Central nervous system mechanisms in Sjögren's syndrome.
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Biomedical subjects
Publications and source records attributed to O P van Bijsterveld.
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AIMS: To assess the course of tear gland function of patients with keratoconjunctivitis sicca (KCS) associated with primary (KCS-PSS) or secondary Sjögren's syndrome (KCS-SSS), and of patients with KCS not related to Sjögren's syndrome (KCS-NS). METHODS: In 106 patients with dry eye an ophthalmic diagnosis of KCS was made. Subsequent evaluations revealed a diagnosis of KCS-PSS in 31, KCS-SS in 19, and KCS-NS in 56 patients. Follow up assessments have been performed 10-12 years after initial diagnosis. RESULTS: At baseline and at follow up tear gland function tests were worse in patients with KCS-PSS compared with the other forms of KCS. At follow up in the KCS-SSS patient group the tear gland function variables returned to marginal normal limits. In contrast with expectation, a marked improvement of the tear gland function variables in the KCS-NS patient group was noted. CONCLUSIONS: In KCS-PSS patients tear gland function is characterised by a steady state situation. In KCS-SSS patients the normalisation of tear gland function variables most probably reflects a remission of the underlying disease. In view of the overall improvement in KCS-NS patients the term age related KCS should be avoided.
OBJECTIVE: To assess long-term outcome in patients with isolated keratoconjunctivitis sicca (KCS), primary Sjögren's syndrome (SS), and secondary SS. METHODS: In 112 patients referred because of dry eyes, an ophthalmologic diagnosis of KCS was made based on results of the Schirmer I test, the tear fluid lysozyme concentration, and rose bengal staining. Subsequent assessments, including sublabial salivary gland biopsy, were performed. Followup assessments were performed 10-12 years after initial diagnosis. RESULTS: Six patients were excluded because no biopsy specimen was available. Seventy-three percent of the remaining 106 patients were female, with a mean age of 53.5 years and a mean symptom duration of 3.9 years. Application of the 1987 classification criteria of Daniels and Talal revealed a diagnosis of isolated KCS in 56 patients, primary SS in 31, and secondary SS in 19. At baseline, 2 of 56 patients with isolated KCS and 8 of 31 with primary SS exhibited mild features of organ-specific autoimmune disease. At followup, 2 of 38 patients with isolated KCS and 4 of 21 with primary SS had developed new features related to autoimmune disease, not necessitating treatment with corticosteroids; none of the patients developed major glandular complications. Three of 30 patients with primary SS died of malignant lymphoma. In 1 of these patients, the possibility could not be excluded that sicca symptoms and infiltrates seen on sublabial salivary gland biopsy had occurred concomitantly with early stages of lymphoma. Malignant lymphoma did not develop in any of the patients with isolated KCS or secondary SS. CONCLUSION: Primary Sjögren's syndrome is characterized by a stable and rather mild course of glandular and extraglandular manifestations, in marked contrast to the increased risk of development of malignant lymphoma in these patients. Since patients with isolated KCS do not have an increased risk for development of malignant lymphoma, a presumptive diagnosis of primary SS should be confirmed in patients with sicca syndrome.
The modern local antibiotics, such as the aminoglycosides and quinolones, are very successful in treating infectious conjunctivitis and keratitis. More notably in some Third World countries, however, suppurative keratitis is found in more than half of the infectious disease cases caused by Fusarium species. Here, of course, treatment should be antifungal. The emergence of some problematic microorganisms is related to contact lens wear. Pseudomonas, for example, have the ability to adhere to contact lenses and thus form microcolonies, which are protected by biofilm that predisposes to infection. Acanthamoeba infections of the cornea are a direct consequence of inappropriate or inadequate disinfection of contact lens systems. Occasionally the diagnosis of herpes simplex manifestations of the outer eye can be very difficult. Even more confusing is the delayed appearance of zoster manifestations, such as pseudodendrites, particularly in cases of zoster sine herpete eruptione. The polymerase chain reaction is of particular value in demonstrating the presence of varicella zoster DNA. Although infectious disease of the outer eye remains common, the incidence and complications have increased because of frequent use of antimicrobial agents. In the under-developed areas of the world, however, infections are still very common, are frequently caused by fungi, and are the cause of serious ocular complications. In the Western World infectious eye disease does not seem to be a major diagnostic or therapeutic point at present. Some organisms that have been in the environment all along, however, have emerged in the past half century as a major problem. Thus, in the past years a number of new techniques in diagnosis as well as new insights in pathophysiology and new developments in treatment have emerged that are of interest.
BACKGROUND: It is generally accepted that the elevated calcium phosphate product in dialysis patients is associated with the development of extraskeletal calcification. There is, however, no clear association between the raised levels of calcium and phosphate ions and the degree of limboconjunctival calcification. This article focuses on the role of tissue devitalisation in the development of ocular calcification. METHODS: Local injury of the outer eye can be visualised by the Lissamine green staining test. We measured the pre- and postdialysis staining score in 38 dialysis patients. The differences between pre- and postdialysis tear fluid secretion and tearfilm stability were also assessed, as was the degree of limboconjunctival calcification. Serum calcium and phosphate levels were measured in all patients. RESULTS: In 14 of the 38 patients, demonstrable tissue injury was present as a result of a recurrent decrease of tear secretion after each dialysis session. There was a statistically significant association between the degree of limboconjunctival calcification and both the difference between the pre- and postdialysis Lissamine green staining score and the total number of haemodialysis sessions. CONCLUSION: Local factors, such as minor tissue injury of the limboconjunctival epithelium, referred to as "local challenger", are more likely to determine the degree of ocular calcification in dialysis patients than are systemic factors. Tissue injury of the outer eye in these patients is the result of a chronic decrease of tear fluid that occurs after each hemodialysis session.
In 8 of 57 patients with chronic renal failure that all had deposition of calcium salts in the limboconjunctival area, a focal hyperaemia of the conjunctiva was observed. This focal hyperaemia developed gradually around one or more greyish, slightly elevated, areas situated in the bulbar conjunctiva in the interpalpebral fissure. Clinically these lesions are very much alike inflamed pingueculae. Three patients showed a diffuse inflammatory reaction of the eye that was characterized by a waxy red episcleral and conjunctival hyperaemia extending beyond the palpebral fissure. The average value of the serum calcium concentration in these patients was particularly high and statistically significantly higher than in patients with calcification but without inflammatory signs and also higher than in patients that showed focal hyperaemia. In addition to the focal hyperaemia and the diffuse hyperaemia, we observed another diffuse hyperaemia located principally in the conjunctival tissue. This conjunctival redness often followed the focal hyperaemia associated with pingueculae or preceded the more acute fiery red episcleral hyperaemia, but it could also be present in isolation.
OBJECTIVES: In 1985 and 1988 a positive effect of treatment of primary Sjögren's syndrome with hydroxychloroquine was reported in two small open studies. To investigate further the clinical and laboratory effects of hydroxychloroquine in primary Sjögren's syndrome a two year study was performed. METHODS: The design of the study included a prospective, placebo controlled, two year double blind crossover trial in 19 patients. RESULTS: A significant decrease in IgG and IgM and a tendency for a decrease in the erythrocyte sedimentation rate (ESR) during treatment with hydroxychloroquine compared with treatment with placebo were found. No beneficial clinical effect of the use of hydroxychloroquine as expressed in preference for treatment with hydroxychloroquine or placebo with regard to symptoms and signs of primary Sjögren's syndrome could be shown, however, nor any relevant change in tear gland activity and sequelae of peripheral tear function deficiency, nor salivary gland scintigraphy. CONCLUSIONS: The use of hydroxychloroquine at a dose of 400 mg daily taken over a 12 month period does not have a worthwhile clinical benefit in patients with primary Sjögren's syndrome despite an improvement of hyperglobulinaemia and slight changes in the ESR and IgM.
In patients with chronic renal failure on regular dialysis treatment, limboconjunctival degenerations and calcifications are commonly observed. In this study three groups of patients were followed over a period of 6 years. The first group consisted of 47 patients with renal failure, the second group of 17 patients with renal failure and hyperparathyroidism not controlled by drugs, and the third group seven patients with primary hyperparathyroidism without renal failure. The aim of this study was to determine the progression of the limboconjunctival changes over time. The hypothesis that an increase in serum calcium and phosphorus concentrations, as a result of tertiary hyperparathyroidism, could possibly add a corneal component to the limbal calcification was also tested. All patients with renal failure (in as much as the degenerative limbal features were not obscured by deposits of lime salts), had a type II white limbus girdle of Vogt. This limbal degeneration was observed in only 45% of controls. In all 47 patients with renal failure conjunctival calcification was observed; 26 of them also had limbal calcification. After 6 years 41 patients had developed limbal calcification. This progression was statistically significant. In 15 out of 17 patients with tertiary hyperparathyroidism a band-shaped keratopathy developed in addition to the limboconjunctival calcification.
In 35 patients with mild, moderate and severe keratoconjunctivitis sicca, an association was found between treatment effect, break-up time value and Rose bengal score. Neither of these tests, used separately, was successful as a clinically valuable predictor of treatment effect as the scatter, in score points, was too large. Analysed together, however, as in a partial regression analysis, an adequate prediction is possible, which is clinically of some value.
We have studied the effect of the aluminum complex of sucrose sulphate (Sucralfate suspension) and the sodium salt of sucrose sulphate (sodium sucrose sulphate solution) on patients with keratoconjunctivitis sicca. Eyes treated with either of these two drugs showed a decrease in painfulness and blurring of vision. On examination the surface area of the corneal lesions, stained with fluorescein, diminished during treatment. As for the difference in effect between the two eyedrops, the solution was better tolerated.
Of 57 patients with chronic renal failure and calcification of the anterior membranes of the eye eight developed inflammatory reactions, clinically indistinguishable from pingueculitis. In three patients an acute inflammatory reaction of the episcleral tissue and the conjunctiva over it developed which we considered to represent the red eye of renal failure. In these patients massive shedding of calcium phosphate salts was clinically evident. Histopathologically in all these patients calcific deposits were observed. Although sporadically polymorphonuclear leucocytes were present in the inflamed tissues we could not demonstrate crystal phagocytosis. We believe that in the red eyes in renal failure and, more specifically, in the red eyes of renal failure a crystal induced inflammatory mechanism is not operative.
Of 57 patients with chronic renal failure who all had deposition of calcium salts in the conjunctival and corneal tissue two developed a brief episode of painful irritation and redness of the conjunctiva and subconjunctiva. This hyperaemia was adjacent to erosions of the corneal epithelium of the eye as a consequence of exfoliation of calcium concretions from the superficial corneal epithelium. Eight patients showed inflammatory reactions of the conjunctivae that were clinically identical to inflamed pingueculae. Three patients showed an inflammatory reaction of the eye that was characterised by a waxy red, more or less diffuse, episcleral and conjunctival hyperaemia extending beyond the palpebral fissure. The average value of the serum calcium concentration in these patients was particularly high and statistically significantly higher than in patients with calcification but without inflammatory signs and also higher than in patients who showed pingueculitis. We propose to reserve the term 'red eye of renal failure' for the latter group of patients.
Laboratory tear function tests, such as the lactoferrin and the lysozyme test, reflect the level of tear gland deficiency and are, therefore, very useful for the clinician in the diagnosis of keratoconjunctivitis sicca (KCS). Although these tests do have an excellent discriminatory ability, they should be used in addition to clinical tests, such as the Schirmer-1 test, the tear film break-up time (BUT) and the Rose bengal (Rb) staining test. Schirmer's test, the most commonly used clinical test, measures tear fluid production. The tear film BUT, on the other hand, is the only test which establishes tear film instability. The Rose bengal score is strongly related to secondary damage of the superficial epithelium of the cornea and conjunctiva in patients with KCS. Thus, combining the results of these various tests facilitates the diagnosis of KCS and also the differentiation between Sjögren's KCS and non-Sjögren's KCS.
The average corneal thickness in a group of patients with KCS did not differ significantly from that in a control group. Within the patient group the corneal thickness decreased with decreasing lysozyme concentrations and also with decreasing Schirmer values, but the correlation was weak in both cases. The average central corneal thickness with severe and very severe KCS was greater than that of patients with mild KCS and the control groups. The average corneal thickness in patients with mild KCS was less than that of the control group, but not significantly so. Because of the comparatively small number of patients with severe KCS, an all over increase in corneal thickness in patients with KCS could not be demonstrated.
In the course of an acute phase of pneumococcal conjunctivitis, a serpiginous corneal ulcer has never been reported to develop. However, if there is a pneumococcal chronic dacryocystitis and a resultant lacrimal conjunctivitis, the association with pneumococcal serpiginous ulcers is significant. This is most likely due to the fact that those serological types that are particularly virulent for the cornea have an affinity to colonize and infect the lacrimal sac.
The authors examined 32 patients with light-dermatosis or vitiligo who were being treated with orally administered Canthaxanthin and betacarotene. Eight had crystalline retinopathy with typical "gold dust" particles in the inner retinal layers, forming a band-shaped zone around the macula and, in more severe cases, also around the optic disk. No deterioration of visual function was found in any of these patients. Crystal deposition was correlated significantly to the total Canthaxanthin dosage but not to the duration of treatment.
Bromovinyldeoxyuridine is a potent and safe antiherpes compound that in combination with a placebo treatment promoted the partial and complete healing of herpetic epithelial disease in 22 patients in average times of 4-6 days and 8.5 days respectively. However, when BVDU was combined with 1.5 X 10(6) IU of recombinant a 2C interferon, partial and complete healing times for keratitis in 19 patients were reduced to 2-6 days and 4-6 days respectively. No toxic effects of the medications were observed in any patient.