Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine / 中国中药杂志

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

Subconjunctival adalimumab for treatment of dry eye disease in Sjögren's syndrome / Tratamento de olho seco com adalimumabe subconjuntival em pacientes portadores da síndrome de Sjögren

ABSTRACT Objective To describe the use of subconjuctival administration of the anti-tumor necrosis factor agent adalimumab for treatment of dry eye in patients with Sjögren's syndrome, and to investigate conjunctival healing. Methods Prospective, nonrandomized, noncomparative interventional case series including consecutive patients with Sjögren's syndrome and dry eye disease treated with subconjunctival adalimumab, who were refractory to conventional treatment. Patients with infectious ocular surface involvement or structural changes in the tear pathway or eyelids were excluded. Data recorded included age, sex, lissamine green staining pattern, Schirmer test results, intraocular pressure, conjunctival mobility, tear break up time and findings of biomicroscopic evaluation, following fluorescein dye instillation. The Ocular Surface Disease Index questionnaire validated for the Portuguese language was used for subjective assessment of patients. Results Eleven eyes of eight patients were studied. Mean patient age was 53±13.4 years. Patients were treated with subconjunctival injection of 0.03 mL of adalimumab and followed for 90 days thereafter. There were no statistically significant objective improvement (objective tests results; p>0.05) and no statistically significant changes in intraocular pressure (p=0.11). Questionnaire responses revealed a significant improvement in ocular symptoms (p=0.002). Conclusion Based on the Ocular Surface Disease Index questionnaire, subconjunctival administration of adalimumab improved dry eye symptoms. However, objective assessments failed to reveal statistically significant improvements.

RESUMO Objetivo Descrever o uso subconjuntival do antifator de necrose tumoral adalimumabe para o tratamento do olho seco em pacientes com síndrome de Sjögren e avaliar a cicatrização conjuntival. Métodos Série de casos intervencionista com desenho prospectivo, não randomizado, não comparativo. O medicamento adalimumabe foi aplicado em região subconjuntival em pacientes com síndrome de Sjögren e olho seco que eram resistentes a outras terapias convencionais. Pacientes com patologias oculares de origem infecciosa ou com alterações estruturais nas vias lacrimais e pálpebras foram excluídos do estudo. Os dados coletados incluíram idade, sexo, teste com lisamina verde, teste de Schirmer, pressão intraocular, mobilidade conjuntival, teste de ruptura do filme lacrimal, e avaliação biomicroscópica com colírio de fluoresceína. Além disso, o questionário Ocular Surface Disease Index validado para a língua portuguesa foi aplicado com objetivo de avaliar subjetivamente a resposta dos pacientes ao tratamento. Resultados Onze olhos de oito pacientes foram estudados. A idade média dos pacientes foi de 53±13,4 anos. A dose aplicada de adalimumabe subconjuntival foi de 0,03mL, e a duração do seguimento foi de 90 dias após a injeção. Não houve melhora estatisticamente significativa nos testes objetivos (todos apresentaram p>0,05). A pressão intraocular também não sofreu variações estatisticamente significativas (p=0,11). Entretanto, por meio do questionário, foi registrada melhora significativa dos sintomas oculares (p=0,002). Conclusão O uso do adalimumabe subconjuntival melhorou os sintomas de olho seco, avaliados por meio do questionário Ocular Surface Disease Index, mas não houve melhora estatisticamente significativa na avaliação objetiva.

Terapia farmacológica y avances terapéuticos en xerostomía e hiposalivación / Pharmacological therapy and therapeutic advancesin xerostomy and hyposalivation

La saliva juega un rol determinante en el mantenimiento y función de los tejidos orales, donde un decremento en los niveles del flujo salival conllevan a una hiposalivación o hiposialia, trayendo consigo una serie de características que propician un ambiente ideal para la instalaciónde microorganismos oportunistas y condiciones nocivas para la saludoral y sistémica de los pacientes. Hoy en día existen múltiples causas que conllevan a una hiposialia, entre ellas el síndrome de Sjõgren, la radioterapia de haz externo, entre otras, los cuales se han puesto a prueba mediante sialogogos farmacológicos como pilocarpina, cevimelina, betanecoly carbacolina, además de alternativas terapéuticas para revertir los signos obtenidos por la hiposalivación y mitigar los síntomas de xerostomía. El objetivo del presente es realizar una revisión de literatura sobre el tratamiento farmacológico en hiposalivación y xerostomía ensíndrome de Sjõgren y radioterapia de haz externo.

Saliva plays a determinant role in the maintenance and function of oral tissues, where a decrease in salivary flow levels leads to hyposalivation or hyposialia, bringing with it a series of characteristics that provide anideal environment for the installation of opportunistic microorganisms and conditions harmful to the oral and systemic health of patients.Today there are many causes that lead to hyposialia, including Sjögren’ssyndrome, external beam radiotherapy, among others, which have beentested by pharmacological sialogogs such as pilocarpine, cevimelin, betanecol and carbacoline, in addition to therapeutic alternativesto reverse the signs obtained by hyposalivation and to mitigate the symptoms of xerostomia. The objective of the present is to make a reviewof the literature on the pharmacological treatment in hyposalivation and xerostomia in Sjögren’s syndrome and external beam radiotherapy.

Síndrome de Sjögren: Caso clínico / Sjögren's syndrome: case report

Introducción: El síndrome de Sjögren (SS) es una enfermedad crónica, autoinmune, que afecta principalmente a las glándulas exocrinas lagrimales y salivales. En niños es una enfermedad rara. Objetivo: Presentar el caso de un adolescente con síntomas inespecíficos, en que la sospecha clínica hizo llegar al diagnóstico de SS. Caso Clínico: Paciente de 12 años, de sexo masculino, con historia de artralgias de 3 años de evolución y xeroftalmia dudosa. El examen físico mostró leve congestión conjuntival, boca seca e hiperlaxitud de rodillas. Pruebas de laboratorio: hemograma y VHS normales, anticuerpos antinucleares (+) > 60, Ro (+) > 60 U, factor reumatoideo (+) 160 UI/ml. Se sospechó SS y se completó el estudio: test de Shirmer, que determinó ojo seco leve; gammagrafía de las glándulas salivales, que mostró disfunción de las glándulas submaxilares y parotídeas; biopsia de glándulas salivales, que mostró focos de infiltrado linfoide acinar y periductal. Se confirmó SS y se inició tratamiento con prednisona 7,5 mg/día e hidroxicloroquina 200 mg/día y tratamientos locales, con buena respuesta. Conclusiones: Los criterios diagnósticos del SS en adultos identifican solo al 39% de los pacientes pediátricos por la baja frecuencia de síntomas de sicca. Aún no existen criterios diagnósticos validados para niños. Un buen diagnóstico permitirá aliviar los síntomas, evitar complicaciones y detectar enfermedades asociadas.

Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune disease that primarily affects the lacrimal and salivary exocrine glands. In children, it is a rare condition. Objective: To present the case of an adolescent with non-specific symptoms, but with a clinical suspicion of SS. Case report: A male 12-year old patient, with history of arthralgias for 3 years and suspicion of xerophthalmia. Physical examination showed mild conjunctival congestion, dry mouth and hypermobility of the knees. Laboratory work: blood count and ESR were normal, antinuclear antibodies (+) > 60, Ro (+) > 60 U, and rheumatoid factor concentration (+) 160 IU/ml. SS was suspected, and a study was carried out: Schirmer test determined mild dry eye, salivary gland scintigraphy showed parotid and submandibular gland dysfunction, and salivary gland biopsy reported focal lymphocytic acinar and periductal infiltration. SS was confirmed and treated with prednisone 7.5 mg/day and hydroxychloroquine 200 mg/day, and local treatment, with good response. Conclusions: The diagnostic criteria for SS in adults identified only 39% of pediatric patients, due to the low frequency of sicca symptoms. Still there are no validated diagnostic criteria for children. A good diagnosis will alleviate symptoms, prevent complications and detect associated diseases.

Histoplasmosis diseminada, linfopenia, y síndrome de Sjögren / Disseminated histoplasmosis, lymphopenia and Sjögren´s syndrome

El síndrome de Sjögren es una enfermedad autoinmune caracterizada por disminución de las secreciones de las glándulas exocrinas; puede presentar también diversas alteraciones hemáticas, entre ellas linfopenia. Presentamos el caso de un varón de 28 años que consultó por cefalea de un mes de evolución a la que se agregaron en las últimas 48 horas vómitos y fiebre. Presentaba lesiones en piel de tronco y cara; no tenía rigidez de nuca. Se demostró infección por Histoplasma capsulatum var. capsulatum en piel y líquido cefalorraquídeo, linfopenia, anticuerpos anti Ro-SSA positivos, baja concentración del trazador en centellograma de glándulas salivales e infiltración linfocitaria en glándulas salivales, lo que permitió confirmar al diagnóstico de síndrome de Sjögren. El tratamiento con anfotericina liposomal e itraconazol mejoró el cuadro clínico. Comunicamos este caso para referir que una infección oportunista, como la histoplasmosis diseminada, puede ser una forma poco común de presentación del síndrome de Sjögren.

Sjögren's syndrome is an autoimmune disease characterized by decreased exocrine gland secretions; patients may also present several hematological abnormalities, like lymphopenia. We describe the case of a 28 year old man who complained of headache a month of duration, with fever and vomiting in the last 48 hours. He also presented skin lesions on trunk and face, without neck stiffness. The diagnosis of duration infection was confirmed by culture from the skin biopsy and spinal fluid specimens; in addition, the presence of lymphopenia, positive anti Ro-SSA antibodies, poor concentration of the tracer in scintigraphy and lymphocytic infiltration in salivary glands confirmed the diagnosis of Sjögren's syndrome. The patient was successfully treated with liposomal amphotericin and itraconazole. We report this case to emphasize that opportunistic infections, such as disseminated histoplasmosis, may be an uncommon clinical presentation of Sjögren's syndrome.

Secondary Sjögren's syndrome and disease activity of rheumatoid arthritis / Síndrome de Sjögren secundária e atividade da artrite reumatoide

OBJECTIVE: To study the relationship of the presence of secondary SS with disease activity, duration in RA. METHODS: Eighty two patients with RA were submitted to Schirmer test, minor salivary gland biopsy, questionnaire on sicca symptoms, DAS-28 4v determination. RESULTS: In this population, 20 (24.3 percent) patients fulfilled the American-European classification criteria for secondary SS. No relation could be found between the presence of secondary SS and disease activity (p = 0.31) and RA duration (p = 0.95). CONCLUSION: Appearance of Secondary SS in RA patients is independent of RA duration or activity.

OBJETIVO: Estudar a associação entre presença de SS secundária e atividade e duração da artrite reumatoide. MÉTODOS: Oitenta e dois pacientes com artrite reumatoide foram submetidos ao teste de Schirmer, biópsia de glândula salivar menor, questionários acerca de sintomas de secura e determinação do DAS28 4v. RESULTADOS: Nesta população, 20 (24,3 por cento) dos pacientes preenchiam os Critérios Americanos Europeus para classificação de SS Secundário. Nenhuma associação foi encontrada entre presençade SS secundário e atividade da doença (p = 0.31) e duração da doença (p = 0.95). CONCLUSÃO: O aparecimento de SS secundário em AR é independente da duração e atividade da AR.

Scintigraphy of the salivary gland in patients with Sjõgren's syndrome treated with pilocarpine / Cintigrafia da glândula salivar em pacientes com Síndrome de Sjogren tratados com pilocarpina

OBJECTIVE: This report describes monitoring of salivary glands through scintigraphy in one patientwith SS before and after the administration of 1% pilocarpine. DISCUSSION: Sjõgren’s Syndrome(SS) is an immune-mediated disease that most commonly attacks the exocrine glands. The diagnosisof SS is based on the objective and subjective criteria that confirm the damage or diminished activityof salivary and lachrymal glands, in turn resulting in xerostomia and xerophthalmia. CONCLUSION:Scintigraphy with [99mTc] pertechnetate can be used to assess the progression of disease activity, thelocation affected and severity on the glands involved. Scintigraphy can also be used to assess xerostomiathrough activity time analyses, numeric indices, visual interpretations, and radiopharmaceuticalpercentages retained in the gland.

OBJETIVO: Este relato descreve a monitoração de glândulas salivares por meio de cintigrafia em umpaciente com Síndrome de Sjogren antes e após administração de pilocarpina a 1%. DISCUSSÃO: ASíndrome de Sjogren (SJ) é uma doença imunomediada que mais comumente ataca as glândulas exócrinas. O diagóstico da SJ é baseado em critérios objetivos e subjetivos que confirmam o dano ou atividadediminuída das glândulas salivares e lacrimais, resultando em xerostomia e xeroftalmia. CONCLUSÃO:Cintigrafia com pertecnato [99mTc] pode ser para determinar a progressão da doença, o local afetado ea severidade do envolvimento glandular. A cintigrafia pode também ser usada para avaliar xerostomiapor análises de atividade no tempo, índices numéricos, interpretação visual e porcentagensradiofarmacêuticas retidas na glândula.

Pulmonary manifestations of primary sjögren’s syndrome.

Sjögren's syndrome (SS) is a complex autoimmune exocrinopathy with multifactorial pathogenesis and multisystem manifestation. It is called primary Sjögren's syndrome (PSS) when the manifestations are seen without any other co-existent rheumatic diseases. The incidence of respiratory system involvement varies widely in the reported medical literature, partly due to lack of a universal agreement over the diagnostic criteria of the disease and the type of study methods employed. Respiratory system manifestations are protean; upper airway symptoms are very common and so is the complaint of dry cough. The PSS patients may develop interstitial lung diseases (ILDs) such as usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), lymphocytic interstitial pneumonia (LIP), bronchiolitis obliterans and organising pneumonia (BOOP), etc. They may also develop the whole spectrum of lymphoproliferative disorders of the lung ranging from LIP to follicular bronchiolitis, nodular lymphoid hyperplasia and low-grade lymphomas. Therapeutic options include symptomatic and supportive measures and corticosteroids as the mainstay of the treatment for ILDs occurring in these patients. In recent years, rituximab (anti-CD20) has emerged as a promising treatment for this disease, though data from controlled trials are still lacking. Pulmonary involvement may be a source of significant morbidity in these patients, though only rarely, it is the cause of death.

Tratamiento del síndrome de sjögren primario con ciclosporina-A: efectos clínicos y biológicos / Treatment of primary sjogren syndrome with ciclosporine-A: clinical an biological effects

Objetivo: Evaluar el efecto de la ciclosporina A (CsA) en el tratamiento del síndrome de Sjögren primario (SSP). Métodos: Se incluyeron nueve pacientes con SSP. Se les suministró CsA (2 mg/kg de peso) durante seis meses. Todos los pacientes fueron evaluados clínicamente cada mes. Se realizó la prueba de Schirmer y la respuesta a CsA se registró por medio de la escala visual análoga durante y después del tratamiento. En suero se determinó el factor reumatoide y los niveles de inmunoglobulinas por nefelometría y los anticuerpos anti-Ro y anti-La por análisis inmunoenzimático. En sobrenadantes de células mononucleares cultivadas por 24 y/o 48 horas. Se cuantificó la producción espontánea de IL-10 e inmunoglobulinas. La IL-10 intracelular en las subpoblaciones CD4+, CD8+, CD19+ y CD14+ fue detectada mediante citometría de flujo. Resultados: El tratamiento fue bien tolerado y sin efectos colaterales. Las manifestaciones oculares mejoraron notablemente en cinco pacientes, en forma moderada en dos, en una no hubo respuesta y en otra no fue evaluable. Las manifestaciones orales mejoraron notablemente en tres pacientes, moderadamente en cinco y en otra no hubo respuesta. Los niveles de inmunoglobulinas tanto en suero como en sobrenadante, se normalizaron en los cinco pacientes que presentaron hipergamaglobulinemia al inicio del estudio. Los niveles de IL-10 disminuyeron en siete pacientes a expensas de las células CD19+. Conclusiones: El tratamiento del SSP con CsA mostró efectos benéficos en la xerostomía y xeroftalmia, aunado a la corrección de los parámetros biológicos estudiados. Por ello la CsA podría ser una alternativa terapéutica promisoria para pacientes con SSP.

Síndrome Sjögren asociado a colagenopatías: presentación de un caso / Sjögren's syndrome associated to collagenophaties

Se describe un Síndrome Sicca en una mujer de 53 años de edad, internada en el Hospital Zenón Santillán, asociado a enfermedades del colágeno tales como: Artritis Reumatoidea, Vasculitis Leucocitoclástica y probable Tiroiditis. Los resultados de sus análisis bioquímicos, Rx de glándulas salivales, gammagrafía y la biopsia del labio inferior, confirman el diagnóstico. Se instituyó tratamiento con Bromhexina y gotas de Pilocarpina (medicación no habitual), obteniendo resultados satisfactorios.

Síndrome de Sjögren y embarazo / Sjögren's syndrome and pregnancy

Se presentan dos casos de pacientes embarazadas con síndrome de Sjögren primario destacando en una de las gestantes la asociación con flebotrombosis

Linfoma de Hodgkin primario de pulmón

Presentamos el caso de una mujer de 75 años, con artritis reumatoidea y síndrome de Sjogren, quien presenta un cuadro clínico de un año de evolución de disnea progresiva hasta el reposo acompañada de tos no productiva. La radiografía y la TAC del tórax mostraron infiltrado interticial bilateral micronodular e infiltrado de ocupación alveolar bibasal, sin la presencia de adenomegalias. Se realizó biopsia pulmonar abierta que fue demostrativa de enfermedades de Hodgkin asociada a cambios de pulmón reumatoideo (neumonia intersticial usual, UPI). No se encontró compromiso linfomatoso extratorácico en los estudios de extensión. Se discute la presentación clínica, radiológica y los hallazgos histológicos de esta infrecuente expresión de la enfermedad de Hodgkin

Corticotherapie et maladies systemiques

Corticosteroid are an essential mean to overcome systemic disorders. Thirty years ago they changed the prognosis of most of these diseases. Adverse effects are numerous and dangerous, especially infectious diseases and bone disorders. Prednisone is the most used drug. The pulse of methyprednisone is less used. In this study, we discuss some principles of the use of corticosteroid and the problems encountered using corticotherapy in systemic disorders

Influência da bromohexine sobre os níveis de lisozima da secreçäo lacrimal, o teste de rosa bengala e os sintomas oculares na síndrome de Sjögren / Influence of bromohexine on tear lysozyme level, rose-bengal test and ocular symptoms in Sjogren's syndrome

Foram estados, em 21 pacientes portadoras de Síndrome de Sjögren primária ou secundária, a influência da bromohexine sobre os níveis de lisozima da secreçäo lacrimal, teste de rosa bengala e sintomas oculares. Realizamos estudo cego com administraçäo de placebo (um comprimido por dia) e bromohexine (um comprimido de 48 mg por dia), durante 2 períodos consecutivos de 3 semanas (21 dias), com avaliaçöes do nível de lisozima lacrimal, sintomas oculares e teste de rosa bengala no dia antecedente ao ínicio do tratamento e após o uso de placebo (22§) e de bromohexine (44§ dia). Näo houve influência estatisticamente significante da bromohexine sobre os parâmetros analisados