Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab 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 and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

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.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

[Effects of the SARS-CoV­2 pandemic on the otolaryngology university hospitals in the field of research, student teaching and specialist training]. / Auswirkungen der SARS-CoV­2-Pandemie auf die universitäre Hals-Nasen-Ohren-Heilkunde im Bereich der Forschung, Lehre und Weiterbildung.

BACKGROUND: From spring 2020, SARS-CoV­2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.

[Effects of the SARS-CoV-2 pandemic on the otorhinolaryngology university hospitals in the field of medical care]. / Auswirkungen der SARS-CoV-2-Pandemie auf die universitäre Hals-Nasen-Ohrenheilkunde im Bereich der Krankenversorgung.

INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8 % to 26.2 ±â€Š14.2 % and in surgical treatments by 65.9 % to 34.1 ±â€Š13.9 %. In contrast, emergency treatment remained unchanged or even increased in 80 % of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90 %. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35 000 outpatients and about 12 000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.

[IgG4-Related Orbitopathy as an Important Differential Diagnosis of Advanced Silent Sinus Syndrome. German version]. / IgG4-assoziierte Orbitopathie als wichtige Differenzialdiagnose eines fortgeschrittenen Silent-Sinus-Syndroms.

BACKGROUND: Immunoglobulin (Ig)G4-related disease is classified as an immune-mediated disease. The etiology of this condition has not been explained to date. Manifestations of the disease are diverse, and simultaneous involvement of multiple organs is not unusual. CASE REPORT: We report the case of a patient referred to us after multiple unsuccessful paranasal sinus operations who presented with enophthalmos and a resultant migratory keratitis with a suspected diagnosis of silent sinus syndrome. Preservation of the orbit was no longer feasible. After five years without a definitive diagnosis, we ascertained that this was a case of IgG4-related disease. DISCUSSION: IgG4-related disease represents an important element in the differential diagnosis of chronic advanced diseases of the orbit and paranasal sinuses. The diagnosis should be considered in the case of unclear disease presentations. Typical histological findings include a storiform pattern of fibrosis, vasculopathy, and tissue infiltration by IgG4 plasma cells.

Omalizumab in patients with NSAIDs-exacerbated respiratory disease.

BACKGROUND: The association of acetylsalicylic acid (ASA) intolerance, chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, or chronic urticaria is known as NSAID-exacerbated respiratory disease (N-ERD). N-ERD patients often suffer from recurrent nasal polyps, severe asthma or also from urticaria. The aim of the present study was to retrospectively analyze the clinical efficacy of anti-IgE antibody treatment with omalizumab in patients with confirmed N-ERD. METHODS: In the open trial with patients receiving verum patients with CRSwNP, confirmed N-ERD by oral or nasal ASA challenges, asthma or chronic urticaria were included in the study. Rhinological and pulmonary parameters were evaluated before and after 3, 6 and 9 months of therapy by rhinological questionnaires (CRS VAS-scores and RSOM-31), nasal polyp (NP)-, ACT-scores and FEV1 values. Urticaria activity was monitored clinically. N-ERD patients with aspirin desensitization were included as control group (follow-up 9 months). RESULTS: In the omalizumab group 16 patients were included (10 female, 6 male, mean age 51 yrs). CRS symptoms, RSOM-31- and NP-score decreased significantly following omalizumab therapy compared to baseline. The ACT-score (MV 16.5 to 20.6) and FEV1values (MV 80 % to 89 %) improved significantly. No urticaria symptoms were reported after 3 months. Oral prednisolone therapy was required in one case and a repeated nasal sinus surgery in an additional case due to progression of NP. In the control group (8 female, 8 male, mean age 45 yrs) the NP-score was unchanged. CONCLUSIONS: Omalizumab is an effective therapy option in N-ERD patients in a 9 month study period.

IgG4-related orbitopathy as an important differential diagnosis of advanced silent sinus syndrome.

BACKGROUND: Immunoglobulin (Ig)G4-related disease is classified as an immune-mediated disease. The etiology of this condition has not been explained to date. Manifestations of the disease are diverse, and simultaneous involvement of multiple organs is not unusual. CASE REPORT: We report the case of a patient referred to us after multiple unsuccessful paranasal sinus operations who presented with enophthalmos and a resultant migratory keratitis with a suspected diagnosis of silent sinus syndrome. Preservation of the orbit was no longer feasible. After five years without a definitive diagnosis, we ascertained that this was a case of IgG4-related disease. DISCUSSION: IgG4-related disease represents an important element in the differential diagnosis of chronic advanced diseases of the orbit and paranasal sinuses. The diagnosis should be considered in the case of unclear disease presentations. Typical histological findings include a storiform pattern of fibrosis, vasculopathy, and tissue infiltration by IgG4 plasma cells.

Masson tumor as a neck mass.

INTRODUCTION: A Masson's tumor is a benign, intravascular tumor, typically located in the fingers. Histologically, a Masson's tumor is characterized by an intravascular endothelial papillary projection associated with thrombi, without atypia or necrosis. The CD 31 and CD 34 stains are the most efficient immunohistological markers to identify the vascular origin. CASE SUMMARY: A 54-year-old man presented with a right lateral neck mass for 3 weeks. The CT scan of the neck showed an oval, well-circumscribed cystic mass, measuring 20mm×9mm, situated over the right sternocleidomastoid muscle, with a peripheral vessel draining into the right anterior jugular vein. The mass was excised surgically, and a pathological report indicated a thrombosed material inside the lumen of a small vein with a differentiated papillary structure; neither nuclear atypia nor necrosis were seen. The patient had an uncomplicated recovery and completed 8 months of follow-up appointments without any evidence of recurrence. DISCUSSION: Intravascular papillary endothelial hyperplasia (IPEH) can be differentiated from angiosarcoma by lack of extension to the perivascular tissue and absence of necrosis and atypia. The pathogenesis is still unknown; surgical excision is the method of treatment. This is an extremely rare presentation of Masson's tumor.

Improvement in tinnitus distress, health-related quality of life and psychological comorbidities by cochlear implantation in single-sided deaf patients.

BACKGROUND: Patients with single-sided deafness (SSD) lack the ability localize sound sources and have difficulty with speech-in-noise hearing. In addition, there is a high prevalence of tinnitus distress. These problems may result in reduced health-related quality of life (HRQoL) and psychological comorbidities. This study aimed to investigate the influence of treatment with a cochlear implant (CI) on HRQoL, tinnitus distress, psychological comorbidities, and audiological parameters in SSD patients. METHODS: This retrospective study included 20 patients with postlingually acquired SSD (13 women, 7 men, mean age 57.0 years). Data on HRQoL were collected with the Nijmegen Cochlear Implant Questionnaire (NCIQ) and the Medical Outcome Study Short Form 36 Survey (SF-36). Tinnitus distress was assessed with the Tinnitus Questionnaire (TQ), psychological comorbidities were evaluated with validated questionnaires, and speech perception and hearing ability were measured with validated speech tests. RESULTS: Postoperatively, the mean total NCIQ score (p < 0.0001) and four subscores improved significantly, as did tinnitus distress (p < 0.05). Anxiety symptoms (Generalized Anxiety Disorder questionnaire, GAD-7) decreased significantly after CI. Speech perception improved significantly, particularly "hearing with background noise" (p < 0.05, Oldenburg Inventory, OI) and "localization" (p < 0.001, OI), as well as the Oldenburg Sentence Test (OlSa) scores for with vs. without CI when speech was presented from the SSD side and noise was presented from the normal hearing side (SSSDNNH; p < 0.005). CONCLUSION: CI in SSD patients is a powerful procedure to improve HRQoL, reduce tinnitus distress, and improve psychological comorbidities. Additionally, it is beneficial for hearing improvement, particularly in noise and for directional hearing.

[Improvement in tinnitus distress, health-related quality of life and psychological comorbidities by cochlear implantation in single-sided deaf patients. German version]. / Verbesserung von Tinnitusdistress, Lebensqualität und psychologischen Komorbiditäten durch Cochleaimplantation einseitig ertaubter Patienten.

BACKGROUND: Patients with single-sided deafness (SSD) lack the ability localize sound sources and have difficulty with speech-in-noise hearing. In addition, there is a high prevalence of tinnitus distress. These problems may result in reduced health-related quality of life (HRQoL) and psychological comorbidities. This study aimed to investigate the influence of treatment with a cochlear implant (CI) on HRQoL, tinnitus distress, psychological comorbidities, and audiological parameters in SSD patients. METHODS: This retrospective study included 20 patients with postlingually acquired SSD (13 women, 7 men, mean age 57.0 years). Data on HRQoL were collected with the Nijmegen Cochlear Implant Questionnaire (NCIQ) and the Medical Outcome Study Short Form 36 Survey (SF-36). Tinnitus distress was assessed with the Tinnitus Questionnaire (TQ), psychological comorbidities were evaluated with validated questionnaires, and speech perception and hearing ability were measured with validated speech tests. RESULTS: Postoperatively, the mean total NCIQ score (p < 0.0001) and four subscores improved significantly, as did tinnitus distress (p < 0.05). Anxiety symptoms (Generalized Anxiety Disorder questionnaire, GAD-7) decreased significantly after CI. Speech perception improved significantly, particularly "hearing with background noise" (p < 0.05, Oldenburg Inventory, OI) and "localization" (p < 0.001, OI), as well as the Oldenburg Sentence Test (OlSa) scores for with vs. without CI when speech was presented from the SSD side and noise was presented from the normal hearing side (SSSDNNH; p < 0.005). CONCLUSION: CI in SSD patients is a powerful procedure to improve HRQoL, reduce tinnitus distress, and improve psychological comorbidities. Additionally, it is beneficial for hearing improvement, particularly in noise and for directional hearing.

The GALEN rhinosinusitis cohort: chronic rhinosinusitis with nasal polyps affects health-related quality of life.

BACKGROUND: Chronic rhinosinusitis (CRS) significantly affects health-related quality of life (HRQoL). Few multinational observational studies have evaluated the impact of CRS with nasal polyps (CRSwNP) on patients’ HRQoL. This study aimed to assess HRQoL outcomes (including analyses by disease severity and impact of comorbidities and refractory disease) in CRSwNP patients from a large European database. METHODOLOGY: Data were analysed from the Global Allergy and Asthma European Network (GALEN) Rhinosinusitis Cohort, including sociodemographic data, patient-reported disease severity (visual analogue scale), and scores on the 36-Item ShortForm Health Survey (SF-36) questionnaire. Differences in mean SF-36 scores were evaluated between patients with CRSwNP and population norms and between subgroups of interest (disease severity, comorbidity, and refractory disease, defined by a history of sinonasal surgery). RESULTS: Patients with CRSwNP (N = 445) had significantly lower mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores vs population norms, demonstrating that CRSwNP negatively affects HRQoL. The presence of comorbidities affected HRQoL, as shown by significant differences in PCS scores in patients with asthma or non-steroidal antiinflammatory drug-exacerbated respiratory disease, compared with patients without asthma. Patients with moderate-to-severe disease had significantly lower PCS scores than patients with mild disease. Severe disease had a significant impact on MCS score. History of surgery had a clinically meaningful negative effect on HRQoL compared with no history of surgery. CONCLUSIONS: CRSwNP patients have significantly lower HRQoL compared with population norms. The impact is greater in patients with greater disease severity, comorbidities, or refractory disease.