Changes In Sarcoidosis Research Articles

Metabolic syndrome may be more frequent in treatment-naive sarcoidosis patients.

Sarcoidosis is achronic granulomatous multisystem inflammatory disease. An association between sarcoidosis and subclinical atherosclerosis has recently been demonstrated. However, there are limited publications on metabolic syndrome (MetS) and its metabolic changes in sarcoidosis. In this study, we evaluated our hypothesis that the frequency of MetS may also be increased in treatment-naive, newly diagnosed sarcoidosis patients. We included 133 newly diagnosed sarcoidosis patients, 133age- and sex-matched controls, and 51untreated rheumatoid arthritis (RA) patients as diseased controls. We then compared the frequency of MetS and MetS-related items in the three groups. The criteria defined for metabolic syndrome in the National Cholesterol Education Program (NCEP) Adult Treatment PanelIII report (ATPIII) were used to diagnose MetS. MetS was more common in sarcoidosis than controls (odds ratio, OR: 5.3; 95% confidence interval, CI 95%: 2.4-11.5; p < 0.001) and was similar to RA. In addition, triglyceride and glucose levels, diastolic blood pressure measurements, and waist circumference of female sarcoidosis patients were significantly higher than in controls. We show that MetS is afrequent feature of sarcoidosis even before treatment is started. Therefore, clinicians should be aware of MetS both during treatment and during the course of the disease to reduce the risk of cardiovascular events.

T-bet Expression in Peripheral Th17.0 Cells Is Associated With Pulmonary Function Changes in Sarcoidosis.

Background: Interferon-gamma (IFN-γ) is a key mediator of sarcoidosis-related granulomatous inflammation. Previous findings of IFN-γ-producing Th17 cells in bronchoalveolar lavage fluid from sarcoidosis patients invokes the transition of Th17.0 cells to Th17.1 cells in the disease's pathogenesis. Since the T-bet transcription factor is crucial for this transition, the goal of this study was to determine if T-bet expression in Th17.0 cells reflects the extent of granulomatous inflammation in sarcoidosis patients as assessed by clinical outcomes.Methods: Using a case-control study design, we identified two groups of sarcoidosis subjects (total N = 43) with pulmonary function tests (PFTs) that either (1) changed (increased or decreased) longitudinally or (2) were stable. We used flow cytometry to measure the transcription factors T-bet and RORγt in Th1, Th17.0, and Th17.1 cell subsets defined by CCR6, CCR4 and CXCR3 in blood samples. We compared the percentages of T-bet+ cells in RORγt+Th17.0 cells (defined as CCR6+CCR4+CXCR3−) based on subjects' PFT group. We also assessed the relationship between the direction of change in PFTs with the changes in %T-bet+ frequencies using mixed effects modeling.Results: We found that T-bet expression in subjects' RORγt+Th17.0 cells varied based on clinical outcome. The T-bet+ percentage of RORγt+Th17.0 cells was higher in the cases (subject group with PFT changes) as compared to controls (stable group) (27 vs. 16%, p = 0.0040). In comparisons before and after subjects' PFT changes, the T-bet+ frequency of RORγt+Th17.0 cells increased or decreased in the opposite direction of the PFT change. The percentage of these T-bet+ cells was also higher in those with greater numbers of involved organs. Serum levels of interferon-γ-induced chemokines, CXCL9, CXCL10, and CXCL11, and whole blood gene expression of IFN-γ-related genes including GBP1, TAP1, and JAK2 were independently positively associated with the T-bet+ frequencies of RORγt+Th17.0 cells.Conclusions: These data suggest that expression of T-bet in Th17.0 cells could reflect the extent of granulomatous inflammation in sarcoidosis patients because they represent a transition state leading to the Th17.1 cell phenotype. These findings indicate that Th17 plasticity may be part of the disease paradigm.

Ultrasonic Predictors of Dry Eye Syndrome in Sarcoidosis

Objective. To identify clinical and morphofunctional changes in the lacrimal gland in sarcoidosis.Material and methods. Ultrasonography was conducted in 53 patients (106 eyes) with a verified diagnosis of systemic sarcoidosis (7 men and 46 women) whose age was 31 to 72 years.Results. Different types of lacrimal gland structural changes in sarcoidosis were detected. Comparing the acoustic and functional findings revealed a high correlation (r &gt; 0.7) between these parameters as vascularization index, a reflex component of tear secretion, and the presence of tubular structures. Types of changes in the acoustic structure of the lacrimal glands were identified, which were designated as edematous and polymorphic changes, as well as atrophic changes with a necrotic component.Conclusion. The findings can be used to diagnose lacrimal gland changes in patients suffering from sarcoidosis.

Dynamics of homeostasis and the outcome of sarcoidosis of the respiratory system in the treatment of corticosteroids

The outcome of sarcoidosis of the respiratory system is closely linked to the state of homeostasis and reactivity. Monitoring their status is possible through immunological, biochemical and hormonal studies. Within common medical institutions re-executing these studies is not always possible for a number of reasons. Therefore, the research for the availability and informative criteria of homeostasis and reactivity state was initiated at the end of XIXth century and continues until now. At the Department of Phthisiopulmonology of the First St.-Petersburg state medical University Academy I. P. Pavlov. University, new accessible and informative diagnostic criteria for estimation the state of homeostatic balance of the organism are developed. They are based on research of the general adaptation syndrome and the discovery of antistress types of adaptive reactions of the organism. In this regard, based on the leukogram evaluation following diagnostic criteria were developed and tested: leukocyte-lymphocytic index, types of adaptive reactions, entropy and redundancy of formed elements of white blood cells, extent of disturbance of homeostasis, indices of proliferation and differentiation of monocytes and reactivity types. Unfortunately, in the pulmonology clinics, they are used today only in single cases. The monitoring of homeostasis and reactivity indicators in patients with respiratory system sarcoidosis had a high working performance. It is established that in sarcoidosis the best treatment effect with corticosteroids with minimal residual changes of respiratory system took place in patients with the appropriate type of reactivity and normal range of other indicators. Pathological reactivity of an organism, especially hyporeactive and areactive types, are always accompanied by formation of pronounced residual sarcoidosis changes in the respiratory tract, which is the basis for the subsequent exacerbation (recurrence) of sarcoidosis.

Sarcoid and the nail: review of the literature

Nail involvement in sarcoidosis is rare, but its presence is often associated with chronic systemic disease. We have reviewed all 33 reported cases of nail involvement with sarcoidosis, including our own case. Nail changes in sarcoidosis, while rare, can include dystrophy (n=10, 30%), onycholysis (n=7, 21%), subungual hyperkeratosis (n=7, 21%), nail hyperkeratosis (n=2, 6%) and longitudinal ridging (n=8, 24%). All reported cases of nail sarcoidosis occurred in the setting of systemic involvement. In almost half of the cases, bony cysts were noted on radiological examination. The presence of nail dystrophy in a patient with sarcoidosis should therefore prompt radiological examination and investigation for systemic involvement.

Differences in Clinical Findings between Caucasians and African Americans with Biopsy-Proven Sarcoidosis

To study the prevalence of ocular manifestations in African American and Caucasian patients with biopsy-proven sarcoidosis at the initial ophthalmic examination and to determine the relationship between angiotensin-converting enzyme (ACE) levels, chest x-ray findings, and ocular signs of sarcoidosis. Retrospective, cross-sectional, observational study. Eighty-one consecutive patients with biopsy-proven sarcoidosis seen at the Doheny Eye Institute from January 1989 through April 2005. Medical records were reviewed to obtain demographic data, biopsy site, initial ocular findings, pulmonary symptoms, and results of serum ACE levels and chest x-rays. Associations between ACE level/chest x-ray stages and ocular manifestations related to sarcoidosis were obtained from these data. Ocular manifestations related to sarcoidosis. Of the 81 patients, 35 were Caucasian; 29 were African American; and the remaining 17 were Hispanic, Asian Indian, and other races. Female patients were older than males (P = 0.05). Sixty-five (80%) of the 81 patients had ocular manifestations related to sarcoidosis. Thirty-three patients (40.7%) had uveitis, 12 (14.8%) had adnexal granulomas, and 25 (30.8%) had keratoconjunctivitis sicca. Of the 33 patients with uveitis, 22 presented with nongranulomatous inflammation. There was no significant association between ocular manifestations related to sarcoidosis and serum ACE levels (P = 0.43) or chest x-ray stage (P>0.99). Of the 29 African American patients, 26 (89.7%) had ocular manifestations related to sarcoidosis, compared with 24 (68.6%) of the 35 Caucasians (P = 0.12). The African American patients were younger (mean age, 44.4 years) than the Caucasian patients (mean age, 52.0) (P = 0.003) and had higher mean ACE levels (P = 0.003). A significantly high proportion of African American males presented with uveitis (P = 0.005), and a significantly high proportion of African American females presented with adnexal granulomas (P = 0.05). The present study reveals that patients with sarcoidosis can present initially with clinical features of nongranulomatous uveitis. Relative to Caucasians, African American patients with sarcoidosis tend to be younger when they first present to the ophthalmologist and to present with uveitis and/or adnexal granuloma. Serum ACE levels and chest x-ray stages may not help predict the occurrence of ocular changes in sarcoidosis.

Long-term Follow-up CT Scan Evaluation in Patients With Pulmonary Sarcoidosis

The aim of the present study was to determine how the pattern and extent of sarcoidosis changes over time on serial high-resolution CT (HRCT) scans and to identify CT scan findings that might be helpful in predicting the prognosis of patients with the disease. The initial and last HRCT scan findings of 40 patients with pulmonary sarcoidosis during a mean follow-up period of 7.4 years (range, 3 to 18 years) were evaluated retrospectively. HRCT scan findings then were correlated with the pulmonary function tests. Parenchymal abnormalities in most patients with a predominant nodular pattern (18 patients) and multiple large nodular pattern (8 patients) disappeared or decreased in size on long-term follow-up CT scans. A conglomeration pattern (five patients) shrank and evolved into bronchial distortion. The shrinkage of the conglomeration pattern correlated with a decline of FEV1/FVC ratio, despite an improvement in FVC. A ground-glass opacity pattern (five patients) and a consolidation pattern (three patients) evolved into honeycombing. The evolution of the ground-glass opacity and consolidation patterns into honeycombing occurred along with a decline in FVC, although the parenchymal abnormalities became smaller. Patients with a predominantly ground-glass opacity pattern and consolidation pattern seen on the initial CT scan had a worse prognosis and were susceptible to developing severe respiratory insufficiency. The predominant patterns seen on the initial HRCT scan may be helpful in predicting the outcomes of patients with sarcoidosis.

Chronic beryllium disease: uncommon disease, less common diagnosis.

Chronic beryllium disease (CBD) is typically considered only when occupational exposure to beryllium is a certainty; however, CBD has also occurred in occupational and environmental settings where exposure was unexpected. When the etiology of a case of granulomatous pulmonary disease is not determined, sarcoidosis is the "diagnosis of exclusion." This diagnosis does not communicate much information about the patient's prognosis, the disease's etiology, or even what disease etiologies were specifically excluded. Some cases of CBD have been called sarcoidosis, allowing exposure to continue for the patient and (at times) other individuals. The granulomatous changes of sarcoidosis are thought to result from an abnormal immune response. While the etiologic agents that can initiate this response are largely unknown, the immunopathogenesis of CBD has been well described, and laboratory methods are available in a few centers that can (if used) identify beryllium hypersensitivity. The potential for exposure and disease to be widely separated in time and location makes it important for health-care and environmental health professionals to be aware of these new diagnostic methods.

A Case of Concomitant Tuberculosis and Sarcoidosis With Mycobacterial DNA Present in the Sarcoid Lesion

A 35-year-old Chinese woman initially presented with histologically and bacteriologically confirmed tuberculous lymphadenitis. She was also found to have thrombocytopenia, elevated serum alkaline phosphatase, and bilateral lung infiltrates. After 15 months of antituberculosis treatment, despite resolution of the cervical lymphadenopathy, she started to experience dyspnea. Chest radiograph appearance, thrombocyte count, and liver biochemistry had all deteriorated as well. Histologic findings from tissues obtained via transbronchial biopsy and open lung biopsy were consistent with sarcoidosis but also showed the presence of mycobacterial DNA by the polymerase chain reaction. She subsequently achieved a very good response clinically, radiographically, hematologically, and biochemically with 1-year of corticosteroid treatment for her sarcoidosis, and she remained relapse-free afterwards. The concomitant presence of tuberculosis and sarcoidosis in this patient together with the presence of mycobacterial DNA in the sarcoid lesion reiterate the possibility that mycobacteria or some of its components may be capable of inducing the immune response and the pathologic changes of sarcoidosis.

The evolutional stage changes in sarcoidosis on gallium-67 scintigraphy.

Gallium-67 scintigraphy has been proven as the imaging modality of choice in monitoring the presence of active disease in sarcoidosis. The purpose of this study is to analyze the patterns of evolutional stage changes of sarcoidosis while on steroid therapy by Ga-67 scintigraphy. Eighty-six consecutive patients with biopsy-proved sarcoidosis are evaluated by Ga-67 scintigraphy. Thirty-six of 86 patients have had a baseline and one to eight follow-up Ga-67 scintigraphs (total 136 studies). The initial follow-up scintigraphs are obtained on average about 4-12 months after the baseline study. Seventeen of 36 patients (47.2%) are in stage IV at the time of the baseline study. Following their first course of corticosteroid therapy, 13 patients remained in the same stage and activity distribution pattern while 13 patients have shown reversion to other stages, eight patients showed complete remission while two patients became active from inactive stage. Evolutional stage changes are seen in 23 patients (63.9%), including eight patients (22.2%) who showed complete scintigraphic remission. The evolutionary stage changes remain quite variable and unpredictable. This, however, should not detract from the usefulness of Ga-67 scintigraphy in the diagnosis and prognostic evaluation of sarcoidosis, particularly when extrapulmonary involvement (Stage IV disease) is present.

Microheterogeneity of acute-phase glycoproteins in patients with pulmonary sarcoidosis.

This study was designed to investigate qualitative changes in the carbohydrate side-chains of two acute-phase glycoproteins, alpha 1-acid glycoprotein (AGP) and alpha 1-antichymotrypsin (ACT), in 37 patients with pulmonary sarcoidosis. The glycosylation profile of AGP and ACT was studied using affinity immunoelectrophoresis with the lectin concanavalin A (conA). Serum concentration of soluble receptor for interleukin-2 (sIL-2R) and activity of serum angiotensin converting enzyme (ACE) were measured by specific enzyme-linked immunosorbent assay (ELISA) and enzyme kinetic assay, respectively. Rocket immunoelectrophoresis and nephelometric assay were used to determine serum concentration of AGP, ACT and C-reactive protein (CRP). In 11 patients with active disease, a decreased reactivity of AGP with conA was found as compared with controls (n = 44) and patients with nonactive sarcoidosis (n = 26). A similar tendency was seen with ACT. In the same group, increased concentrations of serum AGP and higher levels of sIL-2R were detected compared with patients with nonactive sarcoidosis. In the entire sarcoidosis group, there was a negative correlation between ACE activity and AGP and ACT affinity for conA (r = -0.6358, and r = -0.5019, respectively) and a positive correlation with sIL-2R level (r = 0.8241). In nine patients with elevated concentrations of serum CRP, no differences were found in disease activity and glycosylation profile of AGP and ACT when compared to patients with normal serum CRP. The results suggest that in active pulmonary sarcoidosis changes in the glycosylation pattern of acute-phase glycoproteins exist, which are similar in trend and magnitude to those found in other chronic inflammatory diseases. The synthesis and glycosylation of acute-phase proteins in pulmonary sarcoidosis are probably regulated independently.

Systemic and lung protein changes in sarcoidosis. Lymphocyte counts, gallium uptake values, and serum angiotensin-converting enzyme levels may reflect different aspects of disease activity.

BAL lymphocyte percentages, quantitated gallium-67 lung uptake, and SACE levels have all been proposed as measures of disease activity in sarcoidosis. We analyzed 32 paired sera and BAL fluids from sarcoidosis patients by high-resolution agarose electrophoresis to look for protein changes characteristic of systemic or local inflammation and compared the results with those from the above tests. Nine patients (group 1) had serum inflammatory protein changes and increased total protein, albumin, beta 1-globulin (transferrin), and gamma-globulin levels in fluid recovered by BAL. Thirteen patients (group 2) had normal protein levels in sera but abnormal protein levels in BAL specimens. Ten patients (group 3) had normal protein levels in sera and in BAL specimens. Patients in groups 1 and 2 had a disproportionate increase in beta 1-globulin (transferrin) and gamma-globulin levels in their BAL specimens. The BAL lymphocyte percentage changes paralleled the BAL protein level changes, suggesting relationships among the immunoregulatory role of these cells, increased local immunoglobulin synthesis, and the pathogenesis of altered alveolar permeability. Gallium-67 uptake was highest in patients with serum inflammatory protein changes. Thus, systemic inflammation may facilitate pulmonary gallium-67 uptake, possibly by changes in BAL fluid or serum transferrin saturation and/or kinetics. SACE levels showed no relationship to changes in the levels of serum or BAL proteins. These data suggest that the various proposed measures of disease activity reflect different aspects of inflammation in sarcoidosis.

Indices of inflammatory cell activity and pulmonary function in different stages of sarcoidosis.

The present study was carried out to compare radiological and physiological changes in sarcoidosis with biochemical markers for inflammatory cell populations. Of 53 patients with sarcoidosis, 28 had respiratory symptoms and 30 past or present bilateral hilar adenopathy without symptoms. A clinical score based on lung function tests and radiological findings correlated well with elevations of lysozyme and beta2-microglobulin in serum, indicating increased inflammatory cell activity in patients with more severe lung affection. A covariation between beta2-microglobulin and lysozyme was found, suggesting concomitant activation of macrophages and lymphocytes in sarcoidosis. Serum levels of lactoferrin were elevated in patients with a disease of short duration but did not correlate with the severity of the lung affection. The closing volume also seems to be abnormal in the early course of the disease, while elevated lysozyme and beta2-microglobulin levels rather seem to reflect the extent of the pulmonary affection.

Computed Tomography in Pulmonary Sarcoidosis

A group of 34 proven cases of pulmonary sarcoidosis was investigated by computed tomography (CT) to determine whether CT provided any information beyond that obtained from conventional chest films. Computed tomography disclosed a surprisingly high prevalence of minor pleural changes in sarcoidosis, including two patients with small pleural effusions. Unsuspected bullae and isolated "granulomatous" nodules were additionally demonstrated. Increases in lung density and alterations in gravity dependent vascular perfusion were assessed; these may reflect alterations in the vascular bed, and the increased density is possibly due to diffuse invasion of the lung not recognizable by conventional chest X-ray films. Tracheal compression was noted in one case and vertebral densities in three. Prominence of "small air spaces" was recorded in four patients; the nature of the pathology responsible for this finding is at present speculative. While not replacing conventional chest radiography, CT does make a definite contribution to the assessment of pulmonary sarcoidosis.

ÜBER DIE MYOKARDSARKOIDOSE—PATHOLOGISCHE UNTERSUCHUNGEN AN 7 SEKTIONSFÄLLEN UNTER BESONDERER BERÜCKSICHTIGUNG DER HISTOLOGISCHEN VARIATIONEN

The present report consists of seven autopsy cases of myocardial sarcoidosis terminating in death 1 month to 5 years after the onset of symptoms. Histologically, they were classified into the following 4 types: a) diase nonspeciflc Branulation, b) specific granuloma with giant cells, c) diffuse fibrosis with giant cells, and d) nonspeciflc fibrosis. Types a) and b) demonstrate active changes, while c) and d) are sequelae of active inflammation. Morphological changes of sarcoidosis were found not only in myocardium but also in both pericardum and endocardium. Although no Anal conclusions could be obtained as to whether the giant cells appearing in myocardium were of mesenchymal or myogenic origin, the authors favor the latter concept. Changes compatible to sarcoidosis found in other organs in acute cases were scarce and old. On the contrary, more active and variable changes were encountered in protracted cases. The authors consider giant cell myocarditie to be one type of sarcoidosis occurring in the heart.

Pulmonary Sarcoidosis: The Early Roentgen Findings

The pulmonary changes in sarcoidosis are now recognized as constituting one of the most conspicuous manifestations of this bizarre and no longer rare disease. They are usually described as being of one of the following types: (a) lymph node enlargement, (b) miliary or nodular lung densities, or (c) a combination of nodal enlargement and pulmonary infiltration. Are there any particular lesions suggestive or characteristic of early pulmonary sarcoid disease? In an attempt to determine this point, we studied a series of cases of sarcoidosis which we have been privileged to see during the last several years (33 of which were proved by biopsy or necropsy) and reviewed much of the now voluminous literature on the subject. Since sarcoidosis is a disease of protean manifestations and constant changeability, we believe it will be well to consider briefly its salient features before analyzing the purely pulmonic aspects. Clinical Aspects of Sarcoidosis Sarcoidosis is a generalized disease of unknown origin, in which characteristic histologic changes are found in different organs and tissues (17, 19). It is usually of insidious onset and tends to run a chronic, relapsing course. Fairly mild constitutional symptoms are manifested in most cases, and quite severe, even fatal, signs in a few. It is discovered most commonly between the ages of twenty and thirty years, but cases have been reported in patients as young as two months (19) and as old as eighty years (11). It may develop in persons of any race, but seems to occur with somewhat greater frequency in Negroes than in others (12, 13, 14). Although a widespread, disseminated disease, it is often observed in a phase when involvement of only one system is apparent; for example, lesions of the skin, the eyes, or the lungs. The clinical picture varies from case to case, and from time to time in the same case. The victims may have no complaint or may complain of fever, fatigue, or slight dyspnea. Peripheral lymphadenopathy is present at some stage of the disease in about 90 per cent of cases, the nodes being painless, discrete, and movable. Pulmonary involvement (parenchymal or nodal) occurs in a similar percentage of cases. Cutaneous and ocular lesions are seen in about 40 per cent of cases. The usual skin lesions are described as sharply defined, brownish nodules (cutaneous or subcutaneous) distributed over the face or extremities (12). The common ocular finding is a chronic bilateral granulomatous iritis, or iridocyclitis, without much redness or pain. This may regress spontaneously or progress to complete blindness. Hepatomegaly and splenomegaly are fairly frequent. Cardiac and pericardial involvement has been noted. As in Hodgkin's disease, any tissue or structure can be invaded. Infiltration of the salivary apparatus may lead to “Mikulicz's disease,” and of the parotid glands and eyes to “uveo-parotid fever.”