"Dry oral and ocular manifestations and autoantibodies characteristic of primary Sjögren's syndrome in multiple sclerosis".

INTRODUCTION: The relationship between primary Sjögren syndrome (pSS) and demyelinating diseases is still not well understood. These diseases seem to coexist amidst autoimmunity, raising questions about clinical characteristics, relationship with immunomodulatory treatment, and possible common immunological background underlying their pathogenesis. OBJECTIVE: calculate the frequency of dry oral and ocular manifestations and autoantibodies characteristic of primary Sjögren's Syndrome in Multiple Sclerosis. METHODS: 202 patients with multiple sclerosis answered a questionnaire to identify complaints of xerostomia and xerophthalmia, according to diagnostic criteria for primary Sjögren's syndrome; 43 answered positively to at least one question; 27 had comorbidities or used drugs that cause dry symptoms and were excluded; 16 patients were selected for examinations for oral, ocular and serum anti-Ro/SS-A autoantibody evaluation. RESULTS: Eleven (68.75%) patients complained of xerostomia; 14 (87.5%) of xerophthalmia. Sialometry < 0.1 ml/min was observed in three (18.8%); 13 patients underwent minor salivary gland biopsy and histopathological examination: focal score > 1 in three (23.1%). Schirmer test was < 5 mm/5 min in four (25%). Lyssamine green/fluorescein dye score was > 5 in three (18.8%). Anti-Ro/SS-A > 10 UI/mm in two (12.5%). Three (1,49%) patients met current criteria for primary Sjögren's syndrome. CONCLUSIONS: Patients with MS may report xerostomia and/or xerophthalmia even in the absence of comorbidities and use of medications capable of causing these symptoms, which may fulfill the diagnostic criteria for pSS. In this study, the frequency of pSS according to current criteria was within the range observed in the literature with older criteria. But the question remains whether the association between these diseases is fortuitous or whether there is a pathogenic link.

IgG4-related orbital disease. / Enfermedad orbitaria relacionada con Ig-G4.

CASE REPORT: The case is presented of a 64-year-old woman with bilateral palpebral swelling and dacryoadenitis, exophthalmos, and a history of chronic rhinitis and asthma. An increase in serum IgG4 was observed, and an incisional biopsy of lacrimal glands was performed, which showed fibrosis and a lymphoplasmacytic infiltrate with IgG4 producing cells. DISCUSSION: Orbital involvement in IgG4-related disease is frequent. Bilateral dacryoadenitis is the most common manifestation. Histopathology is essential for the diagnosis and to exclude malignancy.

Clinical features and risk factors of neurological involvement in Sjögren's syndrome.

BACKGROUND: To investigated distinct manifestations of Sjögren's syndrome (SS) patients with neurological complications and the potential risk factors associated with neurological complications in SS, and to produce a disease evaluation and neurological involvement prediction for SS. METHODS: 566 patients who fulfilled the 2002 classification criteria for SS from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University were included in the cross-sectional study. Clinical, immunological and histological characteristics were surveyed, and potential risk factors for neurological complications were examined by multivariate analysis. RESULTS: Among 566 SS patients, 184 (32.5%) patients had neurological involvement, with more than 10% got limbs pain, limbs numbness and cerebral infarction, respectively. Of these 184 SS patients with neurological complications, secondary SS (sSS) patients had a higher prevalence of peripheral nervous system (PNS) involvement than primary SS (pSS) patients (31.1 vs. 19%). And sSS patients showed higher total ESSPRI score and higher prevalence of xerostomia and low C3, C4 levels with more liver, articular involvement and saliva gland atrophy, and more severe lymphocyte infiltration in salivary glands than pSS patients. As for the specific factors associated with neurological involvement, low C3 level were found to be significant in pSS or sSS patients who were younger 50 year old, and ANA positivity, cardiac involvement, saliva gland atrophy were demonstrated to be associated in elder pSS patients. And xerophthalmia was found to be associated in sSS patients. CONCLUSION: Low complement (C3) levels, xerophthalmia, ANA positive, cardiac involvement and labial salivary gland histological result were good ways to predict neurological complications in different subgroups of SS, which might provide insight into better clinical decision-making, especially at early stages of the disease.

Exposure keratopathy: Incidence, risk factors and impact of protocolised care on exposure keratopathy in critically ill adults.

PURPOSE: We aimed to determine the rate of exposure keratopathy (EK) in critically ill patients, identify risk factors for developing EK and ascertain the effectiveness of a protocol to prevent EK. MATERIALS AND METHODS: We undertook a two-phase prospective cohort study in a general adult ICU with first-phase being observational and an eye care protocol was introduced in the second-phase. Daily ophthalmic assessment was carried out along with recording of various risk factors. RESULTS: We studied 371 patients. In the first phase, the overall rate of EK was 21% but the rate in mechanically ventilated patients was 56%; χ2 (1, N=257)=80.8, p<0.001. Adjusted odds ratios (AOR) for development of EK was 28.6 (8.19-43.37), 13.0 (3.16-54.38) and 1.2 (1.03-1.33) with incomplete eye closure, mechanical ventilation, and higher sequential organ failure assessment score respectively. Following the introduction of the protocol, the overall rate of EK reduced to 2.6% (3 cases); χ2 (1, N=371)=18.6, p<0.001. CONCLUSIONS: EK is common in critically ill patients and a simple protocol substantially reduces the incidence of EK and is easily achieved in clinical practice.

Aspectos relevantes da síndrome de Sjõgren para o cirurgião-dentista / Sjogren’s syndrome’s relevant aspects for the dental surgeon

A síndrome de Sjõgren (SS), conhecida como síndrome sicca, é uma doença autoimune caracterizada pela hipofunção das glândulas salivares e lacrimais, cuja prevalência na população mundial é de aproximadamente 0,5% a 1%. Por ser uma doença autoimune complexa e de difícil diagnóstico, é sub-diagnosticada e sub-tratada segundo o consenso realizado em 2012 pelo Colégio Americano de Reumatologia (ACR). O Cirurgião-Dentista pode desempenhar papel importante na detecção de possíveis alterações compatíveis com a síndrome, além de auxiliar no tratamento de diversas patologias orais decorrentes da síndrome. Este trabalho tem como objetivo explanar aspectos importantes referentes ao diagnóstico e tratamento da síndrome aqui discutida. A SS apesar de ser considerada uma doença de evolução lenta, em estágios avançados pode ser fatal, principalmente por aumentar as chances dos pacientes virem a desenvolver linfoma não Hodking. O tratamento odontológico dos pacientes com SS deve principalmente ser profilático, com a recomendação do uso de repositores de saliva e controle rígido da higiene bucal.

Sjogren’s syndrome (SS), known as the sicca syndrome, is an autoimmune disease characterized by salivary and lacrimal glands hypofunction which prevalence in the world population is approximatel y around 0,5% to 1%. For being a complex autoimmune disease and with difficult diagnosis, it is sub diagnosed and miss treated according to the consensus occurred in 2012 by the American College of Rheumatology (ACR). The surgeon-dentist (SD) may play a important role on the detection of possible changes compatible to the syndrome, besides can help in the treatment of many oral pathologies caused by the syndrome. This work has the main purpose to explain the important aspects regards to the correct diagnosis and treatment of this syndrome.The SS besides been considered a slow evolution disease, in advanced stages it can be fatal,mainly for increasing the patient’s chances of developing non-Hodking lymphoma. The dental treatment of patients with SS must be prophylactic, with the recomedations of the use of salivary replenishing and careful control of the oral hyigiene.

[Progression of treatment and researches in dry age related macular degeneration].

Age related macular degeneration (AMD) is the leading cause of blindness and visual disability among old patients in Europe and North America. AMD has been divided into two broad clinical categories depending on whether there is a presence of abnormal neovascularization: neovascular (exudative or wet) AMD and dry (or geographic atrophic) AMD. VEGF has been understood as a pathogenesis of wet AMD which allows us to get breakthroughs in treatment. While the progression of dry AMD treatment is very slow because the lack of pathogenesis, no acute loss of vision, and without appropriate standards for treatment. This review tries to introduce about the recent researches and progressions for dry AMD treatment.

Xerophthalmia in a traditional Quran boarding school in Sudan.

PURPOSE: To determine the prevalence of xerophthalmia at a traditional boarding school where children do not receive a diet adequate in vitamin A. MATERIALS AND METHODS: A cross-sectional survey of 406 males residing in a Quranic traditional school was conducted using the World Health Organization xerophthalmia checklist. The association between the prevalence of night blindness and proportion of students staying at the school for 6 consecutive months and those eating solely at the school was investigated. The difference in age between children with night blindness and those without was investigated. Statistical significance was indicated by P<0.05. RESULTS: The prevalence of night blindness, conjunctival xerosis and Bitot's spots was 24%, 12.5% and 1%, respectively. None of the boys had corneal ulceration, corneal scars and corneal xerosis. No significant association was observed between the differences in mean age and development of night blindness (P=0.657). There was a significant association between the duration of stay (cut-off of 6 months continuously) at the institute and the development of night blindness (P=0.023). There was no statistical significance between regularly eating at the maseed and outside the "maseed" and the development of night blindness (P=0.75). CONCLUSION: Children residing at a traditional school are vulnerable to developing xerophthalmia where the diet is inadequate in vitamin A. Institutional caregivers should be made aware of the importance of providing a balanced diet rich in vitamin A. Institutional caregivers should also be educated on the signs and symptoms of vitamin A deficiency for early detection of xerophthalmia.

Cytokines in tear fluid of patients with ocular graft-versus-host disease after allogeneic stem cell transplantation.

PURPOSE: To investigate the profile of cytokines in tear fluid of patients after allogeneic stem cell transplantation (allo-SCT) and determine their relation to the presence and manifestations of ocular graft-versus-host disease (GvHD). METHODS: In this cross sectional study tear fluid was collected in 34 consecutive adult patients that previously underwent allo-SCT (16 with ocular GvHD and 18 without) and 16 age- and gender-matched healthy controls using the Schirmer test under local anesthesia. Tear fluid was analyzed by multiplex immunoassay for the presence of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ. Levels of measured cytokines were correlated with the findings in slit lamp examination and the Ocular Surface Disease Index (OSDI). RESULTS: The levels of IL-6 and IFN-γ in tear fluid in ocular GvHD patients were significantly elevated in comparison to patients without ocular GvHD and healthy controls (p<0.005 for each) The levels of IFN-γ correlated with the Schirmer score (r=-0.48, p<0.0001) and tear break up time (TBUT; r=-0.38, p=0.03). Tear IL-6 levels correlated with complaints of dry eyes (r=0.39, p=0.02), tear production (r=-0.59, p<0.0001), fluorescent staining of the cornea (r=0.42, p=0.01), and with the OSDI score (r=0.40, p=0.005). CONCLUSIONS: IL-6 and IFN-γ were elevated in tear fluid of patients with ocular GvHD and correlated with different symptoms of dry eye disease, suggesting that IFN-γ is elevated during the early stages and IL-6 is involved in later stages of ocular GVHD and exhibits moreover an association with its severity.

[Sjögren's syndrome: diagnosis and systemic manifestations]. / Circonstances de découverte et manifestations systémiques du syndrome de Gougerot-Sjögren.

Sjögren's syndrome is an autoimmune exocrinopathy characterized by keratoconjunctivis sicca, xerostomia and immune-inflammatory systemic manifestations. The diagnosis is easy to establish when the patient presents with sicca complex as a main symptom, or recurring attacks of parotitis. However, it is way more complex when the disease begins with extraglandular features, such as non erosive polyarticular arthritis, Raynaud's phenomenon, peripheral or central nervous system involvement, kidney disease or interstitial pneumonary disease, or even vasculitis. In such circumstances, diagnosis is often delayed several years.

Hereditary gelsolin amyloidosis mimicking Sjögren's syndrome.

Hereditary gelsolin amyloidosis (AGel amyloidosis) belongs to the wide group of amyloidotic diseases, which comprise various hereditary but also sporadic forms, such as inflammation-associated AA amyloidosis, primary or myeloma-associated AL amyloidosis and common Alzheimer's disease and type II diabetes-associated local amyloidoses. AGel amyloidosis caused by a gelsolin G654A gene mutation is autosomally dominantly inherited and presents typically in the 30s with progressive corneal lattice dystrophy, followed by cutis laxa and cranial polyneuropathy. Here, we present a case of sicca syndrome, originally diagnosed as primary Sjögren's syndrome (SS) but later found to represent an initial disease manifestation of AGel amyloidosis, not recognised earlier. This case emphasises both the importance of specific amyloid stainings and comprehensive salivary gland histopathology as well as family history in SS differential diagnostics.

Ocular surface injuries in autoimmune dry eye. The severity of microscopical disturbances goes parallel with the severity of symptoms of dryness.

Autoimmune dry eye (Sjögren's syndrome, SS) is a chronic systemic disease characterized by salivary and lacrimal gland inflammation and tissue damage leading to keratoconjunctivitis sicca and xerostomia. In this review attention has been devoted to the cause of the development of oxidative injuries of the ocular surface of patients suffering from SS. It was shown that lacrimal glands and diseased conjunctival epithelium reveal increased expression of pro-inflammatory cytokines which are released into the tear fluid. A high amount of pro-inflammatory cytokines highly induce the elevated expression and activity of enzymatic systems that generate reactive oxygen and nitrogen species. An abundant amount of these toxic products leads to a decrease in antioxidants and to the formation of cytotoxic related oxidants, such as peroxynitrite. All these factors, together with reactive oxygen species from polymorphonuclear leukocytes, contribute to the development of oxidative injuries at the ocular surface. From the clinical point of view it is important that the level of severity of the above described microscopical disturbances found in conjunctival epithelial cells goes parallel with the level of severity of dry eye symptoms.

A novel scraping cytology score system (SCSS) grades inflammation in dry eye patients.

PURPOSE: We propose a conjunctival Scraping Cytology Scoring System (SCSS) as a reliable method to diagnose and score ocular surface inflammation in dry eye. METHODS: Twenty normal subjects and 46 patients with dry eye of various severities were included in the study. Clinical signs were scored 1-4; an Ocular Surface Disease Index (OSDI) questionnaire was used to grade subjective symptoms. Concentrations of serum albumin and interleukin-6 (IL-6) in tears were evaluated. Scraped conjunctival cytology samples were processed and examined with light microscopy. The number of inflammatory cells was staged and sub-scores were assigned. SCSS resulted from their sum and ranged from 0-12. Statistical evaluation was performed by applying the unpaired Student's t-test and the Spearman's correlation test (significance p < 0.05). SCSS was also analyzed for sensitivity, specificity, ROC curves, likelihood ratio LR+, positive (PPV) predictive value. RESULTS: SCSS was positively correlated to clinical sign score, OSDI score, exudated serum albumin, and IL-6 in either control (Spearman's correlation test always p < 0.05) and in dry eye patients (respectively, p < 0.0001, p < 0.01, p < 0.05, and p < 0.0001). SCSS >or= 4 was selected as the cut-off value for moderate dry eye (LR+ 10,9; PPV 22,5), SCSS >or= 9 was selected as the cut-off value for severe dry eye (LR+ 15,6; PPV 26,2). CONCLUSIONS: SCSS can be applied in any trained laboratory. It is correlated with clinical signs and symptoms, and it shows a diagnostic performance to grade inflammation in dry eye, comparable to more expensive cytokine assay.

Hydroxypropyl cellulose ophthalmic inserts (lacrisert) reduce the signs and symptoms of dry eye syndrome and improve patient quality of life.

PURPOSE: A multicenter, 2-visit, open-label, 4-week study was conducted to determine the acceptability of hydroxypropyl cellulose ophthalmic inserts in adult patients with a history of dry eye syndrome (DES). METHODS: At visit 1, patients (N = 520) were evaluated, screened by slit-lamp biomicroscopy, and completed the Ocular Surface Disease Index (OSDI), a validated measure of quality of life. Patients were trained in the proper placement and use of hydroxypropyl cellulose ophthalmic inserts and were contacted by telephone on day 3 of the study. At week 4, patients were given a clinical evaluation and completed a second questionnaire. Answers determined changes in symptoms and quality of life. Adverse events were monitored throughout the study. RESULTS: Four hundred eighteen patients completed the study and reported significant improvements in discomfort, burning, dryness, grittiness, stinging, and light sensitivity (P = .05) after 4 weeks use of hydroxypropyl cellulose ophthalmic inserts. Significant improvements in clinical signs (keratitis, conjunctival staining, and tear volume) were reported. Contact lens wearers reported significant improvements similar to nonwearers, with a strong trend toward improvement in light sensitivity. Mean OSDI total scores, measuring quality of life, significantly improved by 21.3% (from 41.8 +/- 22.38 to 32.9 +/- 21.97, P < or = .0215). The most commonly reported adverse event leading to discontinuation was blurred vision, observed in 8.7% of patients (n = 45). Compliance during the study was good; 41.5% of subjects were fully compliant. Of the 58.5% of subjects who missed doses, the majority (69.4%) missed only one to five. CONCLUSIONS: Hydroxypropyl cellulose ophthalmic inserts significantly reduced symptoms and clinical signs of moderate to severe DES. They also significantly improved DES in patients wearing contact lenses. Patients experienced a statistically significant improvement in quality of life, as measured by the OSDI, of 21.3%.

Anti-Ro/SSA antibodies in rheumatoid arthritis: clinical and immunologic associations.

OBJECTIVE: To assess the prevalence of anti-Ro/SSA in RA and to analyse clinical and serological features of anti-Ro/SSA positive patients with RA. METHODS: 195 consecutive patients affected by RA were studied by counterimmunoelectrophoresis and ELISA for the detection of anti-Ro/SSA antibodies. Anti-Ro were found in 12 patients, with a prevalence of 6%. These 12 patients were pooled with other 15 patients known to have anti-Ro/SSA antibodies and RA, in order to evaluate their clinical and laboratory features. RESULTS: Anti-Ro positive patients showed a common pattern of joint involvement at onset and a comparable progression of disease compared to anti-Ro negative subjects. In addition, extra-articular manifestations (such as xerophthalmia, xerostomia, scleritis, oral ulcers and amyloidosis) and peculiar autoantibody profile (hypergammaglobulinemia, anti-dsDNA and AMA) were found significantly associated to anti-Ro/SSA positivity. Even though DMARDs withdrawals were more frequently detected in anti-Ro/SSA patients, especially when using gold salts, no statistical difference between the two groups was detected. In addition, anti-TNFalpha treatment did not cause further progression of autoimmunity neither on laboratory nor on clinical ground. CONCLUSION: Anti-Ro/SSA can be detected in about 6% of patients affected by RA. These patients presented a peculiar clinical picture characterised by extra-articular manifestations some of which are known to be anti-Ro/SSA correlated, while others are more disease-specific (amyloidosis, episcleritis). Anti-Ro/SSA are significantly associated with other autoantibodies not specific for RA such as anti-dsDNA and AMA. Treatment with anti-TNF drugs did not cause further progression of autoimmunity neither on laboratory nor on clinical ground.