restriction in the areas of mobility, sleep, energy, and demonstrated pain, social isolation and altered emotional reactions. Part II of the NHP showed that patients experienced difficulties in relation to work, looking after the home, social life, home relationships, sex life, hobbies and holidays. The patients with DPU had significantly more problems with mobility, gardening and choice of clothing than the uncomplicated CU patients. They also suffered more pain, had more problems with work and were more restricted in their hobbies.

Activities of Daily Living↗