Non-specific Orbital Inflammation of Sinonasal Origin

Serum Antibodies Reactive with Eye Muscle Membrane Antigens Are Detected in Patients with Nonspecific Orbital Inflammation

Common fibrin deposition and tissue plasminogen activator downregulation in nasal polyps with distinct inflammatory endotypes

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Nonspecific orbital inflammation (NSOI), colloquially known as orbital pseudotumor, sometimes presents a diagnostic and therapeutic challenge in ophthalmology. This review aims to dissect NSOI through a molecular lens, offering a comprehensive overview of its pathogenesis, clinical presentation, diagnostic methods, and management strategies. The article delves into the underpinnings of NSOI, examining immunological and environmental factors alongside intricate molecular mechanisms involving signaling pathways, cytokines, and mediators. Special emphasis is placed on emerging molecular discoveries and approaches, highlighting the significance of understanding molecular mechanisms in NSOI for the development of novel diagnostic and therapeutic tools. Various diagnostic modalities are scrutinized for their utility and limitations. Therapeutic interventions encompass medical treatments with corticosteroids and immunomodulatory agents, all discussed in light of current molecular understanding. More importantly, this review offers a novel molecular perspective on NSOI, dissecting its pathogenesis and management with an emphasis on the latest molecular discoveries. It introduces an integrated approach combining advanced molecular diagnostics with current clinical assessments and explores emerging targeted therapies. By synthesizing these facets, the review aims to inform clinicians and researchers alike, paving the way for molecularly informed, precision-based strategies for managing NSOI.

The sense of smell in chronic rhinosinusitis

chronic rhinosinusitis (CRS) is a prevalent disease affecting 5-15% of the population, characterized by prolonged inflammation of the mucosa of the paranasal sinuses. Chronic rhinosinusitis with nasal polyps (CRSwNP) accounts for approximately 18-20% of all CRS cases and has a more severe clinical course compared to CRS without nasal polyps (CRSsNP). A particular group of patients includes those with CRSwNP associated with aspirin-exacerbated respiratory disease (AERD), which comprises asthma, rhinosinusitis with polyps, and intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to evaluate the impact of a past COVID-19 infection on sinonasal symptoms and quality of life in patients with chronic polypous rhinosinusitis and aspirin triad based on the analysis of SNOT-22 questionnaire scores and endoscopic assessment results using the Lund-Kennedy scale. The study was conducted among outpatients at the clinic of the State Institution " O.S. Kolomiychenko Institute of Otolaryngology of National Academy of Sciences of Ukraine." Sixty patients aged 18 to 75 years with a diagnosis of chronic polypous rhinosinusitis with NSAID intolerance were selected and divided into two groups: Group 1 (17 patients) who did not have COVID-19 and Group 2 (43 patients) who had a history of COVID-19. Group 2 was further divided into two subgroups: Subgroup 2A (18 patients, who reported no impact of COVID-19 on the course of CRS) and Subgroup 2B (25 patients, who reported a subjective worsening of CRS after COVID-19). A survey was conducted using the SNOT-22 questionnaire, and endoscopic examination of the nasal cavity was performed with assessment using the Lund-Kennedy scale. The analysis of the SNOT-22 results showed that the mean scores in Group 1 were 41.9 ± 17.94, and in Group 2, they were 43.62 ± 20.12, with no statistically significant differences (p=0.812). The mean scores in Subgroups 2A and 2B were 44.3 ± 19.4 and 43.0 ± 21.2, respectively, also with no statistically significant differences (p=0.874). The endoscopic assessment using the Lund-Kennedy scale did not reveal significant differences between the groups (p=0.588). The study results indicate that a past COVID-19 infection did not have a statistically significant impact on sinonasal symptoms in patients with chronic polypous rhinosinusitis and aspirin triad. COVID-19 did not lead to a significant worsening of the clinical course of the disease, warranting further studies to explore the virus's impact on other aspects of respiratory health in patients with AERD.

1. Samantha Meaney, MD* 2. Ana Swafford, MD† 3. Jacob J. Rosenberg, MD†‡ 1. *American University of the Caribbean, Cupecoy, St. Maarten. 2. †Nassau University Medical Center, East Meadow, NY. 3. ‡SUNY at Stony Brook, West Hempstead, NY. An 18-year-old woman presents to the emergency department with 2 days of right eye swelling. The patient was in her usual state of good health until 2 days ago, when she noted swelling around her right eye. She presents to the emergency department today because the swelling has increased during the past 24 hours and she now has eye pain. There is no history of fever, trauma, recent bug bites, allergic rhinitis, or recent upper respiratory tract infection symptoms. In the emergency department the patient is afebrile, yet her right eyelids are swollen and mildly erythematous. She has pain with upward and lateral gaze and some mild limitation of superior and lateral right eye movement. There is no nasal congestion; the rest of her physical examination findings are normal. Several laboratory examinations are performed. A complete blood cell count reveals the following: hemoglobin, 14.7 g/dL (147 g/L); hematocrit, 42.9% (0.43); leukocytes, 4,400/μL (4.4 × 109/L) (35% neutrophils, 44% lymphocytes, 13% monocytes, and 8% eosinophils); and platelets, 238 ×103/μL (238 × 109/L). Serum electrolytes, glucose, blood urea nitrogen, creatinine, and liver enzyme levels are normal. The C-reactive protein level is 3.0 mg/L (28.6 nmol/L), and the erythrocyte sedimentation rate is 1 mm/h. Computed tomography (CT) of her orbits and sinuses is performed ( Figure 1 ). Figure 1. Sinus computed tomogram showing a right-sided septal mass that extends into the inferior rectus muscle and is suggestive of an abscess. There is no evidence of sinus disease. The patient is admitted to the pediatric department and administered intravenous ceftriaxone and vancomycin for presumed right orbital abscess with …

National burden of antibiotic use for adult rhinosinusitis

Recently, significant progress has been made in identifying the cellular and molecular mechanisms responsible for the pathogenesis of chronic rhinosinusitis (CRS). Cohort studies of CRS have led to advances in the clinical understanding of this disease. New therapeutic agents have been approved or are undergoing clinical trials to expand treatment options for this disease. One of the promising areas in medicine is the provision of personalized clinical care. From this perspective, CRS can be divided into three different endotypes depending on the type of underlying inflammatory response. In the United States, CRS with and without nasal polyps is predominantly characterized as the second inflammatory endotype. CRS with nasal polyps (about 17%) and without nasal polyps (up to 20%) belongs to the 1st and 3rd inflammatory endotypes, respectively. And if for the second inflammatory endotype the effectiveness of targeted biological therapy is beyond doubt, then for the first and third inflammatory endotypes the principles of such conservative therapy are under active development. Moreover, large validated studies to confirm associations between CRS phenotypes and endotypes, as well as to find effective biological markers of inflammatory endotypes, remain to be performed.

Orbital inflammation is typically an idiopathic process that occasionally may be identified with a specific local or systemic disease as the causative agent. Orbital inflammatory pseudotumor (also known as idiopathic orbital inflammation syndrome, orbital pseudotumor, nonspecific orbital inflammation, and orbital inflammatory syndrome) is defined as an idiopathic tumor-like inflammation consisting of a pleomorphic cellular response and a fibrovascular tissue reaction. Various rheumatologic disorders are associated with orbital inflammation and must be ruled out in cases of orbital inflammatory pseudotumor, including Wegener's granulomatosis, giant cell arteritis, systemic lupus erythematosus, dermatomyositis, and rheumatoid arthritis. The mainstay of therapy is corticosteroid therapy, although there is an increasing trend toward use of antimetabolites, alkylating agents, cytotoxic agents, and other immunosuppressive agents.

Orbital pseudotumor is nonspecific orbital inflammation (NSOI). It is a benign, non-infectious, space-occupying inflammatory lesion of the orbit. NSOI can affect various tissues in the orbit, such as the lacrimal gland and extraocular muscles. The most common classification is based on clinical presentation. Bacteria, viruses, fungi, or parasites can cause infectious orbital inflammation. It is a diagnosis of exclusion after ruling out inflammatory, infectious, and neoplastic causes. We present a case of a male in his sixties who presented with progressive pain, swelling, blurry vision, and forward protrusion of his right eye. He had no history of trauma or recent illness. His general physical and systemic examination was within normal limits. His ocular examination showed eyelid edema, erythema, eccentric proptosis, and a mature cataract in his right eye. His left eye showed a lenticular opacity. CT orbit revealed a homogenous isodense lesion observed without any globe distortion. A diagnosis of orbital pseudotumor was made. The patient was treated with oral corticosteroids, and an excision biopsy was done, resulting in symptomatic improvement and regression of inflammation at follow-up. In complex cases of inflammatory orbital pseudotumor, particularly those with granulomatous inflammation, some initial success has occurred with monoclonal antibodies against tumor necrosis factor (TNF)-alpha or with lymphocyte depletion using rituximab. Our patient, however, responded well to an excision biopsy and a course of oral steroids.

Immunology-based recommendations for available and upcoming biologics in aspirin-exacerbated respiratory disease

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient's quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0-8) was reduced significantly in the cohort (mean change: -2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (-3.57, p < 0.0001) and smell impairment (-4.0, p < 0.0001) visual analog scale scores (0-10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population.

Idiopathic orbital inflammatory disease (IOID), also called non-specific orbital inflammation (NSOI) or orbital pseudotumor, is an uncommon disorder characterized by nonneoplastic, non- infective, space-occupying orbital infiltration with inflammatory features. The process may preferentially involve any or all of the orbital soft tissues. Histopathological analysis reveals pleomorphic inflammatory cellular infiltration followed by reactive fibrosis. Unilateral disease is typical in adults, although in children bilateral involvement may occur. Intracranial extension is rare. Simultaneous orbital and sinus involvement is also rare and may be a distinct entity [1]. According to Ayurveda, this inflammatory condition on the eye lids can be correlated with Kaphaja Netra Abhishyanda and treated accordingly. Kaphaja Netra Abhishyanda is defined in Ayurveda as a disease affecting all parts of the eye characterised by Guruta (heaviness of lids), Kandu (itching), Pichila (repeated lacrimation), Alpa Vedana (Foreign body sensation) photophobia and burning sensation in eyes etc. An ocular therapeutic called Bidalaka is the application of medicated paste on the eye's outer surface expect eye lashes. Bidalaka is indicated in inflammatory conditions of the eyes. A 72-year-old female patient diagnosed with NSOI on clinical presentation was advised Haridradi Bidalaka for five days. The signs &amp; symptoms were reduced to a very mild degree. The result proved to be effective based on clinical assessment.

Oral Itraconazole in the Treatment of Chronic Rhinosinusitis