Physicochemical and microbiological stability study of two new preservative-free methylprednisolone eye drops.

OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10 mg/mL eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5±3 °C), at room temperature (25±2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/mL eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/mL eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/mL, presented a white precipitate from day 14 and 28, respectively. Non-refrigerated 1 mg/mL eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/mL MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/mL eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

Physicochemical and microbiological stability study of two new preservative-free methylprednisolone eye drops. / Estudio de estabilidad fisicoquímica y microbiológica de 2 nuevos colirios de metilprednisolona sin conservantes.

OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

Prevalence of neonatal lupus in a small group of antibody-carrying mothers and frequency of complete atrioventricular block.

BACKGROUND: Neonatal lupus (NL) is extremely rare and is caused by the transplacental passage of maternal IgG autoantibodies against Ro, La, and/or RNP proteins into the fetal circulation, which can cause congenital complete atrioventricular block (CCAB), permanent skin lesions, and liver involvement. OBJECTIVE: To know the prevalence of NL in patients with CCAB and the clinical course in long-term follow-up. METHODS: From January 1992 to December 2017, patients with CCAB were included. The presence of anti-SSA/Ro and anti-SSB/La antinuclear antibodies in maternal serum confirmed NL. RESULTS: Eight patients were included with a follow-up of 10 ± 6 years; NL was concluded in 62.5%; two were male. One of them was diagnosed in utero, two at birth, and a pacemaker was implanted in them, one at 12 years of age and another at 15. The other two cases were diagnosed at 18 and 26 years of age, and permanent pacemakers were implanted 8 and 5 years later, respectively. In one case, a definitive pacemaker was not implanted in a newborn with only 1 year of follow-up. At delivery, 60% of the mothers were free of rheumatic disease, and altogether, they all had 19 children; none of them presented NL manifestations. CONCLUSIONS: CCAB is rare and frequently associated with a maternal autoimmune disease, practically all of them will require a definitive pacemaker at some point in their lives.

ANTECEDENTES: El lupus neonatal (LN) es extremadamente raro y es ocasionado por el paso transplacentario de auto-anticuerpos maternos IgG contra las proteínas Ro, La y/o RNP a la circulación fetal que puede ocasionar bloqueo aurículo-ventricular completo congénito (BAVCC) permanente, lesiones dérmicas y afectación hepática. OBJETIVO: Conocer la prevalencia de LN en paciente con BAVCC y la evolución clínica en un seguimiento a largo plazo. MÉTODOS: De enero de 1992 a diciembre 2017 se incluyeron paciente con BAVCC. La presencia de anticuerpos antinucleares anti-SSA/Ro y anti-SSB/La en suero materno confirmó LN. RESULTADOS: Ocho pacientes fueron incluidos con seguimiento de 10 ± 6 años, el 62.5 % con LN; dos fueron del sexo masculino. Uno diagnosticado in útero, dos al nacimiento, en ellos se implantó marcapaso; uno a los 12 años de edad y otro a los 15. Los otros dos casos fueron diagnosticados a los 18 y 26 años, se implantó marcapaso definitivo en ellos 8 y 5 años después respectivamente. En un caso no se implantó marcapaso definitivo; un recién nacido con solo un año de seguimiento. Al dar a luz, el 60 % de las madres estaban libres de enfermedad reumática y en conjunto todas tuvieron 19 hijos, ninguno de ellos presentó manifestaciones de LN. CONCLUSIONES: El BAVCC es raro y frecuentemente está asociado a una enfermedad autoinmune materna, prácticamente todos requerirán de marcapaso definitivo en alguna época de su vida.

Operational characteristics of ultrasound in the diagnosis of Sjögren's syndrome.

BACKGROUND AND OBJECTIVE: To determine the operational characteristics of salivary gland ultrasound (SGU) in the diagnosis of Sjögren's syndrome (SS) in a population of colombian patients with dry symptoms. MATERIALS AND METHODS: Study of diagnostic tests in patients with dry symptoms who consecutively attended the rheumatology consultation (2018-2020). Sociodemographic and clinical data were obtained through a survey, paraclinical and ophthalmological tests, minor salivary gland biopsy, unstimulated salivary flow and SGU (score 0-6 based on De Vita) were done. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (Stata 15®) were calculated. The receiver operating characteristics (ROC) curve was developed. RESULTS: 102 patients were included (34 SS and 68 non-SS), mean age 55.69 (±11.93) years, 94% women. Positive ultrasound (score of 2 or more) was more frequent in the SS group, (70.6% vs. 22.1%, P<0.0001). The sensitivity was the same for grade 2 and 3 (70.59%), with a higher specificity (89.71%) for grade 3 (PPV 77.42% NPV 85.92). The ROC curve from the sum of the glands by means of ultrasound was better than those of the independent glands. The ROC curve of the ultrasound presented a greater area under the curve (0.72 [0.61-0.82]) than that of the histological analysis (focus score) (0.68 [0.59-0.78]), P=0.0252. CONCLUSION: Salivary gland ultrasound is a useful and reliable method for the classification of SS. Its use could be considered in the future within the SS classification criteria.

Características operativas de la ecografía en el diagnóstico del Síndrome de Sjögren / Operational characteristics of ultrasound in the diagnosis of Sjögren's syndrome

Antecedentes y objetivo: Determinar las características operativas de la ecografía de glándula salival (EGS) en el diagnóstico del síndrome de Sjögren (SS) en una población de pacientes colombianos con síntomas secos. Materiales y métodos: Estudio de pruebas diagnósticas en pacientes con síntomas secos que asistieron a la consulta de reumatología (2018-2020). Se obtuvieron datos sociodemográficos y clínicos a través de una encuesta, pruebas paraclínicas, oftalmológicas, biopsia de glándula salival menor, flujo salival no estimulado y EGS (puntuación 0-6 basada en De Vita). Se calcularon la sensibilidad, la especificidad y los valores predictivos positivo (VPP) y negativo (VPN) (Stata 15®). Se desarrolló la curva de características operativas del receptor (COR). Resultados: Se incluyó a 102 pacientes (34 con SS y 68 sin SS), edad media ± desviación estándar de 55,69 ± 11,93 años, 94% mujeres. La ecografía positiva (puntuación de 2 o más) fue más frecuente en el grupo de SS, (70,6% vs. 22,1%, p < 0,0001). La sensibilidad fue igual para el grado 2 y 3 (70,59%), con una especificidad mayor (89,71%) para el grado 3 (VPP 77,42% VPN 85,92). La curva COR a partir de la sumatoria de las glándulas por medio de ecografía, fue mejor que las de las glándulas independientes. La curva COR de la ecografía presentó una mayor área bajo la curva (0,72 [0,61-0,82]) que la del análisis histológico (puntuación por focos) (0,68 [0,59-0,78]), p = 0,0252. Conclusión: La EGS es un método útil y confiable para la clasificación del SS. Se podría plantear su uso futuro dentro de los criterios clasificatorios del SS.(AU)

Background and objective: To determine the operational characteristics of salivary gland ultrasound (SGU) in the diagnosis of Sjögren's syndrome (SS) in a population of colombian patients with dry symptoms. Materials and methods: Study of diagnostic tests in patients with dry symptoms who consecutively attended the rheumatology consultation (2018-2020). Sociodemographic and clinical data were obtained through a survey, paraclinical and ophthalmological tests, minor salivary gland biopsy, unstimulated salivary flow and SGU (score 0-6 based on De Vita) were done. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (Stata 15®) were calculated. The receiver operating characteristics (ROC) curve was developed. Results: 102 patients were included (34 SS and 68 non-SS), mean age 55.69 (± 11.93) years, 94% women. Positive ultrasound (score of 2 or more) was more frequent in the SS group, (70.6% vs. 22.1%, P<.0001). The sensitivity was the same for grade 2 and 3 (70.59%), with a higher specificity (89.71%) for grade 3 (PPV 77.42% NPV 85.92). The ROC curve from the sum of the glands by means of ultrasound was better than those of the independent glands. The ROC curve of the ultrasound presented a greater area under the curve (0.72 [0.61-0.82]) than that of the histological analysis (focus score) (0.68 [0.59-0.78]), P=.0252. Conclusion: Salivary gland ultrasound is a useful and reliable method for the classification of SS. Its use could be considered in the future within the SS classification criteria.

Hallazgos de microscopia confocal in vivo de la mucosa de la córnea y la lengua en pacientes con síndrome de Sjögren / In vivo confocal microscopy findings of cornea and tongue mucosa in patients with Sjögren's syndrome

Introducción y objetivos: Nuestro objetivo fue investigar si el síndrome de Sjögren (SS) tenía hallazgos distintivos en la microscopia confocal de la lengua de una manera no invasiva. Materiales y métodos: Este estudio retrospectivo de casos y controles evaluó los hallazgos de la microscopia confocal de córnea y lengua de los ojos derechos de 25 pacientes con ojo seco con deficiencia acuosa y 12 voluntarios sanos sin hallazgos de ojo seco. Hubo un total de 14 pacientes diagnosticados con ojo seco asociado a SS (SSDE), mientras que 11 casos fueron evaluados como ojo seco no Sjögren (NSDE). Resultados: Se observó una diferencia significativa en el recuento de células dendríticas a nivel del nervio subbasal corneal entre los grupos SSDE y NSDE (p=0,018). En el grupo SSDE, las imágenes de microscopia confocal de células inflamatorias dendritiformes hiperreflectantes en la mucosa de la lengua estaban a favor de la inflamación. Sin embargo, estos hallazgos no se encontraron en pacientes con NSDE o en controles. Conclusiones: Este estudio mostró que la microscopia confocal proporcionó una evaluación no invasiva de las células inflamatorias en la lengua de los pacientes con SS.(AU)

Introduction and objectives: We aimed to investigate whether Sjögren's syndrome (SS) had distinctive findings in tongue confocal microscopy in a non-invasive manner. Materials and methods: This retrospective case-control study evaluated corneal and tongue confocal microscopy findings of the right eyes of 25 patients with aqueous deficient dry eye and 12 healthy volunteers without dry eye findings. There were a total of 14 patients diagnosed with SS-associated dry eye (SSDE), while 11 cases were evaluated as non-Sjögren dry eye (NSDE). Results: A significant difference was observed in the dendritic cell count at the corneal subbasal nerve level between the SSDE and NSDE groups (P=.018). In SSDE group, the confocal microscopy images of dendritiform hyperreflective inflammatory cells in the tongue mucosa were in favor of inflammation. However, these findings were not found in patients with NSDE or in controls. Conclusions: This study showed that confocal microscopy provided a non-invasive evaluation of the inflammatory cells in the tongue of SS patients.(AU)

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome / Anticuerpos contra las células parietales como biomarcadores potenciales de enfermedad pulmonar intersticial relacionada con el síndrome de Sjögren primario

Background ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. Methods Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. Results A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). Conclusion APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS (AU)

Antecedentes La enfermedad pulmonar intersticial (EPI) es una manifestación común del síndrome de Sjögren primario (SSp) y está relacionada con un mayor riesgo de muerte. Los anticuerpos anticélulas parietales (AACP) están fuertemente expresados por células epiteliales alveolares proliferantes en los pulmones fibróticos y están relacionados con la disminución acelerada de la función pulmonar en la gibrosis pulmonar idiopática. En este estudio, pretendemos evaluar la aplicación clínica de la AACP en pacientes con EPI con SSp. Método Se revisaron los datos clínicos, de laboratorio, de función pulmonar e imágenes de los pacientes con SSp y se utilizó la ESSDAI para evaluar la actividad de la enfermedad en general. Se registraron 5 características principales de imagen pulmonar de la EPI y 2 radiólogos ciegos experimentados realizaron una puntuación semicuantitativa de HRCT de forma independiente. Comparamos las características clínicas de los pacientes con y sin EPI con SSp y realizamos un análisis de regresión logística de los factores de riesgo de EPI en SSp. Resultados Un total de 74 pacientes con SSp y 40 controles sanos fueron incluidos en el estudio. La EPI es más común en el grupo positivo de AACP que en el grupo negativo de APCA. El nivel cuantitativo de AACP, está positivamente relacionado con la puntuación de imagen. El análisis multifactorial encontró que la larga duración, el aumento de los niveles de AACP y el aumento de los niveles de KL-6 fueron factores de riesgo independientes para la EPI en pacientes con SSp. El área bajo la curva ROC de AACP es de 0,6618 y la concentración umbral fue de 153,82 ng/ml (sensibilidad 45,24% y especificidad 87,50%). Conclusiones Los niveles de AACP son un factor de riesgo independiente y pueden ser biomarcadores potenciales de EPI en pacientes con SSp (AU)

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome.

BACKGROUND: ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. METHODS: Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. RESULTS: A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). CONCLUSION: APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS.

In vivo confocal microscopy findings of cornea and tongue mucosa in patients with Sjögren's syndrome.

INTRODUCTION AND OBJECTIVES: We aimed to investigate whether Sjögren's syndrome (SS) had distinctive findings in tongue confocal microscopy in a non-invasive manner. MATERIALS AND METHODS: This retrospective case-control study evaluated corneal and tongue confocal microscopy findings of the right eyes of 25 patients with aqueous deficient dry eye and 12 healthy volunteers without dry eye findings. There were a total of 14 patients diagnosed with SS-associated dry eye (SSDE), while 11 cases were evaluated as non-Sjögren dry eye (NSDE). RESULTS: A significant difference was observed in the dendritic cell count at the corneal subbasal nerve level between the SSDE and NSDE groups (P=.018). In SSDE group, the confocal microscopy images of dendritiform hyperreflective inflammatory cells in the tongue mucosa were in favor of inflammation. However, these findings were not found in patients with NSDE or in controls. CONCLUSIONS: This study showed that confocal microscopy provided a non-invasive evaluation of the inflammatory cells in the tongue of SS patients.

20% Autologous serum vs. 0.05% cyclosporine and preservative-free artificial tears in the treatment of Sjögren related dry eye / Soro autólogo a 20% versus ciclosporina a 0,05 e lubrificantes oculares sem conservantes no tratamento da síndrome do olho seco relacionada à Sjögren

ABSTRACT Purpose: To compare the 3-month results of treatment with 20% autologous serum or combination treatment with preservative-free artificial tears and 0.05% cyclosporine in patients with dry eye disease due to primary Sjögren's syndrome. Methods: A total of 130 eyes of 65 patients with newly diagnosed dry eye disease due to primary Sjögren's syndrome were included in the study. The patients were divided into two treatment groups: 66 eyes of 33 patients were assigned to the autologous serum treatment group, and 64 eyes of 32 patients were assigned to the combination treatment group. Schirmer test, tear break-up time and Ocular Surface Disease Index (OSDI) scores were recorded at pretreatment and at 3 months of treatment. Results: At 3 months of treatment, the mean Schirmer value and the mean tear break-up time were significantly higher in the combination treatment group (p<0.0001 and p=0.034, respectively). The OSDI score at 3 months was significantly lower in the autologous serum Group (p=0.004). When the two groups were evaluated separately, the improvements in Schirmer, tear break-up time test, and OSDI scores from before to after treatment were statistically significant: p<0.0001, p<0.001, and p<0.0001, respectively, for the authologus serum Group, and p<0.0001, p<0.001, and p<0.0001, respectively, for the combination treatment group. Conclusions: In short-term treatment of dry eye disease due to primary Sjögren's syndrome, treatment with autologous serum was significantly superior to -combination treatment with preservative-free artificial tears and 0.05% cyclosporine in terms of improvement in OSDI scores. Improvements in Schirmer test and tear break-up time scores were significantly superior in the group treated with preservative-free artificial tears and 0.05% cyclosporine.

RESUMO Objetivo: Comparar os resultados de 3 meses de soro autólogo a 20% com um tratamento combinado, ou seja, lubrificantes oculares sem conservantes e ciclosporina a 0,05% em pacientes com síndrome do olho seco devida à síndrome de Sjögren primária. Métodos: Foram incluídos no estudo 130 olhos de 65 pacientes recentemente diagnosticados com síndrome do olho seco devida à síndrome de Sjögren primária. Os pacientes foram divididos em dois grupos de tratamento, 66 olhos de 33 pacientes foram incluídos no grupo de tratamento com soro autólogo e 64 olhos de 32 pacientes foram incluídos no grupo de tratamento combinado com lubrificantes oculares sem conservantes e ciclosporina. Os resultados do teste de Schirmer e do tempo de ruptura do filme lacrimal e os índices de doença da superfície ocular (OSDI) foram registrados antes e depois de três meses de tratamento. Resultados: Três meses após o tratamento, o valor médio do teste de Schirmer foi mais alto com significância estatística no grupo do tratamento combinado com lubrificantes oculares sem conservantes e ciclosporina (p<0,0001) e o tempo de ruptura do filme lacrimal também foi significativamente maior nesse grupo (p=0,034). Também aos três meses, a doença da superfície ocular foi menor com significância estatística no grupo de tratamento com soro autólogo (p=0,004). Quando os dois grupos foram avaliados separadamente, a melhora no teste de Schirmer, o tempo de ruptura e a doença da superfície ocular antes e depois do tratamento tiveram diferenças estatisticamente significativas tanto no grupo de soro autólogo (p<0,0001, p<0,001 e p<0,0001, respectivamente) quanto no grupo de tratamento combinado (p<0,0001, p<0,001 e p<0,0001, respectivamente). Conclusões: No tratamento de curto prazo da síndrome do olho seco devida à síndrome de Sjögren primária, o tratamento com soro autólogo foi significativamente superior ao tratamento com lubrificantes oculares sem conservantes combinados com ciclosporina, em termos de melhora no doença da superfície ocular. As melhoras no teste de Schirmer e no tempo de ruptura do filme lacrimal foram significativamente maiores no grupo de tratamento combinado com lubrificantes oculares sem conservantes e ciclosporina.

Autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution: a clinical comparative study / Colírio de soro autólogo diluído com metilcelulose 0,5% e solução salina 0,9%: um estudo clínico comparativo

ABSTRACT Purpose: This clinical study compared autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution. The subjective criteria for symptom improvement and the objective clinical criteria for response to therapy were evaluated. Methods: This longitudinal prospective study enrolled 23 patients (42 eyes) with persistent epithelial defects or severe dry eye disease refractory to conventional therapy who had been using autologous serum 20% prepared with methylcellulose for > 6 months and started on autologous serum diluted in 0.9% saline solution. The control and intervention groups consisted of the same patients under alternate treatments. The subjective criteria for symptom relief were evaluated using the Salisbury Eye Evaluation Questionnaire. The objective clinical criteria were evaluated through a slit-lamp examination of the ocular surface, tear breakup time, corneal fluorescein staining, Schirmer's test, rose Bengal test, and tear meniscus height. These criteria were evaluated before the diluent was changed and after 30, 90, and 180 days. Results: In total, 42 eyes were analyzed before and after 6 months using autologous serum diluted with 0.9% saline. No significant differences were found in the subjective criteria, tear breakup time, tear meniscus, corneal fluorescein staining, or rose Bengal test. Schirmer's test scores significantly worsened at 30 and 90 days (p=0.008). No complications or adverse effects were observed. Conclusions: This study reinforces the use of autologous serum 20% as a successful treatment for severe dry eye disease resistant to conventional therapy. Autologous serum in 0.9% saline was not inferior to the methylcellulose formulation and is much more cost-effective.

RESUMO Objetivo: Este estudo comparou o colírio de soro au tólogo manipulado com metilcelulose a 0,5% com solução salina 0,9%. Critérios subjetivos de melhora dos sintomas e critérios clínicos objetivos para resposta à terapia foram avaliados. Métodos: Este estudo prospectivo longitudinal envolveu 23 pacientes (42 olhos) com defeitos epiteliais persistentes ou doença de olho seco grave refratária à terapia convencional que usavam colírio de soro autólogo 20% preparado com metilcelulose por mais de 6 meses e iniciaram soro autólogo diluído em solução salina 0,9%. Os grupos controle e intervenção consistiam dos mesmos pacientes sob tratamentos alternados. Os critérios subjetivos para o alívio dos sintomas foram avaliados usando o Salisbury Eye Evaluation Questionnaire. Os critérios objetivos foram avaliados por meio de exame em lâmpada de fenda incluindo: tempo de ruptura da lágrima, coloração da córnea com fluoresceína, teste de Schirmer, coloração com rosa bengala e altura do menisco lacrimal. Esses critérios foram avaliados antes da troca do diluente e após 30, 90 e 180 dias. Resultados: Um total de 42 olhos foram analisados antes e após 6 meses usando soro autólogo diluído com solução salina 0,9%. Nenhuma diferença significativa foi encontrada nos critérios subjetivos, tempo de ruptura da lágrima, menisco lacrimal, coloração com fluoresceína ou rosa bengala. Os resultados dos testes de Schirmer pioraram significativamente em 30 e 90 dias (p=0,008). Não foram observadas complicações ou efeitos adversos. Conclusões: Este estudo reforça o uso do colírio de soro autólogo 20% como um tratamento de sucesso para a doença do olho seco grave resistente à terapia convencional. O soro autólogo diluído em solução salina a 0,9% não foi inferior à formulação de metilcelulose.

Sjogren's syndrome: a neurological perspective / Síndrome de Sjogren: uma perspectiva neurológica

Abstract Sjogren's syndrome (SS) is a complex autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands, resulting in sicca symptoms. Additionally, SS presents with neurological manifestations that significantly impact the nervous system. This review aims to provide a comprehensive overview of the neurological aspects of SSj, covering both the peripheral and central nervous system involvement, while emphasizing diagnosis, treatment, and prognosis.

Resumo A síndrome de Sjogren (SS) é uma doença autoimune complexa caracterizada pela infiltração linfocítica das glândulas salivares e lacrimais, resultando em sintomas sicca. Além disso, a SS apresenta manifestações neurológicas que afetam significativamente o sistema nervoso. Esta revisão tem como objetivo fornecer uma visão abrangente dos aspectos neurológicos da SSj, abordando tanto o envolvimento do sistema nervoso periférico quanto do central, com ênfase no diagnóstico, tratamento e prognóstico.

Encefalitis autoinmune seronegativa asociada a síndrome de Sjögren primario / Autoimmune seronegative encephalitis associated to primary Sjögren's disease

La encefalitis autoinmune es un trastorno inmunomediado que compromete distintos territorios del parénquima cerebral, involucrando frecuentemente la materia gris profunda o la corteza, con o sin compromiso de la materia blanca, meninges o médula espinal. Se asocia frecuentemente con enfermedades autoinmunes o paraneoplásicas, y constituye un reto diagnóstico. Reportamos el caso de una mujer de 55 años con antecedente de síndrome de Sjögren que consultó a Emergencias por cefalea y confusión. El líquido cefalorraquídeo (LCR) presentaba leucocitosis con neutrofilia. En la resonancia magnética nuclear (RMN) cerebral se evidenciaron múltiples imágenes de comportamiento restrictivo, de señal hiperintensa en T2 y FLAIR, a predominio córtico-subcortical a nivel occipital bilateral, hemisferio cerebeloso derecho y parietal derecho. Se descartaron infecciones y neoplasias. El panel de anticuerpos para encefalitis autoinmune aquaporina-4 y anti-MOG en LCR fue negativo. Recibió metilprednisolona endovenosa con mejoría progresiva de los síntomas.

Autoimmune encephalitis is an immune-mediated disorder that affects different areas of the brain parenchyma, often involving deep gray matter or the cortex, with or without involvement of white matter, meninges, or spinal cord. It is frequently associated with autoimmune or paraneoplastic diseases and is a diagnostic challenge. We report the case of a 55-year-old woman with history of Sjögren's syndrome who presented to the emergency department with headache and episodes of confusion. Cerebrospinal fluid (CSF) analysis showed leukocytosis with neutrophilia. Brain MRI revealed multiple restricted diffusion lesions with hyperintense signal on T2 and FLAIR sequences, predominantly in the bilateral occipital region, right cerebellar hemisphere, and right parietal region. Infections and neoplasms were ruled out. The panel of antibodies for autoimmune encephalitis, including Aquaporin-4 and anti-MOG in CSF, was negative. She received intravenous methylprednisolone, leading to symptom improvement.

Validación del ClinESSDAI para Argentina / Validation of ClinESSDAI for Argentina

Introducción: recientemente, en Europa y en idioma inglés, se ha desarrollado el Clinical EULAR Sjögren's Syndrome Disease Activity Index (ClinESSDAI) para evaluar la actividad en pacientes con síndrome de Sjögren primario (SSp). Objetivos: validar el ClinESSDAI en pacientes con SSp en Argentina. Materiales y métodos: estudio de corte transversal. Se utilizó la versión en castellano del EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) validada en Argentina. Para evaluar la validez del constructo, se usó la escala visual análoga (EVA) desarrollada por un reumatólogo experto por dominio del ClinESSDAI y de la EVA global para el puntaje total del ClinESSDAI, mientras que otro profesional en la materia realizó el ESSDAI y ClinESSDAI. Para analizar la reproducibilidad, se estudió a un subgrupo de pacientes, sin mediar cambios en el tratamiento ni en la condición clínica, 10 días después de la evaluación basal. Todos los médicos examinaron a los pacientes desconociendo la evaluación de los demás colegas. Resultados: se incluyeron 47 pacientes con SSp. La correlación entre la EVA global y el ClinESSDAI fue muy buena (Rho 0,7), así como la correlación de la EVA y el ClinESSDAI de cada dominio. El coeficiente de correlación intraclase (CCI) entre el ESSDAI y el ClinESSDAI fue de 0,98. La reproducibilidad fue de 0,93. Conclusiones: el ClinESSDAI es una herramienta válida y reproducible en nuestra población, equiparable al ESSDAI.

Introduction: the Clinical EULAR Sjögren's Syndrome Disease Activity Index (ClinESSDAI) has recently been developed in Europe and in the English language to evaluate activity in patients with primary Sjögren's syndrome (pSS). Objectives: validate the ClinESSDAI in patients pSS in Argentina. Materials and methods: a cross-sectional study. The Spanish version of the ESSDAI, validated in Argentina, was used. To evaluate construct validity, the Visual Analog Scale (VAS) was used, performed by an expert rheumatologist per ClinESSDAI domain, and the global VAS was used for the total score of the ClinESSDAI, while another professional performed the ESSDAI and ClinESSDAI. To evaluate reproducibility, a subgroup of patients was evaluated without changes in treatment or clinical condition 10 days after the baseline evaluation. All physicians were blind to each other's evaluation. Results: 47 patients with pSS were included. The correlation between global VAS and ClinESSDAI was very good (Rho 0.7), as well as the correlation of the VAS and ClinESSDAI of each domain. The intraclass correlation coefficient (ICC) between ESSDAI and ClinESSDAI was 0.98. The reproducibility was 0.93. Conclusions: the ClinESSDAI is a valid and reproducible tool in our population, comparable to the ESSDAI.

Sjogren-Larsson syndrome brain volumetric reductions demonstrated with an automated software / Reduções volumétricas cerebrais da síndrome de Sjogren-Larsson demonstradas com um software automatizado

Abstract Background Sjogren-Larsson syndrome (SLS) is a neurocutaneous disease with an autosomal recessive inheritance, caused by mutations in the gene that encodes fatty aldehyde dehydrogenase (ALDH3A2), clinically characterized by ichthyosis, spastic diplegia, and cognitive impairment. Brain imaging plays an essential role in the diagnosis, demonstrating a nonspecific leukoencephalopathy. Data regarding brain atrophy and grey matter involvement is scarce and discordant. Objective We performed a volumetric analysis of the brain of two siblings with SLS with the aim of detecting deep grey matter nuclei, cerebellar grey matter, and brainstem volume reduction in these patients. Methods Volume data obtained from the brain magnetic resonance imaging (MRI) of the two patients using an automated segmentation software (Freesurfer) was compared with the volumes of a healthy control group. Results Statistically significant volume reduction was found in the cerebellum cortex, the brainstem, the thalamus, and the pallidum nuclei. Conclusion Volume reduction in grey matter leads to the hypothesis that SLS is not a pure leukoencephalopathy. Grey matter structures affected in the present study suggest a dysfunction more prominent in the thalamic motor pathways.

Resumo Antecedentes A Síndrome de Sjogren-Larsson (SSL) é uma doença neurocutânea de herança autossômica recessiva, causada por mutações no gene que codifica a aldeído graxo desidrogenase (ALDH3A2), caracterizada clinicamente por ictiose, diplegia espástica e comprometimento cognitivo. A imagiologia cerebral desempenha um papel essencial no diagnóstico, demonstrando uma leucoencefalopatia inespecífica. Dados sobre atrofia cerebral e envolvimento da substância cinzenta são escassos e discordantes. Objetivo Realizamos uma análise volumétrica do cérebro de dois irmãos com SLS com o objetivo de detectar núcleos profundos de substância cinzenta, substância cerebral cinzenta e redução do volume do tronco encefálico nestes pacientes. Métodos Os dados de volume obtidos da ressonância magnética (RM) cerebral dos dois pacientes usando um software de segmentação automática (Freesurfer) foram comparados com os volumes de um grupo controle saudável. Resultados Redução de volume estatisticamente significativa foi encontrada no córtex do cerebelo, no tronco cerebral, no tálamo e nos núcleos pálidos. Conclusão A redução do volume da substância cinzenta leva à hipótese de que a SSL não é uma leucoencefalopatia pura. As estruturas da substância cinzenta afetadas no presente estudo sugerem uma disfunção mais proeminente nas vias motoras talâmicas.

Síndrome de Sjögren y endodoncia, consideraciones a propósito de un caso / Sjögren's syndrome and endodontics, clinical case and considerations

El síndrome de Sjögren (SS) es una enfermedad autoinmune que afecta a las glándulas salivales y lagrimales. Se expone el caso clínico de una paciente de 67 años de género femenino que consulta por dolor en múltiples dientes; relata sensación de boca seca (xerostomía) y sequedad ocular (xeroftalmia). Al examen intraoral, se observan múltiples caries en superficies atípicas, mucosas secas, saliva espumosa y notoria depapilación lingual. Se sospecha de SS, derivando a medicina interna y confirmándose el diagnóstico. En paralelo, se inicia el tratamiento odontológico, realizando adaptaciones en los procedimientos para aliviar la sintomatología del SS, especialmente durante tratamientos endodónticos.

Sjögren's syndrome (SS) is an autoimmune disease that affects the salivary and lacrimal glands. The clinical case of a 67-year-old female patient who consulted for pain in multiple teeth is exposed. Additionally, she reports a sensation of dry mouth (xerostomia) and dry eyes (xerophthalmia). During the intraoral examination, the following findings are noticed: multiple cavities on atypical surfaces, dry mucous membranes, foamy saliva, and atrophic glossitis. SS is suspected, referring to internal medicine and confirming the diagnosis. In parallel, dental treatment is initiated, making adaptations in the procedures to alleviate the symptoms of SS, especially during endodontic treatments.

Gastrointestinal and Hepatic Involvement in Primary Sjögren's Syndrome: Case Report and Literature Review

Sjögren's syndrome is a systemic autoimmune disease characterized by dry eyes and mouth due to the involvement of exocrine glands. However, it can manifest with GI symptoms that cover a broad spectrum from esophageal and intestinal dysmotility, achalasia, hypochlorhydria, and chronic atrophic gastritis to pancreatic enzyme deficiency, biliary dysfunction, and liver cirrhosis, which varies in its clinical manifestations and is often associated with erroneous approaches. This article reviews the GI manifestations of Sjögren's syndrome. It presents the case of a woman in her eighth decade of life with this syndrome. She showed asymptomatic hepatobiliary disease, documented abnormalities in liver profile tests, and a subsequent diagnosis of primary sclerosing cholangitis, for which she received initial treatment with ursodeoxycholic acid. During her condition, the patient has had three episodes of cholangitis, requiring endoscopic retrograde cholangiopancreatography with no findings of stones, with scant biliary sludge and discharge of purulent bile precipitated by her underlying liver disease. The association between Sjögren's syndrome and primary sclerosing cholangitis is rare and calls for special consideration.

El síndrome de Sjögren es una enfermedad autoinmune sistémica que se caracteriza por la sequedad ocular y bucal debido a la afección de glándulas exocrinas; sin embargo, puede manifestarse con síntomas gastrointestinales que abarcan un espectro amplio desde la dismotilidad esofágica e intestinal, acalasia, hipoclorhidria y gastritis crónica atrófica hasta enzimodeficiencia pancreática, disfunción biliar y cirrosis hepática, que tiene variación en sus manifestaciones clínicas y se asocia con abordajes erróneos en muchas ocasiones. En este artículo se hace una revisión acerca de las manifestaciones gastrointestinales de síndrome de Sjögren y se presenta el caso de una mujer en la octava década de la vida con este síndrome, que cursa con enfermedad hepatobiliar asintomática, documentación de alteración en pruebas de perfil hepático y diagnóstico ulterior de colangitis esclerosante primaria, por lo que recibió un tratamiento inicial con ácido ursodesoxicólico. Durante el curso de su enfermedad ha presentado 3 episodios de colangitis, con requerimiento de colangiopancreatografía retrógrada endoscópica sin hallazgos de cálculos, con escaso barro biliar y salida de bilis purulenta, precipitada por su enfermedad hepática de base. La asociación entre el síndrome de Sjögren y la colangitis esclerosante primaria es infrecuente y justifica una consideración especial.

Diagnostic role of CXCL13 biomarker in primary Sjogren's syndrome patients with parotid non-Hodgkin's lymphoma complication / Papel diagnóstico del biomarcador CXCL13 en pacientes con síndrome de Sjogren primario con complicación de linfoma no Hodgkin parotídeo

Introduction Serum biomarkers are important predictive factors for development of parotid non-Hodgkin's lymphoma (NHL) complication in primary Sjogren's syndrome (pSS) patients. The aim was to evaluate the diagnostic accuracy of serum CXCL13 chemokine in pSS patients with parotid NHL complication. Material and methods Serum CXCL13 chemokine was assessed in 33 patients with pSS [7 with parotid NHL complication (pSS+NHL subgroup) and 26 without NHL (pSS-NHL subgroup)] and 30 healthy subjects. Results The serum CXCL13 levels in pSS+NHL subgroup [175.2 (107.9–220.4) pg/ml] were significantly higher comparing to the healthy subjects group (p=0.018) and the pSS-NHL subgroup (p=0.048). A cut-off value of 123.45pg/ml (Se=71.4%, Sp=80.8%, AUROC=0.747) was established for parotid lymphoma diagnosis. Conclusion The serum CXCL13 biomarker could be considered a valuable tool for the diagnosis of parotid NHL complication in pSS patients (AU)

Introducción Los biomarcadores séricos son factores predictivos importantes para el desarrollo de complicaciones del linfoma no Hodgkin (LNH) parotídeo en pacientes con síndrome de Sjogren primario (SSp). El objetivo fue evaluar la precisión diagnóstica de la quimiocina sérica CXCL13 en pacientes con SSp con complicación del LNH parotídeo. Material y métodos Se evaluó la quimiocina sérica CXCL13 en 33 pacientes con SSp [7 con complicación de LNH parotídeo (subgrupo SSp+LNH) y 26 sin LNH (subgrupo SSp-LNH)] y 30 sujetos sanos. Resultados Los niveles séricos de CXCL13 en el subgrupo pSS+NHL [175,2 (107,9-220,4) pg/ml] fueron significativamente más altos en comparación con el grupo de sujetos sanos (p=0,018) y el subgrupo pSS-NHL (p=0,048). Se estableció un valor de corte de 123,45 pg/ml (Se=71,4%, Sp=80,8%, AUROC=0,747) para el diagnóstico de linfoma de parótida. Conclusión El biomarcador sérico CXCL13 podría considerarse una herramienta valiosa para el diagnóstico de la complicación del LNH parotídeo en pacientes con SSp (AU)

Salivary gland ultrasound in clinical practice: What is its real usefulness?

BACKGROUND: Salivary gland ultrasound (SGU) provides information about structural gland abnormalities that can be graded and used for primary Sjögren's syndrome (pSS) diagnosis. Its potential role as a prognostic marker for detecting patients at high risk of lymphoma and extra-glandular manifestations is still under evaluation. We aim to assess the usefulness of SGU for SS diagnosis in routine clinical practice and its relationship with extra-glandular involvement and lymphoma risk in pSS patients. METHODS: We designed a retrospective observational single-center study. Data was collected using the electronic health records of patients referred to an ultrasound outpatient clinic for evaluation over a 4-year period. Data extraction included demographics, comorbidities, clinical data, laboratory tests, SGU results, salivary gland (SG) biopsy, and scintigraphy results. Comparisons were made between patients with and without pathological SGU. The external criterion for comparison was the fulfillment of the 2016 ACR/EULAR pSS criteria. RESULTS: A total of 179 SGU assessments were included from this 4-year period. Twenty-four cases (13.4%) were pathological. The most frequently diagnosed conditions prior to SGU-detected pathologies were pSS (9.7%), rheumatoid arthritis (RA) (13.1%), and systemic lupus (4.6%). One hundred and two patients (57%) had no previous diagnosis (sicca syndrome work-up); of these, 47 patients (46.1%) were ANA positive and 25 (24.5%) anti-SSA positive. In this study, the sensitivity and specificity of SGU for SS diagnosis were 48% and 98% respectively, with a positive predictive value of 95%. There were statistically significant relationships between a pathological SGU and the presence of recurrent parotitis (p=.0083), positive anti-SSB antibodies (p=.0083), and a positive sialography (p=.0351). CONCLUSIONS: SGU shows high global specificity but low sensitivity for pSS diagnosis in routine care. Pathological SGU findings are associated with positive autoantibodies (ANA and anti-SSB) and recurrent parotitis.

Salivary gland ultrasound in clinical practice: What is its real usefulness? / Utilidad en práctica clínica de la ecografía de glándulas salivales

Background: Salivary gland ultrasound (SGU) provides information about structural gland abnormalities that can be graded and used for primary Sjögren's syndrome (pSS) diagnosis. Its potential role as a prognostic marker for detecting patients at high risk of lymphoma and extra-glandular manifestations is still under evaluation. We aim to assess the usefulness of SGU for SS diagnosis in routine clinical practice and its relationship with extra-glandular involvement and lymphoma risk in pSS patients. Methods: We designed a retrospective observational single-center study. Data was collected using the electronic health records of patients referred to an ultrasound outpatient clinic for evaluation over a 4-year period. Data extraction included demographics, comorbidities, clinical data, laboratory tests, SGU results, salivary gland (SG) biopsy, and scintigraphy results. Comparisons were made between patients with and without pathological SGU. The external criterion for comparison was the fulfillment of the 2016 ACR/EULAR pSS criteria. Results: A total of 179 SGU assessments were included from this 4-year period. Twenty-four cases (13.4%) were pathological. The most frequently diagnosed conditions prior to SGU-detected pathologies were pSS (9.7%), rheumatoid arthritis (RA) (13.1%), and systemic lupus (4.6%). One hundred and two patients (57%) had no previous diagnosis (sicca syndrome work-up); of these, 47 patients (46.1%) were ANA positive and 25 (24.5%) anti-SSA positive. In this study, the sensitivity and specificity of SGU for SS diagnosis were 48% and 98% respectively, with a positive predictive value of 95%. There were statistically significant relationships between a pathological SGU and the presence of recurrent parotitis (p=.0083), positive anti-SSB antibodies (p=.0083), and a positive sialography (p=.0351)...(AU)

Antecedentes y objetivo: La ecografía de glándulas salivales (EGS) proporciona información acerca de las anomalías en la estructura glandular, y puede ser utilizado para el diagnóstico del síndrome de Sjögren (SS). Además, su potencial valor pronóstico para detectar pacientes con riesgo de manifestaciones extra-glandulares, así como el riesgo de linfoma se encuentra aún bajo estudio. El objetivo de nuestro estudio es evaluar la utilidad de la EGS para el diagnóstico del SS en la práctica clínica habitual, y su relación con la afectación extra-glandular, así como el riesgo de linfoma en pacientes con síndrome de Sjögren primario (pSS). Métodos: Realizamos un estudio retrospectivo y observacional en un único centro. La información fue recolectada de la historia clínica electrónica del paciente tras un seguimiento de 4 años. Esta información incluye variables demográficas, comorbilidades, datos clínicos, análisis de laboratorio, los resultados de la EGS, biopsia de glándulas salivales y gammagrafía. Se efectuaron comparaciones entre los pacientes que tenían una EGS patológica con aquellos que tenían un resultado normal. El criterio para establecer la comparación fue cumplir los criterios de ACR/ELUAR 2016 para el diagnóstico de pSS. Resultados: Se realizaron un total de 179 EGS durante el período de 4 años. De estas, 24 (13,4%) resultaron ser patológicas. Las enfermedades más frecuentemente identificadas tras realizar la EGS fueron pSS (9,7%), artritis reumatoide (AR) (4,6%) y lupus eritematoso sistémico (LES) (4,6%). Ciento dos pacientes (57%) no tenían diagnóstico previo (estudio de síndrome seca); de estos, 47 (46,1%) tenían ANA positivo y 25 (24,5%) tenían anti-Ro positivo. La sensibilidad y la especificidad de la EGS para detectar el SS en nuestro estudio fueron del 48 y 98%, respectivamente; con un valor predictivo positivo del 95%...(AU)