Type IV delayed-type hypersensitivity of the respiratory tract due to budesonide use: report of two cases and a literature review

Respiratory type-IV hypersensitivity reactions due to corticosteroids is a rare phenomenon. We describe two such cases. The first is a 37- year-old atopic woman who developed labial angioedema and nasal itching after the use of budesonide nasal spray. A month later, after the first puffs of a formoterol/budesonide spray prescribed for asthma, she noticed symptoms of tongue and oropharyngeal itching and redness with subsequent dysphagia, labial and tongue angioedema, and facial oedema. The second is a 15-year-old non-atopic woman who reported pruritic eruptions around the nostrils after using a budesonide nasal spray. A year later she presented with nasal pruritus with intense congestion and labial and facial oedema after using the same spray. Both patients were evaluated with patch-tests using the commercial T.R.U.E. test, a budesonide solution, and corticosteroid creams. Test evaluation was performed at 48 and 96 hours. In both patients, patch tests were positive to budesonide (++) on the second day. The first patient also had a positive (+) reaction to tixocortol-21-pivalate. All the other patch tests were negative. Clinicians should be aware that hypersensitivity reactions may occur during the use of nasal or inhaled corticosteroids.

Use of modern and traditional products to self-treat symptoms of sexually transmitted infections in South African women

The objective of the study is to investigate products used by women self-treating symptoms of reproductive tract infections (RTIs), including sexually transmitted infections (STIs), and their methods of administration. A household survey using a multi-stage cluster sample design was undertaken in KwaZulu-Natal, South Africa. Women aged 18-60 years were interviewed (n = 867) and information was collected on demographics, reproductive health and sexual behaviours. A fifth of women reported having RTI/STI symptoms (20.5%), of whom 41.9% were treating these symptoms (mostly discharge [79.1%], ulcers [6.8%] and itching [7.7%]). Only three women were using medication prescribed by a health provider, while the remainder were self-treating using traditional medicines and modern products, including antiseptics, soaps, petroleum jelly, menthol creams and alum. Products were administered in various ways. Although RTI/STI treatment is widely available and free in public health facilities, many women are still self-treating. Potential harm of products for self-treatment requires further investigation and efforts should be made to improve STI service uptake.

Effects of high-dose heroin versus morphine in intravenous drug users: a randomised double-blind crossover study

The purpose of this study is to evaluate the effects of high doses of injected opiates as prescribed maintenance in intravenous drugs users. This was accomplished via a randomised double-blind study with crossover at an outpatient clinic in Bern, Switzerland. The subjects were 39 patients with a long history of intravenous opioid use and persistent abuse despite treatment; they were randomly allocated to two groups. Group A was started on controlled injection of graduated doses of morphine up to a satisfying individual dose and was then switched as a double blind to heroin at a randomly determined day between week three and four. Subsequently this group was given heroin for the remaining two to three weeks of the study. Group B was started on heroin and was then switched to morphine in the same manner. Equipotent solutions of 3% morphine and 2% heroin were administered. The main outcome measures were clinical observations, structural interviews and self report of subjective experiences to assess the effects of the drugs. In 16 cases, the study had to be discontinued owing to severe morphine-induced histamine reactions. Thirteen participants in Group B presented these adverse reactions on the day of the switch-over. Full data were thus only obtainable for 17 participants. Average daily doses were 491 mg for heroin and 597 mg for morphine. The findings indicate that heroin significantly produced a lower grade of itching, flushing, urticaria and pain/nausea. A negative correlation between dose and euphoria was observed for both heroin and morphine. The authors concluded that as heroin produces fewer side effects it is the preferred high-dose maintenance prescription to morphine. The perceived euphoric effects are limited in both substances.

Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study

BACKGROUND: Chronic idiopathic urticaria (CIU) is defined by the almost daily presence of urticaria for at least 6 weeks without an identifiable cause. Symptoms include short-lived wheals, itching, and erythema. CIU impedes significantly a patient's quality of life (QoL). Levocetirizine is an antihistamine from the latest generation approved for CIU. AIM: To investigate the efficacy of levocetirizine, 5 mg, and placebo for the symptoms and signs of CIU, as well as for the QoL and productivity. METHODS: The primary criteria of evaluation were the pruritus severity scores over 1 week of treatment and over 4 weeks. The QoL was assessed via the Dermatology Life Quality Index (DLQI). RESULTS: Baseline pruritus severity scores were comparable in the two treatment groups (2.06+/-0.58). After 1 week, levocetirizine was superior to placebo and demonstrated a considerable efficacy (difference=0.78, P<0.001). This efficacy was maintained over the entire study period (4 weeks, P<0.001). The number and size of wheals were considerably reduced compared with placebo over 1 week and over the total treatment period (P

Allergic rhinitis in patients with asthma: the Swiss LARA (Link Allergic Rhinitis in Asthma) survey

OBJECTIVE: To determine the characteristics of asthma (A) and allergic rhinitis (AR) among asthma patients in primary care practice. RESEARCH DESIGN AND METHODS: Primary care physicians, pulmonologists, and allergologists were asked to recruit consecutive asthma patients with or without allergic rhinitis from their daily practice. Cross-sectional data on symptoms, severity, treatment and impact on quality of life of A and AR were recorded and examined using descriptive statistics. Patients with and without AR were then compared. RESULTS: 1244 asthma patients were included by 211 physicians. Asthma was controlled in 19%, partially controlled in 27% and not controlled in 54%. Asthma treatment was generally based on inhaled corticosteroids (ICS) with or without long acting beta 2 agonists (78%). A leukotriene receptor antagonist (LTRA) was used by 46% of the patients. Overall, 950 (76%) asthma patients had AR (A + AR) and 294 (24%) did not (A - AR). Compared to patients with A - AR, A + AR patients were generally younger (mean age +/- standard deviation: 42 +/- 16 vs. 50 +/- 19 years, p < 0.001) and fewer used ICS (75% vs. 88%, p < 0.001). LTRA usage was similar in both groups (46% vs. 48%). Asthma was uncontrolled in 53% of A + AR and 57% of A - AR patients. Allergic rhinitis was treated with a mean of 1.9 specific AR medications: antihistamines (77%), nasal steroids (66%) and/or vasoconstrictors (38%), and/or LTRA (42%). Rhinorrhoea, nasal obstruction, or nasal itching were the most frequently reported AR symptoms and the greatest reported degree of impairment was in daily activities/sports (55%). CONCLUSIONS: Allergic rhinitis was more common among younger asthma patients, increased the burden of symptoms and the need for additional medication but was associated with improved asthma control. However, most asthma patients remained suboptimally controlled regardl-ess of concomitant AR.

Being Moved by the Self and Others: Influence of Empathy on Self-Motion Perception

BACKGROUND: The observation of conspecifics influences our bodily perceptions and actions: Contagious yawning, contagious itching, or empathy for pain, are all examples of mechanisms based on resonance between our own body and others. While there is evidence for the involvement of the mirror neuron system in the processing of motor, auditory and tactile information, it has not yet been associated with the perception of self-motion. METHODOLOGY/PRINCIPAL FINDINGS: We investigated whether viewing our own body, the body of another, and an object in motion influences self-motion perception. We found a visual-vestibular congruency effect for self-motion perception when observing self and object motion, and a reduction in this effect when observing someone else's body motion. The congruency effect was correlated with empathy scores, revealing the importance of empathy in mirroring mechanisms. CONCLUSIONS/SIGNIFICANCE: The data show that vestibular perception is modulated by agent-specific mirroring mechanisms. The observation of conspecifics in motion is an essential component of social life, and self-motion perception is crucial for the distinction between the self and the other. Finally, our results hint at the presence of a "vestibular mirror neuron system".

Is vaginal hyaluronic acid as effective as vaginal estriol for vaginal dryness relief?

In a multicenter, randomized, controlled, open-label, parallel- group trial hyaluronic acid vaginal gel (Hyalofemme) was compared to estriol vaginal cream (Ovestin) in women with vaginal dryness due to various causes. A total of 144 supposedly postmenopausal women below age 70 years were randomized in a 1:1 ratio to either receive hyaluronic acid vaginal gel (5 g per application) or estriol vaginal cream (0.5 g cream per application = 0.5 mg estriol) every 3 days for a total of ten applications, respectively. Exclusion criteria included vaginal infections, conventional contraindications to estrogens, use of vaginal products other than the investigational compounds, being unmarried, pregnant, or breastfeeding. The aim of the study was to test for non-inferiority of hyaluronic acid vaginal gel compared to estriol vaginal cream. The primary efficacy end point was the percentage (%) improvement in vaginal dryness, with the secondary end points being the percentage (%) improvements in vaginal itching, burning, and dyspareunia. Efficacy was assessed by using a visual analog scale (VAS) (0-10; 0 = absent, 10 = intolerable) at baseline (V0), during telephone contact after the third administration (V1), and at the final visit after the tenth administration (V2). Safety parameters included vaginal pH, endometrial thickness, and a vaginal smear for vaginal microecosystem assessment. Adverse events were recorded according to international guidelines. 133 women completed the study. At baseline, participants' characteristics did not differ significantly. Mean age was 54 years, time since menopause was 5 years on average, and cause of menopause was mostly natural. However, mean menstrual cycle days were also reported, although according to inclusion criteria only postmenopausal women were eligible for the study. At V1, an improvement in vaginal dryness was reported by about 49 % of women using hyaluronic acid vaginal gel, and by 53 % of women using estriol vaginal cream (p = 0.31). At V2, the percentage improvement rates were 84 and 89 % (p = 0.13), respectively. Improvement rates for vaginal itching, burning, and dyspareunia at V2 were about 86, 85, and 57 % for hyaluronic acid vaginal gel, and 82, 87, and 62 % for estriol vaginal cream (p[0.05), respectively. After treatment, vaginal pH was significantly lower in estriol-treated women compared to those having received hyaluronic acid. Endometrial thickness did not differ between groups. In the majority of women, the vaginal microenvironment remained unaffected by treatment. However, the proportion of women whose abnormal vaginal microecological results became normal was higher in women using estriol vaginal cream. Adverse events (suspected to be) related to the investigational compounds were minor and included vaginal infection and genital itching. The authors concluded that hyaluronic acid vaginal gel was not inferior to estriol vaginal cream in women presenting with vaginal dryness. They suggest using hyaluronic acid vaginal gel not only as an alternative treatment to vaginal estrogens, but also to consider its general use in women presenting with vaginal dryness of any cause.

Vaginal cytokines do not differ between postmenopausal women with and without symptoms of vulvovaginal irritation.

OBJECTIVE The aim of this exploratory pilot study was to determine if there are differences in vaginal cytokine levels between postmenopausal women with and without vulvovaginal irritative symptoms (itching, burning, or pain). METHODS Postmenopausal women (n = 34) not using hormone therapy and presenting with or without symptoms of vulvovaginal irritation were asked to volunteer for this study. Each participant underwent a vaginal examination and screening for vaginitis using Amsel criteria, pH, and light microscopy. A vaginal lavage with 5.0 mL of sterile saline was carried out, and a peripheral blood sample was obtained. The vaginal lavage and serum samples were assayed for interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α by specific enzyme-linked immunosorbent assays. Results were adjusted for total protein concentration and presented as the amount of cytokines per protein (pg/μg protein). Statistical analysis was performed using SAS version 9.3 (SAS Institute, Cary, NC). The means and SDs of all variables among women with and without vulvovaginal irritation were compared using independent-samples Student's t test. RESULTS A total of 26 postmenopausal women were enrolled into the study (symptomatic, n = 15; asymptomatic, n = 11). The mean (SD) vaginal pH for all participants was 5.9 (1.2). There were no significant differences (P > 0.05) in age, age at menopause, vaginal pH, and vaginal and serum cytokines and chemokines (IL-1β, IL-6, IL-8, and tumor necrosis factor-α) among symptomatic versus asymptomatic women. IL-8 was the most abundant vaginal cytokine, with mean (SD) vaginal IL-8 levels being 4.1 (3.4) and 3.1 (3.9) pg/μg protein in the symptomatic versus asymptomatic groups, respectively (P = 0.55). There were no significant linear correlations (P > 0.05) between serum and vaginal cytokine levels for all endpoints. CONCLUSIONS The presence or absence of postmenopausal vulvovaginal symptoms does not significantly differentiate vaginal inflammatory markers. Serum and vaginal cytokines are not significantly linearly correlated among postmenopausal women with and without symptoms commonly associated with vaginal atrophy, implying that this is a local reaction.

Efficacy and safety of non-hormonal remedies for vaginal dryness: open, prospective, randomized trial

OBJECTIVES To prove non-inferiority of the first non-hormonal vaginal cream in Germany, Vagisan(®) Moisturising Cream (CREAM), compared to a non-hormonal vaginal gel (GEL) for vulvovaginal atrophy (VVA) symptom relief. METHOD This was a 12-week multicenter, open-label, prospective, randomized, two-period, cross-over phase-III trial. The primary endpoint was the cumulative VVA subjective symptom score of the respective treatment period. Secondary endpoints were assessment of single VVA subjective and objective symptoms, VVA objective symptom score, vaginal pH, safety parameters, overall assessment of efficacy, tolerability and evaluation of product properties. In total, 117 women were randomly allocated to either one of the two treatments, each administered for 4 weeks; 92 women were included in the per-protocol analysis (primary analysis). The main outcome measure was cumulative VVA subjective symptom score. RESULTS Regarding VVA symptom relief, results confirmed non-inferiority of CREAM compared to GEL and even indicated superiority of CREAM. Frequency and intensity of subjective symptoms and objective findings were clearly reduced, with CREAM showing better results compared to GEL. Mean VVA objective symptom score significantly decreased; improvement was significantly greater with CREAM. Vaginal pH decreased only following CREAM treatment. Tolerability was superior for CREAM: burning and itching, mostly rated as mild, occurred markedly less often with CREAM than with GEL. Overall satisfaction with treatment efficacy, tolerability and most product properties were rated significantly superior for CREAM. CONCLUSIONS Subjective and objective VVA symptoms were reliably and safely reduced by both non-hormonal topical products. However, efficacy and tolerability of CREAM were shown to be superior to GEL.

Acute hemorrhagic edema of young children: a prospective case series.

Acute hemorrhagic edema of young children is a rare leukocytoclastic vasculitis that has been reported exclusively in small retrospective cases series, case reports, or quizzes. Considering that retrospective experience deserves confirmation in at least one observational prospective study, we present our experience with 16 children (12 boys and 4 girls, 5-28 months of age) affected by acute hemorrhagic edema. The patients were in good general conditions and with a low-grade or even absent fever. They presented with non-itching red to purpuric targetoid lesions not changing location within hours, with non-pitting and sometimes tender indurative swelling, and without mucous membrane involvement or scratch marks. Signs for articular, abdominal, or kidney involvement were absent. Antinuclear or antineutrophil cytoplasmic autoantibodies were never detected. The cases were managed symptomatically as outpatients and fully resolved within 4 weeks or less. No recurrence or familiarity was noted. CONCLUSION This is the first prospective evaluation of hemorrhagic edema. Our findings emphasize its distinctive tetrad: a well-appearing child; targetoid lesions that do not change location within hours; non-pitting, sometimes tender edema; complete resolution without recurrence. What is known • Acute hemorrhagic edema of young children is considered a benign vasculitis. • There have been ≈100 cases reported in small retrospective case series. What is new • The first prospective evaluation of this condition emphasizes its features: febrile prodrome; well-appearing child; targetoid lesions not changing location within hours; non-pitting, sometimes tender indurative edema; absent extracutaneous involvement; resolution within 3 weeks. • Antineutrophil cytoplasmic autoantibodies do not play a pathogenic role.