Summary
According to European Directive 2001/83/EC, test and therapeutic allergens are medicinal products in all Member States of the European Union. This applies equally to prick test and to patch ...test (PT) allergens (haptens). All test allergens commercially marketed in Germany are finished medicinal products requiring marketing authorization (MA). Currently, 211 PT substances are authorized in Germany, and an additional 59 are in an ongoing MA process and are marketable under a transitional provision until a decision on MA is made. The regulatory guidance (CMDh/399/2019) of the Co-ordination Group for Mutual Recognition and Decentralized Procedures—Human (CMDh), published in July 2020, specifies the regulatory requirements for different allergen products. Due to differences in origin and exposure, use, mode of action, and safety risks, the guideline clearly differentiates between products with active ingredients of biological origin (allergen extracts from natural source materials) and products with active ingredients of non-biological origin (hapten-based PT substances). Currently, guideline-compliant patch testing is hampered by the lack of numerous commercial PT allergens from the standard and special test series. Background and possible scenarios for mitigation are presented here.
Summary
Background and objectives
The relevance of contact allergens is subject to constant change due to changing exposures according to consumers’ preferences and legal requirements. The objective ...of this paper is to present trends in contact sensitization from the DKG and IVDK patch test clinics, which have led to changes in the DKG standard series (as of 1.1.2014), as well as the current legal framework which has influenced these trends and the way patch testing is performed.
Patients and methods
The patients from 56 DKG and IVDK patch test clinics from 2010 (n = 13,117), 2011 (n = 13,320) and 2012 (n = 12,529) were analyzed with regard to frequencies of sensitization (hit list) to contact allergens as well as the location of allergic contact dermatitis.
Results
With a sensitization rate of 15 % nickel is still the most frequently recognized contact allergen. An increase can be observed for fragrance mix I (9.1 %), the preservative composition of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) (4.5 %) and methylisothiazolinone (MI) alone (6.8 %). A decline is present for potassium dichromate from above 6 % (2007) to 3 % (2012) and for bufexamac (currently at 0.6 %). Backgrounds, legal requirements and resulting changes to the DKG standard series are illustrated.
Conclusions
The indicated trends demonstrate the relevance of clinical epidemiology and the “sentinel function” of DKG and IVDK with regard to public health and prevention of contact allergies.
Indications for epicutaneous patch testing include the detection or exclusion of allergic contact dermatitis of the skin, transitional mucosa or oral mucosa, suspected delayed-type immune reactions ...to ingredients of implants, and certain drug reactions (maculopapular exanthema, symmetrical drug-related intertriginous and flexural exanthema SDRIFE, acute generalized exanthematous pustulosis AGEP, and fixed drug eruption). When available, allergen preparations that have been pharmaceutically tested and that are approved or marketable as medicinal products should be used. Existing diagnostic gaps can be closed by testing the patient’s own materials in a suitable preparation. Interferences of ultraviolet (UV) light exposure or drugs with patch test reactions have to be considered. In addition to the reading after 48 h and 72 h, a further reading between day 7 (168 h) and day 10 (240 h) is useful, since about 15% of the positive test reactions remain undetected without this late reading. All positive patch test reactions considered allergic must be evaluated with regard to their clinical relevance based on existing exposures.
Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the ...highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper, we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)3) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre‐existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is presensitized to the antigen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilized in AIT redirect the Th2 immune response towards Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three‐to‐five‐year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need.
Background A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate ...whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. Objectives We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. Methods In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table) or placebo subcutaneously once every 2 or 4 weeks for 24 weeks. The primary end point was the change from baseline in mean weekly urticaria activity score after 24 weeks of treatment, as calculated from patients’ diaries. The safety and tolerability of omalizumab were also assessed. Results Of the 49 randomized patients (omalizumab, n = 27; placebo, n = 22), 42 completed the study. At week 24, patients demonstrated a mean reduction in the weekly urticaria activity score from baseline of 17.8 with omalizumab and 7.9 with placebo ( P = .0089). Complete protection from wheal development was observed in 19 (70.4%) patients in the omalizumab group compared with only 1 (4.5%) patient in the placebo group. The rate of adverse events was similar in both groups. Conclusions The results of this study indicate that omalizumab is an effective treatment option for patients with CU with IgE autoantibodies against TPO who are refractory to conventional treatment.
Immuntherapien von Allergien: Aktueller Stand Mahler, Vera; Kleine-Tebbe, Jörg; Vieths, Stefan
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz,
2020/11, Letnik:
63, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Zusammenfassung
Die Allergenimmuntherapie (AIT) wirkt als einzige kausale, krankheitsmodifizierende Therapieform neben einer Symptomlinderung der Progression allergischer Erkrankungen entgegen. ...Dieser Beitrag liefert einen Überblick zu aktuellen immunologischen, regulatorischen und praxisbezogenen Aspekten der AIT. Die neueste Fachliteratur wurde einbezogen. Zudem werden konzeptionelle regulatorische Entwicklungen aus der Abteilung Allergologie der zuständigen Bundesoberbehörde Paul-Ehrlich-Institut dargestellt.
Die derzeit in Deutschland zugelassenen 62 und die weiteren 61 AIT-Produkte, die sich im Entwicklungsprogramm der Therapieallergene-Verordnung (TAV) befinden, umfassen 95 Produkte zur subkutanen (SCIT) und 28 zur sublingualen Behandlung (SLIT) von Allergien gegen Birken‑/Erlen‑/Haselpollen, Gräser- und Kräuterpollen sowie Hausstaubmilben und Insektengifte. Als Wirkstoffe kommen native und chemisch modifizierte Allergenextrakte (Allergoide), adsorbiert an Aluminium, Tyrosin (z. T. Monophosphoryl-Lipid-A-adjuvantiert) oder Laktose, oder als Lyophilisate zum Einsatz.
Die 123 AIT-Produkte unterliegen der staatlichen Chargenprüfung. Individualrezepturen zur Behandlung weniger prävalenter Allergien (z. B. gegen Olivenpollen, Tierhaare, Speichermilben oder Schimmelpilze) unterliegen nicht der behördlichen Chargenprüfung. Besonderer Entwicklungsbedarf besteht für AIT-Produkte zur Behandlung von Kindern.
Als neue Wirkstoffklasse befinden sich Nahrungsmittelallergene in klinischen Phase-II- und Phase-III-Studien. Ein erstes Präparat zur oralen AIT der Erdnussallergie bei Kindern ist derzeit in einem zentralen europäischen Zulassungsverfahren. Die Zulassung kann nur bei positiver Nutzen-Risiko-Bilanz erfolgen. Wissenschaft und Regulation stehen in kontinuierlichem Austausch über die Entwicklung von AIT-Produkten, die dem aktuellen Stand der klinischen Forschung und Regulation in der Europäischen Union entsprechen und eine frühzeitige Kausalbehandlung weitverbreiteter Allergien ermöglichen.
Anaphylaxis to additives in vaccines Mahler, Vera; Junker, Ann-Christine
Allergo journal international,
2022/7, Letnik:
31, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Summary
Anaphylaxis in connection with the administration of vaccines occurs only very rarely. Triggers of immunoglobulin IgE-mediated and non-IgE-mediated anaphylaxis—in addition to the active ...ingredient itself—may be excipients contained in the vaccine due to their special properties. Some of the excipients in medicinal products are the same compounds used as additives in food. Furthermore, residues from the manufacturing process (e.g., chicken egg white, casein, antibiotics, formaldehyde) or contaminants (e.g., from the primary packaging material) may be potential triggers of anaphylaxis in vaccines. This review article provides an overview of ingredients in vaccines that pose an allergenic risk potential. The components of COVID-19 vaccines approved and marketed in Germany are discussed with regard to their potential for triggering anaphylaxis and possible pathophysiological mechanisms involved.
Self-assessment of general health status has a significant influence on patient-related outcomes. The aims of this study were to investigate and compare the level of agreement between patients' and ...dermatologists' assessments of the severity of chronic hand eczema. From the German registry "German Chronic Hand Eczema Patient Long-Term Management Registry" (CARPE), 1,281 pairs of patients with chronic hand eczema and their dermatologists were included. Of these, 788 pairs served as a comparison 2 years after baseline. Concordance analyses found that complete concordance between patients' and dermatologists' assessments were 16.62% at baseline and 11.47% at follow-up. Overall, patients assessed their chronic eczema at baseline as more severe than did the dermatologists; whereas, at follow-up, patients assessed their condition as less severe than the dermatologists' assessment. Bangdiwala's B showed lower values of concordance for womens' and older patients' self-assessment with the dermatologists' assessments. In conclusion, dermatologists should consider the patient's perspective and the individual's assessment of their chronic hand eczema in order to provide effective care in clinical practice.
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