[Show abstract][Hide abstract] 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
Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1237.3-1238. DOI:10.1136/annrheumdis-2015-eular.6115 · 10.38 Impact Factor
[Show abstract][Hide abstract] 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.
The Journal of Rheumatology 04/2015; 42(6). DOI:10.3899/jrheum.141261 · 3.19 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate the long-term response and safety of interleukin-1 receptor antagonist (anakinra) in recurrent pericarditis.
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.
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.
The long-term use of anakinra in monotherapy is associated with persistent control of recurrent pericarditis.
The Journal of pediatrics 06/2014; 164(6). DOI:10.1016/j.jpeds.2014.01.065 · 3.79 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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
Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):705-705. DOI:10.1136/annrheumdis-2012-eular.1177 · 10.38 Impact Factor