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Biomedical subjects

R A Sabroe

Publications and source records attributed to R A Sabroe.

At least 19 recordsLinked to original sources
PubMed2006

Chronic idiopathic urticaria with functional autoantibodies: 12 years on.

It is now recognized that approximately one-third of patients with chronic idiopathic urticaria (CIU) have histamine-releasing autoantibodies directed against either the high-affinity IgE receptor or, less frequently, against IgE. However, there are several unsolved problems relating to the role of such autoantibodies in the disease. Additionally, it is not clear whether CIU with autoantibodies can be classified as an autoimmune disease. The detection of patients with autoantibodies also poses challenges. Firstly, the only in vivo method, the autologous serum skin test, is at best 80% sensitive and specific using in vitro basophil histamine release assays as the verum. Secondly, in vitro tests are only done in a small number of research laboratories, and are not widely commercially available, and thirdly, there is some divergence between results obtained by different methods (functional and immunoassays) used to detect patients with autoantibodies. The presence of autoantibodies may be important clinically in a small group of severely affected, treatment-resistant patients, where immunomodulatory treatments may be helpful.

Autoantibodies↗
PubMed2002

An audit of the use of self-administered adrenaline syringes in patients with angio-oedema.

BACKGROUND: Self-administered adrenaline syringes may be prescribed for patients at risk of life-threatening episodes of angio-oedema or anaphylaxis. OBJECTIVES: To determine whether patients are able to use these syringes appropriately and adequately. METHODS: Twenty-nine consecutive patients who had been prescribed self-administered adrenaline syringes for severe angio-oedema were recruited. All completed a questionnaire (unsupervised), and were asked to demonstrate how to use a dummy syringe. RESULTS: Three of 29 (10%) patients had been prescribed syringes in the absence of severe angio-oedema or collapse. Seventeen of 29 (59%) patients had been prescribed two syringes, and 21 of 29 (72%) kept a syringe with them at all times. Twenty of 28 (71%) patients had had the use of a syringe demonstrated to them with the initial prescription, but two of 29 (7%) had never been shown how to use it. Only six of 26 (23%) patients had been told to telephone for an ambulance after using a syringe. Only seven of 29 (24%) patients would use a syringe for an episode of collapse, whereas eight of 28 (29%) would use one for an episode of lip swelling. Nine of 21 (43%) patients had not been warned about adverse effects, although 13 of 20 (65%) given adrenaline had had at least one adverse effect. Of the 25 patients asked to demonstrate their use of a syringe, only 14 (56%) were able to perform all steps correctly, and three (12%) were unable to perform any of the steps. Despite this, all 29 patients felt confident about giving themselves an injection, and most felt more secure having been prescribed syringes. CONCLUSIONS: As self-administered adrenaline syringes are prescribed for life-threatening events, it is vital that they are given to appropriate patients with adequate written instructions and proper demonstration at the time of the initial prescription. As a result of this study we have developed a more detailed patient information leaflet, and all patients are shown how to use a syringe for a second time when attending the clinic for follow-up.

Adolescent↗
PubMed2002

Lymphocytic infiltrates as a presenting feature of Sweet's syndrome with myelodysplasia and response to cyclophosphamide.

Sweet's syndrome has a well-recognized association with malignancies, around half of which have been acute myelogenous leukaemia. There are also numerous reports of Sweet's syndrome in association with myelodysplasia. We report two patients with Sweet's syndrome in whom the classical histological appearances were preceded by dermal lymphocytic infiltrates. A literature search using PubMed indicates that this phenomenon has not been previously reported. The cases demonstrate the chronicity of Sweet's lesions in association with haematological disease and the need for repeat biopsies to make the diagnosis. We also describe successful treatment with cyclophosphamide, which adds to the list of second-line drugs that may be used in Sweet's syndrome.

Aged↗
PubMed2002

Twice-daily vs. once-daily inpatient dithranol for psoriasis.

The aim of this study was to compare the efficacy and tolerability of twice-daily vs. once-daily regimes of dithranol (anthralin) in Lassar's paste. Over a 4-year period, 61 inpatients with stable plaque psoriasis gave informed consent and entered a randomized controlled trial, having twice or once-daily application of dithranol in Lassar's paste as part of otherwise standard Ingram's regime. Primary outcome measurements were time required in hospital, nursing time, changes in total body surface area affected by psoriasis and thickness of a target plaque and in some patients, an assessment of the recurrence of psoriasis. Doctors were blinded as to the regime being used. At entry, mean patient age, lesional surface area and target plaque thickness were comparable in both groups and no patient had received systemic therapy in the preceding 3 months. Forty-two patients completed the study, two (11%) in the twice-daily group withdrawing due to skin irritation or 'burning'. Mean lesional surface area and target plaque thickness were similar in both groups at hospital discharge. Mean (+/- SD) time spent in hospital was not significantly different in each group, being 13.3 (+/- 6.2) days and 13.9 (+/- 4.5) days for the twice-daily and once-daily groups, respectively (P = 0.36). Duration of hospitalization did not correlate with surface area or plaque thickness on admission. Mean (+/- SD) nursing time spent on treatment was significantly greater in the twice-daily group, at 0.82 (+/- 0.33) hours per day compared with 0.51(+/- 0.25) hours per day in the once-daily group. Relapse rate at 6 months was not different between the two groups.

Administration, Cutaneous↗
PubMed2000

Rituximab in cutaneous B-cell lymphoma: a report of two cases.

We report two patients with primary cutaneous B-cell lymphoma who were treated with rituximab, a new anti-CD20 monoclonal antibody. The first patient, who had a diffuse large B-cell lymphoma of the lower leg, achieved an 85% improvement. The second patient, who had a primary cutaneous B-cell lymphoma, which had undergone high-grade transformation and systemic spread, achieved a minor response of approximately 30%. Both patients subsequently relapsed. The first patient achieved complete clearance with a second course of rituximab given with systemic chemotherapy, but again relapsed. Treatment with rituximab has been reported to produce response rates of 48% in relapsed systemic low-grade or follicular lymphoma, but there are no previous reports of the use of rituximab in primary cutaneous B-cell lymphoma.

Adult↗
PubMed2000

Schnitzler's syndrome: no evidence for autoimmune basis in two patients.

We report two cases of Schnitzler's syndrome in which anti-interleukin-1alpha autoantibodies and functional autoantibodies against the high affinity IgE receptor (FcepsilonRIalpha) or against IgE were absent. One patient responded well to TL-01 phototherapy, a treatment which may be considered in patients with Schnitzler's syndrome if, as is usually the case, they are unresponsive to antihistamine therapy.

Aged↗
PubMed1999

Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria: comparison of patients with and without anti-FcepsilonRI or anti-IgE autoantibodies.

BACKGROUND: Previous studies defining the histopathologic features of patients with chronic idiopathic urticaria (CIU) were performed on wheals of uncertain duration and before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. OBJECTIVE: We sought to determine the timing of the inflammatory infiltrate in the wheals of patients with CIU and to detect differences between patients with and without autoantibodies. METHODS: Immunohistochemistry was used to identify neutrophils (neutrophil elastase), T lymphocytes (CD3), and activated eosinophils (EG2) in biopsy specimens from uninvolved skin and wheals present for less than 4 hours and greater than 12 hours in 22 patients with CIU, as well as in biopsy specimens from the skin of 12 healthy control subjects. Patients were identified as having functional autoantibodies on the basis of their serum-evoked histamine release in vitro from the basophils of 2 healthy donors. RESULTS: EG2(+), neutrophil elastase+, and, to a lesser extent, CD3(+) cells were found in greater numbers in wheals undergoing biopsy at less than 4 and greater than 12 hours than in uninvolved skin (P <.05). Patients without autoantibodies (n = 12) had significantly more EG2(+) cells in wheals of greater than 12 hours' duration than patients with autoantibodies (n = 10; P =.02). There was no other difference between patients with and without autoantibodies in the cutaneous cellular infiltrate. CONCLUSION: Neutrophil and eosinophil accumulation occurs early in the evolution of a wheal in patients with CIU, but eosinophil activation may occur later or be more persistent in patients without autoantibodies.

Adult↗
PubMed1999

Chronic idiopathic urticaria: comparison of the clinical features of patients with and without anti-FcepsilonRI or anti-IgE autoantibodies.

BACKGROUND: Previous studies defining the clinical features of patients with chronic idiopathic urticaria (CIU) were performed before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. OBJECTIVE: Our purpose was to determine whether there are differences between patients with and those without autoantibodies in the clinical features or severity of CIU. METHODS: The clinical features of 107 patients with CIU were evaluated prospectively. Patients were identified as having functional autoantibodies on the basis of the serum-evoked histamine release in vitro from the basophils of 2 healthy donors. RESULTS: Patients with autoantibodies (31%) had more wheals (P = .005), a wider distribution of wheals (P = .009), higher itch scores for the most severe episodes of itching (P = .002), more systemic symptoms (P = .03), and lower serum IgE levels (P < .0005) than patients without autoantibodies. CONCLUSION: The presence of autoantibodies indicates a subset of patients with more severe CIU.

Adolescent↗
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

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

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

Scombrotoxic fish poisoning.

We report the case of a 30-year-old patient who developed scombrotoxic fish poisoning after eating cooked fresh tuna. Symptoms included a bright red rash, tightness of the chest, palpitations, anxiety, mild headache and dizziness, all of which resolved spontaneously within 2-3 h. Such poisoning results from the consumption of spoiled fish of the families Scomberesocidae or Scombridae - in particular tuna, mackerel, skipjack and bonito - which contain high levels of histidine. Incorrect storage of fish allows bacterial histidine decarboxylase to convert histidine to histamine. The ensuing symptoms are thought to result from the ingestion of histamine. Scombrotoxic fish poisoning is preventable by the correct handling and refrigeration of these fish.

Adult↗
PubMed1997

Angiotensin-converting enzyme (ACE) inhibitors and angio-oedema.

Angiotensin-converting enzyme inhibitors (ACEIs) are used increasingly for the treatment of hypertension and chronic heart failure, and they reduce mortality when given after myocardial infarction. Of the patients prescribed these drugs 0.1-0.7% develop angio-oedema, but the association is not widely recognized. In 60% of cases the onset occurs during the first week of treatment; however, it may be considerably delayed. Angio-oedema nearly always occurs on the head and neck, frequently involving the mouth, tongue, pharynx and larynx. The course is unpredictable, and attacks vary in severity from mild to fatal from laryngeal obstruction. Severe ACEI-induced angio-oedema may require emergency treatment with adrenalin and early intubation. The drug should be withdrawn in any patient who presents with ACEI-induced angio-oedema, and treatment continued with an appropriate drug of a different class. Therapy with ACEIs is contraindicated in patients with a prior history of idiopathic angio-oedema, or in patients with hereditary or acquired C1 esterase inhibitor deficiency.

Angioedema↗
PubMed1997

The pathogenesis of chronic idiopathic urticaria.

Chronic idiopathic urticaria (CIU) can be extremely disabling and difficult to treat, with little response to antihistamine therapy. The pathogenic mechanisms of the disease are not well understood, but the primary effector cell is the mast cell. Release of mast cell mediators can cause inflammation and accumulation and activation of other cells, including eosinophils, neutrophils, and possibly basophils. Recent work has demonstrated that about one third of patients with CIU have circulating functional histamine-releasing autoantibodies that bind to the high-affinity IgE receptor (Fc epsilon RI) or, less commonly, to IgE; mast cell-specific histamine-releasing activity that has not yet been fully characterized; no identifiable circulating histamine-releasing activity. The mainstay of treatment of CIU consists of antithistamines, but immunotherapy using plasmapheresis, intravenous immunoglobulin, and cyclosporin may be valuable in severely affected patients with treatment-resistant disease. The response to immunomodulation and the recent finding of an association with HLA DR4 lend further support for an autoimmune basis to CIU in some patients.

Basophils↗
PubMed1997

The effects of topical doxepin on responses to histamine, substance P and prostaglandin E2 in human skin.

The tricyclic antidepressant, doxepin, is known to have H1 and H2 antihistaminic effects. Recently, 5% doxepin cream has been marketed in the U.S.A. for treatment of eczematous dermatoses. We investigated the effects of topical doxepin treatment on histamine-, substance P- and prostaglandin E2- (PGE2) induced responses in the skin of normal and atopic subjects. We compared the effects of topical doxepin with those of the oral antihistamine terfenadine. The weal volume and flare area responses to histamine were significantly reduced by treatment with topical doxepin or oral terfenadine in both normal and atopic subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 10 micrograms/site of histamine in non-atopics and atopics was 48 +/- 8% and 60 +/- 17% with terfenadine, and 54 +/- 12% and 81 +/- 4% with topical doxepin, respectively. The mean percentage reduction in weal volume for the same dose of histamine in non-atopics and atopics was 70 +/- 9% and 63 +/- 16% with terfenadine, and 96 +/- 2% and 89 +/- 6% with topical doxepin, respectively. The flare but not the weal response to substance P was inhibited by both treatments in all subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 200 pmol/site of substance P in non-atopics and atopics was 53 +/- 10% and 73 +/- 4% with terfenadine, and 74 +/- 7% and 75 +/- 4% with topical doxepin, respectively. The cutaneous responses to PGE2 were not affected by either drug. The inhibitory effects of doxepin were as great as those of terfenadine, and doxepin had a significantly greater effect than terfenadine in inhibiting the weal response to histamine and flare response to substance P in normal volunteers (P < 0.05). There was no significant difference between atopics and non-atopics in the percentage reduction of cutaneous responses by oral terfenadine or topical doxepin. Marked sedation occurred in three of the first 10 subjects treated with topical doxepin, necessitating a reduction in dosage for the remaining six subjects. In summary, topical doxepin was as effective as, and sometimes more effective than, a standard dose of oral terfenadine in the inhibition of histamine-induced and axon-reflex-mediated cutaneous responses. The marked sedative effect may limit its clinical use in some patients.

Administration, Topical↗