Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline.

Mucosal leishmaniasis (ML) is a severe form of tegumentary leishmaniasis associated with a persistent inflammatory response. High levels of TNF, IFN-γ, CXCL9 and CXCL10 are found in ML patients, and the association of pentoxifylline with antimony is more effective in decreasing the healing time in ML patients when compared to antimony alone. The present study aimed to investigate the existence of a correlation between cytokine and chemokine production and ML severity and evaluate the potential value of cytokine and chemokine production as marker of therapeutic response in ML patients. This prospective study included 86 subjects in an area of endemic Leishmania braziliensis transmission. Patients diagnosed with ML were classified into clinical stages ranging from I to V according to disease severity. TNF, IFN-γ, CXCL9 and CXCL10 levels were quantified in the supernatant of the mononuclear cell cultures by ELISA before and after treatment with antimony alone or antimony plus pentoxifylline. The median TNF level in the group with mild disease (Stages I-II) was 1064 pg/mL (142-3738 pg/mL), while, in the group with moderate or severe disease (Stages III-V), it was 1941 pg/mL (529-5294 pg/mL) (p = 0.008). A direct correlation was observed between ML clinical severity and levels of TNF production (r = 0.44, p = 0.007). Patients who were treated with antimony and pentoxifylline healed significantly faster than those treated with antimony alone (52 vs. 77 days, hazard ratio = 0.60; 95% confidence interval = 0.38-0.95, p = 0.013). Therapeutic failure was higher in the group that received antimony alone (25% vs. 7%; p = 0.041). There was a significant decrease in CXCL9 after therapy of ML in both groups (p = 0.013; p = 0.043). TNF levels are associated with the severity of mucosal diseases, and pentoxifylline associated with antimony should be the recommended therapy for ML in countries where liposomal amphotericin B is not available.

SPECIAL ARTICLE COVID-19: Safety for the Rhinologist in the Age of COVID-19: Mask Use, Nasal Corticosteroids, Saline Irrigation, and Endoscopic Procedures - Literature Review

Abstract Introduction Coronavirus disease 2019 (COVID-19) has claimed millions of lives. Adequate protection of the professionals involved in patient care is essential in the battle against this disease. However, there is much uncertainty involving safety-relarted topics that are of particular interest to the rhinologist in the context of COVID-19. Objective To evaluate the current evidence regarding three safety-related topics: mask and respirator use, performance of nasal endoscopic procedures, and use of topical nasal and intranasal medications (saline irrigation and nasal corticosteroids). Methods A literature review was performed on the PubMed, Scopus, and Cochrane databases, with standardized search queries for each of the three topics of interest. Results In total, 13 articles on mask use, 6 articles on the safety of nasal corticosteroids, 6 articles on the safety of nasal endoscopic procedures, and 1 article on nasal irrigation with saline solution were included in the final analysis. Conclusion N95 respirators are essential for the adequate protection of otolaryngologists. If reuse is necessary, physical methods of sterilization must be employed. No evidence was found to contraindicate the use of nasal corticosteroids, whether acute (in the management of sinonasal inflammatory conditions) or continued (in patients who use them chronically). Nasal irrigation with saline solution apparently does not increase the risk in the context of COVID-19. Nasal endoscopic procedures should only be performed after testing the patient for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the surgical team must wear full personal protective equipment to prevent aerosol exposure.

Safety for the Rhinologist in the Age of COVID-19: Mask Use, Nasal Corticosteroids, Saline Irrigation, and Endoscopic Procedures - Literature Review.

Introduction Coronavirus disease 2019 (COVID-19) has claimed millions of lives. Adequate protection of the professionals involved in patient care is essential in the battle against this disease. However, there is much uncertainty involving safety-relarted topics that are of particular interest to the rhinologist in the context of COVID-19. Objective To evaluate the current evidence regarding three safety-related topics: mask and respirator use, performance of nasal endoscopic procedures, and use of topical nasal and intranasal medications (saline irrigation and nasal corticosteroids). Methods A literature review was performed on the PubMed, Scopus, and Cochrane databases, with standardized search queries for each of the three topics of interest. Results In total, 13 articles on mask use, 6 articles on the safety of nasal corticosteroids, 6 articles on the safety of nasal endoscopic procedures, and 1 article on nasal irrigation with saline solution were included in the final analysis. Conclusion N95 respirators are essential for the adequate protection of otolaryngologists. If reuse is necessary, physical methods of sterilization must be employed. No evidence was found to contraindicate the use of nasal corticosteroids, whether acute (in the management of sinonasal inflammatory conditions) or continued (in patients who use them chronically). Nasal irrigation with saline solution apparently does not increase the risk in the context of COVID-19. Nasal endoscopic procedures should only be performed after testing the patient for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the surgical team must wear full personal protective equipment to prevent aerosol exposure.

High Anti-Leishmania IgG Antibody Levels Are Associated With Severity of Mucosal Leishmaniasis.

Background: Mucosal leishmaniasis (ML), the most inflammatory form of tegumentary leishmaniasis, is predominantly caused by Leishmania braziliensis. The disease is characterized by the development of lesions, mainly in the nasal mucosa. An exacerbated inflammatory response has been associated with the presence of destructive and disfiguring lesions, with stages of severity ranging from small nodulations to the complete destruction of the nasal pyramid architecture. As Leishmania is an intracellular parasite, most immunological studies have emphasized the cell-mediated immune response, while relatively few studies aimed to investigate the role antibodies in protection against, or the pathology of ML. Methods: Patients with a confirmed diagnosis of ML were classified according to clinical staging criteria. Serum levels of Leishmania-specific IgG, IgG1 and IgG2 antibodies were determined by ELISA before and after treatment with antimony or antimony plus pentoxifylline. Results: Patients in stages IV and V produced higher concentrations of IgG and IgG1 antibodies when compared to those in stage I and II. Significant reductions were seen in the concentrations of IgG and IgG2 antibodies in most patients who responded well to treatment. Conclusions: Our data demonstrate an association between IgG antibody titers and the severity of mucosal disease. The observed reduction in antibody production after successful treatment in most patients preliminarily indicates that these tests can be used to aid in the assessment of therapeutic response.

In Situ Cellular Response Underlying Successful Treatment of Mucosal Leishmaniasis with a Combination of Pentavalent Antimonial and Pentoxifylline.

Mucosal leishmaniasis (ML) is characterized by high production of inflammatory cytokines. Administration of pentoxifylline (PTX), an inhibitor of TNF-alpha, with pentavalent antimony (Sbv), has been successfully used as alternative treatment for refractory ML. Our study aims to investigate the in situ cellular response underlying the effectiveness of this therapy, by evaluating the intensity of the inflammatory infiltrate, cellular composition, and expression of cytokines and granzyme A in lesions from ML before and after treatment with Sbv alone or in combination with PTX. Our data showed no differences in the intensity of inflammatory infiltrate comparing before and after treatment, and comparing between different treatments. However, although the number and frequency of CD4+ and CD8+ cells were not different before and after treatments or comparing different treatments, frequency of CD68+ cells decreased after treatment with Sbv + PTX, but not with Sbv. This was due to a reduction in CD68+ TNF-alpha+ and not in CD68+ IL-10+ cells. The frequency of TNF-alpha+ cells was correlated with the intensity of the inflammatory infiltrate before treatment, but this correlation was lost after treatment with Sbv + PTX. Although the total expression of granzyme A did not significantly change after treatments, a clear trend of decrease was observed after treatment with Sbv + PTX. Interestingly, patients who took longer to heal, regardless of the treatment, displayed a higher frequency of granzyme A+ cells. Our data suggest that treatment with Sbv + PTX acts in CD68+ cells reducing the expression of TNF-alpha but not IL-10, resulting in more efficient modulation of the inflammatory response, accelerating the healing process.

Mucosal leishmaniasis: A Retrospective Study of 327 Cases from an Endemic Area of Leishmania (Viannia) braziliensis.

Mucosal leishmaniasis (ML) is observed only in about 3% of patients with American tegumentary leishmaniasis (ATL) but has a high potential for destructive, disfiguring, and disabling sequelae. Prior reports of clinical and epidemiologic features of ML are limited by small numbers of cases. In this study, we evaluated changes in the demographic features and clinical presentation of ML in an endemic area of Leishmania braziliensis transmission over a period of 20 years. The charts of 327 patients with ML diagnosed between 1995 and 2014 were reviewed. The majority of patients (67%) were male. Age ranged from 8 months to 103 years, with a median age of 38.5 years (interquartile range: 22-58 years). The greatest number of patients was between 19 and 39 years (31%). Over the study period, there was an increase in patients with ML more than 60 years of age, an increase in ML with concomitant cutaneous lesions, a decrease in the period of time between the documentation of cutaneous lesions and the diagnosis of mucosal disease, and an increase in the frequency of patients presenting with stage I and V of ML. Moreover, there was a positive correlation between severity of mucosal disease and both age and the period of time between cutaneous lesion and mucosal disease. Response to therapy of ML remained similar over a period of 20 years. Despite the improvement in medical care during the study period, the prevalence of ML did not change and severe disease continues to be a major challenge for the management of these patients.

Association of Sicca Syndrome with Proviral Load and Proinflammatory Cytokines in HTLV-1 Infection.

The Sjögren syndrome has been diagnosed in patients with HTLV-1 associated myelopathy and dry mouth and dry eyes are documented in HTLV-1 carriers. However the diagnosis of Sjögren syndrome in these subjects has been contested. In this cross-sectional study, we evaluated the role of immunological factors and proviral load, in sicca syndrome associated with HTLV-1 in patients without myelopathy. Subjects were recruited in the HTLV-1 Clinic, from 2009 to 2011. The proviral load and cytokine levels (IFN-γ, TNF-α, IL-5, and IL-10) were obtained from a database containing the values presented by the subjects at admission in the clinic. Of the 272 participants, 59 (21.7%) had sicca syndrome and in all of them anti-Sjögren syndrome related antigen A (SSA) and antigen B (SSB) were negatives. The production of TNF-α and IFN-γ was higher in the group with sicca syndrome (P < 0.05) than in HTLV-1 infected subjects without sicca syndrome. Our data indicates that patients with sicca syndrome associated with HTLV-1 do not have Sjögren syndrome. However the increased production of TNF-α and IFN-γ in this group of patients may contribute to the pathogenesis of sicca syndrome associated with HTLV-1.

Nasolacrimal duct mucocele: case report and literature review.

Introduction Mucoceles are benign expansive cystic formations, composed of a mucus-secreting epithelium (respiratory or pseudostratified epithelium). Nasolacrimal mucocele occurs in a small proportion of children with nasolacrimal duct obstruction and is characterized by a cystic mass in the medial canthus with dilation of the nasolacrimal duct; although dacryocystoceles are rare in adults, they have been reported in patients with trachoma. Objective Discuss clinical aspects, diagnosis, and therapeutic management of mucocele of nasolacrimal duct based on literature review. Resumed Report The authors report a case of bilateral congenital nasolacrimal duct cysts in a 30-year-old man, identified as a tumor in the topography of both lacrimal sacs since birth without associated symptoms. The patient underwent successive surgical treatments, leading to recurrence of the tumor at the right side and recurrent local infections. Conclusion Endoscopic dacryocystorhinostomy has been increasingly used with good results and success rates similar to the external access.

Nasolacrimal Duct Mucocele: Case Report and Literature Review

Introduction Mucoceles are benign expansive cystic formations, composed of a mucus-secreting epithelium (respiratory or pseudostratified epithelium). Nasolacrimal mucocele occurs in a small proportion of children with nasolacrimal duct obstruction and is characterized by a cystic mass in the medial canthus with dilation of the nasolacrimal duct; although dacryocystoceles are rare in adults, they have been reported in patients with trachoma. Objective Discuss clinical aspects, diagnosis, and therapeutic management of mucocele of nasolacrimal duct based on literature review. Resumed Report The authors report a case of bilateral congenital nasolacrimal duct cysts in a 30-year-old man, identified as a tumor in the topography of both lacrimal sacs since birth without associated symptoms. The patient underwent successive surgical treatments, leading to recurrence of the tumor at the right side and recurrent local infections. Conclusion Endoscopic dacryocystorhinostomy has been increasingly used with good results and success rates similar to the external access. .

A proposed new clinical staging system for patients with mucosal leishmaniasis.

Mucosal leishmaniasis (ML) occurs mainly in areas where Leishmania braziliensis is transmitted. It affects predominantly the nasal mucosa and, in more severe forms, can lead to significant tissue destruction. There is no standard method for grading the severity of disease. We categorised 50 patients with ML according to a proposed new clinical staging system. Their age ranged from 10 to 86 y (mean ± SD: 36 ± 16 y) and 43 (86%) patients were male. The different degrees of evolution of mucosal disease, from the initial stage to the more severe long-term cases, enabled ML to be graded into five stages. Stage I is characterised by nodular lesions of the mucosa without ulceration. Stage II is represented by superficial mucosal ulcerations with concomitant fine granular lesions. Stage III is characterised by deep mucosal ulcerations with granular tissue formation. In stage IV there are irreversible lesions leading to perforation of the cartilaginous nasal septum with necrosis. In stage V the nasal pyramid is compromised with alterations of facial features as a consequence of severe tissue destruction. These stages may be useful in characterising the severity of the lesion and optimising therapeutic outcome.

Evolução clínica e tomográfica da osteomielite frontal: relato de caso / Clinical and tomography evolution of frontal osteomyelitis: case report

INTRODUÇÃO: A osteomielite frontal é uma complicação de rinossinusite que pode ter evolução aguda ou crônica. Há reação inflamatória com aumento da pressão intra-óssea, isquemia e necrose local, levando à formação de abscesso ósseo. Não havendo drenagem, ocorrerá descolamento do periósteo, invasão de partes moles e piora da isquemia com posterior sequestro ósseo. MÉTODO: Relato de caso de um paciente internado em serviço de emergência de outra instituição por complicação de rinossinusite que foi encaminhado para o Serviço de Otorrinolaringologia do Hospital Universitário Professor Edgard Santos da Universidade Federal da Bahia. RELATO DE CASO: Paciente masculino, 16 anos, apresentou-se ao serviço de emergência de outra instituição com cefaleia, vômitos e febre que evoluiu com edema periorbitário e frontal à esquerda, cursando com flutuação palpebral e frontal.Submetido à drenagem de abscesso palpebral e frontal, com antibioticoterapia de amplo espectro sem melhora. Encaminhado para o nosso serviço mantendo edema e flutuação em região frontal e edema leve em região periorbitária esquerda. A endoscopia nasal evidenciou edema em meato médio à esquerda e a tomografia computadorizada mostrou sinusite fronto-etmoidal à esquerda e sinais de osteomielite frontal com sequestro ósseo e empiema epidural.Submetido à cirurgia endoscópica nasossinusal, acesso externo para exérese do osso frontal acometido e drenagem do empiema epidural. Evoluiu com remissão da doença. CONSIDERAÇÕES FINAIS: A falência no diagnóstico e no tratamento das complicações da rinossinusite pode levar a sequelas e complicações fatais.O diagnóstico de osteomielite frontal é firmado pela suspeita clinica e confirmado por exames radiológicos.A cirurgia está indicada quando a evolução for insidiosa, havendo sequestro ósseo ou complicações intracranianas.

INTRODUCTION: The frontal osteomyelitis is a complication of rhinosinusitis which can evolve to acute or chronicle. There is inflammatory reaction by the increasing of intraosseous pressure, ischemia and local necrosis, leading to bone abscess formation. There is no drainage, it will occur detachment of the periosteum, soft tissue invasion and worsening of ischemia with subsequent bone sequestration. METHOD: Case report of an inpatient in an emergency service of another institution by the complication of rhinosinusitis who was referred to the Otorhinolaryngology Service of University Hospital Professor Edgard Santos of Federal University of Bahia. CASE REPORT: Male patient, 16 years-old, presented himself to the ER of another institution with cephalea, vomits and fever which evolved to periorbital edema and frontal to the left, moving to palpebral fluctuation and frontal. Subjected to frontal and palpebral abscess drainage, with broad-spectrum antibiotic therapy with no improvement. He was referred to our service keeping edema and fluctuation in region frontal and light edema in left periorbital region. The nasal endoscopy showed edema in meatus to the left and the computerized tomography showed fronto-ethmoid sinusitis to the left and signs of frontal osteomyelitis with bone sequestration and epidural empyema. Subjected to sinasal endoscopy surgery, external Access or removal of the frontal one affected and epidural empyema drainage. Evolved to the remission of the disease. FINAL CONSIDERATIONS: Failure in the diagnosis and rhinosinusitis complication treatment can lead to sequalae and fatal complications. The diagnosis of the frontal osteomyelitis is confirmed by the clinical suspicion and confirmed by radiological examination. The surgery is indicated when the evolution is insidious, there is bone sequestration and intracranial complications.

Complicação orbital e intracraniana devido à rinossinusite aguda: relato de caso / Orbital and intracranial complication resulting from acute rhinosinusitis: case report

Introdução: Dentre as complicações da rinossinusite, as orbitárias são as mais frequentes, e estas, ocorrem na maioria dos casos entre jovens e crianças. Complicações simultâneas envolvendo a órbita e o espaço intracraniano são extremamente raras, mas devem ser tratadas agressivamente pois oferecem alta taxa de morbidade e mortalidade. Relato do Caso: Neste trabalho, os autores relatam um caso de um paciente que se apresentou com celulite pré-septal e abscesso epidural, como complicações simultâneas de uma rinossinusite aguda. No paciente deste estudo, optou-se pelo tratamento clínico associado à cirurgia endoscópica nasossinusal e drenagem neurocirúrgica do abscesso intracraniano. A TC foi suficiente no caso apresentado para a realização do diagnóstico. Comentários Finais: Recomenda-se entretanto, que nos casos de pacientes com complicações da rinossinusite, a investigação da extensão intracraniana seja aprofundada, mesmo quando esta, a princípio não seja tão evidente. Dada a natureza polimicrobiana dessas infecções, uma antibioticoterapia agressiva guiada por cultura e um acompanhamento por equipe multidisciplinar, aumentam consideravelmente as chances de sucesso.

Introduction: Among the rhinosinusitis complications, the orbital are the most frequent ones, occurring mostly in the youngsters and children. Simultaneous complications involving the intracranial orbit and space are extremely rare, but they must be severely treated for they have a high rate of morbidity and mortality. Case report: In this work, the authors report a case of a patient who appeared to have preseptal cellulites and epidural abscess, in the form of simultaneous complications of an acute rhinosinusitis. In the patient of this case, choice was made for a clinic treatment associated with a nasosinusal endoscopic surgery and neurosurgical drainage of the intracranial abscess. CT was enough to achieve the diagnosis of this case. Final commentaries: However, it is recommended that, in cases where patients have rhinosinusitis complications, an extensive intracranial investigation needs to be deepened even when this is not so evident in the beginning. Given the polymicrobial nature of these infections, an aggressive culture-guided antibiotic therapy and a multidisciplinary follow-up significantly increase the likelihood of success.

Acesso endoscópico para tratamento do papiloma nasossinusal: um estudo clínico retrospectivo / Endoscopic treatment of sinonasal papilloma: a retrospective clinical study

Introdução: Papiloma nasossinusal é um tumor benigno com origem no epitélio schneideriano da parede nasal lateral. Sua incidência é rara e de acordo com a literatura responde por 0,5 a 4% de todos os tumores nasais. Objetivo: Reportar a experiência da nossa instituição no tratamento do papiloma nasossinusal invertido utilizando acesso endoscópico e comparar os resultados obtidos com os relatos da literatura. Método: Estudo retrospectivo de todos os pacientes com papiloma nasossinusal que realizaram tratamento cirúrgico puramente endoscópico no ambulatório de Otorrinolaringologia do Hospital das Clínicas da Universidade Federal da Bahia (UFBA), no período de janeiro de 2004 a maio de 2010. Resultados: Um total de 12 pacientes foi incluído neste estudo. O seguimento médio foi de 23 meses. Houve 1 caso de recidiva. Não ocorreu transformação maligna nestes casos. Conclusão: O tratamento do papiloma nasossinusal tem sido amplamente beneficiado com o avanço das técnicas endoscópicas, com taxas de recorrência equivalentes àquelas reportadas por acesso externo. Exames de imagem são fundamentais no planejamento pré-operatório e na decisão da técnica cirúrgica. Um seguimento regular e de longo prazo é essencial para um bom acompanhamento da evolução desta patologia.

Introduction: Sinonasal Papilloma is a benign tumor originating from the epithelium schneiderian lateral nasal wall. Its incidence is rare and according to literature accounts for 0.5 to 4% of all nasal tumors. Objective: To report our institution's experience in the treatment of sinonasal inverted papilloma using endoscopic approach and compare the results with the literature. Methods: A retrospective study of all patients with sinonasal papillomas who underwent a purely endoscopic surgery in the Otorhinolaryngology, Hospital das Clinicas, Federal University of Bahia (UFBA), from January 2004 to May 2010. Results: A total of 12 patients were included in this study. The median follow-up was 23 months. There was one case of recurrence. Malignant transformation has not occurred in these cases. Conclusion: The treatment of sinonasal papilloma has been largely benefited from the advances in endoscopic techniques, with recurrence rates equivalent to those reported for external access. Imaging exams are essential in preoperative planning and the decision of surgical technique. A regular follow-up and long term is essential for a good monitoring of the evolution of this pathology.