Coexistence of axial spondyloarthritis and thromboangiitis obliterans in a young woman.

A peculiar coexistence of axial spondyloarthritis and ischemia of the feet and the fourth finger of the left hand in a young woman, who was a heavy smoker, is discussed in this report. This picture was considered within the context of thromboangiitis obliterans. Positivity of anti-nuclear antibodies and mild elevation of inflammatory parameters were noted. Computed tomography angiograms of upper and lower limbs showed luminal narrowing and occlusion of the left humeral, left anterior/posterior tibial and right anterior tibial arteries. Daily iloprost perfusions were started, and smoking cessation was strongly recommended. Coldness and rest pain in the distal extremities improved within a few weeks. The possibility that spondyloarthritis might precede the clinical picture of thromboangiitis obliterans should be considered in heavy smokers.

A false occult hepatitis B virus infection developed in a patient with psoriatic arthritis under infliximab and methotrexate therapy.

Despite lacking of international guidelines about the management of patients with occult hepatitis B virus infection (OBI) starting TNF-α blockers, there is some evidence from real life settings that these drugs are safe in OBI patients with rheumatic diseases. On the contrary, the management of the so-called false OBI patients appears still undefined. We describe a case of acute hepatitis B virus (HBV) infection occurred in an anti-HBs and anti- HBc positive patient affected by psoriatic arthritis, who had been treated for five years with infliximab. Baseline HBV-DNA analysis had not been performed. Although HBs Ag was still negative and the transaminases in the normal range, HBV-DNA serum analysis surprisingly showed high replication rate. Entecavir was added, and three months later HBV-DNA was no longer detectable. Even if HBs Ag is persistently negative, the assessment of HBV-DNA should be recommended at least at baseline in order to rule out hidden active necro-inflammatory liver disease.

Rituximab treatment for Sjogren syndrome-associated non-Hodgkin's lymphoma: case series.

Five per cent of patients with primary Sjogren's syndrome (pSS) develop malignant non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) and most frequently located in the major salivary glands. Rituximab (RTX), a chimeric monoclonal antibody against the CD20 molecule expressed on the surface of mature B cells that has been approved for the treatment of NHL, has been used to treat pSS-associated lymphoma. We have described two cases: one with MALT lymphoma in the parotid glands and the other with a rare thymus lymphoma accompanied by the rare complication of a bullous pneumopathy. Both were treated with RTX at haematological doses, which was unsuccessful in the patient with a salivary lymphoma; in the case of the patient with a thymus lymphoma, the mediastinum mass disappeared and did not relapse. Both patients experienced an improvement in the subjective symptoms of dryness, and their Schirmer's test and scialoscintigraphy results stabilised. The pulmonary bullae remained unchanged.

Safety of rituximab in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic disease that requires long-term administration of immunomodulatory drugs with a greater risk of side effects like malignancies, serious infections and cardiovascular diseases. Furthermore, patients with RA are more prone than the general population to these manifestations. Safety of rituximab has been evaluated in the short-term (6 months) and in the medium-term (up to 10 years) in patients who had been previously treated with antagonists of tumor necrosis factor (a-TNF) and/or with methotrexate (MTX) and in patients who were not. Data obtained from clinical trials demonstrated that rituximab is well tolerated either after a single course or after multiple courses. The overall rate of adverse events (AEs) was stable after the first three courses. The most frequent adverse event was infusion-related reactions (IRR). Serious infections did not increase after multiple courses. Data from "real life" confirm that treatment with rituximab is well tolerated.

[Treatment of digital ulcers in systemtic sclerosis with endothelin-1 receptor antagonist (bosentan)]. / Prevenzione delle ulcere digitali nella sclerosi sistemica con antagonisti del recettore dell'endotelina (bosentan).

In systemic sclerosis (SSc) occurrence of recurrent digital ulcers (DU) is cause of pain and functional disability of hands. Treatment with vasodilator agents, such as calcium channel blockers, ACE inhibitors, prostanoids, has not shown to be an effective therapy. There is evidence that endotelin-1 (ET-1) is a key mediator in regulation of vascular tone and its enhanced production in SSc is believed to lead to vasoconstriction, vessel remodelling, local ischemia and ulcers of fingertips. Recently, an oral endothelin receptor antagonist, bosentan, has been proved to be effective in the treatment of SSc associated pulmonar arterial hypertension (PAH) and to decrease the development of new DU in patients with SSc. In this study, we assessed the occurrence of new DU in eight patients with SSc associated PAH and one SSc patient with recurrent DU refractory to standard vasodilatation therapy. All patients received bosentan at dosage of 62.5 mg bid for 4 weeks and 125 mg bid thereafter for one year. All patients had 3-4 DU of hands at baseline and one patients had also ulcers at lower limbs. In seven out of nine patients we did not record the occurrence of new DU and we also observed a 50% reduction of existing DU, whereas new DU occurred only in two patients. These data suggest that ET-1 plays a key role in DU induction in SSc patients and that ET-1 inhibition by bosentan can be an effective therapeutic strategy.

[Prevalence of anti-CCP antibodies in systemic sclerosis]. / Prevalenza degli anticorpi anti-peptide ciclico citrullinato (anti-CCP) nella sclerosi sistemica.

Joint involvement in systemic sclerosis (SSc) commonly occurs as arthralgias, while a true arthritis is less frequent. The most common arthritis developing in SSc is rheumatoid arthritis (RA) and its diagnosis may be misled by concomitant joint contracture or tendon sheath involvement due to SSc. Anti-citrullinated cyclic peptide (CCP) antibodies are an emerging tool to diagnose RA and have shown to be more specific than rheumatoid factor. We assessed the prevalence of anti-CCP antibodies in SSc patients and evaluated their sensitivity and specificity for associated RA. Searching for RF and anti-CCP antibodies and joint examination were carried out in sixty consecutive SSc patients. Hands and feet standard x-rays were performed in patients complaining with arthralgia and/or arthritis. Six out of sixty (10%) SSc patients had RA according to 1987 ARA revised criteria. Anti-CCP were detected in 5 patients (sensitivity 83%) and RF was present in all RA patients (sensitivity 100%). However, anti-CCP antibodies had a much higher specificity (94%) than RF (41%) for RA. Our study suggests that anti-CCP antibodies are a useful test to identify patients with SSc having also RA. This is crucial in the management of SSc because may allow an adequate therapy of RA and prevent further joint damage in patients who already have a poor quality of life.

Repeated infusions of low-dose infliximab plus methotrexate in psoriatic arthritis: immediate benefits are not maintained after discontinuation of infliximab.

OBJECTIVE: To assess the long-term efficacy and tolerability of a therapy consisting of infliximab at low dosage plus methotrexate in patients with psoriatic arthritis (PsA). As a second objective, we assessed whether the improvement obtained after 54 weeks of infliximab could be maintained with methotrexate alone. METHODS: A group of 26 patients with peripheral PsA resistant to various DMARDs were treated with infliximab + methotrexate for 54 weeks. RESULTS: The clinical response after the induction period was constant and progressive, with a high percentage of patients achieving an ACR50 response. The ESR and CRP values also declined continuously and gradually, but only CRP returned to normal values. During the follow-up period after 54 weeks, infliximab was stopped and the improvement obtained lasted for 2-6 months. The secondary end point was not achieved, and an extension period was designed. Results at 78 weeks are presented. CONCLUSIONS: Open questions for treating patients with infliximab and methotrexate are the schedule and the length of the administration and how to preserve the improvement obtained after the drug discontinuation.

Infliximab therapy does not modify MMP-2 and MMP-9 serum concentrations in chronic arthritis.

OBJECTIVE: Matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) play a key role in tissue remodelling after processes such as joint destruction in rheumatoid arthritis. Their expression may reflect the disease activity and they could therefore represent a useful marker to assess the efficacy of therapy. In this study MMP-2 and MMP-9 serum were evaluated in patients with chronic arthritis during therapy with the anti-TNFalpha mAb, infliximab. METHODS: Fifty patients with chronic arthritis, 26 with rheumatoid arthritis and 24 with undifferentiated chronic arthritis, were recruited and treated with infliximab (3 mg/kg). Serum concentrations of MMP-2 and MMP-9 were serially measured by gelatine zymography at baseline and after two and fourteen weeks of infliximab therapy. DAS-28 and ACR response criteria were applied to assess disease activity and clinical improvement. Twenty-four healthy donors were included in the study as controls. RESULTS: Although therapy with infliximab induced a statistically significant reduction of the DAS-28 score and improvement of the ACR clinical response, MMP-2 and MMP-9 serum concentrations were not modulated during therapy with infliximab. CONCLUSIONS: Our study provides further evidence that blocking TNFalpha by infliximab is a powerful tool in the management of chronic arthritis. Nevertheless, infliximab does not seem to be able to modify the serum expression of MMP-2 and MMP-9, probably because modification of these enzymes is restricted to the site of joint inflammation and serum detection can not truly mirror the local situation. Additional soluble factors correlating with joint damage should be investigated as possible markers for monitoring anti-TNFalpha therapy.

[The treatment of recurrent uveitis with TNF-alpha inhibitors]. / Il trattamento delle uveiti recidivanti con inibitori del TNFalfa.

OBJECTIVE: Uveitis is a severe manifestation of rheumatic diseases since it can lead to visual impairment and even blindness. Ocular involvement is frequently a clinical challenge because its occurrence often requires changes of the therapeutic strategy. There are growing evidence that tumor necrosis factor alpha (TNFalpha) inhibitors may be an effective treatment of refractory uveitis. Purpose of this study was to evaluate the efficacy and safety of TNFalpha blocking agents in patients with seronegative spondylo-arthropathies (SNSA) and Behcet disease (BD) associated relapsing uveitis. METHODS: Five consecutive patients with chronic or relapsing uveitis were prospectively studied. Two patients with SNSA had recurrent anterior uveitis and three patients had BD associated uveitis (one anterior, two posterior uveitis). All of the patients were taking systemic and topical corticosteroids and three of them were also treated with DMARDs (methotrexate, cyclosporine, sulphasalazine) without clinical benefit. Four patients received infliximab, an anti-TNFalpha monoclonal antibody, at a dosage of 5 mg/kg body weight and one patient was treated with etanercept, a TNFalpha receptor p75-Fc fusion protein, at a dosage of 25 mg twice weekly. RESULTS: Both infliximab and etanercept induced a marked improvement in uveitis and none relapse was observed throughout all the study. Systemic corticosteroids were progressively tapered and stopped in all patients. Also methotrexate and sulphasalazine were discontinued, while cyclosporine dose has been reduced by 30%. No side effects were observed. CONCLUSIONS: Therapy with TNFalpha blockers, infliximab and etanercept, was effective and safe in the treatment of rheumatic disease associated uveitis. A complete remission was achieved even in patients with severe steroid resistant uveitis. Further controlled studies on larger number of patients are needed to better define the different forms of ocular involvement that can benefit from the therapy with TNFalpha inhibitors.

[Prosthetic rehabilitation of edentulous patients after stroke]. / Riabilitazione protesica di pazienti edentuli con esiti di stroke.

AIM: Stroke is actually the 3rd cause of death in the world after cardiovascular diseases and cancer. In Italy, every year there are 100000 new cases; 2/3 of them die or become heavily disabled. The greatest part of patients which survive is old-aged and 70% of patients that survive is a removable denture wearer. METHODS: At the Neurological Clinic of the Polyclinic Hospital of Bari we have studied 14 removable denture wearers that had had a stroke. RESULTS: We observed that 85.7 % of removable dentures were inefficient, in 50% there will need a new removable prosthesis; 50% of persons had a bad dental hygiene; 93% of denture wearers with stroke didn't make an odontoiatric control after stroke. CONCLUSIONS: Although the analysis of the orodental status has been carried out on a limited number of patients, the need of a greater motivation and solicitation in dental check-up is underlined. The role of the dentist in oral rehabilitation and in rehabilitation of post stroke dysphagia in stroke survivors is also examined.

Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes.

OBJECTIVE: We aimed to investigate the expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) on chondrocytes from human healthy and osteoarthritic cartilage. METHODS: We recruited 12 patients with osteoarthritis (OA) undergoing surgical knee replacement. Articular cartilage was split into two zones showing macroscopically and histologically the lowest (MIN) and highest (MAX) degree of osteoarthritic damage. Additional specimens of cartilage were obtained from three healthy donors. Chondrocytes were isolated by enzymatic digestion and freshly processed for NGF protein, Trk A detection and mRNA extraction. NGF-beta mRNA was determined by a reverse transcriptase-polymerase chain reaction (RT-PCR). NGF-beta and TrkA expression was evaluated by immunofluorescence and flow cytometry analysis. RESULTS: NGF-beta-specific mRNA was detected in normal and osteoarthritic chondrocytes. NGF-beta protein levels were low in normal chondrocytes, increased in MIN osteoarthritic cartilage and further enhanced in MAX osteoarthritic cartilage. Likewise, TrkA was scarcely expressed on normal chondrocytes and progressively increased on osteoarthritic chondrocytes based on the extent of anatomic damage. CONCLUSIONS: This is the first study showing that human chondrocytes synthesize NFG-beta and express on their surface the high affinity NGFR (p140 TrkA). Of note, NGF-beta and TrkA were upregulated in osteoarthritic chondrocytes suggesting a role of NGF in the pathophysiology of OA. We can speculate that NGF, like other growth factors, stimulates chondrocyte metabolism in the osteoarthritic process.

Interleukin-10 and interleukin-10 receptor in human osteoarthritic and healthy chondrocytes.

OBJECTIVE: To evaluate the expression of interleukin-10 (IL-10) and interleukin-10 receptor (IL-10R) on chondrocytes from healthy, osteoarthritic, and foetal cartilage from human subjects. METHODS: Articular cartilage was obtained from 12 patients with osteoarthritis (OA) undergoing surgical knee replacement. Chondrocytes were isolated from the two zones of cartilage showing macroscopically and histologically the lowest (MIN) and highest (MAX) extent of osteoarthritic damage. Additional specimens of cartilage were obtained from 3 healthy donors and 3 human foetuses. IL-10 mRNA expression was determined by a reverse transcriptase-polymerase chain reaction (RT-PCR). For detection of intracellular IL-10 protein, chondrocytes were permeabilized and then incubated with R-phycoerythrin (PE) conjugated rat anti-human IL-10 mAb. Cell surface IL-10R was detected by incubation with biotinylated recombinant human IL-10; after washing, bound IL-10 was revealed by fluorescein (FITC) conjugated streptavidin. Positive chondrocytes were analysed by flowcytometry. RESULTS: IL-10 mRNA expression was higher in osteoarthritic than in normal chondrocytes. IL-10 protein intracellular levels were significantly higher in MAX than in MIN osteoarthritic cartilage or in healthy cartilage. Cell surface IL-10R was expressed on osteoarthritic chondrocytes with no difference in the degree of cartilage damage. The highest levels of IL-10 protein and IL-10R were found in foetal cartilage. CONCLUSION: Human chondrocytes synthesise IL-10 and express on their surface IL-10R. Since IL-10 inhibits IL-1 and TNF-alpha expression, its upregulation in osteoarthritic chondrocytes may counteract the detrimental effects of these catabolic cytokines. However, the functions of IL-10 in cartilage may go beyond those activities established in the immunological setting. The high levels of IL-10 and IL-10R in foetal cartilage, an active growing tissue, suggest that IL-10 may play a role in controlling chondrocyte metabolism under physiological conditions.

[Association of systemic sclerosis and psoriatic arthritis: a case report] / Associazione sclerosi sistemica ed artrite psoriasica: descrizione di un caso clinico.

The association of Systemic Sclerosis (SSc) and Psoriatic Arthritis (PsA) is unfrequent; only few cases are reported in literature. We describe a case of a patient with SSc following the onset of PsA. The disease begun with tenosynovitis, polyarthritis in association with psoriasis. After two years, Raynaud's phenomenon and sclerodactyly appeared, and, later, pulmonary interstitial fibrosis and esophageal dysfunction. The existence of a common pathogenesis of the two diseases, SSc and PsA, is discussed.

[Morphologic study of the microcirculation in connective tissue diseases]. / Lo studio morfologico del microcircolo nelle connettiviti.

Capillaroscopy is a non-invasive diagnostic test used to study microvascular abnormalities which are present in many disorders, particularly some rheumatic pathologies, such as connective tissue diseases. In systemic sclerosis, capillaroscopy allows detection of pathognomonic microvascular alterations. In other connective tissue diseases, including systemic lupus erythematosus, dermatopolymyositis, undifferentiated connective tissue diseases, and mixed connective tissue disease, the capillaroscopic patterns, although non-specific, can provide a valid support for the diagnosis. In Raynaud's phenomenon, capillaroscopy enables detection of early microvascular abnormalities that are useful for preclinical diagnosis of secondary Raynaud's phenomenon.

Cogan's syndrome: unsuccessful outcome with early combination therapy.

Interstitial keratitis and vestibuloauditory symptoms (vertigo and hearing loss) are the typical signs of Cogan's syndrome, a rare inflammatory vascular disease. Signs of vasculitis in many organ systems may appear, among which neurologic problems are sometime predominant. The efficacy of glucocorticoids on the ocular and systemic symptoms is established, but their effect on hearing loss is unknown. We describe a case of Cogan's syndrome with neurological involvement in which early treatment with combination therapy (prednisolone and cyclosporin) failed to bring ear inflammation under control.

The role of carotid duplex ultrasound in evaluating plaque morphology: potential use in selecting patients for carotid stenting.

PURPOSE: To study the role of duplex ultrasonography in evaluating plaque morphology and its correlation to neurological symptoms and cerebral infarctions on computed tomographic scans. METHODS: The hospital records of 181 patients (107 males; average age 66 years, range 41 to 89) with > 50% carotid stenosis (29 bilateral lesions) who had undergone duplex ultrasonography, carotid arteriography, and cerebral computed tomography were studied retrospectively. Of 210 duplex examinations, 139 were appropriate for morphological analysis of surface characteristics and echogenicity. RESULTS: Over half of the plaques examined had irregular surfaces (81, 58%) and displayed mixed (i.e., heterogeneous) echogenic patterns (74, 53%). Irregular (68 of 81, 84%) and heterogeneous (65 of 74, 88%) plaques were associated with ipsilateral neurological symptoms (p < 0.0001). Similarly, 44 (54%) of 81 irregular plaques and 42 (57%) of 74 heterogeneous plaques were found in patients with cerebral infarctions in the carotid territory (p < 0.0001). CONCLUSIONS: Heterogeneous and/or irregular plaques were more often associated with both neurological symptoms and infarctions than smooth or homogeneous plaques. These findings may have implications in patient selection for endoluminal therapy.

Chondrocyte phenotyping in human osteoarthritis.

Cell-ECM (extracellular matrix) interactions are believed to play a key role in maintaining the normal structure of tissues such as cartilage. Cell surface adhesion molecules have been reported to mediate chondrocyte binding to ECM proteins in human normal cartilage but the behaviour of these molecules in human osteoarthritic cartilage is unknown. We studied receptor matrix proteins on freshly isolated chondrocytes obtained from 10 patients with osteoarthritis (OA). Chondrocytes were isolated by enzymatic digestion from three zones of the articular cartilage with a different degree of macroscopic and microscopic damage and chondrocyte phenotype was defined by flow cytometry. Chondrocytes strongly expressed beta1, integrin but not beta3 integrin. LFA-1 (CD18/CD11a) and ICAM-1 (CD54) antigens were almost undetectable. Interestingly, beta1 expression was significantly higher in the minimally damaged zone than in the zones with medium and maximum damage. These data show that beta1-integrin-mediated chondrocyte-ECM interactions decrease in osteoarthritic cartilage suggesting that perturbations of chondrocyte-matrix signalling occurs during OA.

Quality of life assessment during six months of NSAID treatment [Gonarthrosis and Quality of Life (GOAL) Study].

OBJECTIVE: To identify the time point of the greatest degree of improvement in daily living activities, pain and depression in patients with osteoarthritis (OA) of the knee during 6 months of treatment with NSAIDs, in order to define compliance and drop-out rate. METHODS: 107 patients were recruited into a multicentre, prospective, randomized, controlled trial comparing two treatments, piroxicam-beta-cyclodextrin (PBCD) and slow release diclofenac (DCL). RESULTS: The greatest improvement in quality of life occurred in both groups after 3 months, with a slight further gain observed by the end of treatment. The Stanford Health Assessment Questionnaire score improved (p < 0.05 vs baseline) at 3 and 6 months with PBCD and at 6 months with DCL. The Arthritis Impact Measurement Scale score improved (p < 0.05 vs baseline) after 6 months in both groups. Significant (p < 0.05 vs baseline) improvement in other psychological and pain scores were recorded in both groups after 3 and 6 months. Compliance with treatment at 3 months was 73% for PBCD and 72% for DCL, and was 60% in both groups at 6 months. CONCLUSIONS: The results of this study indicate that the optimal length of time for an NSAID trial in OA patients is 3 months, when assessment of daily living activities is considered as the main outcome criterion.