Utility of Pre-Hematopoietic Cell Transplantation Sinus CT Screening in Children and Adolescents.

BACKGROUND AND PURPOSE: The clinical benefit of pre-hematopoietic cell transplantation sinus CT screening remains uncertain, while the risks of CT radiation and anesthesia are increasingly evident. We sought to re-assess the impact of screening sinus CT on pretransplantation patient management and prediction of posttransplantation invasive fungal rhinosinusitis. MATERIALS AND METHODS: Pretransplantation noncontrast screening sinus CTs for 100 consecutive patients (mean age, 11.9 ± 5.5 years) were graded for mucosal thickening (Lund-Mackay score) and for signs of noninvasive or invasive fungal rhinosinusitis (sinus calcification, hyperattenuation, bone destruction, extrasinus inflammation, and nasal mucosal ulceration). Posttransplantation sinus CTs performed for sinus-related symptoms were similarly graded. Associations of Lund-Mackay scores, clinical assessments, changes in pretransplantation clinical management (additional antibiotic or fungal therapy, sinonasal surgery, delayed transplantation), and subsequent development of sinus-related symptoms or invasive fungal rhinosinusitis were tested (exact Wilcoxon rank sums, Fisher exact test, significance P < .05). RESULTS: Mean pretransplantation screening Lund-Mackay scores (n = 100) were greater in patients with clinical symptoms (8.07 ± 6.00 versus 2.48 ± 3.51, P < .001) but were not associated with pretransplantation management changes and did not predict posttransplantation sinus symptoms (n = 21, P = .47) or invasive fungal rhinosinusitis symptoms (n = 2, P = .59). CONCLUSIONS: Pre-hematopoietic cell transplantation sinus CT does not meaningfully contribute to pretransplantation patient management or prediction of posttransplantation sinus disease, including invasive fungal rhinosinusitis, in children. The risks associated with CT radiation and possible anesthesia are not warranted in this setting.

Conversion to Chronic Invasive Fungal Sinusitis From Allergic Fungal Sinusitis in Immunocompetence.

A review of the treatment of allergic and invasive fungal sinusitis, as well as a presentation of the first recorded case of a conversion from allergic fungal sinusitis (AFS) to chronic granulomatous invasive sinusitis and the fourth case of invasive fungal sinusitis associated with Curvularia. This immunocompetent patient suffering from chronic AFS converted after repeated high-dose steroid tapers and noncompliance. AFS may present atypically and should be suspected even in immunocompetent patients with sinus disease who report new onset pain and neurologic symptoms. Clinicians should consider the potential complications associated with repeated systemic steroid administration. Laryngoscope, 129:2447-2450, 2019.

Ear, nose and throat involvement in granulomatosis with polyangiitis: how it presents and how it determines disease severity and long-term outcomes.

Ear, nose and throat (ENT) manifestations in granulomatosis with polyangiitis (GPA) represent the most frequent symptoms at disease onset. The aim of the study was to analyse ENT involvement at diagnosis, as well as how it could influence relapse rate, mortality and disease severity. A retrospective non-controlled cohort study was performed including all consecutive diagnosed GPA from 1996 to 2016 in two rheumatology centres of Northern Italy, focusing particularly on ENT presenting signs and symptoms at baseline. Eighty-nine patients (48.3% females) with new onset GPA were evaluated. They were mostly Caucasian (97.7%), middle aged (mean 54.5 years) and more frequently anti-neutrophil cytoplasmic antibodies (ANCA) positive (78.6%) with PR3 specificity (81.4%). At diagnosis, ENT involvement was reported in 71.9% patients, second only to systemic symptoms. These patients were significantly younger at disease onset (0.013), with less frequent renal involvement (0.014) irrespectively to ANCA status, but with significantly higher Vasculitis Damage Index (VDI) (0.001). The most frequent ENT manifestation was sinonasal involvement (58.4%, 73% of which with nasal inflammation/chronic sinusitis and 48% with nasal crusting), while otologic involvement (mainly otitis media/otomastoiditis) was observed in 34.8%. ENT-GPA patients presented a higher survival rate at 5 years (98.1 vs 77.7%, 0.049), and ENT involvement resulted to be an independent predictor of better outcome (OR 0.37, 95% CI 0.2-0.8, 0.019). Our data confirms that ENT involvement is not only one of the key clinical features of GPA, but also could point out a milder GPA subset with lower renal involvement and lower mortality rate, irrespectively to ANCA status.

[Progress of sino-nasal IgG4-related disease].

IgG4-related disease is a newly recognized systemic fibro inflammatory disorder that affects the sino-nasal region. It is a rare and emerging entity that can present with bony and soft-tissue invasion,the final diagnosis of this disease mainly depends on pathological examination and majority of patients receiving corticosteroids responded very well to treatment. Thus,Our goal was to highlight the sino-nasal presentation of this unique disease and to review previously reported cases from 2010 to 2016.We hope that clinical physicians to enhance understanding of the disease in order to ensure early diagnosis and early intervention to prevent serious injury and fibrosis of organs.

Orbital presentation of a nasal midline destructive lesion in a young boy.

Midline Destructive Lesions (MDL) are well known to cause nasal problems. There is a long differential diagnosis of such lesions. However, in the pediatric population, the 2 main diseases to be aware of are Non-Hodgkin's T-cell lymphoma and granulomatosis with polyangiitis (previously known as Wegener's granulomatosis). The authors present the report of a 15-year-old boy who presented with epiphora, chemosis, and limitation of left abduction. CT scan of his orbits suggested a destructive lesion of the ethmoid sinuses. His laboratory investigations revealed a positive ANCA. The patient underwent endoscopic sinus surgery, and this was characteristic for granulomatosis with polyangiitis. He was treated with systemic steroids and then maintained on cyclophosphamide, which controlled his disease activity. This case highlights the need for ophthalmologists to have a high index of suspicion for MDL and concomitant orbital disease.

Air pollutants cause release of hydrogen peroxide and interleukin-8 in a human primary nasal tissue culture model.

BACKGROUND: A component of primary innate defense of the nasal mucosa against inhaled pathogens includes continuous, low-level release of hydrogen peroxide (H2 O2 ) into luminal secretions. Epidemiologically, an association exists between poor air quality and increased prevalence of sinonasal disease. To understand the effects of particulate matter (PM) in nasal mucosa, we studied the release of H2 O2 and interleukin 8 (IL-8) after PM exposure. METHODS: Human nasal specimens were collected from surgery and cultured in serum-free growth medium. Cell integrity and recovery during culture was monitored by lactate dehydrogenase (LDH) release into the medium. Cultures were exposed to PM for 24 hours in the presence/absence of diphenyleneiodonium sulfate (DPI; a nicotinamide adenine dinucleotide phosphate [NADPH] oxidase inhibitor). Luminex cytokine and Amplex-Red H2 O2 assays were performed. RESULTS: LDH levels dropped rapidly within 2 days, indicative of stabilization and cell recovery after harvest. All cultures released H2 O2 into the medium. Exposure to PM (20 µg/cm(2) ) increased H2 O2 levels significantly (94.6 ± 7.7 nM) compared to untreated controls (55.8 ± 4.0 nM; p = 0.001). PM-induced H2 O2 production was partially inhibited by DPI (80.1 ± 3.8nM), indicating that cellular NADPH oxidase may be a primary source of H2 O2 production. Exposure to PM increased IL-8 levels in a dose-dependent fashion (control = 2301 ± 412 MFI; 20 µg/cm(2) = 5002 ± 1327 MFI; 40 µg/cm(2) = 8219 ± 1090 MFI; p = 0.022). CONCLUSION: PM increases the quantity of H2 O2 released by nasal epithelial cells, indicating that PM can contribute to oxidative stress in part by activating a normal cellular defense mechanism. Exposure to PM resulted in elevated IL-8 levels and mucin production in explants. Efforts to reduce airborne PM may lead to reduced H2 O2 and mucin production in sinonasal epithelium.

Relationship between sputum eosinophilia and sinus disease in patients with eosinophilic bronchitis.

BACKGROUND: Sinus disease is commonly seen in patients with asthma, and several studies have been published describing the relationship between sinus disease and the inflammation seen in the sputum of asthmatic subjects. In this article, we expand on this knowledge by studying patients with eosinophilic bronchitis with and without asthma. METHODS: We describe the relationship between the severity of sinus disease determined by the Lund-Mackay score and sputum eosinophilia. Comparisons with blood eosinophil and total immunoglobulin (IgE) measurements are made. RESULTS: We have shown that the severity of sinus disease is positively correlated with sputum eosinophil counts, and the site of sinus disease affected the level of eosinophilia. There was a positive correlation between sputum eosinophils and blood eosinophils, but there was no relationship with blood total IgE levels. CONCLUSIONS: We have confirmed that there is a link between upper and lower airway inflammation and that this is not limited to patients with asthma. The process is associated with systemic inflammation as evidenced by increased blood eosinophils but appears to be independent of IgE.

[Differential diagnosis of rheumatic diseases and blood cancers involving the nasal cavity and accessory sinuses].

AIM: To provide the clinical, laboratory, radiological, morphological, and immunomorphological signs that permit the differential diagnosis to be made in patients with involvement of the nasal cavity and accessory sinuses (NCAS). SUBJECTS AND METHODS: In the period 2009 to 2013, the Laboratory for Intensive Therapy for Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, associated the disease onset with NCAS involvement in 39 (7.6%) of 512 examinees. NCAS involvement was present at disease onset in 100% of the patients with natural killer (NK) cell lymphoma (NK/T lymphoma), in 84.5% of those with Wegener granulomatosis (WG), in 29.5% of those with IgG4-related disease (IgG4-RD), and in 17.5% of those with sarcoidosis. Such an onset could be extremely rarely observed in histiocytosis. RESULTS: Despite the similar clinical manifestations, NCAS involvements in NK/T lymphoma of nasal type and WG at disease onset show clear differences in the laboratory and systemic manifestations of these diseases. The patients with lymphoma have no characteristic laboratory abnormalities at disease onset, except the 100% presence of Epstein-Barr virus (EBV) DNA in blood and, only as a tumor grows, fever appears and there are elevated C-reactive protein and lactate dehydrogenase levels and pronounced destructive changes in the facial bones with mandatory hard palate destruction; at the same time the signs of systemic involvement are virtually absent. The patients with WG at disease onset have fever, high erythrocyte sedimentation rate, elevated C-reactive level, significant anemia, leukocytosis and 90% are found to have anti-neutrophil cytoplasmic antibodies with the rapid development of systemic manifestations: involvements of the lung, kidney, and peripheral nervous system. Destructive changes in the facial bones are minimal and hard palate destructions are absent. The patients with IgG4-RD, sarcoidosis, and juvenile xanthogranuloma have similar clinical and laboratory manifestations in the absence of hemorrhagic nasal discharge, nasal septal perforation, and facial bone destruction, with the practically involvement of the salivary/lacrimal glands and orbital regions. A third of the patients are observed to have different allergic manifestations, moderate eosinophilia, and signs of autoimmune disorders (the presence of rheumatoid and antinuclear factors, hypergammaglobulinemia). Elevated serum IgG4 levels are characteristic of IgG4-RD. CONCLUSION: Blood anti-neutrophil cytoplasmic antibodies, EBV DNA, and IgG4 levels should be determined in all patients with NCAS involvement. Mini-invasive incision biopsies of the nasal mucosa, orbital regions, and major salivary glands should be done, by morphologically verifying the diagnosis of sarcoidosis, histiocytosis, and WG and by making an immunomorphological examination to diagnose NK/T lymphoma and IgG4-RD.

Perplexing lesions of the sinonasal cavity and skull base: IgG4-related and similar inflammatory diseases.

OBJECTIVE: IgG4-related disease (IgG4RD) causing sinonasal and skull base pathology is uncommonly described. We present a series of suspected IgG4RD patients, with a pertinent review of the literature to highlight diagnostic challenges. STUDY DESIGN: Case series. SETTING: Academic tertiary care center. SUBJECTS AND METHODS: Case series of patients with IgG4RD or suspected IgG4RD involving the sinonasal cavity and skull base. RESULTS: We present 4 patients with atypical sinonasal and/or skull base disease who were noted to have IgG4-positive plasma cell infiltration on immunohistochemistry of biopsy specimens. IgG4RD, a recently described entity affecting multiple organs, is characterized by lymphoplasmacytic infiltration and often elevated serum IgG4. IgG4RD can masquerade as malignancy or infection but responds to glucocorticosteroid and immunosuppressant therapy. IgG4RD has been infrequently reported presenting as sinonasal or skull base lesions, and definitive diagnostic criteria for these regions are not established. In our series, IgG4RD was suspected in all 4 patients, but only 1 met all current criteria for definitive diagnosis. All 4 patients, however, responded to corticosteroid therapy, and 1 was placed on long-term azathioprine. CONCLUSION: IgG4RD is rarely described in the sinonasal cavity and skull base, and specific diagnostic criteria for such disease have not been defined. We present a series of patients with IgG4-positive plasma cell inflammatory pathology who were suspected to have IgG4RD. Our series highlights diagnostic challenges associated with these patients. Tumefactive and destructive sinonasal-skull base lesions with a plasma cell-rich infiltrate should incite suspicion of IgG4RD, and immunohistochemistry for IgG4-positive plasma cells should be performed.

Rhinocerebral mucormycosis in a patient with type 1 diabetes presenting as toothache: a case report from Himalayan region of India.

Mucormycosis is an angioinvasive infection caused by ubiquitous filamentous fungi of the order Mucorales. It is a rapidly progressive fatal infection mostly reported in susceptible individuals, such as those with poorly controlled diabetes or those with defects in phagocytic function. Rhinocerebral mucormycosis is the most common type of mucormycosis in diabetic patients. This case report describes a 17-year-old girl with type 1 diabetes mellitus presenting with rhinocerebral mucormycosis. The patient presented with a history of toothache and facial pain with oedema of left half of face, periorbital oedema and depressed conciousness. She had hyperglycaemia with diabetic ketoacidosis and rapidly developed hemiparesis progressing to quadriparesis and died within 3 days of admission. The current report emphasises the importance of having a high index of suspicion when dealing with patients with diabetes presenting with facial pain or cellulitis and prompt initiation of medical therapy along with surgical debridement for control of rhinocerebral mucormycosis.

[Expression and significance of IgG4 in inflammatory disease of nasal cavity and paranasal sinuses].

OBJECTIVE: To study the prevalence of IgG4-positive plasma cells in inflammatory disease of nasal cavity and paranasal sinuses and its association with IgG4-related sclerosing disease (IgG4-SD). METHODS: The expression of IgG4 and IgG in plasma cells of 103 cases diagnosed as inflammatory disease of nasal cavity and paranasal sinuses with dense lymphoplasmacytic infiltrate was studied by immunohistochemistry (EnVision) and quantitatively analyzed by medical image analysis system. RESULTS: Immunohistochemical study showed marked infiltration by IgG4-positive plasma cells (>50 per high-power field) in 28 cases, moderate infiltration (30 to 50 per high-power field) in 23 cases, mild (10 to 29 per high-power field) in 30 cases and negative (<10 per high-power field) in 22 cases (P < 0.05). Twenty-two cases studied fulfilled the diagnostic criteria of IgG4-SD (>50 IgG4-positive plasma cells per high-power field and IgG4-to-IgG ratio > 40%), including 3 cases of chronic sinusitis (3/20), 3 cases of nasal polyps (3/18), 3 cases of inflammatory pseudotumor (3/17), 4 cases of fungal sinusitis (4/20), 1 case of rhinoscleroma (1/12), 7 cases of Wegener's granulomatosis (7/11) and 1 case of Rosai-Dorfman disease (1/2). CONCLUSION: Inflammatory disease of nasal cavity and paranasal sinuses fulfilling the diagnostic criteria IgG4-SD is not uncommon. Definitive diagnosis of IgG4-SD requires correlation with other clinical and laboratory findings. Some cases of unexplained inflammatory disease of nasal cavity and paranasal sinus may represent a member of the IgG4-SD spectrum. IgG4 carries diagnostic value in differential diagnosis of inflammatory disease occurring in nasal cavity and paranasal sinuses.

Immunoglobulin G4-related sclerosing disease of the paranasal sinus.

BACKGROUND: Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. We present a case of a 69-year-old man with maxillary sinus IgG4 sclerosing disease, with orbital invasion treated with rituximab and dexamethasone pulse therapy. Surgery was used as well to debulk the disease and to obtain tissue for diagnosis. METHODS: A PubMed search using the key phrase "IgG4-related Sclerosing Disease" was performed. There were 304 different articles regarding the disease for a multitude of different organ sites. Of the 304 articles, there were 3 articles that reported this disease in the paranasal sinuses. CONCLUSIONS: IgG4-related sclerosing disease is a rare entity in the head and neck. There are documented reports of steroid therapy for this disease, but the patient presented here demonstrated clinical progression of disease with steroids alone. The use of combination therapy of surgery, dexamethasone, and rituximab provided clinical improvement and stable disease determined by radiographic means.

[The assessment of the state of the immune system in the patients presenting with bronchial asthma and concomitant diseases of the nasal cavity and paranasal sinuses].

The objective of the present investigation was to study the influence of diseases of the nasal cavity (NC) and paranasal sinuses (PNS) concomitant with bronchial asthma (BA) on the development of peculiar features of the patients' immune status. Phenotypic characteristics of the main lymphocyte subpopulations from peripheral blood of 101 patients were obtained by means of flow cytometry with the use of fluorescein isocyanate- or phycoerythrin-labeled monoclonal antibodies. Special emphasis was laid on the elucidation of characteristics of humoral and cell-mediated immunity in the patients presenting with BA and concomitant NC and PNS diseases and their comparison with the respective parameters in the patients with isolated lesions in the upper respiratory tract (allergic rhinitis and polypous rhinosinusitis) and lower respiratory tract (bronchial asthma). It was shown that the patients with concurrent lesions of the upper and lower respiratory tracts experience marked intensification of the immune reactions in the form of the elevated number of activated B-lymphocytes (CD23+), serum IgE level, and peripheral eosinophil count.

[Invasive aspergillosis of the maxillary sinus in an immunocompetent patient]. / Aspergillose invasive du sinus maxillaire chez un patient immunocompétent.

INTRODUCTION: Invasive aspergillosis of the maxillary sinus is a severe infection most commonly observed in immunocompromised patients. We report a pseudo-tumoral presentation of invasive aspergillosis of the maxillary sinus, in immunocompetent adult. CASE REPORT: A 70-year-old female patient consulted for chronic rhino-sinusitis resistant to medical treatment. Computed tomography scan revealed a hyperdense mass filling the left maxillary antrum, with erosion of sinus walls. The ethmoidal and right frontal sinuses were involved. The histological and mycological examination of the surgical resection confirmed the diagnosis of invasive aspergillosis. The patient was given voriconazole as first line treatment. The outcome was good at 18 months. DISCUSSION: Invasive aspergillosis of the maxillary sinus is a rare disease, usually observed in immunodepressed patients. It is very rarely observed in immunocompetent patients.

Inflammatory myofibroblastic tumor of the maxillary sinus related with pulp necrosis of maxillary teeth: case report.

Inflammatory myofibroblastic tumor (IMT) is a benign lesion composed of myofibroblasts accompanied by varying numbers of inflammatory cells. Various pathogenetic factors have been proposed, but the etiology of most IMTs remains unknown. This article presents a case of IMT occurring in the left maxillary sinus. A 24-year-old man complained of throbbing pain in the maxillary left molars and swelling of the left cheek. His maxillary left second molar was diagnosed as pulp necrosis and root canal treatment performed. After that, his symptoms continued and he was referred to the Department of Otolaryngology. Computerized tomography disclosed compact soft tissue masses in the left maxillary sinus with obstruction of maxillary ostium. Under general anesthesia, the lesions were fully excised. Histopathologically, the lesions were composed of plump or spindled myofibroblasts. Cells were immunoreactive for smooth muscle actin and ß-catenin, and were negative for ALK1, CD34, and EMA. The diagnosis was IMT of left maxillary sinus. Although it is very rare, IMT should be included as a differential diagnosis in patients with compact masses in maxillary sinus.

Paranasal sinus disease and sputum eosinophilia in prednisone-dependent asthma.

OBJECTIVES: to investigate the extent and characteristics of paranasal sinus abnormalities (anatomic and mucosal) on computed tomographic (CT) sinus scans and to determine whether there is a relationship between these findings and eosinophilic airway inflammation in patients with prednisone-dependent asthma. METHODS: we conducted an observational survey of 15 prednisone-dependent asthmatic patients with respect to measures of airway inflammation and CT sinus scans. The pathologic changes on the CT scans were scored using the Lund-Mackay and JAMA staging systems, and several paranasal bony anatomic variations were recorded. Correlations between CT sinus measures and sputum eosinophil count as well as prednisone dose requirement to control sputum eosinophilia were examined. RESULTS: the JAMA and Lund-Mackay staging systems showed that greater sphenoidal mucosal disease was associated with increased prednisone dose requirements (OR 1.7, p = .05; OR 1.6, p = .021). Generally, both staging systems showed that specific sinus site involvement correlated with higher levels of sputum eosinophils. Mucosal thickening in the sphenoid sinus correlated most closely with sputum eosinophilia, followed by the maxillary and ethmoid sinuses and osteomeatal complex. Finally, there appeared to be a limited role for sinus anatomy as a predictive factor for the dose of prednisone required to control sputum eosinophilia. CONCLUSIONS: sinomucosal thickening, but not sinus anatomy, appears to be an important predictor of prednisone requirement and severity of eosinophilic bronchitis in severe asthma.

Invasive paranasal mucormycosis with peripheral eosinophilia in an immunocompetent patient.

A 53-year-old healthy patient was admitted with unilateral nasal obstruction of one month duration which was suspected to be a malignancy because of mass-like finding on radiology and peripheral eosinophilia. The biopsy of the involved sinus showed tissue invasion by aseptate hyphae suggestive of a zygomycete and tissue infiltration of eosinophilia. He was diagnosed as invasive paranasal mucomycosis and treated with complete endoscopic sinus surgery and amphotericin B deoxycholate. Paranasal symptoms with peripheral eosinophilia might be a presentation of invasive fungal sinusitis.