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.

[Changes in dose and injection pattern in the botulinum toxin long-term therapy of facial dyskinesis]. / Änderung von Dosis und Injektionsmuster der Botulinumtoxin-Langzeittherapie fazialer Dyskinesien.

BACKGROUND: Rare information exists about comparative long-term observations of patients with facial movement disorders. This retrospective analysis deals with the course of different parameters of injection over the time. METHODS: In this study we compared the development of long-term botulinum toxin treatments of patients with blepharospasm, hemifacial spasm and synkinesis. 80 patients (n=30 blepharospasm, n=31 hemifacial spasm, n=19 synkinesis), who had at least 10 consultations for BTA-injections, were included in the retrospective analysis. The development for each entity in total dosage, increase in the number of injection points and change in dosages for each point were evaluated. RESULTS: The over-all dosage in all 3 clinical disorders and for each single disease itself increased continuously over the time. The amount of injection points increased in the treatment of hemifacial spasm and synkinesis. The dosage per point increased most in blepharospasm between the 1. and 25. injection, but was distinctly lower in patients with hemifacial spasm and synkinesis. The increase in dosage in blepharospasm is therefore, in contrast to the other indications, mostly caused by an increase in dosage per point. In patients with hemifacial spasm and synkinesis the escalation of dosage is mainly caused by an increase of the number of injection points. CONCLUSION: These new aspects of the dynamic in the treatment with botulinum toxin enable the physician to understand better the dynamic of these diseases, to optimize treatment protocols.

Granulomatosis with polyangiitis and multiple bilateral cranial nerve palsies: a diagnostic challenge.

BACKGROUND: Granulomatosis with polyangiitis is characterized by vasculitis of small and medium sized vessels and non-caseating granulomas with head and neck symptoms in 95% of those affected. Cranial nerve palsies are rare; while, chronic rhinosinusitis and ear problems are common. CASE REPORT: We describe the serious course and the diagnostic challenge of a patient with granulomatosis with polyangiitis of bilateral mastoids and the right temporal lobe. Initially, the patient showed metachronous bilateral facial palsy with chronic mastoiditis. Repeated surgeries and rheumatologic examinations did not determine a diagnosis. The patient developed additional cranial nerve palsies. Due to progression into the temporal lobe, we removed the affected parts. After 6 months, the diagnosis was revealed by histology. RESULTS AND CONCLUSION: Granulomatosis with polyangiitis is a diagnostic challenge. Persistent reevaluations were necessary for a final diagnosis and to limit the life-threatening disease. Once diagnosed, therapy began with the standard FAUCI-Scheme.

Engineered stem cell-derived microglia as therapeutic vehicle for experimental autoimmune encephalomyelitis.

Inflammation can be prevented in most inflammatory brain diseases, while tissue repair of the lesioned central nervous system (CNS) is still a major challenge. The CNS is difficult to access for protein therapeutics due to the blood-brain barrier. Here, we show that genetically engineered embryonic stem cell-derived microglia (ESdM) are a suitable therapeutic vehicle for neurotrophin-3 (NT3) in experimental autoimmune encephalomyelitis (EAE). The intravenously transplanted ESdM migrated into the inflammatory CNS lesions and engrafted there as microglial cells. EAE afflicted mice treated with ESdM that were genetically modified to express NT3 showed stable recovery from disease symptoms. The NT3-transduced ESdM created an anti-inflammatory cytokine milieu in the spinal cord and promoted neuronal sprouting. Furthermore, mice treated with NT3-transduced ESdM showed less axonal injury and reduced demyelination. Thus, genetically modified ESdM represent a suitable tool to introduce therapeutic neuroprotective and repair-promoting proteins into the CNS in neuroinflammatory diseases.