Comparing cytology, colposcopy and human papillomavirus cervical intraepithelial lesion screening methods in women with systemic lupus erythematosus

Lupus ◽  
2020 ◽  
Vol 29 (9) ◽  
pp. 1060-1066
Author(s):  
Mario García-Carrasco ◽  
Claudia Mendoza-Pinto ◽  
Socorro Méndez-Martínez ◽  
Ariadna Rodríguez-Reyes ◽  
Pamela Munguía-Realpozo ◽  
...  

Objective To compare the performance of cytology, colposcopy and human papillomavirus in detecting cervical intraepithelial lesions in women with systemic lupus erythematosus. Methods Papanicolaou smears (normal, low-grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion), colposcopy findings, human papillomavirus and co-testing (Papanicolaou smear + human papillomavirus) were compared with cervical biopsy findings in women with systemic lupus erythematosus. Sensitivity, specificity, false-positive and false-negative rates, positive and negative predictive values and likelihood ratios of cytologic smears, colposcopy findings, human papillomavirus and co-testing were determined. Results Cytology and colposcopy were performed in 170 systemic lupus erythematosus women (mean age and disease duration of 43.7±12.1 years and 9.7±5.3 years, respectively) and biopsies were performed in 55 patients (38.2% normal, 60.0% low-grade squamous intraepithelial lesion and 1.8% high grade squamous intraepithelial lesion). The sensitivity, specificity, positive predictive value and negative predictive value of cytology were 14.7% (95% confidence interval 5.5–31.8%), 95.2% (95% confidence interval 74.1–99.7%), 83.3% (95% confidence interval 36.4–99.1%) and 40.8% (95% confidence interval 27.3–55.7%), respectively. The sensitivity, specificity and positive predictive value of colposcopy findings were 100.0% (95% confidence interval 87.3–100.0%), 0.0% (95% confidence interval 0.0–19.2%) and 61.8% (95% confidence interval 47.7–74.2%), respectively. The sensitivity and specificity of co-testing were 8.0% (95% confidence interval 1.3–27.5%) and 100.0% (95% confidence interval 71.6–100.0%). The positive predictive value and negative predictive values were 100.0% (95% confidence interval 19.7–100.0%) and 36.1% (95% confidence interval 33.5–38.8%), respectively. Conclusions In systemic lupus erythematosus patients, colposcopy impressions were more sensitive than cytology and co-testing. However, cytology and co-testing were the most specific tests. The results should be interpreted with caution due to the small sample size.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 602.1-603
Author(s):  
E. S. Torun ◽  
E. Bektaş ◽  
F. Kemik ◽  
M. Bektaş ◽  
C. Cetin ◽  
...  

Background:Recently developed EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) have important differences compared to the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria and the revised 1997 American College of Rheumatology (ACR) criteria: The obligatory entry criterion of antinuclear antibody (ANA) positivity is introduced and a “weighted” approach is used1. Sensitivity and specificity of these three criteria have been debated and may vary in different populations and clinical settings.Objectives:We aim to compare the performances of three criteria sets/rules in a large cohort of patients and relevant diseased controls from a reference center with dedicated clinics for SLE and other autoimmune/inflammatory connective tissue diseases from Turkey.Methods:We reviewed the medical records of SLE patients and diseased controls for clinical and laboratory features relevant to all sets of criteria. Criteria sets/rules were analysed based on sensitivity, positive predictive value, specificity and negative predictive value, using clinical diagnosis with at least 6 months of follow-up as the gold standard. A subgroup analysis was performed in ANA positive patients for both SLE patients and diseased controls. SLE patients that did not fulfil 2012 SLICC criteria and 2019 EULAR/ACR criteria and diseased controls that fulfilled these criteria were evaluated.Results:A total of 392 SLE patients and 294 non-SLE diseased controls (48 undifferentiated connective tissue disease, 51 Sjögren’s syndrome, 43 idiopathic inflammatory myopathy, 50 systemic sclerosis, 52 primary antiphospholipid syndrome, 15 rheumatoid arthritis, 15 psoriatic arthritis and 20 ANCA associated vasculitis) were included into the study. Hundred and fourteen patients (16.6%) were ANA negative.Sensitivity was more than 90% for 2012 SLICC criteria and 2019 EULAR/ACR criteria and positive predictive value was more than 90% for all three criteria (Table 1). Specificity was the highest for 1997 ACR criteria. Negative predictive value was 76.9% for ACR criteria, 88.4% for SLICC criteria and 91.7% for EULAR/ACR criteria.In only ANA positive patients, sensitivity was 79.6% for 1997 ACR criteria, 92.2% for 2012 SLICC criteria and 96.1% for 2019 EULAR/ACR criteria. Specificity was 92.6% for ACR criteria, 87.8% for SLICC criteria 85.2% for EULAR/ACR criteria.Eleven clinically diagnosed SLE patients had insufficient number of items for both 2012 SLICC and 2019 EULAR/ACR criteria. Both criteria were fulfilled by 16 diseased controls: 9 with Sjögren’s syndrome, 5 with antiphospholipid syndrome, one with dermatomyositis and one with systemic sclerosis.Table 1.Sensitivity, positive predictive value, specificity and negative predictive value of 1997 ACR, 2012 SLICC and 2019 EULAR/ACR classification criteriaSLE (+)SLE (-)Sensitivity (%)Positive Predictive Value (%)Specificity (%)Negative Predictive Value (%)1997 ACR(+) 308(-) 841527978.695.494.976.92012 SLICC(+) 357(-) 352626891.193.291.288.42019 EULAR/ACR(+) 368(-) 242826693.892.990.591.7Conclusion:In this cohort, although all three criteria have sufficient specificity, sensitivity and negative predictive value of 1997 ACR criteria are the lowest. Overall, 2019 EULAR/ACR and 2012 SLICC criteria have a comparable performance, but if only ANA positive cases and controls are analysed, the specificity of both criteria decrease to less than 90%. Some SLE patients with a clinical diagnosis lacked sufficient number of criteria. Mostly, patients with Sjögren’s syndrome or antiphospholipid syndrome are prone to misclassification by both recent criteria.References:[1]Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019;78:1151-1159.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 623.2-624
Author(s):  
L. Zorn-Pauly ◽  
A. S. L. Von Stuckrad ◽  
J. Klotsche ◽  
T. Rose ◽  
T. Kallinich ◽  
...  

Background:While there have been advances in the therapy of systemic lupus erythematosus (SLE) in recent years, there have been no major new findings in SLE biomarkers [1, 2]. Type I interferon (IFN) plays a pivotal role in the pathogenesis of SLE [3]. In 2008, we first described CD169 / SIGLEC-1 (sialic acid-binding immunoglobulin-like lectin-1), an interferon-induced adhesion molecule on monocytes in SLE patients [4]. For over five years SIGLEC-1 has been routinely assessed in our clinic.Objectives:To evaluate and compare the diagnostic utility of the type I IFN induced SIGLEC-1 with established biomarkers in the initial diagnosis of the disease.Methods:We analyzed retrospectively 232 patients who were on suspicion of SLE at Charité University Hospital Berlin between October 2015 and September 2020. Patients underwent full clinical characterization, and biomarkers were determined in the routine laboratory. Based on the final diagnosis, we divided patients into two groups: A) initial diagnosis of SLE and B) Non-SLE mimicking condition.Results:In 76 patients (32.3 %) SLE was confirmed by fulfilling the EULAR / ACR 2019 classification criteria [5]. SIGLEC-1 was dramatically increased in patients with an initial diagnosis of SLE compared to patients without SLE (p<0.0001). For a threshold of 2500 molecule per monocyte, a sensitivity of 98.7 %, a specificity of 82.1 %, a negative predictive value (NPV) of 99.2 %, and a positive predictive value (PPV) of 72.8 % were calculated for SIGLEC-1. Adjusted to the prevalence of SLE in Germany (36.7 per 100,000 inhabitants [6]) NPV and PPV turned out to > 99.9 % and 0.2 %. We further aimed to compare not only the performance of the tests at a given cutoff but also across all possible measured values. Therefore, we conducted ROC curves analyses (see figure 1). The area under the curve (AUC) of SIGLEC-1 test was significantly higher than that of ANA test (AUC=0.88, p=0.031), C3 (AUC = 0.83, p=0.001), C4 (AUC=0.83, p=0.002), but not than that of the Anti-dsDNA ELISA (AUC=0.90, p=0.163).Conclusion:Our study shows that IFN activity is a hallmark at the onset of the disease and that the interferon biomarker SIGLEC-1 is valuable to rule out SLE in suspected cases.References:[1]Ostendorf L, Burns M, Durek P, Heinz GA, Heinrich F, Garantziotis P, Enghard P, Richter U, Biesen R, Schneider U et al: Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus. N Engl J Med 2020, 383(12):1149-1155.[2]Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok CC, Santiago MB et al: Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med 2020, 383(12):1117-1128.[3]Ronnblom L, Leonard D: Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci Med 2019, 6(1):e000270.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, Haupl T, Rudwaleit M, Riemekasten G, Radbruch A et al: Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum 2008, 58(4):1136-1145.[5]Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL et al: 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Annals of the Rheumatic Diseases 2019, 78(9):1151-1159.[6]Brinks R, Fischer-Betz R, Sander O, Richter JG, Chehab G, Schneider M: Age-specific prevalence of diagnosed systemic lupus erythematosus in Germany 2002 and projection to 2030. Lupus 2014, 23(13):1407-1411.Disclosure of Interests:None declared


2016 ◽  
Vol 39 (2) ◽  
pp. 145-149 ◽  
Author(s):  
Haruyasu ITO ◽  
Kentaro NODA ◽  
Kenichiro HIRAI ◽  
Taro UKICHI ◽  
Kazuhiro FURUYA ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 641.1-641
Author(s):  
Y. B. Joo ◽  
Y. J. Park

Background:Infections have been associated with a higher risk of systemic lupus erythematosus (SLE) flares, but the impact of influenza infection on SLE flares has not been evaluated.Objectives:We evaluated the association between influenza infection and SLE flares resulting in hospitalization.Methods:SLE flares resulting in hospitalization and influenza cases were ascertained from the Korean national healthcare insurance database (2014-2018). We used a self-controlled case series design. We defined the risk interval as the first 7 days after the influenza index date and the control interval was defined as all other times during the observation period of each year. We estimated the incidence rates of SLE flares resulting in hospitalization during the risk interval and control interval and compared them using a Poisson regression model.Results:We identified 1,624 influenza infections among the 1,455 patients with SLE. Among those, there were 98 flares in 79 patients with SLE. The incidence ratio (IR) for flares during the risk interval as compared with the control interval was 25.75 (95% confidence interval 17.63 – 37.59). This significantly increased the IRs for flares during the risk interval in both women (IR 27.65) and men (IR 15.30), all age groups (IR 17.00 – 37.84), with and without immunosuppressive agent (IR 24.29 and 28.45, respectively), and with and without prior respiratory diseases (IR 21.86 and 26.82, respectively).Conclusion:We found significant association between influenza infection and SLE flares resulting in hospitalization. Influenza infection has to be considered as a risk factor for flares in all SLE patients regardless of age, sex, medications, and comorbidities.References:[1]Kwong, J. C. et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med 2018:378;345-353.Table 1.Incidence ratios for SLE flares resulting in hospitalization after influenza infectionRisk intervalIncidence ratio95% CIDuring risk interval for 7 days / control interval25.7517.63 – 37.59Days 1-3 / control interval21.8114.71 – 32.35Days 4-7 / control interval7.563.69 – 15.47SLE, systemic lupus erythematosus; CI, confidence intervalDisclosure of Interests:None declared


Lupus ◽  
2019 ◽  
Vol 28 (13) ◽  
pp. 1571-1576
Author(s):  
S -C Bae ◽  
Y H Lee

Objective The objective of this analysis was to explore associations between paraoxonase-1 levels, gene polymorphisms and systemic lupus erythematosus. Methods Meta-analyses of paraoxonase-1 levels and Q192R and L55M and polymorphisms in systemic lupus erythematosus were conducted. Results Nine articles were incorporated in our meta-analysis, which uncovered that the paraoxonase-1 level was decreased in systemic lupus erythematosus compared to control (standard mean difference = −1.626, 95% confidence interval = −2.829–−0.424, p = 0.008). Ethnicity-specific meta-analysis demonstrated a relation tendency between decreased paraoxonase-1 activity and lupus in Europeans (standard mean difference = −1.236, 95% confidence interval = −2.634–0.163, p = 0.083). Paraoxonase-1 activity was reduced in systemic lupus erythematosus in a single Arab and African population. Decreased paraoxonase-1 activity was found in a small sample of systemic lupus erythematosus patients (standard mean difference = −1.642, 95% confidence interval = −3.076–−0.247, p = 0.021). Ethnicity-specific analysis indicated a relationship between the paraoxonase-1 55 M allele in the Arab systemic lupus erythematosus population. However, a lack of association with systemic lupus erythematosus and the paraoxonase-1 192 R allele was observed. Conclusions Meta-analyses revealed reduced paraoxonase-1 activity in patients with systemic lupus erythematosus and found possible associations between systemic lupus erythematosus and paraoxonase-1 L55M polymorphism in a specific ethnic group.


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