Dupilumab: a delayed response in asthmatic and atopic patients treated for chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a common disease, which was previously approached with sinus surgery or systemic corticosteroids. The advent of biological therapies radically changed the approach to this disease. On the other hand, there is scarce scientific evidence of how specific subsets of patients respond to this treatment. METHODS: this is a monocentric, prospective study investigating the long-term efficacy on biweekly 300 mg dupilumab therapy in CRSwNP, prescribed to 61 patients. Patients were evaluated at baseline and every 2 months for the first 6 months, then at 9, 12, 16, 20 and 24 months. RESULTS: dupilumab proved to be an effective treatment, neatly improving both subjective and objective measurements in CRSwNP. The main finding of the study is the difference between specific subgroups of patients: while the overall response is similar, patients with Th2 comorbidities such as asthma and atopy tend to reach a stable response later, with the improvement ongoing even after 6 months of therapy, while non-asthmatic, non-atopic patients attain an earlier stability in response. CONCLUSIONS: dupilumab provides an excellent long-term control of CRSwNP, but the response in asthmatic and atopic patients appears to be different and delayed when compared to non asthmatic and non atopic ones.

Atypical Tongue Abscesses Mimicking Submucosal Malignancies: A Review of the Literature Focusing on Diagnostic Challenges.

Tongue abscesses are rare conditions that usually follow mucosal disruption due to mechanical trauma or foreign body impaction. They typically manifest abruptly as a rapidly growing, hard mass or swelling in the context of tongue muscles; the patient frequently complains of pain, difficulties in swallowing or speaking, and fever. Nonetheless, the features of its presentation, together with accurate clinical evaluation, blood tests, and appropriate imaging tests, are usually sufficient to easily discern a tongue abscess from a malignancy. However, in rare cases, they may occur with slowly progressing and subtle symptoms, nuanced objective and laboratory findings, and inconclusive radiological evidence, leading to difficult differential diagnosis with submucosal malignancy. Herein, we review the literature, available on Pubmed, Embase, and Scopus, on publications reporting tongue abscesses, with atypical presentation suggesting an oral tumor. Our review confirms that tongue abscesses may manifest as a slowly growing and moderately painful swelling without purulent discharge and minimal mucosal inflammation; in this case, they may constitute an actual diagnostic challenge with potentially severe impact on correct management. Atypical tongue abscesses must therefore be considered in the differential diagnosis of tongue malignancy with submucosal extension, even when other diagnostic elements suggest a neoplasia; in this case, a deep biopsy under general anesthesia is essential for differential diagnosis, and simultaneous drainage of the necrotic and abscessual material may resolve the condition.

Early increase in eosinophil count may predict long-term hypereosinophilia during dupilumab treatment: a 2-year observational study.

KEY POINTS: In a limited subset of patients, dupilumab-induced hypereosinophilia is persistent. Two-month follow-up eosinophil count may predict long-lasting hypereosinophilia.

Use of a Fiberoptic-Laser Approach During Endoscopic Sinus Surgery: A Cadaver Feasibility Study.

Aims: The aim of the present study is to evaluate the clinical applicability of laser energy during an oro-nasal endoscopic approach (ONEA) in the management of the anterior maxillary sinus wall. Methods: An experiment on three adult human cadavers was performed to study the nasal cavities with angled rigid scopes and using the ONEA technique. In order to evaluate the effectiveness of laser energy on the bone, the drilling effect was compared to laser energy (1470 nm diode laser, continuous wave, power 8, 9 and 10 W). Results: Compared to a rigid angled scope, the ONEA technique allowed complete visualization of the anterior wall of the maxillary sinus. Microscopic analysis of frontal bone revealed similar bone Exeresis with high-speed drilling (270.28 µm) and laser approaches (285.73-456.6 µm). Conclusions: The laser ONEA technique is an innovative, mini-invasive, and safe approach to the anterior wall of the maxillary sinus. Additional study is warranted to further develop this technique.

Endoscopic and external dacryocystorhinostomy: A therapeutic proposal for distal acquired lacrimal obstructions.

Endoscopic (END-DCR) and external dacryocystorhinostomies (EXT-DCR) are nowadays considered the gold standard techniques for non-oncologic distal acquired lacrimal disorders (DALO). However, no unanimous consensus has been achieved on which of these surgeries is the most suitable to the individual patient. Herein, we review the available literature of the last 30 years with the aim of defining a simple and reproduceable treatment algorithm to treat DALO. A search of PubMed, EMBASE, Scopus and Cochrane databases was last performed in December 2021 to examine evidence regarding the role of END-DCR and EXT-DCR in primary and revision surgeries. If considered primary surgeries, END-DCR should be preferred in case of intranasal comorbidities, given the possibility to directly visualize and treat potential intranasal pathologies. Conversely, EXT-DCR should be chosen in case of need/preference for local anesthesia, given the major historical experience and wider surgical field that helps to resolve intra-operatory complications (e.g., bleeding) in an uncollaborative patient. In the absence of the abovementioned conditions, the decision of one or other approach should be discussed with the patient. In recurrent cases, END-DCR should be considered the treatment of choice given the major likelihood to visualize the causes of primary failure and directly resolve it. In conclusion, END-DCR should be considered the treatment of choice in revision cases or in primary ones associated with intranasal pathologies, whereas EXT-DCR should be chosen if local anesthesia is needed. In the absence of these scenarios, it is still open to debate which of these two approaches should be used.

Comparison of guidelines for prescription and follow-up of biologics for chronic rhinosinusitis with nasal polyps.

PURPOSE: To compare international and regional guidelines for prescription and monitoring of response to biologics in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: A literature review was performed to identify publications reporting indications for biologic therapy in CRSwNP. A full-text reading identified specific issues for comparison: prior surgery, evidence of type 2 inflammation (T2I), smell function, comorbidities, use of systemic corticosteroids, impact on quality of life, and endoscopic and CT findings were compared for the prescription, while the monitoring of the treatment was described in relation to timing, classification of response and criteria for withdrawal. RESULTS: Ten publications were found. Prior surgery was strictly necessary in five guidelines, while in all the remaining it was variably recommended. A confirmation of T2I was considered necessary in one publication, unnecessary in two, and recommended or constituted only one of the factors to consider in seven. All the other issues analyzed were variably considered. Reevaluation was suggested at 4-6 months and 1 year, mostly assessing improvement in the same criteria used for prescription. CONCLUSIONS: A combination of subjective and objective findings is used for the identification of patients with CRSwNP who are indicated for biologic therapy. Major debate has developed on the need for previous surgery, which is generally recommended, or strictly necessary for some authors. Confirmation of T2I is generally suggested, but compulsory only in a minority of guidelines. Smell function, use of systemic corticosteroids, and the impact on quality of life are the other factors most frequently considered.

Hypereosinophilia management in patients with type 2 chronic rhinosinusitis treated with dupilumab: preliminary results.

PURPOSE: Biological therapies are gaining relevance in the management of CRSwNP with few adverse events reported. Among these, dupilumab, an anti-IL4-Ra monoclonal antibody, is frequently associated with hypereosinophilia (HE) which usually remains silent and progressively resolves, although some cases of systemic involvement occurs. The aim of this paper is to describe our experience and propose a management flowchart for HE during therapy with dupilumab. METHODS: Patients with CRSwNP who satisfied EPOS2020 criteria for biological therapies were included in this prospective study. Each case was discussed in a multidisciplinary meeting with subsequent prescription of dupilumab; all patients were candidates to follow-up bi-monthly for 6 months, while additional blood tests were scheduled in the event of HE. RESULTS: A total of 21 patients with a mean age of 48.4 years were enrolled. Of these, 15 of 21 presented an asthma comorbidity and 9 of 21 ASA sensitivity. Four patients (19%) developed HE with AEC > 1.5 × 109/L, whereas it occurred in 9.5% (two patients) if considered AEC > 3 × 109/L. No cases of hypereosinophilic syndrome were recorded. Following our decision-making flowchart, two patients received short-term corticosteroid therapy, whereas the other two were only eligible for closer follow-up. CONCLUSIONS: During dupilumab therapy, HE may occur and should be considered benign when < 3 × 109/L in the absence of organ involvement. Conversely, in case of HE ≥ 3 × 109/L, an empirical approach with short-term corticosteroid therapy should be considered to debulk the blood from eosinophils and prevent potential organ involvement.

The importance of clinical presentation on long-term outcomes of external dacryocystorhinostomies: Our experience on 245 cases.

PURPOSE: External dacryocystorhinostomy (EXT-DCR) is a surgical approach commonly used to treat post-canalicular acquired lacrimal obstruction whose success rate has been described, equally with endoscopic DCR, to be superior to other available treatments. METHODS: At San Raffaele Hospital, Milan (Italy), from January 2008 to December 2020, 245 EXT-DCRs were performed. All patients underwent routine pre-operative work-up including Jones tests and probing and irrigation of the lacrimal pathway; when necessary, a multidisciplinary approach with nasal endoscopy was performed. The surgical approach was followed by positioning of a bicanalicular stent which was left in place for 6 months. Success was defined as resolution of clinical signs/symptoms and free lacrimal flow on functional test. RESULTS: Of the cases enrolled, 26.9% were treated for recurrent epiphora (group 1), and 73.1% for epiphora associated with chronic dacryocystitis (group 2). After a median follow-up of 71 months, group 1 had success at T0 (1 month) and T1 (long-term) of 81.8% and 60.6%, respectively, compared to 93.8% and 77.7% in group 2. Statistical analysis showed a significant association with surgery both at T0 (p = 0.018) and T1 (p = 0.012) with group 2 showing better outcomes. Additionally, the cosmetic outcome of the external scar was defined as invisible in 91.8% of cases and slightly visible in 8.2%. CONCLUSIONS: External dacryocystorhinostomy provides long-term reliable results particularly in case of chronic dacryocystitis. Moreover, the optimal esthetic outcome of the external scar should be no longer considered the only guiding principle of treatment modality, particularly in the elderly.

A prospective study on the efficacy of dupilumab in chronic rhinosinusitis with type 2 inflammation.

Objective: Treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) includes endoscopic sinus surgery and topic and/or systemic corticosteroids, which have only temporary effects. The development of biologic therapies has provided a new treatment paradigm for CRSwNP. Dupilumab is the only biological approved in Italy for CRSwNP, but its efficacy in a real-life context is still scarce. Methods: We carried out a monocentric prospective study at our institution with a 6-month follow-up on patients administered biweekly 300 mg dupilumab therapy for CRSwNP, prescribed according to EPOS 2020 criteria. Patients were evaluated at baseline and every 2 months. Results: Median values at baseline and 6 months were, respectively, 3/12 and 8/12 for the Brief Smell Identification Test (p = 0.005), 5/8 and 2/8 for the Nasal Polyp Score (p < 0.001), 10/20 and 6/20 for the Lund-Kennedy score (p < 0.001), 65/110 and 14/110 for the Sinonasal Outcome Test (p < 0.001), and 15/25 and 23/25 for the Asthma Control Test score (p = 0.009). Adverse events were mild, consisting mainly in discomfort at the site of injection. Four patients developed asymptomatic hypereosinophilia. The treatment was not discontinued in any patient. Conclusions: Dupilumab was confirmed to be an effective and safe treatment for CRSwNP, as previously seen in registrational studies.

Cocaine-Induced Midline Destructive Lesions: A Real Challenge in Oral Rehabilitation.

Cocaine abuse is associated with severe local effects on mucosal and osteocartilaginous structures, with a centrifugal spreading pattern from the nose, a condition known as cocaine-induced midline destructive lesions (CIMDL). When the soft or hard palate is affected, a perforation may occur, with subsequent oro-nasal reflux and hypernasal speech. Both diagnosis and therapy (surgical or prosthetic) constitute a serious challenge for the physician. The cases of three patients affected by cocaine-induced palatal perforation and treated with a palatal obturator at San Raffaele Dentistry department between 2016 and 2019 are presented. In addition, the literature was reviewed in search of papers reporting the therapeutic management in patients affected by cocaine-induced palatal perforation. All the patients in our sample suffered from oro-nasal reflux and hypernasal speech, and reported a significant impact on interpersonal relationships. The results at the delivery of the obturator were satisfactory, but the duration of such results was limited in two cases, as the progression of the disease necessitated continuous modifications of the product, with a consequent increase in costs and a reduction in patient satisfaction. In conclusion, the therapy for palatal defects in CIMDL includes both reconstructive surgery and prosthetic obturators, the latter being the only possibility in the event of active disease. It successfully relieves symptoms, but the long-term efficacy is strongly related to the level of disease activity.

Melanoma of the lacrimal drainage system: A systematic review.

Melanoma of the lacrimal drainage system (LDSM) is a rare and subtle condition that is frequently misdiagnosed. In the present work, we conducted a systematic review investigating the clinical features, management, and prognosis of LDSM. A structured search, according to PRISMA criteria, was performed in April 2020 and updated in February 2021 on Pubmed, EMBASE, Cochrane, and SCOPUS. The articles found underwent a double-reviewer selection and the main data were extracted. After complete screening, 30 articles reporting 38 cases were included. The time from the first symptom to medical contact ranged from 1 month to 4 years. Surgery was the treatment proposed to all patients, with a variable extension of resection. LDSM is a rare disease that is burdened by poor prognosis. Early diagnosis is crucial, even if difficult to achieve. Surgery and radiotherapy are standardized treatments, while targeted therapy and immunotherapy are attractive prospects.

IgG4-Related Disease of the Oral Cavity. Case Series from a Large Single-Center Cohort of Italian Patients.

A series of destructive and tumefactive lesions of the oral cavity are increasingly recognized as part of the IgG4-related disease (IgG4-RD) spectrum. We herein examined the clinical, serological, radiological, and histological features of a series of patients referred to our clinic because of oral cavity lesions ultimately attributed to IgG4-RD. In particular, we studied 6 consecutive patients out of 200 patients referred to the immunology outpatient unit who presented with erosive and/or tumefactive lesions of the oral cavity. All patients underwent serum IgG4 measurement, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4+ plasma cells/High-Power Field (HPF) for calculation of the IgG4+/IgG+ plasma cell ratio. Six patients (3% of the entire cohort) were diagnosed with IgG4-RD of the oral cavity based on histological evaluation. A major complaint at presentation was oral discomfort due to bulging mass. A mild to no increase in serum IgG4 was observed. Different patterns of organ involvement were associated with oral lesions. Five patients were treated with immunosuppressive therapy and two patients promptly responded to B-cell depletion with rituximab. Watchful waiting was decided in one patient with no major clinical symptoms. Involvement of the oral cavity is an infrequent manifestation of IgG4-RD but should be taken into consideration as a possible differential diagnosis of tumefactive or erosive lesions once neoplastic conditions are excluded. A histological examination of biopsy samples from the oral cavity represents the mainstay for diagnosis of IgG4-RD.