Search

Summary Background Chronic urticaria (CU) is an autoimmune process in some patients. An association between CU and autoimmune thyroid disease has also previously been proposed. Our group has identified functionally significant histamine-releasing autoantibodies in one subset of CU patients (subset 1), predicted by positive autologous intradermal serum tests and positive histamine release from donor basophil leucocytes in vitro. Sera from a second subset of patients (subset 2), all of whom had positive autologous intradermal serum tests, failed to release histamine from donor basophils. A final disease subset (subset 3) has no identifiable skin reactivity (negative autologous serum skin test) or in vitro histamine releasing activity. Objectives In order to examine further the possible relationships between thyroid autoimmunity, thyroid dysfunction and CU, we have examined thyroid autoantibodies and thyroid-stimulating hormone (TSH) levels (an indirect measure of thyroid dysfunction) in the three CU subsets. Patients/methods We studied 182 patients (69% female), of whom 90 had a positive autologous intradermal serum test. Results Eighteen skin test-positive and four skin test-negative patients had thyroid microsomal antibodies (TMA). TSH outside the normal range was found in 13 skin test-positive and one skin test-negative patient. These findings represent clustering of TMA positivity [risk ratio (RR) 4·06, 95% confidence interval (CI) 1·56–10·6] and of abnormal thyroid function (RR 15·5, CI 2·07–11·6) among the skin test-positive patients. However, in the overall study group an elevated TSH was present in seven patients (3·8%, CI 1·6–7·8) comparable to the 5% expected prevalence in the community. Thyroglobulin antibodies (TGA) were present in two of 182 patients. Conclusions There were significant differences between skin test-positive and skin test-negative patients with regard to autoimmune thyroid disease. Evidence for autoimmune thyroid disease and abnormal thyroid function was largely found among the skin test-positive patients, supporting the theory of an autoimmune aetiology in this group.

SummaryBackground 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.

Chronic idiopathic urticaria (CIU) may be severe and refractory to standard therapies. We describe two patients with CIU, neither of whom had detectable autoantibodies, in whom control of the disease was achieved with methotrexate.

Background Vulval carcinoma is a relatively rare disorder that may have various aetiologies. Objectives To document the features and outcome in a series of patients with this disorder. Methods Retrospective analysis of patients presenting to a vulval clinic over a 5-year period. Results Twenty-one women presented with a squamous cell carcinoma (SCC) and two with a verrucous carcinoma (VC). The age range was 43–83 years. Twenty-one had well-established (1–30 years) vulval symptoms prior to developing their tumour. Specific tumour-related symptoms ranged from 3 weeks to 11 months. Eight had had a prior diagnosis of lichen sclerosus (LS) or lichen planus (LP), only two of whom were on regular treatment and follow-up. At presentation, 12 patients had clinical signs of LS, three of LP, and five had some changes of both LS and LP. Two patients had multifocal vulval intraepithelial neoplasia (VIN3). Only one had no evidence of any background vulval skin disease. The commonest histological changes noted in the epithelium either adjacent to or distant from the SCC were those of atrophic LS (n = 8), LS with squamous cell hyperplasia (n = 3), LS with hyperplastic foci and lichenoid infiltrate (n = 4), and LS with differentiated VIN3 (n = 1). Four cases demonstrated the changes of LP, and three showed VIN3. All patients were treated surgically and, in those who had lymphadenectomy, four had positive nodes. There have been two deaths due to metastatic disease, and one further patient has developed a second primary SCC at a different site. Conclusions An underlying skin disorder prior to the development of their carcinoma was found in 22 of 23 patients with vulval SCC and is therefore an important risk factor.

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.

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.

Summary An otherwise healthy 19-year-old pregnant woman developed crusted scabies. She and her husband had previously been treated for scabies. In spite of appropriate treatment both suffered several relapses, and later their infant was also affected. Ultimately, the infection was eradicated. As far as we are aware, this is the first recorded case of crusted scabies occurring in a healthy pregnant woman.

Summary We have investigated the kinetics of the leucocyte infiltrate in delayed pressure urticaria (DPU) in relation to the in vivo expression of the cytokine-regulated cell surface adhesion molecules. E-selectin (endothelial adhesion molecule-1. ELAM-1). intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1). Immunohistochemical analysis was performed on biopsies taken from unchallenged skin, and at 0, 2, 6, 24, 48 and 120 h after weighted rods had been applied to 13 patients with DPU. There was moderate to marked upregulation of E-selectin at 6 and 24 h after application of pressure. At 24 h, more patients showed expression of VCAM-1 on perivascular cells than before pressure. Moderate expression of ICAM-1 was present in some biopsies from both unchallenged and pressure-challenged skin, but there was no clear trend. In DPU, there was a significant increase in the neutrophil count at 2 h after a pressure challenge, with further increases at 6 and 24 h. The median cell counts per high-power field of eosinophils and monocyte/ macrophages increased significantly at 24 h after pressure. Biopsies from four normal controls subjected to an identical pressure challenge showed no detectable changes in adhesion molecule expression or in the cell infiltrate. The findings in four patients with chronic idiopathic urticaria not associated with DPU were qualitatively similar to (but intermediate in severity between) the findings in DPU weals at 6 and 24 h. These results suggest that vascular endothelial activation is an early response to pressure challenge in DPU, and is also present in chronic idiopathic urticaria. The inflammatory infiltrate in DPU differs in intensity, but not in composition, from that in chronic idiopathic urticaria.

Interleukin 1 (IL-1) and interleukin 6 (IL-6) were measured by bioassays in suction-blister exudates from lesional skin, from skin immediately following a pressure challenge, and from control skin (not subjected to pressure) of patients with delayed pressure urticaria. IL-6 activity in lesional exudates was significantly higher than in exudates from the other two sites. IL-1 activity in lesional exudates was not significantly higher than in the control exudates, but significantly less IL-1 activity was found immediately after pressure challenge than from the control site.

This report is based on a 2-day meeting held in Cambridge in January 1990. It picks out some of the recent advances since a previous meeging in 1984.1

SUMMARY The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material. Interleukin 2 and tumour necrosis factor activity, and γ interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides.

Adult Still's disease (ASD) is a rare disorder of unknown aetiology, characterized by an evanescent, erythematous, maculopapular rash, fever, arthralgia, and a variety of systemic features. We report a case which illustrates the typical features of ASD, and manifests the hitherto unreported complication of diffuse cutaneous mucinosis.

SUMMARY We studied blood histamine activity (HA) and cutaneous fibrinolytic activity (CFA) in a patient with polycythaemia rubra vera (PRV) and water-induced pruritus, before and after water exposure. The results suggest that the water-induced itching in PRV is associated with an increase in HA. In addition, markedly increased levels of CFA were found both before and after water exposure. These findings have been previously reported in patients with aquagenic pruritus (AP) but not in patients with PRV. As the water-induced itching in PRV and AP share many common features, these findings suggest that the pathophysiology of the water-induced pruritus in these two conditions may be similar.

SUMMARY Two patients with urticaria evoked at the site of contact of skin with water have been studied. Protection of the skin from contact with water by prior application of petrolatum ointment prevented wealing, but removal of the stratum corneum enhanced wealing. Organic solvents did not themselves evoke wealing, but they enhanced the reaction to subsequent challenge by water. That the release of acetylcholine is an essential step in the pharmacogenesis of wealing in aquagenic urticaria is indicated by the suppressive effect of locally-applied scopolamine on water–evoked wealing. Aquagenic urticaria is also associated with elevated blood histamine levels and degranulation of mast cells in the water–challenged skin. The relationship of acetylcholine and histamine to each other and to contact of water with the skin remains uncertain.

Three patients are described who developed angio-oedema and urticaria after a hot bath challenge and physical exercise. In one patient this was accompanied by a fall in peak expiratory flow rate. Blood levels of smooth muscle biological activity, measured using a bio-assay, increased in all patients after experimental challenge. The association of angio-oedema with cholinergic urticaria is emphasized and possible mechanisms discussed.

The efficacy of oral beta-carotene for the prevention of photosensitivity symptoms in erythropoietic protoporphyria was studied in a controlled cross-over trial in which it was compared with a placebo. No significant difference was found between the 2 preparations. Patients' symptoms showed statistically significant association with sunlight hour records.

A randomized double-blind placebo controlled trial of colchicine in the treatment of 13 patients with delayed pressure urticaria enabled us to assess some of the variables in this disorder. We have modified a previously described method of pressure testing using a calibrated dermographometer and shown a pressure induced papular dose response curve. Assessment of disease activity was based on the number of pressure weals which occurred, the size of delayed pressure induced papules using a dermographometer calibrated at 9.75 x 10(5) pascals for five separate time periods on the back and estimations of erythrocyte sedimentation rate and the acute phase protein levels. We have been unable to show a therapeutic effect using colchicine 0.5 mg bd for I week.