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A cohort of 60 stable dialysis patients (56 haemodialysis, 4 continuous ambulatory peritoneal dialysis) was followed for 1 year to determine the relationship between anticardiolipin (aCL) antibodies and lupus anticoagulant (LA), and clinical events. The outcome measures were death, arterial, venous, and fistula thromboses, and fistula repairs. At baseline 15% had antibodies (5/60 IgG aCL, 3/60 LA, and 1/60 had both); 15 patients had a history of arterial thrombosis (1 patient was aCL positive), seven venous thrombosis (1 patient LA positive), 10 fistula thromboses (1 aCL positive); and 21 had a history of fistula repairs (4 aCL positive). Renal diagnosis, age (66.78 versus 59.67 years) and duration of dialysis (38.11 versus 45.25 months) were similar in patients with and without aCL antibodies or LA. Only the sex ratio showed a female predominance in the aCL- or LA-positive patients compared to the negative patients (3M:6F versus 36M:15F), but this was not significant (P = 0.07). After 1 year there were 10 deaths (1 LA positive), 12 thrombotic events in eight patients (none aCL or LA positive), and nine fistula repairs in seven patients (1 aCL-positive patient). We are unable to show higher rates of death, thrombotic event, or fistula repair in dialysis patients with aCL antibodies or LA followed up for 1 year in one centre. The clinical importance of antiphospholipid antibodies in dialysis patients is uncertain.

We describe a 26-year-old patient with systemic lupus erythematosus and pulmonary and portal hypertension associated with the presence of anticardiolipin antibodies. Postmortem histological examination revealed the presence of recent thromboses of pulmonary and portal vessels. Our findings further support the concept of pulmonary hypertension being part of the antiphospholipid syndrome and suggest that portal hypertension due to intrahepatic portal vein thrombosis might be another manifestation of this syndrome.

Neutrophil and monocyte activation by immune complexes containing IgE from serum and synovial fluid of patients with rheumatoid arthritis is reported. Activation of the inflammatory cells was measured by stimulation of the respiratory burst with production of intracellular hydrogen peroxide. Generation of hydrogen peroxide was analysed by a flow cytometric method, using the fluorochrome dichlorofluorescein. The technique was modified to allow measurement of cell activation of both neutrophils and monocytes by immune complexes in suspension. Ten of 14 polyethylene glycol precipitates from serum of patients with rheumatoid arthritis and 10/16 synovial fluids of these patients could activate neutrophils. A positive relation was found between the activation of neutrophils and the total concentration of immune complexes, the presence of IgG, and the presence of IgE in the immune complexes. Activation of monocytes was also shown, but to a lesser extent (8/14 rheumatoid serum samples and 8/16 rheumatoid synovial fluids activated monocytes). There was a weak correlation between the concentration of IgE immune complexes and the intensity of fluorescence measured in the monocytes.

A 72-year-old rheumatoid arthritis patient is described presenting with acute dyspnoea and peripheral oedema. A pericardial effusion with signs of tamponade was diagnosed. Examination of the pericardial fluid revealed the presence of cholesterol crystals and IgE-containing immune complexes. The significance of these findings in the differential diagnosis of pericardial disease is discussed.

Ultrasonography (US) was evaluated as noninvasive method to determine salivary gland involvement and compared with sialography in patients with Sjögren's syndrome (SS) and patients with only objective xerostomia and/or xerophthalmia. Patients with complaints of dry eyes and dry mouth but with no objective abnormalities served as control group. Ultrasound revealed a decreased parotid gland reflectivity in most of the patients with SS, compared with only 2 patients in the other group (p = 0.002). Our study suggests that US can be a useful, noninvasive method in the diagnostic work-up of patients with sicca complaints.

Natural killer (NK) cell activity and its stimulation by interferons (IFNs) and interleukin-2 (IL-2) are diminished in Sjögren's syndrome and systemic lupus erythematosus (SLE). Serum samples of these patients often contain circulating immune complexes, which may influence NK cell activity. Sixteen patients with Sjögren's syndrome (14/16 immune complex positive), 14 with SLE (9/14 immune complex positive), and 11 controls (immune complex negative) were studied. Mononuclear cells collected from a Percoll gradient were preincubated with recombinant IFN-alpha (rIFN-alpha) (100 U/ml), rIFN-gamma (1000 U/ml), rIL-2 (100 U/ml), or without cytokine. Natural killer cell activity was determined by incubating the mononuclear cells with carboxyfluorescein labelled K562 cells, and the percentage decrease of fluorescence was measured on an FACS Analyzer. In patients with Sjögren's syndrome and SLE NK cell activity and the numbers of cells expressing the NK cell associated antigens CD16 and Leu7 were diminished compared with the controls. Interleukin-2 stimulated NK cell activity significantly in comparison with the non-stimulated value in all studied groups, whereas IFN-gamma only stimulated NK cell activity in both patient groups and IFN-alpha only in patients with Sjögren's syndrome. There was no correlation between NK cell activity, with or without stimulation, and the immune complex concentrations. It is concluded that NK cell activity is decreased in Sjögren's syndrome and SLE and that it may be partially restored by IL-2 and IFN-gamma in both diseases, and by IFN-alpha in Sjögren's syndrome. The decrease of NK cell activity did not correlate with immune complex concentrations; on the other hand, decreased numbers of NK cells (CD16+ or Leu7+) and of cytokine concentrations might be important in the impaired NK cell activity in both diseases.

The prevalence and composition of IgE-containing immune complexes in paired synovial fluid and serum of 42 patients with classical or definite rheumatoid arthritis were studied. IgE-containing immune complexes were found in 15/42 synovial fluids; 15 sera were also positive. The correlation between serum and synovial fluid complexed IgE levels was high (r = 0.77). The mean ratio of synovial fluid/serum levels was 1.96, i.e. significantly higher than 0.33, the synovial fluid/serum ratio for alpha-2-macroglobulin (molecular weight 820 kD), which was taken as high molecular weight control protein (p less than 0.0001). Apart from IgE in immune complex form, monomeric IgE was also significantly higher in synovial fluid compared to serum (ratio = 2.94). Other constituents which could be found in the immune complexes, i.e. anti-IgE antibodies, rheumatoid factors and anticollagen antibodies, were also higher in synovial fluid than predicted. Our results suggest intra-articular production of IgE-containing complexes in the synovial fluid, in addition to possible exudation of the complexes from the serum. These findings provide further evidence for the role of IgE-containing immune complexes in rheumatoid synovitis.

The Saxon test, a simple, reproducible, and low-cost technique to test for xerostomia in adults was applied to 347 schoolchildren who were free from any known disease. The values in children differed significantly from the values in adults and increased slightly with age. The test can easily be performed on samples kept for 8 days at 4 degrees C or at room temperature.

We report a patient with multiple inflammatory reactions to Dacron vascular grafts, simulating infection. A CT-scanning showed dense fibrous tissue surrounding the grafts, with a pseudotumoral aspect and liquification. Ultimately, the Dacron grafts were replaced with polytetrafluoroethylene grafts. The inflammatory reactions subsided quickly and did not recur for a follow-up period of more than two years.

A patient with severe rheumatoid arthritis received d-penicillamine treatment for 16 months. She developed mild pruritus 6 months after d-penicillamine initiation, and severe pemphigus 10 months after d-penicillamine was changed to azathioprine. Subsequent methylprednisolone pulse therapy resulted in a transient clinical remission of pemphigus. A literature review of d-penicillamine induced pemphigus and high dose methylprednisolone pulse therapy is presented.

IgM-rheumatoid factor (RF) interference in the determination of total serum IgE and IgE-containing circulating immune complexes (IgE-CIC) was studied by inhibition experiments in vitro comparing a new ELISA technique free of IgM-RF interference with more widely used RIA methods. It was shown that a considerable overestimation of the IgE content in CIC can exist when high levels of IgM-RF are present in the same serum. The clinical part of this study revealed a dramatic fall in prevalence of IgE-CIC in patients with rheumatoid arthritis (RA) with the ELISA technique, compared with the more conventional RIA method (respectively 1/20 compared to 12/20 positive for IgE-CIC). In these patients, there was a good correlation between the level of IgM-RF and the amount of IgE detected in the CIC by the RIA method (r = 0.87) whereas the RF-interference free ELISA method showed no correlation between these two parameters (r = 0.06). Total serum IgE determination with a solid phase RIA was also influenced by IgM-RF interference, whereas the PRIST method was not affected by the presence of IgM-RF. In conclusion, in patients with rheumatic diseases, IgE-assays using polyclonal rabbit or sheep anti-IgE antibodies are not appropriate and monoclonal anti-IgE antibodies that have been proved not to interfere with IgM-RF should be advocated.

Two cases of eosinophilic fasciitis are described, in which magnetic resonance imaging (MRI) clearly demonstrated thickening of the fascia and increased signal intensity in the superficial muscle fibers correlating with inflammation. MRI is a useful noninvasive imaging technique in the diagnosis of eosinophilic fasciitis and can guide biopsy of selected abnormal areas.

A decrease of natural killer cell activity (NKCA) during human pregnancy might contribute to the acceptance of the allogeneic fetus by the maternal host. The inhibition of NKCA might be due to serum factors derived from the trophoblast. We focused especially on the role of immune complexes, as it has already been described that these complexes depress NKCA and as they are found frequently in retroplacental serum. We have compared the influence of 19 paired retroplacental and peripheral blood sera on NKCA of normal donors. One peripheral and eight retroplacental sera contained immune complexes. Normal donor mononuclear cells were incubated with carboxyfluorescein-labeled K562 cells in the presence of retroplacental serum or peripheral serum. NKCA was measured on a FACS Analyzer. Ten of 19 retroplacental sera inhibited NKCA significantly in comparison to the corresponding peripheral serum (P = 0.003). There was no correlation between NKCA and the immune complex level. We conclude that, as compared to peripheral serum taken at delivery, there is a retroplacental serum-induced inhibition of NKCA, which is not correlated with the presence of immune complexes.

We describe a patient in whom the diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was delayed because her clinical symptoms were similar to those of systemic lupus erythematosus and Sjögren's syndrome and because of a false-negative result on a Western blot test for human immunodeficiency virus. The importance of using different diagnostic tests for AIDS and the pitfalls in diagnosing AIDS in patients who appear to have connective tissue disease are discussed.

Ultrasonography (US) and computed tomography (CT) were studied as noninvasive methods to determine salivary gland involvement and compared with parotid sialography in patients with Sjögren's syndrome (SS) and patients with only objective xerostomia and/or xerophthalmia. Patients with complaints of dry eyes and dry mouth but with no objective abnormalities served as controls. CT was not discriminative between the 2 groups. In contrast, US revealed decreased parotid gland echogenicity in most of the patients with SS, compared with only 1 patient in the group with sicca complaints only (p = 0.005). Our study suggests that US can be a useful, noninvasive method in the diagnostic investigation of patients with sicca complaints.

Two hundred and seventy patients with asthma and/or rhinitis (162 or 60% allergic, 108 or 40% non-allergic) were studied for sinus pathology by means of standard X-rays and tomograms. Sinus pathology was defined as abnormal sinus X-rays, either on standard or tomography. Fifty-four percent of the X-rays were classified as abnormal based on mucosal thickening, loss of translucency of the cavities of polyps. Asthma was significantly more often associated with sinus X-ray abnormalities (65.1%) than rhinitis and/or chronic cough (44.4%). Loss of translucency of the cavities is more frequent in children, whereas mucosa thickening becomes more frequent with progressing age. Since in this prospective study the taking of X-rays of the sinuses was not dependent on or related to temporarily occurring symptoms which could be attributed to acute sinusitis, the presence of sinus abnormalities on X-rays can be considered as an indicator of the chronicity of airways diseases and might provide an indication for prophylactic therapy of the associated airway disease in a continuous way. The importance of sinus tomograms is stressed, since only 32.5% of the patients with mucosa thickening could be detected on standard X-rays.

Serum samples from 57 patients with cystic fibrosis were tested for the presence of IgG, IgA, IgM, IgE, and circulating immune complexes containing IgG, IgA, and IgM. Titres of class specific antibodies to Pseudomonas aeruginosa, and class specific antibodies to Ps aeruginosa in circulating immune complexes, were also measured. According to the Shwachman score the patients were divided into three clinical groups: group 1-moderate and severe disease, group 2-mild disease, and group 3-well. The results of the immunological investigations were correlated with the clinical state of the patients as assessed by the Shwachman score. Serum concentrations of IgG, IgA, and IgM were inversely correlated with the Shwachman score, but the differences between the groups were only significant for IgG and IgA. The same correlations were found for circulating immune complexes containing IgG and IgA. Antibodies to Ps aeruginosa could be detected in most of the patients' serum samples. IgA antibody specific to Ps aeruginosa was the most often raised, even in patients in group 3. It is therefore suggested that IgA antibody specific to Ps aeruginosa could be an early marker of colonisation by Ps aeruginosa and a sensitive measurement of infection with Ps aeruginosa in young children with cystic fibrosis. Moreover, in the circulating immune complexes, class specific antibodies to Ps aeruginosa were found in nearly half the patients. The highest titres of IgG and IgA antibodies specific to Ps aeruginosa in the circulating immune complexes were detected in the patients with the worst clinical state (group 1).

In an earlier study, we reported IgE-containing circulating immune complexes (CICs) in 66.6% of the patients with rheumatoid arthritis who were studied, especially in those with extra-articular manifestations. The present study was undertaken to examine the possible role of these immune complexes in inflammatory cell activation. Twelve patients with classic or definite rheumatoid arthritis, two with primary Sjögren's syndrome, and three patients with systemic lupus erythematosus were studied. Of these 17 patients, 10 were IgE-containing CIC positive, and seven patients were IgE-containing CIC negative. Polyethylene glycol-precipitated IgE-containing CICs and IgG-containing CICs of these patients were coated on plastic wells and incubated with suspensions of neutrophils. As a parameter of cell activation, superoxide release (SOR) was measured by cytochrome C reduction in the supernatant after 30, 60, and 90 minutes. There was a significant SOR up to 38% of the zymosan control when IgE-containing CICs were incubated with neutrophils. Furthermore, there was a significant correlation between the level of IgE-containing CICs and the amount of SOR, but not between the level of IgG-containing CICs and the amount of SOR. These results suggest a possible role for IgE-containing CICs in the activation of inflammatory cells in connective tissue diseases.

We treated four children with clinical symptoms and laboratory findings suggestive of Sjögren's syndrome (SS). We also review the findings in 23 children with the diagnosis of SS whose cases were reported in the literature. We propose that the following criteria for the diagnosis of SS, which are mostly used in adults, should also be applied to children: (1) keratoconjunctivitis evidenced by a Schirmer test and a quantitative rose bengal test; (2) xerostomia shown by a decreased basal and stimulated salivary flow; (3) lymphocytic infiltration in a minor salivary gland biopsy specimen with at least two foci per 4 mm2; (4) laboratory evidence of a systemic autoimmune disorder on the basis of a rheumatoid factor of 1/160 or greater, antinuclear antibody of 1/160 or greater, or extractable nuclear antigen antibodies. Only close observation and long-term follow-up of these patients will allow a better insight in the natural history of SS in children. Those children who do not fulfill these diagnostic criteria also need close and prolonged follow-up study: one of the possibilities is that their conditions will ultimately evolve toward definite SS.

With the conventional, discrete RAST various tests are required to detect IgE of different specificities in the same serum. To overcome this problem and to reduce the costs, a multiple RAST with seven different mixtures was compared with the individual mixture constituents and with the 12 individual allergens currently in use in our department. One grass pollen mixture (gx3), two weed pollen mixtures (wx3, wx4), two tree pollen mixtures (tx5, tx6), one mould mixture (mx1) and one epithelial mixture (ex1) were used. A mixture of mites was not evaluated as there is only one important pathogenic organism in our regions (Dermatophagoides pteronyssinus or House dust mite). For grasses the gx3 mixture offered no advantage over the discrete RAST. The weed mixture wx3 was more sensitive than the most common discrete RAST's but at the cost of specificity. The wx4 mixture should not be used because the specificity is too low. The tree mixtures were not significantly more sensitive than the most common individual tree allergens, and were less specific. Mould mixtures should not be used because there is little cross-reactivity between the individual allergens, thus using a mixture would necessitate the subsequent determination of individual allergens, and the number of tests and the cost would be even higher. Neither should a mixture be used for epithelia because one wants to detect allergies to individual allergens. Moreover, the sensitivity of the epithelial mixture was too low. In general, we suggest the use of a limited panel of discrete RAST's instead of mixtures.

Eighteen patients diagnosed as suffering from MCTD were reexamined during follow-up (mean duration 4.6 years). The clinical features of these patients were compared with those of 19 patients with systemic lupus erythematosus (SLE), 11 with progressive systemic sclerosis (PSS) and 22 with rheumatoid arthritis (RA). Considerable overlapping of abnormal features was found between MCTD and the other syndromes. At the end of the follow-up period, 70 per cent of the cases initially diagnosed as MCTD evolved to a more classical connective tissue disease, i.e., either PSS or SLE. Generally, however, the clinical evolution of the individual MCTD patient was not predictable. Abnormal aortic valve calcifications were found in the MCTD group. Four of the 18 MCTD patients were anti-RNP negative at reexamination. There was a tendency for HLA antigens B7 and B8 to be increased in the MCTD group, but this difference was not statistically significant. Three MCTD patients died before they could be reexamined (two of them from pulmonary hypertension with proliferative endarteritis of the lung vessels and one from septicaemia and multiple cerebral infarctions.

The lymphocyte stimulation responses to the mitogens phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed (PWM) were investigated in 30 hospitalized depressed women undergoing a dexamethasone suppression test (DST). Patients were classified according to DSM-III as having major depression with melancholia, without melancholia, and minor depression. The Hamilton Depression Rating Scale (HDRS) and the State-Trait Anxiety Inventory (STAI) were measured. Patients with major depression showed significantly decreased lymphocyte stimulation induced by PHA, Con A, and PWM as compared to those with minor depression. These differences could not be attributed to age, body weight, weight loss, total number of leukocytes, menopausal status, sleep disturbances, concomitant use of low-dosage benzodiazepines or length of drug-free period before testing. The group mean differences in lymphocyte stimulation counts were not affected by the severity of illness or the severity of state and trait anxiety. There were no significant differences in the lymphocyte responses to PHA, Con A, and PWM between DST non-suppressors and DST suppressors. No significant correlations were established between baseline and post dexamethasone cortisol values and the lymphocyte stimulation counts.

The frequency and severity of the late asthmatic reaction (LAR) was studied in asthmatic children allergic to house dust mite (HDM) or grass pollen (GP) with and without hyposensitization (HS). The four groups were comparable according to their severity of asthma. All children were allergic to HDM (Dermatophagoides pteronyssinus) or GP according to history, skin testing and specific IgE determination via the RAST. The LAR occurred less frequently (29% versus 73%) (P less than 0.001) and was less severe in children receiving HS. The difference was significant between the children allergic to HDM as well as between children allergic to GP. The immediate asthmatic reaction (IAR) was also less severe in children allergic to HDM who received HS, compared to those who never received HS, (P = 0.033) although the PD20 of the HDM challenge (PD20HDM) was not different between the two groups. In children allergic to GP, there was no difference in PD20 of the GP challenge (PD20GP) or in severity of the IAR, whether the children received HS or not. There was no difference between the PD20HDM in patients who developed a LAR and in patients who did not. There was no relation between the type of asthmatic reaction following the allergen provocation test and the level of circulating immune complexes (CIC) and the level of house dust mite-specific IgG (IgGHDM) or grass pollen-specific IgE (IgGGP) in the different groups, determined before the challenge. There was a decrease in the level of IgG containing CIC (IgGCIC) during the LAR. It is concluded that the LAR occurs less frequently and is less severe in asthmatic children who receive HS.

Sequential lung function tests were performed on 17 scleroderma patients who were treated with D-penicillamine (DP) (total of 66 treatment years) and on 10 control scleroderma patients who were not treated or were treated with low-dose prednisone (total of 25 treatment years). Cusum plots showed significant differences between the 2 groups in their cumulative changes in carbon monoxide diffusing capacity (DLCO) (P less than 0.005) and in DLCO/lung volume (P less than 0.02). The end value of the DLCO was greater than 10% lower than the initial value in 3 of the 17 DP-treated patients versus 5 of the 10 control patients (P less than 0.01, Fisher's exact probability test); in 3 DP-treated patients and 8 control patients (P less than 0.003, Fisher's exact probability test), the end value of the DLCO/lung volume was greater than 10% lower than the initial value. We conclude that DP has a beneficial effect on interstitial lung disease in patients with scleroderma.

Biopsy specimens from apparently normal skin of 28 patients with classical or definite rheumatoid arthritis (RA) were examined for the presence of IgE deposition by a direct immunofluorescence technique. IgE deposition was found in 12 patients (43%) and in none of the 10 controls. This deposition was mainly localised on mast cells, and in three patients perivascular IgE staining was also noted. The skin from nine of the 12 patients also showed deposition of IgM and complement C3 or C4 factor, or both. All 12 patients with skin IgE deposition had raised levels of IgM rheumatoid factor (RF) in the serum. Nine of these also had IgE RF. IgE-containing circulating immune complexes (IgE CIC), raised serum IgE levels, and extra-articular (EA) manifestations were present in respectively 10, nine, and eight skin IgE positive patients. It is suggested that IgE and IgE CIC may be involved in the pathogenesis of RA and its EA manifestations.

A 39-year-old Ugandan student is described presenting with general malaise, fever and a pulmonary infiltrate. Open lung biopsy showing infarction and positive ANCA lead to a diagnosis of Wegener's granulomatosis and a treatment with immunosuppressive drugs was instituted. Five weeks after admission, however, sputum cultures turned out to be positive for Mycobacterium tuberculosis. The importance of ANCA-interpretation and the possibility of false positive results is discussed.

A 45-year-old patient is described presenting with severe axial osteoporosis. The presence of maculopapular skin lesions and the combination of osteolytic and osteoblastic bone lesions led to the tentative diagnosis of systemic mastocytosis. This diagnosis was confirmed by measurement of urinary histamine metabolites and by bone biopsy showing increased numbers of mast cells and fibroblast-like cells. The importance of these diagnostic procedures in this rare cause of osteoporosis is discussed.

IgE-containing circulating immune complexes (IgE-CIC) were determined with a 2.5% PEG-precipitation assay in 98 patients with classical or definite rheumatoid arthritis (RA). Of the 45 IgE-CIC positive sera, only 4 had elevated total serum IgE. IgE-CIC positive patients had more active disease than patients without IgE-CIC, as determined by their more swollen joints and higher Ritchie indices (p less than 0.04 and 0.02, respectively). Apart from IgE, other immunoglobulin isotypes, rheumatoid factor (RF) of the IgG-, IgA- and IgM-classes, C3 and antinuclear antibodies could be demonstrated in the IgE-containing PEG-precipitates. IgE-RF could not be demonstrated in serum or in IgE-CIC. Anti-IgE of the IgM-class (IgMaIgE) were frequently found (28/45 patients) in the IgE-positive PEG-precipitates. All 14 patients positive for IgGaIgE in the IgE-CIC were also positive for IgMaIgE in the CIC. As in the serum, there was a good correlation in the CIC between the level of IgGaIgE and the level of IgMaIgE (r = 0.64). The correlation between the respective levels of IgGaIgE and IgMaIgE in serum and in CIC was high (r = 0.93 and 0.79, respectively). On the other hand, only 1 patient was positive for IgAaIgE in the IgE-CIC. We conclude that IgE and aIgE of the IgM- and IgG-classes are frequently present in the immune complex form in RA and that they are correlated with the clinical activity of arthritis.

A simple and sensitive enzyme-linked immunosorbent assay (ELISA) was developed to determine rheumatoid factors (RFs) of IgG, IgA and IgM class. Standardisation was performed with a standard reference serum for IgM-RF, calibrated according to the WHO preparation, and with the serum of a patient containing high levels of IgA- and IgG-RF. The sigmoidal shaped calibration curve was fitted with a computerized four parameter logistic model with simplified mathematical computations. This method provided to be more accurate for measuring RF levels, as judged by the smaller residuals, than logit or log-linear transformations. The considerable reduction in processing time, which is obtained by the computerized analysis of data, makes this method of class-specific RF determination suitable for routine analysis.