Phenotypes of organ involvement in sarcoidosis Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena ...
The European respiratory journal,
01/2018, Letnik:
51, Številka:
1
Journal Article
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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.
Background. Solithromycin, a novel macrolide antibiotic with both intravenous and oral formulations dosed once daily, has completed 2 global phase 3 trials for treatment of community-acquired ...bacterial pneumonia. Methods. A total of 863 adults with community-acquired bacterial pneumonia (Pneumonia Outcomes Research Team PORT class II-IV) were randomized 1:1 to receive either intravenous-to-oral solithromycin or moxifloxacin for 7 once-daily doses. All patients received 400 mg intravenously on day 1 and were permitted to switch to oral dosing when clinically indicated. The primary objective was to demonstrate noninferiority (10% margin) of solithromycin to moxifloxacin in achievement of early clinical response (ECR) assessed 3 days after first dose in the intent-to-treat (ITT) population. Secondary endpoints included demonstrating noninferiority in ECR in the microbiological ITT population (micro-ITT) and determination of investigator-assessed success rates at the short-term follow-up (SFU) visit 5-10 days posttherapy. Results. In the ITT population, 79.3% of solithromycin patients and 79.7% of moxifloxacin patients achieved ECR (treatment difference, –0.46; 95% confidence interval CI, –6.1 to 5.2). In the micro-ITT population, 80.3% of solithromycin patients and 79.1% of moxifloxacin patients achieved ECR (treatment difference, 1.26; 95% CI, –8.1 to 10.6). In the ITT population, 84.6% of solithromycin patients and 88.6% of moxifloxacin patients achieved clinical success at SFU based on investigator assessment. Mostly mild/moderate infusion events led to higher incidence of adverse events overall in the solithromycin group. Other adverse events were comparable between treatment groups. Conclusions. Intravenous-to-oral solithromycin was noninferior to intravenous-to-oral moxifloxacin. Solithromycin has potential to provide an intravenous and oral option for monotherapy for community-acquired bacterial pneumonia. Clinical Trials Registration. NCT01968733.
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.
Approximately 5% to 15% of patients with systemic sarcoidosis develop neurological complications. However, the actual prevalence of subclinical disease may be higher. Symptoms are not specific, and ...may resemble those of other neurological diseases. Hydrocephalus occurs in 6% of patients with neurosarcoidosis. Acute hydrocephalus is extremely rare and when it occurs, it is usually difficult to diagnose, thus leading to possible complications. We present a patient who developed acute hydrocephalus due to neurosarcoidosis, for which he had to be operated on; soon after the operation, cranial infection developed that required definitive drainage system and ventriculoperitoneal shunt had to be implanted. In further complicated clinical course, after four years on corticosteroid therapy (corticosteroid dependent sarcoidosis), he had to be urgently operated on because of significant ventricular catheter adhesions, but several days after the operation he died in coma because of progressive brain edema not responding to treatment. As hydrocephalus due to neurosarcoidosis has high morbidity and mortality, early diagnosis and proper treatment are of utmost importance. Key words: Sarcoidosis; Neurosarcoidosis; Hydrocephalus; Treatment
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.
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 (
F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis.
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
F-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 (
<0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (ρ=0.272,
=0.001).
Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.
Introduction. COVID-19 is responsible for the current global pandemic. Globally, over 15 million people are currently infected, and just over 600,000 have died due to being infected. It is known that ...people with chronic illnesses and compromised immune systems can develop more severe clinical presentation. Tuberculosis (TB) is still one of the biggest epidemiological problems worldwide. Both of these diseases can be misdiagnosed and can manifest in a similar way. We will present a case study of a patient who was initially treated as a COVID-19 infection, with TB being diagnosed later on. The recovery began only after being treated for both diseases simultaneously. Case report. The patient is a 27-year-old male, non-smoker, with no history of any significant diseases. He presented with fever, fatigue and hemoptysis. Computed tomography pulmoangiography had shown massive consolidations and excavations, which could be caused by COVID-19. Despite being treated for COVID-19, there was no clinical improvement. On the follow-up chest X-ray, beside signs of COVID-19, there were also changes that could indicate TB. TB was detected in sputum, using PCR and Mycobacteria Growth Indicator Tube, and only after being treated for both diseases did his condition improve. Conclusion. There are a few reported cases of COVID-19 and TB coinfections, and we believe that there are many more patients with this coinfection being unrecognized
Introduction. Orbit is one of the rarer locations for the metastasis of malignant tumors. The symptoms of orbital tumors are nonspecific, but require detail diagnostics. Methods of visualization, ...such as ultrasound, radiography, computed tomography scan and/or magnetic resonance imaging of the endocranium are a mandatory step in the diagnostics in order to determine not only the spread of the malignancy but also the affliction of the surrounding structures. The orbital manifestations can be the first sign of the malignant disease. Outline of cases. The first case report presents a female patient with ocular symptomatology as a result of a metastasis of previously undiscovered breast cancer, and the second report presents a male patient with undiscovered lung cancer also presenting with ocular symptomatology. Conclusion. An orbital tumor should instigate further diagnostic procedures, as it can be the first sign of a disseminated malignant disease.
Sarcoidosis afflicts the central nervous system more frequently than previously believed. Neurological symptoms are present in roughly one-half of patients, and depend on the location in the central ...nervous system. The probability of spontaneous regression is significantly less when compared to other forms of sarcoidosis, which means that the proper diagnosis and treatment is paramount. Even when properly treated, functional defects are not uncommon. Majority of these patients require immunomodulating drugs and continuous follow-up. New immunomodulating drugs, especially biological agents, have shown to be significantly more effective, with fewer side effects, and are important when corticosteroids could not be applied. Less invasive methods, such as cerebrospinal analysis, help greatly in the diagnostics procedure, and require further research and improvement.
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.
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