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Patient: Female, 19-year-old Final Diagnosis: Systemic lupus erythematosus Symptoms: Cough • Fever • malaise and fatigue • polyarthralgia • skin rash Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Unknown ethiology Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease resulting from dysregulation of the immune response. In genetically predisposed subjects, infections reputedly trigger an immune activation leading to autoimmunity and overt autoimmune diseases such as SLE. Case Report: We report the case of a 19-year-old woman who presented to our hospital reporting high-grade fever, dry cough, and polyarthralgia despite a course of empiric antibiotic and steroid therapy administered by her general practitioner (GP). On physical examination, she had a malar rash, a palpable erythematous maculopapular non-itchy rash over the limbs and trunk, and mild polyarthritis. A contrast computed tomography (CT) scan of the chest showed a pulmonary right upper-lobe consolidation with air bronchogram and multiple necrotizing conglomerate mediastinal lymph nodes. Culturing of collected samples from endobronchial ultrasound-guided trans-bronchial needle aspiration (EBUS-TBNA) of the mediastinal lymph node revealed growth of Mycobacterium kansasii. Antinuclear antibodies (ANA) and lupus anticoagulant (LAC) were positive. A diagnosis of M. kansasii infection associated with SLE was made. She was started on anti-mycobacterial and hydroxychloroquine therapy and entered into a joint rheumatological and infectious disease follow-up. Six months later, a CT scan with positron emission tomography (PET) showed a significant reduction in size of the basal right upper-lobe consolidation and hypermetabolic activity in multiple pulmonary areas and mediastinal lymph nodes. ANA and LAC tests were repeated and remained positive. The decision was made to continue the ongoing therapy course for 1 year in total. Conclusions: Clinical and experimental studies have suggested the association of mycobacterial infections with SLE and as a possible infectious trigger of autoimmunity. We describe a unique case of M. kansasii infection associated with the onset of SLE in a young woman.

Objectives: Osteoporosis and bone erosions are hallmarks of rheumatoid arthritis (RA) since disease onset is underpinned by the inflammatory burden. In this observational study, we aimed to dissect the putative RA-related parameters and bone-derived biomarkers associated with systemic and focal bone loss at disease onset and with their progression.Methods: One-hundred twenty-eight patients with early rheumatoid arthritis (ERA) were recruited at disease onset. At study entry, demographic, clinical, and immunological parameters were recorded. Each ERA patient underwent plain X-rays of the hands and feet at study entry and after 12 months to assess the presence of erosions. After enrollment, each patient was treated according to the recommendations for RA management and followed up based on a treat-to-target (T2T) strategy. At baseline, blood samples for soluble biomarkers were collected from each patient, and plasma levels of osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), Dickkopf-1 (DKK1), and interleukin 6 (IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Seventy-one ERA patients underwent bone mineral density (BMD) measurement at the left femoral neck and second to fourth lumbar spine vertebrae (L2–L4) by dual-energy X-ray absorptiometry (DXA).Results: Among the whole cohort, 34 (26.6%) ERA patients with bone erosions at study entry had a higher disease activity (p = 0.02) and IL-6 plasma levels (p = 0.03) than non-erosive ones. Moreover, at DXA, 33 (46.5%) ERA patients had osteopenia, and 16 (22.5%) had osteoporosis; patients with baseline bone erosions were more likely osteopenic/osteoporotic than non-erosive ones (p = 0.03), regardless of OPG, RANKL, and DKK1 plasma levels. Obese ERA patients were less likely osteopenic/osteoporotic than normal weight ones (p = 0.002), whereas anti-citrullinated protein antibodies (ACPA) positive ERA patients were more likely osteopenic/osteoporotic than ACPA negative ones (p = 0.034). At logistic regression analysis, baseline Disease Activity Score measured on 44 joints (DAS44) [OR: 2.46 (1.11–5.44)] and osteopenic/osteoporosis status [OR: 7.13 (1.27–39.94)] arose as independent factors of erosiveness. Baseline osteopenic/osteoporotic status and ACPA positivity were associated with bone damage progression during the follow-up.Conclusions: Bone erosions presence is associated with systemic bone loss since the earliest phases of RA, suggesting that the inflammatory burden and autoimmune biology, underpinning RA, represent crucial enhancers of bone remodeling either locally as at systemic level.

Background Gastrointestinal (GI) symptoms are seen in majority of patients with Systemic Sclerosis (SSc) and are a common presenting feature of disease. Severe GI involvement may lead to malabsorption which represents a poor prognostic factor. Accordingly, a regular monitoring of gastrointestinal tract involvement and nutritional status appears crucial in SSc patients. Previous studies reported low values of bone mass density (BMD) in SSc patients1. While no specific relationship has emerged between the two conditions, it’s likely that disease related GI involvement may contribute to the alterations in BMD. Objectives To determine if GI-related clinical status was associated to low bone density in our cohort of SSc patients. Methods Two-hundred-ten unselected SSc patients have been enrolled. The 7-items UCLA SCTC GIT 2.0 questionnaire and Malnutrition Universal Screening Tool (MUST) were administered to each patient. A comprehensive medical history was collected. A blood panel for nutritional status was also performed. T-scores and Z-scores at lumbar spine, femoral neck, Ward’s and total hip measured by dual-energy X-ray absorptiometry (GE Lunar Prodigy) were measured. Results In our cohort, 86.7% of patients reported some GI symptoms. The mean UCLA GIT total score was 0.345±0.34 and 51 patients (24.3%) were at risk of malnutrition according to MUST (score ≥1). 53.7% patients had BMD values Patients with spine T-score Femoral neck T-score On the other hand, the comparison of patients with severe, moderate and mild symptoms according to UCLA GIT total score2 showed an association between progressively lower values of spine and total hip T-score and increasing severity of GI symptoms (ANOVA for spine T-score: p=0.015; for total hip T-score: p=0.048). Patients at risk of malnutrition (MUST score ≥1) presented significant lower T-score for all the considered sections (spine and hip) and significant lower total hip Z-score. Conclusions In our SSc cohort gastrointestinal symptoms were frequent and were associated with low BMD. Considering the heterogeneity of GI involvement, UCLA SCTC GIT 2.0 emerged as a useful and feasible tool to assess GI involvement and other associated comorbidities. In particular, SSc patients who report remarkable GI symptoms and are at risk of malnutrition according to MUST may benefit from a stricter control of BMD to promptly detect osteopenia and osteoporosis. References [1] Omair MA, et al. J Rheumatol. 2013 [2] Khanna D, et al. Curr Opin Rheumatol. 2013 Disclosure of Interest None declared

Objective: To evaluate the serum levels of tumour-associated antigens (TAAs) in patients with SSc and interstitial lung disease (ILD) and to define whether their levels mirror the severity and the progression of lung damage. Methods: Data from 80 SSc patients with ILD were collected at baseline and after 2 years as well as from 40 SSc controls without ILD. The occurrence of any malignancy was recorded. Results: At baseline, an increase of at least one TAA was present in 35 SSc patients with ILD compared with 6 SSc patients without ILD (P < 0.0001); this was associated with lower forced vital capacity (FVC) and higher interstitial and alveolar scores. Levels of carbohydrate antigen 15-3 and carcinoembryonic antigen inversely correlated with FVC and directly correlated with alveolar and interstitial scores and their levels were higher in patients who presented a progression of lung damage after 2 years. During 4 years of follow-up, a malignancy was detected in seven patients who already had an increase of at least one TAA. Values of TAAs increased over time in patients who developed cancer, while their trend remained stable in the others. At multivariate analysis, to have three or more TAAs emerged as a strong independent predictor of the development of malignancies [relative risk 24.1 (95% CI 1.8, 315.0), P = 0.02]. Conclusion: TAAs can be elevated in the sera of SSc patients and correlate with the degree of lung damage, suggesting a role as severity biomarkers. Close follow-up is necessary in SSc patients because of the increased cancer risk overall in patients with increased TAAs.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score

Testosterone (T), sex hormone-binding globulin, (SHBG), dehydroepiandrosterone sulfate (DHEAS), and prolactin (Prl) serum levels were measured by electrochemiluminescense immunoassay (ECLIA) in 39 patients with systemic sclerosis (SSc) and compared with serum hormonal levels in control subjects matched for sex and reproductive status. A possible relationship with disease duration and disease severity was examined. Our data show an altered androgen and prolactin (Prl) status in SSc patients, in most cases related to disease duration and disease severity score. We can hypothesize that hormonal dysregulation is a consequence of the chronicity of the disease. The altered hormonal status could result in relative immunological hyperactivity contributing to enhance tissue damage and disease severity.

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.

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. PRL/cortisol ratio, and IL-1beta and TNF-alpha levels were determined in patients with RA and in control subjects at 0600, 1000, 1400, 1800, 2200, and 0200 hours. In patients with RA we observed higher PRL/cortisol ratio at 0200 hours, whereas IL-1beta and TNF-alpha reached their highest serum levels at 0200 and 0600 hours. In patients with RA we observed an imbalance in favor of proinflammatory hormones as opposed to levels of antiinflammatory hormones during nocturnal hours together with increased levels of IL-1beta and TNF-alpha of the diurnal rhythm of disease activity.

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.

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.

Lipid composition plays an important part in the structural and metabolic functions of cell membranes. In particular the production of inflammatory mediators such as prostaglandins and leukotrienes is dependent on polyunsaturated fatty acid precursors. Neutrophil leucocytes participate in inflammatory processes by their phagocytic and killing activities which can be monitored by measuring the photon emission (chemiluminescence). Chemiluminescence was measured in a luminol dependent system after stimulation by either particulate (zymosan) or soluble (phorbol myristate acetate) stimulus in a group of 10 patients with rheumatoid arthritis before and 21 and 45 days after treatment with a diet supplemented with eicosapentaenoic and docosahexaenoic acids. Ten patients with rheumatoid arthritis continuing their usual diet were used as control subjects. A progressive reduction of chemiluminescence stimulated by zymosan and phorbol myristate acetate was found in the patients treated with fish oil supplementation. This result correlated well with the reduction in erythrocyte sedimentation rate and an improvement of clinical parameters. The effects of fish oil derived lipids on neutrophil chemiluminescence are probably due to a change of the lipid composition of the cell membrane which is dependent on the esterification of eicosapentaenoic acid and docosahexaenoic acid in cellular membrane phospholipids. The modification of membrane lipid composition seems to interact in a non-specific way with the metabolic activation of neutrophils during phagocytosis.

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.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.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.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 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.

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; p0.001) 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, p0.001, 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.

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.

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).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.A significant increase of LDH activity with a significant correlation to IgG and IgM aCL were found in small, light platelets with a volume5 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.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.

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.

In order to evaluate the presence of antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE), we measured IgG and IgM anticardiolipin antibodies (aCL) in a group of out- and in-patients of the Rheumatology Division at the Catholic University of Rome. Lupus anticoagulant and VDRL were also measured in 30 patients. One hundred thirteen women and 7 men (mean age 38.5 years, mean disease duration 4.27 years) were studied. The control group consisted of 60 age and sex matched healthy subjects. aCL IgG and IgM were positive in 48 (40%) and 49 (40.8%) patients respectively. aCL IgG correlated positively with the activated partial thromboplastin time. aCL IgM correlated positively with immunoglobulins of the G and M classes and with circulating immune complexes, and negatively with the C4 fraction. aCL antibodies did not correlate with spontaneous abortion or neurologic and psychiatric disturbances, although in women with a history of abortion, aCL IgG concentration was correlated with the number of spontaneous abortions. The presence of aPL does not seem to indicate a subgroup of SLE patients. The occurrence of abortion and/or neurologic and psychiatric disturbances in SLE seems to point to a complex pathogenesis with aPL as one of the causative agents.

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 insulin and C-peptide response to an oral glucose tolerance test (OGTT) and serum growth hormone (GH) response to an intravenous insulin tolerance test (IVITT) were investigated in six non-obese patients, with normal glucose tolerance, affected by diffuse idiopathic skeletal hyperostosis (DISH). Basal serum insulin, C-peptide and GH values were similar in DISH patients and in controls. After OGTT, insulin and C-peptide values were not significantly different in the two groups at any time interval. In contrast, after IVITT, a significant increase in GH concentrations was noted at 30 and 45 minutes in DISH patients when compared to controls. Growth hormone either acting alone or through somatomedin intermediaries results in new bone growth in acromegaly, and the same may be true for DISH. Recent reports suggest that GH promotes tissue growth by stimulating precursor cells in various tissues including cartilage and bone. The increased GH response to IVITT corroborates the hypothesis that GH may act as a bone growth-promoting factor in DISH.

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.

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.

To investigate the presence of reduced bone mineral density (BMD) and to assess determinants of bone loss in rheumatoid arthritis, 45 female patients suffering from non-steroid treated rheumatoid arthritis were submitted to dual photon absorptiometry of the lumbar spine and to laboratory tests for calcium metabolism. The rheumatoid arthritis patients were divided into two groups according to anatomic grade and functional class; no abnormalities in calcium metabolism were detected whereas BMD was significantly lower in the third and fourth grade and in the third and fourth class patients (P less than 0.005 versus controls, versus grades I and II and versus classes 1 and 2). BMD was significantly correlated with age (P less than 0.001) and years postmenopausal (P less than 0.01), but not with duration of disease. By multiple linear regression we derived an equation predictive of BMD. Osteoporosis in rheumatoid arthritis is observed even in non-corticosteroid treated patients; articular lesions with subsequent reduction in physical activity appear to play an important role in axial bone 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.

The AA. report a case of yellow nail syndrome associated with rheumatoid arthritis and monoclonal gammopathy (IgG-lambda). Because of the great variety of the diseases associated with this syndrome, the AA. suggest to control patients periodically to verify the probable appearance of other clinical manifestations.

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+ A TPase 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 auranofininduced diarrhoea. The ability of auranof in 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.

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.

The authors report a case of eosinophilic fasciitis with an histopathological pattern of inflammatory neutrophilic vasculitis associated with the typical inflammatory infiltrate. The presence of this type of vasculitis which may be observed in the initial forms of scleroderma supports the hypothesis of a considerable overlap between these two entities.

Bone GLA protein (BGP) and other biochemical indices of bone turnover were measured in 42 female patients with rheumatoid arthritis (RA) and in a group of normal subjects matched for sex and age. Mean serum BGP concentrations were significantly higher in patients with active arthritis than in patients with mild activity (p less than 0.01) and controls (p less than 0.01). No significant difference was found in serum BGP levels and in other parameters of bone turnover when the patients were stratified according to functional class or duration of disease. There was a correlation between BGP and alkaline phosphatase levels only in RA patients with high activity of disease. Our data suggest an accelerated bone turnover in patients with active RA. We infer that in such patients the impairment of bone metabolism is a determinant of RA-associated osteopenia. Disease activity rather than functional impairment or duration of arthritis should be regarded as a factor in the bone loss of RA.

The growth rate and body weight of male mice of the C 57 Bl/1OJ strain maintained on 15 per cent ethanol solution for periods of one to 12 months was comparable to that of the controls. There was no difference in the liver nitrogen content. However, the liver ADH content of the ethanol groups was significantly higher and the liver glycogen content was significantly lower than that of the controls. Mice paired-fed with the ethanol groups and provided with an additional 300 mg. of sucrose daily grew at a subnormal rate and attained subnormal body and liver weights. The liver nitrogen and liver ADH level was significantly lower than that of the ethanol groups. However, the liver glycogen content of the paired-fed mice was significantly higher than that of the ethanol groups and comparable to that of the control groups. Ethanol calories can be utilized for growth, maintenance of body weight and maintenance of the nitrogen integrity of the liver. The increase in liver ADH content and the pronounced decrease in liver glycogen content are a result of ethanol, per se, rather than a result of reduction in food intake.

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.

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.

Nimesulide is a new non-steroidal anti-inflammatory drug which seems to be characterized by a low inhibitory action on prostaglandin synthesis and a high inhibitory action on oxygen free radicals production. The aim of this trial was to determine the effect of Nimesulide on degenerative joint disease and on non-articular rheumatism. One hundred and forty, 64 females and 76 males aged 51.9 +/- 1.2 years, affected with osteoarthritis or non-articular rheumatism (fibromyalgia, periarthritis, tendinitis, tenosynovitis, bursitis and enthesitis) were studied. Nimesulide was administered at a daily dosage of 200 mg. A significative improvement in the clinical parameters studied was observed in all the patients, but a more remarkable progress was noted in the group with non-articular rheumatism. The incidence of adverse reactions was irrelevant: 2 patients complained of epigastralgia that subsided reducing the daily dosage to 100 mg.