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Notizen: We report a patient who developed hypercalcaemic metastatic cutaneous calcification in association with a cytomegalovirus infection after a liver transplant. The skin nodules disappeared as the hypercalcaemia resolved and the cytomegalovirus infection subsided.

Notizen: Sixteen patients with chronic idiopathic urticaria were skin tested with their own serum, 10 with autologous plasma and five with serum that had been heated to 56° C to inactivate complement. Eight showed a weal and flare response to whole serum, four to plasma and five to heat-treated serum. All serum-positive patients showed the same response to their own plasma and to heated serum, indicating that the mediator concerned is not generated by clotting and is not dependent on a functioning complement pathway. Three control subjects were negative to autologous serum, plasma and heated serum. Local tachyphylaxis was demonstrated in five serum-positive patients on reinjection of the same site with autologous serum on 3 consecutive days. This raises the possibility that the serological mediator may be acting by mast cell degranulation or directly on receptors in blood vessels and that repeated injections could induce a change in the number of receptors. Passage of whole autologous serum from four serum-positive patients through ultrafiltration membranes showed that fractions with a molecular weight of less than 30,000 daltons were still able to produce a positive skin test response, but those less than 1000 daltons were not. All serum fractions from two serum-negative patients and three normal controls were negative. Whole autologous serum from five serum-positive patients and two control subjects was separated by column chromatography. On skin testing with pooled fractions, the greatest response was produced by fractions of 10,000–15,000 daltons in the serum-positive patients, but there was no response in the controls.

Notizen: The concentration of essential fatty acids (EFAs) and their metabolites in plasma phospholipids were measured by gas chromatography in normal individuals, and in patients with ichthyosis vulgaris, acne vulgaris or psoriasis. In all three patient groups, concentrations of arachidonic acid (20: 4ω6) and docosapentaenoic acid (22: 4ω6) were significantly below those in controls, suggesting that these abnormalities may occur in many skin diseases. Concentrations of dihomogammalinolenic acid (20: 3ω6) were low in ichthyosis, normal in acne and elevated in psoriasis. Thus ichthyosis, acne and psoriasis each had a characteristic pattern of EFA metabolites.

Notizen: Background:  Endogenous histamine-releasing factors (HRFs) are involved in 30–60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against the immunoglobulin E (IgE) or the high affinity IgE receptor (FcɛRI) and serum-induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine-releasing assay (the HR-Urtikaria test) in a group of well-characterized CU patients and subsequently determined the frequency of HR-Urticaria-positive sera from a larger population of CU patients.Subjects:  Group 1 consisted of 28 patients with CU (16 were ASST-positive) 20 patients with atopic dermatitis, 24 patients with allergy to birch and nine healthy controls. Group 2 consisted of 873 unselected CU patients.Methods:  White blood cells containing 1–2% basophils from a healthy nonatopic donor were incubated with patients sera in the presence of interleukin (IL)-3. Histamine was measured by the glass fibre method.Results:  Using the ASST as the true outcome, the HR-Urticaria test showed a sensitivity and specificity of 75% in group 1 using a cut-off value for HR of 〉16.5%. None of the controls was positive in the HR-Urticaria test. In group 2, we found no difference in the frequency of positives between male (34.6%, n = 254) and female adults (35.1%, n = 576) but twice as many females as males were tested.Conclusions:  Our studies have shown that the HR-Urticaria test has a good sensitivity and specificity for endogenous HRFs demonstrated by the ASST in patients with CU and that about one-third of unselected patients with CU have a positive result.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.