Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. METHODS: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. RESULTS: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

[Immunodeficiency in chronic rhinosinusitis : An important and often underestimated cause]. / Immundefekte bei chronischer Rhinosinusitis : Eine bedeutende und oft unterschätzte Ursache.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases. Among these patients the prevalence of immune defects is higher than in the healthy general population. METHODS: A selective review of the literature was carried out in PubMed and Medline covering the period between 2008 and 2019. Additionally, recent German publications in journals not listed in the abovementioned databases were analyzed. RESULTS: The diagnostic workflow with respect to the immunodeficiency consists of a detailed anamnesis and physical examination, laboratory tests and the antibody reaction to polysaccharide vaccines and antigens. Beside antibiotic treatment, vaccinations and immunoglobulin replacement are available. Notwithstanding the above, functional endoscopic surgery of the paranasal sinuses should be performed according to guideline recommendations. CONCLUSION: Patients with CRS who do not sufficiently respond to conservative and surgical treatment should be checked for underlying immunodeficiencies.

[Basis for the treatment of eczematous diseases in otorhinolaryngology]. / Grundlage der Behandlung ekzematöser Erkrankungen im HNO-Bereich.

According to Coombs and Gell, cell-mediated immune responses belong to type IV reactions and are borne mainly by T lymphocytes. The eliciting allergens are usually so-called haptens. Haptens are substances which develop to whole antigens only by binding to protein carriers. In otorhinolaryngology, delayed allergic hypersensitivities are apparent mainly as contact eczemata. Facial dermatitis, auricle and ear canal eczema as well as perioral eczema belong to the most common forms of contact dermatitis in ENT patients. The patient's medical history and morphology of the eczema give a strong indication for a proper diagnosis. Verification is carried out by patch test according to the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF, The Association of the Scientific Medical Societies in Germany) guidelines. Hereby the most widespread contact allergens are tested in a so-called "standard block", which can be reduced to an individualized allergen spectrum, based on medical history. For therapy, allergen avoidance is the most important measure which should also be applied prophylactically. Moreover, antiinflammatory treatment of the contact eczema is carried out with tapering topical corticosteroids. Depending on the patient's age, location and severity of the contact eczema, newer class II or III preparations should be chosen. Skin care preparations are helpful to reduce corticosteroid consumption and are indicated additionally after the acute phase treatment. An important differential diagnosis of contact eczema is atopic dermatitis. Whilst contact dermatitis experiences healing by avoiding the triggering noxious agent, genetically determined atopic dermatitis shows a chronic, recurrent course. In addition to topical corticosteroids, calcineurin inhibitors have been approved for treatment of atopic eczema. In all eczema diseases, regular skin care is a necessary measure which contributes mainly to barrier repair.

A randomized, 5-arm dose finding study with a mite allergoid SCIT in allergic rhinoconjunctivitis patients.

BACKGROUND: The safety and tolerability of a mite allergoid subcutaneous allergen immunotherapy (SCIT) product was previously established. The aim of this study (EudraCT number: 2011-000393-61) was to find the optimally safe and effective allergoid dose by evaluating several dosages in patients with house dust mite (HDM)-induced allergic rhinoconjunctivitis (ARC) using a titrated nasal provocation test (TNPT). METHODS: In total, 290 adult ARC patients (148 females; 142 males) with established HDM allergy and with a positive TNPT were randomized to receive placebo or mite allergoid SCIT 6667, 20 000, 50 000 or 100 000 AUeq/ml for 12 months. Patients were updosed weekly, followed by monthly maintenance dosing. The primary study endpoint comprised the clinical response to TNPT after 12 months of treatment. Secondary endpoints included response to TNPT after 6 months, PNIF measurements, symptom and medication scores during the last 8 weeks of treatment, serum immunoglobulins and safety assessments. RESULTS: After 12 months, a dose-response was observed showing statistically significant improvements in the TNPT with SCIT concentrations of ≥20 000 AUeq/ml, while no significantly different outcomes were reached after 6 months. Specific serum IgG and IgG4 levels were dose dependently increased. In the highest dose group, more treatment-emergent adverse events were observed compared with the lower dose groups. CONCLUSION: In this mite allergoid SCIT dose finding study in HDM-induced ARC, concentrations of ≥20 000 AUeq/ml showed both immunological effects and clinical efficacy in the TNPT compared with placebo. The risk-benefit ratio favours 20 000 AUeq/ml and 50 000 AUeq/ml strengths for further clinical development.

sCD95L in serum after spinal cord injury.

STUDY DESIGN: A prospective observational study reporting correlation between sCD95L (serum cluster of differentiation 95 ligand) serum levels and remission after traumatic spinal cord injury (SCI). OBJECTIVES: To describe the correlation between sCD95L serum levels and remission after traumatic SCI in a human protocol compared with animal studies. SETTING: Rhineland-Palatinate (Rheinland-Pfalz), Germany. METHODS: We included 45 patients with traumatic SCI. According to their neurological outcome, patients were divided into two groups, patients with (G1, n=26) and without (G2, n=19) remission. Blood was collected on post-admission and according to a fixed scheme, that is, after 4, 9, 12 h, 1, 3 days and 1, 2, 4, 8, 12 weeks. RESULTS: By comparing G1 with G2, we found a correlation between neurological remission and sCD95L serum concentrations. Consistently elevated levels of sCD95L in G1 between 9 h and 1 month after injury show significantly differing values 7 days after injury. This indicates a correlation between patients with clinically documented neurological remission and elevated sCD95L serum concentrations. CONCLUSIONS: In opposite to animal studies, our patients with neurological remission show on average higher levels of sCD95L compared with patients without. Therefore, spinal cord-injured patients would probably not profit from neutralizing CD95L. Our results present that the transfer of findings from animal studies to humans must always be considered critically. We were able to show that peripheral serum cytokine expression is suitable to state processes after SCI in humans.

[Insect venom allergies : Update 2016 for otorhinolaryngologists]. / Insektengiftallergie : Update 2016 für HNO-Ärzte.

Due to the increasing incidence of hymenoptera venom allergies and the potentially life-threatening reactions, it is important for otolaryngologists working in allergology to have an understanding of modern diagnostic and treatment standards for this allergic disease. Molecular diagnosis with recombinant single allergens from bee and wasp venom components improves the diagnostics of insect venom allergies, particularly in patients with double-positive extract-based test results. Detection of specific sensitizations to bee or wasp venom enables double sensitizations to be better distinguished from cross-reactivity. Based on patient history and test results, the patient is initially advised on avoidance strategies and prescribed an emergency medication kit. Then, the indication for allergen-specific immunotherapy (AIT) is evaluated. The dose-increase phase can be performed using conventional, cluster, rush, or ultra-rush schedules, whereby rapid desensitization (rush AIT) performed in the clinic seems to be particularly effective as initial treatment.

[Role of vitamin D in allergic diseases: Current research status]. / Die Rolle von Vitamin D bei allergischen Erkrankungen : Eine Standortbestimmung.

BACKGROUND: Recent research has focused on the relationship between vitamin D and allergy development. Results show that on the one hand a vitamin D deficiency can be responsible for the emergence of allergies, however, on the other hand a vitamin-D (over-) substitution was also seen in context with an increased allergy development. OBJECTIVE: This article provides an overview on the current state of research and points at the problematic aspects that accompany the assessment of these studies. RESULTS: The paradoxic effect of vitamin D is currently being explained by epigenetic programming in pregnancy, by too low vitamin-D levels or excessive supplementation in newborns. Very recently, a gender-specific impact of vitamin D is also being discussed. CONCLUSION: For a final assessment of vitamin-D effects on the emergence of allergies, further research is necessary. Due to a high level of heterogeneity among current observational studies regarding central aspects of the discussion, randomised clinical trials are recommended.

[Evidence-based treatment options for allergic diseases in otolaryngology: an update]. / Evidenzbasierte Therapieoptionen von Allergien im HNO-Bereich: Ein Update.

Allergic diseases in the area of otolaryngology (ENT) are common, increasing and associated with a number of comorbid disorders, such as bronchial asthma and atopic dermatitis. If allergen avoidance is not possible, allergen-specific immunotherapy is the only causative treatment option. Options for pharmacotherapy are mast cell stabilizers, antihistamines, glucocorticoids, leukotriene receptor antagonists and nasal decongestants. In type 1 allergic reactions, topical glucocorticoids are currently the most effective treatment and are considered to be the first-line therapy together with nonsedating antihistamines. A novel formulation (MP29-02) combining a nasal glucocorticoid and antihistamine in one single preparation has demonstrated an improvement of the effective total nasal symptom score by 39 % in comparison to monotherapy with fluticasone propionate. In type IV allergies, such as eczema treatment with topical glucocorticoids or calcineurin inhibitors is standard.

[Allergies to antibiotic drugs: their importance in otorhinolaryngology]. / Allergien auf Antibiotika: Bedeutung für den HNO-Arzt.

BACKGROUND: In 2009, over 40 million prescriptions for antibiotic drugs were counted in outpatient medical care in Germany. This represents a turnover of more than 750 million euros. With over 80 million daily defined doses (DDD), amoxicillin was the most frequently prescribed antibiotic in Germany in 2008. Given the average of 5775 DDD per doctor, otolaryngologists prescribed more antibiotics than specialists in any other field of medicine in 2008; approximately 82% of these were ß-lactams and tetracyclines. MATERIAL AND METHODS: This article is based on selective literature-based research using the PubMed database. The keywords used in the search were:"allergy","anaphylaxis" and"hypersensitivity", in combination with "penicillin","cephalosporin","carbapenem","cotrimoxazole","macrolide","aztreonam" and"tetracycline". RESULTS: Allergic reactions to antibiotics are among the most frequently reported adverse side effects arising from drug treatment. However, non-allergic adverse side effects owing to drug intolerance are also very common and may be clinically indistinguishable from allergic reactions. Owing to a frequent lack of appropriate diagnostic investigation, the decision to withhold effective standard treatments from patients is often based solely upon anamnestic observations. Up to 10% of respondents in an unselected population report an allergy to penicillin. In 80% of these cases, however, no penicillin-specific IgE-antibodies can be detected. CONCLUSION: A detailed understanding of the symptoms, diagnostic options and possible cross reactions pertaining to allergic reactions to antibiotics, as well to non-allergic adverse side effects with similar clinical appearance, is very important for otolaryngologists. This profound knowledge ensures that the correct diagnostic steps are taken and that appropriate treatment decisions prevent the unnecessary use of reserve antibiotics.

[The NTP in allergy research : open questions regarding nasal provocation tests using allergens]. / Der NPT in der allergologischen Forschung : Offene Fragen bei der nasalen Provokationstestung mit Allergenen.

The nasal provocation test (NPT) is a simple procedure with high specificity and sensitivity that is used in the investigation of allergic and nonallergic diseases. Uniform standards are of particular importance in the clinical setting and for the comparability of clinical and basic allergy research. These standards should cover the composition, dosage and pharmacological formulation of provocative substances (e.g. allergen extracts), the necessity of titration, allergen application methods and the evaluation criteria for a positive NPT reaction. Detection of various mediators and cytokines in nasal discharge can be very useful in the late phase reactions. NPT finds specific applications in studies of local IgE secretion in the nasal mucosa, the diagnosis of analgesic intolerance and in assessments of the efficacy of specific immunotherapies. Additional parameters warranting further evaluation include provocation with cold dry air in nasal hyperreactivity patients and nasal nitric oxide formation. Determination of nasal blood flow during NPT provides an additional clinical parameter.

Electronic superstructure of lead phthalocyanine on lead islands.

Lead phthalocyanine (PbPc) deposited on lead islands on Ag(111) forms two-dimensional crystals of densely packed molecules. For particular orientations, the molecular arrays exhibit an electronic superstructure with an extraordinarily large unit cell. The molecules induce a shift of quantum well states, which are confined to the Pb islands. Patterns formed by PbPc on Ag(111) are drastically different.

Mites and other indoor allergens - from exposure to sensitization and treatment.

House dust mites, cats and dogs are amongst the most frequent sources of indoor allergens in Europe. The fact that the allergens of house dust mites cause allergic disease through inhalation of house dust was discovered in 1964. The diagnosis of mite allergy is regularly complicated by its often nonspecific symptoms, which frequently develop insidiously and by no means always include attacks of paroxysmal sneezing and itching. Antibody-based immunological detection methods can be used to measure exposure to mite allergens. The structure and function of more than 20 allergens from Dermatophagoides pteronyssinus and D. farina are known. Other relevant indoor allergens come from mammals kept in households. Here again, allergens have been described and diagnostic as well as exposure-measurement tools are available. It is important to remember indoor pests and other "unwelcome lodgers" as a possible cause in the case of unexplained symptoms experienced indoors. This short overview summarizes the current key points on the subject of "mites and other indoor allergens". The present article provides an overview of several articles published in a special issue of the German journal Allergologie [February 2015; 38(2)] on the subject of "Mites and other indoor allergens".