Poul Halberg

Mortality and Causes of Death of 513 Danish Patients with Systemic Lupus Erythematosus

A multicentre cohort of 513 clinic attenders with systemic lupus erythematosus (SLE) was retrospectively identified, representing 4185 patient-years of follow-up. Expected numbers of death were calculated by means of age- and sex-specific mortality rates of the general Danish population. The observed number of deaths was 122. The survival rates were 97%, 91%, 76%, 64% and 53% after 1, 5, 10, 15, and 20 years respectively. The overall mortality rate was 2.9% per year (95% CI 2.4-3.5), and the standardized mortality rate (SMR) was 4.6 (95% CI 3.8-5.5). The causes of death included active SLE (n = 19), end stage organ failure due to SLE (n = 16), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32), and other causes (n = 21). SLE was directly related to one third of the excess mortality. In conclusion, SLE patients in the present cohort had a 4.6-fold increased mortality compared with the general population and half of the deaths were caused by SLE manifestations or infections, especially in young patients during the early period of the disease.

A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value.

In this Danish multicentre study, predictive clinical factors of mortality and survival were calculated for 513 patients with systemic lupus erythematosus (SLE), 122 of whom died within a mean observation period of 8.2 years equalling a mortality rate of 2.9% per year. Survival rates were 97%, 91%, 76% and 64% after 1, 5, 10 and 15 years, respectively. The direct causes of death included SLE (n=35_, infections (n=25), malignancy (n=9), cardiovascular disease (n=32) and other causes (n=21). Uni-and multivariate analyses of survival and mortality were performed for all deaths and for SLE-related deaths. Azotaemia (one-fifth of the patients) was a strong predictor of increased overall and SLE-related mortality, but nephropathy per se (one-half of the patients) and large proteinuria (one-sixth of the patients) were unrelated to survival. Haemolytic anaemia had a significant negative influence on survival related to mortality caused by infections. Diffuse central nervous system disease and myocarditis were related to increased SLE-related mortality, whereas photosensitivity predicted a decreased mortality. Non-fatal infections and thrombotic events predicted a decreased overall survival. Since 1980 the mortality caused by SLE manifestations has decreased significantly.

A SPECIFIC ANTIBODY AGAINST THE EPITHELIUM OF THE SALIVARY DUCTS IN SERA FROM PATIENTS WITH SJOGREN'S SYNDROME1

ns syndrome has several patholoiijical. and clinical features in coninion with auto-iininunc tliseases. The pathological findings in Sjogrens syndrome are chronic sialoadenitis antl dacryoadcnitis. The histological changes characteristic of these conditions have many features in common with the changes found in Hashimotos thyreoiditis in which autoimmune mechanisms seem to be ol pathogenic importance. Both diseases arc characterl/.ed hy lymphocytic antl plasma cell infiltration, fihrosis and epithelial changes. In Hashimotos thyreoiditis the epithelium is disorganized so that the follicles are substituted hy clusters and trabeculae (Fig. i A and B). In the initial stages of Sjogrens syndrome the epithelial changes are only seen in the salivary ducts whereas the acini are left intact {12). The epithelium of the salivary ducts becomes disorganized and hyperplastic, tiie lumen disappears resulting in the formation of characteristic epithelial islets (Fig. I C and D). In hoth diseases the fibrosis is progressive and eventually all the glandular tissue is replaced by fibrotic tissue.

Enzyme-Linked Immunosorbent Assay For Determination Of Igm Rheumatoid Factor

A semi-automated enzyme-linked immunosorbent assay (ELISA) for determination of IgM rheumatoid factor was established. Human gammaglobulin (Cohn fraction II) was used as an antigen on a solid phase of polystyrene microtitre trays. The results were read on a spectrophotometer. ELISA and the sheep cell agglutination test were compared in a study of sera from 400 blood donors, 53 patients with active rheumatoid arthritis and of 200 sera received for routine determination of rheumatoid factor. The results of the two tests correlated well. The ELISA procedure was precise, objective, inexpensive and well suited for quantitative routine determination of IgM rheumatoid factor.

Clinical Synovitis and Radiological Lesions in Rheumatoid Arthritis: A Prospective Study of 25 Patients during Treatment with Remission-inducing Drugs

The joints of hands and feet of 25 patients (1150 joints) with rheumatoid arthritis were compared, joint by joint, clinically and radiologically, over 2 years of treatment with remission-inducing drugs. Joints with clinical signs of synovitis decreased from 47% to 17% (p less than 0.001), while the number of joints with radiological lesions increased from 23% to 27% (p less than 0.01). Definite radiological progression of bone lesions was seen in 7% of the joints. Joints with clinical synovitis had a higher risk of progressive bone damage than joints without clinical synovitis (p less than 0.001) and joints in which the clinical signs of synovitis persisted during the study had a higher risk of progressing bone lesions than joints in which the clinical synovitis subsided (p less than 0.001). Progressive bone damage was seen more often in swollen joints than in tender joints without swelling or joints without clinical signs of synovitis (p less than 0.001), the difference in radiological progression between the latter two groups being non-significant. Twenty-one per cent of the joints with progressive bone lesions had no clinical signs of synovitis during the period.

PRECIPITATING ANTIBODIES AGAINST MICROPOLYSPORA PHAENI IN SERA FROM MUSHROOM WORKERS

A new method for determining precipitating antibodies in allergic alveolitis is presented. The principle used is immunoelectrophoresis, either as a counterelectrophoresis or as a crossed immunoelectrophoresis with intermediate gel. Twenty-two mushroom workers without anamnestic signs of allergic alveolitis and 15 control persons were investigated. Twelve mushroom workers (55%) had precipitating antibodies as determined by crossed immunoelectrophoresis, and nine of these persons had antibodies demonstrated with counterelectrophoresis. Thus, the sensitivity seems greater in the crossed immunoelectrophoresis, but we find that the simpler counterelectrophoresis is an excellent screening procedure in patients suspected of allergic alveolitis. In the controls only one person had precipitating antibodies, though the antigen tested for Micropolyspora phaeni exists ubiquitously. It seems probable from this study that the antigenic load is important, although it is remarkable that no mushroom worker with precipitating antibodies against M. phaeni had ever experienced symptoms compatible with allergic alveolitis.

Circulating Immune Complexes in Healthy Persons

The prevalence of circulating immune complexes (CIC) and C4 and C3 activation products (C4 and C3 A.P.) was investigated in sera from 106 blood donors, 100 hospital staff-members, 63 patients with rheumatoid arthritis and active synovitis, and in 25 hospital staff-members who had monthly tests performed during one year. CIC were detected by means of a complement consumption test and a polyethylene glycol precipitation test. C4 and C3 A.P. were demonstrated by means of crossed immunoelectrophoresis. No significant differences in the prevalence of CIC were found between blood donors and hospital staff-members (3 and 9%, respectively) and no age and sex differences were observed. In the longitudinal study of hospital staff-members, a significantly increased incidence of CIC was found during the winter months. CIC were found in 86% of the patients with rheumatoid arthritis. C4 and C3 A.P. were found significantly more often in sera with than without CIC. The significance of CIC detection may be increased by the simultaneous demonstration of C4 and C3 A.P. and by making allowance for seasonal variations.

Circulating Immune Complexes in Rheumatoid Arthritis with Extra-Articular Manifestations

Circulating immune complexes (CIC) and complement C4, C3 and CH50 levels in serum were monitored during 6-30 months in 10 patients with rheumatoid arthritis and extra-articular manifestations (EM). A total of 58 observations were made, 17 at times when new EM emerged, 41 at times when the patients were in a steady state. CIC were demonstrated by two methods, viz. a complement consumption test (CCT) and a polyethyleneglycol (PEG) precipitation assay. The precipitates were analysed for their content of IgG, IgM and IgA. The CCT titre decreased significantly at the time of a new EM, whereas PEG precipitates were found most often at this time. Two types of precipitate could be demonstrated. One consisted of IgG only, which was found most often when the patients were in a steady state. The other one was composed of IgG and other immunoglobulins, most often IgA. The latter type was found most often at the time when the patients developed new EM. Subnormal serum complement levels were demonstrated frequently. The level of C4 was significantly lower at the time of a new EM, compared with the level of patients with RA but without EM. The decrease in anticomplementary effect and the signs of complement activation suggest that the qualitative and quantitative changes in CIC observed at the time of new EM were the cause rather than the consequence of the clinical manifestations.

Alterations in collagen structure in hypermobility and Ehlers-Danlos syndromes detected by Raman spectroscopy in vivo

Patients with hypermobility syndrome (HS) and Ehlers-Danlos syndrome (EDS) were investigated by means of in vivo near- infrared Fourier-transform Raman spectroscopy. HS is a benign and common condition (up to 5 percent of the population of the Western World). EDS is a rare, inherited connective tissue disease characterized by joint hypermobility, skin hyperextensibility, and other, occasionally serious, organ changes. EDS and HS may be related disorders. We investigated 13 patients with HS, 8 patients with EDS, and 24 healthy volunteers by means of in vivo Raman spectroscopy. The patients were classified according to Beighton and Holzberg et al. No difference in age between the three groups was found (HS 41 (33-49), EDS 36 (25-47), controls 37 (31-42); mean, 95% confidence intervals, respectively). Spectral differences were found in the intensity of the amide-III bands around 1245 and 1270 cm-1 in HS and EDS compared with healthy skin (Kruskal-Wallis, p equals 0,02 for intensity ratios (I1245/I1270) between the investigated groups). To elucidate the character of the alterations in the amide-III bands a curve fitting procedure was applied. In conclusion, Raman spectroscopy may aid in the diagnosis of HS and EDS. Moreover the technique may be useful for analyzing the molecular changes occurring in these syndromes.

Acute phase proteins and clinical synovitis activity in patients with rheumatoid arthritis

SummaryA number of laboratory variables, including Hb., ESR and several phase proteins, fluctuated in concord with the clinical signs of synovitis activity in patients with rheumatoid arthritis during a controlled study of 3 disease-modifying anti-rheumatic drugs (DMARD). The correlation between laboratory variables and clinical synovitis was significant in a large patient population but the correlation coefficients were not of such magnitude that any of the laboratory variables reflected clinical synovitis activity in a reliable manner in the individual patients. In patients treated with azathioprine, the response of the Hb, (and consequently of the ESR), was reduced compared to patients given other DMARD. This phenomenon was caused by the bone marrow suppressing effect of azathioprine. However, the effect of azathioprine on the clinical synovitis activity did not differ from that of the 2 other drugs. Similar results were found by reviewing the literature about controlled trials of DMARD. In the present trial the clinical evaluation was performed under optimal conditions. In daily clinical practice the evaluations of the joints may be less than optimal since they may be performed by different rheumatologists with varying experience. Consequently, it may be difficult to do without the unreliable laboratory variables mentioned in the routine assessments of disease activity, unless the quality of routine evaluations of synovitis activity is improved considerably.