The identification of CCL18 as biomarker of disease activity in localized scleroderma.

BACKGROUND: Localized Scleroderma (LoS) encompasses a group of idiopathic skin conditions characterized by (sub)cutaneous inflammation and subsequent development of fibrosis. Currently, lack of accurate tools enabling disease activity assessment leads to suboptimal treatment approaches. OBJECTIVE: To investigate serum concentrations of cytokines and chemokines implicated in inflammation and angiogenesis in LoS and explore their potential to be utilized as biomarker of disease activity. Additionally, to investigate the implication of potential biomarkers in disease pathogenesis. METHODS: A 39-plex Luminex immuno-assay was performed in serum samples of 74 LoS and 22 Healthy Controls. The relation between a validated clinical measure of disease activity (mLoSSI) and serum analytes was investigated. Additionally, gene and protein expression were investigated in circulating cells and skin biopsies. RESULTS: From the total of 39, 10 analytes (CCL18, CXCL9, CXCL10, CXCL13, TNFRII, Galectin-9, TIE-1, sVCAM, IL-18, CCL19) were elevated in LoS serum. Cluster analysis of serum samples revealed CCL18 as most important analyte to discriminate between active and inactive disease. At individual patient level, CCL18 serum levels correlated strongest with mLoSSI-scores (rs = 0.4604, P < 0.0001) and in longitudinal measures CCL18 concentrations normalised with declining disease activity upon treatment initiation. Additionally, CCL18 was elevated in LoS serum, and not in (juvenile) dermatomyositis or spinal muscular atrophy. Importantly, CCL18 gene and protein expression was increased at the inflammatory border of cutaneous LoS lesions, with normal expression in unaffected skin and circulating immune cells. CONCLUSION: CCL18 is specific for disease activity in LoS thereby providing relevance as a biomarker for this debilitating disease.

Hepatobiliary scan showing type II choledochal cyst.

Nuclear medicine hepatobiliary scintigraphy is well established for the evaluation of right upper quadrant pain in cases of possible acute cholecystitis. The authors present a case of type II choledochal cyst shown on a hepatobiliary scan in a patient with possible acute cholecystitis.

Acute Budd-Chiari syndrome, portal and splenic vein thrombosis in a patient with ulcerative colitis associated with antiphospholipid antibodies and protein C deficiency.

We report the case of a female patient who had severe thrombotic complications in peripheral (V. jugularis, subclavia, brachialis, poplitea) and visceral (portal and splenic) veins 4 years after the first diagnosis of severe ulcerative pancolitis. A thrombolysis therapy for subclavian and jugular vein thrombosis was performed without complication, but she soon developed acute thrombosis of the hepatic veins (acute Budd-Chiari syndrome). She quickly recovered after liver transplantation and now - 6 years later - she lives a normal life with continuous anticoagulation and medical therapy of the colitis.3 possible causes for the severe coagulation defect in this patient can be supposed: Thrombocytosis, protein C deficiency and an antiphospholipid antibody syndrome.