Long-Term Perspectives on Chronic Rhinosinusitis with Nasal Polyps: Evaluating Recurrence Rates after Functional Endoscopic Sinus Surgery in the Biologics Era-A 5-Year Follow-Up Study.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with multifactorial etiopathogenesis. This study investigated the recurrence rate and risk factors predicting recurrence in patients subjected to Functional Endoscopic Sinus Surgery (FESS) for CRSwNP. METHODS: Patients affected by CRSwNP who underwent FESS between January 2015 and March 2020 were enrolled. The recurrence rate and the influence of risk factors were assessed. RESULTS: A total of 154 patients were included, 100 males and 54 females, aged 14-82 years (mean age 51.96 ± 16.27; median 52 years). Of 154 patients, 28 presented CRSwNP recurrence in a follow-up period ranging from 6 months to 69 months, with a recurrence rate of 18.2%. The recurrence rate was higher in patients aged between 31 and 50 years and between 51 and 70 years at the time of surgery than in those aged between 14 and 30 years and over 70 years. Furthermore, most patients with recurrence were men (61%), while 39% were women. A higher recurrence rate was observed between non-smokers (50%) and ex-smokers (36%), while only 14% declared themselves habitual smokers. Only four subjects (14%) had a positive family history of CRSwNP. CONCLUSION: To date, no specific biomarkers have been identified in order to determine the appropriate therapy for the patients affected by CRSwNP. Based on our results, we suggest that it is necessary for an accurate assessment of the CRSwNP patients to identify which phenotype/endotype each subject manifests based on medical history, endoscopy, computed tomography, and a laboratory evaluation.

The Impact of Antibiotics and Steroids on the Nasal Microbiome in Patients with Chronic Rhinosinusitis: A Systematic Review According to PICO Criteria.

BACKGROUND: The nasal microbiome represents the main environmental factor of the inflammatory process in chronic rhinosinusitis (CRS). Antibiotics and steroids constitute the mainstay of CRS therapies. However, their impact on microbial communities needs to be better understood. This systematic review summarizes the evidence about antibiotics' and steroids' impact on the nasal microbiota in patients with CRS. METHODS: The search strategy was conducted in accordance with the PRISMA guidelines for systematic reviews. The authors searched all papers in the three major medical databases (PubMed, Scopus, and Cochrane Library) using the PICO tool (population, intervention, comparison, and outcomes). The search was carried out using a combination of the key terms "Microbiota" or "Microbiome" and "Chronic Rhinosinusitis". RESULTS: Overall, 402 papers were identified, and after duplicate removal (127 papers), excluding papers off-topic (154) and for other structural reasons (110), papers were assessed for eligibility; finally, only 11 papers were included and summarized in the present systematic review. Some authors used only steroids, other researchers used only antibiotics, and others used both antibiotics and steroids. With regard to the use of steroids as exclusive medical treatment, topical mometasone and budesonide were investigated. With regard to the use of antibiotics as exclusive medical treatments, clarithromycin, doxycycline, roxithromycin, and amoxicillin clavulanate were investigated. Regarding the use of both antibiotics and steroids, two associations were investigated: systemic prednisone combined with amoxicillin clavulanate and topical budesonide combined with azithromycin. CONCLUSIONS: The impact that therapies can have on the nasal microbiome of CRS patients is very varied. Further studies are needed to understand the role of the nasal microbiome, prevent CRS, and improve therapeutic tools for personalized medicine tailored to the individual patient.

Dupilumab's Impact on Blood Parameters in Nasal Polyposis: 18-Month Follow-Up in Real Life.

Background: Dupilumab represents the first approved biological for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Objective: Aim of this paper is to provide a multicentric real-life study about treatment with dupilumab for CRSwNP with a special focus on blood parameters and IgE, IgG, and IgA. Method: A retrospective data collection was jointly conducted at the Otolaryngology departments of San Camillo Forlanini Hospital and University of Rome "La Sapienza" from December 2020 to January 2023. Results: A total of 130 patients were included in the study. Monitoring our patients for 18 months, we observed a reduction in nasal polyposis and an improvement in symptoms and their impact on quality of life. Regarding blood tests, a transient increase in blood eosinophils was found in most cases. Total IgE showed a gradual decrease in values. IgG and IgA also showed a slight reduction of values, while remaining within normal ranges. Conclusion: To the best of our knowledge, this is the first study to evaluate the impact of dupilumab on several blood parameters in patients receiving treatment for CRswNP. Further studies are needed to confirm our results and to understand the underlying immunological mechanisms.

Sense of smell in chronic rhinosinusitis: A multicentric study on 811 patients.

Introduction: The impairment of the sense of smell is often related to chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP, CRSsNP). CRSwNP is a frequent condition that drastically worsens the quality of life of those affected; it has a higher prevalence than CRSsNP. CRSwNP patients experience severe loss of smell with earlier presentation and are more likely to experience recurrence of their symptoms, often requiring revision surgery. Methods: The present study performed a multicentric data collection, enrolling 811 patients with CRS divided according to the inflammatory endotype (Type 2 and non-Type 2). All patients were referred for nasal endoscopy for the assessment of nasal polyposis using nasal polyp score (NPS); Sniffin' Sticks olfactory test were performed to measure olfactory function, and SNOT-22 (22-item sinonasal outcome test) questionnaire was used to assess patients' quality of life; allergic status was evaluated with skin prick test and nasal cytology completed the evaluation when available. Results: Data showed that Type 2 inflammation is more common than non-type 2 (656 patients versus 155) and patients suffer from worse quality of life and nasal polyp score. Moreover, 86.1% of patients with Type 2 CRSwNP were affected by a dysfunction of the sense of smell while it involved a lesser percentage of non-Type 2 patients. Indeed, these data give us new information about type-2 inflammation patients' characteristics. Discussion: The present study confirms that olfactory function weights on patients' QoL and it represents an important therapeutic goal that can also improve patients' compliance when achieved. In a future - and present - perspective of rhinological precision medicine, an impairment of the sense of smell could help the clinician to characterize patients better and to choose the best treatment available.

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. METHODS: This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. RESULTS: We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. CONCLUSIONS: Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell.

Neuropsychological Functions and Audiological Findings in Elderly Cochlear Implant Users: The Role of Attention in Postoperative Performance.

OBJECTIVES: The present study aimed to investigate in a group of elderly CI users working memory and attention, conventionally considered as predictors of better CI performance and to try to disentangle the effects of these cognitive domains on speech perception, finding potential markers of cognitive decline related to audiometric findings. Methods Thirty postlingually deafened CI users aged >60 underwent an audiological evaluation followed by a cognitive assessment of attention and verbal working memory. A correlation analysis was performed to evaluate the associations between cognitive variables while a simple regression investigated the relationships between cognitive and audiological variables. Comparative analysis was performed to compare variables on the basis of subjects' attention performance. RESULTS: Attention was found to play a significant role in sound field and speech perception. Univariate analysis found a significant difference between poor and high attention performers, while regression analysis showed that attention significantly predicted recognition of words presented at Signal/Noise +10. Further, the high attention performers showed significantly higher scores than low attentional performers for all working memory tasks. CONCLUSION: Overall findings confirmed that a better cognitive performance may positively contribute to better speech perception outcomes, especially in complex listening situations. WM may play a crucial role in storage and processing of auditory-verbal stimuli and a robust attention may lead to better performance for speech perception in noise. Implementation of cognitive training in auditory rehabilitation of CI users should be investigated in order to improve cognitive and audiological performance in elderly CI users.

Measuring Nasal Patency and the Sense of Smell in CRSwNP Patients Treated with Dupilumab.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the most severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with dupilumab in different rhinological units were followed up at 1, 3, 6 and 12 months from the first administration and were considered for this study. At baseline (T0) and at each follow-up, patients underwent nasal endoscopy and completed the sinonasal outcome test (SNOT)-22, a visual analogue scale (VAS) for smell/nasal obstruction, peak nasal inspiratory flow (PNIF) and the Sniffin' Sticks identification test (SSIT). The aim of the present study was to evaluate the effects of dupilumab in patients with severe uncontrolled CRSwNP on recovering nasal obstruction and smell impairment. Moreover, the method between PNIF and SSIT with the highest correlation with patients' response to dupilumab was evaluated. One hundred forty-seven patients were included. All parameters improved during treatment (p < 0.001). At T0, no correlations were found between PNIF and nasal symptoms. Nevertheless, during the following evaluations significant correlations between PNIF changes and both nasal symptoms and NPS were observed (p < 0.05). At T0, SSIT did not correlate with SNOT-22. Similarly to PNIF, during the follow-up SSIT changes significantly correlated with nasal symptom and NPS (p < 0.05). Comparing PNIF and SSIT correlations with SNOT-22 and NPS, PNIF showed a higher correlation with both. Dupilumab improves nasal obstruction and the sense of smell. PNIF and SSIT are effective tools in monitoring patients' response to dupilumab.

A Rare Case of Extracranial Schwannoma of the Hypoglossal Nerve Located in the Parapharyngeal Space Mimicking a Deep Neck Abscess.

Schwannomas are neurogenic benign tumors originating from the myelin sheath of peripheral nerves, and hypoglossal Schwannomas account for 5% of nonvestibular ones. Extracranial localizations are substantially rare, especially those affecting exclusively the parapharyngeal space; for this reason, the retrostyloid neoformations could initially masquerade as a carotid tumor or deep organized neck abscess. The purpose of this report is to highlight the importance of a multidisciplinary approach in the correct management of differential diagnosis.

Surgical Excision of Unusual Sacked Neck and Mediastinum Abscess of Odontogenic Origin.

The most common cause of neck infections is odontogenic abscesses that can often be life-threatening and require a surgical drain associated with antibiotic therapy. We present a case of the surgical management of an odontogenic sack-shaped and walled abscess arising from elements 3.6, 3.7 and 3.8 that reached the laterocervical spaces and anterior mediastinum in a 28-year-old healthy woman. Typical signs and symptoms of cervical complications of dental origin are fever, a neck mass, lymphadenopathy, trismus and odynophagia. The gold standard treatment in these situations is a multidisciplinary approach involving an oral surgeon, ENT specialist and thoracic surgeon to drain the infected material. To the best of our knowledge, this is the first described case report of a dental abscess enclosed in a sack in the deep space of the neck and in the anterior space of the mediastinum.

A silent laryngeal trauma case: an unexpected late fracture of the superior portion of the thyroid cartilage superior horn.

Attempts to analyze clinical unexpected cases of laryngeal fractures based on mild symptoms and physical findings. Even though a laryngeal fracture is rare in a living patient and when happens it is related to severe airways emergency, this case reported seems important to offer a possible differential diagnosis in patients who present with the same symptoms, if no other causes have been detected, like another one benign laryngeal disease.

Benralizumab reduces eosinophils and inflammatory markers in patients with severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: A pilot real-life study.

Chronic rhinosinusitis with nasal polyps (CRSwNP) and Severe Eosinophilic Asthma (SEA) are both frequently sustained by eosinophilic inflammation and are probably the manifestation of a unique disease of upper and lower respiratory tract. We retrospectively observed 11 patients with severe CRSwNP and concomitant SEA under add-on therapy with benralizumab evaluating symptoms using Sino Nasal Outcome Test-22 (SNOT-22), Visual Analogue Scale (VAS), and Asthma Control Test (ACT) and Nasal polyp size by endoscopic and radiological score by Nasal Polyp Score (NPS) and Lund-Mackay Score (LMS). At 6 and 12 months, the expression of cationic eosinophil protein (ECP), Interleukin 17 (IL-17), Interferon gamma (INF-γ), and vascular endothelial growth factor (VEGF) was measured by nasal scraping to assess mucosal inflammation. After 12 months of benralizumab treatment, SNOT-22 decreased from 45 (23-97) to 14 (5-53) (p < 0.05), total VAS of rhinologic symptoms decreased from 30 (17-44) to 9 (5-37) (p ≤ 0.01) and ACT score increased from 10 (5-15) to 24 (20-25) (p ≤ 0.01). NPS decreased from 5 (3-6) to 3 (2-4) after 6 months (p < 0.05) and to 2 (2-3) after one year respectively (p <  0.05) and LMS total score from 21 (15-24) to 17 (8-21) (p ≤ 0.01) after 12 months from starting treatment. Nasal mucosa scraping found differences in INF-γ and VEGF expression in patients compared to 10 healthy subjects, with a normalization of these markers during eosinophils depletion induced by benralizumab. This is the first pilot real-life study conducted with an anti-IL5R monoclonal antibody in severe eosinophilic asthma and severe CRSwNP patients showing that this treatment can induce benefit both diseases not only from the clinical, but also from the inflammatory point of view. Moreover, our research pointed out that INF-γ and VEGF may represent potential response biomarker.

Long-Term Subjective and Objective Assessment of Smell and Taste in COVID-19.

Among the first clinical symptoms of the SARS-CoV-2 infection is olfactory−gustatory deficit; this continues for weeks and, in some cases, can be persistent. We prospectively evaluated 162 patients affected by COVID-19 using a visual analogue scale (VAS) for nasal and olfactory−gustatory symptoms. Patients were checked after 7, 14, 21, 28, 90, and 180 days. A total of 118 patients (72.8%) reported an olfactory VAS < 7 at baseline (group B), and 44 (27.2%) reported anosmia (VAS ≥ 7) (group A) and underwent the Brief Smell Identification Test (B-SIT) and Burghart Taste Strips (BTS) to quantify the deficit objectively and repeated the tests to confirm the sense recovery. Group A patients showed B-SIT anosmia and hyposmia in 44.2% and 55.8% of cases, respectively. A total of 88.6% of group A patients reported ageusia with VAS ≥ 7, and BTS confirmed 81.8% of ageusia and 18.2% of hypogeusia. VAS smell recovery was recorded starting from 14 days, with normalization at 28 days. The 28-day B-SIT score showed normosmia in 90.6% of group A patients. The mean time for full recovery (VAS = 0) was shorter in group B (22.9 days) than in group A (31.9 days). Chemosensory deficit is frequently the first symptom in patients with COVID-19, and, in most cases, recovery occurs after four weeks.

Correlation between olfactory function, age, sex, and cognitive reserve index in the Italian population.

PURPOSE: Loss of smell decreases the quality of life and contributes to the failure in recognizing hazardous substances. Given the relevance of olfaction in daily life, it is important to recognize an undiagnosed olfactory dysfunction to prevent these possible complications. Up to now, the prevalence of smell disorders in Italy is unknown due to a lack of epidemiological studies. Hence, the primary aim of this study was to evaluate the prevalence of olfactory dysfunction in a sample of Italian adults. METHODS: Six hundred and thirty-three participants (347 woman and 286 men; mean age 44.9 years, SD 17.3, age range 18-86) were recruited from 10 distinct Italian regions. Participants were recruited using a convenience sapling and were divided into six different age groups: 18-29 years (N = 157), 30-39 years (N = 129), 40-49 years (N = 99), 50-59 years (N = 106), > 60 years (N = 142). Olfactory function, cognitive abilities, cognitive reserve, and depression were assessed, respectively, with: Sniffin' Sticks 16-item Odor Identification Test, Montreal Cognitive Assessment, Cognitive Reserve Index, and the Beck Depression Inventory. Additionally, socio-demographic data, medical history, and health-related lifestyle information were collected. RESULTS: About 27% of participants showed an odor identification score < 12 indicating hyposmia. Multiple regression analysis revealed that OI was significantly correlated with age, sex, and cognitive reserve index, and young women with high cognitive reserve index showing the highest olfactory scores. CONCLUSION: This study provides data on the prevalence of olfactory dysfunction in different Italian regions.

Diagnostic performance of nasal cytology.

PURPOSE: Nasal pathologies are characterized by a symptomatology that hardly allows to distinguish allergic rhinitis (AR), non-allergic rhinitis (NAR), and chronic rhinosinusitis (CRS). Nasal cytology (NC) has shown increasing importance in helping the clinician to differentiate the various phenotypes of rhinitis. NC allows us to evaluate nasal cellularity by distinguishing AR and various types of NAR. The objective of the study is to assess the diagnostic performance of the NC by evaluating its sensitivity, specificity, and predictive value. METHODS: We recruited 387 patients with persistent rhinitis symptoms, and nasal cytology was performed. The rhinocytogram was obtained by reading for fields and the cellular count was made using quantitative and semi-quantitative grading together. RESULTS: Two hundred and fifteen patients (55.5%; 38 had acute rhinitis, 24 acute sinusitis, 153 chronic rhinosinusitis) out of 387 referred nasal symptoms. Cytological specimen showed a mean of 94 ± 4% ciliated cells, 29 ± 0.2% mucinous cells, 16 ± 0.1% neutrophils, 11 ± 0.08% eosinophils, 4 ± 0.03 lymphocytes, 4 ± 0.03% mast cells, and 4 ± 0.01% other cells. NC was positive in 271 cases (70%). After revision of medical history, 153 patients (39%) were considered positive for NAR. Test sensibility was 100% (95% CI 97-100), specificity was 49.6% (95% CI 43-56%). Positive predictive value (PPV) was 56% (95% CI 50-62%), and negative predictive value (NPV) was 100% (95% CI 96-100%). The positive likelihood ratio was 1.98 (95% CI 1.75-2.25). Accuracy of the test was 69.5% (95% CI 64.6-74.0%). CONCLUSION: Our data showed ability to identify the true-positive patients with NAR but a low ability to identify the true-negative patients, with a global accuracy of 69.5%.

The safety of sublingual immunotherapy, can the rare systemic reactions be prevented?

Introduction: The safety of subcutaneous immunotherapy (SCIT), and particularly the dramatic issue of fatal reactions, has been an obstacle that limited the implementation of a therapy with unique characteristics of action on the causes of allergy. The introduction of sublingual immunotherapy (SLIT) was aimed at solving safety problems while maintaining clinical efficacy.Areas covered: For more than 20 years, SLIT has been based on allergen extracts in drops at low average doses. As evidenced by meta-analyses, the typical adverse events (AE) have consisted of local reactions in the mouth and throat. Unlike the injection route, no correlation was observed between the administered dose and AEs. The development of SLIT products in tablets, based on higher doses than drops, has somewhat changed the concept of SLIT safety. Although large trials, performed to obtain regulatory agency approval, have shown overall high safety, rare anaphylactic reactions have been described.Expert opinion: SLIT is globally safe, and no fatal reactions have ever been reported, but with currently available high biological potency products it is necessary to follow prudential rules, such as the administration of the first dose under medical supervision and the thorough education of patients to avoid taking of higher doses than recommended.

Diagnosis of Obstructive Sleep Apnea in Patients with Allergic and Non-Allergic Rhinitis.

Background and objectives: Rhinitis could be considered a risk factor for obstructive sleep apnea (OSA). Studies were conducted to evaluate the relation between OSA and Allergic rhinitis (AR). Non-allergic rhinitis with eosinophilia syndrome (NARES) is a condition with a symptomatology apparently similar to AR. The aim of this study was to evaluate the different presence of OSA in patients suffering from NARES and AR. Materials and Methods: Sixty patients were enrolled and subdivided into NARES, AR and control groups. NARES and AR diagnosis were performed using ARIA (Allergic Rhinitis and its Impact on Asthma) protocol. All patients were screened for OSA with home sleep apnea testing (HSAT) exam analyzing AHI (Apnea Hypopnea Index) values. Results: Results showed that 60% of patients affected by NARES presented OSA. On the contrary, altered AHI was found only in 35% of patients affected by AR and in 10% of patients belonging to the control group. Conclusions: In conclusion, data showed that there was an increased risk of OSA in NARES patients respect to AR patients and healthy patients.

Long-term omalizumab efficacy in allergic rhinitis.

BACKGROUND: Omalizumab therapy was found to be safe and effective as an add-on therapy for patients with poorly controlled severe asthma. Although several studies over the last decade have demonstrated its efficacy in other Immunoglobulin E related diseases, its use in such conditions is off-label. OBJECTIVE: This study aimed to assess the effectiveness of long-term therapy with Omalizumab in patients with persistent severe allergic rhinitis and inadequately controlled severe asthma. METHODS: Patients with poorly controlled severe asthma and persistent allergic rhinitis were enrolled and treated with Omalizumab for 36 months with every four-week subcutaneous administration. The efficacy assessment included the severity of AR symptoms every six months using Visual Analogue Scale, Asthma Control Test, nasal endoscopy, spirometry, and biomarkers (blood eosinophils and neutrophils, fractional exhaled nitric oxide, total IgE). RESULTS: Eleven patients aged between 26 and 70 years were enrolled, and 10 completed the study. A significant improvement of allergic rhinitis symptoms, Asthma Control Test, and lung function was observed. There was also a reduction in the status of the biomarkers at the end of the study. CONCLUSION: Long-term therapy with Omalizumab was effective and safe in treating severe persistent allergic rhinitis and concomitant asthma.

Giant Cell Arteritis (GCA): Pathogenesis, Clinical Aspects and Treatment Approaches.

Giant Cell Arteritis (GCA), or Horton's Arteritis, is a chronic form of vasculitis of the large and medium vessels, especially involving the extracranial branches of the carotid arteries, in particular, the temporal artery, with the involvement of the axillary, femoral and iliac arteries too. Arterial wall inflammation leads to luminal occlusion and tissue ischemia, which is responsible for the clinical manifestations of the disease. A substantial number of patients affected by GCA present head and neck symptoms, including ocular, neurological and otorhinolaryngological manifestations. The aim of this article is to present pathogenesis, clinical aspects and treatment approaches of GCA manifestations.

Behçet's disease: New insights into pathophysiology, clinical features and treatment options.

Behçet's disease (BD) is a rare systemic vasculitis characterized by oral aphthous ulcers, genital ulcers, ocular lesions and other systemic manifestations. BD occurs most frequently in Eurasian populations along the ancient trading route known as the "Silk Road" which extends from eastern Asia to the Mediterranean basin. The causes of BD are unknown: it is believed to be due to an autoimmune process triggered by an infectious or environmental agent in genetically predisposed individuals. HLA-B51 allele located in the MHC locus, on chromosome 6p, has been the most strongly associated risk factor for BD in areas along the Old Silk Route. Herpes simplex virus-1 and Streptococcus have been postulated as possible environmental triggers of BD. T cell homeostasis perturbation, especially Th1 and Th17 expansion and decreased regulation by Tregs are now supposed to be the cornerstone of BD pathogenesis. The histology shows vasculitis that involves both arteries and veins, and vessels of any size. BD is a systemic vasculitis with significant neutrophil infiltration, endothelial cell swelling, and fibrinoid necrosis. The diagnosis of BD is only supported by clinical criteria and requires the exclusion of other diagnoses based on clinical presentation. There are no pathognomonic laboratorial findings of BD. This rare disease often leads to blindness and fatal systemic involvement. Main causes of death include major vessel disease and central nervous system involvement. Corticosteroids are commonly used to treat clinical manifestations of BD in combination with immunosuppressant drugs. Tumor necrosis factor (TNF)-blocking agents such as Infliximab, Etanercept, and Adalimumab have been reported to have success in patients with BD.

Social geography of Rhinoscleroma and qualitatively and quantitatively abnormal cell-mediated immunity.

Rhinoscleroma is a progressive chronic granulomatous disease of the upper respiratory tract that may extend to the tracheobronchial tract. It is common belief that the pathology is determined by Klebsiella Rhinoscleromatis. In the authors' opinion, the infection with Klebsiella Rhinoscleromatis may not represent the only etiopathogenic factor of the disease. Rhinoscleroma is reported in many countries, but has a peculiar social and geographic distribution, in that it assumes an endemic character only in some regions of the Middle East, West Russia, North Africa, Indonesia, Central and South America. In Europe, most of the cases are reported in Poland, Hungary and Romania. In Italy, Rhinoscleroma is almost exclusively located in the southern and island regions. Rhinoscleroma is predominantly reported in rural areas, in the presence of poor socio-economic conditions, which according to many authors would be a co-factor triggering the disease. In this article, the authors review some inconsistencies in etiology, histology and epidemiology of Rhinoscleroma. Based on the overall picture, they propose that intrinsic factors, possibly of genetic origin, may give rise to the disease, and suggest possible lines of research to distinguish between extrinsic and intrinsic factors as determinants for Rhinoscleroma.