Lymphocyte antigens in systemic lupus erythematosus: studies with heterologous antisera.

Rabbit antisera were produced against pooled living lymphocytes from 25 patients with active systemic lupus erythematosus (SLE). Lymphocytes collected at plasmapheresis or venipuncture were frozen in liquid nitrogen and later coated with rabbit antibody to normal human tonsils and normal thymocytes immediately before intravenous immunization of rabbits. Antisera were subsequently extensively absorbed with normal human tonsillar cells, thymocytes, peripheral blood lymphocytes, erythrocytes, and leukocytes from patients with myelogeneous and lymphatic leukemia until residual base-line immunofluorescent staining of normal human lymphocytes using F(ab)2' of whole antisera averaged less than 5%. Absorbed pepsin-digested antisera detected membrane antigens which were markedly increased (mean 32%) on lymphocytes from patients with active SLE (P less than 0.05). Membrane antigens reacting with absorbed, pepsin-digested antisera were present on both T and B cells but, in most instances, predominated on T cells. Control observations using absorbed pepsin-digested antisera to normal human lymphocytes or peripheral blood lymphocytes from patients with rheumatoid arthritis showed no similar specificity. SLE patients treated with moderate or high dose corticosteroids or immunosuppressive agents (cytoxan or azathioprine) appeared to lose lymphocyte antigens detected by these reagents. Control studies with other connective tissue disease patients, miscellaneous hospitalized subjects, or normal controls showed low levels of reactivity (2-5%). SLE lymphocyte membrane antigens uniquely increased during active disease; this may represent neoantigens or alterations associated with the disease itself.

Effects of the lupus anticoagulant in patients with systemic lupus erythematosus on endothelial cell prostacyclin release and procoagulant activity.

A disturbance in endothelial cell (EC) function may be pathogenetic in the thrombotic tendency of patients with the lupus anticoagulant (LA). The ability of serum from normal subjects and patients with systemic lupus erythematosus (SLE), with and without the LA, to modulate the release of prostacyclin (PGI2) and the expression of procoagulant activity by cultured human EC was investigated. Only the 10% and 20% serum concentrations from patients with SLE-LA produced a significantly greater inhibition of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) release (the stable metabolite of PGI2) than control serum. However, when patients with SLE-LA having Raynaud's phenomenon were excluded from this group, there was then no significant difference between the effect of the patient and control serum. Serum from patients with SLE +/- LA caused a significant increase in EC procoagulant activity compared to healthy controls. The two-stage partial thromboplastin time expressed in seconds decreased from 66 (normal) to 34 (SLE - LA) and 31 (SLE + LA), but there was no significant difference between the patients with and without the LA. The significantly increased EC procoagulant activity induced by serum from patients with SLE +/- LA may account for the observed increased incidence of thrombotic events in patients with SLE. Our data suggest that factors other than decreased prostacyclin release are responsible for the altered hemostasis observed in patients with SLE + LA.

The relationship of anti-DNA antibody idiotypes and anti-cardiolipin antibodies to disease activity in systemic lupus erythematosus.

The detection of anti-cardiolipin antibodies and anti-DNA antibody idiotypes has shown utility in a prospective assessment of 42 lupus patients over a 1-year study period. However, so broad is the range of clinical and serological features included in the diagnostic category of SLE that even a combination of tests will often inadequately reflect disease activity at a given time. For the foreseeable future the value of laboratory investigations will probably lie in supporting clinical judgment of the nature of a patient's illness and the severity of the target organ's dysfunction.

Inappropriate peripheral blood lymphocyte responses to herpes viruses in patients with Behçet's syndrome.

Specific antibody production and the proliferative response of peripheral blood lymphocytes (PBLs) to a variety of viruses, including herpes simplex virus-type-1 (HSV-1) and varicella zoster (VZ), were studied in 7 patients with Behçet's syndrome. None of the patients produced an antibody response against HSV-1 or VZ. Furthermore, none of the patients showed a proliferative response to VZ, and three of them also failed to mount a response to HSV-1. These results suggest that the PBLs of patients with Behçet's syndrome make an inappropriately poor antibody and proliferative response when stimulated by HSV-1 and VZ.

In vitro lymph node and peripheral blood lymphocyte responses to influenza immunization in patients with systemic lupus erythematosus.

Following influenza immunization, in vitro anti-influenza antibody production by peripheral blood lymphocytes (PBM) taken from some patients with systemic lupus erythematosus is shown to be impaired despite apparently normal serum antibody responses. One explanation for this finding could be the sequestration of antibody-producing cells in the lymphoid tissue. In this study, antibody production in vitro by lymphocytes from peripheral blood and lymph nodes was measured in parallel following influenza immunization of SLE patients and normal controls. Antibody production by lymph node cells was confirmed in the presence of an impaired PBM antibody response, suggesting redistribution of antibody-producing cells to the lymphoid tissue. This finding was not however, confined to SLE patients, and the relatively low serum antibody response in these individuals suggests a more generalised impairment of the immune response.

An identical twin pair discordant for rheumatoid arthritis and ankylosing spondylitis.

Both rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have an increased familial occurrence and each disease is associated with the inheritance of specific HLA antigens. We report a pair of identical twin brothers with discordant disease phenotypes: one developed AS at the age of 26, and the other developed RA at the age of 55. The twins possessed both of the disease susceptibility antigens HLA B27 and DR4. Differences in the twins' environmental exposure are discussed.

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. III. Development of a computerised clinical chart and its application to the comparison of different indices of disease activity. The European Consensus Study Group for Disease Activity in SLE.

In the first phase of this study, a data-base containing clinical and laboratory findings of 704 patients with systemic lupus erythematosus (SLE), originating from 29 centres and 14 countries, was used to assess the validity of 4 common indices of disease activity, SLAM, BILAG, SLEDAI and SIS. The physician's judgement of activity was assumed as the unique reference criterion (gold standard). Computer programmes were developed to calculate automatically the 4 activity indices; this computation appeared to correspond with manual computations in a sample of 60 appropriately selected cases. All 4 indices were closely correlated with each other (r in the range of 0.716 to 0.872), and with the physician's score (r in the range of 0.620 to 0.719). In the second phase of the study the activity index developed in part I (ECLAM) was prospectively validated, and its performance compared to that of the other scales, both as a single state index and as a transition index (i.e., its ability to assess disease activity at a single point in time and to detect variations in consecutive readings). A computer-assisted clinical chart was prepared for this purpose. This chart allowed us to calculate automatically all the indices. Two consecutive observation times (time 0, and time 1 three months later) were included in the study protocol. Data on 75 patients from 19 centres were collected, and each patient was observed twice. All the computed indices were closely correlated, both at time 0 (r ranging from 0.725 to 0.884), and at time 1 (r ranging from 0.607 to 0.833).(ABSTRACT TRUNCATED AT 250 WORDS)

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE.

A European Consensus Group study, involving 29 centres from 14 countries, was performed in order to reach agreement on the definition of disease activity in systemic lupus erythematosus (SLE) and to construct a new disease index. Data on 704 lupus patients were collected and analysed, using univariate and multivariate statistical procedures, to select those clinical and laboratory features of the disorder which best correlate with the global assessment of disease activity assigned to the patients by the physician of each participating centre. A combination of 15 clinical and laboratory variables was shown to be the best predictor of disease activity in SLE. A European Consensus Lupus Activity Measurement (ECLAM) was then formulated. This index included the 15 selected variables, weighted (with some adjustments) according to their respective regression coefficients in the multivariate model. ECLAM appears to be an effective instrument for scoring patients with different degrees of disease activity. This is the first SLE disease activity index based on data from a very large number of lupus patients followed at a large number of lupus centres in different countries. It might therefore very well serve as a standardised measure for future European clinical studies. Final assessment of the validity, reliability and sensitivity of this index is now underway.

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. I. A descriptive analysis of 704 European lupus patients. European Consensus Study Group for Disease Activity in SLE.

Using a detailed questionnaire, the cumulative historical and current demographic, clinical and serological data on 704 SLE patients from 29 European centres and 14 countries have been assessed. Ninety-three percent of the patients were Caucasian and the female/male ratio was 10:1. Analysis of the cumulative incidence showed that arthralgia/arthritis (94%), rash (69%), Raynaud's phenomenon (49%), serositis (44%) and renal disease (38%) were the most frequent clinical manifestations. Virtually all the patients (98%) were antinuclear antibody positive, while anti-ds-DNA antibodies (76%), hypocomplementaemia (71%) and anti-Ro(SSA) antibodies (35%) were frequent serological abnormalities. Whilst much of this data is in line with previous reports, it is notable that renal, lung, and central nervous system involvement and the frequency of rheumatoid factor, anti-Sm and anti-RNP antibodies were much lower than in most comparable series in the United States. We assume that ethnic differences and the greater present awareness of lupus could explain this variations. Low dose corticosteroids, non-steroidal anti-inflammatory drugs and anti-malarials were used to treat over half of the patients, 75% of whom were between 15 and 55 years of age. This report offers a useful overview of lupus both clinically and serologically in Europe in the 1990's.

Microvascular filtration in subjects with connective tissue disorders.

A simple non-invasive method for studying microvascular filtration in the non-articular tissues of the forearm is described. Rates of filtration under a standard hydrostatic pressure were measured in 20 normal female subjects and 44 female subjects with connective tissue disorders. An increased mean filtration rate was found in 14 subjects with rheumatoid arthritis. In 20 subjects with systemic lupus erythematosus and 10 subjects with scleroderma no such generalised increase in filtration rates was seen, but isolated cases had very high filtration rates, suggesting a more heterogeneous physiological disturbance. Increased filtration was not associated with the presence of oedema. This confirms doubts raised by other workers about the importance of filtration in the genesis of clinical oedema.

The value of masters educational programmes for specialist registrars in rheumatology.

The training of junior doctors has undergone major changes in recent years. There is now more structure, with defined assessment time points leading to a Certificate of Specialist Training. This certificate provides documentation indicating that the trainee has undergone a satisfactory period of training and that they are sufficiently competent to practise as a specialist, unsupervised. The changes have led to re-examination of the role of, and educational provision for, research training as well as clinical training. In this article we review these issues and argue that the development of masters educational programmes may help to address several concerns.

Muscle Disease in systemic lupus erythematosus: a study of its nature, frequency and cause.

The nature, frequency and cause of clinical features suggesting muscle involvement in systemic lupus erythematosus were studied in 20 patients during "active" disease. Half of these patients experienced varying combinations of myalgia, proximal muscle weakness and muscle tenderness. This group "with muscle features" had a higher incidence of arthralgia and much of their myalgia may simply have been due to pain referred from adjacent joints. However, a greater number of abnormalities were also found in the muscle biopsies of this group and it is likely that polymyositis and steroid myopathy were important contributory factors.

Assessment, investigation, and management of acute monoarthritis.

Trauma is the commonest cause of acute monoarticular joint pain and swelling in patients attending an accident and emergency (A&E) department. However, in a significant minority of patients there will be no history of trauma and consequently a different approach to assessment and investigation is required. Our aim is to offer an outline of how to assess, investigate, and manage a patient with monoarthritis. Despite advances in antibiotic treatment diagnostic delay partly explains why septic arthritis is still associated with considerable morbidity and mortality. It is therefore imperative that joint infection is considered above all other diagnoses. Arthrocentesis is a relatively safe procedure and doctors in A&E medicine are encouraged to develop the skills required to aspirate large joints. In the same way that the A&E department is often portrayed as the shop window of a hospital, the joint can reflect a wide variety of internal diseases. Connective tissue disease, inflammatory bowel disease, sarcoidosis, and vasculitis can all present with a monoarthritis. A non-specific reactive monoarthritis may be a feature of a wide variety of common and uncommon infections including, brucellosis, Lyme disease, and leptospirosis. Drugs are also associated with acute arthritis either through their metabolic consequences or as idiosyncratic drug reactions. The ability for the joint to reflect multisystem disease necessitates close liaison with specialists from other fields. A multidisciplinary approach to the management of these patients is strongly encouraged as some will have unusual diseases that require specialist advice. It is not difficult to appreciate how the patient with monoarthritis can present the clinician with a fascinating diagnostic and therapeutic challenge, which we hope this article will help to unravel.

Oestrogen-induced systemic lupus erythematosus.

The subject of this case report, a 64-year-old white female, was treated for osteoporosis with oestrogens. She developed unequivocal systemic lupus erythematosus, from which she had suffered as a young woman and which had remitted with her menopause at 38. The close relationship of the relapses and remissions of her disease with her hormonal status underlines the importance of endocrine factors in the clinical expression of systemic lupus erythematosus.

Effect of oestrogen therapy on plasma and urinary levels of uric acid.

Uric acid clearance studies were carried out on a low-purine diet in 22 trans-sexual men before and during oestrogen therapy for this condition (stilboestrol in 21 cases, ethinyloestradiol in one). Plasma uric acid fell in 15 of the subjects and urinary uric acid rose in 17 of 20 subjects in whom satisfactory collections were obtained. These changes are significant and it is suggested that hormonal influences are responsible for the known age and sex differences in plasma uric acid.

Metal sensitivity in patients with a hinge arthroplasty of the knee.

Fifty patients who had received a hinge arthroplasty of the knee were investigated for possible metal sensitivity. Patients were patch tested against all the metal constituents of the prosthesis. Positive patch tests were found in 32% of patients. Seventeen patients had either lossening or a persistent sterile discharge from the knee. No correlation was found between these complications and metal sensitivity. It was concluded that metal sensitivity is probably not a primary factor in the pathogenesis of complications, particularly loosening.

Sjögren's syndrome: a study of its neurological complications.

A detailed retrospective study of 105 patients with Sjögren's syndrome (50 primary and 55 secondary cases), showed that 31 had vasculitis and 18 had neurological abnormalities which after full investigation were not attributable to other causes. Most of the neurological symptoms were mild and when found in patients with secondary Sjögren's syndrome were more characteristic of the underlying autoimmune rheumatic disease. We found no significant association between the frequency of either vasculitis or any autoantibodies and the presence of neurological disease, but did confirm a significant association between vasculitis and the presence of antibodies to extractable nuclear antigens. We therefore question whether severe and relapsing neurological disease is common in patients with Sjögren's syndrome.