Angela Mauro

Refractory vasculitic ulcer of the toe in adolescent suffering from Systemic Lupus Erythematosus treated successfully with hyperbaric oxygen therapy

Skin ulcers are a dangerous and uncommon complication of vasculitis. We describe the case of a teenager suffering from Systemic Lupus Erythematosus with digital ulcer resistant to conventional therapy, treated successfully with Hyperbaric Oxygen Therapy. The application of hyperbaric oxygen, which is used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. Further studies are needed to evaluate its role as primary therapy for this group of patients.

Refractory rheumatoid factor positive polyarthritis in a female adolescent already suffering from type 1 diabetes mellitus and Hashimoto's thyroiditis successfully treated with etanercept.

Type 1 diabetes mellitus may be associated with many autoimmune diseases with the common autoimmune pathogenesis. We describe the case of a girl suffering from Type 1 diabetes mellitus and autoimmune Hashimotos thyroiditis since the childhood and, due to the onset of Juvenile Idiopathic Arthritis during adolescence, for three years practiced therapy with an anti-TNF drug, etanercept . Currently her inflammatory markers are normal, arthritis is inactive and diabetes is well controlled. During the treatment with anti-TNF drug we observed a significative reduction of insulin dose, probably due to an increased tissue sensitivity secondary to the suppression of the activity of TNF-alpha. Several clinical trials that have evaluated the effect of immunomodulatory agents in diabetic patients, especially in those with recent onset of disease, were already performed but further studies of longer duration on a larger population are needed to assess the role of biologic drugs and immunotherapy in this group of patients.

Investigational drugs for treatment of juvenile idiopathic arthritis

ABSTRACT Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The improvement of knowledge about the pathogenetic mechanisms of JIA and advances in the understanding of pathways linking inflammation and autoimmunity and functions of multiple transcription factors have translated into new drug development for a tailored treatment directed to specific subpopulations of JIA patients. Areas covered: This review provides a digest of new investigational drugs which are currently or have been recently tested for treatment of JIA, and highlights some early phase clinical trials on rilonacept, givinostat, daclizumab, tofacitinib, and sarilumab. Expert opinion: Several studies have been focused on multiple complementary pathways driving synovial inflammation in JIA or molecules implicated in the inflammatory signature of JIA to deliver durable effects and prevent long-term complications. Since JIA is a complex disorder with multiple faces, identifying new treatment options for patients nonresponsive to the current drug armamentarium is of great relevance. A number of agents have been developed in the very last years, such as givinostat and tofacitinib, showing promising results in some cases, but trials remain in an early phase and few agents are currently under evaluation in a further phase setting. Longer-term use in possibly high numbers of patients and adequate data collection using large-scale registries are necessary to confirm clinical efficacy and provide a well-balanced overview of safety issues related to the drugs presented in this review.

Correction to: A national cohort study on pediatric Behçet’s disease: cross-sectional data from an Italian registry

Following publication of the original article [1], the authors reported that the names of two institutional authors – EUROFEVER and the Paediatric Rheumatology International Trials Organisation (PRINTO) – had been unintentionally omitted in the final online version of the manuscript. The corrected author list is shown in this Correction..

Lysosomal storage disorders for the pediatric rheumatologist: the example of mucopolysaccharydoses

The Mucopolysaccharidoses (MPS) are a group of diseases caused by complete or partial deficiency of lysosomal enzymes responsible for glycosaminoglycans catabolism. Their accumulation within the lysosome leads to cellular damage and organ failure [1,2]. The musculoskeletal system is the most frequently affected one. Joint stiffness, contractures (claw hand), dysostosis multiplex, and carpal tunnel syndrome are some of the most frequent features [3-9]. Often the joint symptoms may be confused with inflammatory arthritides such as Juvenile Idiopathic Arthritis [10,11]. A prompt differential diagnoses is a fundamental step: in MPS patients there are no signs of local inflammation such as swelling, warmth and tenderness, and lack of fever and increased inflammatory markers. In addition, patients with MPS do not respond to anti-rheumatic therapy [12,13]. In addition, characteristic facies, cognitive impairment, short stature, recurrent otitis media, sleep apnea, hearing, vision and heart problems can be present [14,15]. Because of a wide variety of clinical presentation, diagnosis of MPS disorders is often delayed, especially in patients with mild forms and without neurocognitive impairment such as Scheie Syndrome. When clinical features are suggestive for MPS, the diagnosis is confirmed with the assay of urinary GAG concentration, which is a sensitive but not specific method [16] and, as the gold standard with determination of the specific enzyme in cultured fibroblasts, leukocytes, plasma or serum [17]. The genetic sequencing could be used to identify the disease-causing mutation. The managment of MPS disorders requires a multidisciplinary evaluation for multi-organ involvement. The new therapeutic approaches to MPS have drastically changed the natural history of disease. Transplantation of hematopoietic stem cells from bone marrow or umbilical cord can achieve significant benefits. The clinical success of this therapeutic approach depends on age, stage of disease, type of donor and ability to achieve stable engraftment without the development of graft-vs-host disease [18,20]. In early stages of disease, enzyme replacement therapy can benefit musculoskeletal symptoms and lung function [21-23]. This therapy, however, does not cross the blood-brain barrier and has not shown neurocognitive benefit. In conclusion, the goal is the prompt identification of MPS disorders since an early diagnosis could allow early treatment: in this regard, particular attention should be given to an accurate differential diagnosis with chronic inflammatory arthropathies.

AB1024 A Rare Case of Neonatal Antiphospholipid Syndrome

Background Neonatal Antiphospholipid antibody syndrome (APS) is a rare clinical entity linked to the transplacental transfer of antiphospholipid antibodies (aPL). Additional risk factors such as asphyxia, sepsis, arterial or venous catheter, congenital thrombophylia are frequently associated, precipitating the thrombophylic action of aPL. Objectives We describe a case of neonatal thrombotic stroke associated with IgG (but not IgM) aPL. Methods A 6 month old Caucasian child presented to our clinic with a history of seizures, delayed psychomotor development, right hemiparesis and right homonymous hemianopsia. The family history was uncontributive. A placental abruption on the 3rd month of gestation and premature contractions in the second trimester were reported. The child was born at 38 weeks of gestational age with a natural childbirth, and a fetal APGAR index of 9/9. However the mother noticed a left facial hypotrophy since the first days of life, and described a progressively reduced use of his right arm. At 3 months of age the child developed a divergent strabismus, and recurrent partial seizures. Results Cerebral MRI at 6 months of age exhibited changes consistent with ischemic cerebral lesions in the left middle cerebral artery territory with a MR angiography showing a thinning caliber of this vessel. Heart ultrasound was unremarkable. Routine laboratory test including infectious serologies were normal or negative. Prothrombotic risk factors ie PT, APTT, fibrinogen, protein S, protein C, Lupus Anticoagulant, IgM Anticardiolipin antibodies and IgM β2 GP1 were negative or in normal range. IgG anticardiolipin were elevated at 17 U/ml (normal <10), and IgG β2 GP1 were also positive at 59 U/ml (normal <10). Molecular genetic testing demonstrated heterozygosity for G1691A factor V Leiden mutation. Subsequently, at the age of 9 months IgG anticardiolipin and β2 GP1 resulted negative. Testing for aPL was performed 6 months after the delivery in the mother and was negative. The child currently presents a refractory epilepsy and an abnormal neurological status with trunk hypotonia and global developmental delay. Conclusions aPL-related thrombosis is exceedingly rare In the neonatal period. The consequences depend on the type of organ and vessel involved, the vessel size and on the rapid or slow course of the thrombotic process. The most frequently described type of thrombotic events is deep venous thrombosis in the lower extremities, pulmonary embolism, and thrombotic complications in the central nervous system. aPL alone may not be sufficient to cause the ischemic damage, and others prothrombotic conditions are probably implicated. In our patient the heterozygosity for factor V Leiden mutation, placental abruption at the III month of pregnancy and premature contractions may have contributed to the thromboembolic disease in presence of maternal IgG aPL. Disclosure of Interest None declared

AB1025 Chronic Recurrent Multifocal Osteomyelitis (CRMO): The Importance of an Accurate Differential Diagnosis

Background CRMO is a rare auto-inflammatory disorder, characterized by pain related to the presence of multifocal sites of sterile bone inflammation. CRMO is a diagnosis of exclusion established by clinical presentation, imaging studies, and culture-negative bone biopsy. Objectives To compare 2 clinical cases with very similar clinical and radiological presentation but different diagnosis and outcome. Methods Case 1. MM is a 11-year-old boy presented with a 4-months history of progressive left-clavicle pain associated with fever and good response to non-steroidal anti-inflammatory drugs (NSAIDs). Clinical examination revealed right supra-clavicle lymphadenopathy, and functional limitation of left arm with pain elicited by left clavicle palpation. Laboratory tests showed increase of inflammatory markers but normal complete blood count and LDH levels. Chest X-ray and abdominal ultrasonography were negative. Left clavicle MRI was compatible with osteomyeltis and empiric antibiotic therapy was started with clinical improvement. Three months later the patient presented with pain at right shoulder and arm, fever and nocturnal awakenings associated with persistent lymphoadenopathy. Inflammatory markers were increased and infections were excluded. Elbow X-ray and ultrasonography resulted negative as well as bone marrow aspirate. Bone-scintigraphy showed multiple sites of uptake and whole-body MRI showed multiple bone lesions located on both scapulae, clavicles, upper limbs, vertebrae (D5-11), and sternum. A diagnosis of CRMO was hypothesized. Case 2. LP presented at the age of 15 y with lumbosacral pain worsened with back movements, load lifting, and running, and present also at night. NSAIDs therapy was started, with partial improvement. Laboratory tests revealed slight increase of inflammatory markers, while X-Ray of the pelvis and the lumbosacral spine was normal. As an infectious form was initially suspected, broad-spectrum intravenous antibiotic therapy was administered. Whole-body MRI showed multiple bone lesions of the left femur, right sacrum and spine (L4, D12), findings confirmed by bone PET. Bone marrow aspirate excluded the presence of blast cells and extrinsic infiltration. Results In order to obtain a definitive diagnosis bone biopsies were performed in both cases. In Case 1 bone histological examinations revealed lymphoid cells proliferation, and the diagnosis of B-cell lymphoblastic leukemia/lymphoma was confirmed by histological findings on lymph node biopsy. In Case 2 bone biopsy and histological examination showed lympho-histiocytic infiltrate without neoplastic cells. In the hypothesis of CRMO naproxen therapy was administered for 3 months, followed by clinical and radiological improvement. Conclusions In these two cases clinical and radiological (especially whole-body MRI findings) presentations were very similar, and the diagnosis was possible only with histology. Moreover, in Case 2 bone lesions detected with MRI had typical location and findings attributable to autoinflammatory-bone disorders and the patient had a good response to therapy with NSAIDs, unlike Case 1. These two cases point out the difficulties and the caution to correctly diagnose a rare autoinflammatory bone disease. Disclosure of Interest None declared

Refractory systemic juvenile idiopathic arthritis complicated by coxarthrosis

S-JIA has the worst long-term prognosis compared to other types of JIA. Corticosteroids, methotrexate and anti - tumor necrosis factor (TNF) are the most commonly used drugs for it. Recently, newer biologic agents targeting IL-1 and IL-6 have proven their effectiveness in treating s-JIA and in minimizing corticosteroid exposure.

Eosinophilic granuloma: case report

Lameness is a symptom very common in childhood, it depends on inflammatory, neoplastic, infective, orthopedic diseases.

Five cases of rheumatic fever diagnosed after onset of Sydenham chorea

Acute Rheumatic fever is still a challenge for physicians, it is often not diagnosed at onset and adequately treated.