Successful Treatment of Chronic Mucocutaneous Candidiasis Caused by Azole-Resistant Candida albicans with Posaconazole

Refractory or recurrent infections of skin, nails, and the mucous membranes are clinical signs of chronic mucocutaneous candidiasis, frequently associated with immunological defects. Here we describe a 39-years-old female patient, with familial CMC, that presented with an extensive infection caused by an azole-resistant Candida albicans isolate, successfully treated with posaconazole

Exercise-induced anaphylaxis with an Ayurvedic drug as cofactor: A case report

The practice of Indian Ayurvedic medicine is spreading in Western countries and Shilajit is one of the most used drugs, for its antioxidant activities and immunomodulatory effects. Albeit Shilajit has showed a high degree of safety, it can act as cofactor of anaphylaxis, especially in condition at high risk, such as mast cell activation syndrome (MCAS). We reported this case to sensitize practitioners to investigate to the use of complementary and alternative medicine, in case of exercise-induced anaphylaxis (EIAn)

Evaluation of olfactory function as a potential biomarker in patients with mastocytosis

Background: Mastocytosis is a clonal disease characterized by an accumulation of mastcells in various organs, such as skin, bones, lymph nodes, liver, spleen, peripheral and central nervous system, gastrointestinal and nose-pharyngeal tract. The serum tryptase, an enzyme produced almost exclusively by mastcells is considered as a biomarker. The serum concentration of tryptase can therefore be considered a quantitative sign and an indicator of activity of the organism's mast cells. The aim of the study was first to investigate odor threshold (OT), odor discrimination (OD) and odor identification (OI) in mastocytosis patients (MP) compared to age matches healthy controls (HC), then to correlate olfactory function with, serum tryptase. Method: Eighty subjects were enrolled in this study (40 patients with mastocytosis, 18 women and 22 men, mean age 47.9, SD 14.4 and 40 healthy controls, 16 women and 24 men 47.9, SD 14.7). OT, OD, OI and their sum TDI score were evaluated using the psychophysical Sniffin’ Sticks. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive ability. One way between groups Multivariate analyses of variance (MANOVA) was carried out to assess the impact of olfactory function on the mastocytosis. Results: Among MP group, 10 (25%) reported normosmia, one patient functional anosmia and the remaining showed hyposmia. Our results indicated a statistical significant differences between the two groups (MP and HC) for the olfactory function and the MoCA [F(5,74)=504.7, p<0.0005, Wilks' Lambda =0.03, partial η2=0.972]. The analyses of each individual dependent variable, using Bonferroni adjusted alpha level showed significant differences between two groups for OT [F(1,78)=866.6, p<0.0005, partial η2=0.917], OD [F(1,78)=76.6, p<0.005, partial η2=0.495], for TDI [F(1,78)=379.6, p<0.005, partial η2=0.830] and for MoCA [F(1,78)=146.3, p<0.005, partial η2=0.652]. Instead, no statistical significant difference was found for OI [F(1,78)=0.62, p>0.05, partial η2=0.008]. Significant negative correlation was observed between the TDI versus serum tryptase (r=-0.398, p<0.05). Conclusion: Our data suggest that olfactory dysfunction could represent a potential biomarker to be more extensively evaluated for an early diagnosis of Mastocytosis

Idiopathic pyoderma gangrenosum: Successful resolution with Infliximab therapy and proinflammatory cytokines assessment

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis of unknown aetiology, characterized by primarily sterile, painful ulcers with typical violaceous undermined borders and mucopurulent or haemorrhagic exudate. PG is commonly associated with other systemic disorders. Diagnosis of primary idiopathic forms is reached following the exclusion of inflammatory bowel disease (IBD), rheumatic disorders, monoclonal gammopathy and solid tumours (1, 2). Treatment is generally based on corticosteroid and immunosuppressive therapy; however, the recent use of biological drugs has shown their effectiveness

Cofactors, age at onset, allergic comorbidities and gender are different in patients sensitized to omega-5 gliadin and Pru p 3

Abstract Aim of this study is to clarify the impact of cofactors on allergic reactions in patients sensitized to LTP and ω-5-gliadin. We retrospectively examined the charts of our outpatients from January 2015 to July 2019 and identified 157 patients seen for urticaria/angioedema or anaphylaxis after a meal, in presence or absence of cofactors and sensitized to LTPs (Pru p 3 and/or Tri a 14) and/or ω-5-gliadin (Tri a 19). we compared LTPs-positive patients and those sensitized to Tri a 19 in order to assess the difference in cofactors involved and in frequency of clinical presentation. Our data show that exercise is the most frequent cofactor in FDEIAn and the involvement of exercise, alcohol and multiple cofactors was more frequently found in males than in females. We found that exercise, pollen counts peaks and multiple cofactors were more often related to anaphylaxis than mild reactions. Finally, we performed a comparison between patients LTPs+ and Tri a 19+ that showed in the latter group a lower frequency of allergic comorbidities, a higher median age at the onset of symptoms and frequency of alcohol exposure. Our data show that the search for possible cofactors involved in food allergy is essential not only for diagnostic purposes, but also for risk assessment strategies

Mutation of angiopoietin-1 gene (ANGPT1) associates with a new type of hereditary angioedema

Hereditary angioedema (HAE) is a rare genetic disease usually due to mutation within the C1 inhibitor or the coagulation Factor XII gene. However, in a series of patients with HAE no causative variants have been described and the pathophysiology of the disease remains unknown (U-HAE). Identification of causative genes in U-HAE is valuable for understanding the cause of the disease. Objective: We conducted genetic studies in Italian patients with U-HAE to identify novel causative genes. Methods: Among patients belonging to 10 independent families and unrelated index patients with U-HAE disease recruited from the Italian network for C1-INH-HAE (ITACA), we selected a large multiplex family with U-HAE and performed whole-exome sequencing. The angiopoietin-1 gene(ANGPT1) was investigated in all patients with familial or sporadic U-HAE. The effect of ANGPT1 variants was investigated by in silico prediction and using patients and control plasmas and transfected cells. Results: We identified a missense mutation (ANGPT1, c.807G>T, p.A119S) in a family with U45 HAE. The ANGPT1 p.A119S variant was detected in all members of the index family with U-HAE but not in asymptomatic family members, nor in an additional 20 patients with familial U-HAE, 22 patients with sporadic U-HAE, and 200 controls. Protein analysis of the plasma of patients revealed a reduction of multimeric forms and a reduced ability to bind the natural receptor “tunica interna endothelial cell kinase-2” (TIE2) of the ANGPT1 p.A119S variant. The recombinant mutated ANGPT1 p.A119S formed a reduced amount of multimers and showed a reduced binding capability to its receptor. Conclusion: ANGPT1 impairment is associated with angioedema and ANGPT1 variants can be the basis of HAE

Oxidative stress markers in patients with hereditary angioedema

Introduction: Hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) or with normal C1-INH is characterized by recurrent swellings due to uncontrolled production of vasoactive mediators, among which bradykinin (BK) is crucial. Through the binding and activation of the two human BK-receptors, kinins may have dual beneficial and deleterious effects in vascular and inflammation physiopathology by inducing oxidative stress. We aimed to assess the serum concentrations of advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) in patients affected by HAE. Material and methods: Blood samples were collected to measure the serum concentrations of AGEs and AOPPs by spectrofluorimetric and spectrophotometric methods in patients affected by C1-INH-HAE and FXII-HAE during the remission state. Results: We showed that the circulating levels of AOPPs observed on control group (0.94 (0.36) nmol/ mg) were significantly lower than those observed on the C1-INH-HAE group (1.68 (0.47) nmol/mg; p = 0.002) and FXII-HAE (1.50 (0.27) nmol/mg; p = 0.001). Moreover, the circulating levels of AGEs were significantly higher in C1-INH-HAE group (211.58 (151.05) AU/g; p = 0.02) than the FXII group (141.48 (89.59) AU/g), thus demonstrating a state of heightened oxidative stress. Conclusions: Our observations show additional underlying events involved in HAE and are of central importance for further investigations of differences in bradykinin receptors signaling among the two disease subgroups

3D Ultrasound in Pelvic Floor: Is It Useful as a Prognostic Tool in Type of Labor Development and Subsequent Pelvic Floor Diseases?

The objective of our study is to determine the thickness of the pubovisceral fasciculus of the levator ani muscle and the area of the genital hiatus by means of three-dimensional perineal ultrasound, in pregnant women in the 2nd trimester, and to analyze the related maternal, perinatal and postpartum clinical variables. Furthermore, to compare the results of our study with two similar series previously published. An observational, prospective study of pelvic floor ultrasound was carried out, performed at week 20, whose delivery was attended in the obstetrics service of the Hospital General Universitario Gregorio Marañón de Madrid (HGUGM), during the period of August from 2021 to June 2022. Maternal, ultrasound, perinatal and postpartum clinical variables were collected from each participant. During the study period, a total of 54 patients were included in it. The mean gestational age at which the ultrasound was performed was 19.81 ± 0.91 weeks. In relation to the ultrasound variables, the mean thickness of the pubovisceral muscle was 0.87 ± 0.13 cm (95% CI, 0.64–1.38 cm), while, in the plane of minimum dimension of the genital hiatus, the hiatal area at rest was 13.41 ± 3.22 (95% CI, 4.60–18.78) cm2. There is a significant correlation between the age of pregnant women (over 35 years of age) and the increase in the area of the genital hiatus (r = 0.295, p = 0.031). 3D ultrasound of the pelvic floor performed at week 20 of gestation can to be an effective, non-invasive, reproducible and cheap tool in the prognosis of the development of labor and of possible subsequent perineal dysfunctions

A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy

Introduction: Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE type I) or dysfunction (C1-INH-HAE type II) is a rare disease characterized by recurrent episodes of edema with an estimated frequency of 1:50,000 in the global population without racial or gender differences. In this study we present the results of a nationwide survey of C1-INH-HAE patients referring to 17 Italian centers, the Italian network for C1-INH-HAE, ITACA. Methods: Italian patients diagnosed with C1-INH-HAE from 1973 to 2013 were included in the study. Diagnosis of C1-INH-HAE was based on family and/or personal history of recurrent angioedema without urticaria and on antigenic and/or functional C1-INH deficiency. Results: 983 patients (53% female) from 376 unrelated families were included in this survey. Since 1973, 63 (6%) patients diagnosed with C1-INH-HAE died and data from 3 patients were missing when analysis was performed. Accordingly, the minimum prevalence of HAE in Italy in 2013 is 920:59,394,000 inhabitants, equivalent to 1:64,935. Compared to the general population, patients are less represented in the early and late decades of life: men start reducing after the 5th decade and women after the 6th. Median age of patients is 45 (IQ 28-57), median age at diagnosis is 26 years (IQ 13-41). C1-INH-HAE type 1 are 87%, with median age at diagnosis of 25 (13-40); type 2 are 13% with median age at diagnosis of 31 (IQ 16-49). Functional C1INH is ≤50% in 99% of patients. Antigen C1INH is 50% is 95%. This parameter should be therefore considered for initial screening in differential diagnosis of angioedema