Interferon Alpha-2a Treatment for Post-Uveitic Refractory Macular Edema.

Purpose: To assess the efficacy of interferon (IFN) alpha-2a in the treatment of post-uveitic refractory macular edema (ME).Methods: Retrospective cohort of patients with post-uveitic refractory ME, who received subcutaneous IFN alpha-2a injections for at least 3 months. Baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) were compared with those at follow-up visits up to 12 months.Results: Thirty-seven patients were included. Treatment duration (median [interquartile range]) was 14[8-24] months with a follow-up of 17[10-38] months. CMT (mean [standard deviation]) decreased from 438[140] to 335[119] µm after 1 month (p < 0.0001) and remained significantly lower up to 12 months (286[98] µm, p = 0.001). BCVA (0.48[0.33] logMAR at baseline) improved by 0.26[0.33] logMAR (p = 0.001) at 12 months. There were 14 recurrences. Seven patients had treatment side effects, without serious adverse events.Conclusions: IFN alpha-2a was effective, safe, and well tolerated in treating post-uveitic refractory ME.

Imaging in polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause clinically characterized by pain and prolonged morning stiffness affecting the shoulders and often the pelvic girdle and neck. Imaging has substantially contributed to defining PMR as a disease mainly involving extra-articular structures. This review article analyses the role of the different imaging techniques in the diagnosis and follow-up of patients with PMR with particular emphasis on the role of ultrasound, PET/CT and MRI.

Biotherapies in large vessel vasculitis.

The mainstay of therapy of large vessel vasculitides (LVV) remains glucocorticoids (GC). Although most patients initially achieve disease remission, relapses and GC dependence are seen in more than two-thirds of cases. Conventional synthetic disease-modifying antirheumatic drugs (DMARDs) showed little or no steroid sparing effects, while biological agents represent a valid therapeutic option in patients with severe and/or relapsing LVV.

Nailfold capillaroscopic changes in dermatomyositis and polymyositis.

Inflammatory myopathies (IM) are a group of muscle diseases occurring both in children and adults. Nailfold videocapillaroscopy (NVC) alterations are described in IM, but available data are discordant, including differences between polymyositis (PM) and dermatomyositis (DM). The aim of this study was to describe the capillaroscopic differences between PM and DM patients and possible correlation with clinical and serological features. We analyzed 52 unselected patients with IM in a cross-sectional study in a 6-month period. NVC findings of 29 DM and 23 PM patients were compared with those of 52 patients with primary Raynaud's phenomenon. Tortuosities, capillary loss, enlarged and giant capillaries, microhemorrhages, and ramified capillaries were scored by a semiquantitative rating; disorganization of the vascular array, avascular areas, and scleroderma pattern were scored as presence/absence. Sex, mean age, and mean disease duration were similar in both groups. Disorganization of the vascular array, enlarged and giant capillaries, capillary loss, and scleroderma-like pattern were observed almost only in IM patients. Significant differences were observed between PM and DM with higher frequency and mean score of NVC changes in DM. In DM patients with disease duration ≤6 months (14/29 patients), capillary density was significantly reduced (P = 0.039) and giant capillaries more frequent (P = 0.027), compared with patients with longer disease duration, while a scleroderma pattern tended to be more frequent in patients with a disease duration of less than 6 months. On the contrary, no differences were observed for ramified capillaries with regard to disease duration. Capillaroscopic alterations are identified only in DM patients as expression of diffuse microangiopathy; surprisingly, more severe changes were associated with shorter disease duration, while persistence of ramified capillaries with long-standing disease.

[New aspects on the pathogenesis of myositis]. / Neues zur Pathogenese der Myositiden.

Idiopathic inflammatory myopathies (IIM) are chronic inflammatory diseases of muscle characterized by proximal muscle weakness. There are three main groups of diseases, dermatomyositis, polymyositis and inclusion body myositis. The muscle tissue is invaded by the humoral autoantibody producing immune system (B-cells) and by the cellular immune system with autoaggressive and inflammation modulating cells (e.g. dendritic cells, monocytes/macrophages, CD4 + and CD8 + T-cells and natural killer cells). The presence of specific or associated autoantibodies and inflammatory cellular infiltrates with cytotoxic and immune autoreactive properties are characteristic for IIM diseases. The pathogenesis is still unknown; nevertheless, there are several hints that exogenic factors might be involved in initiation and disease progression and bacterial, fungal and viral infections are thought to be possible initiators. Up to now information on prognostic markers to help with decision-making for individual treatment are limited. In addition, there has been only limited therapeutic success including conventional or novel drugs and biologicals and comparative validation studies are needed using similar outcome measurements. Moreover, to facilitate the use and development of novel therapies, elaboration of intracellular and cell-specific regulation could be useful to understand the etiopathogenesis and allow a better diagnosis, prognosis and possibly also a prediction for individualized subgroup treatment.

Pulmonary artery involvement in Takayasu arteritis. PET/CT versus CT angiography.

OBJECTIVES: To report a patient with Takayasu arteritis in whom 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computerised tomography (CT) failed to demonstrate pulmonary artery involvement. METHODS: A patient with Takayasu arteritis underwent PET/CT and CT angiography before and one year after immunosuppressive treatment. RESULTS: Before treatment, PET/CT showed increased FDG uptake in the aortic arch and epiaortic arteries; pulmonary arteries were not visualised. Follow-up PET/CT one year later demonstrated resolution of abnormal vascular FDG uptake. CT angiography of the chest/abdomen prior to treatment revealed circumferential thickening of the ascending aorta, aortic arch, supra-aortic branches, and left inferior intralobar pulmonary artery with normal lumen diameter (27 mm). After therapy, CT angiography revealed decreased aortic wall thickening with complete resolution of intralobar wall thickening. However, the lumen of the central pulmonary artery was increased (32 mm). CONCLUSIONS: PET/CT is very sensitive in depicting active vasculitis, but cannot visualise the pulmonary arteries, presumably because their diameter is below the power of detection of PET/CT. CT angiography or magnetic resonance angiography is required to evaluate pulmonary artery abnormalities.

Tocilizumab in glucocorticoid-naïve large-vessel vasculitis.

Glucocorticoids (GC) are the mainstay of treatment of large-vessel vasculitis (LVV), but a sizeable number of patients relapse upon tapering the GC dose or after discontinuation of GC therapy. In addition, GC cause numerous adverse events. Therefore, in patients with longstanding disease and in those at risk for GC-related adverse events, the use of alternative therapeutic agents should be considered. Interleukin-6 (IL-6) is a key player in the pathogenesis of LVV. Preliminary data suggest the efficacy of the IL-6 receptor inhibitor tocilizumab (TCZ) in patients with LVV. We report 2 treatment-naïve patients with a recent diagnosis of LVV who received monthly TCZ infusions (8 mg/kg body weight) for 6 consecutive months as monotherapy because of relative contraindications and patients' reluctance to take GC. In both cases we observed a complete clinical response and normalisation of inflammatory markers as well as a decrease in vascular FDG uptake and SUV ratio on fluorodeoxyglucose positron emission/computerised tomography. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels rose in both patients after TCZ therapy. TCZ may be an effective alternative to GC treatment for LVV patients at risk for GC-related adverse events. Larger studies are required to confirm our findings.

Epidemiology of psoriatic arthritis.

Epidemiological studies on psoriatic arthritis have long been hampered by the absence of widely accepted classification criteria. The development of the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria has recently provided the framework for conducting epidemiological studies in psoriatic arthritis using uniform recruitment criteria. However, so far, only a minority of studies have adopted such criteria. In addition to the lack of shared classification criteria, differences in study settings, designs, and ascertainment methods have contributed to yield substantial disparities in the estimates of the incidence (from 3,02 to 23,1 cases per 100,000 people) and prevalence (from 49,1 to 420 cases per 100,000 people) of psoriatic arthritis around the globe. Overall, the available data suggests that the prevalence of psoriasis in the general population is approximately 2-3%, with about a third of patients with psoriasis having arthritis. Therefore, psoriatic arthritis may affect 0,3- 1,0% of the population, a frequency not dissimilar from that of rheumatoid arthritis. Future epidemiological studies should be carried out in larger numbers of patients diagnosed using consistent criteria.

[Disease activity assessment in large vessel vasculitis]. / Valutazione dell'attività di malattia nelle vasculiti dei grandi vasi.

Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis involving the central nervous system: case report and review of the literature.

OBJECTIVES: To report a case of biopsy-proven, ANCA-associated vasculitis (AAV) involving the central nervous system (CNS) and to review the relevant literature. METHODS: Descriptive case report of one patient with AAV-related CNS vasculitis and review of the relevant literature (PubMed search from 1966 to February 2010). RESULTS: A 61-year-old female patient with AAV developed cognitive impairment. Cerebrospinal fluid analysis was unremarkable, while magnetic resonance (MR) imaging showed multiple left hemisphere infarctions and MR angiography revealed multiple stenoses of the distal branches of the left median cerebral artery. Treatment with glucocorticoids, cyclophosphamide, and intravenous immunoglobulins led to improvement. CNS vasculitis often arises when vasculitis is active elsewhere. There is no clear preponderance of gender or of age of onset. Both ANCA-positive and -negative cases of CNS vasculitis are documented. The diagnosis is usually based on clinical CNS manifestations and multiple ischaemic (sometimes haemorrhagic) MR lesions mainly affecting the white matter. Angiography is often negative. Treatment with glucocorticoids and cyclophosphamide, sometimes with adjunctive intravenous immunoglobulins, usually improves clinical features and MR lesions. CONCLUSIONS: AAV rarely involves the CNS. CNS vasculitis should be suspected if patients have neurological manifestations consistent with CNS involvement, particularly if they have evidence of disease activity elsewhere, and if MR shows multiple ischaemic (sometimes haemorrhagic) lesions mainly affecting the white matter. Sepsis, coagulation disorders, and severe hypertension must be ruled out. Awareness of this rare but severe complication can allow early recognition and prompt treatment.

[Chronic periaortitis]. / Chronische Periaortitis.

Chronic periaortitis is a rare fibroinflammatory disorder which affects the abdominal aorta and may spread into the retroperitoneum, often encasing the ureters. An aneurysma of the abdominal aorta and vasculitis of the thoracic aorta and of supra-aortic vessels may also coexist. Chronic periaortitis can be idiopathic or secondary to different triggers such as drugs, tumors and infections. Abdominal and/or low back pain is the hallmark symptom. Laboratory markers of inflammation are usually increased. The diagnosis rests on computerized tomography or magnetic resonance imaging, which typically show a retroperitoneal mass displacing the aorta anteriorly and the ureters medially. Positron-emission tomography may assist in defining disease activity and extension. Chronic periaortitis should be differentiated from other fibrosing disorders of various origins. Histology is required in atypical cases to secure the diagnosis. Treatment is based on high-dose steroids with a tapering scheme combined with immunosuppressive agents in refractory or relapsing disease. In case of ureter obstruction early DJ-catheter placement is required. Operative interventions to relieve ureter obstruction are rarely necessary provided immunosuppressive treatment is timely instituted.

Late-onset rheumatoid arthritis and late-onset spondyloarthritis.

Both rheumatoid arthritis and spondyloarthritis may have a late onset. Elderly-onset rheumatoid arthritis is usually defined as rheumatoid arthritis with onset at age 60 or over. It appears to be a heterogeneous disease, with a seropositive subset resembling adult-onset rheumatoid arthritis, and a less severe seronegative subset which sometimes exhibits features overlapping with those of polymyalgia rheumatica. The spondyloarthritis complex includes definite entities as well as undifferentiated forms. Each of these may have a late-onset. Late-onset undifferentiated spondyloarthritis appears to be relatively more frequent than late-onset ankylosing spondylitis. Its clinical spectrum seems to be as broad as that observed in young and middle-aged adults with the exception of distal inflammatory swelling with pitting oedema. A special aspect of the differential diagnosis is the discrimination from other elderly-onset diseases showing the inflammatory swelling with pitting oedema over the dorsum of feet or hands. Psoriatic arthritis frequently begins in the elderly and shows some differences from the younger onset disease. Regarding the management, patients with late-onset rheumatoid arthritis and spondyloarthritis are treated similarly to younger patients taking into account age-related changes in the pharmacokinetics and pharmacodynamics of drugs and the presence of conditions able to reduce medication adherence.

Protein Z G79A and A-13G gene polymorphisms in Italian patients with Behçet's disease.

OBJECTIVE: To investigate potential associations between A-13G and G79A polymorphisms of the protein Z gene and venous thrombosis and other clinical manifestations in Italian patients with Behçet's disease (BD). METHODS: 176 Italian patients who satisfied the International Study Group criteria for BD and 134 healthy age- and sex- matched blood donors were genotyped for A-13G and G79A polymorphisms of the protein Z gene by molecular methods. 113 and 112 of the 176 BD patients were also genotyped for factor V Leiden and prothrombin gene G20210A polymorphisms. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique. The patients were subgrouped according to the presence or absence of clinical manifestations. RESULTS: The distribution of allele and genotype frequencies of A-13G and G79A polymorphisms did not differ significantly between BD patients and healthy controls.The frequencies of carriage rates of protein Z G79A and A-13G polymorphisms in BD patients with and without DVT were similar. Similarly, no associations between thrombotic events and the protein Z gene polymorphisms studied were observed in BD patients carrying factor V Leiden or prothrombin gene G20210A mutations. No significant associations were observed between protein Z polymorphisms and the occurrence of specific clinical findings. CONCLUSION: No association between DVT and A-13G or G79A polymorphisms of the protein Z gene was found in Italian BD patients. Furthermore, these protein Z polymorphisms in BD do not seem to increase the risk of DVT due to factor V Leiden or prothrombin gene G20210A mutations.

Toll-like receptor 4 (TLR4) gene polymorphisms in Italian patients with Behçet's disease.

OBJECTIVE: To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, clinical features, and severity of Behçet's disease (BD). METHODS: A total of 189 Italian patients who satisfied the International Study Group criteria for BD and 210 healthy age- and sex-matched blood donors were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. The patients were subgrouped according to the presence or absence of clinical manifestations. Severity score was calculated. RESULTS: The distribution of allele and genotype frequencies did not differ significantly between the BD patients and the healthy controls. No significant associations were found when BD patients with and those without clinical manifestations were compared. No association between TLR4 polymorphisms and severity score was observed. CONCLUSION: Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, clinical expression of, and severity of BD in Italian patients.

Toll-like receptor 4 (TLR4) gene polymorphisms in giant cell arteritis.

OBJECTIVE: To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, and clinical features of giant cell arteritis (GCA). METHODS: A total of 155 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 210 population-based controls from the same geographical area were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica and severe ischemic complications (visual loss and/or cerebrovascular accidents). RESULTS: The distribution of allele and genotype frequencies did not differ significantly between GCA patients and healthy controls. Carriers of the -299 G allele (G/A+ G/G) [odds ratio (OR) 1.78, 95% confidence intervals (CI) 0.90-3.50)] were more frequent among GCA patients than among the controls, but the difference was not statistically significant. No significant associations were found when GCA patients with and without PMR or with and without severe ischemic complications were compared. CONCLUSION: Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, and clinical expression of, GCA in Italian patients.

Risk factors for severe cranial ischaemic events in an Italian population-based cohort of patients with giant cell arteritis.

OBJECTIVE: To evaluate the impact of traditional cardiovascular risk factors, carotid atherosclerosis and the effect of anti-platelet/anti-coagulant therapy on the occurrence of severe cranial ischaemic events (CIEs) in GCA. METHODS: We identified 180 Reggio Emilia (Italy) residents with biopsy-proven GCA diagnosed between 1986 and 2005. We evaluated data on demographics, clinical features, laboratory investigations, cardiovascular risk factors, anti-platelet/anti-coagulant use and carotid atherosclerosis. RESULTS: Systemic signs/symptoms were significantly less frequent (P = 0.004) and ESR and C-reactive protein (CRP) values at diagnosis were significantly lower (P = 0.03 and P = 0.04, respectively) in patients with CIEs. The prevalence of hypertension and ischaemic heart disease was significantly higher in patients with CIEs than in those without (P = 0.01 and P = 0.006, respectively). Patients treated with anti-platelet/anti-coagulant therapy were significantly more likely to suffer CIEs than those without (P = 0.03), while CIEs were significantly associated with ischaemic heart disease in this subset of patients (P = 0.02). By multivariate logistic regression, we found that the best predictors for the development of severe CIEs included the absence of high (>5.38 mg/dl) CRP levels at diagnosis (OR = 0.31, 95% CI 0.08, 1.20), the absence of systemic manifestations (OR = 0.30, 95% CI 0.08, 1.08), the presence of hypertension (OR = 7.77, 95% CI 0.83, 72.76), and a past history of ischaemic heart disease (OR = 8.65, 95% CI 0.92, 80.95). CONCLUSIONS: In GCA, hypertension, a past history of ischaemic heart disease and a low inflammatory response are associated with a higher risk of developing severe CIEs.