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Papa N.D.,Uoc Day Hospital Reumatologia | Di Luca G.,U.O.S. Chirurgia Vascolare | Sambataro D.,Uoc Day Hospital Reumatologia | Zaccara E.,Uoc Day Hospital Reumatologia | And 9 more authors.
Cell Transplantation | Year: 2015

Digital ulcers (DUs) are a rather frequent and invalidating complication in systemic sclerosis (SSc), often showing a very slow or null tendency to heal, in spite of the commonly used systemic and local therapeutic procedures. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. In the present study, we have tentatively treated long-lasting and poorly responsive to traditional therapy SSc-related DUs by implantation of autologous adipose tissue-derived cell (ATDC) fractions. Fifteen patients with SSc having a long-lasting DU in only one fingertip who were unresponsive to intensive systemic and local treatment were enrolled in the study. The grafting procedure consisted of the injection, at the basis of the corresponding finger, of 0.5–1 ml of autologous ATDC fractions, separated by centrifugation of adipose tissue collected through liposuction from subcutaneous abdominal fat. Time to heal after the procedure was the primary end point of the study, while reduction of pain intensity and of analgesic consumption represented a secondary end point. Furthermore, the posttherapy variation of the number of capillaries, observed in the nailfold video capillaroscopy (NVC) exam and of the resistivity in the digit arteries, measured by high-resolution echocolor-Doppler, were also taken into account. A rather fast healing of the DUs was reached in all of the enrolled patients (mean time to healing 4.23 weeks; range 2–7 weeks). A significant reduction of pain intensity was observed after a few weeks (p < 0.001), while the number of capillaries was significantly increased at 3- and 6-month NVC assessment (p < 0.0001 in both cases). Finally, a significant after-treatment reduction of digit artery resistivity was also recorded (p < 0.0001). Even with the limitations related to the small number of patients included and to the open-label design of the study, the observed strongly favorable outcome suggests that local grafting with ATDCs could represent a promising option for the treatment of SSc-related DUs unresponsive to more consolidated therapies. © 2015 Cognizant Comm. Corp.


Sambataro D.,Uoc Day Hospital Reumatologia | Sambataro G.,Uoc Day Hospital Reumatologia | Zaccara E.,Uoc Day Hospital Reumatologia | Maglione W.,Uoc Day Hospital Reumatologia | And 4 more authors.
Arthritis Research and Therapy | Year: 2014

Introduction: Nailfold videocapillaroscopy (NVC) in systemic sclerosis (SSc) is a procedure commonly used for patient classification and subsetting, but not to define disease activity (DA). This study aimed to evaluate whether the number of micro-haemorrhages (MHE), micro-thrombosis (MT), giant capillaries (GC), and normal/dilated capillaries (Cs) in NVC could predict DA in SSc. Methods: Eight-finger NVC was performed in 107 patients with SSc, and the total number of MHE/MT, GC, and the mean number of Cs were counted and defined as number of micro-haemorrhages (NEMO), GC and Cs scores, respectively. The European Scleroderma Study Group (ESSG) index constituted the gold standard for DA assessment, and scores ≥3.5 and =3 were considered indicative of high and moderate activity, respectively. Results: NEMO and GC scores were positively correlated with ESSG index (R = 0.65, P <0.0001, and R = 0.47, P <0.0001, respectively), whilst Cs score showed a negative correlation with that DA index (R = -0.30, P <0.001). The area under the curve (AUC) of receiver operating characteristic plots, obtained by NEMO score sensitivity and specificity values in classifying patients with ESSG index ≥3.5, was significantly higher than the corresponding AUC derived from either GC or Cs scores (P <0.03 and P <0.0006, respectively). A modified score, defined by the presence of a given number of MHE/MT and GC, had a good performance in classifying active patients (ESSG index ≥3, sensitivity 95.1%, specificity 84.8%, accuracy 88.7%). Conclusions: MHE/MT and GC appear to be good indicators of DA in SSc, and enhances the role of NVC as an easy technique to identify active patients. © 2014 Sambataro et al.


Del Papa N.,Uoc Day Hospital Reumatologia | Caviggioli F.,Multimedica Holding SpA | Sambataro D.,Uoc Day Hospital Reumatologia | Zaccara E.,Uoc Day Hospital Reumatologia | And 8 more authors.
Cell Transplantation | Year: 2015

Autologous fat tissue grafting (AFTG) has been successfully used in the treatment of different sclerotic conditions, including localized scleroderma. Patients with advanced systemic sclerosis (SSc)-related perioral thickening and mouth opening limitation are candidates for this therapeutic approach. AFTG of the lips was performed to improve mouth opening in patients with SSc. We enrolled in the study 20 female patients with diffuse SSc (median age 35 ± 15 years and 11 ± 10 years of disease duration). Two-milliliter fractions of autologous fat drawn from trochanteric or periumbilical areas were injected in eight different sites around the mouth. Baseline and after-treatment mouth opening changes were assessed by measuring interincisal distance and oral perimeter, while skin hardness was tested by digital durometer. Pre- and posttreatment modifications of microvascular architecture were assessed by counting capillaries in the inferior lip videocapillaroscopy (VC) images and by scoring the microvascular density (MVD) in anti-CD34/CD31 immunohistochemical (IH) stained perioral skin biopsy sections. Similarly, histological sections were examined to evaluate dermoepidermic junction (DEJ) modifications. Three months after treatment, both the interincisal distance and oral perimeter significantly increased (p < 0.001). At the same time, a significant skin neovascularization became evident, both considering the VC images (p < 0.001) and MVD scores in IH sections (p < 0.0001). Finally, some skin histological aspects also improved, as shown by the significant changes in DEJ flattening scores (p < 0.0001). The present study suggests that, in patients with SSc, AFTG can improve mouth opening and function, induce a neovascularization, and partially restore the skin structure. © 2015 Cognizant Comm. Corp.


PubMed | Instituto San Giuseppe, Uoc Day Hospital Reumatologia and University of Milan
Type: Journal Article | Journal: Bone marrow transplantation | Year: 2016

We retrospectively evaluated the efficacy of autologous hematopoietic stem cell transplantation (AHSCT) in 18 patients with rapidly progressive diffuse cutaneous systemic sclerosis (rp-dcSSc), and compared their disease outcomes with those of 36 demographically- and clinically-matched patients treated with conventional therapies. Cutaneous involvement, by performing modified Rodnan skin score (mRss), lung diffusion capacity, by measuring diffusing capacity of lung for carbon monoxide (DLCO), and disease activity, by applying the European Scleroderma Study Group (ESSG) scoring system, were the outcome variables measured at the baseline time and then every 12 months for the following 60 months in both the AHSCT-treated patients and the control group. In the AHSCT group, treatment-related mortality was 5.6%. In this group, both mRss and ESSG scores showed a significant reduction 1 year after AHSCT (P<0.002); and these results were maintained until the end of follow-up. Conversely, DLCO values remained stable during the whole period of follow-up. Survival rate of AHSCT group was much higher than that observed in the whole control group (P=0.0005). The probability that the ESSG score and mRss would remain at a high level, and DLCO could decrease, was significantly higher in the control group as a whole and in the subgroup of control patients treated with cyclophosphamide than in the AHSCT group. This study confirms that the AHSCT is effective in prolonging survival, as well as in inducing a rapid reduction of skin involvement and disease activity, and preserving lung function in patients with rp-dcSSc.


Del Papa N.,Uoc Day Hospital Reumatologia | Zaccara E.,Uoc Day Hospital Reumatologia
Best Practice and Research: Clinical Rheumatology | Year: 2015

Systemic sclerosis (SSc) is one of the most complex connective tissue diseases. Although the pathogenesis of SSc still remains elusive, it is generally accepted that initial vascular injury due to autoimmunity might result in the constitutive activation of fibroblasts and fibrosis. All of these three processes interact and affect one another resulting in a polymorphous spectrum of clinical and pathologic manifestations of SSc. The disease pleomorphism poses numerous difficulties in defining the ideal outcomes to be used in clinical trials. Despite significant progress over the past decades, the clinical management of patients with SSc remains a challenge. Novel therapies are currently being tested in the treatment of SSc and have the potential for modifying the disease process and improving the clinical outcomes. However, the evaluation of the studies is still difficult, due to either the small size of included patients or the different types and phases of the scleroderma disease under scrutiny. © 2016 Elsevier Ltd. All rights reserved.


PubMed | Uoc Day Hospital Reumatologia
Type: Journal Article | Journal: Best practice & research. Clinical rheumatology | Year: 2016

Systemic sclerosis (SSc) is one of the most complex connective tissue diseases. Although the pathogenesis of SSc still remains elusive, it is generally accepted that initial vascular injury due to autoimmunity might result in the constitutive activation of fibroblasts and fibrosis. All of these three processes interact and affect one another resulting in a polymorphous spectrum of clinical and pathologic manifestations of SSc. The disease pleomorphism poses numerous difficulties in defining the ideal outcomes to be used in clinical trials. Despite significant progress over the past decades, the clinical management of patients with SSc remains a challenge. Novel therapies are currently being tested in the treatment of SSc and have the potential for modifying the disease process and improving the clinical outcomes. However, the evaluation of the studies is still difficult, due to either the small size of included patients or the different types and phases of the scleroderma disease under scrutiny.


Digital ulcers (DUs) are a rather frequent and invalidating complication in systemic sclerosis (SSc), often showing a very slow or null tendency to heal, in spite of the commonly used systemic and local therapeutic procedures. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. In the present study, we have tentatively treated long-lasting and poorly responsive to traditional therapy SSc-related DUs by implantation of autologous adipose tissue-derived cell (ATDC) fractions. Fifteen patients with SSc having a long-lasting DU in only one fingertip who were unresponsive to intensive systemic and local treatment were enrolled in the study. The grafting procedure consisted of the injection, at the basis of the corresponding finger, of 0.5-1 ml of autologous ATDC fractions, separated by centrifugation of adipose tissue collected through liposuction from subcutaneous abdominal fat. Time to heal after the procedure was the primary end point of the study, while reduction of pain intensity and of analgesic consumption represented a secondary end point. Furthermore, the posttherapy variation of the number of capillaries, observed in the nailfold video capillaroscopy (NVC) exam and of the resistivity in the digit arteries, measured by high-resolution echocolor-Doppler, were also taken into account. A rather fast healing of the DUs was reached in all of the enrolled patients (mean time to healing 4.23 weeks; range 2-7 weeks). A significant reduction of pain intensity was observed after a few weeks (p<0.001), while the number of capillaries was significantly increased at 3- and 6-month NVC assessment (p<0.0001 in both cases). Finally, a significant after-treatment reduction of digit artery resistivity was also recorded (p<0.0001). Even with the limitations related to the small number of patients included and to the open-label design of the study, the observed strongly favorable outcome suggests that local grafting with ATDCs could represent a promising option for the treatment of SSc-related DUs unresponsive to more consolidated therapies.

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