Analysis of circulating osteoclast and osteogenic precursors in patients with Gorham-Stout disease.

PURPOSE: Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients. METHODS: Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin). RESULTS: We found an increase of CD16-/CD14+CD11b+ and CD115+/CD14+CD11b+ osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN. CONCLUSION: The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes.

A pediatric case of TEK-Related malformations and marfanoid habitus: an incidental finding or a feature?

Vascular malformations encompass a wide range of complex vascular lesions. Due to the extreme variability of clinical presentation, classification and their related syndromes presents a challenge. Here we describe a case of a boy presenting with Marfanoid habitus, cutaneous vascular malformations, and severe acute anemia due to ileal venous malformations. Although a panel of genetic markers for the Marfan phenotype was negative, we identified a de novo mutation in the TEK gene in the patient. This case supports expansion of the phenotypic spectrum of TEK-related vascular malformations.

Expanding the spectrum of Gorham Stout disease exploring a single center pediatric case series.

Gorham-Stout Disease (GSD), also named vanishing bone disease, is an ultrarare condition characterized by progressive osteolysis with intraosseous lymphatic vessel proliferation and bone cortical loss. So far, about 300 cases have been reported. It may occur at any age but more commonly affects children and young adults. The aim of this study is to retrospectively review our internal patient series and to hypothesize a diagnostic-therapeutic protocol for earlier diagnosis and treatment. Clinical datasets from our center were examined to identify all GSD patients for collection and analysis. We identified 9 pediatric cases and performed a retrospective case-series review to examine and document both diagnosis and treatment. We found that delay in diagnosis after first symptoms played a critical role in determining morbidity and that multidisciplinary care is key for proper diagnosis and treatment. Our study provides additional insight to improve the critical challenge of early diagnosis and highlights a multidisciplinary treatment approach for the most appropriate management of patients with rare GSD disease. Although GSD is an ultrarare disease, physicians should keep in mind the main clinical features since neglected cases may result in potentially fatal complications.

Herpes Virus Infections During Treatment With Etanercept in Juvenile Idiopathic Arthritis.

Incidence rates for varicella and herpes zoster were similar in patients with juvenile idiopathic arthritis receiving etanercept/methotrexate (n = 85, 184.9 patient-years [PY]) or methotrexate alone (n = 71, 199.4 PY); no complicated varicella or herpes zoster cases were reported; herpes labialis incidence was higher in patients receiving etanercept/methotrexate versus methotrexate alone (0.38 vs. 0.24 PY).

Thricho-rhino-phalangeal syndrome and severe osteoporosis: a rare association or a feature? An effective therapeutic approach with biphosphonates.

Trichorhinophalangeal syndrome (TRPS) is a rare, autosomal dominant malformation syndrome characterized by hair, craniofacial and skeletal abnormalities, skin laxity, deformation of phalanges and anomalies of pelvis, femurs, and tibias. Three subtypes have been described: TRPS I, caused by mutations in TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. We present the case of a 7-year-old boy, affected by TRPS with a severe osteoporosis and several spontaneous bone fractures, an association described only once in the literature, successfully treated with biphosphonates. Bone mineral density (BMD) at dual-energy X-ray Absorptiometry (DXA) was of 0.331 g/cm(2) at lumbar spine with. He had four spontaneous femoral fractures in a year, and for this reason he was been operated for positioning intramedullary osteosynthesis and orthopedic supports. Due to the severity of the clinical and radiological pattern it was established, after approval of the Ethical Committee, to begin off-label therapy with infusions of neridronate at a dose of 2 mg/kg IV every 3 months. The treatment was, in this patient, effective both in terms of clinical (absence of new fractures) and mineralomethric (+45% BMD ath the lumbar level). We therefore suggest that treatment with biphosponates can be taken in account as a possible therapeutic option in case of bone fragility in patients with TRPSI.

Primary Sjögren's syndrome mimicking lymphoma in a pediatric patient. A rare and possibly misdiagnosed condition.

A 12-year-old girl presented at the Oncoemato-logic Department with an acute onset of generalized lymphadenopathy. Lymphoproliferative disorders were highly suspected. Biopsied cervical and inguinal lymph node disclosed neither malignant cells nor monoclonal proliferation of lymphocytes. Revaluating the diagnosis, anamnestic data revealed multiple episodes of bilateral parotid swelling since age one, without systemic symptoms. Laboratory investigations, parotid ecography, Schirmer test revealed Sjogren's syndrome without associated disease. Sjogren syndrome (SS) in childhood is a rare and possibly underdiagnosed condition.

Successful treatment with oral valganciclovir in immunocompetent infant with gastrointestinal manifestations of cytomegalovirus infection.

A 3-month-old male infant was admitted to hospital with anemia. Follow-up controls revealed the presence of specific cytomegalovirus (CMV) antibodies. Virus was isolated from urine, blood, and saliva. At 7 months of age, he presented with melena. Polymerase chain reaction (PCR) of biopsy samples from the duodenum was positive for CMV. Anemia resolved after starting antiviral therapy with oral valganciclovir.

A newborn with multiple fractures as first presentation of infantile myofibromatosis.

Pathological fractures occur in infancy from a variety of causes, but are a rare condition during neonatal period. We describe the case of a male newborn with a metaphyseal fracture of femur and multiple lytic lesions, diagnosed as infantile myofibromatosis.

Outcome of newborns with asymptomatic monomorphic ventricular arrhythmia.

BACKGROUND: Frequent premature ventricular contractions (PVCs), couplets (CPLTs) and episodes of ventricular tachycardia are extremely rare in the neonatal population. Limited information is available with regard to clinical relevance and outcome. OBJECTIVES: To evaluate the clinical characteristics and outcomes of a group of newborns with ventricular arrhythmias without heart disease. PATIENTS AND DESIGN: Between January 2000 and January 2003, 16 newborns with ventricular arrhythmias in the absence of heart disease were studied. The newborns were divided into three groups: PVC group (n = 8), CPLT group (n = 4) and ventricular tachycardia group (n = 4). All patients underwent physical examination, electrocardiography, Holter monitoring and echocardiography at diagnosis and at follow-up (1, 3, 6 and 12 months, and yearly thereafter). RESULTS: Mean (standard deviation, SD) age of the patients was 3 (1.19) days in the PVC group, 3.25 (0.95) days in the CPLT group and 6.5 (9.1) days in the ventricular tachycardia group. Median follow-up was 36 months (range 24-48 months). PVCs disappeared during follow-up in all the neonates, in the PVC group, at a mean (SD) age of 2.1 (1.24) months; in the CPLT group, couplets disappeared at a mean (SD) age of 6.5 (1) months. All patients with ventricular tachycardia were treated; ventricular tachycardia disappeared at a mean (SD) age of 1.7 (0.9) months. Neither death nor complications occurred. CONCLUSIONS: Ventricular arrhythmias in newborns without heart disease have a good long-term prognosis. Frequent PVCs and CPLTs do not require treatment. Sustained ventricular tachycardia or high-rate ventricular tachycardia must be treated, but the prognosis is generally favourable.

Second case of hepatoblastoma in a young patient with Simpson-Golabi-Behmel syndrome.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome associated with multiple congenital anomalies caused by a mutant X-linked recessive trait. The authors report on a 14-month-old male patient affected by hepatoblastoma. As far as is known, this is the second patient reported with SGBS and hepatoblastoma. The observations emphasize that an increased risk of neoplasia in SGBS must be kept in mind, especially in young patients.

Conversion reaction presenting as a polyradiculonevritis.

AIM: To show that conversion reactions should be suspected when symptomatology or instrumental checking does not conform to a precise pathological pattern in its anatomical and physiological keys. METHODS: We report the case of a 14-y-old girl who presented with signs and symptoms of Guillain-Barré polyradiculonevritis. Negative instrumental and laboratory tests led us to consider a possible diagnosis of conversion reaction. RESULTS: After a more detailed history emphasizing the close bond between the patient and her father, a poor peer-relation exchange and psychological stress, we were able to identify conversion reactions through the patient's motor signs. CONCLUSION: Conversion symptoms must be suspected and searched for when the neurologic outline is difficult to clarify, and also in the case of Guillain-Barré syndrome that does not respond to plasmapheresis.