Porzia Dambra

Reactivity to autologous serum skintest and clinical features in chronic idiopathic urticaria

Summary The autologous‐serum skin test (ASST) can cause a wheal‐and‐flare response in some cases of chronic idiopathic urticaria. We subjected 102 patients affected by chronic idiopathic urticaria to this test and studied some clinical parameters to detect any significant differences between ASST‐positive and ASST‐negative patients. The only significant difference we noted between the two groups was the incidence of angioedema (P = 0.01). We suggest that the ASST cannot be used alone either to predict the severity of urticaria or to define it as ‘autoimmune’.

Patients with Hereditary Hemorrhagic Telangectasia (HHT) Exhibit a Deficit of Polymorphonuclear Cell and Monocyte Oxidative Burst and Phagocytosis: A Possible Correlation with Altered Adaptive Immune Responsiveness in HHT

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare genetic disease characterized by mutations occurring in the endoglin and ALK-1, two receptors of transforming growth factor-beta1. From a pathogenic point of view, a possible involvement of the immune system in HHT has been suggested since a mononuclear cell infiltrate was found around the area of telangiectases. Up until now, no information has been available about the role played by leukocytes in HHT and the mechanisms elicited by secretion of their mediators. However, the fact that a deficit of adaptive immunity in HHT has been reported in a companion paper in this issue will represent a great contribution to the understanding of HHT pathogenesis. The purpose of this study was to evaluate whether patients with HHT manifest also alterations in the innate immune response. Therefore, the phenotype of T, B and natural killer lymphocytes, serum immunoglobulin levels, phagocytosis and oxidative burst activity exerted by polymorphonuclear cells (PMN) and monocytes (MO) were analyzed in 22 patients. Twenty individuals demonstrated single or multiple deficits of PMN and MO functions, while the immunophenotype of lymphocytes and serum concentrations of immunoglobulins were normal. To the best of our knowledge, this is the first demonstration of a reduction in PMN and MO functions in HHT, thus suggesting a higher susceptibility to infectious complications in these patients. The relationship between innate immune deficits and T helper 1 and monocyte-derived cytokine dysfunction in HHT, as previously reported, is discussed.

CYCLOSPORIN A IN PATIENTS AFFECTED BY CHRONIC IDIOPATHIC URTICARIA: A THERAPEUTIC ALTERNATIVE

Chronic Idiopathic Urticaria (CIU) is a cutaneous disorder for which there is no identifiable specific etiologic agent. Some recent evidences suggest that CIU might be an autoimmune disease. We analyzed immunological features occurring in CIU and evaluated effectiveness and tolerance of Cyclosporin A (CsA) treatment in patients unresponsive to antihistaminic treatment. Twenty patients with CIU were recruited after a selective diagnostic protocol and were divided into two groups. CsA was prescribed for group 1 and Prednisone for group 2 as control, for 8 weeks. Before and after the therapy we performed on all patients immunological studies. For all patients symptoms disappeared after a few days of therapy. Before therapy all patients showed activated B cells (CD19+CD23+ cells) and among B CD19+ cells, about 20% were CD5+ (cells that synthesize natural autoantibodies). After treatment with Prednisone in group 2, a significant reduction of CD4+ lymphocytes (p + 0,01) was observed. Our findings might support the CIU autoimmune pathogenetic hypothesis. The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and, at dosage used, side effects were rare, mild and reversible. Thus, CsA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments.

Latex hypersensitivity: relationship with positive prick test and patch test responses among hairdressers

Background: Natural rubber latex is a frequent cause of IgE‐mediated allergy in hairdressers; but a non‐IgE‐mediated allergy to latex proteins can also occur. Sixty‐one hairdressers, reporting latex glove‐related symptoms, were enrolled in the study.

Effect of Low-Density Lipoprotein Apheresis on Circulating Endothelial Progenitor Cells in Familial Hypercholesterolemia

Background: Long-term treatment with low-density lipoprotein (LDL) apheresis (LA) has been shown to reduce the incidence of cardiovascular events in patients affected by familial hypercholesterolemia (FH). Data from experimental studies suggest that circulating endothelial progenitor cells (EPCs) can repair the vascular lesions caused by atherosclerosis. Since a reduction of these cells has been demonstrated to predict atherosclerosis progression, the aim of this study was to verify whether LA can increase the percentage of EPCs. Methods: In 15 patients affected by FH periodically treated with LA, the percentage of EPCs was determined before and after performing LA, and compared with the values of 15 control subjects and 15 hypercholesterolemic patients treated with statins. Results: Significant differences were found in FH patients between the pre-apheresis percentages of CD34+/KDR+, defined as EPCs by a wide consensus of opinion, and the values found 24 h after the procedures (0.00868 ± 0.003 vs. 0.01009 ± 0.002%, p < 0.005). Instead, the percentages of CD34+/KDR+/CD133+, considered as an immature subset of EPCs, remained substantially unchanged. However, a significant reduction in the percentage of EPCs was observed in both patient groups as compared to the controls, at all the assessment times. Conclusion: In the short-term LA seems to stimulate mobilization of CD34+/KDR+ cells. Hypercholesterolemic patients show a lower percentage of EPCs than controls. There were no differences in the EPCs percentages between the 2 patients groups, despite the fact that LDL cholesterol levels were higher in the group undergoing LA.

Mast-cell phenotype in urticaria†

. CHRONIC idiopathic urticaria (CIU), a reactive skin and mucosa syndrome of unknown cause, is characterized by the persistence of lesions for more than 6 weeks (1).Mast cells (MC) play an important role in the determination of urticaria, as confirmed by many studies (2). There are two distinct MC subpopulations (3): tryptasepositive, chymase-negative (tMC), and tryptase-positive, chymase-positive (tcMC). Their differentiation occurs as a result of microenvironmental influences. Ten CIU patients aged 19–52 years (six women and four men) underwent punchbiopsy of the lesioned skin (LS). The control samples consisted of biopsies of the healthy skin (HS) of the patients and of 10 healthy subjects (HP: two men and eight women; age range, 20–58 years). The patients discontinued antihistamines 48 h before the biopsy. Tissue sections of 4 mm were immunohistochemically stained with antichymase and antitryptase monoclonal antibodies (Chemicon, USA). Individual stainingswere carriedout to identify chymase or tryptase alone, as well as serial stainings of the same tissue sections with both monoclonal antibodies. Hematoxylin-eosin staining was used to evaluate the inflammatory infiltrate, and toluidine blue to measure the total number of MCs. Total MC were counted under light microscopy at 3100. The percentages of tcMC and tMC were also calculated. The data were compared and analyzed by the Wilcoxon test for independent and paired samples. When we compared the biopsies of LS of patients with CIU and biopsies of healthy subjects, the differences between the mean values of total MC/mm (LS: 126.74u28.7; HP: 90.33u7.39; P=0.0004) and tMC/mm (LS: 30.33u8.54; HP: 4.9u1.05; P=0.0001) were statistically significant, but not those between the values of tcMC/mm (LS: 96.31u20.52; HP: 85.32u7.36; P=0.06). The differences between the mean values of total MC/mm and tMC/mm in comparing the LS and HS biopsies (total MC/mm: 89.74u7.19; tMC/mm: 5.4u1.08) were also statistically significant (P=0.003 and P=0.002, respectively), but not those between HP and HS. The inflammatory infiltrate contained lymphomonocytic elements, granulocytes, neutrophils, and eosinophils in varying amounts and was compatible with that of a late-phase cutaneous reaction. Although the pathogenesis of urticaria is still unknown, the present study shows that the lesioned skin of IU patients contains an increased number of total MC (particularly tMC) in comparison with the lesion-free skin of thesamepatientsandhealthycontrols.The recent observations indicating that MCs can produce a considerable number of cytokines suggest that the activationofMCmay initiate and sustain thedevelopment of the late-phase allergic reaction that we observed, and could influence the chronic inflammatory response. Furthermore, some authors have shown that cytokine products, like proteases, are different in two MC subsets: tcMCs mainly produce IL-4 and in a greater amount than tMCs, whereas only the latter produce IL-5 and IL-6 (4).Our finding that the skin ofCIU patients has increased tMC levels leads us to suppose that an increase in the IL-5 and IL-6 proinflammatory cytokines would explain the recruitment andactivationof eosinophils, basophils, and T cells and the maintenance of phlogosis. We think that an underlying factor in CIU is thealteration inMChomeostasis leading to an imbalance in the normal mechanisms of MC inhibition and activation. The difference between our findings and those of Smith et al. (5) could be due to the differences in our patient selection criteria. In conclusion, on the basis of our own and others’ results, the fundamental role ofMCin the pathogenesis of CIU has been clearly demonstrated. Further in-depth studies of skin MC and their subpopulations should provide insights into the possibility of using drugs directed against MC subtypes and mediators.

Endothelial progenitor cells in sudden sensorineural hearing loss.

Abstract Conclusions: Endothelial progenitor cells (EPCs) are a unique subtype of circulating cells with properties similar to those of embryonal angioblasts. They have the potential to proliferate and to differentiate into mature endothelial cells. EPCs are reduced in patients with vascular risk factors due to a decreased mobilization, an increased consumption at the site of damage or a reduced half-life. The results of this study confirm the existence of an endothelial dysfunction in patients with sudden sensorineural hearing loss (SSHL) and support the vascular involvement in the pathogenesis of the disease. Objective: The aim of this study was to evaluate the concentration of EPCs in patients affected by SSHL. Methods: Twenty-one patients affected by SSHL were evaluated. The number of EPCs was analyzed by flow cytometry analysis of peripheral blood CD34+KDR+CD133+ cells. Results: Circulating levels of EPCs were significantly lower in SSHL patients compared with controls. In particular, CD34+KDR+ cells and CD34+CD133+KDR+ cells were significantly reduced (p < 0.05).

Type I allergy to natural rubber latex and Type IV allergy to rubber chemicals in children with risk factors.

Keywords: natural rubber latex; allergic contact dermatitis; rubber chemicals; Type I hypersensitivity; Type IV hypersensitivity; thiuram mix; tetramethylthiuram monosulfide; carba mix; 1,3-diphenylguanidine; hexamethylenetetramine

Effects of Oral Bacterial Immunotherapy in Children with Atopic Eczema/Dermatitis Syndrome

BackgroundAtopic eczema/dermatitis syndrome (AEDS) is a chronic inflammatory skin disease, affecting 10–20% of children and 1–3% of adults. The purpose of this pilot study was to assess the clinical and anti-inflammatory effect of bacterial and ribosomal immunotherapy with Immucytal® (Pierre Fabre Médicament, France) in children with AEDS.MethodsSeventeen children with allergic and non-allergic forms of AEDS (AAEDS and NAAEDS, respectively), graded moderate to severe (Severity Scoring of Atopic Dermatitis [SCORAD] index of >25), received ribosomal immunotherapy (Immucytal®) once daily according to the standard treatment regimen (4 consecutive days a week for 3 weeks, and then 4 consecutive days a month for 4 months). We assessed the clinical status of AEDS using the SCORAD index at baseline, and after 8 and 20 weeks of treatment. Furthermore, peripheral blood from patients was examined for the frequencies of CD4+ cells expressing interferon (IFN)-ψ and interleukin (IL)-4 using flow cytometry.ResultsThere was a progressive and significant clinical improvement of AEDS, confirmed by a reduction of the SCORAD index over time in both AEDS forms (p < 0.01). Pooled data from the two groups showed that the mean baseline index of 43 was reduced to 17 after treatment. Overall, these data indicate a marked improvement in total clinical severity of AEDS (−62%). Flow cytometry analysis showed that frequencies of the two CD4+ T cell subsets did not differ significantly from the beginning to the end of the study in both forms of AEDS. However, the percentage of CD4+ cells expressing IL-4 in children with AAEDS tended to decrease by the end of treatment with ribosomal immunotherapy. Clinical and laboratory data confirmed that immunotherapy was well tolerated.ConclusionsThe results of this pilot investigation suggest that ribosomal immunotherapy may be beneficial in the management of AEDS in children, and that this could be at least partially explained by a role in restoring the type 2 helper-T cell imbalance seen in allergic patients. Placebo-controlled, randomized clinical trials are recommended in order to confirm these findings.

Adhesion molecules in gonarthrosis and knee prosthesis aseptic loosening follow-up: possible therapeutic implications.

The involvement of the synovium is common in phlogistic processes of various joint diseases. A part from synoviocytes and the other cells in the synovial tissue, circulating cells recruited from peripheral blood also participate in the phlogistic process. The increased expression of adhesion molecules on both circulating and endothelial cell surface may further this recruitment. We studied 15 patients affected by serious gonarthrosis requiring a prosthetic implant (GPI) and 7 with knee prosthesis aseptic loosening (KPL) to evaluate adhesion molecule expression and phlogistic infiltration in the synovium using immunohistochemistry and microscopic analysis. As control we studied 10 subjects affected by degenerative meniscopathies undergoing a selective arthroscopic surgical meniscectomy. Analysis with Kruskal-Wallis test showed no statistical significant differences in the expression of CD54, CD11a, CD11b and CD18 in three groups examined. The model of variance analysis (Friedman test), showed that CD54 expression is greater in patients with GPI and KPL in comparison with the other molecules. Adhesion molecules and their functions are important in arthropathies not only because their evaluation can allow us to identify the degree of inflammation and to predict its evolution, but also because pharmacological control of their expression could have important therapeutic implications.