Salvatore Saitta

Vulvo-vaginal atrophy: A new treatment modality using thermo-ablative fractional CO2 laser

OBJECTIVE To evaluate the efficacy and feasibility of thermo-ablative fractional CO2 laser for the treatment of symptoms related to vulvo-vaginal atrophy (VVA) in post-menopausal women. METHODS From April 2013 to December 2013, post-menopausal patients who complained of one or more VVA-related symptoms and who underwent vaginal treatment with fractional CO2 laser were enrolled in the study. At baseline (T0) and 30 days post-treatment (T1), vaginal status of the women was evaluated using the Vaginal Health Index (VHI), and subjective intensity of VVA symptoms was evaluated using a visual analog scale (VAS). At T1, treatment satisfaction was evaluated using a 5-point Likert scale. RESULTS During the study period, a total of 48 patients were enrolled. Data indicated a significant improvement in VVA symptoms (vaginal dryness, burning, itching and dyspareunia) (P<0.0001) in patients who had undergone 3 sessions of vaginal fractional CO2 laser treatment. Moreover, VHI scores were significantly higher at T1 (P<0.0001). Overall, 91.7% of patients were satisfied or very satisfied with the procedure and experienced considerable improvement in quality of life (QoL). No adverse events due to fractional CO2 laser treatment occurred. CONCLUSION Thermo-ablative fractional CO2 laser could be a safe, effective and feasible option for the treatment of VVA symptoms in post-menopausal women.

Increased serum levels of IL-22 in patients with nickel contact dermatitis

Nickel can elicit both Th1-type andTh2-type responses in vitro (1) inpatients with nickel allergic contactdermatitis,butthiscomplexcytokinecascade has still to be clarified. Therecently discovered Th17 subset,which has crucial functions in hostdefence against infections and hasbeen implicated in the developmentofautoimmunediseases(2),hasbeensupposed to play an important rolein some inflammatory and autoim-mune skin disorders, such as contacthypersensitivity(3)andpsoriasis(4),respectively. Th17 cells are charac-terized by expression of interleukin(IL)-6, tumour necrosis factor-a,granulocyte–macrophage colony-stimulating factor, IL-17A, IL-17F,IL-21, IL-22, and IL-26 (5).Among these cytokines, IL-22,a member of the IL-10 cytokine fam-ily, described as having proinflam-matory activities on liver, pancreas,intestine, and skin (reviewed in 6),has been demonstrated to have a cru-cial function in the development ofdermal inflammation and epidermalacanthosis induced by IL-23 in mice(4). Moreover, IL-22 seems to beinvolved in the pathogenesis of psori-asis in humans, as demonstrated bythehighserumlevelsshowedbypsori-atic patients and the high levels pro-duced by T cells isolated by psoriaticskin (6), where the IL-22 receptor isexpressed on a variety of epithelialtissues(4).However,nodataareavail-ableon thepossibleroleplayed byIL-22in nickel contacthypersensitivityinhumans, thus we measured the circu-latinglevelsofthiscytokineinpatientswith allergic nickel contact dermatitis.We enrolled 31 female patientsaffected by allergic contact dermatitisto nickel (mean age 31.9 years; range17–64 years) diagnosed followingpatch testing in accordance withthe International Contact DermatitisResearch Group guidelines. Bloodsamples were collected after patchtesting during a period of clinicalremission 1 month after nickel con-tact avoidance.15 sex- and age-matched blooddonors, with no contact dermatitisand negative patch tests, were re-cruited as controls. Each subject gavepreviously used written, informedconsent to the study.Serum IL-22 was measured usingan enzyme-linked immunosorbentassay kit (R&D System Europe,Abingdon, UK). All samples wereanalysed in duplicate.Differences in IL-22 blood levelswere assessed by the Student’s t-testfor unpaired comparison, assumingunequal variances. Data were ex-pressed as mean standard devia-tion. A P value <0.05 was consideredto be significant.IL-22 serum levels were signifi-cantly higher in patients affected bycontact dermatitis compared withcontrols (17.10 9.50 pg/ml versus8.61 7.25 pg/ml, P ¼ 0.002)(Fig. 1). No correlation between IL-22 levels and age was found.About 10 years ago, it was demon-stratedthatnickel-specificCD4Tcellsexpressing the cutaneous lymphocyte-associated antigen skin-homingrecep-tor can synthesize and release IL-17and that IL-17 modulates variousproinflammatory functions of kerati-nocytes, especially when actingtogether with interferon-g and IL-4(7). Zheng et al. have recently demon-strated that the injection of IL-23(a Th17-inducing cytokine) into miceears induces a model of psoriasis-likelesions characterized by epidermalacanthosis with inflammatory cellularinfiltration mediated by IL-17 andIL-22. These features decrease inIL-22-deficient mice (4), and theadministration of IL-22 neutralizingautoantibodies reduces acanthosis,inflammatory infiltrates, and expres-sion of Th17 cytokines (8). However,thehistologicalfeaturesfoundinthesemurine models are not exclusivelycharacteristic of psoriasis but of aller-gic contact dermatitis as well.*Theseauthorscontributedequallytothis work.

Occupational asthma due to exposure to iroko wood dust

BACKGROUND Occupational asthma (OA) from iroko wood has been reported primarily in case reports. OBJECTIVE To improve understanding of the pathogenesis of OA induced by iroko wood dust. METHODS Three groups of woodworkers were included in this study: 9 workers who had clinically proven OA from iroko; 10 asymptomatic woodworkers; and 10 woodworkers with asthma. All patients underwent the following tests: a skin test with an iroko aqueous extract, specific IgE determination, and an iroko bronchial provocation test (IBPT). An eosinophil count was determined before and after the IBPT, and a methacholine inhalation test was performed after avoidance of exposure to iroko. Patients were asked to monitor their peak expiratory flow rates during a week at work followed by a weeks vacation. RESULTS In all patients with a personal history predictive of OA from iroko, a reduction of the peak expiratory flow rate and positivity to the IBPT while working with iroko were present. The latter test result showed a dual response, with a decrease in forced expiratory volume in 1 second from 25% to 32% at 10 minutes and a further decrease from 35% to 43% at 8 hours; at 24 hours, the eosinophil count was higher (P = .046). In 4 patients, the intradermal test results with iroko extract were positive, whereas the skin prick test result and the specific IgE determination were negative in all patients. The methacholine test result was also positive. In the control groups, all the test results with iroko extract were negative. CONCLUSIONS Our data suggest that OA due to iroko wood may be induced by immunologic mechanisms other than IgE-mediated immediate hypersensitivity reactions.

Reduced IL-33 plasma levels in multiple myeloma patients are associated with more advanced stage of disease.

Multiple myeloma (MM) is a clonal neoplasm of the bone marrow-resident long lived plasma cells. Like normal plasma cells, MM cells depend on their interactions with bone marrow stromal cells for the survival and production of essential cytokines (Minges Wols et al, 2002). Interleukin-33 (IL-33) is an IL-1 family member that is constitutively expressed by endothelial and epithelial cells (Joshi et al, 2010) and which appears to drive T helper cell type 2 (Th2) responses in several organs (Cevikbas & Steinhoff, 2012). This study analysed the plasma levels of IL33 in 44 MM patients (19 males, 25 females; mean age 66 9 years) and in 13 patients with monoclonal gammopathy of undetermined significance (MGUS; five males, eight females; mean age 63 12 years). No patients had received any treatment for MM during the previous seven days. The study was conducted according to the principles of the Declaration of Helsinki. Informed written consent was obtained. Plasma from 63 sex-matched and age matched normal subjects (35 males, 28 females; mean age 64 11 years) were also included as controls. None of the patients or control subjects had symptoms or laboratory signs of active infections, inflammatory diseases, diabetes, obesity, neurological diseases or severe uraemia. According to the Durie–Salmon staging system, 13 patients were MM disease stage I, 13 patients were stage II, and 18 patients were disease stage III. The paraprotein class was immunoglobulin G (IgG) in 24 patients and IgA in 18 patients; two patient had non-secretory disease. 26 subjects had lytic bone disease and/or pathological fractures. Thirty patients presented an Eastern Cooperative Oncology Group (ECOG) performance status <2 while 14 patients had an ECOG >2. Median plasmocytosis of bone marrow was 47% (range 35–90%). Of the 13 MGUS subjects, the paraprotein class was IgG in 9 and IgA in 4. IL-33 protein levels were measured using the commercially available DuoSet enzyme-linked immunosorbent assay Development System kits (R&D Systems; Minneapolis, MN, USA). The detection limit was 4 0 pg/ml. Data are presented as interquartile range (IQR) and range, except age, which is presented as mean standard deviation. Differences between data series were analysed by the Mann– Whitney test; differences between categorical groups were analysed by the Pearson chi square (v) test. Correlation between two variables was evaluated with Spearman’s rho. Statistical significance was set at P < 0 05. Twenty three of 44 (52 27%) MM patients, eight of 13 (53 33%) MGUS patients and 36 of 63 (57 14%) controls showed detectable levels of IL-33; there was no statistical significant difference in detectability between the three groups (v = 0 365, P = 0 833). IL-33 levels were statistically significantly different between the MM patients (297 8 and 1491 5 pg/ml) and MGUS patients (312 775 and 1579 9 pg/ml) and those measured in controls (1375 3 and 2035 4 pg/ml) (P = 0 001 and (P = 0 03, respectively) (Fig 1). The IL-33 levels in MM patients with kidney failure (creatinine level >88 4 lmol/l) were not statistically significantly different to MM patients who did not have kidney failure (creatinine level 88 4 lmol/l) (1151,75 and 1488 1 vs. 254 175 and 1002 8 pg/ml, P = 0 322). There was no statistically significant difference in IL-33 levels between MM patients with bone lesions and those without (205 1 and 1002 8 vs. 936 55 and 1483 2 pg/ml, P = 0 096). MM patients showed a negative correlation between IL-33 level and stage (P = 0 006, correlation coefficient = 0 692), but not between IL-33 level and Hb concentration (P = 0 301, correlation coefficient = 0 298), b2 microglobulin level (P = 0 817, correlation coefficient = 0 068), and monoclonal component (P = 0 091, correlation coefficient = 0 468). The development of MM involves a series of changes in the bone marrow microenvironment, favouring the growth of the tumour and failure of local immune control. Quantitative and functional alterations in CD4 and CD8 T cells have been described in MM, and cellular immune defects in MM have been shown to negatively correlate with survival (Pratt et al, 2007). A significant impairment of T-cell function has been also described for patients with MGUS (Prabhala et al, 2006). Cytokines and their receptors play essential roles in the development, maintenance and proper functioning of the immune system. In MM, these interactions may have tumour-promoting consequences (J€ ohrer et al, 2012). IL-33 is a recent addition to the ever-growing family of cytokines. To the best of our knowledge, this is the first study to demonstrate decreased concentrations of IL-33 in patients with MM, which might contribute to the changes in the immune system found in these patients. On the other

Serum thyroid autoantibodies in patients with idiopathic either acute or chronic urticaria

In Italy, only one study was conducted on the detection of serum thyroid autoantibodies (ATA) in patients with urticaria. This northern-Italy study reported a 23% rate of ATA positiveness in 52 patients with chronic idiopathic urticaria (CIU). During the years 1998–2006, 688 patients with urticaria were hospitalized at our Division of Allergy and Clinical Immunology. Thyroglobulin and thyroperoxidase autoantibodies (TgAb and TPOAb) were assayed at admission in 144/688 patients. Of the 144 patients (mean age: 42.3±15.8 yr, range 17–84), 95 (72 women and 23 men) had an history of CIU (CIU group) and 49 (44 women and 5 men) did not [acute urticaria group or (AU)]. Of the 144 patients, 37 (25.7%) tested positive for at least one ATA: 31 with CIU (32.6%) and 6 with AU (12.2%, χ2=7.037, p=0.008). Positiveness for TPOAb or TgAb was 30/37 (81.1%) or 17/37 (45.9%); 10/37 (27.0%). Pre-hospitalization duration of CIU was longer in the 31 ATA positive patients compared to the 64 ATA negative patients (207.2±273.4 vs 81.6±106.3 weeks, p=0.015). Pre-hospitalization duration of CIU correlated positively with the log10-trasformed serum concentration of TPOAb in the 25 CIU patients who tested TPOAb positive (r=0.42, p=0.039). We conclude that our rate of 31/95 (32.6%) positiveness for at least one type of ATA in CIU is greater than that of 6 representative international studies published between the years 2000 and 2006 (111/488 or 22.7%, range 15–29%, χ2=4.884, p=0.027).

Gonadotrophin-releasing hormone analogue or dienogest plus estradiol valerate to prevent pain recurrence after laparoscopic surgery for endometriosis: a multi-center randomized trial.

To evaluate the efficacy of dienogest + estradiol valerate (E2V) and gonadotrophin‐releasing hormone analogue (GnRH‐a) in reducing recurrence of pain in patients with chronic pelvic pain due to laparoscopically diagnosed and treated endometriosis.

Clinical significance of circulating interleukin‐23 as a prognostic factor in breast cancer patients

Little is known about specific IL‐23 alterations associated with breast cancer and the data available are still controversial. Therefore, the evaluation of changes in serum IL‐23 levels may add further information on the role of this cytokine in breast cancer patients. The aim of this study was to evaluate prospectively the prognostic importance of circulating IL‐23 in patients with untreated breast cancer, respect to healthy controls, and the association with clinico‐pathological variables. The study involved 50 women diagnosed with stages I–IV breast cancer and 38 healthy controls. Of the 50 breast cancer patients, 37 women were recruited prior to their initial adjuvant chemotherapy and 13 prior to receive first line chemotherapy for metastatic disease. Adjuvant chemotherapy patients were at least in their 4th week post‐surgery. IL‐23 serum concentrations were measured by a quantitative enzyme immunoassay technique. We found a statistically significant higher systemic cytokine value in women with cancer in comparison with the control group (14.52 ± 11.39 pg/ml vs. 6.35 ± 4.63 pg/ml, P < 0.0001). Patients with shorter overall survival presented higher IL‐23 values, suggesting a negative prognostic correlation. There was no significant differences in IL‐23 levels among patients according to the biomolecular characteristics, the different subtypes and the presence of metastatic disease. This work investigated, for the first time, the role of IL‐23 in breast cancer patients showing a significant increase respect the control group. However, further validations are needed in larger studies to better investigate the implications of IL‐23 increase in these patients. J. Cell. Biochem. 113: 2122–2125, 2012.

Chronic idiopathic urticaria and Graves’ disease

Chronic urticaria is a common condition characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions lasting for more than 6 weeks. In about 75% of cases, the underlying causes remain unknown, and the term chronic idiopathic urticaria (CIU) is used to emphasize that wheals develop independently of identified external stimuli. Although CIU affects about 1.0% of the general population, its etiopathogenesis is not yet well understood. It is now widely accepted that in many cases CIU should be regarded as an autoimmune disorder caused by circulating and functionally active IgG autoantibodies specific for the IgE receptor (FceRI) present on mast cells and basophils or for IgE itself. The well-known association of CIU with other autoimmune processes/diseases represents further indirect evidence of its autoimmune origin. Autoimmune thyroid diseases, especially autoimmune thyroiditis, represent the most frequently investigated diseases in association with CIU. Here we review this topic with particular regard to the association between Graves’ disease and CIU. The possible pathogenetic mechanisms and the clinical implications of such an association are discussed.

Serum levels of carbonylated and nitrosylated proteins in mobbing victims with workplace adjustment disorders

AIM Today the most important problem in the work place is psychological abuse, which may affect the health because of high levels of stress and anxiety. There is evidence that most psychiatric disorders are associated with increased oxidative stress but nothing is reported about the presence of oxidative stress in mobbing victims. METHODS This study has been carried out in a group of 19 patients affected by workplace mobbing-due adjustment disorders, in comparison with 38 healthy subjects, to evaluate whether oxidative stress may be induced by mobbing. RESULTS Serum levels of protein carbonyl groups and of nitrosylated proteins, biological markers of oxidative stress conditions, were higher than those measured in healthy subjects. CONCLUSIONS These findings may contribute to a better understanding of the redox homeostasis dysregulation occurring in victims of workplace mobbing.

Interleukin-23 serum levels in patients affected by peripheral arterial disease.

OBJECTIVES To clarify whether interleukin (IL)-23 is involved in peripheral arterial disease (PAD). DESIGN AND METHODS We evaluated IL-23 serum levels, in 29 patients suffering from lower extremity PAD and in 30 healthy subjects. RESULTS IL-23 serum levels were higher during the three times (T0, T1 and T2) compared to the control group, although only statistically significant for T0 and T2: T0 (15.83 ± 22.08 vs. 8.08 ± 8.62 pg ml, p=0.026), T1 (16.10 ± 23.71 vs. 8.08 ± 8.62 pg/ml, p=0.101), T2 (15.06 ± 16.72 vs. 8.08 ± 8.62 pg/ml, p=0.005). CONCLUSION For the first time, our data gives us reason to believe there is an involvement of IL-23 in PAD.