The data project: a shared approach between stakeholders of the healthcare system in definition of a therapeutic algorithm for inflammatory arthritis.

Rheumatic musculoskeletal diseases or RMD [rheumatoid arthritis (RA) and spondyloarthritis (SpA)] are systemic inflammatory diseases for which there are no biomarkers capable of predicting treatments with a higher likelihood of response in naive patients. In addition, the expiration of the anti-TNF blocking drugs' patents has resulted in the availability of anti-TNF biosimilar drugs with the same efficacy and safety than originators but at significantly reduced prices. To guarantee a personalized therapeutic approach to RMD treatment, a board of rheumatologists and stakeholders from the Campania region, Italy, developed a clinically applicable arthritis therapeutic algorithm to guide rheumatologists (DATA project). The general methodology relied on a Delphi technique forecast to produce a set of statements that summarized the experts' consensus. Selected clinical scenarios were discussed in light of the available evidence, and there were two rounds of voting on the therapeutic approaches. Separate discussions were held regarding rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The decision-making factors for each disease were clinical presentation, demographics, and comorbidities. In this paper, we describe a virtuous process between rheumatologists and healthcare system stakeholders that resulted in the development of a shared therapeutic algorithm for RMD patients naive to bDMARDs.

Incidental papillary thyroid cancer diagnosis in patient with adult-onset Still's disease-like manifestations.

Adult onset Still's disease (AOSD) is a systemic inflammatory disease characterized primarily by a triad consisting of daily fever, arthritis and maculopapular exanthema. The pathogenesis and etiology of AOSD are unknown and the diagnosis, which can be very challenging, is often made by exclusion. Here, we report a case of a 61-year-old woman with a history of mild psoriatic arthritis, fever, arthritis and maculopapular exanthema. Her initial laboratory tests showed neutrophilic leukocytosis, hypertransaminasemia, and markedly elevated levels of the erythrocyte sedimentation rate and C-reactive protein. With a presumptive diagnosis of AOSD, based on Yamaguchi criteria, the patient started an extensive diagnostic work-up to exclude other potential differential diagnoses. With fluorodeoxyglucose (FDG) positron-emission tomography, a thyroid nodule with moderate FDG uptakes was detected. The fine needle aspiration biopsy led to diagnosis of papillary thyroid cancer. The history of psoriatic arthritis, the patient's age, and atypical features of the skin rash described as not concomitant with fever flares, suggested a diagnosis of paraneoplastic AOSD-like manifestations.

Leflunomide in psoriatic arthritis: a retrospective study of discontinuation rate in daily clinical practice compared with methotrexate.

OBJECTIVE: To assess the safety profile of leflunomide (LEF) in a two-year retrospective analysis of psoriatic arthritis (PsA) patients (pts) treated in daily clinical practice compared with methotrexate (MTX). PATIENTS: Fourty-two PsA patients with polyarticular involvement or asymmetrical oligoarticular arthritis, satisfying ESSG criteria for the spondyloarthropathies, treated with LEF monotherapy (10-20mg/die without loading dose) between September, 2004 and August, 2006 were reviewed. They were compared with MTX (7.5-15mg/week) users (44 cases). The adverse events (AEs) and the causes of withdrawal were evaluated. RESULTS: At 24 months, cumulative survival rate of pts remaining on drugs was 54.9% in LEF users and 57.0% in MTX users (p > 0.05). The discontinuation rate (DR) for toxicity was higher in LEF group (29.2%) than in MTX group (10.8%) (p = 0.07). The occurrence of AEs was more frequently registered in the first year in both groups. LEF monotherapy showed a significant higher crude incidence for any AEs (38.7 events x100 person-years) compared to MTX (14.3 events x100 person-years) (p < 0.001). The cumulative DR for inefficacy was greater but not statistically significant in MTX group than LEF (28.6% vs. 12.6% respectively; p = 0.056). Finally, DR for other causes accounted for 8.7% vs. 11.0% respectively (p > 0.05). CONCLUSIONS: Our data showed, in a setting of clinical practice, that the rate of PsA pts remaining on drug was comparable between LEF and MTX, and a manageable LEF safety profile during a 24 months of follow-up, even if a greater incidence of DR for AEs was registered than in MTX users.

[Safety of methotrexate in rheumatoid arthritis: a retrospective cohort study in clinical practice]. / Profilo di tollerabilità del methotrexate nell'artrite reumatoide: analisi retrospettiva su una coorte di pazienti ambulatoriali.

OBJECTIVE: To evaluate the treatment duration with MTX monotherapy or in association with DMARDs or TNFalpha inhibitors and the incidence and typology of adverse events (AE) occurred in rheumatoid arthritis (RA) patients. METHODS: A retrospective large cohort study of RA outpatients, consecutively seen from January 2000 to June 2005 was performed. Study group were RA patients classified according to the 1984 ACR criteria for the classification of rheumatoid arthritis. The patients were divided in 3 groups according to the treatment regimen: MTX monotherapy, MTX in combination with DMARD or with anti TNFalpha agents. We analyzed 348 therapeutic cycles, 177 of whom using MTX monotherapy. RESULTS: The 224 RA patients accumulated 800 person-years of follow up. Follow up for each of the groups was: MTX monotherapy 479.4 person-years, MTX in combination with DMARDs 244.5, or with TNFalpha inhibitors, 75.7 person-years. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 years was 58.5 after starting MTX. The incidence of any AE was 8.87 per 100 person-years. From all, 69 (97.2%) AE were no severe. Among those, more frequently were observed at gastrointestinal tract (31%), liver (19.7%), skin (15.5%). Incidence of severe AE (lung adenocarcinoma, 1 case; pancreatitis, 1 case) was 0.25 per 100 person-years, occurring in patients taking MTX monotherapy or MTX in combination with DMARDs, respectively. CONCLUSIONS: These data confirm that methotrexate is well tolerated in clinical practice in the medium-long term. Nevertheless, the occurrence of severe AE require an accurate vigilance for methotrexate toxicity.

Pott's disease of the lower cervical spine in a diabetic patient.

Over the last few years, tuberculosis has steadily been returning to the worlds attention as a major health threat. The spinal localization of tuberculosis (Pott's Disease) represents around 1% of the case histories, in 3-5% of which there is cervical involvement. Diabetes mellitus increases the risk of infectious disease and predisposes to tuberculosis. Here, a rare case is presented of Pott's disease in the lower cervical spine, associated with retropharyngeal abscess in a diabetic patient. The aim of this study is to emphasize the importance of early diagnosis in such patients, so that adequate pharmacological and/or surgical treatment can be initiated to avoid serious complications.

The predictive value of attributes of pain to classify rheumatoid arthritis.

Out of 2300 patients with rheumatic diseases 1627 were analysed to develop a classification of rheumatoid arthritis based on clinical attributes of pain. Of these, 641 patients had the disease and 986 were controls with other rheumatic conditions. For traditional format classification, six of eight variables were selected: pain at a fixed joint; symmetrical pain; continuous pain; pain mainly present at night or in the morning; pain following joint pressure; and pain decreased by load/movement. The occurrence of four or more of these features was associated with a 72.1% sensitivity and a 79.1% specificity. A classification tree constructed on four features that showed the greatest diagnostic power (symmetrical pain, pain mainly present at night or in the morning, pain at joint pressure, continuous pain), was associated with a 75.8% sensitivity and a 77.0% specificity.

Clinical pattern of pain in rheumatoid arthritis.

OBJECTIVE: To evaluate whether rheumatoid arthritis (RA) is associated with a characteristic clinical pattern of pain which may be useful as a criterion to differentiate RA from other rheumatic diseases. METHODS: 2300 patients from the ReumaLink data bank project with definite rheumatic diseases were studied. Of these 907 patients (39.5%) fulfilled the ARA/ACR revised criteria for RA, while 1393 had rheumatic diseases other than RA. The following diagnostic attributes of pain were considered: localization, symmetry, continuity, modulation, relationship with time and with loads/movements, tenderness. RESULTS: After a descriptive analysis, some pain characteristics were selected individually and others were combined. Only 8 variables were considered for a predictive analysis. Univariate analysis showed that symmetric pain is the most potent discriminating item, with 82.2% sensitivity, 69.2% specificity, a 61% positive predictive value and a 83.3% negative predictive value. A higher probability of RA was present in patients with symmetric pain than in those with asymmetric pain (odds ratio = 7.8). A multivariate analysis performed on 1627 patients showed that a specific clinical pattern of pain (symmetrical pain, pain following joint pressure, mainly present at night or in the morning, continuous) could predict RA patients with a 68.9% likelihood. The lack of these symptoms excluded RA with 92% probability. CONCLUSION: The clinical pattern of pain defined by us can predict RA with a 70% probability. This value reaches 86% when the variables "pain in a fixed joint" and "pain decreased by load/movements" are added. These results indicate that determining the clinical pattern of pain is a useful screening tool for suspected RA, in particular early in the disease course.

[The nephrotic syndrome and pheochromocytoma. A report of a rare clinical case]. / Sindrome nefrosica e feocromocitoma. Descrizione di un raro caso clinico.

In clinical practice, the coincidence of nephrotic syndrome with pheochromocytoma is very rare. The case is described of a 23-year-old woman who in June 1988 presented with recurrent hypertensive crises, severe asthenia, abundant sweats, orthostatic hypertension and massive proteinuria. Diagnostic tests performed (abdominal ultrasound and CT, urinalysis, renal function tests, plasma levels of metanephrine and normetanephrine, as well as urinary VMA determination) revealed the presence of a pheochromocytoma of the left adrenal gland combined with nephrotic syndrome. Surgical removal of the left adrenal led to immediate normalization of blood pressure and absence of urinary abnormalities. The authors therefore suggest either an immunological pathogenesis or one due to glomerular hyperfiltration.

Cardiac involvement in rheumatoid arthritis: an echocardiographic study.

Thirty-nine consecutive patients with rheumatoid arthritis (RA) and 40 control subjects were studied by echocardiography in order to assess the incidence of cardiac involvement in this disease. The occurrence of anatomic lesions in our series was lower than that observed in other studies. No differences in mean values of left and right ventricular diastolic function indexes obtained by Doppler echocardiography were found between patients and controls. However, in 26% of patients with RA, left ventricular abnormalities probably secondary to myocardial fibrosis were observed.

Antinuclear antibodies in first-degree relatives of patients with polymyositis-dermatomyositis: analysis of the relationship with HLA haplotypes.

Antinuclear antibodies (ANA), as detected by indirect immunofluorescence on HEp-2 cells, have been investigated in five spouses and 41 first-degree relatives of nine probands with polymyositis-dermatomyositis (PM-DM) and in 41 sex- and age-matched controls. ANA were detected in 12 out of the 41 first-degree relatives and in two controls (chi 2 = 6.97; P less than 0.01). HLA typing was done in four out of the nine families; in two of them only, ANA segregated with a haplotype. ANA positivity was not correlated either to sex or to age or to household contact. Our results show that ANA occur in a significant percentage of first-degree relatives of patients with PM-DM. The finding seems to be genetically conditioned.

Evidence for peripheral impaired glucose handling in patients with connective tissue diseases.

Sixteen patients suffering from rheumatoid arthritis (RA) (n = 8), systemic lupus erythematosus (SLE) (n = 5), and systemic sclerosis (SSc) (n = 3), and 10 healthy subjects matched for age, sex, and body mass index, were submitted to an intravenous (IV) glucose tolerance test (GTT) (0.33 g/kg of body weight in 3 minutes) and to a euglycemic hyperinsulinemic glucose clamp to study insulin response and action. In the euglycemic clamp, along with the two insulin infusion rates (0.5 mU/kg.min from 0 to 120 minutes and 1 mU/kg.min from 121 to 240 minutes), a primed (20 microCi) continuous (0.2 microCi/min) infusion of 3H-glucose allowed determination of glucose kinetics. Our data show that patients versus controls have (1) a significant increase in basal plasma insulin levels (87.2 +/- 14.8 v 41.3 +/- 6.0 pmol/L, P less than .05); (2) similar glucose-induced acute insulin response; and (3) a lower glucose disappearance rate (Rd), glucose metabolic clearance rate (gMCR), and glucose infusion rate (GIR) when the lowest insulin infusion rate was delivered. These differences disappeared when the insulin infusion rate was doubled. Furthermore, basal plasma insulin levels and glucose disappearance rate significantly correlated with the main inflammatory indices of each disease studied. We conclude that in our patients impaired glucose handling is mainly due to peripheral insulin resistance.

[Clinico-developmental aspects in 44 cases of polymyositis/dermatomyositis]. / Aspetti clinico-evolutivi in 44 casi di polimiosite/dermatomiosite.

A retrospective study, paying particular attention to the clinical and evolutive aspects of the disease, was performed on 44 subjects affected by polymyositis/dermatomyositis (PM/DM) and hospitalized at the Institute of Medical Clinics of the 1st School of Medicine of Naples University. On the basis of the different clinical pictures, the cases were classified into the following groups: primary PM (4); primary DM (19); DM/PM associated with malignancy (6); childhood DM/PM (3); PM/DM associated with connective tissue disorders (12). Diagnosis was established in terms of the following criteria: a) symmetrical and mostly proximal bilateral muscle weakness (100%); b) elevation of serum enzymes (86.3%); c) electromyographic findings of myopathy sometimes with fibrillation potentials, increased insertional irritability and pseudo-myotonic discharges (93.1%); d) muscle biopsy changes compatible with a clinical form of polymyositis (83.3% out of 30 cases); e) dermatological manifestations including particularly pink or lilac edema-erythema over the periorbital areas, wine-red maculae, Gottron's sign, "poikiloderma vasculare atrophicans", telangiectasias and skin vasculitis (86.3%). An involvement of the extraneural apparatus and organs was present in 40 patients; the most damaged was the osteoarticular apparatus, followed by esophagus, lung, heart and kidney; such pathology was rarely present in the childhood form. A follow-up of the disease has been performed in 36 cases and the therapy consisted fundamentally of high dose corticosteroids (mostly prednisone), associated, in a minority of cases, with methotrexate. A clinical improvement was observed in most cases and a remission of the disease in part of the latter. However, a worsening of the illness was noticed only in the patients suffering from PM/DM associated with malignancy, and mortality rate was 11.1% in all.

Isolation and characterization of single myocardial cells from the quail, Coturnix coturnix japonica.

1. The enzymatic cell isolation technique was applied to the bird heart resulting in myocytes of which 10-50% maintained their spindle-shaped morphology, excluded the vital dye, Evans blue and tolerated physiological concentration of Ca2+ ions. 2. The length of spindle-shaped myocytes was on average 289 +/- 7 microns, and the maximum width was 10.2 +/- 0.3 microns. The mean length of the sarcomeres was 2.18 +/- 0.03 microns. 3. In electron micrographs the fine structure of the spindle-shaped myocytes looked normal--regular sarcomeric organization with clear A and I bands, mitochondria with tightly located cristae and well-developed sarcoplasmic reticulum (SR). 4. Most (80%) of the spindle-shaped myocytes were quiescent in physiological calcium concentration and practically all of them could be induced to twitch by electric field stimulation. Some beat spontaneously showing mostly slowly-propagating (135 +/- 6 microns/sec at 20 degrees C) contraction waves, so-called phasic contractions. Sometimes spontaneous twitch-type contractions could also be seen.

Isolation and characterization of single myocardial cells from the perch, Perca fluviatilis.

In applying the enzymatic cell isolation technique to the fish heart about 40% of the dispersed myocytes maintained their spindle-shaped morphology, and about half of them tolerated physiological concentration of Ca2+ and excluded the vital dye, Evans blue. The length of spindle-shaped myocytes was on average 133 +/- 3 micron and the maximum width was 4.2 +/- 0.1 micron. The mean length of the sarcomeres was 2.1 +/- 0.1 micron. The sizes of the myocytes did not vary significantly with the weights of the fish. Electron microscopic examinations showed typical fish myocardial cell structure; absence of transverse tubule system, a sparse network of sarcoplasmic reticulum and from a few up to eight or more myofibrils. The cells were mononuclear. Most of the Ca2+-tolerant myocytes were quiescent, but the contraction in them could be induced by electric field stimulation. Both the spontaneous and electrically triggered contractions were of twitch type. The slowly propagating contraction waves, so-called phasic contractions common in isolated mammalian cardiac myocytes, could not be seen at all.