Angela Pakozdi

Utility of a repeat renal biopsy in lupus nephritis: a single centre experience

Background The role of repeat renal biopsy in lupus nephritis (LN) to guide treatment or predict prognosis has been controversial. We assessed glomerular and tubulointerstitial histological characteristics of serial renal biopsies, correlations with clinical variables and the impact on subsequent management. Methods Out of a large single-centre cohort of 270 biopsy-proven LN patients, 66 (24%) had serial biopsies. LN classes based on glomerular pathology were defined according to the International Society of Nephrology/Renal Pathology Society 2003 classification, while tubulointerstitial pathologies were evaluated using the revised Austins semi-quantitative scoring system. Results LN class transitions from proliferative (III and IV) to non-proliferative classes (II and V) were uncommon (n = 4, 7.7%), while non-proliferatives frequently switched to proliferative classes (n = 12, 63.2%) and were more likely to receive increased immunosuppression (P = 0.040). Biochemical or serological variables could not predict these histopathological transitions. Tubulointerstitial score (mean ± standard deviation) progressed from 2.69 ± 2.03 on reference to 3.78 ± 2.03 on repeat biopsy (P = 0.001). Serum creatinine levels correlated with the degree of tubular atrophy on both reference (r = 0.33, P = 0.048) and repeat biopsy (r = 0.56, P < 0.001), and with interstitial scarring (r = 0.60, P < 0.001) on repeat biopsy. Greater interstitial inflammation on reference biopsy was associated with advanced interstitial scarring on repeat biopsies (r = 0.385, P = 0.009). Conclusions Repeat renal biopsy is an important tool to guide management, in particular in those with initial class II or V who flare. Although class transitions cannot be predicted by clinical parameters, serum creatinine level correlates with the degree of tubulointerstitial damage.

PS8:159 Moving with the times: social media use amongst lupus patients

Background Over the last decade the rise in social media use has been almost exponential. There are numerous online platforms where patients can interact for support and information gathering. A study presented at the ACR in 2013 showed lupus patients were willing to participate in Facebook chats for the purposes of disease education.1 We sought to discover current usage of social media amongst an ethnically mixed population attending an inner city tertiary lupus centre. Methods Questionnaires were distributed to consecutive patients attending the Barts Lupus Centre from October 2016 to February 2017. 17 questions asked about patient demographics and patients use of online information and support services, particularly social media platforms, with regards to lupus. Results 84 completed questionnaires were returned. 83% respondents were female. There were 28 South Asians, 26 Whites and 24 Blacks, 2 of other ethnic groups and 2 of mixed race. 64% (n=54) of patients accessed online lupus information and support sites. 45% percent (n=38) of patients reported using social media sites (26% South Asians, 34% Blacks and 34% Whites). Of those using social media 22% (n=8) patients used these tools daily and 30% (n=11) reported weekly use. Facebook (n=20), blogs (n=9), youtube (n=9), and Instagram (n=7) were cited as the most frequently used applications. Most patients (n=30) sought information on the disease, 17 (45%) wanted to find out about new treatments for lupus, 16 (42%) sought new ways to self-manage their disease, 14 (37%) sought interactions with other patients, and 10 (26%) were seeking support online. Patients most commonly wanted information on skin and joint complaints and family planning. 66% (n=56) thought their rheumatology team should have an online social media application to communicate with their patients. Conclusions A significant proportion of our lupus patients (45%) use social media to access information and support for their disease. Facebook, blogs, Instagram and Youtube are commonly used. Social media applications can provide physicians with a tool to interact with lupus patients to improve accessibility to health care and better health outcomes. Reference . Spring NH. 2013ACR/ARHP Annual Meeting, abstract 990.

PS2:43 Is lupus more prevalent in world’s most stressed countries?

Background A number of studies have implicated psychological stress as a trigger for autoimmune diseases. In a questionnaire study involving 120 lupus patients emotional stress was selected in over 75% cases as a trigger for their disease.1 The role of stress as a trigger in lupus however is controversial. Here we study whether there is an association between the prevalence of lupus in various countries and their reported stress measures. Methods We undertook a literature review of the reported prevalence of lupus in various countries across the world. We then recorded the reported stress index in those countries from Bloomberg’s study,2 which utilised seven equally weighted variables: homicide rates, GDP per capita income inequality, corruption perception, unemployment, urban air pollution and life expectancy to rank 74 countries according to stress levels. Pearsons correlation was used to measure association between national stress indices and lupus prevalence Results Results are presented in graph 1. Prevalence data was only available in the literature for limited countries. Of the countries studied no correlation was found between national stress indices and lupus prevalence (r=−0.028, p-value 0.449). Conclusion We found no association between a country’s prevalence of lupus and the measured stressfulness of its living environment.Abstract PS2:43 Figure 1 References . Stojanovich L. Stress as a trigger of autoimmune disease. Abstracts book: 5th International Congress on Autoimmunity, Sorrento, Italy, vol. 355. Autoimmun Rev; 2006. . World Health Organisation. United Nations Office on Drugs and Crime, International Monetary Fund, Central Intelligence Agency World Factbook, Transparency InternationalMay 2013.

10. Reactivation of hepatitis B virus in a patient with psoriatic arthritis treated with methotrexate

Introduction: Transaminitis in psoriatic arthritis treated with disease modifying anti-rheumatic drugs (DMARDs) is common and significant liver damage is three times Health NHS more likely than in rheumatoid arthritis. Commonly described risk factors include non-alcoholic fatty liver disease,obesity, diabetes,alcohol, concomitant non-steroidal antiinflammatory drugs, corticosteroids and other DMARDs. Reactivation of hepatitis B virus (HBV) in patients undergoing immunosuppressive therapy is a well-recognized and potentially fatal complication, yet preventable. Here we report a rare case of HBV reactivation in a patient with psoriatic arthritis shortly after starting methotrexate treatment and to emphasize the importance of baseline screening for chronic HBV infection. Case description: A 30-year old Caucasian male patient was referred with longstanding psoriatic arthritis in May 2017. He had been treated with sulfasalazine in the past but has been without immunosuppression due to family planning since 2011. On examination he had active skin psoriasis and polyarthritis. There was no other significant past medical history,hewasanon-smoker,consumedalcoholsocially anddidnotuse any illicit drugs. He had a long-term female sexual partner. His baseline blood tests including liver function tests were unremarkable. He was started on methotrexate 10 mg once weekly and folic acid 5 mg once weekly. On his two-week monitoring blood test his liver function tests were markedly deranged including alanine aminotransferase (ALT) of 2577 U/Landbilirubin67umol/L.Hedevelopedatransientperiodof jaundice lastedforoneweekbutdidnotseekmedicalattentionandcontinued with themethotrexate. Heattended his follow-up rheumatologyappointment four weeks after starting the methotrexate when he was no longer jaundiced and liver function test revealed improvement in his ALT at 119 U/L. Further liver investigations including a viral hepatitis screen revealed reactivation of HBV. His serology showed positive HBV surface antigen (HBsAg), low titre IgM core antibody, high titre IgG core antibody (anti-HBc), negative e antigen and positive e antibody, with an HBV DNA viral loadof2.11logIU/ml. Discussion: There is a vast amount of evidence that HBV-induced liver inflammation is in fact mainly immune-mediated. HBV replication and expression of viral epitopes in infected hepatocytes is followed by a predominantlyCD8þT-lymphocyteinducedacuteorchronicliver inflammation. In chronic HBV infection, spontaneous intermittent rises in ALT levels preceded by increase in serum HBV DNA are common. Immunosuppressivedrugscantriggertheseflares,andinparticularcorticosteroids can directly stimulate HBV replication. Furthermore, the immunosuppressiveeffectonthehost immunesystemindirectly leads to abundantviral replication. Inaddition,suddenwithdrawalof immunosuppressive drugscan result inanexaggeratedhost immune response leading to potentially life-threatening liver injury. The list of immunosuppressive drugs associated with HBV reactivation has been constantly expanding. The most commonly reported synthetic DMARD associatedwithHBVreactivation ismethotrexate.The riskofHBVreactivationbymethotrexate alone is thereforeconsidered tobe low buthigher with concomitant use of corticosteroids. Young male patients appear to be at highest risk of reactivation, although the risk mostly depends on HBsAgstatus.HBVscreeningstandardsandthepreventionofHBVreactivation have dramatically changed in thepastdecade. Improved recommendations regarding screening for HBV infection prior to starting immunosuppressive agents or chemotherapy have been mastered by variousgastroenterologysocieties. The latest one, forexample, the2017 clinical practice guideline by the European Association for the Study of i10 11–12 October 2017 POSTER CASE REPORTS

Systematic review and the external validity of randomized controlled trials in lupus nephritis

Introduction Randomized controlled trials (RCTs) are considered the gold standard for assessing treatment efficacy. However, sampling bias can affect the generalization of results to routine clinical practice. Here we assessed whether patients with lupus nephritis (LN) seen in routine clinical practice would have satisfied entry criteria to the major published RCTs in LN. Methods A systematic literature search from January 1974 to May 2015 was carried out, identifying all RCTs investigating LN induction treatment. Patients diagnosed with proliferative or membranous LN between 1995 and 2013 were identified from the Barts Lupus Centre database; baseline characteristics were compared with each RCT’s entry criteria to assess hypothetical inclusion or exclusion. Results Of 363 articles, 33 RCTs met inclusion criteria. Of 137 patients newly diagnosed with LN (111 with proliferative/mixed proliferative and 26 with pure membranous LN), 32% would have been excluded from RCT entry (range 8%–73%). The main reasons for exclusion would have been too severe disease, too mild disease, or prior immunosuppressant use, which were exclusion criteria in 26, 20, and 22 RCTs, respectively. A total of 27 patients with LN (20%) were re-biopsied due to flare; 68% of these would have been ineligible to enter RCTs. Conclusion Published RCTs do not truly reflect the heterogeneity of patients with LN in routine practice at our lupus center. The external validity of RCTs could be improved by including more representative patient cohorts. RCTs should be used as a guide but consideration should be given to similarities between individual patients and the characteristics of the trial cohorts before treatment decisions being made.

A7.9 Repeat renal biopsies help to tailor immunosuppression in lupus nephritis

Background and objectives Lupus nephritis (LN) is the major cause of morbidity and mortality in patients with systemic lupus erythematosus. The role of repeat kidney biopsies (RB) to guide treatment or to predict outcome and prognosis has been controversial. In this retrospective study we focused on histological characteristics of RBs and aimed to identify any clinical variables useful to predict histological changes. Methods In a large single-centre cohort of 257 patients from 1988–2014 with biopsy proven LN, 58 (23%) had two or more biopsies (a total of 68 RBs). LN classes based on glomerular pathology were defined according to the ISN/RPS classification. Clinical and laboratory data were obtained from electronic records of patients. Results The median time between initial and RB was 33 months [IQR, 15–84]. Caucasians (n = 7) had a lower RB rate of 14% compared to blacks (n = 36, 32%; p = 0.010). Indication for RB was worsening proteinuria (n = 38, 71%; of which 23 had associated rising creatinine, 61%), rise in serum creatinine alone (n = 6, 11%) and lack of treatment response (n = 9, 17%) defined as <50% reduction in proteinuria. At time of RB, 25 (78%) had raised dsDNA, 33 (73%) had low complements. LN class transition occurred in 33 (49%), most commonly from class II or V to III or IV (n = 11, 36%). Swith from a proliferative to a pure non-proliferative class was rare (n = 3, 4.4%). 5 RB (7%) showed inactive lesions either due to FSGS or advanced sclerosing LN. 42 (65%) had a change in their treatment regime. Immunosuppression was more likely to be escalated in case of a class switch (93%, p = 0.000). The histological transition could not be predicted by any serological or biochemical variables. Conclusion Over a 1/3 of our LN patients showed histological transition to a more aggressive class, based on which the majority (93%) had treatment escalation. Histological transition could not be predicted by clinical values. Hence, we conclude that RB remains an important tool to guide management of selected patients with LN, in particular those with initial class II or V who flare.