ACTH, cortisol and prolactin in active rheumatoid arthritis.

Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1 beta and TNF-alpha circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1 beta and TNF-alpha levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1 beta and TNF-alpha reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients.

Craniocervical junction involvement in rheumatoid arthritis: a clinical and radiological study.

OBJECTIVE: To make a comparative evaluation of different imaging techniques for studying the craniocervical junction involvement in patients with rheumatoid arthritis (RA). Upper cervical spine involvement was compared with clinical and immunological data. METHODS: Patients (n = 47) underwent plain radiographs and computerized tomography (CT) and magnetic resonance (MR) study of the craniocervical junction. Neurological examination following clinical signs of possible atlantoaxial involvement was performed in all patients following the Ranawat classification. RESULTS: Radiographic and MR images showed craniocervical involvement in 41.3% and 61% of the patients, respectively. Immunological data were not correlated with imaging findings, whereas Ranawat class II and III of neurological involvement seem to be predictive of atlantoaxial alteration. CONCLUSION: Conventional radiography allowed us to detect 41.3% of patients with craniocervical involvement, but only in advanced stages of the disease. MR imaging had the unique potential of direct and detailed synovial visualization, especially in the gadolinium enhanced axial images, resulting in the early diagnosis of craniocervical RA.

Serum zinc and copper in active rheumatoid arthritis: correlation with interleukin 1 beta and tumour necrosis factor alpha.

Serum zinc and copper levels and serum interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) levels were evaluated in 57 female patients with active rheumatoid arthritis (RA) to investigate a possible role of IL1 beta and TNF alpha on zinc and copper homeostasis in RA. Serum zinc levels were significantly lower and serum copper levels significantly higher in RA patients when compared with osteoarthritis or asymmetrical psoriatic oligoarthritis patients and with normal controls. No differences were observed in serum IgM rheumatoid factor positive and serum IgM rheumatoid factor negative patients as regards serum zinc and copper concentration. In RA patients the erythrocyte sedimentation rate and acute-phase proteins correlated negatively with serum zinc and positively with serum copper. IL1 beta and TNF alpha were found to correlate negatively with zinc and positively with copper in RA patients. Lower levels of zinc may be due to an accumulation of zinc-containing proteins in the liver and in the inflamed joints in RA. Elevated serum copper levels seem to be linked to the increased synthesis of ceruloplasmin by the liver.

Quality of life assessment during six months of NSAID treatment [Gonarthrosis and Quality of Life (GOAL) Study].

OBJECTIVE: To identify the time point of the greatest degree of improvement in daily living activities, pain and depression in patients with osteoarthritis (OA) of the knee during 6 months of treatment with NSAIDs, in order to define compliance and drop-out rate. METHODS: 107 patients were recruited into a multicentre, prospective, randomized, controlled trial comparing two treatments, piroxicam-beta-cyclodextrin (PBCD) and slow release diclofenac (DCL). RESULTS: The greatest improvement in quality of life occurred in both groups after 3 months, with a slight further gain observed by the end of treatment. The Stanford Health Assessment Questionnaire score improved (p < 0.05 vs baseline) at 3 and 6 months with PBCD and at 6 months with DCL. The Arthritis Impact Measurement Scale score improved (p < 0.05 vs baseline) after 6 months in both groups. Significant (p < 0.05 vs baseline) improvement in other psychological and pain scores were recorded in both groups after 3 and 6 months. Compliance with treatment at 3 months was 73% for PBCD and 72% for DCL, and was 60% in both groups at 6 months. CONCLUSIONS: The results of this study indicate that the optimal length of time for an NSAID trial in OA patients is 3 months, when assessment of daily living activities is considered as the main outcome criterion.

Autonomic nerve dysfunction in systemic lupus erythematosus: evidence for a mild involvement.

Neurologic manifestations are known to occur in patients with systemic lupus erythematosus (SLE) and significantly affect the clinical course of the disease. Nevertheless, the prevalence, pattern and severity of autonomic impairment in such patients have yet to be defined. In the present study a series of 38 female SLE patients was assessed for the presence of autonomic dysfunction. Five noninvasive standardized cardiovascular reflex tests were used. The grading system proposed by Ewing and Clarke was applied to classifying autonomic impairment according to severity. Seventeen out of 38 patients, that is 44.7%, had evidence of autonomic impairment. Most of the patients had a mild degree of dysfunction. No correlation was found for the duration of the disease while an apparent lack of the commonly described chronological sequence of autonomic involvement was observed. We suggest that in SLE patients the prevalence of autonomic impairment, when investigated, does not significantly differ from that of other SLE-associated neurological events. The contribution of a direct immunological damage to components of neural pathways in the pathogenesis of the autonomic involvement can be postulated. Clinical consequences of autonomic impairment in patients with systemic lupus erythematosus need to be elucidated.

Behçet's disease and cardiac arrhythmia.

Only few cases of cardiac conduction disturbances and arrhythmias have been reported in Behçet's disease. We recently observed the case of a 16-year-old woman with Behçet's disease in whom cardiac arrhythmia became the main clinical symptom. This observation and a review of the literature led us to the conclusion that arrhythmia could represent the clinical manifestation of an underlying myocarditis due to Behçet's disease and can be regarded as a feature of cardiac involvement of the disease.

[Integrated role of computerized tomography and magnetic resonance imaging in identifying the early changes in rheumatoid arthritis of the craniocervical junction]. / Ruolo integrato della Tomografia Computerizzata e della Risonanza Magnetica nel rilievo delle alterazioni precoci dell'artrite reumatoide della giunzione cranio-cervicale.

Any cervical spine segment may be affected by rheumatoid arthritis, but destructive changes are most prominent at the craniocervical junction. Cervical involvement is a devastating complication of the disease, because of the risk of a range of neurological complications (paresthesia, cervical myelopathy, vertebro-basilar insufficiency), and even sudden death from medullary compression. However, the incidence of both cervical rheumatoid arthritis and its neurological complications are still debated, being respectively reported in 17-86% and 11-70% of the patients, according to the variability in neurological and radiologic classification systems adopted by the authors. To assess the incidence of cervical rheumatoid arthritis and the integrated role of different imaging techniques in its diagnosis, 38 consecutive patients (29 women and 9 men) with rheumatoid arthritis according to the American Rheumatism Association criteria were examined. The average age was 60 years (range: 27-70 years) with a mean disease duration of 6.6 years (range: 6 months-25 years). All the patients underwent conventional radiography of the cervical spine, unenhanced Computed Tomography (CT) of the craniocervical junction and unenhanced and Gadolinium-enhanced Magnetic Resonance Imaging (MRI) of the cervical spine. Cervical spine involvement was demonstrated in 25/38 (66%) patients 20 women and 5 men, with an average age of 57 years and a mean disease duration of 8.5 years. In 13 of them (mean disease duration: 12.7 years), the diagnosis was made with radiography which showed atlantoaxial and subaxial subluxations and/or erosions. Of the 12 patients with negative conventional radiography (mean disease duration: 2.5 years), 4 were identified with both CT and MRI (synovial pannus and erosions). 3 with MRI only (joint effusion/hypervascularized synovial pannus), and 5 exhibited questionable CT findings which were clarified only by MR demonstration of inflammatory tissue contiguous to suspicious irregularities of the cortical bone of the odontoid process. 52% (13/25) of cervical rheumatoid arthritis patients were identified with plain radiographs, 68% (17/25) with CT and 100% (25/25) with MRI. Our preliminary data show that a specific tool for the diagnosis is recommended even in the early disease phases since rheumatoid arthritis commonly affects the craniocervical junction. Studying the craniocervical region is clinically difficult, and diagnostic imaging assessment is essential. Conventional radiography allowed to detect more than half the patients with cervical rheumatoid arthritis, but only in advanced disease stages. On the contrary, MRI had the unique potential of direct and detailed synovial visualization, thus permitting the diagnosis of cervical involvement even in the early phases of the inflammatory process, when CT findings were still negative or questionable.

Slow progression of joint damage in early rheumatoid arthritis treated with cyclosporin A.

OBJECTIVE: To evaluate the ability of low-dose cyclosporin A (CsA) to control radiologic disease progression, and to assess the clinical efficacy and tolerability of CsA, compared with conventional disease-modifying antirheumatic drugs (DMARDs), in patients with early active rheumatoid arthritis (RA). METHODS: In this long-term, multicenter, prospective, open, blinded end point, randomized trial, 361 consenting patients with early (<4 years since diagnosis) active RA were enrolled. Of the eligible patients, 167 were treated with CsA at 3 mg/kg/day, and 173 with DMARDs. The decision to use conventional antirheumatic drugs as controls was based on the fact that joint erosion could be expected to occur after 1 year regardless of the type of DMARD being used. The possibility of switching therapies in both groups was intended to keep the largest possible number of patients in the study. RESULTS: Blinded evaluation of hand and foot radiographs after 12 months of treatment showed that CsA led to a significant (P < 0.001) delay in the mean +/- SD progression in the eroded joint count (1.3 +/- 3.1 versus 2.4 +/- 3.0 for the control group) and in the joint damage score (3.6 +/- 8.9 versus 6.9 +/- 9.1 for the control group), both measured by the Larsen-Dale method. When only the patients without erosion at baseline were considered (37 in the CsA-treated group and 54 in the control group), erosion appeared in only 10.8% of the CsA-treated patients, but in 51.8% of the controls (P = 0.00005). Low-dose CsA was as effective as traditional DMARDs in controlling clinical symptoms. Maintenance on the initially prescribed treatment regimen ("survival on treatment") was also better at 12 months with CsA than with DMARDs (89.2% versus 77.5%; P = 0.002). The tolerability of CsA was acceptable. CONCLUSION: These 12-month results suggest that low-dose CsA decreases the rate of further joint damage in previously involved joints as well as the rate of new joint involvement in previously uninvolved joints, in patients with early RA.

A study of serum androgen and cortisol levels in female patients with rheumatoid arthritis. Correlation with disease activity.

Androgen status and the role played by androgens in the pathogenesis of rheumatoid arthritis (RA) in female patients are a matter of debate. In the present study serum testosterone (T), DHEAS, sex hormone binding globulin (SHBG) and cortisol levels were determined in 55 RA women, both in pre- and post-menopausal (M) status, and in a group of healthy subjects. Patients were divided into two groups according to disease activity and a correlation analysis of hormonal levels against serum IL1beta levels was performed. No significant differences were found in serum T levels between RA patients and controls, both in preM (1.38 +/- 0.4 vs 1.35 +/- 0.3 nmol/l; p = ns) and in postM status (1.21 +/- 0.2 vs 1.10 +/- 0.2 nmol/l; p = ns). Serum SHBG levels were lower in RA patients than in control subjects, both in pre and in postM status. DHEAS levels were significantly lower in preM RA patients than in controls (2.34 +/- 1.2 vs 5.93 +/- 1.6 mu mol/l; p < 0.001) while cortisol levels were significantly higher in preM active RA patients than in controls (466.2 +/- 30.3 vs 411 +/- 66.2 nmol/l; p = 0.02). IL1beta levels were significantly higher in RA patients than in controls both in pre- and postM subjects (70 +/- 33.8 vs 23.1 +/- 2.9 and 92 +/- 27.4 vs 31.9 +/- 3.1 fmol/l, p < 0.001, respectively). Although androgen status could play a role in the pathogenesis of RA, at present it is not possible to exclude the influence of RA itself on sex hormone profile.

[Quantitative ultrasonography in the evaluation of postmenopausal osteoporosis. Comparison with dual energy x-ray absorptiometry]. / Ultrasonografia quantitativa nello studio dell'osteoporosi postmenopausale. Confronto con l'assorbimetria a raggi X a doppia energia.

In order to compare the capacities of quantitative ultrasonography and dual energy X-ray absorptiometry to measure bone mineral density (BMD) in postmenopausal women, 45 postmenopausal patients were studied. They were divided into two groups on the basis of the results of absorptiometry: Group A (20 patients) had BMD values within normal limits, and Group B (25 patients) had BMD values lower than 1 standard deviation (SD) of the average for an age and sex matched population. Ultrasonography of the non-dominant heel was carried out on both groups to determine broadband ultrasound attenuation (BUA), speed of sound (SOS) and bone velocity (BV). A negative correlation between age and BMD, BV, SOS, and BUA was observed in all subjects. A positive correlation between BMD and BV and between BMD and SOS was found. In Group A, age correlated negatively with BMD, BUA, SOS and BV, and BMD correlated positively with BV. In Group B, age correlated negatively with BMD, and BMD correlated positively with BV and SOS. BV values were significantly elevated in Group B. The study evidenced a relationship between ultrasonography and absorptiometry in determining bone density in postmenopausal women. As ultrasonography and absorptiometry provided comparable information on bone density, we point out that ultrasonography can be used as a simple and sensitive indicator for postmenopausal osteoporosis.

[Keratoconjunctivitis sicca in rheumatoid arthritis: correlation with the autoantibody pattern]. / Cheratocongiuntivite secca nell'artrite reumatoide: correlazione con il pattern autoanticorpale.

In order to evaluate the autoantibody pattern of subjects affected by rheumatoid arthritis (RA) with clinical features of keratoconjunctivitis, we studied 32 out- and in-patients (26 women, 6 men, average age 52 years, average disease duration 5.5 years) at the Division of Rheumatology, Catholic University of Rome. We found keratoconjunctivitis sicca and xerostomia in 22 (68.75%) patients with RA. Rheumatoid factor was present in 17 (53.1%) patients, antinuclear antibodies (ANA) were observed in 15 (48.4%) patients, and anti-rheumatoid arthritis nuclear antigens (RANA) in 22 (68.7%) patients; anti-SSA antibodies were confirmed in 3 (9.4%) patients and anti-SSB antibodies in 2 (6.2%) patients. None of the patients evidenced anti-U1RNP. Although keratoconjunctivitis sicca and xerostomia correlated significantly with the presence of rheumatoid factor, we found no relationship between these two conditions and ANA or anti-RANA antibodies. The high frequency of keratoconjunctivitis sicca and xerostomia in our RA patients is the expression of extra-articular involvement in this disease and is correlated with the presence of rheumatoid factor. ANA and anti-RANA antibodies may represent aspecific polyclonal activation in RA.

Platelet lactate dehydrogenase activity in systemic lupus erythematosus: correlation with anticardiolipin antibodies.

OBJECTIVE: To evaluate lactate dehydrogenase (LDH) activity in platelet subpopulations in systemic lupus erythematosus (SLE) and to correlate platelet LDH activity with concentrations of anticardiolipin antibody (aCL). METHODS: Twelve female patients with SLE and 12 age matched female control subjects were studied. Platelets were separated on the Percoll gradient, their density values controlled by density marker beads. LDH activity was measured after platelet lysis, expressed as nU/fl. ELISA were used to measure levels of IgG and IgM aCL. RESULTS: A significant increase of LDH activity with a significant correlation to IgG and IgM aCL were found in small, light platelets with a volume < 5 mu 3 compared to large, dense platelets and to controls. LDH activity did not correlate with immunoglobulin classes, anti-DNA antibodies, and complement fractions in small and large SLE platelets. CONCLUSION: Our data suggest a possible chronic activation of subpopulations of small platelets in patients with SLE independent of thrombotic process. Low levels of aCL can mediate small platelet activation. Quantitative and qualitative analysis of the small, light platelets can serve a clinical diagnostic purpose as an in vivo platelet activation index in SLE.