Cryptococcosis mimicking cutaneous cellulitis in a patient suffering from rheumatoid arthritis: a case report.

BACKGROUND: Cryptococcus neoformans is an encapsulated yeast and the most frequent cryptococcal species found in humans. Cryptococcosis is considered an opportunistic infection as it affects mainly immunosuppressed individuals. In humans, C. neoformans causes three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis. CASE PRESENTATION: An 81-year-old woman developed severe necrotizing cellulitis on her left arm without any preceding injury. The patient had been treated with systemic corticosteroids over twenty years for rheumatoid arthritis (RA). Skin biopsies of the wound area were initially interpreted as cutaneous vasculitis of unknown etiology. However, periodic acid Schiff staining and smear analysis later revealed structures consistent with Cryptococcus neoformans, and the infection was subsequently confirmed by culture. After the initiation of therapy with fluconazole 400 mg per day the general condition and the skin ulcers improved rapidly and the patient was discharged to a rehabilitation facility. Subsequently surgical debridement and skin grafting were performed. CONCLUSIONS: Opportunistic infections such as cryptococcosis can clinically and histologically mimic cutaneous vasculitis and have to be investigated rigorously as a differential diagnosis in immunosuppressed patients.

Oncostatin M mediates STAT3-dependent intestinal epithelial restitution via increased cell proliferation, decreased apoptosis and upregulation of SERPIN family members.

OBJECTIVE: Oncostatin M (OSM) is produced by activated T cells, monocytes, and dendritic cells and signals through two distinct receptor complexes consisting of gp130 and LIFR (I) or OSMR-ß and gp130 (II), respectively. Aim of this study was to analyze the role of OSM in intestinal epithelial cells (IEC) and intestinal inflammation. METHODS: OSM expression and OSM receptor distribution was analyzed by PCR and immunohistochemistry experiments, signal transduction by immunoblotting. Gene expression studies were performed by microarray analysis and RT-PCR. Apoptosis was measured by caspases-3/7 activity. IEC migration and proliferation was studied in wounding and water soluble tetrazolium assays. RESULTS: The IEC lines Caco-2, DLD-1, SW480, HCT116 and HT-29 express mRNA for the OSM receptor subunits gp130 and OSMR-ß, while only HCT116, HT-29 and DLD-1 cells express LIFR mRNA. OSM binding to its receptor complex activates STAT1, STAT3, ERK-1/2, SAPK/JNK-1/2, and Akt. Microarray analysis revealed 79 genes that were significantly up-regulated (adj.-p ≤ 0.05) by OSM in IEC. Most up-regulated genes belong to the functional categories "immunity and defense" (p = 2.1 × 10(-7)), "apoptosis" (p = 3.7 × 10(-4)) and "JAK/STAT cascade" (p = 3.4 × 10(-6)). Members of the SERPIN gene family were among the most strongly up-regulated genes. OSM significantly increased STAT3- and MEK1-dependent IEC cell proliferation (p<0.05) and wound healing (p = 3.9 × 10(-5)). OSM protein expression was increased in colonic biopsies of patients with active inflammatory bowel disease (IBD). CONCLUSIONS: OSM promotes STAT3-dependent intestinal epithelial cell proliferation and wound healing in vitro. Considering the increased OSM expression in colonic biopsy specimens of patients with active IBD, OSM upregulation may modulate a barrier-protective host response in intestinal inflammation. Further in vivo studies are warranted to elucidate the exact role of OSM in intestinal inflammation and the potential of OSM as a drug target in IBD.

Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis.

OBJECTIVE: Vascular injury and endothelial cell (EC) activation are pathogenic hallmarks of systemic sclerosis (SSc; scleroderma). Human CD90 is highly expressed on activated ECs and can be shed from the cell surface. This study was conducted to examine whether soluble CD90 (sCD90) is elevated in the sera of patients with SSc and linked to pulmonary involvement and in particular, pulmonary arterial hypertension (PAH). METHODS: sCD90 serum concentrations were assessed in 76 patients with SSc and related to clinical data, lung function, 6-minute walk distance, echocardiography, bronchoalveolar lavage fluid, and laboratory parameters. Thirty-one healthy volunteers and 29 patients with idiopathic retroperitoneal fibrosis (IRF) served as controls. RESULTS: sCD90 serum concentrations were elevated in patients with SSc compared to healthy volunteers (P = 0.001) and patients with IRF (P = 0.01). SSc patients with pulmonary fibrosis (P = 0.006) and patients with PAH (P < 0.001) had increased sCD90 serum concentrations compared to patients without the respective pulmonary manifestation of SSc. sCD90 levels correlated with diffusing capacity for carbon monoxide (n = 65; r = -0.348, P = 0.005) and systolic pulmonary artery pressure (n = 53; r = 0.469, P < 0.001). Receiver operating characteristic curve testing determined an optimal cutoff value of ≥626 ng/ml with a sensitivity of 68% and a specificity of 83% for PAH (area under the curve 0.773, 95% confidence interval 0.648-0.898; P < 0.001). CONCLUSION: sCD90 concentrations were increased in the sera of SSc patients, particularly in patients with vascular involvement of the lungs. These data suggest that sCD90 should be further evaluated as a marker for diagnosis of PAH in SSc.

CCL18 -- potential biomarker of fibroinflammatory activity in chronic periaortitis.

OBJECTIVE: Promising therapeutic approaches have emerged in chronic periaortitis, whereas peripheral blood biomarkers are lacking. CC-chemokine ligand 18 (CCL18) is known as a marker of fibrotic activity and prognosis in pulmonary fibrosis. We investigated whether CCL18 levels are increased in patients with chronic periaortitis and are associated with clinical, laboratory, and imaging findings. METHODS: In this retrospective study, serum concentrations of CCL18 were assessed in 30 patients with chronic periaortitis and related to clinical data, laboratory variables, and imaging studies. Serum levels were compared to 15 apparently healthy volunteers and 15 controls with aortic sclerosis. RESULTS: Serum concentrations of CCL18 were increased in patients with chronic periaortitis (median 197.6 ng/ml, range 73.7-301.0) compared to healthy volunteers (median 34.6 ng/ml, range 22.6-70.4; p < 0.0001) and controls with aortic sclerosis (median 50.4 ng/ml, range 24.5-141.2; p < 0.0001). CCL18 levels correlated with (n = 30; r = 0.461, p = 0.01) and increased with the transversal diameter of the periaortic mantle < 5, 5-10, and ≥ 10 mm (p = 0.008). Contrast enhancement (p = 0.044), treatment naivety (p = 0.042), and the occurrence of systemic symptoms (p = 0.007) were associated with higher CCL18 levels. During followup, changes of CCL18 correlated with changes of the transverse diameter of the periaortic mantle (n = 17; r = 0.512, p = 0.033). CONCLUSION: Serum concentration of CCL18 reflects fibroinflammatory activity and extent of disease in patients with chronic periaortitis.

CCL18 production is decreased in alveolar macrophages from cigarette smokers.

It is generally known that cigarette smoke alters the activation of alveolar macrophages (AM). CC Chemokine Ligand 18 (CCL18) is a marker of alternatively activated macrophages and is highly expressed in the lung. This study examines the influence of chronic cigarette smoking on the expression of CCL18 by AM. Bronchoalveolar lavage (BAL) and serum were obtained from ten smokers and 14 non-smokers. CCL18 protein concentrations were measured in serum and BAL fluid (BALF) as well as in supernatants from BAL-cells by enzyme-linked immunosorbent assay. In this study we show that the CCL18 production of BAL-cells from smokers was significantly decreased compared to BAL-cells from non-smokers. The BALF CCL18 protein concentration per macrophage cell count was significantly reduced in smokers. Furthermore, we show a decrease in CCL18 production from BAL-cells after stimulation with LPS. This decrease in CCL18 production was only shown in BAL-cells from non-smokers, which is probably due to chronic LPS exposure of smokers, resulting in LPS hypo-responsiveness. No statistically significant difference of CCL18 concentrations was found in BALF or serum of smokers versus non-smokers. CCL18 production by BAL-cells is down-regulated by chronic cigarette smoking and LPS contamination in cigarette smoke might be one factor involved. Thus this article gives further evidence that chronic cigarette smoking alters the phenotype of AM and that the M2 marker CCL18 is down-regulated in smokers macrophages.