Is there a role for laser speckle contrast analysis (LASCA) in predicting the outcome of digital ulcers in patients with systemic sclerosis?

OBJECTIVE: Digital ulcers (DUs) represent one major burden for patients with systemic sclerosis (SSc). The objectives of our study were to evaluate blood flow in SSc-DUs with laser speckle contrast analysis (LASCA) and to correlate the skin perfusion to clinical and laboratory data. METHODS: Forty DUs in 31 consecutive patients with SSc according to 2013 ACR/EULAR criteria (20 with limited cutaneous disease, 3 males) were prospectively examined with LASCA. Clinical and laboratory data were collected at the same time. DUs were classified according to clinical features and presence of infection. RESULTS: At LASCA analysis, patients with diffuse SSc had lower mean values of blood flow compared with those with limited disease at the finger affected by DUs (88.80 vs 44.40, p = 0.036) and at the periulcer area (p = 0.041). The presence of infection was associated to a higher flow at the finger with DU (103.02 vs 58.05 p = 0.04), at the level of ulcer (217.63 vs 67.15, p < 0.001), and at the periulcer area (p = 0.001). The ratio between the blood flow at the ulcer area and the finger base (UA/FB) showed a bimodal trend in patients with infected DUs and in those without infections. Infection was positive correlated to the time of healing (HT) (r = 0.648, p = 0.023), while in DUs without infection a negative correlation to HT (r = - 0.46, p = 0.015) was identified. CONCLUSIONS: This study demonstrates for the first time that the UA/FB ratio may predict the healing time of DUs in SSc patients and may be crucial for the prognostic stratification of patients. Infection remains one of the main predictors of DU healing.Key Points• The prognostic value of laser speckle contrast analysis (LASCA) in patients with digital ulcers (DUs) in systemic sclerosis remains to be clarified.• LASCA may be able to predict the haling time of the digital ulcers.• The presence of infection of the wound bed may greatly influence the LASCA parameters and the healing time of the digital ulcer.

Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study.

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.

Muscular vasculitis confined to lower limbs: description of two case reports and a review of the literature.

Muscular involvement is common during systemic vasculitides, such as polyarteritis nodosa. However, in rare cases, muscular involvement can be the only clinically evident feature of the disease. The clinical pattern of isolated muscular vasculitis may mimic several other inflammatory muscle disorders, such as idiopathic inflammatory myositis, and may represent a challenge in differential diagnosis. Herewith, we present two clinical cases as examples of peculiar clinical and histopathological characteristics of isolated muscular vasculitis. Our patients were successfully treated with steroids and immunosuppressive agents. Moreover, we provide a review of the recent existing medical literature. Our cases suggest the importance of performing muscle biopsy in patients with muscular symptoms to guide the diagnosis and the treatment.

One year in review 2016: systemic sclerosis.

Systemic sclerosis is a rare acquired systemic disease characterised by a complex pathogenesis and multi organ involvement. Every year, novel insights into the pathogenesis, diagnosis and treatment of this severe disease are published. Herewith, we provide an overview of the most significant literature contributions published over the last year.

Thigh magnetic resonance imaging for the evaluation of disease activity in patients with idiopathic inflammatory myopathies followed in a single center.

INTRODUCTION: In patients with idiopathic inflammatory myopathies (IIM), magnetic resonance imaging (MRI) has been proposed as a useful tool for diagnosis and follow-up. It may identify muscle inflammation (edema) and fatty infiltration for evaluation of disease activity and damage. Little information is available on the role of MRI in assessment of large cohorts of adult patients with IIM. METHODS: Fifty-one patients underwent MRI of the thigh muscles, laboratory tests, and clinical evaluation, including Physician Global Assessment (PGA) of myositis activity and the Manual Muscle Test 8 (MMT8). RESULTS: Muscle edema correlated significantly with creatine kinase values (P = 0.017) and PGA (P < 0.001). A significant correlation between edema and MMT8 values (P = 0.025) was observed when patients with muscle fatty infiltration were excluded. With respect to clinical diagnosis, the sensitivity of MRI was 92.3%, and specificity was 83.3%. CONCLUSIONS: MRI appears to provide additional information that complements clinical and biochemical examinations. Muscle Nerve 54: 666-672, 2016.

Adult-onset Still's disease: an Italian multicentre retrospective observational study of manifestations and treatments in 245 patients.

Adult-onset Still's disease (AOSD) is a systemic inflammatory condition of unknown aetiology characterized by typical episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. Given the lack of data in Italian series, we promote a multicentric data collection to characterize the clinical phenotype of Italian patients with AOSD. Data from 245 subjects diagnosed with AOSD were collected by 15 centres between March and May 2013. The diagnosis was made following Yamaguchi's criteria. Data regarding clinical manifestations, laboratory features, disease course and treatments were reported and compared with those presented in other published series of different ethnicity. The most frequent features were the following: arthritis (93 %), pyrexia (92.6 %), leukocytosis (89 %), negative ANA (90.4 %) and neutrophilia (82 %). As compared to other North American, North European, Middle Eastern and Far Eastern cohorts, Italian data show differences in clinical and laboratory findings. Regarding the treatments, in 21.9 % of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biologics have been shown to be effective in 48 to 58 patients. This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects.

Development of de novo major involvement during follow-up in Behçet's syndrome.

The primary aim of the study was to evaluate the incidence of de novo major involvement during follow-up in a cohort of patients with Behçet's syndrome (BS); the secondary aim was to analyse the epidemiological profile and the long-term outcome of those patients who developed new major involvement. Among our cohort of 120 BS patients, we evaluated all subjects who had no major organ involvement during the early years of their disease; specifically, at disease onset, the 52% of the cohort presented a prevalent mucocutaneous involvement. The primary outcomes were represented by the following: Hatemi et al. (Rheum Dis Clin North Am 39(2):245-61, 2013) the incidence of de novo major involvement during the follow-up and Hatemi et al. (Clin Exp Rheumatol 32(4 Suppl 84):S112-22, 2014) the use of immunosuppressive drugs during the follow-up. We have defined the development of de novo major involvement during the follow-up as the occurrence of severe ocular, vascular or CNS involvement after a latency period from the diagnosis of at least 3 years. Among 62 patients characterized by a mild onset of disease, we observed that after at least 3 years from the diagnosis, 21 BS patients (34%) still developed serious morbidities. Specifically, three patients developed ocular involvement, nine patients developed neurological involvement and nine patients presented vascular involvement. Comparing main epidemiological and clinical findings of the two groups, we observed that patients who developed de novo major involvement were more frequently males and younger; furthermore, 95% of these patients were characterized by a young onset of disease (p < 0.001). Being free of major organ complication in the first years of BS is not necessary a sign of a favourable outcome. Globally, the development of de novo major involvement during the coursfce of BS suggests that a tight control is strongly recommended during the course of the disease.

Epidemiology and management of neuropsychiatric disorders in Behçet's syndrome.

Behçet's syndrome (BS) is a systemic, chronic, relapsing vasculitis, typically characterized by recurrent orogenital ulcers, ocular inflammation and skin manifestations; articular, vascular, gastroenteric and neurological involvement may also occur. Besides the other clinical features of BS, it seems relatively frequent that patients with BS develop a neurobehavioural syndrome, characterized by euphoria, bipolar disorders and paranoid attitudes, loss of insight/disinhibition, and indifference to their disease, defined as 'neuro-psycho-BS'. To date, the pathogenetic mechanism underlying neuro-psycho-BS has not been determined. It may be secondary to organic neurological involvement, or it may be related to poor quality of life and the relapsing course of the disease. Another engaging theory suggests that it could be related to the frequent observation of psychiatric symptoms during relapses or, in some cases, in the phases preceding reactivation of the disease; these elements suggest that psychiatric disorders in BS could represent a crucial element, whether a psychiatric subset or a distinct clinical feature of the disease. Moreover, it has been reported that cognitive impairment in BS can be seen with or without central nervous system involvement. Globally, psychiatric symptoms have been described as being multifaceted, ranging from anxiety disorders to depressive-bipolar disorders or to psychotic ones. In addition, some psychological characteristics of BS patients seem to predispose them to maladaptive stress management, which may lead to stress-related disorders, including anxiety and depression. Therefore, the aims of this review are to explore the epidemiology of neuro-psycho-BS by evaluating the relationship between the stress system and the multifaceted psychiatric manifestations in BS, and to summarize the therapeutic strategy used.

Prognostic value of flow-mediated dilation in patients with systemic lupus erythematosus: a pilot prospective cohort study.

This pilot study evaluated the predictive value of flow-mediated dilation (FMD) for damage accrual in a cohort of SLE patients. Thirty-eight female SLE patients without cardiovascular involvement were enrolled. Clinical history, traditional cardiovascular risk factors, laboratory parameters, disease activity and damage and brachial artery FMD were collected at study entry and after a mean follow-up of 4.5 years. At enrollment, 18 patients (47%) presented active disease; mean FMD was 7.9 ± 3.1%, with no statistically significant differences between women with active and inactive disease. During the follow-up, 3 patients died and 14 accrued organ damage. Baseline FMD did not predict death and damage accrual. FMD showed significant decline over time, which was greater in patients with poor outcome (-3.9% vs -1.9%, p = 0.03). In conclusion, in a cohort of SLE patients, baseline FMD was not predictive of damage accrual. However, the latter was associated with progressive loss of FMD.

Isolated aortitis versus giant cell arteritis: are they really two sides of the same coin?

OBJECTIVES: The aim of the study was to compare epidemiological data, clinical findings and results of investigations in patients with isolated aortitis and those with giant cell arteritis (GCA) to establish whether patients with isolated aortitis differ from those with GCA. METHODS: We reviewed the medical notes of all patients consecutively seen in two Rheumatology centres in the last two decades with a suspicion of GCA, searching for cases characterised by abnormal [18F] fluorodeoxyglucose (FDG) PET uptake of the aorta. 'Isolated aortitis' was defined as increased FDG uptake in the aorta not explained by atherosclerosis in the absence of FDG uptake in other large vessels. RESULTS: Comparing the epidemiological and clinical data of patients with isolated arteritis with those with GCA, we observed many statistical significant differences. First of all, the male/female ratio was reversed, with a predominant male involvement in isolated arteritis. Moreover, the mean age of patients with isolated arteritis was significantly lower than that of GCA patients (62 vs. 78.4 yrs; p<0.0001). None of the patients with isolated aortitis presented at any time of the disease course the typical symptoms of GCA, while in a low percentage of cases constitutional symptoms represented the only clinical features. Beside the aortic arch, the sites more frequent involved were the thoracic and abdominal tracts, in all cases without an uptake of the aortic branches. CONCLUSIONS: It is not known whether our patients with isolated aortitis represent variants of GCA or TA, nor is it known how they will evolve, but we can certainly conclude that these patients have a different epidemiologic and clinical profile, and do not necessarily represent two sides of the same coin.

Improved survival in limited scleroderma-related pulmonary artery hypertension.

Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO2) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO2 <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO2 are predictors of survival and may assist in planning treatment.

Cancer-associated myositis: a 35-year retrospective study of a monocentric cohort.

This study is aimed at retrospectively studying cancer-associated inflammatory myopathies (CAM) in a cohort of patients with inflammatory myopathies. CAM were diagnosed if the tumor was diagnosed 2 years before or after disease onset. One hundred and sixty-two patients were included, 27 (17 %) had CAM. A significant association was observed between CAM and dermatomyositis (DM), older age and dysphagia at disease onset. CAM have lower creatine kinase (CK) levels at onset and a low prevalence of autoantibodies. In conclusion, the association of male sex, older age, DM, dysphagia at onset, lower CK, and autoantibodies negativity carries a high suspicion of CAM.

Alteration of microcirculation is a hallmark of very early systemic sclerosis patients: a laser speckle contrast analysis.

OBJECTIVES: To investigate blood flow and microvascular reactivity by laser speckle perfusion imager (Perimed, Jarfalla) in consecutive patients affected by Raynaud's phenomenon at baseline and following dynamic stimulations. METHODS: Skin blood flow in the dorsum of the hand was measured at baseline and after cold test and post-occlusive hyperemia test in 56 consecutive subjects affected by Raynaud's phenomenon (RP), 20 primary (PRP) and 36 secondary to systemic sclerosis (SSc). Twenty healthy subjects (HS) were studied as controls. RESULTS: After cold test, SSc had a significant reduction of blood flow (-58%) as compared to HS (-19%) (p=0.01). Recovery time was significantly higher in SSc (58 minutes) as compared to HS (18 minutes) and PRP (19 minutes) (p=0.006 and 0.0016, respectively). Peak flow after ischaemic test was significantly reduced in SSc (+237%) as compared to PRP (+485%) (p=0.0068). Post-ischaemic hyperemic area under the curve (AUC) was blunted in SSc (79U/sec) compared to PRP (167 U/sec) (p=0.0126). Proximal distal gradient was noticed in 74% of HS, 45% of PRP and 36% of SSc (p=0.01). Homogeneous pattern of flux distribution was significantly different between HS (95%), PRP (80%), and SSc (16%) (p<0.0001). Among SSc patients, a significant difference in ischaemic challenge was shown between patients with early-SSc versus patients with definite-SSc. CONCLUSIONS: Our preliminary results indicate a clearcut alteration of the dynamic of microcirculation in SSc-RP as compared to PRP and HS. Among SSc patients, early-SSc is a separate entity as compared to established disease.

When the heart is burning: amino-terminal pro-brain natriuretic peptide as an early marker of cardiac involvement in active autoimmune rheumatic disease.

BACKGROUND: We evaluated the influence of inflammation on cardiac endocrine function in autoimmune rheumatic disease (RD) patients with preserved left ventricular systolic function. METHODS: 160 consecutive RD patients (29 males, age 55 ± 14 years, left ventricular ejection fraction, LVEF, 63 ± 5%: inflammatory polyarthritis: 13%, systemic sclerosis: 25%, connective tissue diseases: 39%, systemic vasculitides: 23%) and 120 healthy controls (24 males, 55 ± 10 years) underwent clinical, echocardiographic evaluation and blood sampling for erythrocyte sedimentation rate, C-reactive protein (CRP), fibrinogen and plasma NT-proBNP. RESULTS: A significant correlation was found between plasma NT-proBNP and inflammatory markers (all p<0.001), with CRP and diastolic dysfunction being the only independent predictors of NT-proBNP level. RD patients with active disease (57%) showed higher values of inflammatory markers and NT-proBNP (all p<0.01). Patients with subclinical cardiac involvement (Stage B by ACC/AHA HF-classification) had higher NT-proBNP (p<0.001) than controls and patients only at risk for HF (Stage A). NT-proBNP showed a significant diagnostic accuracy in discriminating stage B (n=93) versus stage A patients (n=67, AUC=0.755 ± 0.038, p<0.001) and controls (AUC=0.834 ± 0.030, p<0.001). CONCLUSION: Higher CRP and the presence of left ventricular diastolic dysfunction were independently associated with higher NT-proBNP. NT-proBNP might be used in RD as a marker of both disease activity and subclinical cardiac involvement.

Thyroid cancer in systemic lupus erythematosus: a case-control study.

CONTEXT: Although advances in treatment have permitted patients with systemic lupus erythematosus (SLE) to live longer, the rates of several types of cancers in these patients appear to be increasing. OBJECTIVE: We used a prospective study to investigate the prevalence and features of thyroid cancer in SLE patients. DESIGN AND PATIENTS: The prevalence of thyroid cancer in 153 unselected SLE patients was compared with that in two population-based, gender- and age-matched control groups: 1) 459 subjects from an iodine-deficient area (iodine-deficient control) and 2) 459 subjects from an iodine-sufficient area (iodine-sufficient control). Thyroid function was assessed by measuring circulating thyroid hormones and autoantibodies, thyroid ultrasonography, and where necessary, fine-needle aspiration cytology. MAIN OUTCOME AND RESULTS: The levels of circulating TSH, and anti-thyroglobulin and anti-thyroperoxidase antibodies were significantly higher in SLE patients (P < 0.001 for all). In addition, patients with SLE also exhibited a higher prevalence of hypothyroidism (P < 0.001). Five cases of papillary thyroid cancer were detected among SLE patients, whereas no cases were observed among iodine-deficient controls (P = 0.001), and only one case was observed among iodine-sufficient controls (P = 0.001). Among SLE patients with confirmed thyroid cancer, 80% showed evidence of thyroid autoimmunity, whereas only 31% of SLE patients without thyroid cancer exhibited evidence of thyroid autoimmunity (P = 0.02). CONCLUSIONS: These data suggest that the prevalence of papillary thyroid cancer in SLE patients is higher than in age-matched controls, particularly in patients with thyroid autoimmunity. Consequently, careful thyroid surveillance is recommended during the follow-up of these patients.

Vascular reactivity in patients with undifferentiated connective tissue diseases.

INTRODUCTION: Endothelial dysfunction is an early event in the development of atherosclerotic disease. We investigated endothelial function in the peripheral circulation of patients with undifferentiated connective tissue diseases (UCTDs), in comparison to healthy controls. METHODS: In 15 young UCTD patients (mean age 39 years) with inactive disease and without cardiovascular risk factors and in 15 age-matched controls we evaluated endothelial function in the brachial conduit artery and in the forearm microcirculation. The first district was assessed by flow mediated dilation (FMD) and response to glyceryl trinitrate, and forearm microcirculation by blood flow changes (strain-gauge venous plethysmography) in response to intra-arterial acetylcholine (Ach) and sodium nitroprusside (SNP). Nitric oxide (NO) availability was evaluated by repeating Ach in the presence of intraarterial N(G)-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor. RESULTS: FMD and response to GTN were similar in UCTD patients and controls. UCTD patients showed a reduced response to Ach (P<0.001) and SNP (P<0.01) as compared to controls. In healthy controls l-NMMA infusion significantly (P<0.001) reduced the vascular response to Ach, while in UCTD patients l-NMMA failed to affect vasodilation to Ach. In UCTD patients, vascular responses were unrelated to clinical manifestations or autoantibody profile. CONCLUSIONS: Young UCTD patients are characterized by reduced endothelium-dependent and -independent vasodilation in the forearm microcirculation, but not in peripheral conduit arteries. Reduced NO availability was indirectly observed. These results suggest that in the absence of traditional risk factors, inactive systemic autoimmune diseases impair NO-dependent but also endothelium-independent vasodilation selectively in the microcirculation.

Occurrence of organ-specific and systemic autoimmune diseases among the first- and second-degree relatives of Caucasian patients with connective tissue diseases: report of data obtained through direct patient interviews.

Studies have demonstrated a familial aggregation of systemic and organ-specific autoimmune diseases. The aim of the present survey was to obtain, by patient interviews, a preliminary estimate of the prevalence of systemic and organ-specific autoimmune diseases among the first- and second-degree relatives of Caucasian patients with connective tissue diseases (CTD) or inflammatory arthritis followed at our unit. Between June 2007 and January 2008, 626 patients and 85 controls (patients with osteoarthritis, osteoporosis, or fibromyalgia) were interviewed. Three hundred ten patients (50%) versus 21 controls (25%) were found to have at least one relative affected with an autoimmune condition (p < 0.0001). The most common conditions were organ-specific autoimmune diseases: 160 (34%) autoimmune thyroid (AT) disease, 112 (24%) psoriasis, 21 vitiligo, and 19 insulin-dependent diabetes mellitus. Systemic autoimmune diseases were reported in 126 relatives: rheumatoid arthritis (66 cases, 14%), 16 sacroileitis, and CTD (43 cases). A significant difference was observed in the prevalence of AT disease between the relatives of the patients and controls (3% versus 0.5%). In conclusion, these data confirm the high prevalence of autoimmune conditions, particularly of AT disease, among the relatives of patients.