scholarly journals Using genetics to differentiate patients with similar symptoms: application to inflammatory arthritis in the rheumatology outpatient clinic

2019 ◽  
Author(s):  
Rachel Knevel ◽  
Saskia le Cessie ◽  
Chikashi C. Terao ◽  
Kamil Slowikowski ◽  
Jing Cui ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Medical Records ◽  
Genetic Information ◽  
Inflammatory Arthritis ◽  
Genetic Data ◽  
List Type ◽  
Diagnostic Efficiency ◽  
Diagnostic Challenge ◽  
Discriminative Ability ◽  
Icd Codes

ABSTRACTSlow developing complex diseases are a clinical diagnostic challenge. Since genetic information is increasingly available prior to a patient’s first visit to a clinic, it might improve diagnostic accuracy. We aimed to devise a method to convert genetic information into simple probabilities discriminating between multiple diagnoses in patients presenting with inflammatory arthritis.We developed G-Prob, which calculates for each patient the genetic probability for each of multiple possible diseases. We tested this for inflammatory arthritis-causing diseases (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathy, psoriatic arthritis and gout). After validating in simulated data, we tested G-Prob in biobank cohorts in which genetic data were linked to electronic medical records: -1,200 patients identified by ICD-codes within the eMERGE database (n= 52,623);-245 patients identified through ICD codes and review of medical records within the Partners Biobank (n=12,604);-243 patients selected prospectively with final diagnoses by medical record review within the Partners Biobank (n=12,604). The calibration of G-Prob with the disease status was high (with regression coefficients ranging from 0.90-1.08 (ideal would be 1.00) in all cohorts. G-Prob’s discriminative ability was high in all cohorts with pooled Area Under the Curve (AUC)=0.69 [95%CI 0.67-0.71], 0.81 [95%CI 0.76-0.84] and 0.84 [95%CI 0.81-0.86]. For all patients, at least one disease could be ruled out, and in 45% of patients a most likely diagnosis could be identified with an overall 64% positive predictive value. In 35% of instances the clinician’s initial diagnosis was incorrect. Initial clinical diagnosis explained 39% of the variance in final disease prediction which improved to 51% (P<0.0001) by adding G-Prob genetic data.In conclusion, by converting genotypes into an interpretable probability value for five different inflammatory arthritides, we can better discriminate and diagnose rheumatic diseases. Genotypes available prior to a clinical visit could be considered part of patients’ medical history and potentially used to improve precision and diagnostic efficiency in clinical practice.

scholarly journals Using genetics to prioritize diagnoses for rheumatology outpatients with inflammatory arthritis

2020 ◽  
Vol 12 (545) ◽  
pp. eaay1548 ◽  
Author(s):  
Rachel Knevel ◽  
Saskia le Cessie ◽  
Chikashi C. Terao ◽  
Kamil Slowikowski ◽  
Jing Cui ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Inflammatory Arthritis ◽  
Simulated Data ◽  
Disease Status ◽  
International Classification Of Diseases ◽  
Risk Scores ◽  
Diagnostic Efficiency ◽  
Genotype Information ◽  
Icd Codes ◽  
Record Review

It is challenging to quickly diagnose slowly progressing diseases. To prioritize multiple related diagnoses, we developed G-PROB (Genetic Probability tool) to calculate the probability of different diseases for a patient using genetic risk scores. We tested G-PROB for inflammatory arthritis–causing diseases (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathy, psoriatic arthritis, and gout). After validating on simulated data, we tested G-PROB in three cohorts: 1211 patients identified by International Classification of Diseases (ICD) codes within the eMERGE database, 245 patients identified through ICD codes and medical record review within the Partners Biobank, and 243 patients first presenting with unexplained inflammatory arthritis and with final diagnoses by record review within the Partners Biobank. Calibration of G-probabilities with disease status was high, with regression coefficients from 0.90 to 1.08 (1.00 is ideal). G-probabilities discriminated true diagnoses across the three cohorts with pooled areas under the curve (95% CI) of 0.69 (0.67 to 0.71), 0.81 (0.76 to 0.84), and 0.84 (0.81 to 0.86), respectively. For all patients, at least one disease could be ruled out, and in 45% of patients, a likely diagnosis was identified with a 64% positive predictive value. In 35% of cases, the clinician’s initial diagnosis was incorrect. Initial clinical diagnosis explained 39% of the variance in final disease, which improved to 51% (P < 0.0001) after adding G-probabilities. Converting genotype information before a clinical visit into an interpretable probability value for five different inflammatory arthritides could potentially be used to improve the diagnostic efficiency of rheumatic diseases in clinical practice.

scholarly journals Dual threat of comorbidity of celiac disease and systemic lupus erythematosus

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110122
Author(s):  
Yimin Ma ◽  
Duanming Zhuang ◽  
Zhenguo Qiao
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Celiac Disease ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Failure To Thrive ◽  
Severe Malnutrition ◽  
Systemic Lupus ◽  
Electrolyte Disorders ◽  
Diagnostic Challenge ◽  
Immune Mediated

Celiac disease (CD) is a chronic immune-mediated intestinal disease that is characterized by production of autoantibodies directed against the small intestine. The main clinical manifestations of CD are typically defined as those related to indigestion and malabsorption. These manifestations include unexplained diarrhea or constipation, abdominal pain, bloating, weight loss, anemia, failure-to-thrive in children, and decreased bone density. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinical manifestations, which may also involve the gastrointestinal tract. Comorbidity of CD and SLE is rare, and the overlapping symptoms and nonspecific clinical presentation may pose a diagnostic challenge to clinicians. We report here a case of SLE with CD, which mainly manifested as recurrent diarrhea, uncorrectable electrolyte disorders, and severe malnutrition. Through review, we hope to further improve our understanding and diagnostic level of this combination of diseases.

scholarly journals AB1046 JOINT MANIFESTATIONS IN A COHORT OF PATIENTS WITH SARCOIDOSIS IN A THIRD LEVEL HOSPITAL.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1814.3-1814
Author(s):  
I. Madroñal García ◽  
C. Aguilera Cros ◽  
L. Mendez Diaz
Keyword(s):  
Medical Records ◽  
Unknown Etiology ◽  
Joint Involvement ◽  
List Type ◽  
Chi Square ◽  
Exact Test ◽  
Approximate Result ◽  
Chronic Course ◽  
Level Hospital ◽  
Larger Sample

Background:Sarcoidosis (S) is a systemic granulomatous disease of unknown etiology, which most frequently affects the ganglion, lung and skin, although it can affect other organs, including the musculoskeletal system.Objectives:- Describe the clinical, analytical and radiological characteristics of patients diagnosed with S presenting joint manifestations.- To assess the association between patients who have joint manifestations and the use of corticosteroids (C) and immunosuppressants (IS), with respect to those without joint involvement.Methods:Retrospective descriptive study of patients with diagnosis of S with joint manifestations, treated in our Hospital from 2017 to 2019. Data were obtained by reviewing medical records. Chi square tests and Fisher’s exact test have been performed to establish the differences described in the objectives.Results:From a database of 102 patients with S, 18 presented joint manifestations (50% women), with a mean age of 57 ± 6 years. Of these patients, 4 (22.2%) have presented positive ANA. Regarding the clinic, 3 patients presented the association of polyarthritis and bilateral ankle swelling, 8 patients presented with polyarthritis, 3 monoatritis and 4 patients presented bilateral ankle swelling. 61.1% had fever at the onset of the disease.14 patients (77.8%) had high ACE values at the onset of the disease, without presenting significant differences with respect to all patients diagnosed with S who do not have joint involvement.All patients received treatment with C and 10 patients (55.5%) needed an IS treatment, finding no differences with respect to patients who do not have joint involvement (p=0.92).On the course of the disease, the majority of patients with joint involvement have a chronic course (72.2%). Nor were significant differences found when compared with patients who have no joint involvement (p = 0.73).Conclusion:Patients with joint involvement in our study have been 17.6% (18), an approximate result to that described in the literature (over 10%), although our result may be increased by the fact that the patients who are followed in Rheumatology present or have presented joint involvement. No significant differences were found between patients with S who presented joint involvement and those who did not, with respect to the initial ACE values, treatment and disease course. Prospective, multicenter and larger sample studies are necessary to better understand these associations.Disclosure of Interests:None declared

scholarly journals Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

2020 ◽  
Vol 21 (9) ◽  
pp. 3389 ◽  
Author(s):  
Konstantinos Melissaropoulos ◽  
Kalliopi Klavdianou ◽  
Alexandra Filippopoulou ◽  
Fotini Kalofonou ◽  
Haralabos Kalofonos ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Immune Checkpoint ◽  
Inflammatory Arthritis ◽  
Immune Checkpoint Inhibitors ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Musculoskeletal Complaints ◽  
Moderate Severity ◽  
Rheumatic Manifestations ◽  
New Onset

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. Their clinical efficacy is well-documented, but the side effects associated with their use are still under investigation. These drugs cause several immune-related adverse events (ir-AEs), some of which stand within the field of rheumatology. Herein, we present a literature review performed in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICIs. The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis. Non-musculoskeletal rheumatic manifestations are less frequent, with the most prominent being sicca, vasculitides and sarcoidosis. Cases of systemic lupus erythematosus or scleroderma are extremely rare. The majority of musculoskeletal ir-AEs are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation. In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed. Oncologists should periodically screen patients receiving ICIs for new-onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.

scholarly journals EQ-5D-3L full health state discriminates between drug and placebo in clinical trials of systemic lupus erythematosus

Rheumatology ◽  
2021 ◽  
Author(s):  
Julius Lindblom ◽  
Alvaro Gomez ◽  
Alexander Borg ◽  
Sharzad Emamikia ◽  
Dimitris Ladakis ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Patient Reported Outcome ◽  
Health State ◽  
Full Health ◽  
Chi Square ◽  
Discriminative Ability ◽  
Exact Test ◽  
Patient Reported

Abstract Objectives To investigate the discriminative ability of EQ-5D-3L full health state (FHS) in clinical trials of SLE, and identify factors associated with FHS after treatment. Methods Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials of belimumab (N = 1684) were utilised. FHS was defined as a response of no problems in all five EQ-5D-3L dimensions, yielding an index score of 1. The Pearson’s chi-square or Fisher’s exact test was employed for comparisons, and logistic regression for adjustments and assessment of independence. Results We demonstrated higher EQ-5D-3L FHS frequencies among patients given standard therapy (ST) plus the licensed belimumab dose versus ST alone (26.1% versus 19.4%; P = 0.001; week 52), and within SRI-4 responders versus non-responders (27.0% versus 19.8%; P &lt; 0.001; week 52) from week 36 to 52. In multivariable regression analysis, SLEDAI-2K (OR: 0.90; 95% CI: 0.87 − 0.94; P &lt; 0.001) and SLICC/ACR Damage Index (OR: 0.79; 95% CI: 0.69 − 0.91; P = 0.001) scores were independently associated with lower FHS frequencies at week 52, while adding monthly infusions of belimumab 10 mg/kg to ST favoured FHS perception (OR: 1.60; 95% CI: 1.15 − 2.24; P = 0.006). Add-on belimumab 10 mg/kg yielded higher FHS frequencies in antimalarial users versus non-users (29.9% versus 20.1%; P = 0.011), and in anti-dsDNA and anti-Sm positive versus negative patients (31.4% versus 13.4%; P &lt; 0.001 and 33.0% versus 22.6%; P = 0.010, respectively), whereas no significant differences were observed in patients given ST alone. Conclusion EQ-5D-3L FHS distinguished belimumab from placebo and responders from non-responders, and exhibited known-group validity in subgroup analysis. FHS may prove a useful patient-reported outcome in SLE studies.

scholarly journals Generating real-world evidence from unstructured clinical notes to examine clinical utility of genetic tests: use case in BRCAness

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yiqing Zhao ◽  
Saravut J. Weroha ◽  
Ellen L. Goode ◽  
Hongfang Liu ◽  
Chen Wang
Keyword(s):  
Targeted Therapy ◽  
Data Quality ◽  
Real World ◽  
Genetic Information ◽  
Genetic Data ◽  
Real World Data ◽  
Rule Based ◽  
Clinical Notes ◽  
Real World Evidence ◽  
F Measure

Abstract Background Next-generation sequencing provides comprehensive information about individuals’ genetic makeup and is commonplace in oncology clinical practice. However, the utility of genetic information in the clinical decision-making process has not been examined extensively from a real-world, data-driven perspective. Through mining real-world data (RWD) from clinical notes, we could extract patients’ genetic information and further associate treatment decisions with genetic information. Methods We proposed a real-world evidence (RWE) study framework that incorporates context-based natural language processing (NLP) methods and data quality examination before final association analysis. The framework was demonstrated in a Foundation-tested women cancer cohort (N = 196). Upon retrieval of patients’ genetic information using NLP system, we assessed the completeness of genetic data captured in unstructured clinical notes according to a genetic data-model. We examined the distribution of different topics regarding BRCA1/2 throughout patients’ treatment process, and then analyzed the association between BRCA1/2 mutation status and the discussion/prescription of targeted therapy. Results We identified seven topics in the clinical context of genetic mentions including: Information, Evaluation, Insurance, Order, Negative, Positive, and Variants of unknown significance. Our rule-based system achieved a precision of 0.87, recall of 0.93 and F-measure of 0.91. Our machine learning system achieved a precision of 0.901, recall of 0.899 and F-measure of 0.9 for four-topic classification and a precision of 0.833, recall of 0.823 and F-measure of 0.82 for seven-topic classification. We found in result-containing sentences, the capture of BRCA1/2 mutation information was 75%, but detailed variant information (e.g. variant types) is largely missing. Using cleaned RWD, significant associations were found between BRCA1/2 positive mutation and targeted therapies. Conclusions In conclusion, we demonstrated a framework to generate RWE using RWD from different clinical sources. Rule-based NLP system achieved the best performance for resolving contextual variability when extracting RWD from unstructured clinical notes. Data quality issues such as incompleteness and discrepancies exist thus manual data cleaning is needed before further analysis can be performed. Finally, we were able to use cleaned RWD to evaluate the real-world utility of genetic information to initiate a prescription of targeted therapy.

The clinical relevance of anti-dsDNA antibodies determined by the Elia™ dsDNA assay in patients with negative indirect immunofluorescence on the HEp-2 cell

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Robier ◽  
Maximiliane Haas ◽  
Franz Quehenberger
Keyword(s):  
Indirect Immunofluorescence ◽  
Lupus Erythematosus ◽  
Medical Records ◽  
Clinical Relevance ◽  
Solid Phase ◽  
Clinical Importance ◽  
Discoid Lupus Erythematosus ◽  
Combined Use ◽  
Significant Difference ◽  
Dsdna Antibodies

AbstractObjectivesData on the clinical importance of the detection of anti-dsDNA antibodies in patients with negative indirect immunofluorescence on the HEp-2 cell (IIF) are sparse and are especially not available for all common commercially available assays. This study aimed to assess the clinical significance of anti-dsDNA antibodies determined by the Elia™ dsDNA assay in patients with negative IIF.MethodsWe retrospectively examined the medical records of 234 consecutive subjects with detectable anti-dsDNA antibodies determined by the Elia™ dsDNA assay.ResultsA total of 124 subjects with detectable anti-dsDNA autoantibodies were IIF-negative, but yielded positive or borderline results in the Elia™ CTD screen assay for antinuclear antibodies (ANA). Within this group, 6/49 IIF-negative patients (12%) with ANA-associated systemic autoimmune rheumatic disorders (AASARD) and 118/185 subjects (64%) with various other diseases (Non-AASARD) were identified. There was no statistically significant difference with regard to the concentrations of anti-dsDNA antibodies (p=0.53) between the AASARD and the Non-AASARD group. Within the AASARD group, four patients diagnosed with systemic lupus erythematosus (SLE, treated), discoid lupus erythematosus (untreated), indetermined connective tissue disease (untreated) and polymyositis (treated) had positive anti-dsDNA autoantibodies, whereas two patients with treated SLE, thereby one in remission, had borderline concentrations of anti-dsDNA antibodies.ConclusionsOur findings suggest that the detection of anti-dsDNA antibodies in IIF-negative patients can be of clinical relevance in some cases. Our results further support the combined use of IIF and solid-phase assays in screening algorithms for ANA, in order to avoid overlooking potentially important autoantibody entities.

The protection of genetic information

2010 ◽  
pp. 91-113
Author(s):  
Juri Monducci
Keyword(s):  
Genetic Information ◽  
Personal Data ◽  
Genetic Data ◽  
Case Law ◽  
Genetic Determinism ◽  
Genetic Identity ◽  
Statutory Protection ◽  
Right Not To Know ◽  
Genetic Makeup ◽  
The Right

The law pertaining to personal data has developed in Italy over a thirty-year span that took us from recognition of such data in the case law, in 1975, to its statutory protection, in 2003. This evolution would subsequently come to the point of specifically regulating the processing of genetic data as data revealing an individual's genetic makeup, thereby also revealing the biological future of individuals and their offspring: this information describes an individual at a core level where the deepest, most unchangeable traits are found and can therefore nurture what is nowadays referred to as genetic determinism, which reduces the person to a complex of genetic data and so ignores the whole layer of characteristics that make each of us unique. There is, then, a discriminatory risk inherent in the processing of genetic data, and equally clear are the psychological implications of such processing, so much so that the need has arisen to have rules in place aimed at regulating the biotechnologies and genetics in particular. These rules have given birth to the so-called fourthgeneration rights, inclusive of the right to ones genetic identity and the right not to know ones genetics (although this is something that had been discussed earlier, too), and it is to a discussion of these rights that this essay is devoted.

Non-central serous chorioretinopathy in a patient with systemic lupus erythematosus and hydroxychloroquine retinopathy

2021 ◽  
Vol 14 (1) ◽  
pp. e237243
Author(s):  
Diogo Hipolito-Fernandes ◽  
Maria Elisa Luís ◽  
Rita Flores ◽  
Rita Anjos
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Central Serous Chorioretinopathy ◽  
Vision Loss ◽  
Subretinal Fluid ◽  
Ophthalmological Examination ◽  
Systemic Lupus ◽  
Diagnostic Challenge ◽  
Hydroxychloroquine Retinopathy ◽  
The Right

Subretinal fluid accumulation in a patient with systemic lupus erythematosus (SLE) may represent a diagnostic challenge. We present a case of a 43-year-old man with baseline diagnosis of SLE and hydroxychloroquine-associated maculopathy who reported progressive vision loss on the right eye, associated with corticosteroids use for an arthritic crisis. Ophthalmological examination did not reveal any acute finding. On optical coherence tomography, subretinal fluid in the perifoveal area was visible on the right eye, with corresponding enlargement of the visual field defect. An increased choroidal thickness was also visible. Fluorescein angiography revealed, on the right eye, two pinpoint areas of leakage and indocyanine green angiography signs of choroidal vascular hyperpermeability. Considering a diagnosis of a non-central central serous chorioretinopathy, corticosteroids use was interrupted, with resolution of the subretinal fluid. This case illustrates the relevance of a multimodal imaging approach to guide the diagnosis of patient with an SLE with subretinal fluid.

scholarly journals Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus

2020 ◽  
Author(s):  
Sarthak Gupta ◽  
Shuichiro Nakabo ◽  
Jun Chu ◽  
Sarfaraz Hasni ◽  
Mariana J. Kaplan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
General Population ◽  
Lupus Erythematosus ◽  
Preventive Measures ◽  
Type I Interferon ◽  
Type I ◽  
List Type ◽  
Signal Transducer ◽  
Systemic Lupus

AbstractObjectivesAnti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE). Recently, an association of these autoantibodies with severe COVID-19 was reported in the general population. We assessed whether having pre-existing anti-IFNα autoantibodies was associated with COVID-19 infection in SLE patients.MethodsPatients with SLE who developed COVID-19 between April 1st to October 1st, 2020 were studied. Biobanked pre-COVID-19 plasma from these SLE subjects and healthy controls were tested for anti-IFNα IgG autoantibodies by ELISA. The ability of plasma anti-IFNα autoantibodies to block signal transducer and activator of transcription 1 (STAT1) phosphorylation by recombinant human IFNα in vitro was assessed by flow cytometry.ResultsTen SLE subjects with COVID-19 were identified. A 40% of these subjects had stable autoantibodies against IFNα for up to three years preceding COVID-19 diagnosis. A 50% of the subjects with these autoantibodies neutralized IFNα induced STAT1 phosphorylation.None of the other SLE samples blocked IFNα signaling.ConclusionsWe noted an increased prevalence of pre-existing anti-IFNα autoantibodies in SLE patients with COVID-19 compared to the reported prevalence in lupus patients and the general population with severe COVID-19. Autoantibodies against IFNα in SLE patients may be pathogenic and patients with them maybe at-risk of developing COVID-19.Key MessagesWhat is already known about this subject?-Anti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE) and have recently been associated with severe COVID-19 in the general population.What does this study add?-SLE subjects with COVID-19 had an increased prevalence of pre-existing anti-IFNα autoantibodies compared to the reported prevalence in lupus patients and the general population with severe COVID-19.-Plasma from 50% of subjects with these autoantibodies were able to block in vitro activity of IFNα.-SLE patients with pre-existing anti-IFNα autoantibodies had more severe COVID-19 manifestations.How might this impact on clinical practice or future developments?-Anti-IFNα autoantibodies may be pathogenic and could prove to be a helpful prognostic marker to predict which SLE patient may develop COVID-19 and inform preventive measures and management of this subset of patients.

Sign in / Sign up

Export Citation Format

Share Document