[Anakinra, a recombinant human IL-1 receptor antagonist, in clinical practice. Outcome in 60 patients with severe rheumatoid arthritis]. / Anakinra, antagonista umano ricombinante del recettore dell'IL-1, nella pratica clinica. Outcome in 60 pazienti con artrite reumatoide severa.

OBJECTIVE: We evaluated both the efficacy and safety of anakinra in daily routine rheumatoid arthritis clinical practice. METHODS: We studied 60 cases, including patients with previous anti-TNFalpha exposure, treated with anakinra (100 mg/daily s.c.) in combination with methotrexate (7.5-10 mg/week i.m.) or leflunomide (20 mg/die) in a two year observational study. Efficacy measures were assessed using the American College of Rheumatology (ACR) response criteria. Safety was evaluated according to a modified World Health Organization adverse reaction term dictionary. RESULTS: At week 14, ACR 20% response criteria have been fulfilled by 53 (91.3%) out of 58 patients, 51 (87.9%) of them achieving also an ACR 50%and 15 (25.8%) an ACR 70%response. Thirteen patients touched 102 weeks of treatment: ACR 20% response was achieved in 92.3%, while ACR 50% and ACR 70% were respectively found in 84.6% and 38.4% of the cases. The mean decrease in HAQ score was 0.38, p<0.001. Of the 16 patients who were previously treated with anti-TNFalpha blockers, 81.2% responded to anakinra. There was no significant difference in the ACR response between groups with and without previous anti-TNFalpha exposure. Seventeen patients (28.3%) stopped anakinra because of side-effects (5%) or failure to respond (23.3%). Only 4 cases of pulmonitis, of which 2 have been hospitalised, and 1 case with tuberculosis (previously treated with infliximab) were observed. CONCLUSIONS: Our clinical experience confirms that anakinra is effective and safe in the treatment of rheumatoid arthritis. Anakinra seems also useful in patients with previous anti-TNFalpha blockers failures. Even though major adverse events were rare, clinicians should be aware of such a possibility.

Primary biliary cirrhosis: when and why does the disease develop?

Primary biliary cirrhosis is a chronic cholestatic liver disease with an autoimmune pathogenesis, that generally develops in adult life, often in perimenopausal age. The clinical features are heterogeneous, ranging from an asymptomatic presentation to end-stage liver disease. Primary biliary cirrhosis is unknown in children and its natural history has yet to be elucidated. Following a Canadian report of primary biliary cirrhosis in two girls (16 and 15 years old), we describe a clinical case developing at 17 years of age. A temporal association between Borrelia Burgdorferi infection and diagnosis of primary biliary cirrhosis was observed.

[Efficacy of Carbopol 974P (Siccafluid) in the treatment of severe to moderate keratoconjunctivitis sicca in patients with primary Sjögren's syndrome not responding to standard treatment with artificial tears]. / Efficacia di Carbopol 974P (Siccafluid) nel trattamento della cheratocongiuntivite sicca di grado moderato-severo in 60 casi con S. di Sjögren primitiva.

OBJECTIVE: To determine efficacy and safety of Carbopol 974P in the treatment of severe to moderate keratoconjunctivitis sicca (KCS) in patients with primary Sjögren's syndrome (SS) not responding to standard treatment with artificial tears. METHODS: 60 patients (57 F, 3 M, mean age 52.5+/-12.0, mean disease duration 12.2+/-7.1 yrs) affected with primary SS diagnosed according to the European Community Study Group criteria were studied. Foregoing medications for SS and artificial tears for KCS have not been changed within 3 and 2 months respectively prior to the study onset. In all cases Carbopol 974P was added because symptoms of KCS were not adequately controlled with traditional lubricants. Schirmer I test, B.U.T. (break up time), rose Bengal-stain, clinical ophthalmological examination (i.e. fluorescein staining, keratis, corneal infiltrates and ulcers) and a questionnaire for dry eye symptoms (range 0-30) were performed at entry (T0) and after 2 (T1) and 12 (T2) weeks. Assessment of global efficacy was obtained by VAS 0-100 at T2 either by patients and by the ophthalmologist. RESULTS: Lachrymal tests significantly improved after 2 and, even more, after 12 weeks. Clinical ophthalmologic picture also ameliorated: a remarkable reduction of fluorescein positive lesions was demonstrated from 71.6% of the cases at T0 to 38.3% at T2. Total score of symptoms (T0: 16.1+/-7.3) dropped to 11.9+/-6.6 (T1) (p=0.000) and then to 6.7+/-5.3 (T2) (p=0.000). Global efficacy expressed by patients and physician was 74.8+/-15.9 and 76.6+/-13.0, respectively. No adverse events (blurred vision, allergy) were reported throughout the study. CONCLUSIONS: Our study seems to demonstrate that addition of Carbopol 974P to the traditional therapeutic armamentarium for moderate to severe KCS is useful and well accepted in patients with primary SS in which management of ocular symptoms is unsatisfactory.

[Incidence and management of infusion reactions to infliximab in 186 italian patients with rheumatoid arthritis: the Padua experience]. / Frequenza e trattamento delle reazioni all'infusione di infliximab in 186 pazienti con artrite reumatoide: esperienza di Padova.

OBJECTIVE: We report the incidence and treatment of infusion reactions to infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor alpha, in a large cohort of patients with rheumatoid arthritis. PATIENTS AND METHODS: One hundred eighty six patients with rheumatoid arthritis treated with infliximab for a total of 216.6 patient years were retrospectively evaluated. Patients received 2160 infliximab infusions at the Division of Rheumatology at the University Hospital of Padua from May, 2000 to April, 2004. Specific treatment protocols for initial and subsequent acute infusion reactions were followed and the outcomes documented. RESULTS: The overall incidence of infusion reactions to infliximab was 0.8% (19 out of 2160 of infusions), affecting 10.2% of patients (19 out of 186). Mild, moderate, or severe acute reactions occurred in 0.1% (3 of 2160), 0.6% (13 of 2160), and 0.04% (1 of 2160) of infliximab infusions, respectively. Delayed infusion reactions occurred in 0.09% (2 of 2160) of infusions. Use of specific treatment protocols resulted in rapid resolution of all acute reactions to infliximab. With a prophylaxis protocol, all patients who experienced an initial mild acute reaction were able to receive additional infusions. CONCLUSIONS: Using appropriate treatment protocols, infliximab infusion reactions were effectively treated and prevented in patients with mild acute reactions upon retreatment. In the case of moderate to severe infusion reactions, the risks and the benefits of the continuation of infliximab therapy need to be carefully considered.

Dermatomyositis and malignancy of the pharynx in Caucasian patients: report of two observations.

The association between dermatomyositis and malignancy of the pharynx is rare among whites but not uncommon among Far Eastern and north African populations. We report two cases of Caucasian Italian patients with dermatomyositis associated, respectively, with nasopharyngeal and tonsillar carcinomas. The relationship between dermatomyositis and malignancy is also discussed.

[Infections in patients with rheumatoid arthritis receiving anti-cytokine therapy: biological mechanisms and clinical aspects]. / Farmaci anti-citochine ed infezioni nei pazienti affetti da artrite reumatoide: meccanismi biologici ed aspetti clinici.

Different animal studies show that several proinflammatory cytokines are essential for natural resistance to specific infections, particularly versus intracellular organisms. However, uncontrolled overproduction of some proinflammatory cytokines, in diseases such as rheumatoid arthritis, can be just as dangerous to the host as the absence of the same cytokines. Reduction in the production and/or activities of proinflammatory cytokines in rheumatoid arthritis remains a therapeutic objective for many patients. The tumour necrosis factor-alpha (TNF-alpha) blockers infliximab, etanercept and adalimumab and the recombinant interleukin 1 (IL-1) receptor antagonist anakinra are effective in patients with active rheumatoid arthritis. However, there is a growing body of clinical evidence that neutralization of TNF-alpha is associated with an increased risk of opportunistic infections, including mycobacterial diseases. Blockade of IL-1 activity with the IL-1 receptor antagonist (IL-1Ra) appears, at present, to be relatively safe. Postmarketing experience and pharmacovigilance programs are necessary to determine the overall safety profile of the new agents. At this time, treating physicians must weigh carefully the benefits of biologics against their safety, particularly in patients at risk of infection.

Adult Henoch-Schönlein purpura with glomerulonephritis and paroxysmal nocturnal haemoglobinuria: an uncommon association.

Henoch-Schönlein purpura (HSP) is considered to be a small blood vessel systemic vasculitis. Numerous microorganisms have been implicated in triggering HSP. We describe an unusual case of HSP with glomerulonephritis and renal failure requiring haemodialysis in a young adult man who subsequently developed paroxysmal nocturnal haemoglobinuria (PNH) with several haemolytic episodes. Bacterial infections, especially those of the respiratory and urinary tract, might trigger both the diseases.

[Prevalence and clinical features of fibromyalgia in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome]. / Prevalenza e caratteristiche cliniche della fibromialgia nelle connettiviti maggiori: lupus eritematoso sistemico, sclerosi sistemica e sindrome di Sjögren primitiva.

BACKGROUND: We studied the prevalence of fibromyalgia in 3 different groups of patients affected respectively with systemic lupus erythematosus, systemic sclerosis (scleroderma) and primary Sjögren's syndrome. The typical fibromyalgia findings encountered in these diseases were examined. METHODS: We enrolled 250 consecutive outpatients: 100 with systemic lupus erythematosus, 50 with systemic sclerosis, 100 with primary Sjögren's syndrome and 2 control groups (30 healthy subjects and 75 patients with primary fibromyalgia). Fibromyalgia features were evaluated by algometry, VAS for pain, Mc Gill Pain Questionnaire and Fibromyalgia Impact Questionnaire. RESULTS: Fibromyalgia has been found in 1 case (1%) with systemic lupus erythematosus, 1 case with systemic sclerosis (2%), 22 cases (22%) with primary Sjögren's syndrome and in 1 (3.3%) of the healthy controls. The number of tender points was significantly higher (p<0.01) in the patients with Sjögren's syndrome in comparison with the other groups. Fibromyalgic findings were similar in the patients with primary fibromyalgia and Sjögren's syndrome with fibromyalgia, unless for both poor sleep and low algometric thresholds which were more frequently found in primary fibromyalgia (respectively p<0.001 and p=0.05). CONCLUSIONS: Our study suggests that fibromyalgia is relatively frequent in primary Sjögren's syndrome, while in systemic lupus and systemic sclerosis its prevalence is not different from that found in the healthy controls. Typical fibromyalgia findings, except algometric values, were similar between the cases with Sjögren's syndrome plus fibromyalgia and fibromyalgia alone.

[Rhinopharyngeal carcinoma and dermatomyositis: description of a clinical case]. / Carcinoma del rinofaringe e dermatomiosite: descrizione di un caso clinico.

Nasopharyngeal carcinoma has long been reported as the predominant type of cancer associated with dermatomyositis in many several Asian countries, including Hong Kong, Singapore, and Southern-Cina. Dermatomyositis is one of the idiopathic inflammatory myopathies showing characteristic cutaneous manifestations. Reviews from the western literature have demonstrated that certain cancers, such as ovarian and breast carcinoma in women and lung and prostate carcinoma in men, are highly associated with DM relative to the general population. We report the case of a Caucasian Italian patient with nasopharyngeal carcinoma and dermatomyositis. Considering the rarity of nasopharyngeal carcinoma among whites, both the detection and the report of each new case are noteworthy in defining the geographic and ethnic distribution of this tumor.

[Surgical treatment of the impingement syndrome and of the rotator cuff tears: personal experience in 134 cases]. / Il trattamento chirurgico del conflitto subacromiale e della rottura della cuffia dei rotatori: esperienza personale in 134 casi.

The time-course covered by the original definition of scapulo-humeral periarthritis suggested by Duplay through the more recent term of subacromial impingement syndrome coined by Neer, follows the identification of the pathogenetic mechanisms leading to chronic subacromial impingement and degenerative tears of the rotator cuff. The Authors recall the functional-anatomic development evolution of the shoulder and the disequilibrium between the depressor and the elevator muscles which may promote the chronic friction against the acromion. However, the actual pathogenesis of the impingement still remains controversial. We evaluated 134 patients (81F, 53M, mean age 56.4 years) with chronic subacromial impingement syndrome. In 92 cases (69%) non traumatic tears of the rotator cuff were also present as confirmed by ultrasonography in 94 cases, CT in18 cases and magnetic resonance in 102 cases. The different tear patterns of the rotator cuff were classified as suggested by Ellman (L shaped, L reverse, triangular, trapezoidal and massive with retraction) and clinical results were analyzed following Sahlstrand clinical criteria and Costant numerical scale. According to the anatomical damage, patients were divided into those with impingement without severe cuff tendinopathy (42 cases), those with rotator cuff tears without loss of motion of the shoulder (32 cases) and those with cuff tears and loss of active motion (60 cases). The different surgical techniques and rehabilitation procedures after surgery are also reported. After a mean follow-up of 1.3 years (range 8 months - 2 years), good or excellent results were obtained in 91% of the patients without rotator cuff tears, in 87% of the patients with tears but without loss of motion and in 75% of the cases with loss of active motion. Our data demonstrate that in the majority of patients with chronic impingement syndrome and rotator cuff tears, surgical treatment shows high success rates. When surgery is associated with a careful rehabilitation programme it may frequently allow patients to return to their baseline function.

[Comparison of ultrasonography and sialography vs. magnetic resonance in the diagnosis of the primary Sjogren's syndrome]. / La risonanza magnetica nucleare nella diagnosi della sindrome di Sjögren primitiva. Confronto con le metodiche ecografica e scialografica.

To date there is no agreement as to which imaging technique is best for the evaluation of the oral component of primary Sjögren's Syndrome (SS). The purpose of the present study has, therefore, been to determine the reliability of Magnetic Resonance (MR) in the evaluation of salivary alterations in patients with SS. The study involved 23 patients suffering from SS according to the European criteria. All the patients underwent ultrasonography and MR of the major salivary glands, parotid sialography and biopsy of the minor salivary glands. The first control group was made up of 50 healthy subjects who underwent parotid ultrasonography. The second control group comprised 23 subjects who underwent MR of the head and neck for other non parotid pathology. The ultrasonography, MR and sialography images were evaluated by a single observer during a single session and scored from 0 to 4. In the SS patients ultrasonography was abnormal in all 23 cases (100%): 3 patients showed grade 1 alterations (13%); 5 grade 2 (21.7%); 9 grade 3 (39.1%); 6 grade 4 (26.1%). In the healthy controls, grade 0 was found in 36 subjects (72%) while the remaining 14 subjects revealed grade 1 alterations (28%). Using MR imaging only one of the SS patients showed grade 0 alterations (4.3%), 7 showed grade 1 alterations (30.4%), 9 grade 2 (39.1%), 5 grade 3 (21.7%) and only 1 grade 4 (4.3%). MR imaging sensitivity was 95.8% while specificity was 100%. For ultrasonography, considering grade 1 as non pathological, we found a sensitivity of 88.4% and specificity of 100%. The MR score for SS patients was compared to that obtained with sialography and ultrasonography. There was a good correlation between MR and sialography (r = 0.528, p = 0.010) while the correlation between MR and ultrasonography was not statistically significant. This study confirms that, of the diagnostic procedures available for evaluation of salivary gland involvement in SS, the most useful initial examination is ultrasonography. When there is some doubt or there are subtleties, MR is a valid alternative to classical sialography.

[Diagnosis and classification of primary Sjögren syndrome. Comparison of 3 criteria sets in 219 cases]. / Diagnosi e classificazione della sindrome di Sjögren primitiva. Confronto fra tre gruppi di criteri in una casistica di 219 pazienti.

In spite of all recent years' international meetings, the question of diagnostic criteria of primary Sjögren's syndrome (pSS) is still under debate. The aim of our study is to define sensitivity, specificity and diagnostic accuracy of 3 sets of criteria: those of the European Community Study Group (ECSG), those proposed by Fox, and those proposed by Daniels. We considered 219 subjects complaining of dry mouth and/or dry eyes and/or parotid swelling, evaluated for pSS. The following parameters were considered golden standard for the diagnosis of pSS: focus score > or = 2 foci/mm2, double positivity for SSA and SSB antibodies, and a sialographic grade > or = 2. Our study demonstrates that ECSG criteria show a high sensitivity and a good specificity, resulting in a diagnostic accuracy similar, and sometimes higher, than that obtained with Fox and Daniels' criteria.

[Imaging in major salivary gland diseases] / Diagnostica per immagini nelle malattie delle ghiandole salivari maggiori.

Most of the salivary glands diseases are characterized only by a few distinct clinical patterns. Medical history and clinical examination are still considered of great relevance. However, in order to obtain a definite diagnosis, imaging techniques are required in most of the cases. Salivary glands ultrasonography (US) is the technique to be used as the first because US can easily differentiate calculosis, inflammatory diseases and tumors. Sonography is also frequently needed to perform needle aspiration or biopsy (FNAC). Sialography should be used essentially for assessing chronic sialoadenitis as well as Sjögren's syndrome. At present, Magnetic Resonance sialography should be preferred because of the greater sensibility in diagnosing inflammatory diseases of the salivary glands. It allows to evaluate both intraglandular oedema and nodules, so that incannulation of the salivary duct is not required. Computer Tomography (CT) and Magnetic Resonance imaging (MR) are useful when neoplasm are suspected, particularly if deep areas of the gland, which cannot be visualized by US, are involved. Sequential scintigraphy is currently employed for assessing the functional status of all the 4 major salivary glands and evaluating the chronic evolution of glandular damage.

[Primary Sjögren's syndrome. A longitudinal study of 68 patients]. / Sindrome di Sjögren primitiva. Studio longitudinale di 68 pazienti.

There are only few studies, regarding primary Sjögren's syndrome (pSS) long-term clinical course. Moreover, it has been often studied in a restricted number of patients, employing different recruitment and diagnostic criteria. During a 10 years follow-up, we longitudinally evaluate clinical course as well as severe complications and mortality rates in 68 patients with pSS, diagnosed according to the Fox's criteria. Patients were divided into 2 groups according to the autoantibodies pattern detected at the diagnosis: anti-Ro and/or La positive and anti-Ro La negative. Glandular manifestations of pSS were distinctively present in the majority of patients already at time of the diagnosis and serological findings remained typically constant during the whole follow-up. Increased IgG, IgA and ESR as well as low C4 serum levels were significantly prevalent in the Ro and/or La positive group. Finally, we did not found any significant increase in the mortality rate of pSS patients in comparison with the general population.

Effects of cyclosporin on joint damage in rheumatoid arthritis. The Italian Rheumatologists Study Group on Rheumatoid Arthritis.

According to the most recent literature, few antirheumatic drugs can claim disease-controlling properties over the anatomical joint damage in rheumatoid arthritis (RA). A small number of studies have favored one or another of the available agents, in particular parenteral gold salts, sulphasalazine and methotrexate, but the evidence regarding their efficacy is not convincing when analysed using methodological criteria known to be important in evaluating radiologic evidence of joint damage. The radiologic results in long-standing RA patients have shown that CsA may be of benefit in reducing disease progression. Data from the second year of a clinical trial designed to compare the disease-controlling, anti-rheumatic properties of CsA with those of conventional disease-modifying anti-rheumatic drugs (DMARDs) in early RA support the hypothesis that CsA may be useful in delaying the appearance of new joint erosion.

Esophageal motor function in primary Sjögren's syndrome: correlation with dysphagia and xerostomia.

The incidence of dysphagia in patients with primary Sjogren's syndrome (pSS) has been underestimated and all too often ascribed to xerostomia, without considering the possible presence of esophageal motor abnormalities affecting other nonscleroderma connective tissue diseases. Esophageal and salivary functions were prospectively evaluated in 27 females who met the four criteria proposed by Fox for the diagnosis of pSS, using esophageal manometry after wet swallows and Saxon's test, respectively. Dysphagia was graded using a standard symptoms questionnaire and results were compared with those obtained in a group of 21 healthy controls. Seven patients with pSS (26%) had no swallowing discomfort, 2 (7.4%) had mild dysphagia, 7 (26%) had moderate dysphagia, and 11 (40.6%) had severe dysphagia. Saxon's test revealed an overall decrease in the salivary flow rate compared to controls, with no difference between patients with or without dysphagia. Esophageal manometry demonstrated the absence of any lower or upper esophageal sphincter function abnormalities in all patients. In the patients with pSS as a whole, manometric study of the esophageal body showed a motor pattern comparable with that of controls, with no difference between patients with and without dysphagia. Defective peristalsis, ie, the presence of simultaneous contractions in more than 30% of wet swallows was detected, however, in the distal tract of the esophagus of six patients (22.2%) and in the proximal tract of three (11.1%). All these patients had severe dysphagia and the modified Saxon's test revealed a salivary secretion comparable with that of patients with a normal peristalsis. Dysphagia is a very common complaint in patients with pSS and does not seem to correlate with xerostomia, which is a constant and typical finding of the disease. About one third of patients with pSS have an abnormal esophageal peristalsis that is responsible for severe dysphagia, whereas decreased salivary outflow exacerbates the swallowing discomfort. This has to be taken into account and justifies the routine use of esophageal manometry in patients with pSS. The cause of dysphagia in pSS patients without peristaltic disorders of the esophagus has to be investigated.