Immunopathological abnormalities in the normal skin of patients with rheumatoid arthritis in relation to clinical and serological findings: a one year follow up study.

Fifty two patients with seropositive rheumatoid arthritis (RA) were studied over a period of one year to investigate possible relationships among changes of circulating immune complexes (CIC), deposits of immunoglobulins and complement around the cutaneous blood vessels, clinical activity of the disease, and the presence of extra-articular manifestations (EAM). The presence or absence of IgM and C3 in and around the cutaneous blood vessels correlated significantly with the presence or absence of extra-articular features in cross sectional and longitudinal studies. Patients with evidence of these cutaneous immune deposits also had a greater prevalence of CIC as determined by the Clq binding assay (ClqBA) or polyethylene glycol (PEG) assay for IC containing IgM (IgM IC). Although the degree of perivascular mononuclear cell infiltration around the blood vessels in the papillary dermis was related to the patients' clinical state at the initial assessment, it did not correlate with the later changes in the activity of the joint disease or the occurrence of EAM. Thus the deposition of immunoglobulin or complement, or both, seems to be independent of cellular infiltration. The meaning of these cellular infiltrates is not yet fully understood. Our study has shown that many patients with RA who appeared to have only joint disease in fact had subclinical systemic disease as reflected by a positive skin biopsy or CIC. Moreover, the disappearance of IgM deposits from the skin correlated with the disappearance of EAM and improvement of joint disease.     

Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity.

Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03).     

Perivascular infiltration in normal skin of patients with rheumatoid arthritis: association with rheumatoid factors and HLA-DR antigens.

The relation between immunohistological findings in biopsy specimens of apparently normal skin, HLA antigens, and rheumatoid factors (RF) was studied in 120 patients with rheumatoid arthritis (RA), selected for treatment with D-penicillamine. Perivascular infiltration (PVI) of more than three mononuclear cells was present in 77 (68%) of 114 patients, accompanied usually by the presence of IgM or C3, or both, in immunofluorescence studies. The number of perivascular cells was associated significantly with the titre of circulating RF. A weak relation of both perivascular cellular infiltration and RF with HLA-DR3 and DR4 did not reach statistical significance. It is concluded that the histological presence of perivascular inflammation is associated mainly with deposition of RF. It is suggested that the first is merely an epiphenomenon of the latter. PVI was not prognostic for the occurrence of the clinical syndrome of rheumatoid vasculitis. For practical purposes skin biopsies do not appear to be useful in the evaluation of individual patients with RA.     

Immunoglobulin and complement deposition in skin of rheumatoid arthritis and systemic lupus erythematosus patients.

Rheumatoid arthritis (RA) was differentiated from systemic lupus erythematosus (SLE) by direct immunofluorescent techniques on skin specimens, using monospecific antisera for IgG, IgM, C3, C1q, properdin, and fibrin. Of 30 patients with RA studied, 20 had dermal vessel deposits of immunoglobulins and complement components in unaffected skin without the characteristic dermal-epidermal junctional fluorescence of SLE. Of 24 SLE patients studied, 24 had granular deposits of immunoglobulins and complement components in unaffected skin at the dermal-epidermal junction.     

Relation between patients' own health assessment and clinical and laboratory findings in rheumatoid arthritis

Health status encompasses not only physical aspects, but also psychological and social aspects. A multidimensional health status questionnaire was used in 69 Dutch patients with rheumatoid arthritis to assess their physical, psychological and social well being. The same day clinical and laboratory data were recorded. The health status questionnaire provided additional information to clinical and laboratory findings. The various clinical and laboratory measures of disease activity reflect aspects other than the self-reported measure of physical well being. As such they are not interchangeable. Furthermore clinical and laboratory measures of physical well being appeared to be unrelated with psychological and social measures. In contrast, the patients' self-report of physical well being was related only with depressive mood and to some extent with anxiety.     

An idiopathic hypereosinophilic syndrome mimicking seronegative rheumatoid arthritis: 20-year follow-up with clinical and laboratory findings.

A clinical case of idiopathic hypereosinophilic syndrome mimicking seronegative rheumatoid arthritis with a twenty year follow-up is reported. The patient showed other sign of the disease, such as pericarditis, gastroenteritis and hepatomegaly. Among the laboratory findings the elevated levels of aldolase and LDH 2, never reported previously, are stressed.     

Late onset rheumatoid arthritis: clinical and laboratory comparisons with younger onset patients

We aimed to compare the clinical and laboratory profiles of the patients presenting late onset rheumatoid arthritis (LORA) with younger onset rheumatoid arthritis (YORA) patients. During the period between January 1995 and December 2004, 124 patients with LORA were identified from a retrospective chart review of inpatients and outpatients. They were compared with 150 YORA patients examined during the same period including their clinical and laboratory findings. The mean ages of the patients with LORA and YORA were 71.7+/-5.9 years, and 52.1+/-11.5 years, respectively. The gender ratio (female/male) was 1.48 in LORA and 2.85 in YORA (p = 0.012). The average ages of the disease onset were 42.2+/-10.4 years in YORA and 68.4+/-4.6 years in LORA. The duration of the diagnosis was longer in LORA than in YORA (20.7+/-14.3 months versus 10.3+/-6.2 months, p < 0.001). Rheumatoid arthritis (RA) duration was shorter in LORA than in YORA (43.5+/-64.4 months versus 126.3+/-101.0 months, p < 0.001). Although LORA patients had more significant frequent shoulder joint involvements (p < 0.001), proximal interphalangeal (PIP), metacarpophalangeal (MCP), elbow, metatarsophalangeal (MTP) and ankle involvements were common in YORA. Wrist, knee and hip involvements were not different in the groups. Classical rheumatoid hand deformities, interstitial lung disease and Sj?gren's syndrome (SS) were significantly lower in LORA than in YORA. LORA patients had more common weight loss, myalgia, lymphadenopathy, polymyalgia rheumatica (PMR)-like syndrome and neuropathy. The frequencies of RF, ANA, anti-SSA/Ro and anti-SSB/La positivities were lower in LORA than in YORA, whereas elevated erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) and anemia associated with chronic disease were higher in LORA. Patients with LORA, according to the accepted international criteria, present with different clinical and laboratory profiles when compared with younger patients. These results suggest that age may influence the presentation of RA at onset.     

Antibodies to DNA in patients with rheumatoid arthritis and juvenile rheumatoid arthritis.

Antibodies to double-stranded DNA (DSDNA) were found in 18 patients with RA, in 5 patients with JRA, and in 5 patients with undiagnosed connective tissue disease. Five patients had clinical features consistent with both RA and SLE, 11 with only RA, and 5 with only JRA. Based on these observations, the presence of serum anti-DSDNA antibodies should not be used as a sole criterion in the diagnosis of SLE.     

CPPD crystal deposition disease in patients with rheumatoid arthritis

The aim of this study was to assess the frequency and the outcome of patients suffering from rheumatoid arthritis in which calcium pyrophosphate dihydrate (CPPD) crystal deposits were found to coexist in synovial fluid analysis. Such association was more frequent than previously believed with CPPD crystals found in 25.8% of 93 patients with rheumatoid arthritis. As a group, a trend toward a worse outcome was suggested by more frequent prostheses of the lower limb.     

P wave dispersion in patients with rheumatoid arthritis: its relation with clinical and echocardiographic parameters

P wave dispersion (PWD) is a sign for the prediction of atrial fibrillation (AF). The aim of this study was to assess P wave dispersion and its relation with clinical and echocardiographic parameters in patients with rheumatoid arthritis (RA). Thirty RA patients (mean age 49 ± 10 years) and 27 healthy controls (mean age 47 ± 8 years) were included in the study. We performed electrocardiography and Doppler echocardiography on patients and controls. Maximum and minimum P wave duration were obtained from electrocardiographic measurements. PWD defined as the difference between maximum and minimum P wave duration was also calculated. Maximum P wave duration and PWD was higher in RA patients than controls (P = 0.031 and P = 0.001, respectively). However, there was no significant difference in minimum P wave duration between the two groups (P = 0.152). There was significant correlation between PWD and disease duration (r = 0.375, P = 0.009) and isovolumetric relaxation time (r = 0.390, P = 0.006). P wave duration and PWD was found to be higher in RA patients than healthy control subjects. PWD is closely associated with disease duration and left ventricular (LV) diastolic dysfunction.     

Correlation of clinical and serological findings in patients with rheumatoid arthritis treated for one year with interferon-gamma

Results of a large therapeutic trial of interferon-gamma in patients with rheumatoid arthritis (RA) are described. Of 110 RA-patients enrolled in this clinical trial, 46 were treated with interferon-gamma for 12 months. During the treatment period, dosage was reduced on an individual basis. There was a correlation between the improvement of clinical parameters, such as pain or morning stiffness, and the improvement of laboratory parameters such as erythrocyte sedimentation rate, anemia, leucocytosis or thrombocytosis. Interferon-gamma was well tolerated, and no organ toxicity was detected.     

The extra-articular deposition of fibrinogen antigenic material in patients with rheumatoid arthritis.

Experimental suction blisters were elicited on extensor and flexor sites or forearm skin of patients both with rheumatoid arthritis and without rheumatoid diseases. The blister fluid obtained was investigated, together with rheumatoid bursa fluid and rheumatoid noduli material by crossed and quantitative immunoelectrophoresis for fibrinogen antigenic material, plasminogen and inhibitors of fibrinolysis. In rheumatoid noduli and rheumatoid bursa fluid, fibrinogen degradation products identical with those previously described in rheumatoid synovial fluid and in bullous dermatosis were found (3, 14). On the other hand, no fibrinogen antigenic material was found in the experimental suction blisters. These results indicate that the fibrinogen degradation products in rheumatoid inflammatory exudate are probably not specific for a rheumatoid process, but rather part of a general mechanism in inflammation.     

Thyroid ultrasonography related to clinical and laboratory findings in patients with silent thyroiditis.

We summarized the clinical course of 10 patients with silent thyroiditis and evaluated the clinical usefulness of ultrasonography, in combination with clinical and laboratory findings, for the differentiation from Graves' disease. Serum T3 and T4 were increased in all cases, and the ratio of T3/T4 (ng/micrograms) was 17.8 +/- 3.6 (SD). But in 3 of 10 patients the ratio was greater that 20. TSH receptor antibody (TRAb) and thyroid stimulating antibody (TSAb) were negative in all cases. The estimated thyroid volume by ultrasonography was 18.4 +/- 5.5 ml, which was slightly increased but significantly lower than those in Graves' disease (p less than 0.05). The internal texture of the thyroid showed a decreased echogenicity with a mean echo level of 70.4 +/- 15.4. There was a weak positive correlation between the echo level at the onset of thyrotoxicosis and the lowest T3 level during the clinical course (p less than 0.05). It is suggested that ultrasonography gives a useful information to the diagnosis and outcome of patients with silent thyroiditis.     

Radiographic assessment in relation to clinical and biochemical variables in rheumatoid arthritis

Radiographs of hands and feet were obtained from 125 consecutive patients with rheumatoid arthritis (RA) and the degree of destruction was assessed numerically on a 200-point scale using Larsen's standard radiographs as reference. The method is shown to possess a satisfactory degree of reproducibility. In 96 of these 125 patients, values of another 15 simultaneously determined clinical and biochemical variables were obtained. On applying linear and quadratic multiple regression analysis to this set as well as to the male and female subsets, an 'automatic' selection procedure (stepwise regression) proved duration of disease to be the most important factor relating to the 'Larsen index'. The 96 patients were therefore ranked with respect to duration of disease and divided into 4 subsets of equal magnitude. In the 3 subsets with duration of disease less than 21 years, stepwise regression produced in the final step linear or quadratic combinations not containing duration of disease but correlating quite well with the 'Larsen index' (R = 0.64-0.96). A similar result was obtained upon performing an analogous procedure in the female subset. In all instances, positive contributions of varying degree were obtained from Ritchie's index, ESR, a-antitrypsin (A1-AT), orosomucoid, fibrinogen, and IgM, while negative correlations were associated with ceruloplasmin, IgG, and IgA.