NAILFOLD VIDEOCAPILLAROSCOPY FEATURES OF PATIENTS WITH ANTISYNTHETASE SYNDROME

Background: Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). As in inflammatory myopathies, nailfold videocapillaroscopy (NVC) alterations have been sporadically described also in ASSD patients, but no elucidating data are available. Objectives: To investigate the possible specific NVC features of ASSD patients. Methods: Within the framework of a multicenter study, we retrospectively analyzed NVC images of ASSD patients, after excluding patients with overlap syndrome with systemic sclerosis. Two operators in a blind manner re-evaluated all patients with at least one image per finger. For each patient, we examined number of capillaries (mean number of capillaries per mm in the distal row), enlarged and giant capillaries, micro-hemorrhages, avascular areas, ramified capillaries, and the presence of a scleroderma (SSc)-like pattern, according to manfredi et al. Finally, we correlated NVC features with clinical and serological findings of ASSD patients. Results: The NVC of 54 ASSD patients were analyzed (males/females 1/6.8, mean age 55.79, CI95% 51.9\u201359.9 years, mean disease duration 59.4, CI95% 27.9\u201390.9 months). Raynaud's phenomenon (RP) was recorded in 51.9% of patients, arthritis in 79.6%, myositis in 53.7%, and ILD in 92.6%. NVC alterations were observed in 53.7% of AASD patients. Nineteen patients (35.2%) showed a SSc-like pattern; the main features were disarrangement of hairpin and angiogenetic aspects (42.6%), avascular areas (38.9%), giant capillaries (27.6%), and microhemorrhages (20.4%). Finally, the mean number of capillaries was reduced (7.8\ub12/mm). No significant association was recorded between SSc-like pattern and the presence of arthritis, myositis, and ILD, nor with RP. Among other NVC features, angiogenesis was significantly associated to female gender (p=0.031), while microhemorrhages were inversely associated to the presence of arthritis (0.033). No association was observed between NVC features and autoantibodies profile. Of interest, in 58% of patients with ILD we observed at least a NVC alteration vs no patients without ILD (p=0.04). Finally, in patients with RP NVC alterations were recorded in 15/28 patients (53.6%) and a SSc-like pattern in 11/28 (39.3%), while only 57.9% of patients with SSc-like pattern had a clinically manifest Raynaud's phenomenon. Conclusions: Despite preliminary, the present is the first study concerning NVC in AASD patients. Regardless of the presence of Raynaud's phenomenon, NVC alterations are frequently observed; in particular, a SSc-like pattern is recorded in more than 1/3 of patients. NVC should be performed in all ASSD patients at diagnosis regardless of the presence of RP in the patient history and during follow-up. ASSD should be always considered in the screening of RP. A prospective multicenter study has been planned to identify specific patterns and possible associations between NVC findings and clinical and serological features of ASSD

Cryoglobulinemic vasculitis and skin ulcers. Our therapeutic strategy and review of the literature

Objective: Cryoglobulinemic vasculitis (CV) involving small- and medium-sized vessels is very frequently associated with hepatitis C virus and may be responsible for multiple organ involvement and skin ulcers (SU). Skin ulcers are often non-healing cutaneous lesions, possibly complicated by local infection and gangrene; they may severely affect the patients[U+05F3] quality of life and the overall prognosis. Therefore, the treatment of cryoglobulinemic SU is particularly challenging in the clinical practice.The present work evaluated the prevalence and correlations of cryoglobulinemic SU with other clinico-epidemiological features of CV; moreover, our long-term experience with the management strategies of these cutaneous lesions was compared with the world literature on this topic. Methods: The study included 126 CV patients (24 male and 102 female, aged 69 ± 11.2 SD years, disease duration 7 ± 6.9 SD years), followed at our Rheumatology Unit during the past decade. All patients were carefully evaluated regarding the entire cryoglobulinemic syndrome with particular concern for clinical characteristics and treatment of SU. Results: Among 126 CV patients, 36 individuals (29%) experienced at least one episode of SU, more commonly localized at the lower limbs. Patients with complicating SU showed significantly higher percentage of purpuric manifestations (p < 0.01) and liver (p < 0.001), peripheral nerve (p < 0.02), and/or thyroid involvement (p = 0.019).Therapeutic approach to SU included both systemic (immunosuppressors, corticosteroids, and/or plasma exchange) and local treatments. Local treatments consisted of sharp or surgical debridement as well as interactive dressing according to the condition of wound bed, perilesional skin, and the possible presence of infection, detected in 29 of 36 (81%) individuals in our Rheumatology unit. All patients underwent analgesic treatment for SU-related background pain as well as procedural pain, which was critical for an effective local SU management.The large majority of patients with SU healed at a variable time interval according to the severity of the single lesion; only five patients with very severe, non-healing SU needed amputation.The updated review of the literature revealed the presence of SU in around a quarter of CV patients. Among systemic treatments, the anti-CD20 monoclonal antibody rituximab represents one of the most effective and frequently employed therapies; however, the available data focusing on local therapeutic approach are generally limited to anecdotal observations. Conclusions: Overall, the treatment of cryoglobulinemic SU should be tailored to the single patient[U+05F3]s conditions using combined systemic and local treatments; lesional sharp debridement and interactive dressing as well as procedural pain management were decisive, particularly for more severe, non-healing cutaneous lesions

COST ANALYSIS RELATED TO SUBCUTANEOUS IMMUNOGLOBULINS IN PATIENTS WITH INFLAMMATORY MYOPATHIES AND IMMUNE-MEDIATED CHRONIC NEUROPATHIES. RESULTS OF AN OPEN LABEL STUDY

Background: Intravenous Immunoglobulins (IVIg) represent a relevant treatment option in various immune-mediated disorders such as idiopathic inflammatory muscle diseases (IIMD), immune-mediated chronic neuropathies (IMCN), hematologic autoimmune diseases, Still disease, Felty syndrome, systemic lupus erythematosus, vasculitis, some organ-specific autoimmune disease, and atopic diseases. The IVIg treatment is expensive and need of hospital-based assistance for administration; the recent avaibility of home-therapy with subcutaneous immunoglobulins (SCIg) may significantly reduce costs and improve the patient's quality of life. Objectives: The primary objective was to perform an analysis of costs of SCIg administration in patients affected by IIMD or IMCN compared to that of previous IVIg treatments. Methods: We prospectively evaluated 6 consecutive patients (3 males and 3 females, mean age 65,3 years, range 63 - 77), 2 affected by IIMD in the context of polymiositis and 4 by IMCN, 3 in the context of vasculitis and 1 in the context of undifferentiated connective tissue disease. All patients were previously treated with IVIg at the dosage of 2g/Kg monthly, (mean monthly dosage 143 g, range 98 – 160, average patient weight 71,5 kg, range 49 - 80), with good clinical and humoral response. After a mean therapy duration of 49.8 months (range 12 – 125) all patients were shifted to SCIg at the dosage of 10 g twice a week (80 g monthly). Each patient was followed-up by humoral and clinical evaluation, including Medical Research Council (MRC) score to quantify muscle strength and INCAT Sensory Score to evaluate sensory symptoms. The costs of the two therapeutic strategies were also compared, excluding indirect costs (absences from work and productivity losses, transport and parking, health care sector costs). Results: In 5/6 patients, we observed the maintenance of clinical and humoral status after a mean follow-up of 21 months (range 4 - 51), in particular we observed a stability in MRC score in patients presenting loss of strenght and INCAT score in patients presenting sensory symptoms. Furthermore, the treatment with SCIg was well-accepted and preferred to IVIg by all patients. In one patient SCIg were discontinued after 2 weeks, because of the appearance of a haemorrhagic lesions nearby the injection site (in the same patient IVIg have been stopped because of a hypertensive crisis during the infusion). Direct cost associated to IVIg amount to 252€ for 5 g of immunoglobulins (7,056€ monthly, considering a protocol of 2 g/kg/monthly and a patient-weight of 70kg), while direct costs associated to SCIg (20g weekly) amount to 6,400€/monthly, with a saving of 656€/monthly and 7,872€/yearly. In our case-series the annual saving was 9,686.40€/patient (from 86,486.40€ to 76,800€, for IVIg and SCIg, respectively). Conclusions: Our experience suggests that the shift to SCIg from IVIg in patients affected by IIMD and IMCN is feasible, cost-effective, safe and well-accepted by patients. Further studies are needed to evaluate the effectiveness of SCIg in first-line therapy of these diseases

Current treatment of hepatitis C-associated rheumatic diseases.

ABSTRACT: The hepatitis C virus (HCV) is both hepatotropic and lymphotropic, responsible for a great number of hepatic and extrahepatic immune-system disorders that comprise the so-called HCV syndrome. HCV-associated rheumatic diseases are characterized by frequent clinico-serological overlap; therefore, correct classification of individual patients is necessary before therapeutic decisions are made. This is particularly difficult to do, however, because of the coexistence of viral infection and complex autoimmune alterations. In this context, mixed cryoglobulinemia syndrome (MCs) represents the prototype of virus-related autoimmune-lymphoproliferative diseases. MCs can be treated at different levels by means of etiological treatment with antivirals (peg-interferon-alpha plus ribavirin) aimed at HCV eradication and/or pathogenetic/symptomatic treatments directed to both immune-system alterations and the vasculitic process (rituximab, cyclophosphamide, steroids, plasmapheresis, and so on). In clinical practice, the therapeutic strategy should be modulated according to severity/activity of the MCs and possibly tailored to each individual patient's conditions. Cryoglobulinemic skin ulcers may represent a therapeutic challenge, which should be managed by means of both local and systemic treatments. HCV-associated arthritis should be differentiated from the simple comorbidity of HCV infection and classical rheumatoid arthritis. It may be treated with low doses of steroids and/or hydroxychloroquine; the use of biologics (rituximab) may be considered in more severe cases. Primary Sj\uf6gren's syndrome is rarely associated with HCV infection, while sicca syndrome and myalgia are frequently detectable in hepatitis C patients, with or without cryoglobulinemic vasculitis. Other autoimmune rheumatic disorders (poly/dermatomyositis, polyarteritis nodosa, osteosclerosis, fibromyalgia, and so on) have been reported as potentially associated with HCV infection in patient populations from different countries, suggesting the role of genetic and/or environmental co-factors. The therapeutic approach to these disorders should be decided according to each individual patient's evaluation, including hepatic, virological, and immunological findings

Carotidynia Possibly due to Localized Vasculitis in a Patient with Latent Mycobacterium tuberculosis Infection.

Carotidynia is a syndrome characterized by tenderness of the carotid artery near the bifurcation due to numerous, heterogeneous causes. Here we reported the case of a 31-year-old Moroccan woman with right-sided neck pain and tenderness with irradiation to ipsilateral ear, eye, and occipital region. Clinical symptoms and imaging findings were suggestive of primary variant of carotidynia syndrome. In particular, color-Doppler ultrasonography revealed a concentric wall thickening of the distal common carotid artery, while thoracic magnetic resonance showed localized perivascular enhancement of the soft tissue in the right medial-distal common carotid artery in T1-weighted images, without intraluminal diameter variation. Moreover, careful clinicoserological and imaging investigations (cranial, cervical, and thoracic angiocomputed tomography and magnetic resonance) excluded well-known disorders potentially responsible for carotidynia syndrome. The patient was scarcely responsive to nonsteroidal anti-inflammatory drugs, but clinical symptoms resolved after three months. Of interest, the patient showed latent Mycobacterium tuberculosis infection (positive tuberculosis interferon-gamma release assay; QuantiFERON-TB Gold); this finding suggested a possible triggering role of mycobacterial antigens in the immune-mediated mechanism responsible for localized carotid injury

PAP-TEST FEATURES IN A COHORT OF SYSTEMIC SCLEROSIS PATIENTS

Background: Increased incidence of malignancies was frequently reported in systemic sclerosis (SSc), as well as for other autoimmune diseases. Besides the previously observed association with lung cancer1 and the increased risk for breast cancer2, no association with cancer of the cervix has been described in literature. However, cervical uterus malignancy is one of the most frequent cancer in women so that public health programs of screening have been established in several countries worldwide. In Italy, the pap cytology test is recommended every 3 years for all women between 25 and 64 years old. Objectives: To investigate pap-test features in SSc patients. Methods: We retrospectively evaluated a cohort of 80 consecutive female SSc patients (mean age 51.2±12SD years, disease duration 7.9±5.8SD years, limited/diffuse skin subsets 72/8), who underwent to pap cytology tests as screening for cancer of the cervix, during the period between January 1st, 2008 and December 31th, 2014. All patients came from the same geographical area (province of Modena, Northern Italy). Clinical, serological, and instrumental data of SSc patients were collected and related to cytological findings. Results: At gynaecological and pap test evaluations, 55 (68.7%) patients were negative, while 20 (25%) presented inflammatory alterations (i.e. chronic cervicitis); while atypical cells related to cancer or pre-cancerous lesions were found in 5 (6.2%) cases. Namely, 2 women showed cervix cancer (one of them in situ), 1 a vulvar melanoma, 1 a vulvar intraepithelial neoplasia, and 1 an endocervical polyp with immature squamous metaplasia at histology. The frequency of cervix cancer in our series seems to be clearly higher in comparison to the incidence registered in the same geographical area and in the same years (standardized rate 8, 95%IC 5.2-10.7 cases out of 100,000 subjects). At statistical analysis, the atypical cytological findings correlated with serum anti-Scl70 autoantibodies (4/5 vs. 19/75; p=0.022); moreover, the patients with these alterations tended to be older (median 65, range 46-67), if compared to the whole series (p=0.052). No statistical correlations with skin or visceral involvements, smoking history, treatment with immunosuppressors were found. Conclusions: In our SSc patients' series, we found a relatively high frequency of cancerous lesions of the cervix by means of pap test. A significant correlation with anti-Scl70 autoantibodies was also found. These preliminary findings need to be verified in larger controlled epidemiological studies

Gynaecological Screening for Cervical and Vulvar Malignancies in a Cohort of Systemic Sclerosis Patients: Our Experience and Review of the Literature

Background. Increased incidence of cancer was frequently reported in scleroderma (SSc), but no association with gynaecological malignancies was described in literature. Objectives. To investigate gynaecological neoplasms in SSc patients. Methods. In this cross-sectional analysis, we evaluated 80 SSc patients, living in the same geographical area. We considered all patients undergoing gynaecological evaluation, including pap test as screening for cervical cancer, between January 2008 and December 2014. Results. 55 (68.7%) patients were negative and 20 (25%) presented inflammatory alterations, while cancer or precancerous lesions were found in 5 (6.2%) cases (2 showed cervical cancer (one of them in situ), 1 vulvar melanoma, 1 vulvar intraepithelial neoplasia, and 1 endocervical polyp with immature squamous metaplasia). The frequency of cervical cancer in our series seems higher in comparison to the incidence registered in the same geographical area. The presence of atypical cytological findings correlated with anti-Scl70 autoantibodies (p = 0.022); moreover, the patients with these alterations tended to be older (median 65, range 46-67), if compared to the whole series (p = 0.052). Conclusions. A relatively high frequency of gynaecological malignancies was found in our SSc series. In general, gynaecological evaluation for SSc women needs to be included in the routine patients' surveillance

Thyroid involvement in hepatitis C - associated mixed cryoglobulinemia

The prevalence and clinical features of thyroid involvement in patients with hepatitis C virus-associated mixed cryoglobulinemia (MC+HCV) have been reviewed

PATIENTS WITH MIXED CRYOGLOBULINEMIA AND HCV INFECTION, IN PRESENCE OR ABSENCE OF AUTOIMMUNE THYROIDITIS, HAVE HIGH SERUM LEVELS OF (CXC MOTIF) LIGAND (CXCL)9 AND CXCL11 CHEMOKINES

No data are present in the literature regarding chemokine (CXC motif) ligand (CXCL)9 and CXCL11 circulating levels in cryoglobulinemia associated with hepatitis C (MC+HCV), in presence/absence of autoimmune thyroiditis (AT). Serum CXCL9 and CXCL11 have been measured in 38 MC+HCV patients without AT (MCo), 38 MC+HCV patients with AT (MC+AT), and in matched controls without (control 1) or with thyroiditis (control 2). Serum CXCL9 and CXCL11 were significantly higher: in control 2 than control 1 (p&lt;0.05); in MCo than control 1 and control 2 (p&lt;0.001, for both); in MC+AT than control 1 and control 2 (p&lt;0.0001, for both), and than MCo (p=0.01, for both). Our study demonstrates markedly high serum levels of CXCL9 and CXCL11 in patients with MC+HCV compared to healthy controls; in MC+HCV patients increased CXCL9 and CXCL11 levels were significantly associated with the presence of AT. Moreover, a strong relation between circulating CXCL9 and CXCL11 in MC+HCV has been shown