Violeta Mihailovic-Vucinic

Differences in symptom severity and health status impairment between patients with pulmonary and pulmonary plus extrapulmonary sarcoidosis

BACKGROUND Although sarcoidosis most commonly affects the lungs, it is a multisystemic disease that often involves other organs. In this study, we compared fatigue, dyspnea, and the impact upon the activities of daily living and health status scores between patients with isolated pulmonary and pulmonary plus extrapulmonary sarcoidosis. METHODS In this cross-sectional study, we investigated 81 biopsy proven sarcoidosis patients. Fatigue was assessed by the standardized Fatigue Scale (FS). Dyspnea was determined by the Baseline Dyspnea Index (BDI) and the Modified Medical Research Council (MRC) Dyspnea Scale. Activities of daily living were assessed with the List of Daily Activities (DAL). Health status was measured by two standardized questionnaires: a generic measure--fifteen-dimensional measure of health-related quality of life (15D), and a respiratory-specific measure--St Georges Respiratory Questionnaire (SGRQ). Patients were excluded if they had an associated illness that could influence their health status. RESULTS Statistically significant differences were demonstrated between the isolated pulmonary group and the pulmonary plus extrapulmonary group for fatigue (FS-total score: 2.4+/-0.64 vs. 2.8+/-0.62, p=0.007), dyspnea (BDI: 8.45+/-2.44 vs. 5.92+/-1.84, p<0.001; there was no statistically significant difference in MRC), activities of daily living (DAL: 4.33+/-2.93 vs. 5.87+/-2.40, p=0.014), and health status (SGRQ-total score: 33.07+/-22.81 vs. 43.69+/-21.55, p=0.04). CONCLUSION There are significant and clinically relevant differences in the severity of symptoms, restrictions of activities of daily living and impairment of health status between the patients with isolated pulmonary and pulmonary plus extrapulmonary sarcoidosis. Patients with pulmonary plus extrapulmonary sarcoidosis are more impaired in all these categories.

Verifying Sarcoidosis Activity: Chitotriosidase Versus ACE in Sarcoidosis – A Case-Control Study

Summary Background: Until now, a proper biomarker(s) to evaluate sarcoidosis activity has not been recognized. The aims of this study were to evaluate the sensitivity and specificity of the two biomarkers of sarcoidosis activity already in use (serum angiotensin converting enzyme – ACE and serum chitotriosidase) in a population of 430 sarcoidosis patients. The activities of these markers were also analyzed in a group of 264 healthy controls. Methods: Four hundred and thirty biopsy positive sarcoidosis patients were divided into groups with active and inactive disease, and groups with acute or chronic disease. In a subgroup of 55 sarcoidosis patients, activity was also assessed by F-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis. Results: Serum chitotriosidase activities were almost 6 times higher in patients with active sarcoidosis than in healthy controls and inactive disease. A serum chitotriosidase value of 100 nmol/mL/h had the sensitivity of 82.5% and specificity of 70.0%. A serum ACE activity cutoff value of 32.0 U/L had the sensitivity of 66.0% and the specificity of 54%. A statistically significant correlation was obtained between the focal granulomatous activity detected on 18F-FDG PET/CT and serum chitotriosidase levels, but no such correlation was found with ACE. The levels of serum chitotriosidase activity significantly correlated with the disease duration (P<0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (ρ=0.272, P=0.001). Conclusions: Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.

Neurosarcoidosis: Two case reports with multiple cranial nerve involvement and review of the literature

BACKGROUND Involvement of the central nervous system is registered in a relatively small number of patients with sarcoidosis. In this article we present two cases with various neurological symptoms that fulfill criteria for neurosarcoidosis (NS). In addition, we review the literature on NS with special attention to isolated cranial nerve involvement. METHODS AND RESULTS First patient: Neurological examination identified multiple cranial neuropathy, moderate right-sided hemiparesis, polyradiculoneuritis of the lower limbs and positive meningeal signs. Laboratory tests showed serum and cerebrospinal fluid (CSF) inflammatory abnormalities, with increased values of the angiotensin-converting enzyme (ACE). CSF analysis also showed presence of 9 oligoclonal IgG bands. Brain and spine magnetic resonance imaging (MRI) revealed diffuse meningopathy, and focal granulomatous lesion in the body of the L5 vertebra. Lung sarcoidosis was confirmed by additional diagnostic procedures. The patient was treated with Methylprednisolone and a tapering course of oral Prednisone, which reduced the pain in the back and legs and improved the strength of the right leg. However, the other neurological deficiencies remained. After confirming lung sarcoidosis, the patient received Methotrexate in addition to Prednisone but during the following 2 years the patients condition progressively worsened and ended in death. Second patient: Neurological findings showed weakness of the right n. oculomotorius and the right n. trochlearis, as well as the right-side face weakness. We found raised level of the ACE in serum and CSF. Thorax high-definition computed tomography (HDCTT) showed ribbon-like domains of discrete changes in the pulmonary parenchyma. MRI of the brain showed multiple white matter lesions. This patient also received Methylprednisolone followed by Prednisone, and after two months, ocular motility normalized. CONCLUSION The diagnosis of NS is always a challenge. For this rerason definitive diagnosis requires the exclusion of other causes of neuropathy. Multiple cranial neuropathies should always arouse suspicion of NS.

Utility of angiotensin-converting enzyme activity in aqueous humor in the diagnosis of ocular sarcoidosis

Purpose: Many studies include elevated activity of angiotensin-converting enzyme (ACE) in serum in sarcoidosis and in ocular sarcoidosis as well, but there are only a few analyzing ACE activities in aqueous humor. The aim of this study is to illuminate the diagnostic value of ACE in aqueous humor in patients with ocular sarcoidosis. Methods: We analyzed twenty patients with ocular sarcoidosis and 18 patients with nonocular involvement. All patients have biopsy-positive sarcoidosis of the lungs and/or mediastinal lymph nodes. Blood samples for ACE serum levels were obtained from all patients. Aqueous humor samples were taken by paracentesis with a 25-gauge needle in local anesthesia. With appropriate statistical tests, we compared ACE activity in serum and aqueous humor in patients with and without ocular sarcoidosis. Results: The majority of our patients with ocular sarcoidosis were female (12/20), also in the group with systemic sarcoidosis and without ocular involvement (12/6). Mean age of the whole analyzed group of sarcoidosis patients was 45 ± 6 years. There is no statistically significant difference in ACE activity in serum between two groups of patients (with and without ocular sarcoidosis). There is statistically significant difference in ACE activity in aqueous humor among patients with ocular and nonocular sarcoidosis. ACE activity in aqueous humor is significantly higher in patients with ocular sarcoidosis. Conclusion: Increased ACE activity in aqueous humor can point to a diagnosis of ocular sarcoidosis, without the need for ocular biopsy.

The Health Benefits of Vitamin D Relevant for Tuberculosis

Summary Vitamin D has an important role in numerous physiological functions. Vitamin D receptors are characterized by polymorphisms and presence in different tissues including a number of cells of the immune system. The role of vitamin D as a biological inhibitor of inflammatory hyperactivity is of particular importance. Hypovitaminosis D has been associated with many serious chronic diseases, such as autoimmune, infectious and cardiovascular diseases as well as some types of cancer. Vitamin D has an influence on the immune res ponse to tuberculosis. Calcitriol (1,25-dihydro xycholecalciferol), the major active form of vitamin D, has shown in vitro activity against Mycobacterium tuberculosis. It has been found that susceptibility to chronic mycobacterial infections is strongly correlated with a low vi tamin D intake and particular VDR alleles. Vitamin D deficiency might predispose the individuals infected with Myco bacterium tuberculosis to develop tu-ber culosis. Calcitriol binds to vitamin D receptors and modulates immune responses by regulating the transcription of genes responsive to vitamin D. Faster conversion of sputum mycobacterial culture in patients with pulmonary tuberculosis is associated with being a carrier of the t allele of the T a q I vitamin D receptor polymorphism. On the contrary, slower spu tum culture conversion in pulmonary tuberculosis has been found in the carriers of the f allele of the FokI vitamin D receptor polymorphism. The results of in vitro studies, clini-cal research and population studies indicated that vitamin D deficiency might be a strong risk factor for developing TB. Vitamin D is an inexpensive, easily accessible vitamin, relevant for the prevention of tuberculosis. In addition, vitamin D could contribute to the success of tuberculosis treatment.

Postponed diagnosis of alpha-1 antitrypsin deficiency

Milica Stojković-Lalošević1, Mihailo Stjepanović2, Nataša Čolović3,4, Jasmina Marić-Živković2, Violeta Mihailović-Vučinić2,3, Mirjana Stojković1,3 1Clinical Center of Serbia, Clinic of Gastroenterology and Hepatology, Belgrade, Serbia; 2Clinical Center of Serbia, Clinic of Pulmology, Belgrade, Serbia; 3University of Belgrade, School of Medicine, Belgrade, Serbia; 4Clinical Centre of Serbia, Clinic of Hematology, Belgrade, Serbia

Administering the Sarcoidosis Health Questionnaire to sarcoidosis patients in Serbia

Objective: The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. Methods: This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. Results: The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. Conclusions: The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients.

The 18F PET/CT scan in patients with chronic sarcoidosis

Introduction: Sarcoidosis is chronic systemic granulomatous disease most involving the lung.New markers of activity are important due to lack of sufficiently sensitive and specific .The aim : Performed 18F-FDG PET / CT scan in clinical problems of chronic sarcoidosis. Method: Previously histological obtained sarcoidosis are enrolled : 58 patients (mean age 54.4 ± 12 years ; 23 – 40% men and 35-60% women). PET scan performed and also after 20 months of finished therapy. Resuls: PET scan is verified inflammation in 54(93.1%)patients (SUVmax 8.84 ± 3.52). MDCT scan was positive in 49(84,48%) patients. Significant difference between the two methods not verified (p = 0.238, McNemar9s test).Spirometry findings:Ventilatory restriction is the main findings in 22 % and obstruction findings in 8 (14%) patients- age over 50 years with fibrotic chest ray findings. Markers of activity are higher in patients with positive findings on 18F-FDG PET / CT scan , compared to the group with negative results (p = 0.002, Mann-Whitney test). Specified group of 16( 28%) patients with positive PET but normal ACE and Ca in 24h urine,was obtained .Chitotriosidase levels significantly correlated with the findings of the 18F-FDG PET / CT scan in 57 patients. Logistic regression (univariate and multivariate) indicates significant correlation (p=0.001),positive PET scan findings and the modifying treatment. Control findings of PET scan after 14-22 months, obtaine reduction in SUV (8.84 vs.4.4) . Located SUV were significantly correlated with the subjective perception of the state of patients (P = 0.019). Conclusion: 18F-FDG PET / CT scan is the significant diagnostic method in determining the sites of inflammation in patients with chronic sarcoidosis.