Severe extra-glandular involvement and pleural effusions complicating primary Sjogren's syndrome: a case report.

BACKGROUND: Sjogren's syndrome, an autoimmune disease of the exocrine glands, results in keratoconjunctivitis sicca, xerostomia, and dental caries. It is often overlooked, considered by clinicians to be a benign disease. However, it can cause life-threatening extra-glandular complications that affect multiple organ systems. CASE PRESENTATION: Here we present a 78-year-old Caucasian woman with a history of primary Sjogren's syndrome (pSS) whose symptoms of keratoconjunctivitis sicca were managed managed conservatively. She was evaluated for sub-acute shortness of breath. Imaging showed severe bronchiectasis with features of lymphocytic interstitial pneumonia. She also had exudative bilateral pleural effusions and skin ulcers, likely vasculitic in origin. The workup was significant for anti-Ro antibody, pancytopenia, hypocomplementia, cryoglobulinemia and monoclonal gammopathy, all of which reflect disease severity. Although there was no evidence of malignancy, she developed B-cell non-Hodgkin lymphoma during follow-up. CONCLUSIONS: Primary Sjogren's syndrome can result in severe multi-organ disease. Pleural effusions are a rare complication of pSS, with only ten cases reported in the literature over the last 30 years, and tend to respond well to steroids. Prognostic biomarkers for disease severity include hypocomplementia, cryoglobulinemia, monoclonal gammopathy, and hypergammaglobulinemia. In this report we review the literature and the management of the disease.

Minor salivary gland transplantation for severe dry eye disease due to cicatrising conjunctivitis: multicentre long-term outcomes of a modified technique.

AIM: To report the clinical outcomes of autologous minor salivary gland transplantation (MSGT) for the treatment of severe dry eye disease caused by cicatrising conjunctivitis. METHODS: This was a retrospective case series of patients undergoing MSGT at four different centres from 2016 to 2018. The technical modifications included en bloc harvesting of a 20 mm×15 mm mucosa-gland-muscle complex and fixation of the glands to the superior bulbar surface anchored to the superior rectus muscle. The primary outcome measure was improvement in best-corrected visual acuity (BCVA). Secondary outcome measures were change in Schirmer test scores and grades of conjunctival and corneal fluorescein staining, grades of corneal neovascularisation, opacification and keratinisation. RESULTS: 21 eyes of 19 patients underwent MSGT, with a median follow-up duration of 3 years. The median BCVA improved from a baseline value of 20/500 to 20/125 at 1 year (p=0.0004) and 20/80 at 3 years (p=0.0002) after surgery. The proportion of cases with BCVA ≥20/200 improved from 38% at baseline to 67% at 1 year (p=0.0294), 78% at 2 years (p=0.0227) and 93% at 3 years (p=0.0015) after surgery. There was a significant improvement (p<0.0036) in Schirmer scores, conjunctival and corneal staining scores as well as grades of corneal neovascularisation and opacification after surgery. There were no serious sight-threatening complications in the transplanted eyes or at the donor site. CONCLUSIONS: Long-term improvement in the visual acuity, ocular surface environment, and keratopathy was noted after MSGT performed in severely dry eyes using a modified technique.

[Oxidative stress correction in the treatment of severe keratoconjunctivitis sicca in patients with Sjorgen's syndrome]. / Korrektsiia oksidativnogo stressa v lechenii tiazhelykh form sukhogo keratokon''iunktivita pri sindrome Shegrena.

PURPOSE: To evaluate the antioxidative effect of artificial tears in the treatment of keratoconjunctivitis sicca (KCS). MATERIAL AND METHODS: The study included 43 patients (60 eyes) with severe KCS: 38 women (50 eyes) and 5 men (10 eyes) aged from 27 to 76 years (in average 52 years). Patients were randomly divided into 2 groups; all patients used therapeutic silicone hydrogel soft contact lens (SCL) and instillations of 0.05% Cyclosporin A (CyA) 2 times a day. Patients of the first group (22 people, 30 eyes) used 0.15% hyaluronic acid. In the second group, patients (21 people, 30 eyes) used a tear substitute with similar surface-active component, but with antioxidant properties. The results of the treatment were evaluated using basic and additional research methods at 1, 3, 6 and 12 months. RESULTS: Corneal epithelialization was achieved after 1 month of conservative treatment in all patients who wore SCLs and were treated with instillations of 0.05% CyA and artificial tears. Then the lenses were removed and the patients were switched to instillations of CyA and artificial tears. Comparative analysis of the results showed that higher functional indicators were achieved in the second group, where patients used Artelac Rebalance drops with antioxidant properties. CONCLUSION: Improvement of clinical and functional parameters in the treatment of severe forms of KCS was achieved by direct action on both links of pathogenesis with minimal amounts of the drugs and the frequency of their use. Subsequent supportive therapy contributed to stabilization of the results and further increase of the functional parameters.

Optimising tear replacement rheology in canine keratoconjunctivitis sicca.

Dry eye is a substantial problem in a large number of human and canine patients. Numerous laboratory models for tear deficiency exist using genetically predisposed rodent models, animals treated with topical anti-muscarinics, or those kept in environments with increased air flow to produce the ocular surface changes seen in human patients. Canine keratoconjunctivitis sicca, seen in many thousands of dogs kept as companion animals, can provide a valuable spontaneous model for testing tear replacement medications that might better model disease in human patients, existing as it does in an outbred population that live in the same environments as their owners. Here the development of a crosslinked hyaluronic acid topical drop is described together with the results of trials on dogs with spontaneous keratoconjunctivitis sicca. Although hyaluronic acid in its native form in tear replacement drops shows a Newtonian rheology, the crosslinked product described here behaves in a non-Newtonian manner, with the same shear thinning shown by the tear film itself. The crosslinked product thus shows itself as a potentially valuable tear replacement medication for the human dry eye population as well as for dogs with the same condition.

Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia.

INTRODUCTION: "Dry eye" or "keratoconjunctivitis sicca" is a multifactorial disease estimated to have a worldwide prevalence of 5-33%. Conventional therapies targeting the ocular surface with artificial tears, anti-inflammatories, punctal closure, eyelid hygiene, and antibiotics do not provide relief in all patients, especially those with neuropathic-like ocular complaints (wind hyperalgesia and photophobia). We anticipated that ocular transcutaneous electrical nerve stimulation (TENS) would alleviate symptoms of ocular pain, photophobia, and dryness in these latter individuals. METHODS: All individuals who received electrical stimulation between May 10, 2016 and April 6, 2017 for the treatment of chronic ocular pain at the oculofacial pain clinic of the Miami Veterans Administration Hospital were included in this retrospective review. All patients had symptoms of dryness along with other neuropathic-like symptoms (e.g., photophobia) and minimal signs of tear dysfunction. Ocular pain intensity, symptoms of dryness, and light sensitivity were compared pre-treatment and five min post-treatment via a two-tailed paired Student's t-test. RESULTS: The use of TENS significantly reduced the mean pain intensity in both the right and left eyes five min after treatment compared to prior to treatment (p < 0.05, paired t-test). The use of TENS significantly decreased light sensitivity in both eyes (p < 0.05). The findings for symptoms of dryness, however, were equivocal with a significant decrease in the left eye but not the right (p < 0.05, paired t-test). DISCUSSION: Our data indicate that TENS may similarly provide analgesia in patients with dry eye symptoms as it does for many other chronic pain conditions. Furthermore, the noted effect on symptoms of photophobia and dryness suggest that all may be linked by similar trigeminal-thalamic-cortical pathways. Prospective studies with electrical stimulation of dry eye are needed to further elucidate its benefit and mechanism of action.

The Use of Conjunctival Pedicle Flaps to Prevent Corneal Perforation in Graft-Versus-Host Disease.

PURPOSE: We report the clinical outcomes of two chronic graft-versus-host disease (cGVHD) corneal thinning cases that were successfully treated with conjunctival pedicle flaps in an effort to prevent impending corneal perforation. METHODS: The patients were treated with topical and systemic corticosteroids, therapeutic contact lenses, lubricants, and punctual plugs. Conjunctival pedicle flaps were used because conventional treatments had failed, and corneal perforation was imminent. RESULTS: Both patients were successfully treated with conjunctival pedicle flaps. Following conjunctival flap removal, one patient had corneal clarity restored following penetrating keratoplasty. CONCLUSIONS: Conjunctival pedicle flaps provided a strong barrier for the corneal surface and stabilized anterior chamber in cGVHD patients with impending corneal perforation following allogeneic hematopoietic stem cell transplant.

Avaliação de células T regulatórias e pefil de ativação de linfócitos T na ceratoconjuntivite seca associada ao HTLV-1 / Regulatory T cells evaluation and T lymphocyte activation profile in keratoconjunctivitis sicca associated with HTLV-1

O HTLV-1 é o agente etiológico da leucemia /linfoma de células T do adulto (ATLL), da paraparesia espástica tropical/ mielopatia associada ao HTLV-1 (HAM/TSP) e da uveíte. Além destas, a ceratoconjutivite seca (CCS), doença multifatorial da lágrima e da superfície ocular, tem sido descrita com maior frequência em indivíduos infectados pelo HTLV-1. Assim como em outras doenças associadas, a CCS tem sido relacionada a uma elevada carga proviral. As células T regulatórias (Treg) são importantes na manutenção da homeostase do sistema imunológico e um comprometimento da imunorregulação exercido por elas pode contribuir para o ambiente inflamatório observado na CCS. Este estudo objetivou avaliar os linfócitos Treg de pacientes com CCS associada à infecção pelo HTLV-1. Foram realizados ensaios de imunofenotipagem por citometria de fluxo para avaliar a frequência de linfócitos T ativados (HLA-DR+) e de células T CD4+ e CD8+ regulatórios (FOXP3+), bem como a produção de IL-10 e TGF-β por estas células. Foram avaliados 37 pacientes infectados pelo HTLV-1 e assintomáticos para HAM/TSP, sendo 27 com diagnóstico positivo para a manifestação ocular (CCS), 10 com diagnóstico negativo (ASS), além de 17 voluntários não infectados pelo vírus (NI). As frequências de linfócitos T CD4+FOXP3+, CD8+FOXP3+, CD4+HLA-DR+ e CD8+HLA-DR+ foram significativamente maiores nos grupos CCS e ASS, quando comparados aos indivíduos não infectados. Quanto à produção das citocinas imunossupressoras, foi observada uma maior frequência de linfócitos T CD4+FOXP3+ duplo produtores de IL-10 e TGF-β no grupo CCS quando comparado ao grupo ASS. Com relação aos linfócitos CD8+FOXP3+, o grupo CCS apresentou uma maior frequência de células mono produtoras de IL-10 quando comparado ao ASS. Nossos resultados sugerem que a menor frequência de células Treg CD8+ produtoras de TGF-β em indivíduos infectados pelo HTLV-1 com CCS, pode contribuir para a intensificação da ativação celular e fisiopatologia da doença.

HTLV-1 is the causative agent of leukemia/lymphoma adult T-cell (ATLL), tropical spastic paraparesis / myelopathy associated with HTLV-1 (HAM / TSP) and uveitis. In addition, keratoconjunctivitis sicca (KCS), a multifactorial disease of the tear and of the ocular surface, has been more frequently reported in patients infected with HTLV-1. As for other HTLV-1-associated diseases, KCS has been related to a high proviral load. Regulatory T (Treg) cells are important in maintaining the homeostasis of the immune system. An impairment in the immunoregulation function of Treg may contribute to the inflammatory environment observed in the KCS. This study aimed to evaluate the Treg cells of patients with KCS associated with HTLV-1. Frequency of activated T cells (HLA-DR+) and CD4+ and CD8+ Treg cells (FOXP3+), as well as IL-10 and TGF-β production by Treg were quantified using flow cytometry. Thirty-seven HTLV-1 individuals were included (27 asymptomatic for HAM/TSP with positive diagnosis of ocular manifestation (KCS), 10 with negative diagnosis (ASS - asymptomatic). Seventeen non-infected individuals were included as controls (NI). The frequencies of CD4+ FOXP3+ T cells, CD8+FOXP3+, CD4+HLA-DR+ and CD8+HLA-DR+ were significantly higher in KCS and ASS groups when compared to non-infected individuals. As the production of immunosuppressive cytokines, a higher frequency of CD4+ FOXP3+ double producers of IL-10 and TGF-β in the KCS group was observed when compared to group ASS. Regarding the CD8+FOXP3+ lymphocytes, the KCS group had a higher frequency of mono cells producing IL-10 when compared to the ASS. Our results suggest that the lower frequency of Treg cells CD8+ TGF-β-producing in individuals infected with HTLV-1 with KCS, may contribute to the intensification of cellular activation and pathophysiology of the disease.

Uveodermatologic syndrome concurrent with keratoconjunctivitis sicca in a miniature poodle dog.

A 5-year-old, intact female miniature poodle dog was presented with chronic ophthalmic problems, facial poliosis, nasal depigmentation and multiple areas of alopecia over the trunk. Bilateral uveitis preceded dermatologic signs by 5 months and gradually worsened. The dog was diagnosed as having uveodermatologic syndrome (UDS) concurrent with keratoconjunctivitis sicca (KCS). Treatment with immunosuppressive drugs resolved the dermatologic lesions, but uveitis continued to progress.

Syndrome uvéodermatologique concomitant à une kératoconjonctivite sèche chez un caniche miniature. Une chienne caniche miniature intacte âgée de 5 ans a été présentée avec des problèmes ophtalmiques chroniques, une poliose faciale, une dépigmentation nasale et plusieurs plaques d'alopécie sur le tronc. L'uvéite bilatérale a précédé les signes dermatologiques 5 mois auparavant et elle s'est graduellement aggravée. La chienne a été diagnostiquée comme atteinte du syndrome uvéodermatologique concomitant à une kératoconjonctivite sèche. Le traitement avec des immunodépresseurs a résolu les lésions dermatologiques, mais l'uvéite a continué de progresser.(Traduit par Isabelle Vallières).

Neutralization of ocular surface TNF-α reduces ocular surface and lacrimal gland inflammation induced by in vivo dry eye.

PURPOSE: The purpose of this study was to investigate the effectiveness of tumor necrosis factor (TNF)-α blocker for treatment of dry eye (DE)-induced inflammation and determine a more effective method to suppress lacrimal gland inflammation. Efficacy of topical versus systemic administration of TNF-α blockers was determined using a murine dry eye (DE) model. METHODS: The TNF-α blocker HL036 was developed by modification of the TNF receptor I. Protein purity, binding affinity, and clearance of TNF-α was compared with etanercept. Using DE-induced C57BL/6 mice, corneal erosion and goblet cell counts were measured after subcutaneous or topical treatment with etanercept or HL036. Inflammatory cytokines in cornea and lacrimal glands were determined by quantitative RT-PCR and ELISA. RESULTS: HL036 showed TNF-α binding affinity comparable to etanercept, as measured by surface plasmon resonance. HL036 concentration was significantly higher in cornea and anterior segment than etanercept and effectively eliminated TNF-α on ocular surfaces. Etanercept was preferentially concentrated in the posterior segment. Corneal erosion and goblet cell counts were improved only with topically applied etanercept and HL036. Ocular surface IFN-γ, IL-6, and IL-21 were significantly decreased by topical HL036. DE-induced lacrimal gland IFN-γ and IL-6 expression was effectively suppressed by topical etanercept and HL036. CONCLUSIONS: Topical TNF-α blockers effectively suppressed lacrimal gland and corneal inflammation by suppressing IFN-γ, IL-21, and IL-6. Differences in TNF-α affinity, clearance, and local concentration of blockers may account for the anti-inflammatory effects in different ocular regions.

Disruption of TGF-ß signaling improves ocular surface epithelial disease in experimental autoimmune keratoconjunctivitis sicca.

BACKGROUND: TGF-ß is a pleiotropic cytokine that can have pro- or anti-inflammatory effects depending on the context. Elevated levels of bioactive TGF-ß1 in tears and elevated TGF-ß1mRNA transcripts in conjunctiva and minor salivary glands of human Sjögren's Syndrome patients has also been reported. The purpose of this study was to evaluate the response to desiccating stress (DS), an experimental model of dry eye, in dominant-negative TGF-ß type II receptor (CD4-DNTGFßRII) mice. These mice have a truncated TGF-ß receptor in CD4(+) T cells, rendering them unresponsive to TGF-ß. METHODOLOGY/PRINCIPAL FINDINGS: DS was induced by subcutaneous injection of scopolamine and exposure to a drafty low humidity environment in CD4-DNTGFßRII and wild-type (WT) mice, aged 14 weeks, for 5 days. Nonstressed (NS) mice served as controls. Parameters of ocular surface disease included corneal smoothness, corneal barrier function and conjunctival goblet cell density. NS CD4-DNTGFßRII at 14 weeks of age mice exhibited a spontaneous dry eye phenotype; however, DS improved their corneal barrier function and corneal surface irregularity, increased their number of PAS+ GC, and lowered CD4(+) T cell infiltration in conjunctiva. In contrast to WT, CD4-DNTGFßRII mice did not generate a Th-17 and Th-1 response, and they failed to upregulate MMP-9, IL-23, IL-17A, RORγT, IFN-γ and T-bet mRNA transcripts in conjunctiva. RAG1KO recipients of adoptively transferred CD4+T cells isolated from DS5 CD4-DNTGFßRII showed milder dry eye phenotype and less conjunctival inflammation than recipients of WT control. CONCLUSIONS/SIGNIFICANCE: Our results showed that disruption of TGF-ß signaling in CD4(+) T cells causes paradoxical improvement of dry eye disease in mice subjected to desiccating stress.

The complexity of Sjögren's syndrome: novel aspects on pathogenesis.

In Sjögren's syndrome, like in most other autoimmune diseases, the enigma leading to a pathogenic attack against self has not yet been solved. By definition, the disease must be mediated by specific immune reactions against endogenous tissues to qualify as an autoimmune disease. In Sjögren's syndrome the autoimmune response is directed against the exocrine glands, which, as histopathological hallmark of the disease, display persistent and progressive focal mononuclear cell infiltrates. Clinically, the disease in most patients is manifested by two severe symptoms: dryness of the mouth (xerostomia) and the eyes (keratoconjunctivitis sicca). A number of systemic features have also been described and the presence of autoantibodies against the ubiquitously expressed ribonucleoprotein particles Ro (Sjögren's-syndrome-related antigen A - SSA) and La (SSB) further underline the systemic nature of Sjögren's syndrome. The original explanatory concept for the pathogenesis of Sjögren's syndrome proposed a specific, self-perpetuating, immune mediated loss of acinar and ductal cells as the principal cause of salivary gland hypofunction. Although straightforward and plausible, the hypothesis, however, falls short of accommodating several Sjögren's syndrome-related phenomena and experimental findings. Consequently, researchers considered immune-mediated salivary gland dysfunction prior to glandular destruction and atrophy as potential molecular mechanisms underlying the symptoms of dryness in Sjögren's syndrome. Accordingly, apoptosis, fibrosis and atrophy of the salivary glands would represent consequences of salivary gland hypofunction. The emergence of advanced bio-analytical platforms further enabled the identification of potential biomarkers with the intent to improve Sjögren's syndrome diagnosis, promote the development of prognostic tools for Sjögren's syndrome and the long-term goal to identify possible processes for therapeutic treatment interventions. In addition, such approaches allowed us to glimpse at the apparent complexity of Sjögren's syndrome.

[Keratoconjunctivitis sicca during folicular conjunctivitis in adult patients with Chlamydia pneumoniae etiology (summarizing twelve years study)]. / Keratoconjunktivitis sicca (KCS) pri folikulární konjunktivitide u dospelých pacientu s etiologií Chlamydia pneumoniae (souhrnná dvanáctiletá studie).

AIM: Following the previous study observing keratoconjunctivitis sicca (KCS) after treated follicular conjunctivitis of chlamydial etiology from the years 1999-2002, at this time the authors would like to point out the possible connection between KCS appearance and Chlamydia pneumoniae infection. MATERIAL: In the Department of Ophthalmology, during the period of 12 months (in the years 2009 - 2010), there were treated 11 adult patients (6 women and 5 men) in the age of 28 - 81 years (median, 50 years) with follicular conjunctivitis lasting on average 2.5 years and caused by Chlamydia pneumoniae, and simultaneously were diagnosed the symptoms of KCS, out of the total number of 37 examined patients with similar clinical findings. METHODS: The diagnosis of chlamydial infection in clinical symptoms of follicular conjunctivitis and simultaneous signs of KCS was established partly according to the serologic positivity of chlamydial genus (anti-LPS) and/or species (anti-Ch. pneumoniae and anti-Ch. trachomatis) IgG, IgM, and IgA antibodies together with simultaneous anti-cHSP60 IgG positivity, further using conjunctival prints examined by means of indirect immunofluorescence method using specific monoclonal antibodies; in conjunctival smears and peripheral leucocytes was tested also the presence of Chlamydia pneumoniae DNA. The main subjective complaints of the patients were burning sensation, sticking, or foreign-body sensation; the itching and lacrimation were less common. Among clinical signs dominated the hyperemia and the edema of the lower fornix; the tortuosity of the vessels and the follicles were not always present. The KCS diagnosis was confirmed by Bengal rose staining. RESULTS: In 10 patients, the positive IgA and/or IgM anti-Ch. pneumoniae antibodies were detected. Simultaneously, the positive anti-cHSP60 IgG were confirmed, out of them medium- and high-positive findings were in 7 patients, and anti-LSP antibodies IgA and/or IgM in 8 of them. Positive smears were found in 6 patients. In 2 persons of this group of treated patients, the general serologic findings were not significant, but the Chlamydia pneumoniae infection was confirmed by Chlamydia pneumoniae DNA positivity in peripheral leucocytes; in these 2 patients, the symptoms lasted for one half of the year. As the side findings were the confirmations of active Chlamydia trachomatis infection in other 4 patients of the whole group. The patients with Chlamydia pneumoniae infection were treated systemically by macrolide antibiotic azithromycine for 12 days. After the treatment, above all else the clinical signs of conjunctival inflammation disappeared, but remained KCS symptoms, which were disappearing only slowly. The optimal supporting therapies were lubricant drops with different concentration of sodium hyaluronide without preservatives. Control microbiological examinations during 6 months after the treatment termination confirmed negative smears findings, but the antibody levels were not decreased significantly. CONCLUSION: This study confirmed the possible connection between the KCS and Chlamydia pneumoniae infection in simultaneous clinical signs of follicular conjunctivitis. Along with that the study pointed out the necessity of simultaneous evaluating of the microbial findings and clinical symptoms to consider the systemic antibiotic treatment.

Sicca symptoms, and lacrimal and salivary flow in Albanian patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis affects primarily the synovial joints, but is often accompanied by extra-articular manifestations, including lacrimal and salivary gland involvement. The aim of the present study was to estimate the prevalence of ocular and oral sicca symptoms and reduced lacrimal and salivary flow in rheumatoid arthritis and the relation between sicca symptoms and objective measures of lacrimal and salivary flow. METHODS: We examined 88 consecutive hospitalized patients with rheumatoid arthritis and 88 age- and gender-matched healthy controls. The examination included the standardized questionnaire for keratoconjunctivitis sicca and xerostomia which forms part of the European criteria for Sjögren's syndrome, the Schirmer's I test and measurement of unstimulated whole salivary flow rate. RESULTS: A significantly higher proportion of patients (40.9%) reported ocular sicca symptoms than healthy matched controls (8.0%). Further, a significantly higher proportion of patients (44.3%) reported oral sicca symptoms compared to controls (13.6%). 48.9% of the patients had low Schirmer I score, compared to 20.5% of controls. Reduced salivary flow was found in 27.3% of patients, compared to 9.1% of controls. The differences in lacrimal and salivary flow between patient and control group were statistically significant. The minimum prevalence of secondary Sjögren's syndrome was 14.8%. Weak association was observed between sicca symptoms and the objective measures of lacrimal and salivary flow in patients, and no association was detected in control subjects. CONCLUSIONS: Sicca symptoms and reduced lacrimal and salivary flow were common manifestations in rheumatoid arthritis and should be given adequate consideration during management of patients with rheumatoid arthritis.

Anticentromere antibody positive Sjögren's Syndrome: a retrospective descriptive analysis.

INTRODUCTION: A subgroup of patients with primary Sjögren's Syndrome (SS) and positive anticentromere antibodies (ACA) were recognized as having features intermediate between SS and systemic sclerosis (SSc). Our goal was to describe this group clinically and serologically and define its tendency to evolve to full blown SSc. METHODS: Among 535 patients with primary SS we identified 20 ACA positive (ACA+/SS). We compared them to 61 randomly selected ACA negative SS patients (ACA-/SS), 31 ACA positive SSc patients with sicca manifestations [SSc/(+) sicca] and 20 ACA positive SSc patients without sicca manifestations [SSc/(-) sicca]. RESULTS: Prevalence of ACA among SS patients was 3.7%. Cases and controls did not differ in sex ratio and age at disease onset. ACA+/SS patients had a lower prevalence of dry eyes, hypergammaglobulinaemia, anti-Ro and anti-La antibodies and a higher prevalence of Raynaud's phenomenon and dysphagia compared to ACA-/SS patients. They also had lower prevalence of telangiectasias, puffy fingers, sclerodactyly, Raynaud's phenomenon, digital ulcers and gastroesophageal reflux in comparison to both of the SSc subgroups and a lower prevalence of dyspnoea and lung fibrosis compared to the SSc/(+) sicca subgroup. Two patients originally having ACA+/SS evolved to full blown SSc. Four deaths occurred, all among SSc patients. Kaplan Meier analysis showed a significant difference between cases and controls in time from disease onset to development of gastroesophageal reflux, telangiectasias, digital ulcers, arthritis, puffy fingers, xerostomia, hypergammaglobulinaemia and dysphagia. CONCLUSIONS: ACA+/SS has a clinical phenotype intermediate between ACA-/SS and SSc and shows little tendency to evolve to SSc.

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.

Idiopathic sclerosing peritonitis.

Sclerosing encapsulating peritonitis (SEP) is a rare complication of chronic peritoneal dialysis and beta-blocker (practolol) usage. The authors report a case of idiopathic SEP developing in a 39-year-old woman with associated ovarian cysts and kerato-conjunctivitis sicca syndrome. These associations have not been reported previously. The histological diagnosis of SEP was made after laparotomy for intestinal obstruction. The patient continues to have chronic intestinal failure, managed conservatively by long-term parenteral nutrition and steroids for more than 12 years.

[Dry eye syndrome in rheumatoid arthritis patients]. / Syndrom suchého oka u pacientu s revmatoidní artritidou.

The aim of this cross-sectional study was to review the incidence of the dry eye syndrome in rheumatoid arthritis (RA) patients, evaluate the association among the incidence of the dry eye syndrome, presence of positive rheumatoid factor (RF), the RA stage, and the duration of the disease. The group consisted of altogether 100 patients, 16 men and 84 women; the average age was 58.9 years (SD 14.6). The average duration of RA was 12.3 years, SD 11.0. In each patient, the Schirmer test I was performed, the presence of the LIPCOF (Lid Parallel Conjunctival Folds) on the slit lamp was assessed, the BUT (Tear Break-Up Time) was measured and vital fluorescein staining was performed. In each patient the data of the presence or absence of the RF in the serum, RA severity according to the X-ray examination, and the disease duration were recorded. The Pearson's association test for nominal variables was used for statistical evaluation of the association between the rheumatoid arthritis presence and the dry eye syndrome. In our group of 100 patients, the Schirmer test I was positive in 67% of patients. Positive BUT was marked in 84 % of patients. The conjunctival folds were present in 45 % of patients only. The pathological findings after cornea fluorescein staining appeared in 18 % of patients. The dry eye syndrome incidence was marked in 74% of patients with RA. Subjective difficulties were declared by 38.3% of patients only. The local treatment was already established in 23.0% of patients only. We did not find statistically significant correlation between the RF positive rheumatoid arthritis appearance and dry eye syndrome, nor between the stage of the rheumatoid arthritis and presence of the dry eye syndrome. We proved statistical connection between the presence of dry eye syndrome and the duration of rheumatoid arthritis longer than 10 years. Keratoconjunctivitis sicca is the most common ocular complication in rheumatoid arthritis patients. We proved the connection between the dry eye syndrome presence and duration of the RA longer than 10 years; we did not find the dependence among the RF presence and stage of the rheumatoid arthritis and the appearance of the dry eye syndrome. The early diagnosis of the dry eye syndrome and the effective local therapy may prevent very serious corneal complications, which are difficult to treat.

Postenucleation orbital sialocele in a dog associated with prior parotid duct transposition.

An orbital sialocele developed in a dog following enucleation for protracted glaucoma. This eye had historically been treated for keratoconjunctivitis sicca by parotid duct transposition approximately 5 years previously, and the duct was ligated distally at the time of enucleation. One month following enucleation, the dog presented with a fluctuant conical-shaped swelling ventrolateral to the orbital socket. Surgical exploration revealed a dilated, fibrotic distal portion of the previously transposed parotid duct, and saliva, within the enucleated orbit. The distal portion of the duct and saliva-containing tissues from within the orbit were excised. The remaining proximal normal portion of the parotid duct was re-routed into the oral cavity. Clinicopathologic and histologic examination of the excised orbital contents and dilated portion of duct revealed a sterile sample of saliva and moderate chronic periductal fibrosis. At a 6-month re-evaluation there was no evidence of recurrence of the sialocele, and the parotid duct was functional.