Specific allergen immunotherapy (AIT) is the only therapeutic method with positive impact on natural course of allergic disease - affecting clinical development (including the progression of rhinitis to asthma) and new sensitisations. The actual problem is the increasing number of patients manifesting poly-sensitivity in allergy skin tests and / or in specific IgE tests. Usually, AIT is not recommended in such individuals. The objective we are facing is that in many patients tested as poly-reactive, we have to distinguish in which cases it is a true polysensitization, and when it is due to cross-reactivity of specific IgE antibodies induced by panallergens. This may really determine when AIT may be an appropriate course of action. The article focuses on this problem in more detail, applying the long time Czech and Slovak experience with allergy testing and allergen immunotherapy.
- MeSH
- Allergens MeSH
- Asthma MeSH
- Desensitization, Immunologic * MeSH
- Skin Tests MeSH
- Humans MeSH
- Cross Reactions MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Alergenová imunoterapie (AIT) je jedinou léčebnou metodou, která může ovlivnit přirozený průběh alergické nemoci – vývoj nových senzibilizací i klinický vývoj, včetně progrese rýmy do astmatu. Z tohoto důvodu je žádoucí úvaha o její indikaci u každého pacienta s alergií na inhalační alergeny. Problémem současnosti je narůstající počet alergiků, u nichž se klinické projevy alergie kombinují (alergická rýma s příznaky očními, kožními, astmatickými). V praxi narůstá počet tzv. polyvalentních pacientů, u kterých prokazujeme v kožním testu mnohočetné pozitivní odpo - vědi a AIT se proto nedoporučuje. V článku tento problém rozebíráme podrobněji, se snahou poskytnout orientaci v pojmech jako polyalergie, polyvalence, polyreaktivita, polysenzibilizace. V žádném případě nejde o hru se slovy, protože u mnoha „polyvalentních pacientů“ může jít ve skutečnosti jen o projev zkřížené reaktivity specifických IgE protilátek v alergenovém testu, ne oskutečnou polysenzibilizaci, aAIT může být v takovémto případě vhodná.
Allergen immunotherapy (AIT) is the only therapeutic method able to change natural course of allergic disease – both development of new sensitivities and clinical development, including progress from rhinitis to asthma. From this point of view it is desirable to consider AIT in every patient with allergy to inhaled allergens. Problem of present is increasing number of patients with combined allergic symptoms (allergic rhinitis with eye, skin and asthmatic symptoms). In praxis the number of so called polyvalent patients is increasing, in whose the AIT is not recommended. In this review we deal with terms as polyallergy, polyvalence, polyreactivity, polysensitisation. It is not „a play with words“, because in many „polyvalent patients“ in reality it may be only manifestation of cross reactive specific IgE antibodies in allergy test, no true polysensitivity, and in such cases AIT may be appropriate.
- Keywords
- zkřížená reaktivita,
- MeSH
- Allergens immunology adverse effects therapeutic use MeSH
- Hypersensitivity drug therapy immunology MeSH
- Administration, Inhalation MeSH
- Desensitization, Immunologic utilization MeSH
- Diagnosis, Differential MeSH
- Immunization MeSH
- Immunotherapy MeSH
- Humans MeSH
- Pollen immunology adverse effects MeSH
- Patient Selection MeSH
- Cross Reactions MeSH
- Check Tag
- Humans MeSH
Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
- MeSH
- Allergens MeSH
- Rhinitis, Allergic * complications MeSH
- Asthma * diagnosis epidemiology etiology MeSH
- Humans MeSH
- Multimorbidity MeSH
- Rhinitis * diagnosis epidemiology complications MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Background: Omalizumab is an efficient drug for patients with uncontrolled severe allergic asthma (SAA). However, little is known about the differences in omalizumab treatment outcomes among patients with different types of atopic sensitization. Here, we assessed the effect of sensitization to individual allergens or their combinations on the outcomes of anti-IgE therapy in patients with SAA. Methods: We performed a post hoc analysis of data of subgroups of patients enrolled in the Czech Anti-IgE Registry (CAR). The patients were evaluated at baseline and 16 weeks and 12 months after omalizumab treatment initiation. We analyzed the dependence of primary treatment outcomes [global evaluation of treatment effectiveness (GETE) after 16 weeks of treatment, a reduction in severe exacerbation rate (ER), and an improvement in the asthma control test (ACT) result during 12 months of treatment] and secondary outcomes [a reduction in systemic corticosteroid (SCS) use, an improvement in lung functions, and a fraction of exhaled nitric oxide] of patients with SAA treated with omalizumab for 12 months on sensitization to different perennial aeroallergens. We assessed sensitization to house dust mites, molds, and pets at baseline using skin prick tests and/or specific IgE measurement (semiquantitative evaluation). We compared polysensitized patients (sensitized to all tested allergens) with monosensitized (single positivity) or partially polysensitized patients (combined positivity but not to all allergens). Results: We enrolled 279 patients (58.3% women, mean age 52.9 years). Omalizumab treatment presented an 82.8% response rate (according to GETE). It significantly reduced severe asthma exacerbations and SCS use, and improved the ACT result in 161 responders. We identified a subgroup of responders with distinct sensitization patterns (polysensitization to all tested perennial allergens) with higher odds of being responders (OR = 2.217, p = 0.02) and lower tendency to improve ACT result (OR 0.398, p = 0.023) and reduce ER (OR 0.431, p = 0.034) than non-polysensitized patients. Conclusions: The clinical benefit of sensitization for patients with SAA receiving omalizumab may be particularly dependent on sensitization pattern. Polysensitized patients showed a higher tendency to be responders (GETE), but a lower tendency to improve the ACT result and reduce ER than non-polysensitized patients.
- Publication type
- Journal Article MeSH
Orálny alergický syndróm je prejavom skríženej reaktivity špecifických IgE protilátok vo č i homológnym molekulám, ktoré sa nachádzajú v peli a potravinách. Metodika: Súbor pozostával z 344 pacientov s prejavmi alergickej nádchy v jarnom období, ktorí mali pozitívny kožný prick test na pe ľ brezy. 198 pacientov (57,56 %) udávalo prejavy orálneho alergického syndrómu a 146 pacientov (42,44 %) nemalo tieto prejavy. U 102 pacientov s orálnym alergickým syndrómom sme vyšetrili senzibiliza č ný profil pomocou metodiky komponentovej diagnostiky ImmunoCAP ISAC. Výsledky: Orálny alergický syndróm v našom súbore naj č astejšie spôsobovali jablko, lieskovec, vlašský orech, arašid, brosky ň a, mrkva. Na alergénové komponenty PR-10 rodiny bolo senzibilizovaných 43,94 %, na profilíny 4,55 % a na lipid transfer proteíny 4,55 %. Záver: Nepo- tvrdili sme súvislos ť medzi senzibilizáciou na proteíny prenášajúce lipidy a vä č ším výskytom anafylaktických reakcií. Senzibilizácia na CCD bola spojená s výraznou polysenzibilizáciou.
Oral allergy syndrome (OAS) is syndrome of cross reactivity to homologous molecules in pollen and food. Method : 344 birch pollen allergic patients was investigated. 198 patients (57,56 %) referred oral allergy syndrome, 146 patients (42,44 %) didn ́t. Sensitization profiles was evaluated in 102 patients with OAS by component diagnostics ImmunoCAP ISAC. Results: Apple, hazelnut, walnut, peanut, peach and carrot caused the most often oral allergy syndrome in our patients. Hypersensitivity to allergen component of the PR 10 family was in 43,94 %, to profilins 4,55 %, to lipid transfer proteins 4,55 %. Conclusions : We didn ́t prove connection between sensitization to lipid transfer proteins and anaphylactic reactions. Sensitization to CCD was accompanied with polysensitization.
- MeSH
- Allergens * immunology adverse effects MeSH
- Betula adverse effects MeSH
- Immunization methods MeSH
- Humans MeSH
- Nuts MeSH
- Fruit MeSH
- Food Hypersensitivity * diagnosis epidemiology etiology MeSH
- Pollen immunology adverse effects MeSH
- Respiratory Hypersensitivity * diagnosis etiology immunology MeSH
- Rhinitis, Allergic, Seasonal * diagnosis epidemiology etiology MeSH
- Vegetables MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Farmakologickou léčbu alergické rhinokonjunktivitidy lze rozdělit na symptomatickou či kauzální. Symptomatická léčba je používána topická (oční kapky, nosní spraye) a celková (antihistaminika, antileukotrieny). Významně efektivní jsou kombinované lokální přípravky. Při léčbě alergické rhinitidy jsou preferovány nosní steroidy samostatně či v kombinaci s lokálním antihistaminikem před systémovými antihistaminiky. Alergenová imunoterapie představuje jedinou kauzální léčbu alergických onemocnění, která snižuje výskyt astmatu. Při správné volbě dominujícího alergenu je vhodná i pro polysenzibilizované osoby.
We can distinguish symptomatic and causative pharmacologic treatment of allergic rhinitis. It is used topic (eye drops, nasal spray) and systemic (antihistamines and antileukotriene drugs) for a relief of the symptoms. High effective are local combination drugs. It is recommended to prefer nasal steroids alone or in combination with local antihistamines to systemic antihistamines. Allergen-specific immunotherapy represents the only causative treatment of allergic diseases which is able to decrease the incidence of asthma. An appropriate choice of dominant allergen is a possible way for polysensitized people.
Alergenová imunoterapie (dále AIT) je jediným terapeutickým postupem v léčbě alergických onemocnění, který kauzálně zasahuje do vývoje specifické imunologické přecitlivělosti a svým účinkem je schopen tlumit proces alergizace atopika. Obecně přijatý model mechanismu účinku AIT předpokládá přesun od Th2/Th0 klonu (který je u atopika v převaze) ve prospěch Th0/Th1 klonu pomocných T lymfocytů s dokladovanými změnami v interleukinové síti a následných etážích imunitní odpovědi. Užití AIT se však jeví jako omezené u polysenzibilizovaných astmatiků s koincidencí alergických chorob. Máme pro tyto pacienty v současné době možnost alergenové vakcinace? Výzkum v oblasti terapeutik je též zaměřen na antagonisty IgE protilátek, z nichž jako perspektivní z hlediska účinnosti i bezpečnosti se jeví rhuMAb-E25 (recombinant human monoclonal antibody-E25). Rekombinantní technologií byla připravena molekula, která je z 95 % tvořena lidským imunoglobulinem IgG1, ke kterému je v oblasti hypervariabilních úseků připojena myší anti-IgE protilátka. RhuMAb-E25 (následné označení omalizumab) se selektivně váže na konstantní doménu Fc e 3 sérového IgE (tedy v místě vazby IgE s vysoko- a nízkoafinními buněčnými receptory) s následným snížením jeho sérové koncentrace. Lék je aplikován v subkutánní formě pacientům (6 – 75 let) s diagnózami alergické rýmy a bronchiálního astmatu. U diagnózy bronchiálního astmatu vedla léčba anti-IgE protilátkami ke snížení, u části pacientů až k vysazení inhalačních kortikosteroidů, k poklesu četnosti exacerbací, ke snížení spotřeby krátkodobě působících inhalačních beta - 2 mimetik současně se zlepšením skóre astmatu. Dle závěrů klinických studií lze říci, že léčba anti-IgE protilátkami vykazuje systémovou biologickou aktivitu a svým komplexním působením zasahuje podstatu alergického onemocnění. Kombinace AIT s terapií anti-IgE protilátkami se jeví jako perspektivní u pacientů s koincidencí alergických chorob a u polysenzitizovaných jedinců, kde užití alergenové vakcinace je omezené.
Allergen immunotherapy (AIT) is the only therapeutical method in treatment of allergic diseases which causally intervenes development of specific immunological hypersensitivity and is able to suppress allergic sensitisation of an atopic patient. According to present knowledge, helper T-lymphocytes are deemed the target of the modulation intervention of therapy. Shift from Th2/ThO clone (prevailing in atopic patients) in favour of Th0/Th1 clone is supposed. This shift is verified by changes in interleukins production and in following stages of immune response. The use of allergen immunotherapy in polysensitized asthmatics with coincidence of allergic diseases seems to be limited. Do we have a possibility of allergen vaccination for these patients at this time? Due to these reasons the research in the therapeutic field is also focused on IgE antagonist antibodies, out of these the perspective one according to efficacy and safety is rhuMAb-E25 (recombinant human monoclonal antibody-E25). The molecule was prepared by recombinant technology. This molecule is formed by 95% of human immunoglobulin IgG1 to which in hypervariable parts is connected mouse anti-IgE antibody. RhuMAb-E25 (here-after called omalizumab) is selectively bound to the constant domain Fc e 3 of the serum IgE (that means on the binding place of IgE with high-affinity and lowaffinity cellular receptors) with the following decrease of the serum IgE concentration. The drug is applicated in the subcutaneous form to the patients (the age of 6 to 75 years) with diagnosis of allergic rhinitis and bronchial asthma. With diagnose of bronchial asthma the anti-IgE treatment led to the decrease and with some patients to the break down of inhaled corticosteroids and also to the decrease of exacerbations, to the decrease of the consumption of the rescue medication with the improvement of the quality of life. According to the results of clinical studies it is possible to say the anti-IgE treatment proves the systemic biologic activity and with its complex influence affects the base of allergic disease. Combination treatment with anti-IgE plus specific immunotherapy in polysensitized patients seems to be perspective where the use of allergen vaccination is limited.
- MeSH
- Allergens pharmacology therapeutic use MeSH
- Hypersensitivity drug therapy immunology MeSH
- Asthma drug therapy immunology MeSH
- Immunoglobulin E antagonists & inhibitors administration & dosage pharmacology MeSH
- Immunoglobulin G physiology MeSH
- Immunotherapy methods MeSH
- Combined Modality Therapy methods MeSH
- Humans MeSH
- Omalizumab MeSH
- Check Tag
- Humans MeSH
