A European-Japanese study on peach allergy: IgE to Pru p 7 associates with severity.

BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.

Component-resolved diagnosis and beyond: Multivariable regression models to predict severity of hazelnut allergy.

BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double-blind placebo-controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.

Invasive dermatophyte infection with Trichophyton interdigitale is associated with prurigo-induced pseudoperforation and a signal transducer and activator of transcription 3 mutation.

Invasive dermatophyte infection, with extension beyond the dermis, in immunocompetent hosts is exceptionally rare. Dermatophytes are keratinophilic and are usually confined to the stratum corneum, hair and nails. Susceptibility to dermatophyte infections is incompletely understood, but inherited mutations in key signalling pathways of the innate immune system have been identified. We report the first case of an invasive dermatophyte infection associated with abrupt onset of a prurigo-induced pseudoperforation and a loss-of-function mutation in signal transducer and activator of transcription 3 (STAT3).

Corticosteroids in management of anaphylaxis; a systematic review of evidence.

SUMMARY: As anaphylaxis is a medical emergency, there are no randomized controlled clinical trials on its emergency management. Therefore, current guidelines are mostly based on data from observational studies, animal and laboratory studies. Although epinephrine is the mainstay of recommended treatment, corticosteroids are also frequently used. This review evaluates the evidence on the use of corticosteroids in emergency management of anaphylaxis from published human and animal or laboratories studies. Thirty original research papers were found with 22 human studies and eight animal or laboratory studies. The average rate of corticosteroid use in emergency treatment was 67.99% (range 48% to 100%). Corticosteroids appear to reduce the length of hospital stay, but did not reduce revisits to the emergency department. There was no consensus on whether corticosteroids reduce biphasic anaphylactic reactions. None of the human studies had sufficient data to compare the response to treatment in different treatment groups (i.e. corticosteroids, epinephrine, antihistamines). Animal studies demonstrated that corticosteroids act through multiple mechanisms. These modulate gene expression, with effects becoming evident 4 to 24 hours after administration. A much quicker response has been detected within 5 to 30 minutes, through blockade of signal activation of glucocorticoid receptors independent of their genomic effects. Therefore, we conclude that there is no compelling evidence to support or oppose the use of corticosteroid in emergency treatment of anaphylaxis. However, based on the available data, it appears to be beneficial and there was no evidence of adverse outcomes related to the use of corticosteroids in emergency treatment of anaphylaxis.

The EuroPrevall outpatient clinic study on food allergy: background and methodology.

BACKGROUND: The EuroPrevall project aimed to develop effective management strategies in food allergy through a suite of interconnected studies and a multidisciplinary integrated approach. To address some of the gaps in food allergy diagnosis, allergen risk management and socio-economic impact and to complement the EuroPrevall population-based surveys, a cross-sectional study in 12 outpatient clinics across Europe was conducted. We describe the study protocol. METHODS: Patients referred for immediate food adverse reactions underwent a consistent and standardized allergy work-up that comprised collection of medical history; assessment of sensitization to 24 foods, 14 inhalant allergens and 55 allergenic molecules; and confirmation of clinical reactivity and food thresholds by standardized double-blind placebo-controlled food challenges (DBPCFCs) to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple and peach. RESULTS: A standardized methodology for a comprehensive evaluation of food allergy was developed and implemented in 12 outpatient clinics across Europe. A total of 2121 patients (22.6% <14 years) reporting 8257 reactions to foods were studied, and 516 DBPCFCs were performed. CONCLUSIONS: This is the largest multicentre European case series in food allergy, in which subjects underwent a comprehensive, uniform and standardized evaluation including DBPCFC, by a methodology which is made available for further studies in food allergy. The analysis of this population will provide information on the different phenotypes of food allergy across Europe, will allow to validate novel in vitro diagnostic tests, to establish threshold values for major allergenic foods and to analyse the socio-economic impact of food allergy.

Autosomal recessive chronic granulomatous disease presenting with cutaneous dermatoses and ocular infection.

Dermatoses such as eczematous dermatitis and cutaneous infection are recognized presentations of primary immunodeficiency (PID). However, atopic dermatitis affects approximately 10% of infants, and cutaneous infections are not uncommon in children, therefore the challenge for the dermatologist is to distinguish the few patients that have PID from the many that do not. We report on a 6-year-old girl who was ultimately diagnosed with autosomal recessive chronic granulomatous disease (AR-CGD) after presenting to various hospitals with dermatitis, scalp plaques recalcitrant to treatment, and recurrent infections over a 3-year period, and describe some aspects of her diagnosis and management. This report highlights the importance of considering rare disorders such as AR-CGD in the differential diagnosis of recurrent or recalcitrant dermatological infections in children.

Penile granulomatosis presenting as pseudoangioedema.

Many conditions may present as angioedema. We report a case of a 46 year-old man presenting with intermittent episodes of penile swelling. Following a series of investigations, he was diagnosed with genital granulomatosis. Ano-genital granulomatosis is a rare chronic inflammatory condition and that can present as diffuse penile, scrotal, vulvar or ano-perineal swelling with non-caseating non-necrotising granulomas on histology.

Resection margins, lymph node harvest and 3 year survival in open and laparoscopic colorectal cancer surgery; a prospective cohort study.

INTRODUCTION: Laparoscopic colorectal cancer surgery has been gaining popularity in the last decade. However, there are concerns about adequate lymph node dissection and safe resection margins in laparoscopic colorectal cancer surgery. This study was aimed at comparing the lymph node (LN) clearance and surgical resection margins and 3-year survival for open and laparoscopic colorectal cancer surgery. METHOD: A pre-tested interviewer administered questionnaire was used to assess the adoption of the laparoscopic approach by Sri Lankan surgeons. Data was collected prospectively from patients who underwent open or laparoscopic colorectal cancer surgery at the University Surgical Unit of the National Hospital of Sri Lanka from April 2016 to May 2019. The histopathology records were analysed to determine the longitudinal and circumferential resection margins(CRM) and the number of lymph nodes harvested. The resection margins were classified as positive or negative. The total number of LN examined was evaluated. Presence of local recurrence and liver metastasis was determined by contrast enhanced CT scan during 3-years of follow up. Chi square, T test and z test for proportions were used to compare CRM, LN harvest and survival rates between the groups. RESULTS: Of the surgeons interviewed only 11 (18.4%) performed laparoscopic colorectal cancer surgery. A total of 137 patients (83 males and 54 females) were studied. Eighty-one procedures were laparoscopic and 56 procedures were open. All patients had clear longitudinal resection margins. Seventy-eight patients in the laparoscopic group (96%) and 51 patients (91%) in the open group had clear CRM (p > 0.05). A total of 2188 LNs (mean 15.9) were resected in all procedures. Six-hundred-eighty-nine lymph nodes were removed during open procedures (mean 12.3, SD 0.4) and 1499 (mean 18.5, SD 0.6) were removed during laparoscopy (p < 0.05). At 3 years follow-up the disease-free survival in the laparoscopic and open colon cancer patients was 27/41 (65.8%) and 16/29 (55.1%) respectively (p = 0.35). Disease free survival in the laparoscopic and open rectal cancer patients was 23/38 (60.5%) and 13/25 (52.0%) respectively (p = 0.40). Four patients were lost during follow-up. DISCUSSION AND CONCLUSION: CRM was comparable in the two groups. Laparoscopic group had a significantly higher LN harvest. Three-year survival rates were similar in the two groups. Acceptable results can be obtained with laparoscopic colorectal cancer surgery.

IgE-mediated allergy to local anaesthetics: separating fact from perception: a UK perspective.

Local anaesthetic (LA) agents have been routinely used in dentistry, ophthalmology, minor surgery, and obstetrics since the late nineteenth century. Reports relating to adverse reactions and LA allergy have appeared in the published literature for several years. However, the incidence of true, IgE-mediated LA allergy remains uncertain and is presumed to be very low. We critically reviewed the English language literature on suspected LA allergy and its investigation with the aim of estimating the reported prevalence and analysing the role of different tests currently used to identify and confirm LA allergy. Twenty-three case series involving 2978 patients were identified and analysed. Twenty-nine of these patients had true IgE-mediated allergy to LA, thus confirming the reported prevalence of LA allergy in large series to be <1% (0.97%). The protocols used in the investigation of these patients have also been discussed. Evidence from this review confirms the rarity of IgE-mediated allergy to LA and supports an investigation strategy based on using the clinical history to select patients for skin testing and challenge. We believe that such a triage process would alleviate pressures on allergy services without compromising patient safety.

NOD2 polymorphisms in clinical phenotypes of common variable immunodeficiency disorders.

Common variable immunodeficiency disorders (CVIDs) are a heterogeneous group of diseases characterized by hypogammaglobulinaemia and consequent susceptibility to infection. CVID patients commonly develop a variety of additional manifestations for which the causative factors are not fully understood. Two such manifestations are granulomatous disease and enteropathy. Because the ability to predict complications would aid clinical management, we continue to search for possible disease modifier genes. NOD2 acts a microbial sensor and is involved in proinflammatory signalling. Particular mutations of the NOD2 gene are associated with Crohn's disease including gly908arg, leu1007finsc and arg702trp polymorphisms. We hypothesized that NOD2 polymorphisms may be a disease modifier gene towards an enteropathic or granulomatous phenotype within CVIDs. Sequence-specific primers returned genotypes for 285 CVID patients from centres across the United Kingdom and Europe. We present the frequencies of the different phenotypes of patients within our international cohort. Arg702trp polymorphisms were significantly less frequent than wild-type (WT) (P = 0·038) among international CVID patients with splenomegaly. Gly908arg polymorphisms were more prevalent than WT in UK patients with autoimmune disorders (P = 0·049) or enteropathy (P = 0·049). NOD2 polymorphisms were not more prevalent than WT in CVID patients with clinical phenotypes of granulomata. UK allele frequencies of 0·014, 0·056 and 0·026 were found for gly908arg, arg702trp and leu1007finsc NOD2 polymorphisms, respectively. These do not differ significantly from UK immunocompetent controls confirming, as expected, that in addition these NOD2 polymorphisms do not confer susceptibility to CVIDs per se.

National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study.

BACKGROUND: The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO-containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX). As a consequence the risk of anaphylaxis to neuromuscular blocking agents (NMBA) will be increased. METHODS: National PHO consumptions were derived from the United Nations International Narcotics Control Board (INCB) database. IgE and IgE antibodies to PHO, MOR, SUX and P-aminophenyl-phosphoryl choline (PAPPC) were measured in sera from atopic individuals, defined by a positive Phadiatop test (>0.35 kU(A)/l), collected in nine countries representing high and low PHO-consuming nations. RESULTS: There was a significant positive association between PHO consumption and prevalences of IgE-sensitization to PHO and MOR, but not to SUX and PAPPC, as calculated both by exposure group comparisons and linear regression analysis. The Netherlands and the USA, did not have PHO-containing drugs on the markets, although the former had a considerable PHO consumption. Both countries had high figures of IgE-sensitization. CONCLUSION: This international prevalence study lends additional support to the PHO hypothesis and, consequently, that continued use of drugs containing this substance should be seriously questioned. The results also indicate that other, yet unknown, substances may lead to IgE-sensitization towards NMBAs.

The role of skin-homing T cells in extrinsic atopic dermatitis.

BACKGROUND: T cells that express Cutaneous Lymphocyte-Associated antigen (CLA) have the potential of migrating to the skin, and are hypothesized to play a role in cutaneous atopic disease. AIM: To investigate the immune phenotype and cytokine responses to Der p 1 stimulation of CLA+ T cells in extrinsic atopic dermatitis (EAD). DESIGN: In vitro testing, with controls. METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from EAD patients (n=27) and non-atopic healthy individuals (n=22). Phenotypic analysis of naive, CLA+ and non-CLA+ memory/effector CD4+ and CD8+ T cells used markers of cell activation, differentiation, adhesion, apoptosis and chemokine receptor expression. Cytokine responses in these cells were studied following Der p 1 stimulation. RESULTS: CLA+ T cells from EAD patients expressed significantly higher levels of CD25, HLA-DR, CD38, CD71, CXCR1, CXCR2 and lower levels of bcl2, CCR5, CCR7, CXCR3, and CD62L (p<0.05). DISCUSSION: In EAD patients, CLA+ T cells express increased levels of markers associated with activation, adhesion and apoptosis, show differences in the level of expression of differentiation markers and display a distinct chemokine receptor preference, compared with cells from healthy controls. These data suggest a significant role for CLA+ T cells in the pathogenesis of cutaneous atopic disease.

Patterns of disease among adults hospitalized with dengue infections.

BACKGROUND: Recent years have seen an increase in dengue infections among adults in Sri Lanka, with similar trends seen in many other countries. Data on the natural history and outcome of dengue in adults are quite limited. AIM: To study clinical and laboratory findings in adult dengue patients hospitalized in Sri Lanka during a recent major dengue epidemic. DESIGN: Prospective observational study. METHODS: Clinical, laboratory and demographic information were collected from adult patients with confirmed dengue infections (n = 108) treated in a general medical ward in Sri Lanka from 24 April to 31 July 2004. RESULTS: There were 68 male and 40 female patients, mean age 26.6 years. Dengue fever (DF) was seen in 33 (30.6%) and dengue haemorrhagic fever (DHF) in 75 (69.4%). Of the 37 (34.3%) with primary dengue infections, 19 (51.4%) developed DF and 18 (48.6%) developed DHF. Overall, 42 patients (38.9%) had bleeding manifestations. These adults showed differences in clinical and laboratory findings, disease severity and mortality, compared to children seen during the same epidemic. Secondary dengue infections were significantly associated with development of severe disease (OR 5.0, 95%CI 1.9-13.5, p < 0.001). Mortality was 3.7%. DISCUSSION: Pooling data on adult dengue patients from different regions should help us to understand the natural history of disease in this group. It would also help in developing evidence-based treatment guidelines and allocating limited and scarce health resources. Our data contribute towards this goal.

Pathogenesis of liver involvement during dengue viral infections.

The dengue virus can infect many cell types and cause diverse clinical and pathological effects. We describe clinical and experimental observations that suggest that liver involvement occurs during dengue infections, and we outline the possible role played by host immune responses in this process.

Pregnancy outcomes of antiphospholipid syndrome: In a low resource South Asian setting.

PROBLEM: Antiphospholipid syndrome is associated with recurrent pregnancy loss, and specific treatment improves pregnancy outcome. Laboratory diagnosis is limited in South Asia. We assessed management outcomes of definite/probable antiphospholipid syndrome treated at a tertiary centre in Sri Lanka. METHOD: Descriptive cross-sectional study of pregnancy outcomes with heparin and aspirin therapy. OUTCOME MEASURES: miscarriage, intrauterine death and live birth when compared to previous untreated pregnancies. RESULTS: Of 646 gestations in 145 women, 146 (22.6%) received specific treatment. In the preceding pregnancies without specific treatment, the rates of miscarriage, late fetal loss, stillbirth and live birth were 60%, 26%, 8% and 7%, respectively. Following specific treatment with low-dose aspirin ± low-molecular weight heparin in 146 pregnancies (145 women), the rates of miscarriage, late fetal loss, stillbirth and live birth were 14%, 10%, 3% and 74%, respectively. Mean birth weight was 2.54 ± 0.62 kg, preterm births complicated 32 (29.6%) with a mean gestational age at delivery 33.7 ± 2.6 weeks, with three neonatal deaths. Maternal complications were: pre-eclampsia 16 (10.9%), gestational diabetes 28 (19.2%), antepartum haemorrhage in 1 patient. Only 73/145 (50.3%) women had laboratory confirmation of antiphospholipid syndrome, while others were treated empirically. Live births in diagnosed vs. empiric treatment - 80.8% vs. 67.1%. CONCLUSION: Pregnant women with clinical antiphospholipid syndrome when treated with low-dose aspirin and heparin, the live birth rate of 7% in the previous pregnancy resulted in live births of 74% in a resource limited South Asian setting.

Excessive fibrinolysis: the coagulopathy following Merrem's hump-nosed viper (Hypnale hypnale) bites.

In 56 patients with proven hump-nosed viper (Hypnale hypnale) bites, 12 (21.4%) developed continued oozing of blood from the site of the bite and a prolonged clotting time. Further investigations showed low fibrinogen levels and increased fibrinogen degradation products in plamsa. The bleeding time, platelet count, prothrombin time, and partial thromboplastin time with kaolin were normal. The bite of this snake can be complicated with a coagulopathy in which excessive fibrinolysis seems to be the main abnormality.

Reporting notifiable diseases: methods for improvement, attitudes and community outcome.

Notification is an important source of health information. However, it suffers from the serious limitation of under-reporting, especially in 'third world' countries. The aims of this study were to assess the impact of a special notification nurse and ward notification register on the rate of notification from a general medical unit, the knowledge and attitudes of intern medical officers regarding notification, and the community outcome of notification in a Sri Lankan setting. Overall, appointment of a special nurse improved notification rates from 9.7% to 62.1%, and the addition of a special ward notification register further improved the rate to 95.1% The results also indicated that, although a majority of intern medical officers were aware of notifiable diseases and the importance of notification, only a few of them always notified notifiable diseases. One of the main reasons given for this was that the majority of them felt that no useful action was taken on notifications by the preventive health authorities, a view that was held because there was no feedback information regarding the notifications. However, during the period of this study nearly 80% of all notifications were successfully investigated by the relevant medical officer of health office. The appointment of a nurse dedicated to notification and introduction of a ward notification register could greatly improve notification rates. Better communication between curative and preventive health sectors would improve attitudes of doctors regarding notification.

Use of early aspirin in suspected acute myocardial infarction by General Practitioners in Sri Lanka.

Early low dose aspirin therapy is beneficial in myocardial infarction (MI). This study investigated the use of early aspirin therapy in patients with suspected MI by General Practitioners (GP). Patients with MI who were referred to our unit by GPs were studied to see whether aspirin therapy had been initiated before referral. A questionnaire was sent to GPs to test their attitudes and practices regarding early aspirin therapy in suspected MI. Our results indicate that few patients with MI had been given early aspirin therapy. Only a minority of GPs were aware of the benefits of early aspirin therapy in MI, and very few prescribed it. Even when it was prescribed, the dose and route of administration were wrong in most instances.

Changing prescribing behaviour: early low dose aspirin in suspected acute myocardial infarction.

INTRODUCTION: Evidence obtained from large clinical trials would be of limited value, if such evidence does not reach the provider of care, and even when it reaches them, if they do not change their clinical behaviour accordingly. The aim of our study was to assess the effectiveness of intervention, aimed at changing prescribing behaviour of general practitioners (GPs) with regard to early low dose aspirin in patients with suspected acute myocardial infarction (MI). METHODS: A total of 96 GPs were sent a questionnaire assessing their knowledge and practices with regard to use of low dose aspirin in acute MI in November 1995 (Q1), June 1996 (Q2) and September 1996 (Q3). An 'intervention' was carried out with a view to changing GP prescribing of low dose aspirin is suspected acute MI after the first two questionnaires were sent. RESULTS: The results of this study seem to show that an intensive 'intervention' achieved success in changing prescribing behaviour of GPs. Although the intervention resulted in a overall significant increase in the prescription of low dose aspirin in suspected acute MI, it was seen that in the GPs who were aged <40 years the success achieved with the 'intervention' was greater when compared with that seen in those older than 40 years. CONCLUSION: Dissemination of information on new practices in medicine are important in the process of continuing medical education for doctors. A 'personal intervention' such as is described in this study seems to have good effect.