Acromegaly and joint pain: is there something more? A cross-sectional study to evaluate rheumatic disorders in growth hormone secreting tumor patients.

PURPOSE: The aim of the present study was to evaluate the rheumatic profile in acromegalic patients to better characterize joint pain. METHODS: The immunological pattern (rheumatoid factor; antinuclear antibodies-ANA, extractable nuclear antigens-ENA-Ab; anti-citrullinated protein antibodies; erythrocyte sedimentation rate) was evaluated in 20 acromegaly subjects (AS) and 20 control subjects (CS). Bilateral joint ultrasound of hands/wrists and nail capillaroscopy were also performed. RESULTS: Articular pain was more frequent in AS than in CS (p = 0.027). No difference was detected in immunological parameters. ANA and ENA-Ab were positive in only 10% of AS and in 5% of CS, while no difference was found in anti-citrullinated protein antibodies. No difference was detected between rheumatoid factor positivity, but threefold higher IgG were detected in AS compared to CS. The erythrocyte sedimentation rate was significantly higher in AS than CS (p = 0.040), while in AS, there was a trend in increased Power Doppler (PWD) articular uptake. The capillaroscopic evaluation showed a significant difference in almost each parameter (presence and number of tortuous capillaries, capillary enlargements, and hemorrhages), showing a moderate-to-severe microangiopathy in AS. CONCLUSION: The results of our study suggest that joint damage in acromegaly has not an autoimmune etiology. Increased erythrocyte sedimentation rate levels and PWD alteration in acromegalic population reflect a possible inflammatory nature, while the capillaroscopic findings suggest a moderate-to-severe microangiopathy that could help to identify patients with a greater macroangiopathic risk.

Th1- and Th17-Related Cytokines in Venous and Arterial Blood of Sclerodermic Patients with and without Digital Ulcers.

The earliest clinical manifestation of SSc is usually Raynaud's phenomenon, a small-arteries vasospasm driven by vascular tone dysregulation and microcirculatory abnormalities, resulting in digital ulcers (DU) in up to 50% of patients. Many cytokines as well as growth factors have been shown to play a role in promoting vascular smooth muscle cell proliferation and fibroblast activation, leading to ischemic damage as well as skin fibrosis. We aim to investigate a possible difference in venous and arterial blood levels of many cytokines (Th1- and Th17-related), GM-CSF, and endothelin-1 (ET1) in patients with and without DU. In the same patients, the correlations between capillary damage, evaluated by nailfold videocapillaroscopy (NVC), extension of skin fibrosis, calculated by modified Rodnan skin score (mRSS), and cytokines, ET-1, and GM-CSF levels were also measured. Patients with DU showed venous levels of IL-1ß (p=0.024), IL-6 (p=0.012), IL-22(p=0.006), and TGF-ß (p=0.046) significantly higher compared to arterial levels and arterial levels of GM-CSF and TNF-alpha significantly higher compared to venous levels (p < 0.001). NVC abnormalities were correlated with arterial TNFa and venous IL22, IL23, and IL17 levels and negatively correlated with venous ET-1 levels, whereas mRSS showed a negative correlation with IL-21(ρ = -0.427, p=0.050). The increased Th17-cytokine levels in venous compared to arterial blood of patients with DU suggest local cytokine production on ulcer site. The higher TNFa and GM-CSF levels in arterial blood of DU patients support the attempt to mitigate the hypoxic damage, and the correlation between Th17-cytokines, mRSS, NVC, and ET1 agrees with the potent profibrotic stimulus at the onset of the disease, which decreases as the SSc progresses.

Neuromuscular taping enhances hand function in patients with systemic sclerosis: a pilot study.

Hand functioning is often impaired in patients with Systemic sclerosis. Neuromuscular Taping is a novel application of tape able to improve functioning. The aim of this study was to evaluate the possible role of this application in the hand functionality of patients with Systemic sclerosis. Women with a diagnosis of SSc has been recruited and evaluated using different scales before and immediately after NMT application and after one, three and six months. Fifty-three women has been evaluated and Cochin Hand Functional Disability scale, Hand Mobility in Sclerodermia, Modified Rodnan Skin Score and Dreiser Algo - Functional Index scores showed statistical significant differences during all the period; moreover a reduction of pain and Raynaud Phenomenon's and an improvement of finger flexion has been observed. Application of NMT in patients with Systemic sclerosis have showed beneficial effect and future studies are needed to confirm these results.

Th-17 cytokines and interstitial lung involvement in systemic sclerosis.

The two phenotypes of both limited and diffuse systemic sclerosis (SSc) have different forms of pulmonary involvement: pulmonary arterial hypertension (limited phenotype) or interstitial lung disease (ILD) (diffuse phenotype). We aimed to investigate whether Th17-related cytokines, as measured in exhaled breath condensate (EBC) and in serum were connected to ILD in diffuse SSc patients. We found that for both limited and diffuse SSc, the EBC levels of all cytokines and most of the cytokine serum levels were significantly higher in patients than in controls, while, the EBC levels of Th-17 cytokines and the serum levels of IL-10 and TNF-α were significantly higher in diffuse than in limited SSc. Moreover, the thoracic CT-scan score of ILD was significantly associated with the EBC levels of IL-1 beta and with the serum IL-23, TNF-α and IL-10 levels, whereas lung carbon monoxide diffusing capacity was negatively related to the EBC levels of IL-1 beta, IL-17 and serum IL-10. Serum IL-23 was also inversely correlated with vital capacity. In conclusion, in diffuse SSc patients our results show a clear link between Th-17 cytokines measured both in EBC and in serum with interstitial lung involvement. This highlights how important it is to target Th-17 cytokines when developing new treatments for lung fibrosis.

Suboptimal methotrexate use in rheumatoid arthritis patients in Italy: the MARI study.

OBJECTIVES: Methotrexate (MTX) is the first choice in the treatment of rheumatoid arthritis (RA), but the doses and regimens vary significantly. For this purpose, we conducted an observational study on the use of MTX for RA in Italy (MARI study). METHODS: The MARI study included 1,327 RA patients on MTX treatment for at least 12 months, at 60 Italian rheumatology units. Concomitant medications with corticosteroids, other DMARDs or biological therapies were recorded. The clinical assessment included the Disease Activity Score 28 (DAS28) and the serological positivity for the rheumatoid factor or for the anti-citrullinated protein antibodies. RESULTS: The included patients were treated with either oral (n=288) or parenteral (n=1039) MTX. Only 15.5% of the total number of the patients was on adequate MTX dose (i.e. ≥ 15 mg for the oral route of administration and >12 mg for the parenteral one). The initially established MTX dose was modified in 37.1% of the patients, for intolerance or clinical criteria. A DAS28 remission (DAS28 <2.6) was observed only in 58.5% of the cases, while 52.9% of the patients still presenting an active form of the disease were on suboptimal doses of MTX. CONCLUSIONS: The weekly dose of MTX prescribed for the treatment of RA is often suboptimal, even in conditions of inadequate control of the disease activity. The recommendations for the use of MTX in RA patients should take into account the efficacy and tolerability data derived from its use in real clinical practice.

Efficacy of bosentan in the treatment of Raynaud's phenomenon in patients with systemic sclerosis never treated with prostanoids.

The objective of this study was to evaluate the efficacy of the endothelin receptor antagonist, bosentan, in patients with Raynaud's phenomenon secondary to systemic sclerosis never treated with prostanoids and without digital ulcers. The study design is a preliminary, prospective open label trial. The patients recruited took one 62.5 mg dose of bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 24 weeks. Of the 10 patients recruited, all completed the study. The reduction in Raynaud's phenomenon attacks at week 24 from the baseline was statistically significant (Δ-1.3, P=0.0126). The Raynaud's condition score showed a statistically significant improvement (Δ-1.4, P=0.0279), as did the visual analog pain scale (Δ-1.5, P=0.0016) at the 24th week. Bosentan appears to be effective and may be a valid alternative for the treatment of severe secondary Raynaud's phenomenon for patients where prostanoids therapy is contraindicated or refused.

Catastrophic antiphospholipid syndromes in systemic lupus erythematosus.

The objective of this study was to look for the occurrence of catastrophic antiphospholipid syndromes (APS) and to try to detect discriminating factors for predicting a worse prognosis, related to Lupus anticoagulant (LA) and antiphospholipid antibodies (aPL), in systemic lupus erythematosus (SLE) with main renal involvement. Regression, recursive partition and logistic regression analyses were applied to our 80 SLE patients prospectively followed up since 1980. Immunologic and other laboratory parameters including beta 2-glycoprotein 1 dependence, resistance to activated protein C caused by a substitution on the coagulation factor V gene, induction of monocyte procoagulant activity. Regression studies demonstrated an overall worse prognosis in term of both thrombosis and death for the group of LA/aPL positive patients (33/80). However, recursive partition analysis was able to isolate a small high risk-subgroup (8/33) characterized by persistent LA/aPL antibodies positive result, widespread signs of noninflammatory vasculopathy (skin, brain, kidney) and renal pathology mimicking that of thrombotic microangiopathy or arteriolosclerosis, also in the absence of classic SLE-nephritis. Only in this subset, three catastrophic APS were recorded, while, in traditional SLE nephritis, even persistent LA/aPL positive results (sometimes after one previous thrombosis) did not seem to imply a particularly severe prognosis. All serologic criteria employed are unable to identify high-risk patients. We conclude that catastrophic APS is a rare event in renal SLE. Before more predictive serologic markers become available, a simple algorithm, dealing with clinical data and renal histologic patterns, may help physicians to identify putatively high risk-LA/aPL antibodies in SLE patients with main renal involvement. This ominous subset does not belong to the group of classic SLE-nephritis.

Primary biliary cirrhosis: lung involvement.

Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p < 0.01) and with the presence of circulating anti-centromere antibodies (p < 0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

[Blood chemical parameters in the monitoring of inoperable bronchogenic carcinoma]. / Parametri ematochimici nel monitoraggio del carcinoma broncogeno non operabile.

Serum variations of 3 standard lung cancer markers (ferritin, carcinoembryonic antigen, gastrointestinal cancer antigen) were assessed in 27 patients with inoperable lung cancer diagnosed histologically and confirmed by cytology and/or histology. The study reveals that ferritin is the most sensitive marker.

[Chemotherapy of pulmonary carcinoma. Considerations and a proposal of a system of the evaluation of clinical course]. / Chemioterapia nel carcinoma polmonare. Considerazioni e proposta di un indice di valutazione dell'evoluzione clinica.

With absolutely no attempt to reject chemotherapy of lung cancer as useless, particularly now that extremely effective antiblastic products are available, it is however suggested that we should think carefully before adopting treatments of doubtful efficacy that may prolong the patient's life but also increase his suffering in that they produce extremely unpleasant side effects without having much influence on the basic symptoms. In such cases it may be the physician's painful duty to withhold treatment.