Form Of Allergy Research Articles

Modelling the health economic impact of managing cow milk allergy in South Africa

Objective: To quantify the health economic impact of managing cow milk allergy (CMA) in South Africa, from the perspective of healthcare insurers in both the private and public sectors and parents/carers of CMA sufferers.Methods: A decision model depicting the management of CMA in South Africa was constructed, using information obtained from interviews with paediatric specialists in the private and public sectors with relevant clinical experience. The model was used to estimate the expected 12-monthly levels of healthcare resource use and corresponding costs (at 2007/08 prices) attributable to managing CMA sufferers following an initial consultation with a paediatrician.Results: The expected 12-monthly cost incurred by an insurer attributable to managing a CMA sufferer following an initial consultation with a paediatrician was estimated to be R2,430.4 (€202.0) and R1,073.7 (€89.0) in the private and public sector, respectively. The expected 12-monthly cost incurred by parents/carers following an initial consultation with a paediatrician was estimated to be R43,563.1 (€3,634.0) and R24,899.9 (€2,076.9) in the private and public sector, respectively. The time taken for a CMA sufferer to be put on an appropriate diet and achieve symptom resolution was estimated to be 24 days in the private sector and 18 days in the public sector. The total cost to manage an annual cohort of 18,270 newly diagnosed infants with CMA in South Africa in the first year following presentation to a paediatrician was estimated to be R22.1 (€1.8) million for healthcare insurers and R489.1 (€40.8) million for parents/carers. The expected costs to insurers were driven by visits to general paediatricians and prescriptions for dermatological drugs in both the private and public sectors. The expected costs to parents/carers were driven by over-the-counter (OTC) purchases of clinical nutrition preparations.Limitations: The intolerance rates were derived from a study among 1,000 infants with CMA in the UK, healthcare resource use was not collected prospectively and the study period was limited to 1 year following presentation to a paediatrician and does not consider the impact of CMA in subsequent years. However, most children outgrow this form of allergy by the time they reach 2 years of age.Conclusion: CMA imposes a substantial socio-economic burden in South Africa, especially on parents/carers of CMA sufferers. Any strategy that reduces this burden should potentially lead to higher compliance with clinicians’ recommendations, thereby improving health outcomes associated with treatment and should also release healthcare resource use for alternative use.

Suspected recurrent anaphylaxis in different forms during general anesthesia

We report on a patient who presented with recurrent severe shock during general anesthesia. The patient was a man scheduled for lung surgery whose first attack was a coronary spasm, which was followed by a second shock with severe bronchospasm and hypotension 4 weeks later. An elevated serum tryptase concentration was observed, and subsequent skin testing revealed negative reactions to some drugs administered in this case. This case serves to alert anesthetists to the possibility of some different forms of allergy and highlights the importance of rigorous investigation of all the reagents and phenomena.

New Applications for Sublingual Immunotherapy in Allergy

Specific immunotherapy is the only treatment targeting the causes, and not only the symptoms, of allergic diseases. Sublingual immunotherapy (SLIT) was introduced and developed to solve the problem of the adverse reactions, uncommon but possibly severe and rarely fatal, to the traditional subcutaneous immunotherapy (SCIT). The evidence of SLIT efficacy concerns rhinitis and asthma caused by sensitization to pollens and to house dust mites, but there are increasing data suggesting that SLIT could be applied in forms of allergy hardly feasible for SCIT because of its poor safety (this is true for food allergy and latex allergy) or could be considered for new applications, such as atopic dermatitis or baker's asthma. In particular, there are placebo-controlled trials indicating good efficacy and safety of SLIT in patients allergic to latex and to foods and in children with atopic dermatitis, that indicate SLIT as a real treatment option in such clinical entities. This article also discusses some patent related to the field.

A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation

BackgroundThe identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes.ResultsTo test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4+ cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, IL7R, was selected for further validation. The expression levels of IL7R in allergen challenged CD4+ cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies.ConclusionWe propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.

Platelet Activation During Allergic Inflammation

Blood platelets, apart from their traditional and well-recognised function in haemostasis, play an essential and active role in allergic inflammation e.g. through their participation in cell recruitment from blood to site of immune reactivity as a result of direct interactions with leukocytes, and through the release of inflammatory mediators. Platelet activation may occur during human allergic reactions both systemically and locally at the site of allergic inflammation as a result of an IgE-dependent process and as a secondary event caused by other inflammatory or immune stimuli. Altered platelet function as measured by platelet secretion, expression of surface molecules, aggregation, adhesion or arachidonic acid metabolism has been found in patients suffering from allergic diseases. These blood elements have been implicated in the pathogenesis of allergic diseases associated with the so-called atopic diathesis. This paper reviews the platelet activity and reactivity in allergic inflammation, along with our own findings concerning platelet release reaction and the phenomenon of platelet aggregation in patients with different clinical forms of allergy.

Cosmetic and radiological outcome following the use of synthetic hydroxyapatite porous-dense bilayer burr-hole buttons

Cranial neurosurgical procedures utilising burr-holes lead to development of cosmetically unacceptable puckered scars on the scalp over burr-hole sites. Ceramics, especially Hydroxyapatite (HA) are good bone substitutes owing to their biocompatibility and osteoconduction i.e. ability to lay down bone over the implant by fibrovascular invasion and later bone formation. The Sree Chitra Tirunal Institute for Medical Sciences and Technology in India has pioneered research in this direction and has developed a unique porous-dense bilayer HA burr-hole button. This study evaluates the safety, cosmetic effect, as well as the radiological outcome following implantation of these bilayer HA buttons. Sixty-five HA buttons were implanted in 22 patients who underwent cranial neurosurgical procedures at the Sree Chitra Tirunal Institute for Medical Sciences and Technology. We assessed the cosmetic outcome (absence of puckered scar over burr hole sites, absence of allergic reactions or infections associated with the implant) as well as the radiological outcome with X-rays at specified intervals and looked for interference in the postoperative neurological imaging due to the implants. There were no adverse events related to the HA buttons in the form of allergic reactions or infections. The implants persisted as radio-dense opacities on skull X-rays of recipients for up to two years. It did not lead to artefacts on postoperative CT or MR imaging of the brain. In particular, the HA buttons could be subtracted on Digital Subtraction Angiography and did not obstruct visualisation of the cerebral vasculature. The bi-layer porous-dense HA buttons are useful in preventing cosmetic defects over burr-hole sites on the scalp after cranial neurosurgical procedures. It does not interfere with current radiological imaging methods in the postoperative phase.

Antiallergic Effects of Probiotics1,

A considerable part of the Western population suffers from some form of allergy, and the incidence is still rising with no sign of an end to this trend. Reduced exposure to microbial allergens as a result of our hygienic lifestyle has been suggested as one of the possible causes. It has also been suggested that probiotics may provide safe alternative microbial stimulation needed for the developing immune system in infants. This idea is supported by the fact that allergic infants have been observed to have an aberrant intestinal microbiota. They were shown to have more clostridia and fewer bifidobacteria and, in addition, to have an adult-like Bifidobacterium microbiota. Clinical trials have shown that the standard treatment of infants with atopic eczema, extensively hydrolyzed infant formula, can be significantly improved through the addition of Lactobacillus rhamnosus GG or Bifidobacterium lactis Bb-12. It has also been shown possible to halve the incidence of allergy in at-risk infants through administration of L. rhamnosus GG to expecting mothers and subsequently to their infants during the first half-year of life. Many mechanisms have been proposed for these beneficial effects, ranging from improved mucosal barrier function to direct influences on the immune system. However, the exact mode(s) of action are not yet known. For the future, elucidation of these mechanisms will be an important target. Another important area will be the investigation of interactions between probiotics and other food components that influence allergies. This will enable optimization of probiotic use for the allergic subject.

Trends in the Pharmacology of Inflammatory and Allergic Eye Disorders

Ocular allergies are one of the most common diseases presenting to the general ophthalmologist. Allergic eye disease includes a spectrum of different clinical entities: the seasonal and perennial allergic conjunctivitis and the more severe forms vernal keratoconjunctivitis and atopic keratoconjunctivitis. A wide spectrum of topical pharmacological agents has been developed for the treatment of the different forms of ocular allergy. These include mast cell stabilizers, pure antihistamines, new dual-acting agents with antihistamine and mast-cell stabilizer properties and non-steroidal antiinflammatory drugs (NSAIDs). All these drugs are very effective in controlling signs and symptoms of mild and moderate forms of allergic reaction and are mainly free of adverse reaction in the chronic use. Topical corticosteroids remain the mainstay in the aggressive treatment of sight-threatening forms of allergic conjunctivitis, although their long-term use is limited by the risk of severe ocular side effects. For this reason, newer immunosuppressive drugs, such as cyclosporine and tacrolimus, have been tested in the treatment of some forms of ocular allergy demonstrating an high safety profile. New potential therapeutic strategies include the modulation of the immune system through a switch of the allergic response from a Th2-dominated immune profile towards a Th1 response.

The difficulties of diagnosing food-dependent exercise-induced anaphylaxis in childhood - a case study and review

We describe a case report of peanut and hens egg-dependent exercise-induced anaphylaxis in a 13-yr-old child, and assess the fundamental importance of careful investigations to differentiate food-dependent exercise-induced anaphylaxis from other forms of allergic reactions.

Costimulation of mast cells by 4-1BB, a member of the tumor necrosis factor receptor superfamily, with the high-affinity IgE receptor

Mast cells are the major effector-cell type for immediate hypersensitivity and other forms of allergic reactions. Expression of 4-1BB, a member of the tumor necrosis factor receptor superfamily, is induced at mRNA and protein levels on stimulation through the high-affinity receptor for immunoglobulin E (IgE; FcepsilonRI). In this study, we present evidence that agonistic anti-4-1BB antibodies can enhance FcepsilonRI-induced cytokine production and secretion. Consistent with this, 4-1BB-deficient mast cells exhibit reduced degranulation and cytokine production on FcepsilonRI stimulation. Analysis of 4-1BB ligand (4-1BBL)-deficient cells supported this notion. As a potential mechanism for these defects, we identified a defect in Ca2+ flux induced by FcepsilonRI stimulation. The defective Ca2+ flux could be accounted for by the reduced activity of Lyn/Btk/phospholipase C-gamma2 pathway and constitutive interactions between 4-1BB and Lyn. Therefore, FcepsilonRI-inducible 4-1BB plays a costimulatory function together with FcepsilonRI stimulation.

Selective Haptenation of Cellular or Extracellular Protein by Chemical Allergens: Association with Cytokine Polarization

Sensitizing chemicals can cause different forms of allergy, allergic contact dermatitis, or sensitization of the respiratory tract. These discrete types of chemicals induce in mice qualitatively divergent immune responses; contact allergens provoke preferential type 1 responses, whereas respiratory allergens stimulate selective type 2 responses. We have questioned whether the ability of chemicals to initiate polarized immune responses is in part a function of the nature of their association with protein. Cytokine secretion profiles provoked following topical exposure of BALB/c mice to dinitrochlorobenzene (DNCB), dinitrofluorobenzene (DNFB), fluorescein isothiocyanate (FITC), trimellitic anhydride (TMA), and dinitrobenzenesulfonyl chloride (DNBSCl) were compared with the distribution of covalent binding to U937 cells and/or to serum proteins in vitro. DNCB and DNFB each provoked a type 1 cytokine secretion profile, with high levels of IFN-gamma, but relatively low levels of type 2 cytokines IL-4, -5, and -10. The converse selective type 2 phenotype was seen following equivalent exposure to TMA, FITC, or DNBSCl. Each chemical bound covalently to U937 cells and to serum proteins, when incubated with cells or serum alone. When incubated with cells and serum together, DNCB and DNFB bound selectively to cellular protein, whereas TMA, FITC, and DNBSCl bound selectively to serum. These investigations show that the distribution of antigen formation of chemical allergens in an in vitro model system segregates with the type of cytokines secreted from activated lymph node cells in an in vivo mouse model. Chemical allergens that stimulate type 1 cytokine secretion profiles bind selectively to cellular proteins, whereas others that provoke type 2 cytokine profiles bind preferentially to serum proteins.

Superallergens: a novel mechanism of IgE‐mediated activation of human basophils and mast cells

SummaryHere we report that specific proteins induced in vivo by viruses (e.g. protein Fv), viral proteins (e.g. gp120) or bacterial proteins (e.g. protein L and protein A) can activate human mast cells and basophils (FcεRI+ cells) to release proinflammatory mediators and cytokines, thereby functioning as immunoglobulin superallergens. Protein Fv acts as an endogenous immunoglobulin superallergen by interacting with IgE VH3+. Similarly, gp120 of HIV‐1 is a viral superallergen activating FcεRI+ cells through interaction with IgE VH3+. Protein A of Staphylococcus aureus functions by interacting with IgE VH3+. Finally, Peptostreptococcus magnus, protein L and a fragment denoted B1–B4 induce mediator release from FcεRI+ cells through interaction with κ light chains of IgE bound on human FcεRI+ cells. Thus, we have identified a novel mechanism by which endogenous, bacterial and viral proteins specifically activate FcεRI+ cells, thereby acting as immunoglobulin superallergens. The in vivo implications of IgE‐mediated activation of human FcεRI+ cells by these immunoglobulin superallergens have yet to be defined. However, it is not inconceivable that endogenous, bacterial and viral superallergens play a pathophysiological role in certain forms of allergic reactions.

Efficacy of Aprotinin in Reducing Blood Loss in Paediatric Patients Undergoing Major Spinal Surgery.

Blood loss during corrective surgery for scoliosis and the requirement for homologous blood is an important issue in paediatric spinal surgery. This is particularly pertinent in cases of scoliosis secondary to underlying neuromuscular disease where anaemia may be less well tolerated, both intra-operatively and post-operatively, due to multiple organ dysfunction. Despite the introduction of techniques to minimise the necessity to transfuse homologous blood (pre-deposit autologous donation, cell salvage and isovolaemic haemodilution), it is often required. This brings with it the potential risks of allo-immunization and infective complications. In the UK homologous blood is an increasingly precious resource following the recent exclusion of donors who have themselves received blood products in the last ten years in view of the potential risk of new variant CJD.Aprotinin, a serine proteinase inhibitor (now produced by recombinant technology) with antifibrinolytic properties and the ability to preserve platelet function has been shown to reduce blood loss in major cardiac surgery and liver transplantation. Its effectiveness in the orthopaedic setting has generated more varied reports, however in the setting of spinal surgery for idiopathic scoliosis it has recently been shown to reduce intra-operative blood loss and the requirement for homologous transfusion.We report here our experience with the use of aprotinin in a group of paediatric patients undergoing surgery for scoliosis secondary to an underlying neuromuscular disorder and its effect on intra-operative blood loss. 33 successive patients referred to our institution were allocated to receive aprotinin (n=18) or not (n=15). For those who received the drug a test dose of 50,000KIU was followed by a loading dose of 10,000KIU/kg over 30 minutes. A maintenance infusion was set up at 5,000KIU/hour for the duration of the procedure.The demographics of the two groups were not significantly different. The median age of those children receiving aprotinin was 12 years (7–15) and those who did not 13 years (7–17), [p=0.09]. The median weight of the children receiving aprotinin was 40kg (25–55) and those who did not 38.5kg (21–55), [p=0.74]. The procedures undertaken were posterior spinal fusion (n=26), anterior and posterior fusion (n=3), insertion of growing rods (n=2) and correction of kyphoscoliosis (n=2). All procedures were performed by one of three consultants. The operative time in the two groups was not significantly different, 6.5 hours (4.1–8.9) in those who received aprotinin and 5.7 (4.4–7) in those who did not [p=0.54].There was however a significant reduction in blood loss in the group who received aprotinin, with an average reduction of 51.6%. Median losses for those who received aprotinin were 1380ml (380ml–2380ml) and 2849ml (1047ml–4651ml) for those who did not [p=0.01]. No adverse events in the form of allergic reactions were observed in the children who received the drug. We conclude that aptotinin is a safe and effective pharmacological intervention which can be used in spinal surgery to reduce operative blood loss. This should translate into a reduced requirement for homologous blood although this was not determined in this study. Evaluation of this secondary endpoint is ongoing.

Mice reveal new, severe form of allergy

Mice reveal new, severe form of allergy

Allergic and immunologic disorders of the eye. Part II: Ocular allergy

Allergy affects more than 15% of the world population, and some studies have shown that up 30% of the US population has some form of allergy. Most of these patients have various target organs for their allergies, and most have ocular involvement. The ocular component may be the most prominent and sometimes disabling feature of their allergy. Some are affected for only a few weeks to months, whereas others have symptoms that last throughout the year. The seasonal forms may present to clinical allergists, whereas the more chronic forms may present to ophthalmologists. Thus, in the second of this 2-part review series (Part I: Ocular Immunology appeared in the November issue of the Journal), an overview is provided of the spectrum of ocular allergy that ranges from acute seasonal allergic conjunctivitis to chronic variants of atopic keratoconjunctivitis. With a better understanding of the immunologic mechanisms, we now can develop better treatment approaches and design further research in intervention of allergic eye diseases. (J Allergy Clin Immunol 2000;106:1019-32.)

CONTROVERSIAL FORMS OF IMMUNOTHERAPY

Allergen immunotherapy is a well-established treatment for certain forms of allergy. Numerous properly controlled studies document its efficacy. There are no known long-term adverse consequences, and the immediate side effects and dangers are known and can be minimized when the treatment is used properly. There is a clear need to find ways to enhance its efficacy and perhaps its use in conditions such as food anaphylaxis. There is a need to reduce the risk of life-threatening systemic reactions, cost, and inconvenience. This will occur only with scientifically rigorous basic research and controlled clinical trials. Clinical use of unconventional immunotherapy procedures in practice is unwarranted. It is necessary for physicians who use such treatments to know whether the necessary studies are available showing evidence of efficacy and safety superior to conventional immunotherapy. Such studies are the responsibility of those who propose new treatments.

Technical and ethical problems associated with patch testing.

When relevant allergens are identified by patch testing, and patients can avoid them in their environment, improvement of dermatitis is the rule. Some forms of chronic dermatitis may not clear completely, but patients are usually satisfied with modification of their previously more severe problem. In 1981 when asked what he felt were the five most important advances in clinical dermatology during the 20th century, Dr. Marion B. Sulzburger, an icon in American dermatology, said that, "The increased use and usefulness of the patch test and the international standardization of test concentrations and methods" was number one. Those of us who are enthusiastic patch testers and fascinated by the evaluation of patients with irritant and allergic contact dermatitis would agree. It is a thrilling clinical experience to be able to tell a machinist that he need not stop his lifelong occupation, but instead will do fine if he will simply avoid the waterless hand cleanser he has been using which is preserved with glutaraldehyde. The woman whose facial dermatitis has embarrassed her for years and clears when she stops using the Quaternium-15 preserved moisturizer that you have identified in your patch testing is grateful to you forever, and again happy in her own life. In 1991, my research assistants, Patricia Norris and Mary Lou Belozer, and I studied 30 university hospital workers who answered our advertisement asking for individuals who believed they were troubled by their rubber gloves (unreported study). By evaluating these people through history, physical examination, and patch testing, we were able to prove glove relatedness in 14 of them. Nine of the 14 had contact urticaria to latex, and only 5 had allergic contact dermatitis to rubber glove ingredients. Fifteen of our patients had irritant dermatitis. In this study, none of the patients with allergic contact dermatitis to glove ingredients had contact urticaria. However, since that time, we have observed a number of patients who had both forms of allergic reaction. Three of our patients who presented with nummular (patchy) hand dermatitis also had contact urticaria to latex, but no positive patch tests. With latex glove avoidance, their dermatitis resolved; an example of how scratching urticaria can eventuate in longer lasting dermatitis in some people ("the itch that rashes"). The patients presented to their dermatologist with dermatitis, but their true initiating event was urticaria which lasted only hours. The gratifying part of this study was that patch testing and contact urticaria testing allowed us to discover the 5 patients with allergic contact dermatitis and the 9 patients with contact urticaria who could benefit from glove alternatives. We were also able to assure patients in the remainder of the group that their hand eczema was not glove induced, but rather was related to their wet work. In most instances, therapeutic intervention helped, but in several cases job changes were required. Patch testing, when done properly, produces exciting results. When done improperly, it confuses and misleads patients and results in embarrassment to physicians who cannot properly interpret their results. Should a physician choose to include patch testing in his or her evaluation of patients with contact dermatitis it is essential, in my view, that he or she have highly developed skills in the diagnosis and treatment of skin diseases, and that these physicians be elaborately trained in the techniques of application and the methods of interpretation of patch tests.

Allergen testing in patients with type I hypersensitivity.

Around 1 in 6 people have some form of allergy.1 The more common presentations include seasonal and perennial rhinitis, acute urticaria, immediate reactions to food and drugs and the early phase of atopic eczema and asthma. All of these are IgE mediated and classified as immediate (type I) hypersensitivity. Other presentations of hypersensitivity include transfusion reactions (type II; antibody reactions with antigens on cell surfaces), farmer's lung and bird fancier's disease (type III; immune complex-mediated reactions) and contact dermatitis and fixed drug eruptions like late reactions to antibiotics (type IV; delayed-type cell-mediated reactions).2 In this article we review the tests used for investigating patients with suspected type I hypersensitivity and consider their value in management.

Chronic allergic conjunctivitis

Chronic allergic conjunctivitis (CAC) or perennial allergic conjunctivitis (PAC) is the most frequent form of allergy of the conjunctiva that is encountered in Northern Europe, particularly in city areas. Itching, redness of the mucosa, swelling of the lids and tearing are the main symptoms. Seasonal factors and associated rhinitis are often noted. Symptoms may respond to antiallergic drugs. In contrast, there are generally no specific signs of the disease on slitlamp examination. Most of the time the mucosal aspect (papillary, follicular or atrophic type) is common to other forms of conjunctival allergy. Non-specific factors may predispose to the appearance of CAC, such as an intolerance to a contact lens, a local infection, or a trauma of the eye. Astigmatism, heterophoria and photosensitization may also be triggering agents for the appearance of symptoms of an authentic CAC in an atopic patient. The close association between allergic and non-specific factors may explain the possibility of unilateral forms of CAC and, most of all, the frequent association of CAC to other forms of chronic conjunctivitis. The diagnosis relies on good clinical evaluation of both symptoms and signs. Serum IgE levels are elevated in no more than 30% of cases while tear levels of IgE are more often pathological (over 50% of cases); skin-testing remains the best method for confirming the diagnosis. In most cases it indicates an allergy to house dust and/or mites. Elimination of the offending allergen is the first treatment in CAC. Antiallergic drugs are also effective, such as antihistamines and mast cell stabilizers, nedocromil sodium being very efficient in this respect. In cases where this kind of treatment cannot be pursued indefinitely, specific desensitization to house dust or mites is effective and induces a prompt resolution of symptoms, whereas signs will persist a long time. All non-specific factors associated with the allergy should also be carefully considered and treated, although results are better in pure rather than associated clinical forms of CAC.

Recurrent Eosinophilic Cystitis: A Case Responsive To Steroids

We report a case of eosinophilic cystitis that was responsive to prednisone but that recurred when the drug was withdrawn. The cause of eosinophilic cystitis remains an enigma but it probably represents a form of allergy. Investigation of etiology and therapeutic options are discussed.