The global burden of chronic urticaria for the patient and society.

Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1 -antihistamines, even at higher doses, and third- and fourth-line therapies (omalizumab and ciclosporin) control the disease only in two-thirds of H1 -antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.

Implication of VDR Rs7975232 and FCGR2A Rs1801274 Gene Polymorphisms in the Risk and the Prognosis of autoimmune Thyroid Diseases in the Tunisian Population.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) that cause hypothyroidism and hyperthyroidism, respectively. The vitamin D receptor (VDR) and the Fey receptor IIA (FcγRIIA), are implicated in the etiology of AITD. This study was conducted to examine the implication of VDR rs7975232 and FCGR2A rs 1801274 variations in the susceptibility and the prognosis of AITD in the Tunisian population. The rs7975232 and rs1801274 (R131H) polymorphisms were analyzed in 162 controls and 162 AITD patients (106 HT and 56 GD) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification of refractory mutation system-PCR (ARMS-PCR), respectively. No significant difference was demonstrated for the rs7975232 between patients and controls. However, a significant association was shown between the rs1801274 polymorphism and AITD or HT in the dominant (p = 0.03 or p = 0.01), codominant (p = 0.019 or p = 0.026) and allelic (p = 0.011 or p = 0.012) models. The rs7975232 was associated with the absence or the presence of anti-thyroglobulin antibody, with the age of AITD and GD patients during the first diagnosis (p = 0.01 and p = 0.009, respectively) and with a high T4 level at the beginning of HT disease. However, the FCGR2A gene polymorphism was associated with a low T4 level at the beginning of GD disease. In conclusion, this study indicates that only the FCGR2A variation could be related to AITD and HT susceptibility and that VDR and FCGR2A gene variations constitute factors to prognosticate the severity of AITD, HT and GD.

Defining and measuring 'eczema control': an international qualitative study to explore the views of those living with and treating atopic eczema.

BACKGROUND: Atopic eczema (also known as eczema) is a chronic, inflammatory skin condition that often afflicts patients' health and well-being. The Harmonising Outcome Measures for Eczema (HOME) initiative recommends that 'long-term control of eczema' is measured in all clinical trials 3 months or longer in duration. However, little has been published on what eczema control means to those living with or treating atopic eczema. OBJECTIVES: To (i) develop understanding of what eczema control means to patients, carers and clinicians and (ii) explore the feasibility and acceptability of different ways of measuring eczema control in the long term. METHODS: Online focus groups explored patients/carers experiences in the UK, the United States, the Netherlands, France, Sweden and Japan, and an international online survey gathered views of clinicians. The framework method was used to analyse the focus groups, and thematic analysis was used to analyse survey data. All findings were integrated into a theoretical framework to create overarching themes that cut across these diverse groups. RESULTS: Eight focus groups with patients (16 years+) and eight groups with carers of children took place (N = 97). Sixty-two people took part in the survey. Eczema control was described as a multifaceted construct involving changes in disease activity, the treatment and management of the condition and psychological, social and physical functioning. Patient/carer measurement allows personal accounts and frequent measurement, whilst clinician measurement was deemed less subjective. The burden on patients/carers and issues for analysing and interpreting data should be considered. CONCLUSIONS: This study formed the basis of judging the content validity and feasibility of measurement instruments/methods to assess control of eczema in clinical trials. This online approach to an international qualitative study is an example of how core outcome set developers with limited resources can engage with multiple stakeholder groups on an international basis to inform consensus meeting discussions.

The new 8th edition of TNM staging and its implications for skin cancer: a review by the British Association of Dermatologists and the Royal College of Pathologists, U.K.

The 8th edition of TNM (tumour, node and metastasis) has numerous and important changes compared with the 7th edition. Public Health England and the Royal College of Pathologists, U.K., have adopted the 8th edition of TNM (TNM8) published by the Union for International Cancer Control for skin cancer staging. These changes will have an impact on the management and commissioning of melanoma and nonmelanoma skin cancer (NMSC). The T1-T3 categories for NMSC staging require the clinician to measure the maximum dimension (usually diameter) of every potential invasive cancer. For squamous, basal and adnexal carcinomas, but not Merkel cell carcinoma (MCC), the T1-T3 categories are defined by new 20-mm and 40-mm divisions based on the maximum dimension of the lesion. In addition, new risk factors upstage T1 or T2 to T3. For melanoma, mitotic index no longer influences separation of pathological stage (pT1). There is a new, additional stratification level at 0·8-mm Breslow thickness. Subdivision pT1b, with a negative sentinel lymph node biopsy (SLNB) of pN0, is now stage IA compared with the previous IB. For MCC, SLNB is now included specifically in the pN staging system. The pT1 subdivision requires clinical information as to whether histologically involved nodes were clinically occult or detectable. For both melanoma and MCC the clinician must state whether the lymph nodes are occult or clinically detectable. Eyelid carcinoma continues to have a staging system different from that in general skin and the system is substantially revised in TNM8.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Professional knowledge of accident and emergency doctors on the management of dental injuries.

BACKGROUND: Accident and emergency (A&E) doctors are often the first to assess dental and dento-alveolar injuries. Early diagnosis and appropriate management is essential for a good long-term prognosis of restored dental aesthetics and function. OBJECTIVE: To evaluate A&E doctors' knowledge of the management of dental injuries, and appropriate onward referral. DESIGN AND SETTING: A cross-sectional survey using a questionnaire sent to A&E doctors of all grades at all nine A&E hospitals in South Wales over a consecutive five-month period. METHOD: Data relating to the level of knowledge of emergency management of dental trauma were analysed. The relationship between doctor's level of experience and previous training received on the management of common dento-alveolar trauma was considered. Data were analysed for Pearson correlation coefficients. RESULTS: The response rate to the questionnaire was 72% (n = 118). There was a negligible correlation between the career grade of the doctors and their knowledge of the management of dental injuries (r = 0.128, p < 0.001). A strong positive linear correlation (r = 0.928, p < 0.001) was found between those with prior training and their knowledge of dental injury management. CONCLUSIONS: The findings from this study suggest that A&E doctors have only partial knowledge of the management of dental injuries, though appropriate training can significantly increase knowledge.

Assessment of Euphorbia retusa and Pulicaria undulata activity against Leishmania major and Toxoplasma gondii.

Leishmaniasis and toxoplasmosis are parasitic protozoal diseases that pose serious health concerns, especially for immunocompromised people. Leishmania major and Toxoplasma gondii are endemic in Saudi Arabia and are particularly common in the Qassim Region. The present work was conducted to evaluate the in vitro antileishmanial and antitoxoplasmal activity of methanolic extracts and phytochemical fractions from two plants, Euphorpia retusa and Pulicaria undulata, which are ethnobotanical agents used to treat parasitic infection. Whole E. retusa and P. undulata plants were extracted with methanol and fractionated using petroleum ether, chloroform, ethyl acetate, n-butanol, and water and then were tested in vitro against L. major promastigote and the amastigote stages of T. gondii; the cytotoxicity of the extracts was tested against Vero cell line. The methanolic extracts of E. retusa and P. undulata exhibited promising antitoxoplasmal activity against T. gondii with EC50 values 5.6 and 12.7 µg mL-1, respectively. The chloroform fraction of P. undulata was the most potent, exhibiting an EC50 of 1.4 µg mL-1 and SI value of 12.1. It was also the most active fraction against both L. major promastigotes and amastigotes, exhibiting an EC50 of 3.9 and 3.8 µg mL-1 and SI values 4.4 and 4.5, respectively. The chloroform fraction from P. undulata is a very good candidate for the isolation of active antitoxoplasmal and antileishmanial ingredients; therefore, further phytochemical analysis for active compound isolation is highly recommended.

Evaluation of the in vitro antileishmanial activities of bioactive guided fractionations of two medicinal plants.

The organisms of the genus Leishmania are flagellated protozoan parasites and are the causative agents of leishmaniasis. This disease is a major health problem, especially in tropical countries. Currently, cutaneous leishmaniasis is treated by chemotherapy using pentavalent antimonials, but these drugs have serious organo-toxicity, drug resistance on several occasions, and low efficiency in controlling the infection. The present work is carried out to evaluate the in vitro antileishmanial activity of methanolic extracts and phytochemical fractions of two plants ethnobotanically used against leishmaniasis and skin infection, Calotropis procera and Rhazya stricta leaves against Leishmania major promastigote and amastigote stages and cytotoxicity against the Vero cell line. The leaves of C. procera and R. stricta were extracted with methanol and fractionated by petroleum ether, chloroform, ethyl acetate, n-butanol, and water. The methanolic extracts of the leaves of C. procera and R. stricta exhibited antileishmanial activity against L. major promastigotes with IC50 values of 66.8 and 42.4 µg mL-1, respectively. While their CC50 2.3 and 298 µg mL-1 and their SI 0.03 and 7.03 respectively. However, the fractionations of the methanolic extract of C. procera leaves revealed antiparasitic activity against both L. major promastigote and amastigote stages in vitro, which significantly increased with polarity with the exception of n-butanol. Hence the best activity was revealed by the water fraction (IC50 of 26.3 and 29.0 µg mL-1) for the two stages. In conclusion, further phytochemical investigation should be performed for the C. procera water extract in terms of antileishmanial active ingredient isolation that may enhance the possibility of avoiding toxic substances and overcome the low SI (1.1 and 1.01).

Modulation of ultraviolet-induced hyperalgesia and cytokine upregulation by interleukins 10 and 13.

1. Exposure to midrange ultraviolet radiation (UVB) is known to produce skin inflammation similar to sunburn. The aim of this study was to characterize the hyperalgesia and cytokine upregulation induced by UVB and their modulation by antiinflammatory cytokines. 2. Acute exposure of the dorsal skin of mice to UVB (200, 250 and 300 mJ cm(2)) resulted in a dose-dependent decrease in the latencies of the hot plate and tail flick tests, without evident signs of skin lesions. 3. The observed hyperalgesia displayed a biphasic temporal evolution with an acute phase (3 - 6 h) and a late (48 - 96 h) phase. 4. Exposure to UVB (300 mJ cm(2)) elicited significant upregulation of interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha and nerve growth factor (NGF), determined by ELISA in the exposed skin. This upregulation was more important during the acute phase of hyperalgesia. 5. Daily treatment of mice, with i.p. injections of either IL-10 or IL-13 (1.5, 7.5 and 15 ng in 100 microl saline) produced a dose-dependent attenuation of the UVB-induced hyperalgesia. 6. Treatment with the highest doses of either IL-10 or IL-13, produced significant attenuation of the levels of the cytokines and NGF by UVB, with relatively more pronounced effects by IL-13. 7. Acute exposure to moderate amounts of UVB results in a systemic hyperalgesia related to the upregulation of cytokine and NGF levels, since both were prevented by treatment with antiinflammatory cytokines.

Ossification of the penis: report of two cases.

Two patients with histologically proven penile ossification are reported from Africa, for the first time, in this communication. The aetiological causes in these patients are unclear and the pathogenesis of the condition is discussed.

Role of serum TRAIL level and TRAIL apoptosis gene expression in multiple sclerosis and relation to brain atrophy.

One of the presumed pathological mechanisms of multiple sclerosis (MS) is the failure of apoptosis of autoreactive T lymphocytes. This study aimed to determine the relationship of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA gene expression ratio and serum TRAIL levels with MS and brain atrophy. This study was conducted on 53 relapsing-remitting Egyptian MS patients and 25 matched healthy volunteers. The expression of TRAIL in peripheral blood lymphocytes was analyzed by reverse transcription polymerase chain reaction, serum levels of soluble TRAIL (sTRAIL) were determined by enzyme-linked immunosorbent assay and brain MRI measured "black holes" and the bicaudate ratio as a measure of brain atrophy in all patients. The serum TRAIL level was lower in MS patients compared to controls but no difference was seen in the TRAIL mRNA gene expression ratio. No significant correlation was detected between the serum TRAIL level and the TRAIL mRNA expression ratio in either group. No statistically significant correlation was found between serum TRAIL levels or the TRAIL mRNA expression ratio with the number of black holes or the bicaudate ratio on MRI. Apoptosis of T lymphocytes is decreased in MS patients, which could be useful when designing treatments. There was no difference in the TRAIL mRNA gene expression ratio between MS patients and controls.

Diagnostic utility of the oesophageal balloon distension test in the evaluation of oesophageal chest pain.

BACKGROUND: Oesophageal balloon distension test (EBDT) has been advocated for the evaluation of functional oesophageal noncardiac chest pain (NCCP), but its diagnostic utility remains unclear. AIM: To prospectively assess the diagnostic yield of EBDT in clinical practice and compare its yield with standard oesophageal tests. METHODS: Over a period of 6 years, patients with chest pain and negative cardiac work-up underwent sequential testing with endoscopy/biopsy, oesophageal manometry, 24 h pH study and EBDT to elucidate an oesophageal source for their symptoms. Patients with a definite abnormality, for example, erosive oesophagitis on oesophagogastroduodenoscopy (EGD) were designated as having positive test and excluded from further work up. RESULTS: Of 348 (m/f = 105/243) suspected NCCP patients, 16 (5%) were excluded; 332 (95%) underwent oesophageal testing. Among these, 48 (14%) had macro/microscopic oesophagitis on endoscopy, 7 (2%) had achalasia and 96 (28%) had excessive acid reflux (pH study). The remaining 181 (52%) patients underwent EBDT; 128 (37%) had oesophageal hypersensitivity. Chest pain was reproduced in 97/128 (75%) subjects. There were no adverse effects. CONCLUSIONS: Oesophageal testing can reveal an oesophageal source for chest pain in 86% of NCCP subjects. The majority (42%) of patients had gastro-oesophageal reflux disease (GERD). Oesophageal balloon distension test identified hypersensitivity in over one-third of subjects. The oesophageal balloon distension test provides useful diagnostic information and should be performed routinely in patients with NCCP after excluding GERD.

Investigation of esophageal sensation and biomechanical properties in functional chest pain.

BACKGROUND: There is limited and conflicting data regarding the role of esophageal hypersensitivity in the pathogenesis of functional chest pain (FCP). We examined esophageal sensori-motor properties, mechanics, and symptoms in subjects with FCP. METHODS: Esophageal balloon distension test was performed using impedance planimetry in 189 (m/f = 57/132) consecutive subjects with non-cardiac, non-reflux chest pain, and 36 (m/f = 16/20) healthy controls. The biomechanical and sensory properties of subjects with and without esophageal hypersensitivity were compared with controls. The frequency, intensity, and duration of chest pain were assessed. KEY RESULTS: One hundred and forty-three (75%) subjects had esophageal hypersensitivity and 46 (25%) had normal sensitivity. Typical chest pain was reproduced in 105/143 (74%) subjects. Subjects with hypersensitivity demonstrated larger cross-sectional area (P < 0.001), decreased esophageal wall strain (P < 0.001) and distensibility (P < 0.001), and lower thresholds for perception (P < 0.01), discomfort (P < 0.01), and pain (P < 0.01) compared to those without hypersensitivity or healthy controls. Chest pain scores (mean +/- SD) for frequency, intensity and duration were 2.5 +/- 0.3, 2.2 +/- 0.2, and 2.2 +/- 0.2, respectively, and were similar between the two patient groups. CONCLUSIONS & INFERENCES: Seventy-five per cent of subjects with FCP demonstrate esophageal hypersensitivity. Visceral hyperalgesia and sensori-motor dysfunction of the esophagus play a key role in the pathogenesis of chest pain.

Kinetics and thermodynamics of adsorption of cadusafos on soils.

Laboratory batch experiments were designed to study the adsorption of cadusafos on two types of soils: clay loamy and sandy, collected from two regions around the Nile Delta in Egypt. The adsorption process is fast reaching equilibrium in 60 min, decreases with increasing soil mass and independent on pH in the range 3-11. The experimental results were well fitted to linear partition model, and to a lesser extent to Freundlich non-linear model, Temkin and Dubinin-Radushkevich models. However, the 1/n parameter of Freundlich relation being of value around one supported the linear partition model. The K(d) values obtained from the linear model were 4.20 and 2.74 L/g for sandy and clay soils, respectively. The energy of adsorption calculated from D-R equation was 4.36 and 5.04 kJ/mol for clay and sandy soils, respectively, in the range assigned to physical forces. This kind of weak interaction, together with pH-independence implies that for the studied soils the organic content (that is higher in the clay soil) is not a major parameter in the adsorption of cadusafos. Water movement taking place more readily in sandy soil caused increased uptake relative to the case of clay soil. The higher uptake in sandy soil denotes that cadusafos may be mobile with a potential to leach and eventually pollutes ground water and surface water. The kinetics of adsorption was well fitted by the pseudo-second order equation. The intraparticles diffusion is of lower significance in case of sandy soil than in clay soil. Thermodynamic parameters indicated that the adsorption is spontaneous, endothermic accompanied by increase in entropy.

Tertiary lymphoid tissues generate effector and memory T cells that lead to allograft rejection.

Tertiary lymphoid tissues are lymph node-like cell aggregates that arise at sites of chronic inflammation. They have been observed in transplanted organs undergoing chronic rejection, but it is not known whether they contribute to the rejection process by supporting local activation of naïve lymphocytes. To answer this question, we established a murine transplantation model in which the donor skin contains tertiary lymphoid tissues due to transgenic expression of lymphotoxin-alpha(RIP-LT alpha), whereas the recipient lacks all secondary lymphoid organs and does not mount primary alloimmune responses. We demonstrate in this model that RIP-LT alpha allografts that harbor tertiary lymphoid tissues are rejected, while wild-type allografts that lack tertiary lymphoid tissues are accepted. Wild-type allografts transplanted at the same time as RIP-LT alpha skin or 60 days later were also rejected, suggesting that tertiary lymphoid tissues, similar to secondary lymphoid organs, generate both effector and memory immune responses. Consistent with this observation, naive T cells transferred to RIP-LT alpha skin allograft but not syngeneic graft recipients proliferated and differentiated into effector and memory T cells. These findings provide direct evidence that tertiary lymphoid structures perpetuate the rejection process by supporting naïve T-cell activation.

Topical tacrolimus in dermatology.

Tacrolimus and cyclosporin A are potent immunosuppressants that are used systemically to treat several inflammatory skin conditions successfully. They differ in their structure and tacrolimus is 10-100 times more potent than cyclosporin A. They have similar side-effects. They have been used topically in various clinical studies. Topical cyclosporin A is largely ineffective whereas topical tacrolimus is effective in treating atopic dermatitis. Topical tacrolimus has not been studied sufficiently in treating psoriasis although it has been used successfully in allergic contact dermatitis, erosive mucosal lichen planus and pyoderma gangrenosum.

Torsades de pointes with terfenadine ingestion.

Torsades de pointes (TDP) is a ventricular tachycardia that can deteriorate into ventricular fibrillation. TDP has been associated with terfenadine use in cases of liver disease, electrolyte abnormalities, concomitant administration of drugs that inhibit cytochrome P-450, or deliberate overdose. This report describes the first case of TDP in a healthy patient taking the recommended therapeutic dosage of terfenadine.

Kawasaki disease: an update.

Kawasaki disease is one of the commonest vasculitides seen in children. It presents with prolonged fever and a polymorphic exanthem. It is a major cause of acquired heart disease in western society. Its exact cause is not known, but exposure to a superantigen has been suggested as a possible aetiological factor. Diagnosis of Kawasaki disease still relies on clinical criteria (Table 1) and investigations are done mainly to exclude other diseases and to detect early or established cardiac complications. Coronary complications can be reduced significantly by the use of intravenous immunoglobulin therapy combined with oral aspirin. The serious consequences of Kawasaki disease require a heightened awareness of this condition when dealing with childhood exanthems.

Use of a bilingual medical history questionnaire in the emergency department.

STUDY OBJECTIVE: To demonstrate that a complete and rapid clinical history can be obtained using a self-administered, bilingual questionnaire. DESIGN: A post-test experimental design was used to evaluate time spent obtaining the history and information completeness for the two groups. SETTING: Urban county emergency department. PARTICIPANTS: All patients were non-English-speaking Hispanic women who presented with gynecologic complaints. METHODS: Fifty-five patients completed a history questionnaire in Spanish on a form that displayed their responses in English on the carbon copy. In the control group, a history was obtained using a bilingual interpreter. RESULTS: Average completion time was significantly less (t = 14.38; P < .0001) for the experimental group (chi 2 = 5.67 minutes; SD, 1.89) than for controls (chi 2 = 14.58 minutes; SD, 4.19). There was no statistical difference in review criteria for documentation between groups. CONCLUSION: Using a bilingual questionnaire to obtain a clinical history results in more rapid patient evaluation without affecting the quality of information obtained.