P Picco

Hospital Universitario 12 de Octubre, Madrid, Madrid, Spain

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Publications (116)540.05 Total impact

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    Preview · Article · Sep 2015 · Pediatric Rheumatology
  • R Papa · P Nozza · C Granata · R Caorsi · M Gattorno · A Martini · P Picco

    No preview · Article · Sep 2015 · Pediatric Rheumatology
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    Preview · Article · Sep 2015 · Pediatric Rheumatology
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    Full-text · Article · Sep 2015 · Pediatric Rheumatology
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    ABSTRACT: Background PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) is an ultra-rare autosomal dominant, auto-inflammatory disease associated to mutations in the PSTPIP1/CD2BP1 gene. The therapeutic approach during recurrences consists of steroids, while no agreement exists on the chronic management. Evidences on the use of biologics are anecdotal and variable results have been reported. Objectives To evaluate the long-term response to treatment with IL1 antagonist in six patients affected by PAPA syndrome. Methods Six patients (M:F=3:3; 4 pediatric, 1 young adult and 1 adult, mean age 18 years, range 3-50) affected by PAPA syndrome were enrolled and treated with IL1 blockers (5 patients Anakinra, 1 patient Anakinra followed by Canakinumab). Three patients were already treated with anti-TNFα monoclonal antibodies without benefit. Data were collected retrospectively (mean follow-up 26 months, range 4-38). The frequency of articular and cutaneous flares in the 24 months before starting therapy where compared to those occurred during anti-IL1 regimen. Acute phase reactants (ESR, CRP, SAA) were assessed at the last visit before the study enrolment and at last follow-up. Results All the patients displayed a significant decrease in frequency of disease flares (Table) and normalization of acute phase reactants. Three patients were asymptomatic during whole follow-up. Patient#4, with a severe and persistent pyoderma gangrenosum, displayed a partial response to Anakinra partially due to a poor compliance to daily s.c. administration. The shift to Canakinumab lead to a fast and complete resolution of the skin manifestations. Conclusions The long-term use of IL1 blockers is associated to satisfactory and persistent control of clinical manifestations and laboratory findings in PAPA syndrome. Disclosure of Interest M. Finetti: None declared, R. Caorsi: None declared, D. Marotto: None declared, A. Buoncompagni: None declared, A. Omenetti: None declared, B. Lattanzi: None declared, F. Minoia: None declared, P. Picco: None declared, M. Jorini: None declared, A. Martini Grant/research support from: Unrestricted grants from SOBI and Novartis, Speakers bureau: Speaker's fees, M. Gattorno Grant/research support from: Unrestricted grants from SOBI and Novartis, Speakers bureau: Speaker's fees
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background SAVI syndrome is a recently identified condition associated to mutations of TMEM173. Up to know only few cases of this disease have been described. Objectives To describe the clinical manifestation of an Italian patient affected by SAVI syndrome Results The girl, first born from healthy, not relatives parents, at the age of 8 months started to present erythematosus-infiltrated skin lesions with pustular evolution and finally hesitating in scars in 15-20 days. From the age of three years chilblains and severe nail dystrophy appeared. At the age of 8 years the girl presented a severe pneumonia, requiring prolonged antibiotic therapy. The chest CT performed showed, in addition to the lung infiltrate, the presence of diffuse interstitial thickening with ground-glass appearance. A restrictive framework was detected at spirometry (FVC 51%). The autoantibodies detection revealed positive ANA (1: 160), ANCA (1:80) and Coombs test; rheumatoid factor was slightly increased. Anti-DNA and ENA were negative. The skin biopsy revealed a predominantly granulomatous nodular dermatitis, with aspects of deep granulomatous folliculitis and secondary fibrosis. The lung biopsy revealed focal hemorrhage, edema and predominantly lymphocytic inflammatory aggregates in the peribronchial interstitial areas with aspects of capillaritis and contiguous focal subatelettasia with alveolar cavity filled of macrophages. In the following months, in light of the progression of the disease, steroidal treatment (prednisone 1 mg/kg/day) was started with improvement of clinical manifestation, anemia and normalization of inflammatory markers. However attempts to reduce such therapy were followed by an exacerbation of the clinical picture. In the attempt to reduce steroidal treatment, the child was treated wit both immunosuppressive (azathioprine) and biologic (etanercept) drugs, without clear improvement. Unsatisfactory growth was also detected. In the following months the child started to present a mild renal involvement with microscopic hematuria and hypertension, requiring anti-hypertensive treatment. Given the evocative framework, interferon gene signature was performed, revealing a significant activation; the molecular analysis of TMEM173 gene showed the presence of the de novo Val155Met mutation, already described as causative of SAVI syndrome. The child continued to present persistent severe microcytic anemia, requiring erythrocytes' transfusions, despite high levels of erythropoietin. Bone marrow aspiration was therefore performed, that revealed dysmaturative signs in the in erythroid progenitors. Conclusions This report of the first Italian patient with SAVI syndrome confirms the presence of the previously described clinical manifestations. Persistent hematuria and hypertension are reasonably signs of an underlying renal involvement, not previously described in this condition. Thus a renal biopsy is needed for confirmation. The origin of severe anemia is still unclear. Thus a possible deregulatory effect of mutated STING protein on bone marrow progenitors has to be investigated and is actually under study in our patient. Disclosure of Interest None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background ADA2 deficiency, a recently described disease, is characterized by systemic vasculopathy and episodes of strokes. The defect is due to a loss of function mutation of CECR1 gene, codifying for Adenosine Deaminase 2 protein. This protein regulates the catabolism of extracellular adenosine, which we have recently shown is an important regulator of Class Switch Recombination in B lymphocytes. Accordingly DADA2 patients can present hypogammaglobulinemia. Objectives The aim of the project is to characterize peripheral B-cell compartment of two patients to directly address if ADA2 mutation affects B-cell function. Methods Two brothers (15 and 7 years old) carrying mutations in CECR1 were followed up from the age of two. They showed similar clinical history with livedo reticularis, fever, vasculitis and neurological symptoms caused by haemorragic strokes. Both presented early hypogammaglobulinemia requiring intravenous immunoglobulin replacement therapy. Remarkably after etanercept treatment serum Igs slowly increased to a normal level. We analyzed peripheral B-cell phenotype by flow cytometry, in vitro B-cell proliferation and differentiation to plasmacells in response to CpG, BCR and T cell help. Results Flow cytometer analysis showed a significative reduction of total B cells compared with age matched controls. Intriguingly a defect in the memory B-cell compartment (CD19+CD27+) was observed. We found that the rate of proliferation and differentiation to Igs secreting cells is lower as compared to normal controls and it is not supported by autologous T cells. Conclusions Our findings suggest that ADA2 defect could lead to a reduced formation of T cell dependent memory B cells. References Disclosure of Interest None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Type I interferons (IFN) are secreted molecules that play a major role in the response to viral infection. However, defective regulation of this pathway may result in an excessive α/β-IFN immunity presenting with severe inflammatory phenotype1. The two prototypic genetic diseases linked to increased α/β-IFN immunity are Aicardi-Goutières syndrome (AGS) and spondyloenchondrodysplasia with immune dysregulation (SPENCD). In the case of AGS, mutations in several genes have been identified leading to excessive type I IFN production as the result of inappropriate stimulation of the type I IFN response pathway. More recently, two new clinical phenotypes, STING associated vasculopathy with onset in infancy (SAVI)2 and a familial inflammatory syndrome with systemic lupus erythematosus (SLE)-like manifestations3, have also been linked to an increase of type I IFN – in both cases as a result of TMEM173 gain of function dominant mutations. All of these conditions have been grouped under the name of type I interferonopathies. Type I IFN has been also implicated in the development of the autoimmune and inflammatory complications characteristic of SLE. Objectives To assess the predictive value of blood IFN signature for the identification of type I interferonopathies. Methods We tested a cohort of pediatric rheumatologic patients using a qPCR based IFN gene signature assay4. Expression of 6 type I IFN-related genes (IFI27, IFI44L, IFIT1, ISG15, RSAD2, SIGLEC1) was quantified by standard RT-PCR techniques. An IFN score was calculated for each patient using the median fold change of gene expression related to a healthy control. Patients were selected based on the presence of the following features: i) atypical or incomplete SLE-like symptoms occurring in infancy or in preprepubertal age; ii) vasculopathy (skin ulcers, chilblains, strokes) iii) panniculitis with or without lypodistrophy iv) interstitial lung disease in the context of systemic inflammation. Results We screened 8 patients from the rheumatology unit of the Gaslini Children's Hospital, Genova (Italy). 6 out of 8 patients had a positive signature with an IFN score ranging from 3.8 to 18.2. Based on the clinical presentation and the result of the IFN score we further analysed one patient for mutations affecting TMEM173 gene and we identified the previously reported V155M variant. Molecular screening for genes associated to type I Interferonopathies and whole exome sequencing is ongoing for selected patients. Conclusions These preliminary results show that the blood IFN signature can be predictive of the diagnosis of type I interferonopathies and suggest that a genetic cause should be suspected in atypical cases of SLE-like disease and/or vasculopathy with skin chilblains and with an early onset. As already observed in the case of IL1-β and autoinflammatory conditions, knowledge of the defect responsible for a disease will allow the development of more effective targeted therapy. References Disclosure of Interest None declared
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey. International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course. A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide. The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.
    No preview · Article · Apr 2015 · The Journal of Rheumatology
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    ABSTRACT: Anaplasma phagocytophilum, an obligate intracellular bacterium, is the causative agent of human granulocytic anaplasmosis (HGA), a tickborne infection usually manifesting as fever, malaise, cytopenia, spleen enlargement, and hepatitis. Herein, we report a case of a 14-year-old girl with HGA whose whole-body magnetic resonance imaging (MRI) disclosed an unusual picture characterized by small, widespread punctuate millimetric nodules, hypointense on T1-weighted and hyperintense on STIR sequences. This firstly reported finding may represent an alternative tool for identifying atypical infectious diseases.
    Preview · Article · Dec 2014
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    Preview · Article · Nov 2014 · The Journal of Rheumatology
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    Full-text · Article · Sep 2014 · Pediatric Rheumatology
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    Full-text · Article · Sep 2014 · Pediatric Rheumatology
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    Full-text · Article · Sep 2014 · Pediatric Rheumatology
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    ABSTRACT: Objective To evaluate the long-term response and safety of interleukin-1 receptor antagonist (anakinra) in recurrent pericarditis. Study design Fifteen patients (12 children, 3 adults) were enrolled in a multicenter retrospective study. All the patients were corticosteroid-dependent and 14 had received colchicine. Anakinra was given at 1-2 mg/kg/d. The primary outcome of the study was a reduction of at least 70% of disease flares after anakinra treatment compared with the pretreatment period. Secondary outcomes were: (1) number of complete or partial responders to anakinra and time for complete response; (2) number of patients who discontinued other ongoing treatments (non-steroidal anti-inflammatory drugs, corticosteroid, colchicine) and time needed for discontinuation; (3) number of relapses during continuous anakinra treatment; and (4) number of relapses during anakinra tapering or discontinuation. Results All patients treated had a complete response within a few days and were able to rapidly withdraw concomitant treatments, including corticosteroids. During daily treatment, no patient had a relapse of the disease; 14 patients started tapering and 6 of them experienced a relapse, with a prompt response after anakinra reintroduction. Overall, after a median follow-up of 39 months (range 6-57), a 95 % reduction of flares was observed compared with pretreatment period. Conclusion The long-term use of anakinra in monotherapy is associated with persistent control of recurrent pericarditis.
    Full-text · Article · Jun 2014 · The Journal of pediatrics
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    ABSTRACT: Viral vasculitides have been previously reported in the literature, the role of infections in their pathogenesis ranging from direct cause to trigger event. Here we report the case of a 3-year-old immunocompetent girl who developed a systemic vasculitis leading to ileal perforation, mimicking a full blown picture of Henoch-Schönlein purpura. High dosage steroid treatment was started, with good response. The anatomopathological examination of the resected gastrointestinal tract showed features of necrotising vasculitis and cytomegalovirus (CMV)-related inclusion bodies in the endothelial cells, with direct correlation to vascular damage. The causative role of viral infection was revealed by the presence of CMV DNA in patient's blood and positive IgG titer against the virus. Steroid therapy was then tapered: the patient achieved clinical remission, which still persists after a six-months follow-up. Our report suggests that CMV vasculitis is probably more frequent than previously thought, even in immunocompetent patients, with a protean clinical presentation, mimicking other types of vasculitides.
    No preview · Article · May 2014 · Clinical and experimental rheumatology
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    ABSTRACT: Background Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare autosomal dominant autoinflammatory disorder due to mutations in the CD2 binding protein 1 (CD2BP1) gene. This syndrome is featured by pyoderma gangrenosum, cystic acne and recurrent pyogenic sterile arthritis, with increased serological acute phase reactants during active disease. However, the clinical presentation and response to treatment display significant individual variability. The therapeutic approach during recurrences consists of steroids, while no agreement exists on the chronic management. Recent evidence suggests the possible use of anti-TNFα monoclonal antibodies (Punaro et al.), while the efficacy of Adalimumab (IgG1 humanized monoclonal anti-TNFα antibody) has been described only in a few cases and not yet proven. Objectives To evaluate the response to treatment with Adalimumab (IgG1 humanized monoclonal anti-TNFα antibody) in 3 PAPA patients followed in a single Center. Methods Three patients (M:F=2:1, mean age 13 years, range 5-22 years) with a molecular diagnosis of PAPA syndrome (mutations E256G, E250K, E250Q) were enrolled and treated with Adalimumab (patients#1-2: 40 mg/15 days, patient#3: 20 mg/15 days). Results Clinical outcomes evaluated were the frequency of articular and cutaneous flares in the 12 months before starting therapy compared to those occurred during Adalimumab regimen, whereas laboratory tests (ESR, PCR) were assessed at the last visit before the study enrolment and at end of treatment. Patient#1 (F, E256G+) presented both articular and cutaneous involvement. During the 25 months of treatment, she had only mild decrease in the frequency of articular recurrences (3 episodes/year before vs 1 episode/year after treatment) and pyoderma gangrenosum episodes (12 episodes/year before vs 4 episodes/year after treatment); however, a worsening size of the cutaneous lesions occurred, requiring surgical removal in one occasion. Patient#2 (M, E250K+) displayed only cutaneous involvement in the 12 months before starting Adalimumab administration, with persistent pyoderma gangrenosum on the left arms. Following the treatment period (3 months), he showed the persistence of the lesion, without clinical improvement. Reactivation of the articular symptoms was not observed. Patient#3 (M, E250Q+) was affected by recurrent arthritis localized to left elbow, ankles and knees, without cutaneous involvement. During the 9 months of treatment, he didn’t show any clinical improvement, with no significant changes in the frequency of articular episodes (10 episodes/year before vs 8 episodes/year after treatment). No difference in the levels of acute phase reactants were observed for all three patients before and after Adalimumab treatment. Conclusions Taken together, these findings suggest that our cohort of PAPA patients didn’t gain any benefit from Adalimumab administration, nor at clinical or serological level. Thus, further research is needed in order to explore novel therapeutic approaches. Disclosure of Interest None Declared
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    Full-text · Article · Dec 2013 · Pediatric Rheumatology
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    Preview · Article · Dec 2013 · Pediatric Rheumatology
  • No preview · Article · Nov 2013 · Clinical and experimental rheumatology

Publication Stats

2k Citations
540.05 Total Impact Points

Institutions

  • 2015
    • Hospital Universitario 12 de Octubre
      Madrid, Madrid, Spain
  • 1991-2015
    • IRCCS Istituto G. Gaslini
      • Department of Experimental and Laboratory Medicine
      Genova, Liguria, Italy
  • 2001-2014
    • Università degli Studi di Genova
      • Dipartimento di Medicina sperimentale (DIMES)
      Genova, Liguria, Italy
  • 2002
    • University of Florence
      • Dipartimento di Medicina Sperimentale e Clinica
      Florens, Tuscany, Italy
  • 1995
    • Galliera Hospital
      • Department of Nuclear Medicine
      Genova, Liguria, Italy
    • University of Pavia
      • Department of Diagnostic, Paediatric, Clinical and Surgical Science
      Ticinum, Lombardy, Italy