Sarcoidosis is an inflammatory disease characterised by enhanced production of reactive oxygen species and alterations in the circulating lipid profile. Both attributes are thought to play a role in ...its pathogenesis. However, current knowledge regarding the significance of blood oxidative stress/anti-oxidant defence as well as alterations in lipid status parameters in sarcoidosis is scarce. The aim of our study was to assess these parameters and their inter-relationships, as well as their potential for patient-control discrimination.
Oxidative stress status and anti-oxidant defence parameters were determined in serum and erythrocytes and lipid status parameters were assessed in the serum of 213 treated sarcoidosis patients and 90 controls.
Malondialdehyde, superoxide anion, total oxidant status, prooxidant–antioxidant balance and triglycerides were significantly higher whereas total anti-oxidant status, superoxide dismutase activity and HDL-cholesterol were significantly lower in sarcoidosis patients compared with controls. Total sulfhydryl group content was higher in patients compared with controls. Serum and erythrocyte malondialdehyde exhibited the strongest ability to predict disease presence. Elevated oxidative stress was characterised by higher clinical accuracy compared with lipid status abnormality. Some oxidative stress and lipid status markers were significantly associated in sarcoidosis.
Sarcoidosis is characterised by increased oxidative stress, diminished overall anti-oxidative protection and alterations in the circulating lipid profile. Both oxidative stress and lipid status parameters demonstrated the potential to discriminate sarcoidosis from controls which was particularly evident from the point of view of oxidative stress status parameters. Association between these parameters may indicate an increased risk for atherosclerosis development.
► Elevated serum and erythrocyte oxidative stress status were observed in sarcoidosis. ► Lipid status abnormality was noted in sarcoidosis. ► Serum and erythrocyte MDA strongly predict disease among oxidative stress markers. ► Serum oxidative stress parameters had the best discriminative potential. ► Connection between oxidative and lipid status may indicate risk for atherosclerosis.
Respiratory tract involvement occurs at some time during the course of most patients with sarcoidosis. There are many articles on lung function impairment in sarcoidosis, but the definite, unique ...guideline considering the correlation between the clinical, radiologic, and biochemical findings of the disease is lacking. During the last few years, most of the literature has focused on follow-up studies, presenting primarily the effects of the treatment on lung function impairment in patients with sarcoidosis. This study focuses on airflow impairment, diffusion impairment, and bronchial hyperresponsiveness in sarcoidosis. The topic has already been explored, but this time the authors emphasize lung function impairment and its correlation with the course of the disease. Considering the course of sarcoidosis, a significantly higher number of patients with diffusion impairment have the chronic form of the disease. The bronchial challenge test (BCT) was performed in patients with chronic sarcoidosis at the time they experienced relapse of disease activity. A high number of patients with positive BCT is significant in light of their disease. Further analyses, not only functional, but immunologic, are necessary to examine the potential correlation between positive BCT and the activity of sarcoidosis.
Summary 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 George's 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.
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
(rs10741657),
(rs10877012),
(rs7041; rs4588), and
(rs2228570
genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients.
For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method.
Subjects carrying the CC genotype of
rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover,
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
gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients.
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.
The decision for treating patients with chronic systemic sarcoidosis is often difficult and controversial. Methotrexate (MTX) has been used to treat patients with chronic forms of the disease for ...years, although prospective, randomized studies assessing the efficacy and toxicity of this agent are lacking. This is the follow-up study of 91 patients with the chronic form of pulmonary and extrapulmonary sarcoidosis who were treated with MTX. All patients experienced treatment with corticosteroids before they were administered MTX. Most of the patients treated with MTX showed improvement on chest radiographs, lung function tests, and extrapulmonary signs of the disease 6 months after the treatment began. No side effects that would cause the patients to discontinue the treatment were observed.
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.
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.
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.
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.
Matrix metaloproteinases (MMPs) and their specific inhibitors - tissue inhibitors of matrix metalloproteinases (TIMPs) play an important role in pulmonary extracellular matrix destruction. ...Sarcoidosis is an inflammatory disease affecting multiple organs. It has been reported that MMP-9 and TIMP-1 levels were increased in bronchoalveolar lavage fluid and induced sputum of sarcoidosis patients. The aim of our study was to evaluate MMP-9, TIMP-1 and MMP-9/TIMP-1 complex concentrations and MMP-9/TIMP-1 ratio in sarcoidosis patients, their relationship with inflammatory markers and their ability do predict the existence of disease. We included 101 sarcoidosis patients and 50 healthy subjects. Serum samples were analyzed. Besides routine biochemical parameters, high-sensitive C-reactive protein (hsCRP), serum amyloid A (SAA), MMP-9, TIMP-1 and MMP-9/TIMP-1 complex concentrations were measured. MMP-9 (P<0.05), hsCRP, SAA and TIMP-1 (P<0.001) concentrations were significantly increased in patients whereas MMP-9/TIMP-1 complex was higher in patients, but with marginal significance. In sarcoidosis, TIMP-1 correlated significantly positively with inflammatory parameters (P<0.05). Uni-variate analysis showed that MMP-9, TIMP-1, hsCRP and SAA had the ability to predict the existence of sarcoidosis. In the model consisted of MMP- 9, TIMP-1, hsCRP and SAA, only SAA remained significant predictor of disease (P<0.01). Results showed the significance of MMP-9 and TIMP-1 in sarcoidosis.
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