Background/Objective Women with systemic lupus erythematosus (SLE) are at increased risk for cervical neoplasia likely due to infection with high-risk human papillomavirus (HR-HPV) and should be considered for HPV vaccination. We sought to determine the frequency of HR-HPV infection and uptake of HPV vaccination in our regional female lupus population. Methods For this medical records review study, data were analyzed from our electronic health records EPIC for women with International Classification of Diseases-10 or International Classification of Diseases -9 billing codes for SLE seen June 6, 2007, to May 1, 2017. This study was approved by the Central Michigan University/Covenant Medical Center institutional review board. Statistical analyses consisted of Student t test, χ2, and Z test for proportions using SPSS v. 24 software. Results A total of 1349 women with SLE were identified, mean age of 53 years, 70.8% white, 20.8% African American, with 49% exposed to cigarette smoke. High-risk HPV testing performed in 195 (14.5%; mean age, 50 years) showed 16.9% (33/195) were positive, with those testing positive for HR-HPV being slightly younger (p < 0.05). Comparing our proportion testing positive for HR-HPV (0.169) versus National Health and Nutrition Examination Survey (0.088), we calculated a Z = 3.99 (p < 0.001) indicating HPV infection is significantly higher (2×) in our female SLE cohort. Only 16.0% (38/238) of the 238 women eligible to receive an HPV vaccine were tested for HR-HPV with 9 being positive and only 4.6% (11/238) vaccinated. Conclusions Human papillomavirus infection is a serious health issue in women with SLE, but HPV testing and vaccination rates remain low. Efforts should be directed to promote awareness of the importance of HPV vaccination in this high-risk population.

INTRODUCTIONCervical intraepithelial neoplasia (CIN) is increased in women with systemic lupus erythematosus (SLE). Cervical neoplasia is caused by human papilloma virus (HPV) infection which persists and causes malignant transformation of infected cervical cells. Women with lupus have impaired immune systems which can facilitate HPV persistence. We hypothesized that women with SLE who developed CIN would be younger, have more severe disease and received more immunosuppressive treatment. To test this hypothesis, a case-control study was conducted focusing on two key variables, SLE disease severity and immunosuppressive treatment, which we believed would be the major determinants of CIN development in SLE.METHODSA case control analysis was performed to compare the clinical characteristics of SLE women with cervical neoplasia (cases) to SLE women without cervical neoplasia (controls). Formalin fixed blocks of neoplastic cervical tissue were obtained from 113 women with SLE and tissue histology confirmed by 2 pathologists. Clinical data was obtained by retrospective chart reviews. Logistic regression was used to evaluate for any significant differences in clinical variables between the cases and the controls. Two sets of controls were used for comparison with a 2:1 match for each control group to cases group.RESULTSUsing matched controls adjusting for age and race, logistic regression analysis showed no significant difference between cases and controls for any of the clinical variables. In particular, there were no significant differences between cases vs. matched and vs. unmatched controls for factors related to SLE (disease severity, use of immunosuppressive drugs), chronic metabolic diseases (hypertension, diabetes) and HPV risk factors (marital status, smoking, gravidity parity).CONCLUSIONThe key finding of this study is that SLE patients who develop CIN are not clinically different from SLE patients who do not develop CIN. Thus, lupus disease severity and immunosuppressive treatment were not susceptibility factors for CIN in our female lupus cohort.

Objective: To determine frequency, transcription and integration rates for high risk Human papillomavirus (HR HPV) types 16 and 18 in neoplastic cervical tissue of women with systemic lupus erythematosus (SLE).Methods: Cervical tissue of cervical intraepithelial neoplasia 1 (CIN 1) or greater severity were obtained from 112 women with SLE. HPV typing and integration was assessed by polymerase chain reaction (PCR) using primers specific for HPV 16 and 18 located in the open reading frames E7, E2, and E5. A commercially available kit was employed for transcriptional analysis of samples positive for HPV DNA types 16 or 18.Results: For the 112 SLE patients, 80.3% of the cervical biopsies were CIN 1 or CIN2, 15.2% CIN 3, and 4.5% carcinoma in situ/invasive cancer. HPV DNA 16 and 18 were detected in 20.5%, mostly type 16. Low integration and transcription rates were seen. There was no association of disease severity or immunosuppressive drugs with the presence of HPV DNA or RNA.Conclusion: The paucity of HR HPV along with lack of detectable viral transcripts, are unexpected findings and suggest HPV is latent in CIN lesions in SLE. Host-HPV interactions in this group of immunosuppressed women warrant further study.

Background Eltrombopag activates the thrombopoietin (TPO) surface receptor on the megakaryocyte, which increases the production of platelets, and rapidly improves circulating platelet numbers in patients with immune thrombocytopenic purpura (ITP). This allows for rapid tapering and/or cessation of corticosteroid therapy. Less is known about the platelet response to this drug in ITP associated with systemic lupus erythematosus (SLE).Methods A retrospective review was performed of the clinical course of three consecutive patients, each with SLE-associated ITP who were initially treated with corticosteroids or other immunomodulatory therapy. These patients were treated with eltrombopag at the DMC Center for Bleeding Disorders and Thrombosis. Eltrombopag was administered according the package insert, with an initial dose of 50mg daily, with weekly, then monthly monitoring of platelet counts and dose adjustments. Some immunomodulatory agents (e.g. hydroxychloroquine) were continued to control non hematologic SLE manifestations.Results All three patients maintained acceptable platelet counts (>50,000/mm(3) for >3 years) following tapering and cessation of corticosteroids. The drug was well-tolerated and there were no adverse events, and specifically no thrombotic events.Conclusion Eltrombopag is effective as a rapidly acting corticosteroid sparing therapy for patients with ITP associated with SLE. This is important in reducing corticosteroid related side effects and morbidities in treating SLE patients with ITP. Larger studies are needed to ascertain safety and efficacy of eltrombopag in SLE patients with ITP, particularly those with coexisting antiphospholipid antibodies.

Our aim was to better define the coagulation abnormalities in patients with systemic lupus erythematosus who had thrombosis or high-risk clinical settings for thrombosis. Clinical and laboratory data of 111 patients with lupus referred for coagulation assessment because of thrombosis, pregnancy loss or high-risk clinical settings for thrombosis were reviewed retrospectively. Increased activity of procoagulant factors and decreased activity of anti-coagulant factors were observed well above the expected 5% prevalence. All comparisons were significant at the P < 0.001 level. Anticardiolipin antibodies were present in 70.5% of patients tested (55/78) in this high-risk group, but usually in low titres. Platelet hyperfunction was detected in the majority of patients tested (85.7%, 78/91). Hypercoagulability in lupus is complex and is better defined by assessing multiple haemostatic factors in addition to platelet function. Platelet hyperfunction contributes significantly to thrombophilia in lupus and this is the key finding of our study.

Systemic lupus erythematosus is a chronic multi-system autoimmune disease that occurs predominantly in women of childbearing age. The risk of complications and adverse fetal outcomes in pregnant women with lupus is high. Moreover, pregnancy can cause flares of lupus disease activity necessitating maternal immunosuppressive intervention. Interestingly, many potential complications of pregnancy present as symptoms of lupus making diagnosis and treatment a challenge. Advancing technology and better understanding of the maternal-fetal dyad in lupus have improved outcomes in lupus pregnancies over the last 40 years. This article will briefly review the important issues in pregnancies complicated by lupus and provide a general guideline to physicians for monitoring and treatment.

International Journal of Gynecology & ObstetricsVolume 89, Issue 3 p. 295-296 Brief communications Ominous cervical cytopathology in women with lupus J.P. Dhar, Corresponding Author J.P. Dhar [email protected] Department of Internal Medicine/Division of Rheumatology, Wayne State University School of Medicine, The Detroit Medical Center and Henry Ford Health Systems, Detroit, MI, USACorresponding author. 3500 15 Mile Road Sterling Heights, 48310 MI, United States. Tel.: +1 313 916 2646; fax: +1 313 577 8554.Search for more papers by this authorL. Essenmacher, L. Essenmacher Center for Health Care Effectiveness Research, Wayne State University School of Medicine, Detroit, MI, USASearch for more papers by this authorJ. Ager, J. Ager Center for Health Care Effectiveness Research, Wayne State University School of Medicine, Detroit, MI, USASearch for more papers by this authorR.J. Sokol, R.J. Sokol Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, USASearch for more papers by this author J.P. Dhar, Corresponding Author J.P. Dhar [email protected] Department of Internal Medicine/Division of Rheumatology, Wayne State University School of Medicine, The Detroit Medical Center and Henry Ford Health Systems, Detroit, MI, USACorresponding author. 3500 15 Mile Road Sterling Heights, 48310 MI, United States. Tel.: +1 313 916 2646; fax: +1 313 577 8554.Search for more papers by this authorL. Essenmacher, L. Essenmacher Center for Health Care Effectiveness Research, Wayne State University School of Medicine, Detroit, MI, USASearch for more papers by this authorJ. Ager, J. Ager Center for Health Care Effectiveness Research, Wayne State University School of Medicine, Detroit, MI, USASearch for more papers by this authorR.J. Sokol, R.J. Sokol Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, USASearch for more papers by this author First published: 07 April 2005 https://doi.org/10.1016/j.ijgo.2005.02.006Citations: 9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References [1]Cibere J., Sibley J., Haga M. Systemic lupus erythematosus and the risk of malignancy. Lupus. 10: 2001; 394–400 [2]Dhar J.P., Kmak D., Bhan R., Pishorodi L., Age J., Sokol R.J. Abnormal cervicovaginal cytology in women with lupus: a retrospective cohort study. Gynecol Oncol. 82: 2001; 4–6 [3]Nyberg G., Eriksson O., Westberg N.G. Increased incidence of cervical atypia in women with systemic lupus erythematosus treated with chemotherapy. Arthritis Rheum. 24: 1981; 648–650 [4]Bertansky S., Ramsey-Goldman R., Gordon C., Joseph L., Boivin J.F., Rajan R., et al. Factors associated with abnormal Pap results in systemic lupus erythematosus. Rheum Advance Access 2004 (July 27); 1–4 Citing Literature Volume89, Issue3June 2005Pages 295-296 ReferencesRelatedInformation

Objective: The purpose of this study was to evaluate pregnancy. outcomes before and after of lupus. design:Study Successive selection criterion applied to 148 lupus and 78,905 non-lupus pregnancies, generated 3 groups: lupus group, 84 pregnancies (not-yet-diagnosed group, 15 women; already-diagnosed group, 69 women), and control group, 51,000 pregnancies. Three-way analysis of variance and the chi-squared test were used for analyses.Results: Stillbirth outcome was increased in the lupus group compared with the control group (odds ratio, 4.84 [95% CI, 1.72,11.08]); the not-yet-diagnosed group (odds ratio, 9.89 [95% Cl, 1.09,42.63]), and the already-diagnosed group (odds ratio, 3.85 [95% Cl, 1.02,10.31]). Considering > 1 pregnancy per patient would have overestimated the stillbirth rate. Stillbirth risk was increased significantly in severe maternal disease that was marked by central nervous system involvement. The already-diagnosed group had more hypertensive complications (P =.001 and.0001). Both lupus groups showed a significantly greater proportion of preterm 3 births (P =.03), growth restriction (P =.019), and infants in the very low birth weight category (P =.021) compared with the control group.Conclusion: Poor fetal outcomes are seen in pregnancies that are complicated by lupus, even before clinical appearance of disease, which supports a predisease state. (C) 2005 Mosby, Inc. All rights reserved.

The objective of this study was to evaluate whether fetal growth has improved or gestational duration has increased over time. We hypothesized improved outcomes that might be attributable to advances in lupus intervention. A cohort analysis of pregnancy outcomes from 1985-2002 in women with lupus was performed at our center. The Wayne State University Lupus Registry was linked to the Wayne State University Perinatal Database to obtain all pregnancies in women with lupus delivered at our institution. The control population consisted of demographically similar non-lupus pregnancies from the Wayne State University Perinatal Database There were 473 singleton deliveries in 327 women with lupus delivered at our institution. To ensure statistical independence, we calculated the mean birth weight and gestational age in the first pregnancy per parturient delivered at our center, leaving us with 327 pregnancies in 327 women with lupus (first pregnancy group). The control group consisted of 78,905 deliveries at our center during the same period. The mean birthweight and gestational age for the first pregnancy group was significantly decreased (2790 grams and 36 weeks, respectively) compared to the control group (P<0.0001). Gestational age and birthweight did not significantly change over time. However, when birthweight percentiles over time were analyzed, a statistically significant increase in fetal growth was seen (r = −0.098, r2 = 0.10, P = 0.041). Fetal growth in pregnancies complicated by lupus improved over the 18 years of this study. Because there were no major changes in the characteristics of the sample, we speculate that this improvement might reflect advancing technology of care and improved intervention, as originally hypothesized, most notably aggressive thrombophilia assessments and treatment, as well as concurrent rheumatologic care during pregnancy. Any change in "spontaneous" gestational duration over time might be hidden by changes in obstetric intervention.

The primary objective was to accurately assess stillbirth rates in pregnancies complicated by lupus. Additionally, we assessed stillbirth rates over time to determine if improvements in lupus care may have been associated with a decrease in the stillbirth rate in lupus-related pregnancies. A cohort analysis of pregnancy outcomes from 1985-2002 in women with lupus was performed at our center. The Wayne State University Lupus Registry was linked to the Wayne State University Perinatal Database to obtain all pregnancies delivered at our institution. The control population consisted of all non-lupus pregnancies from the Wayne State University Perinatal Database from the same period. There were 473 pregnancies in 327 women with lupus delivered at our institution. The control group consisted of 78,905 deliveries. To ensure statistical independence, we calculated the stillbirth rate only in the first pregnancy per parturient (first pregnancy group) delivered at our center, leaving us with 327 pregnancies in 327 women with lupus. In the first pregnancy group, the stillbirth rate was four times that of the control group (55.05/1000 vs 13.3/1000, odds ratio 4.31 [2.51,6.99]). The stillbirth rate over time was assessed using results of all deliveries. Although there was a tendency for stillbirth rates over time to decline, this was not statistically significant. Stillbirth rates are increased markedly in women with lupus. Given the large sample and limitation to one pregnancy per patient, this should represent one of the most reliable estimates of stillbirth rate and relative risk. Improvement in outcome that might be anticipated with improved care is not yet detectable using the severe adverse outcome of stillbirth.

OBJECTIVE:The aim of this study was to review Pap smear reports in women with systemic lupus erythematosus and compare them to a large control population.METHODS:Pap smear results of 29 women with a diagnosis of lupus seen consecutively were compared to those of a control population of 747 women attending the gynecology clinic at the same medical center during the same year. Records of lupus patients were reviewed to obtain clinical data. Fisher's exact test and chi(2) analysis were used to determine statistical significance, as appropriate.RESULTS:Of 29 women with lupus, 1/29 had high-grade squamous intraepithelial lesions (HGSIL) and 6/29 had low-grade squamous intraepithelial lesions (LGSIL). The control population of 747 women had 9/747 with HGSIL and 63/747 with LGSIL. chi(2) and Fisher's exact tests showed that the lupus population had a statistically significant increase in Pap smear reports of dysplasia compared to the control group (P < 0.021 for HGSIL/LGSIL combined, P < 0.036 for LGSIL alone). Examination of serial Pap smear results revealed that 45% of the lupus patients had cervical dysplasia at some time.CONCLUSION:Women with lupus have an increased prevalence of cervical dysplasia. Serial observation revealed dysplastic cytologies in nearly half of the patients, suggesting that this may be a more common problem than previously reported. Serial prospective studies are needed to assess better the risk of premalignant cervical lesions in lupus.