Gorham-Stout Disease: A Diagnostic and Treatment Protocol

Program: Abstracts - Orals, Poster Previews, and Posters
Session: FRI 224-247-Metabolic and Genetic Bone Disorders
Friday, March 6, 2015: 1:00 PM-3:00 PM
Hall D-F, Bone & Calciotropic Hormones (San Diego Convention Center)

Poster Board FRI-241
Natascia Di Iorgi, MD1, Nadia Vercellino2, Pietro Dal Monte2 and Mohamad Maghnie, MD3
1Istituto G. Gaslini, University of Genova, Genova, Italy, 2Istituto G.Gaslini, Genova, Italy, 3University of Genova, Genova, Italy
Background. Gorham-Stout syndrome (GSD) is a rare disorder characterized by lymphangiomatosis, invasion of soft tissues, osteolysis associated with severe bone morbidity and potentially lethal in the presence of chilothorax. Although bone lesions are due to abnormal vessels proliferation, new lines of investigations point out the role of osteoclastogenic cytokines (1). As the management  of GSD is not univocal and outcomes are unpredictable we build a multifaced protocol in order to study its natural history, biomarkers of disease severity and to treat uniformly patients.

Methods. Seven patients (5M and 2F,  3 mts-26.0 yrs of age) with GSD diagnosed by biopsy underwent clinical, biochemical (Ctx, BAP, PTH, 25OHD, D-Dimer), karyotype, CGH-array and imaging  evaluations (Total Body -TB- and spine DXA and STIR Total Body MRI) at baseline, after 6 months and than yearly. All patients presented osteolysis at baseline (clavicle n=1, ribs n=2, femur n=1, sternum n=1, omerus n=1, scapula n=2, ulna n=1, cranial basis) and 1 lately (parietal bone), 3 reported pathological fractures (clavicle n=1F, femur n=1M, rib n=1M) and 4 chylothorax. Three M underwent INFα2b treatment (1500000UI/m2on alternate days), 2M pamidronate for 1 year and 2M and 1F zolendronate therapy due to severity of disease or recidivism.  

Results. Three out of 4 patients with a multifocal/extended GSD form presented low bone mineral density (BMD) for age and sex (Z-score): 1M and 1F at the TB scan and 2M and 1F at the spine (Z-scores between – 2.8 and –1.1) with mildly increased bone turnover markers and elevated D-Dimer at baseline and during disease recurrency of bone or pleura. TB Stir MRI revealed aspecific involvement (hyperintensity in STIR and hypointensity in T1) of multiple skeletal sites far from the primary localization in all, but also new foci of disease in 2 subjects. Five patients reached 4 years follow up; subjects on bisphosphonates showed acutely reduced bone pain, increased BMD of about 1 Z-score during follow up and significant reduction of D-Dimer. Karyotype and CGH were normal in all the patients tested. All patients are still alive.

Conclusion.As chilothorax or fragility fractures may be early complications of a massive osteolysis in GSD, a multidisciplinary team is warranted. Our preliminary findings suggest the potential usefulness of: 1) STIR TB MRI technique in detecting early skeletal foci of disease, although further evaluations are needed to support its sensitivity, 2) DXA scan in characterizing the severity of GSD and 3) anti-angiogenic and anti-reabsorption therapies in GSD control.

(1)Dellinger MT et al, Bone 2014; 47-52

Nothing to Disclose: ND, NV, PD, MM

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