Alfredo N. C. Santana

Lung cyst: An unusual manifestation of Niemann–Pick disease

Abstract:  Niemann–Pick disease is a rare inherited autosomal recessive disorder, currently classified into six subtypes and characterized by the intracellular accumulation of sphingomyelin in the liver, spleen, lungs, bone marrow or brain. The main pulmonary abnormalities described in high‐resolution computed tomography (HRCT) of the chest consist of thickening of the interlobular septa and ground‐glass opacities. This case report describes a patient with subtype B Niemann–Pick disease characterized by cysts and ground‐glass opacities that were detected on HRCT of the chest.

Treatment of ANCA-Associated Vasculitis

To the Editor: Dr Bosch and colleagues conducted a systematic review of treatment of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, including Wegener granulomatosis. However, their article did not discuss the increased incidence of thromboembolic events in patients with Wegener granulomatosis and the possible role of anticoagulation in these patients. The incidence of thromboembolic events in Wegener granulomatosis is as high as in patients with previous idiopathic venous thromboembolism (7.0 cases/ 100 patient-years vs 7.2 cases/100 patient-years, respectively). Considering that prophylactic use of warfarin is an effective method of preventing thromboembolic events in patients with previous idiopathic venous thromboembolism, it is possible that prophylactic anticoagulation may also have a role in patients with Wegener granulomatosis who have no contraindications to warfarin. This may be especially important during disease activity because 81% of thromboembolic events in persons with active Wegener granulomatosis occur during this phase. However, this would need to be addressed by a randomized clinical trial.

Connecting the dots: hypoxia, pulmonary fibrosis, obstructive sleep apnea, and aging.

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Circulating endothelial progenitor cells in ANCA-associated vasculitis: the light at the end of the tunnel?

The main clinical features of ANCA-associated vasculitis (AAV) are inflammation and necrosis of small vessels, thrombus formation and endothelial injury [1–3]. In this issue of Rheumatology, Závada et al. [4] conclude that low numbers of circulating endothelial progenitor cells (EPCs) are associated with increased propensity for early relapse of AAV. The therapeutic potential of EPCs in AAV may exist in the form of four different scenarios. First, although disease remission is achieved by most patients, morbidity (pulmonary fibrosis, chronic renal failure and neuropathy) is present in 90% of the patients with AAV [3]. Consequently, it is important to decrease morbidity in this disease. This decrease may be possible by increasing EPC levels, considering that EPC augmentation (by drugs—statins, GM-CSF or VEGF—or by transplantation) has been associated with good outcomes in other diseases with vascular inflammation/endothelial injury, such as ischaemic stroke (good functional outcome and reduced infarct growth), acute myocardial infarction (improved global left ventricular ejection fraction, reduced end-systolic left ventricular volume reduction, increased coronary blood-flow reserve and improved myocardial viability), coronary artery disease and atherosclerosis [3, 5, 6]. Although GM-CSF may mobilize stem cells to re-endothelize damaged vessels, it cannot be used in AAV patients, considering that the resulting neutrophilia may trigger a relapse [3]. Secondly, at present, thrombosis in AAV represents a novel clinical conundrum. The incidence of thromboembolic events in WG/AAV is as high as in patients with previous idiopathic venous thromboembolism (7.0 cases/100 patient-years vs 7.2 cases/100 patient-years, respectively) [2, 7, 8]. Considering that the prophylactic use of statins is an effective method to prevent thromboembolic events in healthy men and women with low-density lipoprotein (LDL) cholesterol levels <3.4mmol/l and highsensitivity CRP levels of 519.05 nmol/l, it is possible that prophylactic statins may also benefit AAV patients [9]. Prophylactic use of statins may be especially important during disease activity, because 81% of thromboembolic events take place in individuals with active vasculitis. The possible benefits of statins in thrombosis are mediated by increasing EPC levels, reducing vascular inflammation (anti-inflammatory effect), decreasing platelet aggregation and inhibiting thrombus formation [8, 9]. However, the possible benefits of statins in AAV patients would need to be addressed by a randomized controlled trial. Thirdly, other important scenarios in AAV are treatment resistance and disease relapse. At 6 months, the remission rate in patients treated with cyclosphosphamide is 90%, and relapse rates at 18 months are 40–50% [1, 4, 7]. Considering that EPC participates in the repair of damaged endothelium and can prevent endothelial activation, low EPC levels may predispose to early AAV relapse [4]. In addition, the increase in EPC levels (by transfusion or drug administration, such as statins) may diminish the rates of treatment resistance and disease relapse, and may still shorten the duration of treatment with immunosuppressants, which are associated with cancer, haemorrhagic cystitis, pulmonary fibrosis and infection [1, 4]. Finally, AAV is still associated with accelerated atherosclerosis. Sangle et al. [10] showed that patients with systemic vasculitis have an increased prevalence of abnormal ankle-brachial pressure index, denoting a high risk of cardiovascular disease. Consequently, the increase in EPC levels in AAV (by transfusion or drug administration) could also improve the cardiovascular outcome, as observed in acute myocardial infarction and ischaemic stroke [5, 6]. The study by Závada et al. [4] has some drawbacks. First, there is continuing debate about the perfect method for EPC assessment (early endothelial outgrowth cultivation method or flow cytometric approaches), and the EPC assessment may influence the results obtained. Therefore, it is important to repeat this study with flow cytometric approaches. Secondly, among the 41 patients enrolled for the initial EPC sampling, 31 patients had active disease and 10 were in remission. Furthermore, only 10 patients were sampled twice during the course of the disease. Nevertheless, the ideal design of this study would have been to enrol 41 patients with active disease for the initial EPC sampling and to have all the 41 patients sampled again after disease remission. Thirdly, there was no significant difference in EPC numbers between the subgroups of AAV patients with and without active disease, while this difference was verified in another study, corroborating the need for more studies in this field of research [4]. Fourthly, the limited number of patients of the referred study did not allow a robust multivariable regression analysis, precluding any definitive assumptions [4]. Regardless of some divergent results regarding EPCs in AAV, it seems clear that EPCs have some role in this disease [3, 4]. Considering all these data, the increase in EPC levels in AAV may represent the light at the end of the tunnel. EPC increase may solve the problems of chronic morbidity, thromboembolic events, treatment resistance, disease relapses, secondary malignancy, opportunistic infection and accelerated atherosclerosis in AAV. However, this use needs to be addressed by a randomized controlled trial.

Outras vasculites pulmonares

Among the various forms of pulmonary vasculitis are microscopic polyangiitis, Takayasus arteritis, Behcets syndrome and Henoch-Schonlein purpura, as well as those forms related to rheumatologic diseases. The diagnosis is made through analysis of clinical manifestations, together with radiological and pathological findings.

Bone marrow necrosis successfully treated with corticosteroid.

Abstract:  A 60‐yr‐old white woman with CREST syndrome (calcinosis cutis, Raynauds phenomenon, esophageal involvement, sclerodactyly, telangectasia), idiophatic portal hypertension and esophageal varices presented with a 2‐month history of bone pain and severe anemia, requiring erythrocyte transfusion every 5–7 d. Initial laboratory findings were hemoglobin (Hb) 4.4 g/dL, platelets 15 × 109/L, white blood cell count (WBC) 2.7 × 109/L. Bone marrow biopsy showed large areas of BMN, and cultures of bone marrow aspirate were negative. The patient was started on intravenous pulse methylprednisolone (1000 mg/d for 3 d) followed by oral prednisone (1 mg/kg/d), and did not require erythrocyte transfusion thereafter. On the 40th day, our patient had Hb 11.6 g/dL, platelets 120 × 109/L, WBC 6.2 × 109/L. Here, we describe the first report of BMN in a patient with CREST syndrome, the first description of successful treatment with intravenous pulse corticosteroid and discuss the possible immune mechanisms involved in the present case.

Supine Systolic Blood Pressure and 1-Year Mortality in Patients With Acute Chest Pain

To the Editor: Dr Stenestrand and colleagues analyzed data from 119 151 participants in the Registry of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA) who were treated for chest pain in the intensive care unit from 1997 to 2007. The study reported that absolute 1-year mortality was 40.3% higher in quartile 1 (Q1, supine systolic blood pressure 128 mm Hg) compared with quartile 2 (Q2, supine systolic blood pressure 128-144 mm Hg), adjusted for age; sex; smoking status; diastolic blood pressure; use of antihypertensive medication and nitroglycerin at admission; and use at discharge of antihypertensive, statin, antiplatelet, and anticoagulant drugs and other lipid-lowering medication. As a study limitation, the authors said that “it is possible that factors not present in the RIKS-HIA database, such as malnutrition or anemia, might explain part of the relatively poor prognosis associated with low admission systolic BP.” However, another possible confounder is sleep apnea, an important pathophysiological and prognostic factor in cardiovascular disease. Sleep apnea may have been more prevalent in Q1 than in Q2: individuals in Q1 were older and had higher heart rate than those in Q2, and sleep apnea is generally more prevalent among older individuals and is associated with higher heart rate. Despite a greater prevalence of -blocker use in Q1 than in Q2, Q1 participants had higher heart rate, possibly due to a more intense sympathetic activation in Q1, consistent with associated sleep apnea. Relative to Q2, Q1 participants had greater prevalence of aspirin and statin use and lower total cholesterol levels and diastolic blood pressure, traditionally associated with better prognosis in chest pain. Consequently, it is possible that a negative prognostic factor in chest pain such as sleep apnea was not evaluated. In previous studies, sleep apnea was present in up to 57% of patients with acute coronary syndrome, being associated with increased coronary restenosis, major adverse cardiac events, and cardiac death. Based on these data, undiagnosed or untreated sleep apnea might explain, at least in part, the poor prognosis associated with low admission supine systolic blood pressure in acute chest pain in the study by Stenestrand et al. However, this hypothesis would have to be addressed by a prospective clinical study.