The association of silent thyroiditis with active systemic lupus erythematosus.

Autoimmune thyroid disorders have been shown to occur in patients with connective tissue diseases. Hypothyroidism and thyrotoxicosis have been recognized in systemic lupus erythematosus (SLE). Moreover, a high prevalence of antithyroid antibodies has been found in patients with SLE. We studied thyroid function in a group of SLE female patients without a history or clinical diagnosis of thyroid disease and then correlated the prevalence of abnormal function test results with the laboratory indexes of active disease and with the presence of antithyroid antibodies. The SLE patients had significantly lower T4 levels than the controls. Basal TSH and TSH concentrations after TRH stimulation were significantly higher in patients with active SLE in comparison to both patients with inactive SLE and to controls. 45.5% of patients with active SLE presented antithyroid antibodies. Antithyroglobulin and antimicrosomal antibodies were not found in patients with inactive SLE nor in controls. Our results confirm the existence of a mild hypothyroidism in SLE that is clinically silent. The altered thyroid function appears to be dependent on the activity of the systemic autoimmune process.

Microvascular capillaroscopic abnormalities in rheumatoid arthritis patients.

Microvascular circulation was investigated by nailfold capillaroscopy in 32 patients affected by rheumatoid arthritis (RA). In all the patients elongated and tiny capillaries as well as tortuousity were the main shape abnormalities of the capillary loops. Higher subpapilar venous plexus (SPVP) visibility was evidentiated in patients presenting antinuclear and anti-RANA antibodies. No differences in the capillaroscopic pattern were found between rheumatoid factor positive and rheumatoid factor negative patients. In conclusion, elongated and tortuous capillaries seem to be the main alterations in RA, although they are not specific to the disease and are not correlated with the presence of rheumatoid factor. Higher SPVP visibility may be an expression of the endothelial damage induced by antinuclear antibodies in vessel walls.

Sensorineural hearing loss in rheumatoid arthritis.

Hearing function was tested in 20 patients affected by rheumatoid arthritis. Audiological examination was performed by pure tone audiometry thresholds, tympanometry, a stapedial reflex threshold test and auditory brainstem responses (ABR). Hearing impairment was observed in 55% of patients. Conductive hearing loss and the absence of stapedius reflex were never recorded. Five patients with abnormal audiograms had normal ABR and normal stapedial reflex thresholds while 6 patients showed abnormalities in their audiograms, stapedial reflex thresholds test and ABR. Abnormal audiometric results associated with normal ABR are compatible with cochlea involvement, while abnormal audiometric results associated with an altered ABR and stapedial reflex test may be due to retrocochlear involvement. Sensorineural hearing loss appeared to significantly correlate with active disease and with the presence of rheumatoid factor.

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.

Prevalence of diabetes mellitus in common rheumatic diseases.

Association between diabetes and some rheumatic diseases have been proposed. The aim of our work is the evaluation of the prevalence of diabetes mellitus (DM) in a population of patients affected by some common rheumatic disease. We evaluated 356 consecutive out-patients [205 (71.66%) women and 101 (28.34%) men] attending the Rheumatology Unit of the Dept. of Internal Medicine of the Catholic University of Rome. The control group consisted of 200 out-patients, age and sex matched, who were examined in the Dept. of Surgery. The diagnosis of rheumatic patients were osteoarthritis (OA) (45.5%), rheumatoid arthritis (RA) (34%) and periarthritis (PA) (20.5%). The prevalence of diabetes mellitus in our rheumatic population was 5.78% in RA, 6.17% in OA, 10.9% in PA. The prevalence of DM in the control group was 4%. Our data suggest that the prevalence of DM in OA and RA patients is similar to that of general population, while it is significantly higher in PA patients probably for an active role of microangiopathy and hyperglycemia in the genesis of such disease.

Asymptomatic and symptomatic gastroduodenal patients affected by rheumatic disease treated with non-steroidal anti-inflammatory drugs.

It is becoming more apparent that the common gastritis and ulcer complications associated with non steroidal anti-inflammatory drugs (NSAID's) are distinct from classic peptic ulcer disease. To assess the incidence of gastrointestinal lesions and the existence of correlation with gastrointestinal symptoms, patients affected by rheumatic diseases treated with NSAIDs were carefully questioned to evaluate gastrointestinal symptoms and then underwent an esophagogastroduodenoscopic examination. The study demonstrates a relevant absence of gastrointestinal symptoms with an high incidence of gastric mucosal lesions in this patients. Asymptomatic lesions seem to be a characteristic feature of NSAID gastropathy. The blockade of synthesis of prostaglandins, due to the inhibition of cyclooxygenase by NSAIDs, may create an environment conducive to gastritis or ulcer disease and may be responsible of the absence of gastrointestinal symptoms.

Lack of correlation between anticardiolipin antibodies and peripheral autonomic nerve involvement in systemic lupus erythematosus.

The presence of anticardiolipin antibodies has recently been related to a clinical complex in which both central and peripheral neurologic damage is included. A series of 27 female patients affected by systemic lupus erythematosus (SLE) was tested for the presence of peripheral autonomic neuropathy and serum anticardiolipin antibody (ACA) levels were determined in each patient by ELISA. Peripheral autonomic impairment was detected in 40.7% of SLE patients and a large number (77.7%) of patients had elevated levels of ACA. No relationship was found between presence of ACA (both for IgG and IgM classes) and the autonomic neuropathy.

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.

Serum levels of interleukin-1b, tumour necrosis factor-a and interleukin-2 in rheumatoid arthritis. Correlation with disease activity.

Cytokines are potent immunoregulatory factors and may be directly involved in the disordered immunoregulation found in chronic rheumatic diseases. Interleukin-1b (IL-1b), Interleukin-2 (IL-2) and Tumour Necrosis Factor-a (TNF-a) have been implicated in the pathogenesis of rheumatoid arthritis (RA) as mediators of chronic inflammation. Serum levels of IL-1b and TNF-a measured by radioimmunoassay were significantly higher in patients with RA than in healthy controls of similar sex and age while serum levels of IL-2 were significantly lower in the same patients. Further IL-1b and TNF-a were significantly elevated in RA patients with active disease and IL-2 was significantly reduced when compared with patients with low active disease. Serum IL-1b and TNF-a appear to correlate with systemic inflammation, and systemic features of RA may result from dissemination of cytokines produced in the synovium. The role of IL-2 in RA remains controversial. Reduced levels of IL-2 may be an expression of a deficiency of T-cells to produce IL-2 in the active phases of RA or may be due to a possible absorption of IL-2 by lymphocyte receptors.

Serum osteocalcin as an index of bone turnover in active rheumatoid arthritis and in active psoriatic arthritis.

Juxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05 +/- 1.27 ng/ml vs 4.83 +/- 0.88 ng/ml; p less than 0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.

Effect of oral gold salt therapy on bile acid absorption in rheumatoid arthritis patients.

Several studies pointed out an altered stool pattern as the most common side effect of auranofin therapy. The major mechanism in the aetiology of auranofin-induced impairment in bowel habit seems to be the inhibition of Na+/K+ ATPase in the gut. In vitro experiments proved that auranofin can affect active bile acid (BA) reabsorption in rat terminal ileum; this action, due to the ability of the drug to reduce Na+ pump activity by inhibiting Na+/K+ ATPase, may make a significant contribution to the auranofin-induced diarrhoea. The ability of auranofin to reduce the Na+ gradient necessary for active BA reabsorption, however, could cause a decrease of serum BA levels in patients taking auranofin before or without the development of an overt diarrhoea. We measured fasting and postprandial serum conjugated BA levels in 10 female rheumatoid arthritis patients before and after one month and two months' auranofin treatment. No patient developed diarrhoea during the chrysotherapy. When oral gold salt therapy was started, we observed a slight decrease in serum BA levels, but difference was not statistically significant. We can conclude that auranofin therapy does not cause BA malabsorption in patients who do not develop diarrhoea during the treatment.

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.

Concentration of serum bile acids as an index of hepatic damage in systemic lupus erythematosus.

The aim of this work is to evaluate the concentration of serum bile acids (SBA) as an index of impaired liver function in systemic lupus erythematosus (SLE) patients versus usual laboratory tests of hepato-biliary system diseases. In patients with SLE the mean fasting SBA concentration was 9.6 +/- 1.4 mumol/L; in normal subjects the concentration was 2.9 +/- 0.6 mumol/L (P less than 0.01). In patients with SLE, mean gamma-glutamyl transpeptidase (GGTP) concentration was 31.5 +/- 5.9 mU/ml versus 10.05 +/- 1.1 mU/ml in controls (P less than 0.01). The bromsulphalein (BSP) excretion test, 45 minutes after injection, was 6.8 +/- 1% in SLE patients versus 2.8 +/- 0.4% in controls (P less than 0.02). No significant difference was found between these two groups of subjects with respect to leucine aminopeptidase (LAP), alkaline phosphatase (AlPh), glutamic-oxalacetic transaminase (SGOT), glutamic-pyruvic transaminase (SGPT), bilirubin serum rates. SBA rate was abnormal in 50% of the SLE patients; GGTP rate and the BSP excretion test were abnormal in 38% and 27% respectively. Our findings show the presence of an actual liver impairment in SLE patients, significantly demonstrated by fasting SBA concentration, GGTP rate and BSP excretion test. Other liver function tests are less useful in evaluating hepatic damage in SLE.

Thrombosis, recurrent abortions and intrauterine foetal death in a patient with lupus anticoagulant.

The authors describe a case report of a patient suffering from thrombosis and recurrent abortions. Routine coagulation screening was abnormal and investigation showed the presence of a circulating anticoagulant. High titres of anticardiolipin antibodies were demonstrated. Antinuclear antibodies were slightly positive and antinative DNA antibodies were present. Lupus anticoagulant activity and anticardiolipin antibodies seem to be strong markers of a thrombotic tendency.

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.

Acute rheumatoid factor positive (IgM) polyarthritis associated with a Klebsiella pneumonitis.

The authors report a case of a patient suffering from acute polyarthritis with a high rheumatoid factor titre, associated with a Klebsiella pneumonitis. A polyclonal B lymphocyte activation or a possible cross reaction between rheumatoid factor and an antigen related to Klebsiella may explain the elevated production of rheumatoid factor observed.

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.

Clinically silent inflammatory gut lesions in undifferentiated spondyloarthropathies.

Gastrointestinal inflammation or infection can be associated with various forms of arthritis, such as, acute reactive arthritis triggered by enteritis due to gram-negative bacteria or ankylosing spondylitis and peripheral arthritis in relation to Crohn's disease and ulcerative colitis. Using colonoscopy, we have found a high prevalence of clinically silent inflammatory lesions in 38 patients (24 males and 14 females) affected by undifferentiated spondyloarthropathies (SpA). Microscopic inflammatory lesions were present in all the patients. Three patterns of nonspecific chronic inflammatory alterations were observed. No difference was noted between patients taking or not taking nonsteroidal anti-inflammatory drugs. Direct immunofluorescence demonstrated the presence of IgG, IgA, IgM, C3, C4 and fibrinogen in 75% of the specimens examined. The finding of chronic inflammatory gut lesions hypothesizes that a local activation of the immune system depending on the persistence of intestinal microbial antigens or toxins, due to impaired elimination or increased exposition, may have a part in the pathogenesis of SpA.

Chronic active hepatitis and Behçet's syndrome.

In a patient with Behcet's syndrome the finding of five times the normal level of serum transaminase accompanied by weakness may be correlated to the syndrome itself. We performed needle biopsy of the liver in our patient which showed piecemeal necrosis and portal lympho-monocytic infiltration extending into the lobule. It is interesting that HLA B5 and B27 antigens were present. Simultaneous occurrence of chronic active hepatitis and Behcet's syndrome may imply the same autoimmune pathogenesis, as we suggest in this work.

Relapsing polychondritis with severe aortic insufficiency.

Relapsing polychondritis (RP) is a rare disease characterized by auricular, nasal and respiratory tract chondritis, ocular inflammation, inflammatory polyarthritis and cardiovascular abnormalities. Here we describe a patient with a five-year history of mild nasal and auricular chondritis, which suddenly developed into a severe aortic insufficiency with rest dyspnea. The pathogenesis and the management of this rare connective tissue disease are discussed.