Pasquale Mansueto

Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity.

OBJECTIVES:Non-celiac wheat sensitivity (WS) is considered a new clinical entity. An increasing percentage of the general population avoids gluten ingestion. However, the real existence of this condition is debated and specific markers are lacking. Our aim was thus to demonstrate the existence of WS and define its clinical, serologic, and histological markers.METHODS:We reviewed the clinical charts of all subjects with an irritable bowel syndrome (IBS)-like presentation who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge in the years 2001–2011. One hundred celiac disease (CD) patients and fifty IBS patients served as controls.RESULTS:Two hundred and seventy-six patients with WS, as diagnosed by DBPC challenge, were included. Two groups showing distinct clinical characteristics were identified: WS alone (group 1) and WS associated with multiple food hypersensitivity (group 2). As a whole group, the WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls. There was also a higher frequency of positive serum assays for IgG/IgA anti-gliadin and cytometric basophil activation in “in vitro” assay. The main histology characteristic of WS patients was eosinophil infiltration of the duodenal and colon mucosa. Patients with WS alone were characterized by clinical features very similar to those found in CD patients. Patients with multiple food sensitivity were characterized by clinical features similar to those found in allergic patients.CONCLUSIONS:Our data confirm the existence of non-celiac WS as a distinct clinical condition. We also suggest the existence of two distinct populations of subjects with WS: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.

Randomized placebo‐controlled trial comparing fluticasone aqueous nasal spray in mono‐therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis

Background Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first‐line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms.

Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy.

BACKGROUND To date, no predictive tests for the clinical response to allergen-specific immunotherapy (ASI) are available. Therefore an in vivo or in vitro test would be of great value. OBJECTIVE We sought to evaluate pretreatment parameters used in diagnosing allergic rhinitis and determining serum specific IgE (s-IgE) levels, serum total IgE (t-IgE) levels, and blood eosinophil counts and to identify whether can be used to predict clinical improvement in monosensitized patients with allergic rhinitis with or without asthma treated with immunotherapy. METHODS We analyzed 279 patients who had undergone 4 years of ASI administered either by means of the subcutaneous immunotherapy (76 patients) or sublingual immunotherapy (203 patients) routes. Serum t-IgE and s-IgE levels, blood eosinophil counts, and serum s-IgE/t-IgE ratios were calculated and tested for correlation with clinical response to ASI. Receiver operating characteristic curves were determined. Predicted probabilities and predictive areas under the curve were calculated. RESULTS The clinical response to ASI was effective in 145 (52.0%) of 279 total patients, 42 (55.2%) of 76 patients treated with subcutaneous immunotherapy, and 103 (50.7%) of 203 patients treated with sublingual immunotherapy. A significant correlation was found between the serum s-IgE/t-IgE ratio and the clinical response to ASI, with high ratios (>16.2) associated with an effective response. The sensitivity and specificity of the area under the curve of the ratio were higher than those of serum s-IgE and t-IgE alone. CONCLUSION The calculation of the serum s-IgE/t-IgE ratio for predicting the clinical response to ASI offers an advantage over measuring t-IgE and s-IgE levels in monosensitized patients for the following allergens: grass, Parietaria judaica, Olea europea, and house dust mite.

Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome.

Central fat distribution is increased in anovulatory women with polycystic ovary syndrome (PCOS) compared with ovulatory PCOS and matched controls. Among secreted adipocytokines, this is reflected mainly in lower levels of adiponectin.

New Insight into Immunity and Immunopathology of Rickettsial Diseases

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered.

Prevalence of organ-specific and non organ-specific autoantibodies in healthy centenarians

In the present study we have investigated the prevalence of organ-specific and non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women; age range 101-106 years), using as controls 54 healthy old (33 men and 21 women, age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). We assayed sera of each group for the following organ-specific autoantibodies, anti-gastric mucosa (anti-PCA), anti-thyroglobulin (anti-Tg) and non organ-specific autoantibodies, anti-cardiolipin (anti-APA IgG and IgM), anti-nuclear antigens (anti-ANA), anti-double strand DNA (anti-ds-DNA), anti-extractable nuclear antigens (anti-ENA). Finally, natural anti-alpha-galactosyl (anti-alpha-GAL) antibodies were also analyzed. As expected, in the old subjects there was a significant increase of prevalence of anti-Tg and anti-PCA autoantibodies. By contrast, in centenarians the prevalence of organ specific anti-Tg and anti-PCA antibodies was not significantly different from that observed in controls aged less than 60 years. The prevalence of non organ-specific autoantibodies anti-APA (IgG), anti-APA (IgM), anti-ANA, was significantly increased both in the elderly and centenarians when compared with the prevalence observed in sera from the young. Anti-ENA and anti-dsDNA antibodies were not detected in all groups studied. Finally, the prevalence of natural anti-alpha-GAL antibodies significantly increases with age, including centenarians. In conclusion, we confirm and extend the results previously obtained by other authors. In fact, as already described, the prevalence of organ-specific autoantibodies in the elderly is not seen after the tenth decade of life. Interestingly, the prevalence of non organ-specific autoantibodies is instead increased in these subjects, suggesting that different mechanisms are involved in the pathogenesis of these autoantibodies. Particularly, these autoantibodies could be the expression of a damaged tissue process rather than of an autoimmune one, as suggested by data concerning natural antibodies.

Non-celiac wheat sensitivity as an allergic condition: personal experience and narrative review.

Objectives:Non-celiac wheat sensitivity (NCWS) is a newly described clinical entity characterized by symptoms, which can involve the gastrointestinal tract, the nervous system, the skin, and other organs. There is little data on the pathogenesis of NCWS and it is probable that different pathogenic mechanisms are involved in the different clinical manifestations of the disease. The only common denominator of NCWS “syndrome” is wheat consumption: the symptoms disappear on exclusion of wheat from the diet, and reappear on wheat consumption. The objective of this study was to review our prior data regarding NCWS and to review relevant medical literature regarding NCWS, with particular attention to the hypothesis that NCWS patients could suffer from non-immunoglobulin E (IgE)-mediated wheat allergy.Methods:We reviewed our data on 276 patients diagnosed with NCWS by means of double-blind placebo-controlled (DBPC) wheat challenge. The data indicating a possible wheat allergy diagnosis were examined and other data in the literature were reviewed; we review the role of serum immunoglobulin G antibodies and the basophil activation assay in food allergy, and the histology findings in the food allergy diagnosis.Results:The comparison between patients suffering from NCWS and presenting with irritable bowel syndrome (IBS) and controls with IBS not due to NCWS showed that NCWS was characterized by: a personal history of food allergy in the pediatric age (0.01), coexistent atopic diseases (0.0001), positive serum anti-gliadin (0.0001) and anti-betalactoglobulin (0.001) antibodies, positive cytofluorimetric assay revealing in vitro basophil activation by food antigens (0.0001), and a presence of eosinophils in the intestinal mucosa biopsies (0.0001).Conclusions:Patients with NCWS and multiple food sensitivity show several clinical, laboratory, and histological characteristics that suggest they might be suffering from non-IgE-mediated food allergy. However, other pathogenic mechanisms need to be considered.

Comparative effect of tacrolimus 0.1% ointment and clobetasol 0.05% ointment in patients with oral lichen planus.

BACKGROUND Oral lichen planus (OLP) is considered to be an autoimmune disease of unknown aetiology that affects the mucosae, especially the oral cavity. OBJECTIVE We compared tacrolimus 0.1% ointment and clobetasol 0.05% ointment for the treatment of OLP. PATIENTS AND METHODS A total of 32 patients (20 females and 12 males; all white, Italian origin, mean age of 43.6+/-18.4 years; 16 patients per treatment group) were treated with tacrolimus or clobetasol ointment for 4 weeks in a randomized, double-blind, clinical trial. Pain severity, burning sensation, and mucosal lesion extension were assessed using a four-point scale. RESULTS At the end of the treatment period, symptom scores were significantly lower in the tacrolimus group than in the clobetasol group. CONCLUSION The results of this study suggest that tacrolimus 0.1% ointment is more effective than clobetasol propionate 0.05% ointment in the treatment of OLP. However, other studies are needed to confirm the effectiveness of this treatment before it can be recommended for use in clinical practice.

A Cytologic Assay for Diagnosis of Food Hypersensitivity in Patients With Irritable Bowel Syndrome

BACKGROUND & AIMS A percentage of patients with symptoms of irritable bowel syndrome (IBS) suffer from food hypersensitivity (FH) and improve on a food-elimination diet. No assays have satisfactory levels of sensitivity for identifying patients with FH. We evaluated the efficacy of an in vitro basophil activation assay in the diagnosis of FH in IBS-like patients. METHODS Blood samples were collected from 120 consecutive patients diagnosed with IBS according to Rome II criteria. We analyzed in vitro activation of basophils by food allergens (based on levels of CD63 expression), as well as total and food-specific immunoglobulin (Ig)E levels in serum. Effects of elimination diets and double-blind food challenges were used as standards for FH diagnosis. RESULTS Twenty-four of the patients (20%) had FH (cows milk and/or wheat hypersensitivity); their symptom scores improved significantly when they were placed on an elimination diet. Patients with FH differed from other IBS patients in that they had a longer duration of clinical history, a history of FH as children, and an increased frequency of self-reported FH; they also had hypersensitivities to other antigens (eg, egg or soy). The basophil activation assay diagnosed FH with 86% sensitivity, 88% specificity, and 87% accuracy; this level of sensitivity was significantly higher than that of serum total IgE or food-specific IgE assays. CONCLUSIONS A cytometric assay that quantifies basophils after stimulation with food antigens based on cell-surface expression of CD63 had high levels of sensitivity, specificity, and accuracy in diagnosing FH. This assay might be used to diagnose FH in patients with IBS-like symptoms.

Food-additive-induced urticaria : A survey of 838 patients with recurrent chronic idiopathic urticaria

Background: Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1–3% of the population in the USA and Europe and accounts for nearly 75% of all ‘ordinary’ chronic urticaria (CU) cases. Methods: We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. Results: The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. Conclusions: Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU.