A rare case of primary sinonasal tuberculosis presented with phlyctenular keratoconjunctivitis in a pediatric patient: A case report and literature review.

RATIONALE: Tuberculosis is a common cause of phlyctenular keratoconjunctivitis, especially for patients who live in a high endemic area of tuberculosis. We report a rare case of pediatric phlyctenular keratoconjunctivitis associated with primary sinonasal tuberculosis. PATIENT CONCERNS: A 7-year-old boy presented with a 5-month history of redness of the left eye accompanied by mild visual impairment. Physical examination revealed elevated pinkish-white nodules with a circumcorneal hypervascularized lesion on the left conjunctiva. DIAGNOSIS: Computed tomography revealed an enhancing soft tissue mass in the left maxillary sinus with bone destruction. Histopathology of maxillary tissue showed chronic inflammation without granuloma. Special stain, culture and polymerase chain reaction for mycobacterium were initially negative. Left maxillary sinus tuberculosis was diagnosed by positive Mycobacterium tuberculosis polymerase chain reaction from formalin-fixed paraffin-embedded maxillary tissue. INTERVENTIONS: Two month of oral isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 10 months of oral isoniazid and rifampicin without topical eye drops agent were prescribed. OUTCOMES: Two months after initiation of treatment, the phlyctenular lesion had significantly improved. A follow-up computed tomography showed a significant reduction in the size of the maxillary sinus lesion and the extent of adjacent bone destruction. LESSONS: Primary sinonasal tuberculosis is an uncommon cause of phlyctenular keratoconjunctivitis in children. When microbiological and histopathological evidences are absent, polymerase chain reaction analysis has a crucial role in the diagnosis of tuberculosis, especially in patient with uncommon presentation.

Effect of highly effective modulator treatment on sinonasal symptoms in cystic fibrosis.

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor is a highly effective modulator for cystic fibrosis (CF) patients homozygous or heterozygous for F508del. Effects of the drug on sinonasal symptoms have not been studied. METHODS: Adult participants were prospectively evaluated at baseline and after three months of treatment using validated questionnaires assessing sinonasal symptoms (SNOT-22) and CF-related quality of life (CFQ-R). RESULTS: Forty-three participants completed the study; 23 were taking other CF transmembrane conductance (CFTR) modulators at the time of study participation. There was a significant improvement in mean SNOT-22 from 34.8 (29.4-40, 95% confidence interval) to 24.4 (19.9-29.0) (p = 0.000003) and in the Respiratory domain of the CFQR from 60.6 (57.1-64.1) to 83.3 (79.4-87.2) (p = 0.0000002), both achieving a minimal clinically important difference. Patients previously taking CFTR modulators experienced a greater benefit in sinonasal and respiratory symptoms. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor is associated with significant improvement in sinonasal symptoms; previous use of CFTR modulators is associated with greater benefit.

Hematoma subperiosteal orbitário secundário a barotrauma em aviação civil / Orbital subperiosteal hematoma secondary to barotrauma in civil aviation

RESUMO Os diagnósticos diferenciais que compõem as proptoses agudas são, muitas vezes, desafiadores. A anamnese e o exame clínico exigem do oftalmologista atenção especial aos detalhes que permitem diferenciar quadros relativamente benignos e autolimitados de quadros que evoluirão com incapacidades permanentes. Relatamos o caso de uma paciente de 49 anos que, durante viagem de avião, apresentou dor ocular, hematoma periorbitário e proptose do olho esquerdo súbitos. Referia diplopia aguda incapacitante. Exames de tomografia e angiorressonância magnética confirmaram diagnóstico de sinusopatia do seio etmoidal esquerdo e hematoma subperiosteal da órbita esquerda, associado ao barotrauma. Apesar de raro, o diagnóstico de hematoma subperiosteal não traumático deve ser considerado diferencial em relação a proptoses agudas, sendo a anamnese fundamental para essa elucidação diagnóstica.

ABSTRACT Differential diagnoses of acute proptosis are often challenging. History and clinical examination require from ophthalmologists special attention to details, which make it possible to differentiate relatively benign and self-limited conditions from those that will progress to permanent disabilities. We report a 49-year-old female patient who had sudden eye pain, periorbital hematoma and proptosis of the left eye during a commercial flight. She also complained of disabling acute diplopia. Computed tomography and magnetic resonance angiography imaging confirmed the diagnosis of subperiosteal hematoma of the left orbit, associated with left ethmoid sinus disease. Although rare, non-traumatic subperiosteal hematoma should be considered in differential diagnoses of acute proptosis, and history taking is fundamental to elucidate the picture.

[IManagement of patients with relapsed primary naso-sinusal tuberculosis]. / Gestion de la rechute d'une tuberculose naso-sinusienne primaire.

Primary naso-sinusal tuberculosis (TB) is a relatively rare or exceptional disorder characterized by polymorphic or non-specific clinical manifestation. Diagnosis is based on anatomo-pathological examination and mycobacteriology test of biopsy specimen. Predictor of good outcome is early conventional anti-tuberculous antibiotic therapy. However, our study reports recurrence at this rare site in an immunocompetent patient despite early suitable TB treatment and good adherence with therapy. Relapse was correlated with underdosing of rifampicin. This study highlights the diagnostic, etiological and therapeutic management of this relapse. Our experience could help clinicians to better manage this uncommon condition.

Rhino-Orbito-Cerebral Mucormycosis in Diabetic Disease Mucormycosis in Diabetic Disease.

The authors present their experience about clinical evidences that include patients with an untreated diabetes who developed rhino-orbito-cerebral mucormycosis (ROCM). They were treated with endoscopic sinus surgery and medical treatment with intravenous, intradural therapy, and sinus washes with amphotericin B. The ROCM is a disease with a rapid evolution and an increase in mortality rate, especially if the fungus enters the cranial cavity. Therefore, it would be necessary in all diabetic patients with sinus symptoms, headaches, visual changes, suspect a mucormycosis, and perform a careful radiology assessment and a nasal endoscopy. Often, despite an early diagnosis and rapid treatment for ROCM, it is not possible to stem the disease, which ends with the patient's death.

Identification of the environmental source of infection for a domestic ferret with cryptococcosis.

Cryptococcosis, caused by the Cryptococcus gattii and C. neoformans species complexes, is an environmentally acquired mycosis affecting a broad range of host species. Among 9 communally housed ferrets, a 5-y-old castrated male ferret domiciled in an outdoor enclosure in Sydney, Australia was diagnosed with sinonasal cryptococcosis. Clinical signs resolved during 18 mo of itraconazole therapy, but the ferret was eventually euthanized because of splenic hemangiosarcoma. At postmortem, microscopic foci of persistent cryptococcosis were detected. The diagnosis raised concerns that the owners and other ferrets were exposed to a common environmental source of infection, thus prompting an investigation. Soil samples, swabs of a hollow eucalypt log (used for behavioral enrichment), and nasal swabs from 8 asymptomatic ferrets were collected. Nasal exudate (obtained at diagnosis) and tissues (collected at postmortem) were available from the clinical case. Bird seed agar culture resulted in a heavy growth of Cryptococcus spp. from one environmental site (the log), one nasal swab, and nasal exudate and tissues from the clinical case. All other samples were culture-negative. Sub-cultured isolates from the log were a mixture of C. gattii molecular type VGI and C. neoformans molecular type VNI. Ferret isolates were a similar mixture of C. gattii VGI (all disease isolates) and C. neoformans VNI (nasal-colonizing isolate). Multilocus sequence typing further revealed the ferret isolates as identical to environmental isolates collected from the log, confirming the log as the source of clinical disease and nasal colonization. The log was removed to prevent further exposure to a high environmental load of Cryptococcus spp.

Resveratrol and ivacaftor are additive G551D CFTR-channel potentiators: therapeutic implications for cystic fibrosis sinus disease.

BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in defective Cl- transport and cause chronic bacterial infections in the upper and lower airways of cystic fibrosis (CF) patients. Ivacaftor is a CFTR potentiator that improves Cl- transport in CF patients with at least 1 copy of the G551D mutation. Resveratrol is also a potent CFTR potentiator that increases determinants of mucociliary transport. The objective of this study is to determine whether resveratrol and ivacaftor improve Cl- secretion in G551D CFTR over either agent alone. METHODS: Fisher rat thyroid cells (FRT) transfected with G551D CFTR and human sinonasal epithelial cells (HSNE) containing the CFTR G551D mutation were subjected to pharmacologic manipulation of transepithelial ion transport in Ussing chambers. Activity was further evaluated using whole-cell patch clamp methods in G551D FRT cells. RESULTS: In G551D FRT cells, resveratrol (100 µM) and ivacaftor (10 µM) significantly increased Cl- transport (change in short-circuit current, δISC = µA/cm2 ) compared with single-agent and dimethylsulfoxide vehicle controls (resveratrol + ivacaftor 4.97 ± 0.57 vs ivacaftor 0.74 ± 0.12 vs resveratrol 2.96 ± 0.52 vs control 0.74 ± 0.12; p < 0.001). Maximal Cl- secretion (20 µM forskolin) was also significantly enhanced (p < 0.0001). Activity was confirmed in G551D HSNE (resveratrol + ivacaftor 4.48 ± 0.39 vs ivacaftor 1.05 ± 0.11 vs. resveratrol 0.84 ± 0.3 vs control, 0.0 ± 0.02; p < 0.001), and whole-cell patch clamp analysis in G551D FRT cells (resveratrol + ivacaftor -2535 ± 179.3 pA vs ivacaftor -1408.9 ± 101.3 pA vs resveratrol; -766.2 ± 71.2 pA; p < 0.0001). CONCLUSION: Additive improvement in G551D CFTR-mediated Cl- secretion suggests that resveratrol could enhance ivacaftor therapy in these patients and improve CF-related rhinosinusitis.

Outcomes and factors affecting them in patients with rhino-orbito-cerebral mucormycosis.

AIM: To report the frequency and factors affecting patients', globe and vision survivals in rhino-orbito-cerebral mucormycosis (ROCM). METHODS: This is a retrospective study of 63 patients (79 eyes) with biopsy-proven ROCM at a university hospital 2008-2016. Systemic and ophthalmic manifestations, imaging, management and final outcomes were recorded. Globe survival was defined as no exenteration and vision survival as final visual acuity of light perception and more. RESULTS: Mean age was 55.5 (SD 12.9) years with no gender preference. Diabetes was the most common underlying disease (68.3%). Patient survival was observed in 57.1 % (36/63). Presence of frozen eye (OR 4.6), nasal mucosal involvement (OR 7.3) and shorter duration of antifungal therapy (OR 1.03) were significantly associated with lower patient survival. Exenteration did not significantly change the survival. Globe survival was detected in 43% (34/79). Higher white blood cell (WBC) count was associated with a lower globe survival (p=0.02). Vision survival was observed in 25.3% (20/79) in whom younger age was significantly associated with a worse vision survival. CONCLUSION: Patient, globe and vision survivals were 57%, 43% and 25%, respectively. Exenteration did not affect the patients' survival. While frozen eye and nasal mucosal involvement were significantly associated with a lower survival, higher WBC count significantly increased the risk of exenteration.

The accessibility of topical treatment in the paranasal sinuses on operated cystic fibrosis patients assessed by scintigraphy.

BACKGROUND: Nasal irrigations with antibiotics are used to eradicate Pseudomonas aeruginosa from the upper airways in patients with cystic fibrosis (CF) and thereby avoid lung colonisations; nevertheless, the efficacy is uncertain. METHODOLOGY: The aim of this study was to investigate the accessibility and durability of solutions in the sinuses before and after sinus surgery. The participants irrigated their noses with radioactively marked saline and were evaluated using a dynamic SPECT/CT scan. The preoperative and postoperative (after 30 days) examinations were compared. RESULTS: Twelve CF patients were included. In 10 out of the 24 scanned maxillary sinuses an improvement was seen postoperatively compared with the preoperative fluid volume. Notably, in 7 out of the 24 sinuses the mucosa was so swollen postoperatively that no fluid was detected. Ten patients had developed their frontal sinuses. We observed no fluid in the frontal or sphenoid sinuses, neither before nor after surgery. At best, a mean of 23% of the maxillary sinuses were filled with fluid; thus, all sinuses had postoperatively areas of the mucosa that did not have contact with the fluid. A mean of 76% of the initial volume was present after 30 min in the maxillary sinuses. CONCLUSION: Fluid-depositing using nasal irrigation will not sufficiently or not at all get in contact with all the sinus mucosa despite of sinus surgery. Thus, the efficacy of topical deposition of antibiotics is presumably reduced.

Sphenoid sinus mucocele masquerading as retrobulbar optic neuritis: a case report.

Objective: To describe an infrequent instance of sphenoid sinus mucocele presenting as retrobulbar optic neuritis and highlight the value of imaging in the diagnosis and treatment plans. Methods: A woman aged 26 noted a sub-acute decrease in vision in the right eye, which mimicked optic neuritis. Magnetic resonance imaging (MRI) indicated a large mass in the sphenoid sinus, which was in favor of mucocele. Results: Endoscopic sphenoidotomy and marsupialization of the mucocele were carried out, and the diagnosis was confirmed by pathology. The patient was also administered a high dose of corticosteroid, upon which progression of the disease was halted. Unfortunately, no significant improvement in vision was achieved. Conclusions: This report emphasized the important role of imaging in differentiating between different causes of optic neuropathies. A high level of clinical skepticism along with appropriate imaging studies can help diagnose rare causes. With timely management, gratifying results may be achieved.

Delivery of Topical Therapies.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease of the sinonasal passages. Similar to other chronic inflammatory diseases, an essential component of the long-term control is prolonged medical therapy. To minimize the risk of adverse effects and cumulative complications of systemic medications, topical sinonasal therapy has become the primary strategy for prolonged medical therapy. The objective of this review article is to describe the evidence for the most common topical sinonasal delivery techniques. Evidence supports that high-volume irrigations provide the most reliable delivery of medical therapy to the paranasal sinuses. Low-volume nasal sprays and drops provide reliable delivery to the nasal cavity and a degree of penetration into the middle meatus and olfactory cleft; however, they do not reliably penetrate the paranasal sinuses. Sinus surgery and the head down-forward position optimize the delivery of high-volume irrigations into the paranasal sinuses. Additionally, high-volume irrigations assist in overcoming unfavorable nasal anatomy such as septal deviation and turbinate hypertrophy.

Unusual cause of maxillary sinus mass with proptosis.

We report a case of a 21-year-old Indian man with an 8-month history of left-sided headache, maxillary sinus mass, proptosis and swelling of the left temple, whose contrast-enhanced CT scans of the paranasal sinuses showed an enhancing, destructive soft tissue mass involving the left maxillary sinus, orbit, infratemporal fossa and anterior cranial fossa, suggestive of a malignancy or chronic granulomatous disease. Histopathological examination of the sinus mass, which was debulked and partially excised via an endoscopic approach, suggested a diagnosis of immunoglobulin G4-related sclerosing disease of the maxillary sinus. Subsequent immunohistochemical staining and biochemical tests confirmed the diagnosis. We highlight the importance of considering this increasingly recognised but rare entity that can mimic a malignant lesion with its clinical and radiological features but which, unlike the latter, has a very good prognosis with appropriate treatment.

The Role of Adjunctive Therapies in the Management of Invasive Sino-Orbital Infection.

OBJECTIVE: Invasive sino-orbital fungal infections are life-threatening complications of immunonosupression that are difficult to treat. Currently there are no standard treatment guidelines. The most widely accepted therapy includes parenteral anti-fungal therapy and surgical debridement of sinuses with orbital exenteration, a procedure that is not only disfiguring, but may increase morbidity. Injection of retrobulbar Liposomal Amphotericin B (L-AMB) is an alternative approach that provides local administration to infected tissues. The adjunct use of anti-fungal retrobulbar injections not been extensively reviewed in treating sino-orbital infection. We are reporting the multimodal approach of using L-AMB retrobulbar injections in combination with sinus debridement, intravenous (IV) anti-fungal therapy, and hyperbaric oxygen (HBO) for the management of sino-orbital infection. METHOD & RESULTS: Review of literature of 12 cases and retrospective evaluation of one patient with sino-orbital Aspergillus flavus infection on chemotherapy for T-cell acute lymphocytic leukemia treated with retrobulbar Amphotericin B, IV anti-fungal agents, and hyperbaric oxygen therapy. Clinical characteristics, radiographic features, management techniques, and clinical outcomes are described. CONCLUSION: Retrobulbar Amphotericin B injection may be an effective adjunct to hyperbaric oxygen and parenteral anti-fungals in the control of sino-orbital fungal infections.

Chlorogenic Acid Activates CFTR-Mediated Cl- Secretion in Mice and Humans: Therapeutic Implications for Chronic Rhinosinusitis.

OBJECTIVES: Salubrious effects of the green coffee bean are purportedly secondary to high concentrations of chlorogenic acid. Chlorogenic acid has a molecular structure similar to bioflavonoids that activate transepithelial Cl(-) transport in sinonasal epithelia. In contrast to flavonoids, the drug is freely soluble in water. The objective of this study is to evaluate the Cl(-) secretory capability of chlorogenic acid and its potential as a therapeutic activator of mucus clearance in sinus disease. STUDY DESIGN: Basic research. SETTING: Laboratory. SUBJECTS AND METHODS: Chlorogenic acid was tested on primary murine nasal septal epithelial (MNSE) (CFTR(+/+) and transgenic CFTR(-/-)) and human sinonasal epithelial (HSNE) (CFTR(+/+) and F508del/F508del) cultures under pharmacologic conditions in Ussing chambers to evaluate effects on transepithelial Cl(-) transport. Cellular cyclic adenosine monophosphate (cAMP), phosphorylation of the CFTR regulatory domain (R-D), and CFTR mRNA transcription were also measured. RESULTS: Chlorogenic acid stimulated transepithelial Cl(-) secretion (change in short-circuit current [ΔISC = µA/cm(2)]) in MNSE (13.1 ± 0.9 vs 0.1 ± 0.1; P < .05) and HSNE (34.3 ± 0.9 vs 0.0 ± 0.1; P < .05). The drug had a long duration until peak effect at 15 to 30 minutes after application. Significant inhibition with INH-172 as well as absent stimulation in cultures lacking functional CFTR suggest effects are dependent on CFTR-mediated pathways. However, the absence of elevated cellular cAMP and phosphorylation the CFTR R-D indicates chlorogenic acid does not work through a PKA-dependent mechanism. CONCLUSION: Chlorogenic acid is a water-soluble agent that promotes CFTR-mediated Cl(-) transport in mouse and human sinonasal epithelium. Translating activators of mucociliary transport to clinical use provides a new therapeutic approach to sinus disease. Further in vivo evaluation is planned.

Implications of endodontic-related sinus aspergillosis in a patient treated by infliximab: a case report.

INTRODUCTION: Sinus aspergillosis is a potential complication after root canal therapy of antral teeth. Indeed, zinc oxide-eugenol cement overfilling in the sinus may promote fungal infection. Moreover, if sinus aspergillosis triggers chronic sinusitis with aspergilloma, it may also lead to invasive phenomena, especially for immunocompromised patients. METHODS: We reported a sinus aspergillosis case of a patient treated with infliximab (Remicade; Janssen Biologics BV, Leiden, Netherlands). The purpose of this article was to explore the mechanisms of this pathosis, especially the impact of the root canal sealer overextension, which is a contributing factor for fungal infection. The surgical management and the follow-up are also described. RESULTS: Six months after surgery, the patient showed no clinical signs and presented with a healthy and airy right maxillary sinus on the computed tomography scan. CONCLUSIONS: In conclusion, prevention and screening of aspergillosis of maxillary sinus may be considered before starting an anti-tumor necrosis factor alpha therapy.

Ivacaftor and sinonasal pathology in a cystic fibrosis patient with genotype deltaF508/S1215N.

In patients with Cystic Fibrosis and a type III mutation, ivacaftor (Kalydeco(®), Vertex) can increase the opening time of the CFTR channel and improve chloride transport. Research showed significant improvement of lung function and increase in weight following ivacaftor use. However, ivacaftor showed to have adverse events on the sinonasal system as well, such as upper respiratory tract infections, nasal congestion and headaches. This case report showed a positive effect of ivacaftor on the sinonasal pathology in a 17 year old patient with CF. After 5 months of ivacaftor use, the CT-sinus showed complete resolution of the opacification of the paranasal sinuses and a decrease in symptoms of sinonasal disease. This positive effect of ivacaftor on sinonasal pathology seems promising, therefore more research is needed to evaluate the effect of ivacaftor on the upper airways in CF.