Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission.

The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.

King's Sarcoidosis Questionnaire (KSQ) - Validation study in Serbian speaking population of sarcoidosis patients.

INTRODUCTION: Sarcoidosis is a multiorgan, multisystem chronic disease of unknown etiology and unpredictable course. Health status is reduced in sarcoidosis and assessing it is a difficult multitask effort due to many faces this disease might have. Recently, a new questionnaire for assessing health status in sarcoidosis was developed by a group of authors from England-King's Sarcoidosis Questionnaire (KSQ). The benefit of KSQ is the ability to develop the best care plan for the patient, as well as to differentiate the efficacy of the administered treatment. OBJECTIVE: The aim of this study was to validate the KSQ in Serbian speaking population of sarcoidosis patients. The test itself is a modular, multi-organ health status measure for patients with sarcoidosis for use in clinic and the evaluation of therapies. The correlation of KSQ with different clinical course of sarcoidosis (acute vs chronic disease) and with the clinical outcome status (COS) in sarcoidosis was also investigated. METHODS: A total of 159 biopsy positive sarcoidosis patients participated in this study. The average age of the participants was 49.67, majority was female (67.3%) and majority had only pulmonary form of sarcoidosis (71.7%). KSQ - new disease-specific health status instrument, was compared with 5 other already existing instruments already used and validated in sarcoidosis (Saint George Respiratory Questionnaire- SGRQ, Daily Activity List -DAL, Fatigue Assessment Scale- FAS, Medical Research Council dyspnea scale-MRC, Borg Dyspnea Scale and 15D as general questionnaire. RESULTS: KSQ has significant correlation with other quality of life questionnaires already used in sarcoidosis. Translated version of KSQ shows significant internal reliability, similar to the original KSQ. Serbian version of KSQ has significant correlation with different clinical course of sarcoidosis and with COS as well. The translated version of KSQ is reliable sarcoidosis specific instrument for assessing health status in these patients.

Genetic and geographic influence on phenotypic variation in European sarcoidosis patients.

Introduction: Sarcoidosis is a highly variable disease in terms of organ involvement, type of onset and course. Associations of genetic polymorphisms with sarcoidosis phenotypes have been observed and suggest genetic signatures. Methods: After obtaining a positive vote of the competent ethics committee we genotyped 1909 patients of the deeply phenotyped Genetic-Phenotype Relationship in Sarcoidosis (GenPhenReSa) cohort of 31 European centers in 12 countries with 116 potentially disease-relevant single-nucleotide polymorphisms (SNPs). Using a meta-analysis, we investigated the association of relevant phenotypes (acute vs. sub-acute onset, phenotypes of organ involvement, specific organ involvements, and specific symptoms) with genetic markers. Subgroups were built on the basis of geographical, clinical and hospital provision considerations. Results: In the meta-analysis of the full cohort, there was no significant genetic association with any considered phenotype after correcting for multiple testing. In the largest sub-cohort (Serbia), we confirmed the known association of acute onset with TNF and reported a new association of acute onset an HLA polymorphism. Multi-locus models with sets of three SNPs in different genes showed strong associations with the acute onset phenotype in Serbia and Lublin (Poland) demonstrating potential region-specific genetic links with clinical features, including recently described phenotypes of organ involvement. Discussion: The observed associations between genetic variants and sarcoidosis phenotypes in subgroups suggest that gene-environment-interactions may influence the clinical phenotype. In addition, we show that two different sets of genetic variants are permissive for the same phenotype of acute disease only in two geographic subcohorts pointing to interactions of genetic signatures with different local environmental factors. Our results represent an important step towards understanding the genetic architecture of sarcoidosis.

Rotational thromboelastometry (ROTEM) profiling of COVID-19 patients.

We evaluated coagulation abnormalities via traditional tests and rotational thromboelastometry (ROTEM) in a group of 94 patients with confirmed SARS-CoV-2 infection and different severity of pneumonia (34 moderate, 25 severe, 35 critical) with the hypothesis that ROTEM parameters differed by coronavirus disease 2019 (COVID-19) severity. Shorter than normal clotting time (CT) and higher than normal maximum clot firmness (MCF) in extrinsic rotational thromboelastometry (EXTEM) and fibrinogen rotational thromboelastometry (FIBTEM), shorter than normal EXTEM clot formation time (CFT), and higher than normal α-angle were classified as markers of hypercoagulable state. Increment in the number of patients with ≥2 hypercoagulable parameters, higher EXTEM (P = .0001), FIBTEM MCF (P = .0001) and maximum lysis decrement (P = .002) with increment in disease severity was observed (P = .0001). Significant positive correlations between IL6 and CT EXTEM (P = .003), MCF EXTEM (P = .033), MCF FIBTEM (P = .01), and negative with ML EXTEM (P = .006) were seen. Our findings based on analysis of different disease severity groups confirmed that a hypercoagulable ROTEM pattern characterized by clot formation acceleration, high clot strength, and reduced fibrinolysis was more frequent in advanced disease groups and patients with high IL6. These results supported the need for different thromboprophylaxis approaches for different severity groups.

Predictors of cough-specific and generic quality of life in sarcoidosis patients.

BACKGROUND: Cough is frequent symptom in sarcoidosis and its impact on patient's quality of life (QoL) has not been adequately addressed so far. OBJECTIVES: The goal of this study was to determine the significant predictors of cough-specific and generic QoL in sarcoidosis patients. METHODS: In the prospective study 275 sarcoidosis patients administered Patient Reported Outcomes instruments for measurement of dyspnea (Borg and MRC scales) and fatigue (Fatigue Assessment Scale (FAS) and Daily Activity List (DAL)), as well as patients' QoL (cough-specific Leicester Cough Questionnaire (LCQ) and generic tool - 15D). The LCQ contains 3 domains covering physical, psychological and social aspects of chronic cough. Pulmonary function tests (spirometry and diffusing capacity for carbon monoxide) and serum angiotensin converting enzyme (sACE) were also measured. RESULTS: Dyspnea measured by Borg scale and impairment of daily activities determined by DAL instrument as well as sACE were the strongest predictors of all cough-specific QoL domains. Mental aspect of patients' fatigue was significantly correlated with all domains except with psychological LCQ domain. Regarding the generic QoL, the following significant predictors were: dyspnea measured by MRC scale, overall fatigue determined by FAS and physical domain of the LCQ. CONCLUSION: It is important to measure both cough-specific and generic QoL in sarcoidosis patients since they measure different health aspects and their predictors can be different. We demonstrated that physical domain of cough-specific QoL is significant predictor of generic QoL. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 158-168).

Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers.

INTRODUCTION: Sarcoidosis is a rare multisystem granulomatous disease with unknown etiology. The interplay of vitamin D deficiency and genetic polymorphisms in genes coding for the proteins relevant for metabolism of vitamin D is an important, but unexplored area. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in CYP2R1 (rs10741657), CYP27B1 (rs10877012), DBP (rs7041; rs4588), and VDR (rs2228570) genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients. MATERIAL AND METHODS: For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method. RESULTS: Subjects carrying the CC genotype of CYP27B1 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, DBP rs4588 AA genotype was shown to be a susceptibility factor, where carriers of this genotype had eight times higher odds for developing sarcoidosis. In addition, the A allele of the DBP gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients. CONCLUSIONS: These results suggest that patients with vitamin D deficiency should be regularly tested for genetic modifiers that are related to sarcoidosis in order to prevent development of serious forms of sarcoidosis.

Tuberculosis outbreak among high school students in Novi Pazar, Serbia 2016: a retrospective-cohort study.

INTRODUCTION: Between February and November 2016, 17 tuberculosis (TB) cases were identified among high school students in Novi Pazar, Serbia. The objectives of our study were to describe the outbreak, to identify potential risk factors and to evaluate the applied control measures. METHODOLOGY: The outbreak was described by time, person and place. A retrospective cohort study was conducted. Attack rates, unadjusted relative risks (RR) and 95% confidence intervals (CI) were calculated. Multiple log-binomial regression analysis was performed to calculate adjusted RR. RESULTS: Sixteen of the total 17 cases occurred among grade 3 students, AR 5.5%. Previous TB family history, (RR = 5.29; 95% CI = 1.63-17.12), spending time with a known TB case at school (RR = 5.38; 95% CI = 1.48-19.55) and exposure to secondhand smoke (RR = 3.37; 95% CI = 1.11-10.29) were all significantly and independently associated with the occurrence of TB. CONCLUSIONS: Delayed diagnosis and reporting resulted in delayed initiation of the contact investigation and non-identification of latent TB cases probably favored the occurrence of this outbreak in a low incidence country. Public health authorities should consider revising the existing guidelines, promoting inter-sectorial collaboration and increasing awareness of public health professionals.

Patient, Healthcare System and Total Delay in Tuberculosis Diagnosis and Treatment Among Serbian Population.

Currently, topical are studies that examine different reasons for delay of tuberculosis (TB) diagnosis and its impact on disease prognosis. The aim was to examine three time periods associated with treatment delay: patient related, health system related and total delay. This retrospective-prospective study included 100 consecutive patients hospitalized at Department of Pulmonology, Clinical Center of Serbia, in the period from March to December 2015. Study results showed median patient delay to be 92.5 days. Total delay was affected by patient related delay. Median healthcare delay was 18.5 days. Patients that reported excessive alcohol consumption were more likely to have prolonged time to seek medical help. Years of alcohol consumption yielded moderate positive correlation with patient related delay (r=0.362, p <0.001). Correlation between the number of cigarettes and patient delay was moderate, positive and statistically significant (r=0.314, p=0.001). Delay in seeking medical help was more likely in patients with negative family history of TB. There was no difference in the effect of the presence of symptoms on patient related delay (p>0.05). Clinical characteristics such as patient TB category and chest radiograph abnormalities were not associated with prolonged patient related delay (p>0.05). Study results point to the importance of health education and/or health intervention in the population group at a high risk of TB.

Phenotypes of organ involvement in sarcoidosis.

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.

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.

Clinical Features of Ocular Sarcoidosis in Patients with Biopsy-proven Pulmonary Sarcoidosis in Serbia.

PURPOSE: To analyze clinical characteristics of ocular sarcoidosis in a group of biopsy-proven sarcoid patients treated at the single referral center for sarcoidosis in Serbia. METHODS: A prospective study carried out on 88 biopsy-proven sarcoid patients between January 2012 and December 2014. All patients underwent complete ophthalmological examination. RESULTS: Ocular sarcoidosis was present in 32 patients (36.4% of all) and included: eyelid skin lesions (2.3%); orbital inflammation (2.3%); conjunctival lesions (7.9%); anterior uveitis (2.3%); intermediate uveitis (1.1%); posterior uveitis (15.9%); panuveitis (5.7%), and neuro-ophthalmologic manifestations (9.1%). Complications included cataract (20.4%); glaucoma (5.7%); cystoid macular edema (3.4%); epiretinal membrane formation (4.5%); macular atrophy (2.3%); and choroidal neovascularization (1.1%). Binocular visual impairment was present in one patient (1.1%), due to complications of posterior uveitis (macular scars). CONCLUSIONS: Patients in Serbia demonstrated ocular sarcoidosis as the first most common site of extrapulmonary sarcoid manifestations, with more often neuro-ophthalmologic lesions than in other European populations.

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.

Verifying Sarcoidosis Activity: Chitotriosidase versus ACE in Sarcoidosis - a Case-control Study.

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 .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.

Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk.

RATIONALE: Genetic variation plays a significant role in the etiology of sarcoidosis. However, only a small fraction of its heritability has been explained so far. OBJECTIVES: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. METHODS: Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1,726 German sarcoidosis cases and 5,482 control subjects were genotyped for 128,705 single-nucleotide polymorphisms using the Illumina Immunochip for the screening step. The remaining 3,955 cases, 7,514 control subjects, and 684 parents of affected offspring were used for validation and replication of 44 candidate and two established risk single-nucleotide polymorphisms. MEASUREMENTS AND MAIN RESULTS: Four novel susceptibility loci were identified with genome-wide significance in the European case-control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1), and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA-DPB1 (rs9277542), and found another novel independent signal near IL23R (rs12069782) on chromosome 1p31.3. CONCLUSIONS: Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17 signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics.

Treatment of neurosarcoidosis--innovations and challenges.

INTRODUCTION: Sarcoidosis affects the central nervous system more frequently than it used to be believed. While the cranial nerves are most frequently affected, neurosarcoidosis can involve other nervous system tissues as well. TREATMENT OF NEUROSARCOIDOSIS: Although a lot of drugs have proved useful in treating neurosarcoidosis, corticosteroids are still the gold standard in treatment of these patients. Therapeutic protocols differ regarding the dose of these drugs. Symptomatic neurosarcoidosis should always be treated with pulse corticosteroid therapy. People with diabetes, high blood pressure, osteoporosis and tuberculosis should be carefully monitored, as they are prone to complications associated with treatment with corticosteroids. In cases when treatment with corticosteroids does not show the desired results or therapy is discontinued due to the development of side effects, there are other pharmacologic options, such as methotrexate, mycophenolate mofetil, cyclophosphamide, chloroquine, azathioprine, thalidomide, and infliximab. It should be noted that the treatment response to the above mentioned regimens, except for infliximab, is relatively slow compared to corticosteroids; therefore, corticosteroids should be taken into account in all states and particularly in the acute phase of the disease. CONCLUSION: It is the existence of different forms of the disease, lack of local diagnostic criteria and different and non standardized therapy that makes the treatment of this disease difficult. Despite advances in pharmacotherapy and radiological diagnosis, it is necessary to develop better diagnostic strategies in order to set the optimal therapeutic approach.

Diagnosis of neurosarcoidosis--necessity of biopsy.

INTRODUCTION: Sarcoidosis can affect any part of the central nervous system presenting with an extremely diverse clinical picture. Clinical presentations actually depend on the localization ofgranulomas in the central nervous system. Making diagnosis according to the localization and the clinical variations is often a clinical challenge. DIAGNOSIS OF NEUROSARCOIDOSIS: Diagnosis is based on the clinical picture, clinical and radiological findings (magnetic resonance imaging with contrast endocranium), laboratory findings (angio-tenzin-converting enzyme and chitotriosidase in cerebrospinal fluid); however, it is necessary first to exclude all other possible causes of granulomatous inflammation. Recent studies in patients with neurosarcoidosis show a high value of at least one marker of the disease. The safest way and the gold standard in diagnosing this disease would be histopathological confirmation, which is rarely performed due to its invasiveness. CONCLUSION: New diagnostic methods will contribute to better methods of bypassing invasive procedures, and they will significantly facilitate the diagnosis of neurosarcoidosis, which is a real challenge even for experienced clinicians who deal with this disease.

Radiological presentation of neurosarcoidosis.

INTRODUCTION: In diagnostics of neurosarcoidosis, radiological diagnostic procedures are available, non-invasive and they contribute significantly to the diagnosis of this disease. The aim of this paper is to present a brief overview of the radiological diagnostic methods, their application, and their importance in daily clinical work with these patients. RADIOLOGICAL PRESENTATION OF NEUROSARCOIDOSIS: Magnetic resonance is the method of choice in diagnostics of this disease. Computed tomography can also be helpful in patients with contraindications for magnetic resonance, although it is less precise in assessing the involvement of the periventricular white matter, hypothalamus, and cranial nerves. The number of lesions and the degree of involvement of the parenchyma and leptomeninges are better seen by magnetic resonance than by computed tomography scan. It is important to note that the magnetic resonance imaging may be normal in patients with neurosarcoidosis, especially in patients with cranial neuropathy, or in patients treated with corticosteroids. There is a number of variability in the occurrence of neurosarcoidosis on radiological images. CONCLUSION: Radiological procedures are on the very top of diagnostic pyramid of this disease due to their availability, non-invasiveness, and precision.

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 patient's 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.

Sarcoidosis of the pleura--A case report.

INTRODUCTION: Pleural involvement is an uncommon manifestation of sarcoidosis. It may manifest as pleural effusion, pneumothorax, pleural thickening and nodules, hydropneumothorax, trapped lung, hemothorax, or chylothorax. The incidence of pleural effusion with sarcoidosis ranges from 0% to 5% but has been reported to be as high as 7.5%. Pleural effusions complicate sarcoidosis in < 3% of patients. CASE REPORT: We reported a 64-year-old male patient with chronic multiorgan sarcoidosis. This patient developed pleural sarcoidosis with massive pleural effusion several years after the diagnosis of sarcoidosis. A definitive diagnosis of a sarcoid pleural effusion was based on a biopsy demonstrating noncaseating granuloma. The patient responded well to the treatment (methotrexate and methylprednisolone) with a complete withdrawal of pleural effusion following five weeks of the treatment beginning. CONCLUSION: The presented patient is a rare case of pleural involvement of sarcoidosis with massive effusion, who responded well to the treatment.