The European Rare Disease Network for HHT Frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care.

Hereditary haemorrhagic telangiectasia (HHT) is a complex, multisystemic vascular dysplasia affecting approximately 85,000 European Citizens. In 2016, eight founding centres operating within 6 countries, set up a working group dedicated to HHT within what became the European Reference Network on Rare Multisystemic Vascular Diseases. By launch, combined experience exceeded 10,000 HHT patients, and Chairs representing 7 separate specialties provided a median of 24 years' experience in HHT. Integrated were expert patients who focused discussions on the patient experience. Following a 2016-2017 survey to capture priorities, and underpinned by more than 40 monthly meetings, and new data acquisitions, VASCERN HHT generated position statements that distinguish expert HHT care from non-expert HHT practice. Leadership was by specialists in the relevant sub-discipline(s), and 100% consensus was required amongst all clinicians before statements were published or disseminated. One major set of outputs targeted all healthcare professionals and their HHT patients, and include the new Orphanet definition; Do's and Don'ts for common situations; Outcome Measures suitable for all consultations; COVID-19; and anticoagulation. The second output set span aspects of vascular pathophysiology where greater understanding will assist organ-specific specialist clinicians to provide more informed care to HHT patients. These cover cerebral vascular malformations and screening; mucocutaneous telangiectasia and differential diagnosis; anti-angiogenic therapies; circulatory interplays between anaemia and arteriovenous malformations; and microbiological strategies to counteract loss of normal pulmonary capillary function. Overall, the integrated outputs, and documented current practices, provide frameworks for approaches that augment the health and safety of HHT patients in diverse health-care settings.

Epidemiological, clinical and endoscopic features of epistaxis severity and quality of life in Hereditary haemorrhagic telangiectasia: a cross-sectional study.

BACKGROUND: Epistaxis is the main complaint in patients with Hereditary haemorrhagic telangiectasia (HHT). Even though the role of epistaxis in affecting the quality of life (QoL) is well-known, little is known about epidemiological and clinical factors contributing to epistaxis severity and QoL. METHODOLOGY: This is a cross-sectional study, including adult patients with HHT with epistaxis. All patients underwent an otolaryngological evaluation with nasal endoscopy. Epistaxis severity was graded using the FID score, and QoL was evaluated with the Short-Form Health Survey (SF-36). Descriptive statistics were produced for demographic characteristics; the Shapiro-Wilk test was used to test the normal distribution of quantitative variables. Correlation between the quantitative variables was evaluated with Pearson's correlation coefficient. Both univariate and multivariate linear regression models were fitted to find associations between demographic or clinical factors and the FID score or SF-36. RESULTS: A total of 234 patients with HHT were included in the study. The univariate analysis highlighted the association between high blood pressure, septal perforation, nocturnal epistaxis, surgery, blood transfusion, hormonal therapy and both FID score and QoL. Sex, allergic rhinitis and nasal polyposis were neither related to epistaxis severity nor perceived health. CONCLUSIONS: Epistaxis severity and QoL in patients with HHT are influenced by several clinical factors both dependent and independent from HHT. Some of the results are consistent with those already published, but for the first time, we extended the analysis to different clinical parameters, such as endoscopic findings, never assessed before.

FID Score: an effective tool in Hereditary Haemorrhagic Telangiectasia - related epistaxis.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a rare disease characterized by a multisystemic vascular dysplasia and epistaxis, that is the most common cause of disability and social impairment. Patient management strictly depends on the severity of this symptom; therefore, it is of paramount importance for the clinicians to effectively grade epistaxis severity. The aim of this report was to validate the Frequency, Intensity and Duration score (FID) for grading epistaxis severity in patients with HHT; we studied repeatability and external validity comparing FID score with Epistaxis Severity Score (ESS). METHODS: This is a descriptive, observational study that included 264 adult HHT patients with epistaxis. Diagnosis of HHT was established with Curacao criteria or positivity at genetic testing. Nosebleed severity was evaluated according to the FID score and the ESS. The first 30 patients were included in the validation of the FID score, which was graded on days 0, 1, 3 and 7. In the remaining 234 patients, a comparison between the ESS and FID score was performed. RESULTS: The statistical analysis performed in order to validate the FID score showed very good agreement between scores calculated on different days; analysis comparing the FID score with the ESS revealed a high correlation between the two grading systems. CONCLUSIONS: The FID score is a quick, easy and precise tool for evaluating HHT-related epistaxis and could be a possible alternative to the ESS. The FID score meets the need for an intuitive and smart grading system that is easy to manage in clinicians’ hands.

Human infections due to Schizophyllumcommune: Case report and review of the literature.

Schizophyllumcommune is an environmental basidiomycetous fungus, causing occasional, predominantly respiratory, infections in humans. Although S. commune is considered an emerging pathogen, some authors pointed out the possibility that the increase in the diagnosed cases may be also due to recent advances in diagnostic technologies now allowing a more prompt and precise identification at the species level. Here we describe the first Italian case of chronic non-invasive fungal rhinosinusitis due to S. commune in an immunocompetent subject and update the literature review on S. commune sinusitis published between 2012-2019. A timely diagnosis is important to avoid local and systemic complications due to infection with this fungus. In our case, prompt identification at species level was only possible with the use of MALDI-TOF mass spectrometry and confirmed by sequence analysis of ribosomal DNA ITS regions, due to the difficulty in achieving a correct and rapid identification using routine morphological analysis.

Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT. METHODS: To provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK. RESULTS: Although HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban (n = 15), Rivaroxaban (n = 14), and Dabigatran (n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin. CONCLUSIONS: Currently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban.

Synchronous Parotid (Mammary Analog) Secretory Carcinoma and Acinic Cell Carcinoma: Report of a Case.

Mammary analogue secretory carcinoma (MASC) is a recently described low-grade salivary gland malignancy with histologic, immunohistochemical and molecular similarities to secretory carcinoma of the breast, including a specific t(12;15)(p13;q25) resulting in an ETV6-NTRK3 gene fusion. Ultrasound and magnetic resonance imaging frequently document a macrocystic structure. The main differential diagnosis of secretory carcinoma is with low grade acinic cell carcinoma (AciCC). The two can be differentiated with immunohistochemical stains for S100, mammaglobin, carbonic anhydrase VI and DOG-1; the identification of the specific translocation can help to characterize non-typical cases. We report a unique case of synchronous MASC and AciCC presenting in a parotid gland and discuss the implications of the correct identification of the two tumors.

Interventional sialendoscopy for radioiodine-induced sialadenitis: quo vadis?

Salivary gland toxicity is a common adverse effect of radioactive iodine (131I) for the treatment of thyroid cancers with a prevalence ranging from 2% to 67% of the 131I exposed population. Recently, sialendoscopy has been introduced as an attractive diagnostic and therapeutic tool for management of patients with radioiodine-induced sialadenitis that is unresponsive to standard medical treatments. The objective of the current review was to assess the impact of this procedure on outcomes in patients suffering from radioiodine sialadenitis. Overall, eight studies were included and 122 patients underwent 264 sialendoscopic procedures. Duct stenosis and mucous plugs were observed in 85.7% of endoscopic findings, supporting the role of ductal obstruction in the pathophysiology of radioiodine sialadenitis. In total, 89.3% of patients experienced complete or partial resolution of sialadenitis recurrences without any major adverse events, and parotidectomy was advocated in only 1 case. However, outcomes mainly concerned subjective reports and only two clinical experiences evaluated objective measurement with dissimilar results. Limited to few studies, xerostomia and obstructive symptoms responded differently after sialendoscopy. The optimal timing of salivary gland videoendoscopy needs to be further analysed in order to define the best management of radioiodine-induced obstructive sialadenitis.

Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia.

In this work nasal powder formulations of thalidomide were designed and studied to be used by persons affected by hereditary hemorrhagic telangiectasia as a complementary anti-epistaxis therapy, with the goal of sustaining the effect obtained with thalidomide oral treatment after its discontinuation for adverse effects. Three nasal powders were prepared using as carriers ß-CD or its more hydrophilic derivatives such as hydropropyl-ß-CD and sulphobutylether-ß-CD and tested with respect to technological and biopharmaceutical features after emission with active and passive nasal powder devices. For all formulated powders, improved dissolution rate was found compared to that of the raw material, making thalidomide promptly available in the nasal environment at a concentration favouring an accumulation in the mucosa. The very limited transmucosal transport measured in vitro suggests a low likelihood of significant systemic absorption. The topical action on bleeding could benefit from the poor absorption and from the fact that about 2-3% of the thalidomide applied on the nasal mucosa was accumulated within the tissue, particularly with the ß-CD nasal powder.

Sialendoscopy in juvenile recurrent parotitis: a review of the literature.

Juvenile recurrent parotitis (JRP) is the second most frequent salivary gland disease in childhood, defined as a recurrent non-suppurative and non-obstructive parotid inflammation. The recurring attacks actually represent the most dramatic and serious aspect of this pathology, since they significantly influence the quality of life, and there are no recognized therapies to avoid them. In recent years, there are reports of many international experiences related to the management of JRP by sialendoscopy. In this context, several authors have stressed the striking role of sialendoscopy in the prevention of JRP attacks. The objective of the current review is to overview the existing literature with particular regards to diagnostic and therapeutic outcomes after the application of sialendoscopy in patients suffering from JRP.

Posterior lacrimal sac approach technique without stenting in endoscopic dacryocystorhinostomy.

The purpose of this study is to evaluate the effectiveness of endoscopic dacryocystorhinostomy by the posterior lacrimal sac approach without use of lacrimal stents or harvest of mucosal flaps as a valid surgical procedure for the treatment of an obstruction of the lacrimal pathways. A retrospective evaluation was conducted in a cohort of 75 patients between 2007 and 2011. A total of 78 endoscopic dacryocystorhinostomies were analyzed in 75 patients. After a mean follow-up of 25.7 months (minimum 12 months), 93.3% had a complete relief of symptoms after surgery. Our experience appears to confirm that the endoscopic posterior lacrimal sac approach with no stent insertion or mucosal flaps creation is a good alternative to other known endoscopic procedures.

Sudden clinical course of an unusual ENT tumour: clinical pictures of extramedullary plasmacytoma secondary to multiple myeloma.

Extramedullary plasmacytoma (EMP) is a rare monoclonal plasmacytic proliferation involving upper airways in 80% of cases. The heterogeneous pattern of frequency in the head and neck area may result in insidious clinical expressions that are potentially lethal for the patient. The presentation and management of two suggestive clinical photographs characterized by sudden and aggressive EMP development secondary to multiple myeloma are discussed.

Early onset of a nasal perivascular epithelioid cell neoplasm not related to tuberous sclerosis complex.

Perivascular epithelioid cell neoplasms are a group of rare tumours reported in various organs under a variety of designations. Such tumours are of interest primarily because of the distinctive morphology of their cell population and their immunoreactivity with melanocytic and myoid markers. There is a strong association between perivascular epithelioid cell neoplasms and tuberous sclerosis complex. Perivascular epithelioid cell neoplasms very rarely occur in the upper aero-digestive tract. To date only three cases of nasal perivascular epithelioid cell neoplasms have been reported in the literature. The present report refers to a 22-year old woman, without any stigmata of tuberous sclerosis complex, with early onset of a polypoid nasal mass with pathological and immunohistochemical features entirely compatible with those of a perivascular epithelioid cell neoplasm.

Adenoid hypetrophy: definition of some risk factors.

Adenoids removed for airway obstruction and-or recurrent infections have been studied to identify a possible mechanism to explain chronicity. In this regard, macrophages may play a relevant pathogenic role as well as neutrophils during bacterial infections and eosinophils in allergic inflammation. Therefore, this study aimed at investigating some mediators as surrogate markers of inflammation in children who had to undergo to adenoidectomy. Globally, 67 children (25 females, 42 males, mean age 4.9 years), affected by persistent obstruction caused by adenoid hypertrophy were consecutively enrolled into the study. Blood samples were collected from patients and controls to determine serum CD163, Myeloperoxidase (MPO) and ECP. There were significant differences between patients and controls for serum CD163 (p less than 0.0001); MPO (p less than 0.0001); serum ECP (p less than 0.0001). This study demonstrated some risk factors for severe AH: apnoea, recurrent respiratory infections, and high serum CD163 levels.

Nasal polyposis in children.

Nasal polyposis is a chronic inflammatory disease affecting the nasal cavity and the paranasal sinuses. It is a relatively common disease, occurring in 1-4 % of the general population, but it is rarely described in the pediatric population. Most of the published series include children presenting with other underlying systemic diseases, mainly cystic fibrosis. The aim of the present study was to describe the characteristics of the patients suffering from nasal polyposis, evaluated at the Pediatric Clinic of the University of Pavia (Italy) over the last 17 years. 56 consecutive pediatric patients referring to our Pediatric Department had a diagnosis of nasal poyposis over the last 17 years. All children underwent allergy evaluation, nasal endoscopy, CT scan of the paranasal sinus, and Functional Endoscopic Sinus Surgery. The mean age of the present cohort was of 11.8 years and most of the patients were male. 50% of the patients presented with unilateral, polyposis, mostly with a diagnosis of antrochoanal polyp. 4 patients presenting with bilateral polyposis suffered from cystic fibrosis. Main symptoms at diagnosis included nasal obstruction, snoring and rhinorrhea 32% of the patients presented at least a positivity to skin prick test, for major inhalant and food allergens. Nasal polyposis in children could represent an alert sign for other underlying systemic diseases. Nasal endoscopy should therefore be prescribed when a diagnosis is suspected. To properly treat a patient presenting with nasal polyposis, it is necessary to integrate medical and surgical skills through a multidisciplinary approach.

Occult sinusitis may be a key feature for non-controlled asthma in children.

Sinusitis is frequently associated with asthma. The diagnosis and management of patients with asthma associated with sinusitis are often challenging, though sometimes unsatisfactory. Detection and treatment of sinusitis in asthmatics may lead to a better control of asthma symptoms. Most of the studies regarding the relationship between sinusitis and asthma have been conducted in adults. The aim of the present study was to evaluate the presence of sinusal comorbidity in children with un-controlled asthma both clinically and through nasal endoscopy after the first 6 months of treatment. The present study included 294 consecutive asthmatic children (97 males, mean age 7.3 years). Asthma diagnosis, severity assessment and treatment were performed according to GINA guidelines. Twenty-one patients with non-controlled asthma presented with endoscopic features of sinusitis, but without any clinical sign or symptom. We defined such condition occult sinusitis. Not only overt sinusitis, but also occult sinusitis could be a significant comorbidity in asthmatic patients. For this reason, it may be beneficial to determine the presence of sinus inflammation in children with non-controlled asthma, even when they do not present clinical signs or symptoms of upper airways involvement.

Adenoids during childhood: the facts.

Adenoids are constantly exposed to viral and bacterial agents as well as to allergens. They play a major role in the upper airways immunity, being effector organs in both mucosal-type and systemic-type adaptive immunity. Because of both their immunological function and their specific location, adenoids are considered to be as reservoirs of viruses and bacteria. Reiterative infections may therefore contribute both to Eustachian tube dysfunction and to tissue hypertrophy. Nasal endoscopy is a key diagnostic tool to detect both adenoid hypertrophy and adenoiditis. Moreover, such a procedure may be very helpful in detecting bacterial biofilms that could justify the concomitant presence of recurrent episodes of otitis media, chronic and occult sinusitis in children. Even though the connection between allergies and adenoidal diseases is not completely clear, allergic diseases cause an inflammatory state that influences adenoidal tissue as well, configuring the picture of allergic adenoiditis, a condition in which adenoid tissue exhibit numerous IgE positive mast cells. Several studies are still needed to better understand the relationship between allergies and infections and the influence they play on adenoids during childhood.

Adenoid assessment in paediatric patients: the role of flexible nasal endoscopy.

Adenoid hypertrophy is the most common cause of nasal obstruction in paediatric patients. Over the years, various methods to assess the adenoid size were proposed such as the posterior rhinoscopy and the radiological examination of the nasopharynx. Nasal endoscopy was introduced for children in the 80's, and nowadays this is a known and diffuse method in routine practice. The purpose of this article is to describe the personal experience in the assessment of the adenoid size in children, with a particular regard to the flexible nasal endoscopy, and to analyse the literature reports. The personal technique is described in performing nasal endoscopy in paediatric patients, reporting advantages and possible disadvantages of the procedure. A retrospective analysis was conducted on 6036 children since 1999 to 2010. In most cases children fully collaborated to complete the exam. No major or minor complications (such as nose bleedings or other traumatic injuries) were observed. No topical intranasal decongestant, local or general anaesthesia were used in our series. In our opinion, nasal endoscopy in children is a reliable, safe, accurate, easily tolerated and dynamic diagnostic method to assess the adenoid size.

The evolution of the adenoidectomy: analysis of different power-assisted techniques.

Techniques and instruments for adenoidectomy have considerably changed over the years. With the introduction in Otolaryngology of power-assisted instruments for endoscopic sinus surgery, the classic adenoidectomy performed with curette or adenotome has evolved, with an improved patients' outcome and a better satisfaction of the surgeon. The purpose of this article is to describe and critically analyze the literature reports about different methods of power-assisted adenoidectomy. We performed a literature search (Medline) to identify all available reports. We discussed the surgical techniques and reviewed advantages and disadvantages of each method. The techniques can be schematically divided in non-endoscopic, usually performed with a laryngeal mirror, and endoscopic-assisted. The endoscopic control can be obtained either trans-nasally or trans-orally, as well as the microdebrider can be inserted in the nasal cavity or maneuvered through the oral cavity. Some authors reported the usage of the power-assisted instruments in performing the entire adenoidectomy; while, according with other authors, the microdebrider can be used as a step of the surgical procedure, for a combined adenoidectomy. In conclusion, all the methods seem to be safe and effective, and the personal experience of the surgeon should guide the choice of the instruments. However, we personally consider the endoscopic techniques as the most suitable, and among these the Transoral Endonasal-Controlled Combined Adenoidectomy (TECCA) should be considered as the most ergonomic technique to perform a power-assisted adenoidectomy.

Endoscopic treatment of maxillary inverted papilloma.

OBJECTIVES: Evaluate the efficacy of endoscopic treatment in maxillary inverted papilloma (IP). METHODOLOGY: Between July 2002 - April 2008, 20 patients affected by maxillary localization of IP were treated in our Clinic. All patients underwent endoscopic treatment consisting of an endoscopic medial maxillectomy (simple or extended), or attachment-site endoscopic tumour surgery. RESULTS: The cohort was composed of 20 patients (male: 15, female: 5), mean age 58 years, and included 21 endoscopic resections of maxillary IP. Minimum follow-up: 24 months, mean follow-up: 50 months. We registered only 1 case of tumour persistence/recurrence after 15 months, which underwent a second endoscopic treatment. No association with malignant lesions was noted. The efficacy of the endoscopic treatment was 95% (19/20 cases) after primary surgery, and 100% after endoscopic revision. CONCLUSIONS: Our experience demonstrates the efficacy of endoscopic treatment in maxillary IP. Based On its reduced morbidity in comparison to external approaches and its good control of the disease, we consider it our standard treatment for maxillary-originated inverted papilloma.

Rhinosinusitis and otitis media: the link with adenoids.

Rhinosinusitis and otitis media are very common diseases observed in pediatric patients. A clear association has been reported in literature between these two conditions. Even concordance in the microbiologic findings has been reported. These findings lead to a discussion in regard to a possible relationship between the two diseases and an eventual interference of another concomitant condition promoting this association. A key role in the linkage between rhinosinusitis and otitis media has been attributed to hypertrophic adenoidal tissue because of its mechanical obstruction of both choanae and Eustachian tube orifices. Recently some works in literature evidenced the presence of bacterial biofilms on adenoids and suggested a responsibility of bacterial biofilms in both chronic rhinosinusitis and otitis media. The debate is still active and more investigations are needed to clarify these topics.