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Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care. ispartof: ALLERGY vol:74 issue:7 pages:1219-1236 ispartof: location:Denmark status: published

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional., EAACI -European Academy of Allergy and Clinical Immunology(undefined), info:eu-repo/semantics/acceptedVersion

The prevalence of respiratory allergic diseases has been increasing in Southern Africa both in urban and in rural environments. Various factors may contribute toward this situation, namely, exposure to aeroallergens, such as grass pollens and house dust mites. However, other irritant environmental triggers, such as exposure to tobacco smoke and certain indoor and outdoor fumes, may also play a relevant part. Furthermore, certain parasitic and mycobacterial infections may act as allergic disease risk modifiers, although such an influence should be confirmed. Finally, certain cultural and socioeconomic factors may also influence accessibility to healthcare and adherence to treatment of these diseases. Keywords: asthma, rhinitis, prevalence, Southern Africa

Rhinosinusitis is a significant health problem, causing significant morbidity and resulting in considerable financial cost. Some patients suffer persistent or recurrent symptoms despite receiving optimal medical and surgical treatment. Rhinosinusitis can be acute or chronic, acute often due to viral or bacterial infections and chronic which is classified into chronic with nasal polyposids or chronic rhinosinusitis without nasal polyposis. The disease affects the quality of life significantly and presents a significant burden on health costs globally. The anatomical linkage of the nose with the paranasal sinuses facilitates a common pathology in both organs. Chronic rhinosinusitis (CRS) has heterogeneous origins, including viruses, bacteria, fungal infections, anatomical abnormalities, polyposis, and aspirin sensitivity. Other conditions such as human immunodeficiency virus acquired immunodeficiency and cystic fibrosis may also be predisposing factors. Nasal polyposis is often associated with increased numbers of Th2 lymphocytes, fibroblasts, goblet cells, mast cells, and eosinophils, with upregulation of IL-13 and the release of specific IgE to staphylococcal enterotoxins. There is recent evidence that antibiotic treatment may not be as effective as higher doses of intranasal steroids in acute uncomplicated rhinosinusitis, especially in those with allergic disease. The broad inflammatory basis of the pathology of CRS also reveals a cellular infiltrate theoretically suppressed by intranasal corticosteroids. This has been confirmed in recent clinical studies of CRS with or without polyps. A treatment approach based on such studies reported in the European Position Paper on Rhinosinusitis guidelines and a guideline summary are presented. The current review represents the proceedings of a session (3 talks) by the authors at the first Middle East-Asia Allergy, Asthma, Immunology Congress in 2009. Keywords: rhinosinusitis, nasal polyposis, corticosteroids

Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide. Keywords: urticaria, angioedema

Background. Hereditary angio-oedema (HAE) is an autosomal dominant condition caused by a deficiency in the C1-esterase inhibitor protein, resulting in increased bradykinin release. It presents clinically with recurrent attacks of angio-oedema, commonly affecting the limbs, face, upper airway and gastrointestinal tract. Little is known about this condition in sub-Saharan Africa. Objectives. To analyse and report on the clinical presentation and treatment of patients with HAE in the Western Cape Province, South Africa. Methods. A retrospective analysis was conducted on a series of 60 cases of HAE seen between 2010 and 2015 at the Allergy Diagnostic and Clinical Research Unit, University of Cape Town Lung Institute, and the Allergy Clinic at Groote Schuur Hospital, Cape Town. The findings in 43 cases of type 1 HAE are described. Parameters assessed included age, gender, age of diagnosis, duration of illness, family history, identifiable triggers, average duration of attack, number of attacks per year and type of attack. Results. A total of 43 patients were included in this study. Of these, 65.1% (28/43) were female. The median age at diagnosis was 20 years (interquartile range (IQR) 10 - 27) and the median duration of illness 10.5 years (IQR 6 - 22). Of the patients, 62.8% (27/43), 32.6% (14/43) and 4.7% (2/43) were of mixed ancestry, white and black African, respectively; 51.2% (22/43) were index cases, with the remaining 48.8% (21/43) diagnoses via family member screening, 12 families making up the majority of the cohort. The mean (standard deviation) duration of an acute attack was 49 (25.8) hours, and 64.3% (27/42), 71.4% (30/42), 14.3% (6/42) and 88.1% (37/42) of patients experienced facial or upper airway, abdominal, external genitalia and limb attacks, respectively. Danazol for long-term prophylaxis was used in 21 patients, while C1-inhibitor concentrate (Berinert) was accessed for short-term prophylaxis in only four patients. Acute life-threating attacks were treated with fresh frozen plasma in 11 patients, and only four accessed icatibant. The mortality rate for the period 2010 - 2015 was 4.5% (2/43). The prevalence of HAE in the Western Cape was estimated to be 1:140 000. Conclusions. HAE occurs in South Africans of all ethnicities, and life-threatening attacks occur in almost two-thirds of patients. Despite limited therapeutic options and very limited access to gold-standard therapies available in the developed world, our mortality rate is very low, with both the deaths related to inability to access emergency treatment rapidly.

Background: Nonsedating H1-antihistamines are recommended for the treatment of urticaria by the recent EAACI/GA2LEN/EDF guidelines. The aim of this study was to compare the efficacy, after 4 weeks of treatment, with levocetirizine 5 mg and desloratadine 5 mg, both once daily in the morning, in symptomatic chronic idiopathic urticaria (CIU) patients. Methods: This multi-center, randomized, double-blind study involved 886 patients (438 on levocetirizine and 448 on desloratadine). The primary objective was to compare their efficacy on the mean pruritus severity score after 1 week of treatment. Mean pruritus severity score over 4 weeks and pruritus duration score, number and size of wheals, mean CIU composite score (sum of the scores for pruritus severity and numbers of wheals), quality of life, and the patient’s and investigator’s global satisfaction with treatment, were secondary efficacy measures. Results: Levocetirizine led to a significantly greater decrease in pruritus severity than desloratadine over the first treatment week; mean pruritus severity scores of 1.02 and 1.18 for levocetirizine and desloratadine, respectively (P

Atopy in defined as an inherited predisposition to produce immunoglobulin E (IgE) antibodies in response to natural exposure to minute quantities of environmental allergens, manifesting clinically with atopic diseases. These include food allergy, eczema, asthma, seasonal and persistent rhinitis and urticaria. Not all allergic diseases are atopic in nature.Examples of non-atopic allergic diseases include allergy to drugs (e.g. penicillin), venoms (e.g. bee sting allergy) and some occupational allergies.The cornerstone of the clinical diagnosis of any atopic disease in a detailed history, followed by specific IgE sensitivity testing. This requires knowledge of the patient's presenting symptoms, his family history and a careful knowledge of the environment in which the patient lives or works.History taking is time consuming, but always rewarding and the most cost effective part of the clinical evaluation. The history guides the clinician as to the most appropriate clinical or laboratory test and can ...

Complement component C6 is one of five terminal complement components incorporated into the membrane attack complex. Complete deficiency of C6 (C6Q0) leads to an increased susceptibility to Neisseria meningitidis infections, and affected individuals typically present with recurrent meningococcal disease. There is a relatively high prevalence of C6Q0 in the Western Cape, South Africa and three frameshift mutations have previously been described to be responsible for C6Q0 in this area—879delG, 1195delC, and 1936delG (current nomenclature). We have now genotyped a further nine genetically independent individuals with C6Q0, confirming previous reports that the most common defect in the Western Cape is 879delG. Moreover, we report the first identification of the 878delA mutation within the Western Cape, which has previously only been reported in individuals of African descent living in the United States or Europe. We also investigated the genotype of an Irish C6Q0 individual and her sibling, and report two previously undescribed mutations. One mutation alters a tyrosine codon to a stop codon within exon 10. The second mutation is within the 5′ donor splice site of intron 3, and would, in all probability, disrupt splicing. These two mutations were shown to segregate independently. We also discuss the nomenclature for reporting C6 and C7 gene mutations, as the current nomenclature does not follow the recognised guidelines.

Objective To obtain a current understanding of the mechanisms, clinical indications, efficacy, and safety of sublingual immunotherapy (SLIT) for the treatment of children and adults with allergic rhinitis, asthma, and allergic conjunctivitis. Methods A MEDLINE and Index Medicus search for peer-reviewed articles on SLIT was performed. Results Since the approval of SLIT by the World Health Organization in 1988, the efficacy and safety of SLIT have been confirmed in several new double-blind, placebo-controlled studies for monosensitized patients who are allergic to house dust mites, grass pollens, ragweed, and birch pollen. Documented immunologic responses to SLIT have included a decrease in serum eosinophilic cationic protein and interleukin 13 (IL-13) levels, an elevation in IL-12 levels, a reduction in late-phase responses, and increases in IgG4/IgE ratios. A Cochrane review of 22 studies confirmed the efficacy and safety of SLIT for patients with allergic rhinitis. A long-term asthma study showed sustained efficacy 5 years after discontinuing the vaccine. The safety of SLIT has been confirmed in postmarketing studies, and severe systemic adverse effects have never been reported. In view of its safety profile, SLIT is taken by the patient at home (away from specialized centers), and no specialized resuscitation facilities are required. Conclusion SLIT is a safe and effective therapeutic option for patients with allergic rhinitis and asthma. Because of its efficacy, safety, and ease of administration, it has been accepted in Europe, Southern Africa, Australasia, Southeast Asia, and the Middle East as a promising therapeutic option that can significantly alter the natural history of allergic disease without the risks of injection immunotherapy.

In 2004 the World Allergy Organization’s Specialty and Training Council conducted a survey of World Allergy Organization (WAO) member societies to obtain information about the status of the specialty of allergy worldwide. Responses were received from 33 countries, representing a population of 1.39 billion people, of whom it was estimated that 22% may suffer from some form of allergic disease. Allergy was reported by 23 respondents to be a certified or accredited specialty in their country, and the number of certified allergists per head of population ranged from 1:25 million to 1:16,000. Allergists were ranked as the fifth most likely clinicians to see cases of allergic asthma, third most likely to see allergic rhinitis, and fourth most likely to see eczema or sinusitis. Nine countries only reported that children with allergic diseases would be seen by a pediatrician with appropriate training. The survey results highlight a pressing need for the development of allergy services worldwide.

Summary Background Epidemiological studies have shown an inverse relation of mycobacterial infection and the frequency of allergic diseases and asthma. Recent evidence suggests that allergic inflammation may be inhibited in the presence of chronic and persistent infections, such as that by Mycobacterium tuberculosis (MTB). The relation of tuberculin skin test (TST) size, an accepted marker of MTB infection and the frequency of allergic disease symptoms has not been reported from an area where MTB infection is endemic. Objective To investigate the association of TST and allergic disease symptoms, in children living in a tuberculosis (TB) endemic area. Methods In this cross-sectional study, 841 children aged 6–14 years from randomly selected household addresses in two poor communities of Cape Town, South Africa, were investigated with TST and standardized International Study on Asthma and Allergies in Childhood-based questionnaire on allergic disease symptoms. Results Children with positive TST (10 mm) were significantly less likely to have allergic disease symptoms, in particular allergic rhinitis (AR) (adjusted odds ratio 0.43; 95% confidence interval 0.24–0.79) than those with negative TST. This association remained significant after adjusting for possible confounders and correcting for the effect of clustering (>1 child per household address) in the sample. There was a significant inverse linear trend in the relation of TST size in millimetre and the frequency of allergic disease symptoms, in particular AR (P

Allergic diseases are on the increase, affecting 30–40% of the population. Histamine remains the most important mediator of clinical reactions in allergic diseases such as rhinitis, urticaria, and food and drug allergies.The need for more effective and safe antihistamines is critical and intensive drug development has become more demanding and competitive.Although the old “first generation” antihistamines were effective, major limitations included their strong potential for sedation and their anti-cholinergic side effects. Not only could patients not function well in their normal daily activities, but these medications posed an important risk for safety, particularly for motor vehicle drivers and machine and precision instrument operators. Unacceptable side effects were a particular problem in the elderly.In May 2001, CONGA, an international consensus group, convened to formulate guidelines for the development of new antihistamines. Several important areas were reviewed and a document of recommend...

Background: Exposure to organic dust produced by birds often gives rise to an immune response, e.g. IgG antibodies, but intense exposure can lead to high concentrations of IgG antibodies and the development of allergic alveolitis, often known as ‘bird fancier’s lung’. The aim of this study was to establish the distribution of bird-specific IgG antibodies in exposed and nonexposed individuals and compare a nonquantitative and quantitative method in evaluating raised levels of IgG antibodies. Methods: Sera were collected in Sweden and South Africa and levels of IgG antibodies specific to pigeon, budgerigar and parrot antigens were quantified using the UniCAP system. Results were compared to the precipitation in gel assay. The IgG antibody values of symptomatic patients without precipitating antibodies (non-PP group; n = 51) and patients with precipitating antibodies (PP group; n = 34) were analyzed and compared to nonexposed asymptomatic blood donors (BD group; n = 73) and environmentally exposed pigeon breeders (n = 11). Results: The IgG antibody response of the analyzed groups in Sweden and South Africa did not vary significantly from each other. IgG antibody responses were the strongest to pigeon antigens with clear increased IgG antibody levels in the PP group [geometric mean (GM) 603 mg/l] compared to the non-PP (GM 6.9 mg/l) and BD group (GM 5.0 mg/l). Threshold values, calculated as the GM value from the BD group plus 3 standard deviations (99% confidence interval), were 9.8, 10.8 and 10.0 mg/l for pigeons, budgerigars and parrots, respectively. Comparison of the two methods resulted in a good concordance with a level of agreement of 94.1% (kappa statistic = 0.83). Conclusions: The UniCAP system for the detection of bird-specific IgG antibodies is a highly reproducible, generally available, quantitative method for routine diagnostic testing and monitoring of exposed subjects with a very high level of agreement to the precipitating gel assay.

Twenty years ago, the prevalence of atopic sensitization and bronchial hyper-responsiveness (BHR) in Xhosa children in a rural location in South Africa was very low. The aim of this study was to document the current prevalence of these two indices by comparing traditional rural Xhosa children, recently urbanized Xhosa children and established city white children, and to consider factors that may account for the observed increase in all of these groups. One thousand four hundred and fifty-seven school children aged 10-14 years from the rural Transkei, from a recently urbanized peri-urban area and from urban Cape Town areas were studied using a questionnaire. Four hundred and eighteen children had histamine challenges, and 492 tests for atopy were also conducted. As determined by bronchial challenge with histamine, 17% of rural and 34.4% of recently urbanized Xhosa children had increased BHR, a marked increase from the 0.03% and 3.17% prevalence of increased BHR previously found using the exercise challenge. The prevalence of increased BHR in white urban children was 33%. Sensitization to one or more aero-allergens, as indicated by CAP RAST tests, was present in 16.6% of the rural Xhosa children with normal BHR and in 62.5% of those with increased BHR, a striking increase from that of previous studies. Atopic sensitization to one or more aero-allergens, as indicated by a skin prick test (SPT), was found in 42.3% of the recently urbanized Xhosa children and 45% of urbanized white children. We have also documented sensitization to house dust mites in the rural Xhosa children for the first time. Passive cigarette smoking was not identified as a risk factor for increased BHR or atopy. Wood smoke in the indoor environment did not play a role in the rural Xhosa children's BHR. Ascaris infection does not appear to play any modifying role in the development of increased BHR in the rural or urban children. We have found that increases in BHR in the rural and recently urbanized Xhosa children develop independently of increases in atopy. Our results challenge the 'hygiene' hypothesis as a complete explanation for the recent dramatic worldwide increases in allergic diseases.

Objective To evaluate the effect of fexofenadine on driver behavior, decision-making, and reaction time in a blinded, randomized, parallel, placebo-controlled study. Methods A total of 259 male and female adult volunteers participated in a standardized BMW advanced driving test (the skid-pan test; Pretoria, South Africa) and a decision and reaction test of the Vienna Psychomotor Test System. The psychomotor test focused on mean decision times, mean reaction time, decision errors and reaction errors. After a baseline pretest run, the test was repeated 2.6 hours after ingesting either fexofenadine hydrochloride (180 mg) or placebo (the posttest; 1:1). Results Two hundred fifty-five volunteers were included in the final efficacy analysis (195 males and 60 females). There was a reduction in the road test time going from the pretest to the posttest, signifying a learning effect, and an increase in the decision time. Although there was a consistent increase in the number of errors committed in the road test, decision time, and reaction time, there were no significant differences between the placebo and the fexofenadine groups. Although significant differences were observed between men and women for the road test time ( P P P = 0.003), there were no differences between the fexofenadine and placebo groups in these subgroups. Conclusions No differences were found between the fexofenadine and placebo groups on reaction times, decision-making, driver behavior, or adverse effects.

The safety and efficacy of a 1% cream formulation of pimecrolimus, a selective, nonsteroid immunomodulator, was studied in infants with atopic dermatitis (AD).During a 6-week double-blind phase, 186 infants with mild/moderate AD were randomly assigned to twice-daily pimecrolimus cream 1% or vehicle. All patients were subsequently treated with open-label pimecrolimus for 20 weeks.At the end of the double-blind phase, 54.5% and 23.8% of patients in the pimecrolimus and vehicle groups, respectively, were clear or almost clear of AD (P.001). Similar improvements were observed in the Eczema Area and Severity Index, pruritus assessment, and the care giver's assessment. By the first return visit, 69.9% and 36.5% of pimecrolimus and vehicle-treated patients, respectively, achieved absent or mild pruritus. Efficacy during the double-blind phase was maintained throughout the open-label phase. Vehicle-treated patients transferring to open-label pimecrolimus rapidly achieved disease control comparable to those receiving continuous pimecrolimus. There were no significant differences between groups in application site reactions or skin infections. Most adverse events were mild or moderate and unrelated to treatment.Pimecrolimus was safe in infants with AD, with rapid and sustained efficacy. Pimecrolimus holds promise as a valuable new treatment option for the youngest patients with AD.

Allergic diseases are quite prevalent worldwide, and the incidence of allergy is increasing everywhere [1-7]. Because allergic and immunologic processes overlap all organ systems, allergy is not always taught in medical schools as a separate subject. Indeed, lack of recognition of the specialty and of the need to teach about allergic and immunologic diseases results in allergy not being included at all in some medical school curricula [8]. With an estimated 22% of the global population experiencing allergic and immunologic diseases, it is time to recognize and strengthen education in allergy and immunology [8]. The World Allergy Organization (WAO), an alliance of 74 national and regional allergy societies, created this consensus document to establish educational guidelines for worldwide application to help identify and correct allergy education and training deficiencies and to define appropriate competencies. In creating this consensus, it is recognized that each country has its own principles and goals in medical education at the undergraduate and postgraduate levels. This document defines what WAO considers medical practitioners should know to care appropriately for allergic patients.

Cytokine responses accompanying sublingual immunotherapy (SLIT) responder phenotypes have not previously been reported.To investigate clinical and cytokine responses of house dust mite (HDM) sensitive patients with allergic rhinitis receiving HDM SLIT or placebo for 2 years.Sixty adults were randomized to receive SLIT or placebo. Clinical symptoms were measured using the Total 5 Symptom Score (TSS5) and Juniper Rhinitis Quality of Life Questionnaire. HDM specific IgE, IgG, skin prick tests, and HDM-stimulated release of interleukin (IL) 5 and interferon γ (IFN-γ) in peripheral blood mononuclear cells was studied at 0, 6, 12, and 24 months and IL-13, IL-4, and IL-10 at 0 and 24 months.A total of 32 of 39 SLIT and 16 of 21 placebo patients completed the study. There was significant clinical improvement in both the SLIT and placebo groups. Median T5SS decreased from 14.75 to 5.25 in the SLIT group (P.001) and 12.7 to 6.0 in the placebo group (P = .003). The median quality-of-life score also decreased in the SLIT group (P.001) and the placebo group (P.001). A subgroup analysis of patients found a 60% or greater improvement (on the T5SS and the Juniper Rhinitis Quality of Life Questionnaire) in the good responders group and a 30% to 59% improvement or no improvement in the intermediate responders group. This subgroup analysis also found more good responders in the SLIT group (47%) compared with the placebo group (25%; P = .07). Significant decreases in the IL-5/IFN-γ (P.001), IL-13/IFN-γ (P.001), and IL-4/IFN-γ (P = .03) ratios were found in the combined good clinical improvement group at 24 months.A good clinical response (≥60% improvement in both TSS5 and quality of life) is associated with significant decreases in IL-5, IL-13, and IL-4 relative to IFN-γ during 2 years of SLIT therapy for HDMs.

Background The prevalence of food allergy in South Africa is unknown, but previously thought to be rare in black South Africans. This study aimed to determine the prevalence of, and risk factors for, IgE-mediated food allergy in South African children with atopic dermatitis (AD). Methodology This was a prospective, observational study in a paediatric university hospital in Cape Town. Children with AD, aged 6 months to 10 yrs, were randomly recruited from the dermatology clinic. They were assessed for sensitization and allergy by questionnaire, skin prick tests, Immuno Solid Phase Allergen Chip (ISAC) test and incremental food challenges. Results 100 participants (59 black Africans and 41 of mixed race) were enrolled, median age 42 months. There were high overall rates of food sensitization (66%) and food allergy (40%). Egg (25%) and peanut (24%) were the most common allergies. Black participants had comparable sensitization (69% vs. 61%) but lower allergy rates (34% vs. 46%) than mixed race participants. This was especially evident for peanut allergy (15% Blacks vs. 37% mixed race allergic to peanut, p = 0.01). Early-onset AD (

Background: The hypothesis that in atopic diseases the T-helper response is skewed toward a T H 2-type cytokine response was based on studies with mitogen stimulation, T-cell clones, or both. Objective: Using primary cultures, we investigated (1) whether atopic asthmatic patients have a T H 2 response and nonatopic subjects have a T H 1 response to allergen and (2) whether atopic patients have a decreased ability to mount T H 1 immune responses to mycobacterial antigens. Methods: The responses of PBMCs to allergen (house dust mite [HDM]) or purified protein derivative of Mycobacterium tuberculosis (PPD) stimulation from 10 severely and 14 moderately asthmatic patients (all allergic to HDM) were compared with those of 17 nonatopic healthy black (Xhosa) children. Results: HDM-stimulated proliferation, IL-5 release, and the IL-5/IFN-γ ratio were significantly increased in subjects with atopic asthma, whereas IFN-γ release was not significantly different. IL-4 levels were below the level of detection. PPD-stimulated proliferation, IL-5 release, IFN-γ release, and the IL-5/IFN-γ ratio were not significantly different among the groups. Each group had a significantly higher IL-5/IFN-γ ratio in response to HDM than to PPD (a T H 1 stimulus). Conclusion: Our study, which used primary cultures to investigate the hypothesis that nonatopic subjects have a T H 1 response to allergens, indicates that HDM stimulates a T H 2 cytokine response in both atopic and nonatopic subjects but that the response is enhanced in atopic patients. Our results with PPD suggest that normal and atopic asthmatic subjects can have a T H 1 cytokine response to mycobacteria, but there is a subgroup of atopic subjects that have a T H 2 response. (J Allergy Clin Immunol 2000;106:84-91.)

Sixteen years after the first report of latex allergy in healthcare workers at Groote Schuur Hospital, Cape Town, in 1997, latex allergy remains an occupational risk and an ongoing challenge for healthcare institutions in South Africa, particularly those that have not yet adopted stringent latex-powdered glove avoidance measures.

The term rhinitis implies inflammation of the lining of the nose. Characteristic symptoms are a blocked nose, anterior and posterior rhinorrhea, sneezing and itching. Not all cases of chronic rhinitis have an allergic basis. Chronic non-allergic rhinitis is defined as a condition where ongoing rhinitic symptoms are present for many months (as for persistent allergic rhinitis) but there is no IgE basis. Many common conditions may present as chronic rhinitis, which will need to be investigated and managed on their own merits. Not all cases of chronic rhinitis respond to allergic rhinitis therapy: continued attempts to manage chronic rhinitis as allergic rhinitis may be hampered by pathophysiological conditions where other specific therapy may be required. Chronic rhinitis impacts on patient quality of life, and therefore therapy is important. Managing patients with chronic rhinitis requires attention to patient education in order to achieve the maximal therapeutic benefit of medication. This update is intended to provide clinicians with a sound basis for management of a common condition.

Summary Background Measurement of markers of eosinophil activation in asthmatics provides information indicative of ongoing inflammatory processes in the airways. Objectives This study was eonducted to determine the correlations between serum markers of allergie inflammation with spirometry parameters in asthmatic children in different treatment groups. Methods Blood eosinophils. serum levels of eosinophil cationic protein (ECP). eosinophil protein X (EPX), myeloperoxidase (MPO) and tryptase were measured simultaneously with serial measurements of FEV1/FVC, FEF25–75 and FEF in 60 children with acute asthma on admission and after 2, 14, 30 and 60 days. Group A received bronchodilators only (n= 20). group B received sodium cromoglycate (SCG) (n= 20) and group C received oral and/or inhaled corticosteroids (n= 20). Results Oral steroid treatment (2 mg /kg/day). given at the onset of the asthma attack, resulted in significant reduction in the ECP and EPX levels in all the children. However, these reduced ECP and EPX levels were not sustained in the children, even in those who continued on maintenance steroid treatment. Significant, but inconsistent, correlations between ECP, EPX with total eosinophil count, percentage eosinophils and spirometry parameters were observed at the different time-points. Tryptase levels were normal in all subjects. There were no significant correlations between myeloperoxidase levels and the spirometry parameters or eosinophil parameters. Serial monitoring of ECP and EPX levels was found to be of some use in predicting clinical outcome in certain steroid-dependent asthmatics (group C) but of no value in the mild asthmatics (group A). Conclusion While elevation of ECP, EPX and MPO in the serum of childhood asthmatics suggests ongoing inflammation and may inversely correlate with spirometry parameters in some patients, the relationship between these markers and airway function is not a simple one.

Summary Complete complement component 6 deficiency (C6Q0) is a co-dominant genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. Affected individuals have two affected alleles which can be homozygous or compound heterozygous for the particular gene defects they carry. This disorder has been diagnosed relatively frequently in Western Cape South Africans. Affected patients are prescribed penicillin prophylaxis. In 2004 we commenced a clinical follow-up study of 46 patients. Of these, 43 had family age-matched C6 sufficient controls. Participants were classified as either (i) well, or (ii) having a serious illness (SI) or died (D). An SI was a long-term illness that did not allow the performance of normal daily activities. Among 43 patients, 21 were well and 22 were SI/D, while among 43 matched controls, 35 were well and eight were SI/D. This difference is highly significant. Among all 46 C6Q0 patients, those who had had recurrent infection had significantly more SI/D than those who had suffered none or one infection. Thus, this work demonstrates the long-term serious outcome of repeated meningococcal disease (MD) episodes. We investigated the frequencies of four C6Q0 pathogenic mutations known to affect Cape patients (828delG, 1138delC, 821delA and 1879delG) in 2250 newborns. A total of 103 defective alleles (2·28%) and three affected C6Q0 individuals were detected. For all defects combined, 5·24 affected subjects (C6Q0) are expected among 10 000 individuals. What is still unknown is the number of C6Q0 individuals who suffer MD or other infectious diseases.

Atopic dermatitis (AD) is a chronic and disabling condition that has a major impact on financial and social resources of the individual and the community. Its incidence is increasing dramatically, and no cure is available. Pharmacological treatment is only partially effective. The evidence that diet plays a role in children with atopic dermatitis is now irrefutable. Prophylactic measures can prevent or limit the development of AD, and partially restricted diets can modify the disease's course or severity. This study reports the reactions to various foods as perceived by parents of 112 children affected by AD. It demonstrates that many foods exacerbate AD and that reactions are caused by two distinct groups of food. The commonest triggers of cutaneous symptoms are tomatoes, oranges, sweets, pineapple, chocolate, and softdrinks preserved with sulfur dioxide. These foods result in symptoms in 30% to 49% of the children. The traditional IgE reaction type foods, namely egg, fish, milk, and peanut, resulted in reactions in 14% to 25% of the children, and with many non-cutaneous symptoms. The study further shows that allergen avoidance measures are not practiced in our community, and that sound advice is not often proffered. Practical advice on prophylactic dietary preventative measures and dietary management of children with atopic dermatitis is presented.

There is comparatively little information on health-related quality of life (HRQoL) in subjects with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western Europe and North America. The primary aim of this investigation was therefore to review and assess the information in the public domain on HRQoL in AR/C patients from diverse regions of the world, represented by different countries, including Argentina, Australia, Brazil, Russia, Singapore, South Africa and Turkey. Second, in view of the absence of a standardized definition for 'AR control', the review aimed to determine whether a working definition of AR/C can be inferred from validated tests or other instruments documented to date. Despite the comparatively low number of studies, this review demonstrated that overall the symptoms of AR/C impair the HRQoL of patients in these regions by adversely impacting sleep, daily activities, physical and mental status and social functioning, similar to that demonstrated in much larger numbers of studies of AR/C patients in Europe and the United States. Furthermore, the findings of the review suggest that 'overall' control of the disease should encompass reduction of nasal and ocular symptoms, as well as improvements in HRQoL, comorbid conditions and cognition. Although some instruments are currently available for measuring control of AR, none are capable of assessing all these aspects, emphasizing the need to develop appropriate new instruments.

The For Angioedema Subcutaneous Treatment (FAST)-3 study was a phase III, randomized, double-blind, placebo-controlled study of icatibant (bradykinin B(2) receptor antagonist) in subjects with hereditary angioedema (HAE) resulting from C1-INH deficiency or dysfunction (type I/II).To investigate icatibant efficacy and safety in subjects with acute HAE attacks.Subjects with moderate to very severe cutaneous or abdominal symptoms received icatibant (n = 43) or placebo (n = 45). Five subjects with laryngeal (mild-to-moderate) first attacks received icatibant (n = 3) or placebo (n = 2), and 5 subjects with severe laryngeal first attacks received open-label icatibant.Cutaneous or abdominal attacks: icatibant significantly reduced median times (vs placebo) to 50% or more reduction in symptom severity (2.0 vs 19.8 hours; P.001, primary endpoint), onset of primary symptom relief (1.5 vs 18.5 hours; P.001, key secondary endpoint), or almost complete symptom relief (8.0 vs 36.0 hours; P = .012) and provided a shorter time to initial symptom relief (0.8 vs 3.5 hours; P.001). For laryngeal attacks, median time to 50% or more reduction in symptom severity was 2.5 hours (icatibant) and 3.2 hours (placebo). No icatibant-treated subject required rescue medication before symptom relief occurred. The incidence of adverse events (AEs) was similar in icatibant- and placebo-treated subjects (41% and 52%, respectively). All icatibant-treated subjects experienced injection site reactions, but none reported clinically relevant changes in safety parameters or serious AEs.FAST-3 demonstrated that icatibant was effective and generally well tolerated in subjects with acute HAE attacks.Clinicaltrials.gov Identifier: NCT00912093.

Kikuyu grass (Pennisetum clandestinum) is widely used as a grazing pasture in Africa and, although it is extensively cultivated as a lawn for sports fields and domestic gardens, its allergenicity has never been studied in vitro. Using an extract of Kikuyu grass pollen, polyacrylamide gel electrophoresis, Western blotting and a monoclonal anti-human IgE antibody, the specific IgE binding, in the serum of 160 allergic and non-allergic patients in the Cape Town area, to a Kikuyu grass extract was studied. IgE in the sera of 43/104 known grass-allergic individuals bound to Kikuyu grass on the Western blots. In addition, 4/28 'non-allergic' control subjects were found to have Kikuyu grass-specific IgE. Five different profiles of specific IgE reactivity to Kikuyu grass antigens were observed. In 29/43 patients, IgE bound to two dominant 48 and 70 kD allergens in the Kikuyu extract. Although a degree of cross-reactivity with Bermuda grass (Cynodon dactylis) was found in immunoabsorption studies, the 48 and 70 kD allergens appear to be unique to Kikuyu grass. Exposure of heparinized blood from Kikuyu grass-positive patients to the Kikuyu extract stimulated the release of histamine from their basophils in vitro. Kikuyu grass pollen is thus identified as an important aero-allergen in South Africa.

Pimecrolimus and topical corticosteroids (TCS) combination therapy may provide an alternative treatment for patients with severe atopic dermatitis (AD), with faster clearance of disease flares, consequently reducing the duration of TCS treatment.To assess the safety profile of pimecrolimus cream 1% combined with fluticasone versus fluticasone alone in paediatric patients with severe AD.Patients (n = 376) were randomized to a combination of pimecrolimus cream 1% with fluticasone or vehicle plus fluticasone for 4 weeks. The primary outcome measure was the frequency of clinically relevant pre-defined adverse events (AEs) associated with the topical use of corticosteroids in patients with severe AD.Erythematous rash was the only AE, occurring more frequently in the combination group, while there were no noticeable differences in the frequency of other AEs of clinical interest between treatment groups. Efficacy variables were comparable between the two groups. A trend for greater time to relapse was observed for the combination of pimecrolimus cream 1% with fluticasone in patients who were clear at the end of treatment, with a marked improvement in facial AD.In paediatric patients with severe AD the overall safety profile of pimecrolimus cream 1% combined with fluticasone was similar to that of fluticasone alone.

The Free State province of South Africa is traditionally considered to be a haven for outdoor allergens such as grass pollens, which cause severe hayfever symptoms in the grass pollen season, and maize pollens, particularly in the rural areas.

Atopic eczema is a common problem in general practice. The underlying disorder is a barrier dysfunction of the skin, but exacerbations of eczema can be triggered by a range of external and internal factors. In young children, dietary factors are important triggers of exacerbations and specific IgE sensitivity to common allergens may be confirmed by skin prick testing or ImmunoCap® RAST tests. True sensitivity to foods is best confirmed by a controlled food challenge, and cut off values have been published which indicate the predictive values of blood or skin tests for true food sensitivity to guide the clinician. Elimination of identifiable triggers, the use of emollients and topical corticosteroids remain the mainstay of treatments. Calcineurin inhibitors have a place for treatment of selected cases. The use of systemic corticosteroids is discouraged and patients who do not respond to emollients, specific food avoidance and corticosteroids topically should be referred to a dermatologist. The role of maternal diet in preventing the development of eczema in the offspring remains controversial.

Udgivelsesdato: 2009-Dec

The diagnosis and management of asthma in young children is difficult, since there are many different wheezy phenotypes with varying underlying aetiologies and outcomes. This review discusses the different approaches to managing young children with wheezy illnesses presented in recently published global guidelines. Four major guidelines published since 2007 are considered. Helpful approaches are presented to assist the clinician to decide whether a clinical diagnosis of asthma can, or should be made in a young child with a recurrent wheezy illness and which treatments would be appropriate, dependent on risk factors, age of presentation, response to initial treatment and safety considerations. Each of the guidelines provide useful information for clinicians assessing young children with recurrent wheezy illnesses. There are differences in classification of the disease and treatment protocols. Although a firm diagnosis of asthma may only be made retrospectively in some cases and there are several effective guidelines to initiating treatment. Consistent review of the need for ongoing treatment with a particular pharmacological modality is essential, since many children with recurrent wheezing in infancy go into spontaneous remission. It is probable that newer biomarkers of airway inflammation will assist the clinician as to when to initiate and when to continue pharmacological treatment in the future.

SUMMARYTwo sensitive sandwich ELISAs based on monoclonal antibodies directed to native C6 and C7 allowed the detection and quantitation of these complement proteins in 20 out of 37 serum samples from individuals who had previously been classified as deficient in these proteins as assessed by immunochemical and/or functional assays. Furthermore, serum from four C6-deficient and one combined C6-/C7-deficient individual showed an increase in the terminal complement complex (TCC) and a decrease in native C6 and C7 after complement activation as assayed by specific ELISAs. Despite their (incomplete) deficiencies, these individuals therefore possess functionally active terminal complement proteins with respect to their ability to generate the TCC. As these individuals have no history of a susceptibility to neisserial infections, even low concentrations of functionally active C6 and C7 may provide sufficient protection against those micro-organisms whose destruction requires TCC formation.

Chronic urticaria (CU) in childhood remains a challenge for investigation, and its etiology is largely unknown. Autoantibodies to the high-affinity IgE receptor (FcepsilonRI) are believed to play a role in the pathogenesis of this disease in adults.To determine the prevalence of autoantibodies to FcepsilonRIalpha on basophils in children with CU vs atopic eczema dermatitis syndrome (AEDS).Eighty children with CU were compared with 38 children with AEDS. In addition to complete blood cell counts and total IgE measurements, CAP-RASTs to egg, codfish, soy, milk, and peanut were performed. Stool samples were examined for parasites, and autologous serum skin testing and a functional anti-FcepsilonRIalpha assay were conducted to detect autoantibodies.No significant differences were observed between children with CU and controls in mean basophil or eosinophil counts. Twenty (26%) of 77 children with CU and 31 (82%) of 38 with AEDS had positive CAP-RAST results (P.001). Only 2.5% of the children with CU and 0% with AEDS had stool samples positive for parasites (P = .005). Anti-FcepsilonRIalpha autoantibodies were positive in 37 (47%) of 78 children with CU and in none of 33 with AEDS. Non-IgG histamine-releasing factors were found in 10 (13%) of 78 children with CU.Children have a similar prevalence of autoantibodies to the FcepsilonRIalpha as has been previously published for adults. Few have type I allergies, and parasite infestation is also uncommon. Further studies are required to investigate the predictive value of the autoantibodies in these children with respect to clinical profile, requirements for medications other than antihistamines, and remission rates.

Background This randomized study examined the efficacy and safety of levocetirizine in pediatric patients with perennial allergic rhinitis. Health-related quality of life (HRQL) was also investigated, which is particularly relevant in children because of the effects of rhinitis on learning, social activities, and comorbidity. Objective To evaluate the effect of levocetirizine on the Total 4 Symptoms Score, the 50% response rate, the Pediatric Rhinitis Quality of Life Questionnaire (PRQLQ), and investigators' global evaluation of symptom improvement. Methods Double-blind, placebo-controlled, randomized, multicenter trial of levocetirizine, 5 mg once daily for 4 weeks, in 306 children with perennial allergic rhinitis aged 6 to 12 years. There were 154 children in the levocetirizine arm and 152 in the placebo group who completed daily diary cards, and the PRQLQ and investigators' global evaluations were conducted at 3 visits. Results The levocetirizine group showed a significant improvement in 2-week and 4-week Total 4 Symptoms Score compared with placebo ( P = .001 and P = .008, respectively). The 50% response rate for the first 2 weeks was 12.3% for the levocetirizine group compared with 3.9% for the placebo group ( P = .01). The investigators' global evaluation also favored levocetirizine, because 57.1% of the children in the levocetirizine group were considered markedly or moderately improved compared with 44.7% in the placebo group. Levocetirizine also provided a significantly greater HRQL improvement than placebo at 2 weeks ( P = .01), and the frequency of adverse events did not differ significantly from those seen in the placebo group. Conclusion The study confirmed the efficacy of levocetirizine in relieving symptoms of perennial allergic rhinitis in children between 6 and 12 years of age. A HRQL benefit greater than placebo was shown. The treatment was well tolerated.

Background Although the cytolytic, neurotoxic, and hemolytic actions of snake venoms are well known, the ability of airborne inhaled snake venom of the spitting cobra to induce asthma in snake handlers has not been reported. Objective To report the allergenicity of inhaled snake venom in a snake handler who developed increasing hypersensitivity to airborne venom, produced by spitting cobras during public demonstrations. Methods Serum samples were obtained from 2 handlers (our study patient and another snake handler who reported developing wheezing when handling spitting cobras), and desiccated venom was obtained from 9 species to which the handlers were exposed. Serum from an asymptomatic and nonatopic snake handler exposed to the same snake species was used as a control. Phosphate-buffered saline extracts were prepared from the desiccated venom, proteins in the venom extracts were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting was performed. Inhibition enzyme-linked immunosorbent assays (ELISAs) were performed to demonstrate cross-reactivity. Results The study patient had never been previously bitten by a cobra. Wheezing occurred rapidly on inhalational exposure and was reversed by inhalation of salbutamol. The patient had developed IgE antibodies to 9 different snake venoms on Western immunoblots, with major IgE binding proteins of 59 to 63 kDa and 8 to 15 kDa. The cross-reactive nature of the IgE epitopes in the venoms in the different species was also confirmed by 50% inhibition of IgE binding in an ELISA by preincubation with unrelated species. Life-threatening sensitivity of the patient was sustained after a long period of avoidance. Conclusions We propose that aerosolized snake venom be considered a new potential source of allergens that may result in anaphylaxis on subsequent exposure. Further studies of the development of specific IgE sensitization following snakebites and the risks of such sensitization should be conducted on snake handlers, particularly those who demonstrate the spitting species.

The fact that breastfeeding may protect against allergic disease remains controversial, with hardly any reports from developing countries. This study investigated the association between allergic disease in children and prolonged breastfeeding. Data were collected from a 15% random sample of households from two poor suburbs of Cape Town, South Africa. Parents completed a validated International Study on Asthma and Allergies in Childhood questionnaire on allergic diseases for children aged 6–14 yrs. Other questions included breastfeeding duration, maternal smoking and parental allergy. Results were adjusted for possible confounders and for possible clustering within the household. Out of the 861 children included in the study, allergic disease in general, and hay fever in particular, were significantly less frequent in those with prolonged (≥6 months) breastfeeding. There was a significant linear inverse association between breastfeeding duration and allergic disease in children without allergic parents, but not in children with an allergic predisposition. In conclusion, these results from a developing country suggest a protective effect of prolonged breastfeeding on the development of allergic disease, particularly hay fever, in children born to nonallergic parents. This protective effect was not found in children with an allergic predisposition.

Spina bifida children have a high prevalence of latex allergy in studies reported from Europe and the USA. This study investigated the prevalence of latex allergy in a cohort of 24 spina bifida children at the Red Cross Children's Hospital from Cape Town, South Africa. The children were investigated using a detailed questionnaire, skin prick tests (ALK-Abello), ImmunoCap RASTs, Western blotting and ELISA, using the purified latex proteins Hev b1 and Hev b3 and whole latex preparation. A low overall prevalence of latex sensitization of 16.7% was found in the children. Children who were sensitive reacted to water insoluble to Hev b1 and Hev b3 proteins. The low prevalence of latex sensitization in the South African children may not be entirely explained by stringent latex avoidance. The children were from a low socioeconomic social status and ‘hygiene’ and other factors should be considered.

Background: Recent reports of fatal asthma cases associated with swarms of locusts affecting African countries have highlighted the importance of this insect in causing asthma morbidity and mortality. However, only limited information is available about the allergic health outcomes such as asthma and its determinants in exposed individuals. In this study, workers exposed to the African migratory locust Locusta migratoria were evaluated for allergic health outcomes as well as the nature of the offending allergens. Methods: Ten scientists and technicians exposed to locusts in a laboratory were investigated for locust-related allergy using questionnaires and immunological tests. The presence of allergy was determined by quantification of specific IgE and IgG to L. migratoria using the UniCAP® system and via skin-prick testing (SPT). The allergens were characterized by Western blot and ImmunoCAP inhibition assays. Results: Six of the 10 workers experienced symptoms ranging from urticaria and rhinoconjuctivitis to asthma. Seven individuals demonstrated sensitivity on SPT and five had specific IgE antibodies to L. migratoria. Significant cross-reactivity was demonstrated for allergens in the locust faeces, body and wings but not to cockroach allergens. Novel allergens with molecular weights of approximately 70 kDa were identified in locust wings, which are distinctly different from other known allergen sources from locusts. Conclusion: Exposure to L. migratoria allergens is a potential sensitizer in exposed individuals. Raised levels of locust-specific IgE can be readily quantified. The wings of this insect species have been identified as a novel allergen source.