Paolo Manganelli

Power Doppler sonography in the assessment of synovial tissue of the knee joint in rheumatoid arthritis: a preliminary experience

Objective: To investigate the intra-articular vascularisation of the synovial pannus in the knee of patients with rheumatoid arthritis (RA) with power Doppler ultrasonography (PDS) and an echo contrast agent and correlate the area under the time-intensity curves with the clinical findings and laboratory measures of disease activity. Method: Forty two patients with RA (31 women, 11 men) with history and signs of knee arthritis, classified according to a modified index of synovitis activity (active, moderately active, and inactive), were studied. Clinical and functional assessment (number of swollen joints, intensity of pain, general health—visual analogue scale, disability index—Health Assessment Questionnaire, Ritchie articular index) and a laboratory evaluation were made on all patients. Disease activity was evaluated using the disease activity score (DAS) and the chronic arthritis systemic index (CASI) for each patient. All patients were examined with conventional ultrasonography and PDS before injection of intravenous ultrasound contrast agent (Levovist). The quantitative estimation of the vascularisation of the synovial membrane was performed with time-intensity curves and calculation of the area under the curves. Results: The mean (SD) value of the area underlying time-intensity curves was 216.2 (33.4) in patients with active synovitis, 186.8 (25.8) in patients with moderately active synovitis, and 169.6 (20.6) in those with inactive synovitis. The mean value of the areas differed significantly between the patients with active and those with inactive synovitis (p<0.01). The mean value of the area under the curve of the entire group was weakly correlated with the number of swollen joints (p=0.038), but a strong correlation was found with composite indexes of disease activity such as the DAS (p=0.006) and CASI (p=0.01). No correlation was found with age, disease duration, and other laboratory and clinical variables. Conclusion: PDS may be a valuable tool to detect fractional vascular volume and to assist clinicians in distinguishing between inflammatory and non-inflammatory pannus. The transit of microbubbles of ultrasound contrast across a tissue can be used to estimate haemodynamic alterations and may have a role in assessing synovial activity and the therapeutic response to treatment of synovitis of the knee joint.

Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthritis: Report of five cases and review of the literature

SummaryPneumonitis is emerging as one of the most unpredictable and potentially serious, adverse effects of treatment with MTX. Its prevalence in rheumatoid arthritis (RA) has been estimated from several retrospective and prospective studies to range from 0.3% to 18%. On the other hand, MTX-induced pneumonitis seems to be very rare in psoriatic arthritis (PsA).Our review of 194 RA patients and 38 PsA patients receiving MTX has identified four RA patients and one PsA patient with MTX-induced pneumonitis, giving a prevalence of 2.1% and 0.03%, respectively. Diagnosis was suggested by clinical history and radiographic findings, but the bronchoalveolar lavage plays an important role both in excluding infectious agents and in providing information for understanding the pathogenesis of lung injury. The presence of a lymphocyte alveolitis with a predominance of CD4+ T cells in 3 RA patients and CD8+ T cells with a concomitant increase in neutrophils in another case suggests that immunologically mediated reactions may be one damage mechanism in MTX-induced pneumonitis. Although risk factors for MTX-induced pulmonary toxicity are poorly understood, the presence in 3 out of 5 of our patients of pre-existing lung disease, represented by diffuse interstitial changes on chest X-ray, and mild bronchial asthma in two RA patients and by pulmonary silicosis in the patient with PsA may account for a predisposition to the development of MTX pneumonitis.

Peripheral neuropathy in Wegener’s granulomatosis, Churg–Strauss syndrome and microscopic polyangiitis

Objective: To compare the clinical aspects of peripheral neuropathy associated with Wegener’s granulomatosis (WG), Churg–Strauss syndrome (CSS) and microscopic polyangiitis (MP). Methods: Cohort study conducted in a single university hospital. Patients were included when a definite diagnosis of WG, CSS or MP was made according to the current classification criteria in our hospital, between 1999 and 2006. All patients underwent periodically clinical and electrophysiological screening for peripheral neuropathy, assessment of disability, and clinical and laboratory evaluation during a mean follow-up of 38 months. Results: Sixty-four consecutive patients diagnosed with WG (26 patients), CSS (26 patients) and MP (12 patients) were recruited. Peripheral neuropathy occurred in 27/64 patients: six with WG, 15 with CSS and six with MP. Neuropathy occurred earlier in the disease history in CSS and MP compared with WG. Among patients with WG, those who developed peripheral neuropathy during follow-up were older than those without neuropathy both at the time of onset and of diagnosis of vasculitis. Distal symmetric polyneuropathy was present in 11 patients, and single or multiple mononeuropathy in 16. Patients with WG had a less severe form of mononeuritis multiplex than CSS or MPA patients. Disability and pain were greater in patients with mononeuropathy, although one-third of them were painless. Relapses of neuropathy were extremely infrequent. Conclusions: Peripheral neuropathy in WG occurs less frequently, later in the disease course and in a milder form than in CSS and MP. Single or multiple mononeuropathy associated with these subsets of vasculitis can often be painless.

Ultrasonography and Colour Doppler Sonography of Salivary Glands in Primary Sjo¨gren’s Syndrome

Abstract: To examine either the ultrasonographic (US) features of the parotids and submandibular glands or the blood flow alterations that may occur in the salivary glands of patients with primary Sjo¨gren’s syndrome (pSS) we studied 30 female patients with pSS and 30 controls suffering from dry mouth not due to pSS. All measurements were taken by the same examiner, who used the same equipment to avoid interobserver variability. The US parameters recorded (parenchymal homogeneity, echogenicity, size of the glands and posterior glandular border) were scored according to a previously described scoring system. For each waveform, peak systolic velocity (PSV) and resistive index (RI) were measured at the external carotid artery in the examination of the parotids and at the facial artery within the submandibular glands before and during lemon juice stimulation. On the basis of the degree of chronic inflammatory changes at minor salivary gland (MSG) biopsy, chronic sialadenitis (CS) was defined as mild in 10 and severe in 20 pSS patients. Abnormal US scores were obtained in 26/30 (86.6%) pSS patients and in 9/30 (30%) controls. Moreover, in pSS patients the US scores were sigificantly higher than in the control group (p=0.0001). The mean (± SD) difference between the PSV values taken from parotids and submandibular glands before and during lemon juice stimulation was statistically significant (p=0.003 and p=0.01, respectively) in the controls. On the other hand, no significant changes in the PSV values were found in the whole group of pSS patients. However, the changes in PSV values before and during lemon juice stimulation were statistically significant in both parotids (p=0.019) and submandibular glands (p=0.012), and not significantly different from those in the controls in pSS patients with mild CS. The variability of RI taken from the salivary glands before and during lemon juice stimulation was not statistically significant in either pSS patients or controls. US abnormalities were detected in the majority of pSS patients and their severity was significantly greater than those recorded in the controls. Of the colour Doppler sonographic (CDS) parameters only PSV was influenced by the degree of chronic inflammation, as shown at the MSG biopsy, suggesting that PSV may reflect the vascular changes occurring in the salivary glands during the course of an autoimmune disease such as pSS.

Peripheral neuropathy in essential mixed cryoglobulinaemia.

The prevalence of various forms of peripheral neuropathy has not been previously assessed in large series of patients with essential mixed cryoglobulinaemia (EMC). Clinical and electrophysiological signs of peripheral neuropathy were observed in 21 of 37 EMC patients, consisting of polyneuropathy in 19, mononeuropathy or multiple mononeuropathy in eight, and both in six. The various forms of peripheral neuropathy occurred differently in the subgroups of EMC. Isolated polyneuropathy was more common with type II (eight of 10) than type III EMC (two of eight). Multifocal neuropathy, in association with polyneuropathy, was the most common form in type III EMC (five of eight). Patients with peripheral neuropathy and type II EMC were significantly older than type II EMC patients without neuropathy, regarding present age and age of onset of EMC. Patients with peripheral neuropathy and type III EMC tended to have higher values of ESR and IgM than type III EMC patients without neuropathy. Electrophysiological findings and sural nerve biopsy specimens (nine cases) showed prominent axonal changes. Vascular changes included vasculitis and alterations of the endoneurial microvessels in type II and type III EMC. Our findings suggest that distinct pathogenic factors are implicated in the subgroups of cryoglobulinaemic neuropathy, possibly inducing different types of vascular changes underlying polyneuropathy or, respectively, mononeuropathy and multiple mononeuropathy.

OPG/RANKL system imbalance in a case of hepatitis C-associated osteosclerosis: the pathogenetic key?

Hepatitis C-associated osteosclerosis (HCAO) is an impressive example of acquired diffuse osteosclerosis in adults, recently described in ten patients infected with hepatitis C virus (HCV). Its hallmark is a painful and generalized increase of bone mass. Bone biopsies show enhanced accretion rate, usually without histological abnormalities. The HCAO pathogenesis is hitherto unknown. HCV might induce a slow bone cell infection and the production of bone growth factors, such as insulin-like growth factors. Recently, receptor activator of nuclear factor-κB (RANK), its ligand (RANKL), and soluble decoy receptor osteoprotegerin (OPG) have been identified as a pivotal cytokine system in the bone remodeling control. We describe the 11th case of HCAO. Notably, the patient’s bone biopsy showed the presence of a high number of OPG-positive osteoblasts, a slight increase of RANKL-positive stromal cells, and a dramatic reduction of the osteoclasts. Moreover, OPG serum levels were increased. These findings reported here for the first time are consistent with a pathogenetic role of the OPG/RANKL system imbalance in HCAO.

Pulmonary Involvement in Sjögren’s Syndrome

In this study we tried to value the frequency and the characteristics of the physiological abnormalities affecting the lungs in Sjögrens syndrome (SS). We studied 18 female nonsmokers (average age 53 years). The diagnosis has been made on the presence of at least two of the following abnormalities: keratoconjunctivitis sicca (Schirmers test), xerostomia (scanning of the salivary glands, lip biopsy) and collagen vascular disease. We made the following tests: clinical examination, chest roentgenogram, spirometry, TGV, RAW and SAW valuation, study of the flow-volume curves, diffusion capacity test, bronchoalveolar lavage, bronchial biopsy. The physiological results have demonstrated the presence of a restrictive syndrome affecting above all the small airways (MEF25-32.7%) and a decrease of the diffusion capacity (DLCO-25%). There is, moreover, a constant lymphocytic infiltration of the bronchial mucosa and of the lungs interstitium. In conclusion the pulmonary involvement in SS seems to be constant, unpredictable and of remarkable clinical-physiological importance.

Bronchoalveolar Lavage in Chronic Eosinophilic Pneumonia

We describe 6 patients with chronic eosinophilic pneumonia (CEP) investigated clinically and by bronchoalveolar lavage (BAL). The BAL findings of these 6 patients were compared with those of 293 patie

Clinical and subclinical alveolitis in connective tissue diseases assessed by bronchoalveolar lavage

Subclinical alveolitis, as assessed by bronchoalveolar lavage (BAL) cell analysis, may be present in the lower respiratory tract of a high proportion of symptomless patients with connective tissue diseases (CTDs) with normal chest roentgenograms. The distribution of BAL cell types, mainly macrophages, lymphocytes, and polymorphonuclear neutrophils, varies according to type of CTD and to the presence of associated interstitial lung disease (ILD). Nevertheless, subclinical alveolitis can be classified into two major groups: lymphocyte and neutrophil alveolitis. A mixed, lymphocyte and neutrophil alveolitis may be detected as well. Subclinical alveolitis, particularly in systemic sclerosis, frequently is associated with abnormalities of lung parenchyma as assessed by computed tomography (CT) scan, supporting the hypothesis that it may be associated with the development of overt ILD. Close follow-up of these patients is needed to better determine whether subclinical alveolitis precedes ILD and whether early detection of subclinical alveolitis in CTDs may identify those patients who are at risk for the development of ILD in the future.

Remitting Seronegative Symmetrical Synovitis with Pitting Oedema in a Patient with Myelodysplastic Syndrome and Relapsing Polychondritis

Abstract: Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) may be the inaugural manifestation of different rheumatic diseases of the elderly, malignancies and myelodysplastic syndromes (MDS). Relapsing polychondritis (RP) is a rare systemic disorder characterised by an inflammatory process involving predominantly cartilaginous structures, the cardiovascular system and organs of special sense. We report on a 72-year-old man with RS3PE and MDS, refractory anaemia subtype, diagnosed at the same time as RS3PE. Several months later the patient presented a clinical and pathological picture compatible with RP. Although the association between RP and MDS is well known, no previous cases of RS3PE preceding RP have been reported. This case confirms that RS3PE may herald many diseases, among others autoimmune disorders such as RP.