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Spezifische Immuntherapie bei der Behandlung von Patienten mit atopischer Dermatitis Ergebnisse einer plazebokontrollierten Doppelblindstudie
Abstract
Background: Specific immunotherapy (SIT) is the only causative method of treatment in the case of IgE-mediated allergic disease. There is extensive literature on the use of SIT in the management of respiratory allergies and insect venom hypersensitivity, but there is a paucity of published data concerning its use as a therapeutic approach in atopic dermatitis (AD). Objective: A double-blind placebo-controlled trial was conducted over a period of 12 months in order to evaluate the efficacy of SIT in the management of atopic dermatitis attributable to house dust mites or grass pollens. Methods: A total of 20 patients (5 - 40 years old) with AD and monovalent sensitization to airborne allergens (house dust mites or grass pollens) were enrolled in the study. SIT was performed using aluminum hydroxide-adsorbed allergen preparations administered by subcutaneous injection. Clinical efficacy of the treatment was assessed using the clinical score W-AZS index. Serum concentration of total IgE and allergen-specific IgE were measured, as were various immunological parameters including ECP, SIL-2R, IFN-y, IL-4, IL-5 and IL-10. Results: The mean value of W-AZS index in the SIT group before treatment was 87.6 ± 15.8 patients, and this decreased to 38.8 ± 34.4 patients after 12 months of therapy (p < 0.01). In the placebo group, the mean W-AZS index before treatment was 86.3 ± 15.7 patients and after 12 months of therapy it increased to 111.9 ± 41.7 patients. Comparative statistical analysis indicated a significant difference between the 2 groups in favor of patients treated with the active allergy vaccines (p < 0.01). Serum levels of specific IgE in the SIT group showed a tendency to decrease, whilst those in the placebo group tended to increase. Serum concentrations of selected immunological parameters including ECP, SIL-2R, IFN-y, IL-4, IL-5 and IL-10 were monitored before and after treatment, but did not show significant differences. Conclusion: Allergen-specific immunotherapy appeared to be an effective method of treatment for atopic dermatitis as judged by significant improvement in clinical index in cases with well-documented IgE-mediated allergic disease.
... Allergen-specific immunotherapy is the only causal treatment for AD-patients. Indications for allergen-specific immunotherapy in AD-patients include cases with insufficient response to existing treatment and documented allergy to IgE-dependent airborne allergens [3,[28][29][30][31]. Allergen-specific immunotherapy for AD shows considerable clinical efficacy in treatment of patients with signs of being allergic to both year-round and seasonal airborne allergens, especially in patients allergic to one allergen group [3,31]. ...
... Allergen-specific immunotherapy for AD shows considerable clinical efficacy in treatment of patients with signs of being allergic to both year-round and seasonal airborne allergens, especially in patients allergic to one allergen group [3,31]. So far, clinical effects with the use of allergen-specific immunotherapy in patients allergic to dust mites and pollens have been documented best [30,31]. There are no contraindications to deallergize patients with AD or concomitant other atopic diseases, such as allergic rhinitis or mild bronchial asthma [3,31]. ...
... While planning the therapy for AD-patients, allergological diagnostics should not be limited to skin prick tests, but should be supplemented with measurement of asIgE levels for proper allergens by means of brand new diagnostic methods, e.g. component-resolved [29][30][31]. ...
The treatment goal in atopic dermatitis is eliminating clinical symptoms of the disease, preventing exacerbations and complications, as well as improving patients' quality of life. In cases of severe atopic dermatitis and lack of response it is recommended to introduce systemic therapy. Patients ofter require multi-specialist consultations, and occasionally hospitalization. It is not recommended to use acupuncture, acupressure, bioresonance, homeopathy, or Chinese herbs in the treatment of atopic dermatitis.
... Wskazaniem do SIT u pacjentów z AZS jest niewystarczająca odpowiedź na dotychczasowe leczenie z udokumentowanym uczuleniem na IgE-zależne alergeny powietrznopochodne [15,[81][82][83]. Na podstawie danych literatu-kOMeNTarze i OMÓWIENIA WYTYCZNYCH rowych i doświadczeń własnych można stwierdzić, że SIT w AZS wykazuje dużą skuteczność kliniczną w leczeniu chorych z objawami uczulenia na alergeny powietrznopochodne całoroczne i sezonowe, szczególnie u pacjentów uczulonych na jedną grupę alergenów [15,84]. Najlepiej udokumentowane są efekty kliniczne uzyskiwane przy zastosowaniu SIT u pacjentów uczulonych na roztocze kurzu domowego i pyłki roślin [84,85]. ...
... Na podstawie danych literatu-kOMeNTarze i OMÓWIENIA WYTYCZNYCH rowych i doświadczeń własnych można stwierdzić, że SIT w AZS wykazuje dużą skuteczność kliniczną w leczeniu chorych z objawami uczulenia na alergeny powietrznopochodne całoroczne i sezonowe, szczególnie u pacjentów uczulonych na jedną grupę alergenów [15,84]. Najlepiej udokumentowane są efekty kliniczne uzyskiwane przy zastosowaniu SIT u pacjentów uczulonych na roztocze kurzu domowego i pyłki roślin [84,85]. Nie ma przeciwwskazań do odczulania pacjentów z AZS i współistniejącymi innymi chorobami atopowymi, takimi jak alergiczny nieżyt nosa czy łagodna astma oskrzelowa [15,83]. ...
... O powodzeniu SIT decyduje właściwy dobór składu szczepionek i kolejności ich podawania u chorych na AZS z alergią wieloważną. Przy planowaniu SIT u chorych na AZS diagnostyka alergiczna nie powinna się ograniczać do wykonania SPT, lecz powinna być uzupełniona oznaczeniami poziomu asIgE dla odpowiednich alergenów [84,85]. Objawy niepożądane występują głównie w fazie indukcji SIT i mają charakter łagodny oraz przejściowy. ...
... Allergen immunotherapy is indicated in patients with AD in cases of inadequate response to previous treatment with documented IgE-mediated allergy to airborne allergens [15,[81][82][83]. Based on literature and our own experience we can conclude that AIT in AD has a high clinical efficacy in the treatment of patients with symptoms of allergy to perennial and seasonal aeroallergens, particularly those who are allergic to one group of allergens [15,84]. To date, the clinical effects of using AIT have been best documented for patients allergic to house dust mites and pollen [84,85]. ...
... Based on literature and our own experience we can conclude that AIT in AD has a high clinical efficacy in the treatment of patients with symptoms of allergy to perennial and seasonal aeroallergens, particularly those who are allergic to one group of allergens [15,84]. To date, the clinical effects of using AIT have been best documented for patients allergic to house dust mites and pollen [84,85]. There are no contraindications for desensitization of AD patients with other coexisting AD like allergic rhinitis or mild asthma [15,83]. ...
... The correct composition of the vaccines and the order of their administration in AD patients with polyvalent allergy determines the success of AIT. When planning AIT in patients with AD, allergic diagnosis should not be limited to skin prick tests but should be supplemented with assessment of the level of specific IgE to the respective allergens [84,85]. Side effects tend to occur mainly during the induction phase of AIT and are usually mild and transient. ...
Atopic dermatitis (AD) is a condition frequently encountered in medical practices across the country. More than 60% of children with AD are at risk to develop allergic rhinitis or asthma (the atopic march). Patients with AD have a unique predisposition to colonization or infection by Staphylococcus aureus. Treatments for AD need to rapidly control symptoms of the disease, improve quality of life and prevent exacerbations. Given the chronic and relapsing nature of the disease, therapies need to encourage good compliance and be well tolerated.
... Allergen immunotherapy is indicated in patients with AD in cases of inadequate response to previous treatment with documented IgE-mediated allergy to airborne allergens [15,[81][82][83]. Based on literature and our own experience we can conclude that AIT in AD has a high clinical efficacy in the treatment of patients with symptoms of allergy to perennial and seasonal aeroallergens, particularly those who are allergic to one group of allergens [15,84]. To date, the clinical effects of using AIT have been best documented for patients allergic to house dust mites and pollen [84,85]. ...
... Based on literature and our own experience we can conclude that AIT in AD has a high clinical efficacy in the treatment of patients with symptoms of allergy to perennial and seasonal aeroallergens, particularly those who are allergic to one group of allergens [15,84]. To date, the clinical effects of using AIT have been best documented for patients allergic to house dust mites and pollen [84,85]. There are no contraindications for desensitization of AD patients with other coexisting AD like allergic rhinitis or mild asthma [15,83]. ...
... The correct composition of the vaccines and the order of their administration in AD patients with polyvalent allergy determines the success of AIT. When planning AIT in patients with AD, allergic diagnosis should not be limited to skin prick tests but should be supplemented with assessment of the level of specific IgE to the respective allergens [84,85]. Side effects tend to occur mainly during the induction phase of AIT and are usually mild and transient. ...
A b s t r a c t Atopic dermatitis (AD) is a condition frequently encountered in medical practices across the country. More than 60% of children with AD are at risk to develop allergic rhinitis or asthma (the atopic march). Patients with AD have a unique predisposition to colonization or infection by Staphylococcus aureus. Treatments for AD need to rapidly control symptoms of the disease, improve quality of life and prevent exacerbations. Given the chronic and relapsing nature of the disease, therapies need to encourage good compliance and be well tolerated.
... Stanowisko ekspertÓw Sekcji Dermatologicznej Polskiego Towarzystwa Alergologicznego i Sekcji AlergoLogicznej Polskiego Towarzystwa DermatoLogicznego z objawami uczulenia na aLergeny powietrznopochodne całoroczne i sezonowe, szczegÓlnie na jedną grupę aler-genÓw [15' 84]. Najtepiej udol<umentowane są efekty l<tiniczne przy zastosowaniu S|T u pacjentÓw uczutonych na roztocze l<urzu domowego i pyłl<i rośtin [84,85]. Nie ma przeciwwsl<azań do odczuLania pacjentÓw z A,ZS i ze wspÓłistn iejącymi in nymi chorobam i atopowym i, tal<im i ja|< alergiczny nieŹyt nosa czy łagodna astma oSl(rzelowa [15,83]. ...
... Zazwy czaj objawy niepoządane SlT mają charal<ter łagodny, przemi)ający i dotyczą przede wszystl<im objawÓw s|<Órnych. Jedna|< stosując S|| musimy byĆ zawsze przygotowani na interwe n cję fa rm al<ologiczn ą i pos i ad a Ć zabezpieczen ie a nestezjologiczne[85]. Atergenowa im munoterapia swoista powin na byĆ prowadzona systematycznie przynaj m n iej przez 4-5 lat, przez [e|<arza specjatistę, przy spełnionych waru n kach bezpiecze ń stw a, z uwzględnien iem możliwości wystąpienia rea|<cji niepoŹądanych[84,85].Leczenie alternatywneNie ma wysIarczających dowodÓw na s|<utecznośĆ nienasyconych |<wasÓw tłuszczowych stosowanych doustnie Lub miejscowo, kąpieLi w solan|<ach czy krochmalu.Nie potwierdzono też zasadności stosowania ziÓł chiń-s|<ich w leczeniu AZS. Bral<uje dowodÓw na skutecznośĆ lecze n ia AZS al<upun kturą, homeopatią' aromaterapią[15].Wydaje się, że suplementacja witaminą D lub E moze byĆ przydaIna w teczeniu AZS, ale Wymaga to datszych l<ontrolowanych badań, zan i m powstaną bezpośred n ie rel<omendacje[15]. ...
... A smaller DBPC study involving 20 patients with HDM-or grass pollen sensitization also showed objective and subjective symptom relief accompanied by immunological changes under ASIT. 130 Another large, randomized double-blind placebo-controlled study investigated 168 adult AE patients for 18 months. The study did not reveal efficacy in the AE patients studied, but a subgroup analysis showed statistical significance of SCORAD reduction in subgroup of severe AE patients with SCORAD > 50. ...
This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease‐modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen‐specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress‐induced exacerbations. Therapeutic patient education (‘Eczema school’) is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.
... In recent years, different attempts to perform systematic review and meta-analysis on AIT in AD were made. The first systematic review of the literature was conducted by Bussmann et al. [57], who analyzed 10 studies [13,14,21,23,[25][26][27]36,40,58,59] distinguishing among placebo-controlled and observational studies. The authors concluded that the overall effect was in favor of AIT, but no conclusion and recommendation could be formulated at that moment. ...
Introduction: Atopic dermatitis (AD) is a chronic relapsing skin disease, characterized by flare-up due to the exposure to allergens in patients sensitized to them. Currently, therapy of AD is mainly based on symptomatic treatment and avoidance of irritating/allergenic factors, house dust mites being particularly important. Allergen immunotherapy (AIT) is suggested to be the only etiologic treatment, to modify the natural history of the disease.
Areas covered: The aim of this review is investigating the putative role of AIT in AD through the evaluation of the most recent scientific literature. Several studies have been conducted since 1970, with promising results in improving the clinical outcome of AD, but they often lack the necessary scientific rigorousness. Moreover, heterogeneity of the studies makes it very difficult to compare and to analyze data in a systematic review or meta-analysis.
Expert commentary: As a result of the above-mentioned limitations, the treatment of AD with causative aeroallergen can nowadays be suggested only as an add-on therapy in selected patients who are non-responsive to the traditional therapy.
... Auch zeigte sich in den Behandlungsgruppen , denen höhere Hausstaubmilbenkonzentrationen injiziert worden waren, ein reduzierter Verbrauch von topischen Glukokortikosteroiden. In einer weiteren doppelblinden, placebokontrollierten Studie, die allerdings mit weniger Patienten (n=20) mit monovalenter Hausstaubmilben-oder Gräserpollensensibilisierung durchgeführt worden war, konnte von Silny et al. ebenfalls eine Verbesserung des objektiven Hautbildes und der subjektiven Symptome Juckreiz und Schlaflosigkeit gezeigt werden (Silny et al. 2006). In einer 2007 publizierten randomisierten , Placebo-kontrollierten Studie zur sublingualen Immuntherapie (SLIT) bei atopischem Ekzem, die noch nicht in den o.g. ...
This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti‐inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long‐term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long‐term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti‐inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.
The introduction of glucocorticosteroids in dermatology was the greatest progress for eczema patients in the second half of the twentieth century. For atopic dermatitis, mostly mild to moderate strength steroids are adequate. The application of topical glucocorticosteroids in the correct vehicle should be timely limited and ended via a “tandem therapy.” Proactive strategies with once or twice weekly applications of the effective substance have proven helpful. The most important side effects of topical glucocorticosteroids include skin atrophy and the common manifestation of perioral rosacea-like dermatitis which occurs especially in young women after topical corticosteroids.
Zusammenfassung
Bei dem Krankheitsbild der Neurodermitis handelt es sich um eine chronische oder chronisch‐rezidivierende, nichtkontagiöse, entzündliche Hauterkrankung mit in der Regel starkem Juckreiz. Darüber hinaus besteht ein Risiko für komplizierte Verläufe mit bakteriellen oder viralen Superinfektionen. Sowohl die genetische Prädisposition als auch zahlreiche Auslösefaktoren spielen für die Erstmanifestation und das Auftreten der Erkrankungsschübe eine wichtige Rolle, so dass auch die Therapiekonzepte vielfältig sind. Bei zahlreichen für die Neurodermitis zur Verfügung stehenden Behandlungsoptionen gilt es, in Abstimmung mit den Patienten bzw. Eltern erkrankter Kinder fallorientiert einen optimalen Behandlungsplan aufzustellen, der im Verlauf ggf. erneut angepasst werden muss.
Die vorliegende Kurzfassung der S2k‐Leitlinie gibt einen Überblick über alle bisher zur Verfügung stehenden, evidenzbasierten Diagnoseverfahren und Therapiemöglichkeiten sowie über die entsprechenden Empfehlungen, die durch die an dieser Leitlinie beteiligten Fachgesellschaften und Verbände ausgesprochen werden. Diese Empfehlungen wurden auf der Grundlage der bislang zu dem jeweiligen Verfahren vorliegenden klinisch‐wissenschaftlichen Datenlage, die in der ausführlichen Fassung dieser Leitlinie (unter www.awmf.org und jddg.org ) beschrieben ist, konsentiert.
Die atopische Dermatitis (AD) ist eine der häufigsten chronisch entzündlichen Hauterkrankungen mit zunehmender Prävalenz. Ungefähr 80% der erwachsenen Patienten mit AD haben Sensibilisierungen gegenüber saisonalen sowie perennialen Aeroallergenen und/oder Lebensmittelallergenen, die als Provokationsfaktoren für die Entstehung und Unterhaltung von Ekzemen dienen können. Neben vielfältigen befundadaptierten lokalen und systemischen Therapiemöglichkeiten der AD spielen das Erkennen und nach Möglichkeit auch die konsequente Meidung dieser Provokationsfaktoren eine herausragende Rolle im Krankheitsmanagement. Während die klinische Wirksamkeit einer SIT bei Patienten mit allergischer Rhinitis, Asthma bronchiale und Insektengiftallergie gut belegt ist, wird der Stellenwert dieser Therapie bei der AD nach wie vor kontrovers diskutiert. Inzwischen gibt es doppelblinde, placebokontrollierte klinische Studien, die eine gute Wirksamkeit der SIT bei Patienten mit AD zeigen. Bei der Nahrungsmittelallergie gibt es erste kasuistische Hinweise und klinische Studien mit kleinen Patientenzahlen für die Wirksamkeit einer SIT sowohl mit den Nahrungsmitteln selbst als auch mit kreuzreaktiven Aeroallergenen. Auch hier sind doppelblinde, placebokontrollierte Studien an größeren Patientenkollektiven notwendig, um die klinische Wirksamkeit und immunologische Wirkmechanismen der SIT bei Nahrungsmittelallergie näher zu untersuchen.
Background:
Specific allergen immunotherapy (SIT) is a treatment that may improve disease severity in people with atopic eczema (AE) by inducing immune tolerance to the relevant allergen. A high quality systematic review has not previously assessed the efficacy and safety of this treatment.
Objectives:
To assess the effects of specific allergen immunotherapy (SIT), including subcutaneous, sublingual, intradermal, and oral routes, compared with placebo or a standard treatment in people with atopic eczema.
Search methods:
We searched the following databases up to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), Web of Science™ (from 2005), the Global Resource of EczemA Trials (GREAT database), and five trials databases. We searched abstracts from recent European and North American allergy meetings and checked the references of included studies and review articles for further references to relevant trials.
Selection criteria:
Randomised controlled trials (RCTs) of specific allergen immunotherapy that used standardised allergen extracts in people with AE.
Data collection and analysis:
Two authors independently undertook study selection, data extraction (including adverse effects), assessment of risk of bias, and analyses. We used standard methodological procedures expected by Cochrane.
Main results:
We identified 12 RCTs for inclusion in this review; the total number of participants was 733. The interventions included SIT in children and adults allergic to either house dust mite (10 trials), grass pollen, or other inhalant allergens (two trials). They were administered subcutaneously (six trials), sublingually (four trials), orally, or intradermally (two trials). Overall, the risk of bias was moderate, with high loss to follow up and lack of blinding as the main methodological concern.Our primary outcomes were 'Participant- or parent-reported global assessment of disease severity at the end of treatment'; 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'; and 'Adverse events, such as acute episodes of asthma or anaphylaxis'. SCORing Atopic Dermatitis (SCORAD) is a means of measuring the effect of atopic dermatitis by area (A); intensity (B); and subjective measures (C), such as itch and sleeplessness, which we used.For 'Participant- or parent-reported global assessment of disease severity at the end of treatment', one trial (20 participants) found improvement in 7/9 participants (78%) treated with the SIT compared with 3/11 (27%) treated with the placebo (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.02 to 7.96; P = 0.04). Another study (24 participants) found no difference: global disease severity improved in 8/13 participants (62%) treated with the SIT compared with 9/11 (81%) treated with the placebo (RR 0.75, 95% CI 0.45 to 1.26; P = 0.38). We did not perform meta-analysis because of high heterogeneity between these two studies. The quality of the evidence was low.For 'Participant- or parent-reported specific symptoms of eczema, by subjective measures', two trials (184 participants) did not find that the SIT improved SCORAD part C (mean difference (MD) -0.74, 95% CI -1.98 to 0.50) or sleep disturbance (MD -0.49, 95% CI -1.03 to 0.06) more than placebo. For SCORAD part C itch severity, these two trials (184 participants) did not find that the SIT improved itch (MD -0.24, 95% CI -1.00 to 0.52). One other non-blinded study (60 participants) found that the SIT reduced itch compared with no treatment (MD -4.20, 95% CI -3.69 to -4.71) and reduced the participants' overall symptoms (P < 0.01), but we could not pool these three studies due to high heterogeneity. The quality of the evidence was very low.Seven trials reported systemic adverse reactions: 18/282 participants (6.4%) treated with the SIT had a systemic reaction compared with 15/210 (7.1%) with no treatment (RR 0.78, 95% CI 0.41 to 1.49; the quality of the evidence was moderate). The same seven trials reported local adverse reactions: 90/280 participants (32.1%) treated with the SIT had a local reaction compared with 44/204 (21.6%) in the no treatment group (RR 1.27, 95% CI 0.89 to 1.81). As these had the same study limitations, we deemed the quality of the evidence to also be moderate.Of our secondary outcomes, there was a significant improvement in 'Investigator- or physician-rated global assessment of disease severity at the end of treatment' (six trials, 262 participants; RR 1.48, 95% CI 1.16 to 1.88). None of the studies reported our secondary outcome 'Parent- or participant-rated eczema severity assessed using a published scale', but two studies (n = 184), which have been mentioned above, used SCORAD part C, which we included as our primary outcome 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'.Our findings were generally inconclusive because of the small number of studies. We were unable to determine by subgroup analyses a particular type of allergen or a particular age or level of disease severity where allergen immunotherapy was more successful. We were also unable to determine whether sublingual immunotherapy was associated with more local adverse reactions compared with subcutaneous immunotherapy.
Authors' conclusions:
Overall, the quality of the evidence was low. The low quality was mainly due to the differing results between studies, lack of blinding in some studies, and relatively few studies reporting participant-centred outcome measures. We found limited evidence that SIT may be an effective treatment for people with AE. The treatments used in these trials were not associated with an increased risk of local or systemic reactions. Future studies should use high quality allergen formulations with a proven track record in other allergic conditions and should include participant-reported outcome measures.
BACKGROUND: Allergen-specific immunotherapy (allergen-SIT) is the only treatment directed at the cause of IgE-mediated allergic diseases. However, there is controversy over the use of SIT for patients with atopic dermatitis. OBJECTIVE: We performed a systematic review and meta-analysis to assess the efficacy of SIT for patients with atopic dermatitis. METHODS: We performed manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane databases (through December 10, 2012) for randomized controlled trials that compared SIT with placebo for patients with atopic dermatitis. The outcome of interest was a dichotomous variable, in terms of treatment success; a meta-analysis was performed by using a random-effects analysis. Subgroup analyses were carried out to evaluate the effects of long-term treatment (more than 1 year), SIT for severe atopic dermatitis, SIT for children, and subcutaneous and sublingual administration of immunotherapy. RESULTS: We analyzed 8 randomized controlled trials that comprised a total of 385 subjects. We found that SIT has a significant positive effect on atopic dermatitis (odds ratio [OR], 5.35; 95% CI, 1.61-17.77; number needed to treat, 3; 95% CI, 2-9). SIT also showed significant efficacy in long-term treatment (OR, 6.42; 95% CI, 1.50-27.52) for patients with severe atopic dermatitis (OR, 3.13; 95% CI, 1.31-7.48), and when administered subcutaneously (OR, 4.27; 95% CI, 1.36-13.39). CONCLUSIONS: A meta-analysis provides moderate-level evidence for the efficacy of SIT against atopic dermatitis. However, these findings are based on an analysis of a small number of randomized controlled trials, with considerable heterogeneity among trials.
The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.
Die atopische Dermatitis (AD) ist eine chronisch inflammatorische Hauterkrankung aus dem atopischen Formenkreis, die mit charakteristischen ekzematösen Läsionen einhergeht. Neben vielfältigen befundadaptierten lokalen und systemischen Therapiemöglichkeiten der AD spielt das Erkennen und nach Möglichkeit auch die konsequente Meidung von Provokationsfaktoren eine herausragende Rolle im Krankheitsmanagement. Aeroallergene wie Hausstaubmilben, Pollen und Tierepithelien stellen bei entsprechend sensibilisierten Patienten wichtige Provokationsfaktoren dar. Während die klinische Wirksamkeit einer spezifischen Immuntherapie (SIT) bei Patienten mit allergischer Rhinitis, Asthma bronchiale und Insektengiftallergie gut belegt ist, wird der Stellenwert dieser Therapie bei der AD kontrovers diskutiert. Inzwischen gibt es doppelblinde, placebokontrollierte klinische Studien, die eine gute Wirksamkeit der SIT bei Patienten mit AD und einer Sensibilisierung gegenüber Hausstaub und Gräserpollen zeigen, sodass die SIT in ausgewählten Fällen einen Behandlungsansatz darstellen kann. Bis die SIT jedoch als Behandlungsoption in der Routineversorgung von Patienten mit AD angesehen werden kann, sind weitere klinische Studien an größeren Patientenkollektiven erforderlich.
The goal was to assess the effectiveness of specific immunotherapy (SIT) in reduction of symptoms and medication score in patients with immunoglobulin E (IgE) mediated extrinsic form of atopic dermatitis (AD); and to assess the effectiveness of oral immunotherapy (OIT) as "active" treatment to achieving tolerance for food(s) in patients with IgE mediated food allergy.
Computerized bibliographic searches of MEDLINE (1998-2010) were supplemented by hand searches of reference lists. Studies were included if they were double-blind randomized controlled trials comparing subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) or OIT with placebo. However uncontrolled studies and case reports were also included.
Thirty-two studies were analyzed. Because of the high heterogeneity of the AD studied only results of 2 placebo controlled studies 1-SCIT and 1-SLIT respectively were comparable. Among OIT studies: 4 carried out with control groups were analyzed.
From 36% to 92% of patients treated with OIT reached tolerance to cow's milk or egg; a rate of 8% to 53% reached partial tolerance. The patients had either clinical history of severe systemic reactions to foods: anaphylaxis, or mild to moderate reactions. Regarding SIT for AD: 72% of patients treated with house dust mite SCIT and 54% treated with SLIT had a significant improvement of SCORAD-Index.
This review found that OIT with cow's milk or egg is effective in achieving full tolerance or partial tolerance in the majority of patients with IgE mediated food allergy. SIT may represent an additional therapeutic tool for the treatment of extrinsic AD in properly selected patients.
Aeroallergens are relevant eliciting factors of allergic rhinoconjunctivitis and bronchial asthma but also of atopic eczema. The use of allergen-specific immunotherapy as in respiratory atopic diseases is controversial in patients with atopic eczema, but refined diagnostic methods to characterize subgroups of patients with relevant allergies and the results of smaller controlled studies give rise to new approaches in this field. This article reviews the theoretical problems and practical results associated with allergen-specific immunotherapy in atopic eczema.
Although immunotherapy is not accepted as a curative treatment for atopic dermatitis (AD), most studies have shown positive effects of immunotherapy on AD patients. The serum levels of CC chemokine ligand 17 (CCL17), CCL22 and CCL18 have been reported to be highly correlated with disease severity, which suggests important roles for CC chemokines in the pathogenesis of AD.
The purpose of this study was to investigate the changes in clinical and immunologic markers before and after immunotherapy and to find which CC chemokines correlate with clinical improvement after immunotherapy with house dust mite (HDM) allergens in AD patients.
A total of 20 AD patients who were sensitized to HDM allergens through a skin-prick test and Pharmacia CAP system were treated with subcutaneous immunotherapy using HDM allergens (treatment duration 12-60 months). Eczema area and severity index scores in 20 patients with AD decreased significantly after immunotherapy (P < 0.001). Serum total immunoglobulin E (IgE) and Dermatophagoides pteronyssinus-specific IgE levels tended to decrease after treatment although this was not statistically significant, and the D. farinae-specific IgE level showed no change. Serum CCL17, CCL22 and CCL18 levels decreased significantly from baseline after treatment (P = 0.043, 0.017 and <0.001, respectively). The percentage reductions in serum CCL17 and CCL22 level were significantly correlated with reductions in disease severity (P = 0.007, R(2) = 0.301 and P = 0.037, R(2) = 0.177, respectively).
We suggest that CCL17 and CCL22 are good immunological marker candidates that can be used to assess clinical improvement after immunotherapy in AD patients.
House dust mite (HDM) allergens are perennial indoor allergens, which may play a role as allergic trigger factors in atopic dermatitis (AD). Facilitated by their high enzymatic activity, HDM allergens are capable of penetrating the impaired epidermal skin barrier in patients with AD, gaining access to immune cells. In this way, HDM allergens induce both allergic reactions of the immediate type and allergic reactions of the delayed type, which contribute to impairment of AD. Because allergen reduction achieved by encasing strategies does not always lead to significant improvement of clinical symptoms, specific immunotherapy (SIT) might represent an attractive therapeutic option for long-time treatment of this subgroup of patients with AD. However, systematic studies on the effectiveness of SIT in patients with AD are rare. Furthermore, data on the immunologic changes induced by SIT in patients with AD are not well studied. In this review, we provide an overview of the pathogenic impact of HDM allergens as an example for aeroallergens on the course of AD. In addition, we discuss prophylactic and therapeutic options for the treatment of HDM allergy in patients with AD, including a summary of the current data available on SIT as a potential therapeutic option for patients with AD.
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