Pancreatitis as the presenting symptom of abdominal sarcoidosis.

We present a 60-year-old woman with non-pulmonary sarcoidosis manifesting as acute pancreatitis, possibly due to hypercalcaemia. Pancreatitis in sarcoidosis is rare, particularly as a presenting symptom. This case demonstrates that sarcoidosis should be included in the differential diagnosis of pancreatitis with hypercalcaemia, even without pulmonary signs of sarcoidosis.

Granulomatous lung disease in a patient with a family history of hematological disorders.

BACKGROUND: A 29-year old patient presented with granulomatous lung disease and a family history of myelodysplastic syndrome/acute myeloid leukemia. She appeared to be a carrier of a mutation in the transcription factor GATA2. The case adds to the recent described heterogeneous clinical manifestations and syndromes in which, against a background of hematologic disorders, GATA2 mutations have been demonstrated, such as the Monomac and Emberger syndromes. In patients with a granulomatous disease and a history of (familial) hematologic disorders, the occurence of GATA2 mutations should be considered, as to gain further insight in the occurrence of granulomatous disease in a possible distinct phenotype among GATA2 mutation carriers.

Is there a competition for oxygen availability between respiratory and limb muscles?

If a competition between the oxygen demands of limb and respiratory muscles happens, hypoxia may favor redistribution of blood flow from peripheral to respiratory muscles during heavy exercise. This hypothesis was tested in eighteen lowlanders and 27 highlanders at 4350m altitude. During an incremental exercise, the regional tissue oxygen saturation (rSO2) and tissue hemoglobin concentration ([Hbt]) of the intercostal muscles and vastus medialis were monitored simultaneously by NIRS. The intercostal and vastus medialis rSO2 values were lower at altitude than at sea level (-10%, p<0.001) and decreased similarly during incremental exercise (p<0.001) while [Hbt] values increased. At maximal exercise, the intercostal rSO2 was lower than the vastus medialis rSO2 in lowlanders (-7%, p<0.001). In highlanders the time patterns were similar but intercostal rSO2 was less decreased at exercise (p<0.05). Maximal exercise performed in hypoxia did not alter the kinetics of rSO2 and [Hbt] in peripheral muscles. These findings do not favor the hypothesis of blood flow redistribution.

Pulmonary arterial hypertension in limited cutaneous systemic sclerosis: a distinctive vasculopathy.

Systemic sclerosis-associated pulmonary arterial hypertension (SScPAH) has a worse prognosis and response to pulmonary arterial hypertension (PAH) therapy than idiopathic PAH (IPAH). These differences have not yet been explained. Knowledge concerning histological pulmonary vasculopathy in SScPAH is limited in contrast to IPAH. Therefore, we explored patterns of vasculopathy in SScPAH compared with IPAH. Parameters of vasculopathy were assessed from lung tissue of eight PAH patients with limited cutaneous systemic sclerosis and 11 IPAH patients. Lung tissue was obtained at autopsy (n = 15), explantation (n = 3) and biopsy (n = 1). Pulmonary arterial/arteriolar intimal fibrosis was identified in all SScPAH patients and in three IPAH patients (p = 0.003). Fibrosis of pulmonary veins/venules was found in all SScPAH patients and in three IPAH patients (p = 0.003). In four SScPAH patients, fibrosis of veins/venules was focal and associated with capillary congestion as in pulmonary veno-occlusive disease (PVOD). Of the IPAH patients, 10 had unequivocal evidence of plexogenic arteriopathy compared with none of the SScPAH patients (p = 0.001). SScPAH is characterised by small vessel intimal fibrosis, which is associated with a PVOD-like pattern in some cases. This might explain its different clinical behaviour from IPAH. Small vessel intimal fibrosis may provide clues to elucidation of differences in pathogenetic mechanisms between the groups.

Molecular subtypes of systemic sclerosis in association with anti-centromere antibodies and digital ulcers.

The objective of this study was to identify molecular profiles that may distinguish clinical subtypes in systemic sclerosis (SSc). Large-scale gene expression profiling was performed on peripheral blood (PB) from 12 SSc patients and 6 healthy individuals. Significance analysis of microarrays, two-way hierarchical cluster analysis and PANTHER (Protein ANalysis THrough Evolutionary Relationships) ontology classification were used to analyze the data. Quantitative PCR was applied for validation in a cohort of 43 SSc patients. The results show that the expression of genes involved in immune defense, cell cycle and signal transduction was significantly elevated in PB of SSc patients (n=12) compared with healthy individuals (n=6). SSc patients could be stratified into subgroups based on differential expression of genes induced by type I interferon (IFN) and genes involved in antimicrobial (AM) activity. Differential expression of type I IFN or AM signature genes was validated and extended in an independent cohort of 31 patients by quantitative PCR. Low expression of IFN response genes was associated with the presence of anti-centromere antibodies, whereas increased expression was associated with the appearance of digital ulcers. In conclusion, patients with SSc can be classified on the basis of differential expression of immune defense genes. Differences in the activity of the type I IFN response program stratify patients into two clinically relevant subgroups.

Possible role of imatinib in clinical pulmonary veno-occlusive disease.

The platelet-derived growth factor receptor inhibitor imatinib has demonstrated clinical and haemodynamical improvement in both animal models of pulmonary hypertension (PH) and patients with PH. It has been suggested that anti-proliferative effects on pulmonary vascular smooth muscle cells are responsible for these beneficial effects. The current study describes a patient with pulmonary arterial hypertension associated with a suspected pulmonary veno-occlusive disease. Treatment with imatinib resulted in rapid clinical improvement and decrease of ground-glass opacities and lobular septal thickening on high-resolution computed tomography. Based on these findings and on in vitro effects of imatinib on permeability of the endothelium, the authors hypothesise that the rapid clinical outcome is partly due to effects of imatinib on vascular integrity.

Right ventricular contractility in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension.

Since systemic sclerosis (SSc) also involves the heart, the aim of the present study was to evaluate possible differences in right ventricular (RV) pump function between SSc-associated pulmonary arterial hypertension (PAH; SScPAH) and idiopathic PAH (IPAH). In 13 limited cutaneous SScPAH and 17 IPAH patients, RV pump function was described using the pump function graph, which relates mean RV pressure ((RV)) and stroke volume index (SVI). Differences in pump function result in shift or rotation of the pump function graph. (RV) and SVI were measured using standard catheterisation. The hypothetical isovolumic (RV) ((RV,iso)) was estimated using a single-beat method. The pump function graph was approximated by a parabola: (RV) = (RV,iso)[1-(SVI/SVI(max))(2)], where SVI(max )is the hypothetical maximal SVI at zero (RV), enabling calculation of SVI(max). There were no differences in SVI and SVI(max). Both (RV) and (RV,iso) were significantly lower in SScPAH than in IPAH ((RV) 30.7+/-8.5 versus 41.2+/-9.4 mmHg; (RV,iso) 43.1+/-12.4 versus 53.5+/-10.0 mmHg). Since higher pressures were found at similar SVI, the difference in the pump function graph results from lower contractility in SScPAH than in IPAH. Right ventricular contractility is lower in systemic sclerosis-associated pulmonary arterial hypertension than in idiopathic pulmonary arterial hypertension.