R du Toit

Clinical features and outcome of lupus myocarditis in the Western Cape, South Africa

Background African American ethnicity is independently associated with lupus myocarditis compared with other ethnic groups. In the mixed racial population of the Western Cape, South Africa, no data exists on the clinical features/outcome of lupus myocarditis. Objectives The objective of this study was to give a comprehensive description of the clinical features and outcome of acute lupus myocarditis in a mixed racial population. Methods Clinical records (between 2008 and 2014) of adult systemic lupus erythematosus (SLE) patients at a tertiary referral centre were retrospectively screened for a clinical and echocardiographic diagnosis of lupus myocarditis. Clinical features, laboratory results, management and outcome were described. Echocardiographic images stored in a digital archive were reanalysed including global and regional left ventricular function. A poor outcome was defined as lupus myocarditis related mortality or final left ventricular ejection fraction (LVEF) <40%. Results Twenty-eight of 457 lupus patients (6.1%) met inclusion criteria: 92.9% were female and 89.3% were of mixed racial origin. Fifty-three per cent of patients presented within three months after being diagnosed with SLE. Seventy-five per cent had severely active disease (SLE disease activity index ≥ 12) and 67.9% of patients had concomitant lupus nephritis. Laboratory results included: lymphopenia (69%) and an increased aRNP (61.5%). Treatment included corticosteroids (96%) and cyclophosphamide (75%); 14% of patients required additional immunosuppression including rituximab. Diastolic dysfunction and regional wall motion abnormalities occurred in > 90% of patients. LVEF improved from 35% to 47% (p = 0.023) and wall motion score from 1.88 to 1.5 (p = 0.017) following treatment. Overall mortality was high (12/28): five patients (17.9%) died due to lupus myocarditis (bimodal pattern). Patients who died of lupus myocarditis had a longer duration of SLE (p = 0.045) and a lower absolute lymphocyte count (p = 0.041) at diagnosis. LVEF at diagnosis was lower in patients who died of lupus myocarditis (p = 0.099) and in those with a persistent LVEF < 40% (n = 5; p = 0.046). Conclusions This is the largest reported series on lupus myocarditis. The mixed racial population had a similar prevalence, but higher mortality compared with other ethnic groups (internationally published literature). Patients typically presented with high SLE disease activity and the majority had concomitant lupus nephritis. Lymphopenia and low LVEF at presentation were of prognostic significance, associated with lupus myocarditis related mortality or a persistent LVEF < 40%.

Empirical Evaluation of Conditions Influencing the Polymerase Chain Reaction: Enterotoxigenic Escherichia coli as a Test Case

False polymerase chain reaction (PCR) results may be obtained under unfavourable reaction conditions. Therefore optimal conditions for the different factors influencing a specific PCR method should be determined before introduction to a clinical diagnostic laboratory. This study has concentrated on the detection of heat-labile enterotoxin-producing E. coli by PCR, with empirical evaluation of various factors. Template was prepared by heat-lysis of E. coli, and this was shown to be adequate for PCR detection. The results showed that deviation from the optimal conditions of any of the following conditions may lead to false results: lysis of bacterial cells, denaturation temperature during cycling, annealing temperature, primer concentration, enzyme concentration, magnesium concentration and ion concentration. Three different detection methods for PCR product were also evaluated. As little as one bacterium can be detected after 35 cycles of PCR amplification with 32P-labelled oligonucleotide probe. An alkaline phosphatase-labelled probe was 10-fold less sensitive, whereas 100 bacteria in 10 microliters of the original sample suspension were necessary to give a positive signal after gel electrophoresis. The information in this study may be useful to those who wish to introduce PCR tests to diagnostic laboratories.

The diagnostic accuracy of integrated positron emission tomography/computed tomography in the evaluation of pulmonary mass lesions in a tuberculosis-endemic area

BACKGROUND Integrated positron emission tomography/computed tomography (PET-CT) is a well-validated modality for assessing pulmonary mass lesions and specifically for estimating risk of malignancy. Tuberculosis (TB) is known to cause false-positive PET-CT findings. OBJECTIVE To investigate the utility of PET-CT in the evaluation of pulmonary mass lesions and nodules in a high TB prevalence setting. METHODS All patients referred for the evaluation of a solitary pulmonary nodule or mass and who underwent PET-CT scanning over a 3-year period were included. The PET-CT findings, including maximum standardised uptake value (SUVmax), were compared with the gold standard (tissue or microbiological diagnosis). The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy for malignant disease were calculated according to the SUVmax cut-off of 2.5 and a proposed cut-off obtained from a receiver operating characteristic (ROC) curve. RESULTS Forty-nine patients (mean (standard deviation) age 60.1 (10.2) years; 29 males) were included, of whom 30 had malignancy. Using an SUVmax cut-off of 2.5, PET-CT had a sensitivity, specificity, positive and negative predictive value and diagnostic accuracy for malignancy of 93.3%, 36.8%, 70.0%, 77.8% and 71.4%, respectively. After a ROC curve analysis, a suggested SUVmax cut-off of 5.0 improved the specificity to 78.9% and the diagnostic accuracy to 86.7%, with a small reduction in sensitivity to 90.0%. CONCLUSIONS The diagnostic accuracy of PET-CT in the evaluation of pulmonary mass lesions using the conventional SUVmax cut-off of 2.5 was reduced in a TB-endemic area. An SUVmax cut-off of 5.0 has a higher specificity and diagnostic accuracy for malignancy, with a comparable sensitivity.

Oral v. pulse intravenous cyclophosphamide: A retrospective analysis of adverse events in a setting with a high burden of infectious disease

BACKGROUND Cyclophosphamide (CPM) is still considered to be the first-line treatment for many life-threatening autoimmune conditions. It does, however, carry a significant risk of serious adverse events, especially infections. At present CPM is administered as either a daily oral dose (DOC) or an intravenous pulse (PIVC). There is uncertainty regarding the safety profiles of both regimens in settings with a high burden of infectious diseases. OBJECTIVE To compare the frequency and nature of adverse events related to the use of DOC and PIVC in such a setting. METHODS A cohort of patients treated with CPM for autoimmune diseases at Tygerberg Academic Hospital, Cape Town, South Africa, from 1 January 2008 to 31 May 2013 was studied. We compared participants receiving DOC and PIVC with regard to disease characteristics and the occurrence of major adverse events. RESULTS A total of 134 participants (92 DOC and 42 PIVC) were included. Participants in the DOC group were treated for longer (174 v. 101 days; p<0.01) and with higher cumulative doses (17 276 v. 3 327 mg; p<0.01). Risk of infection was similar in the two groups, although there were 6 deaths from leucopenic sepsis in the DOC group (v. 0; p=0.18). Nadir leucocyte counts were also lower in the DOC group (median 3.8 v. 5.3 × 109/L; p=0.02). CONCLUSION Infection rates in the two groups were similar, but DOC was associated with longer treatment duration, greater cumulative CPM doses and more severe leucopenia. If resources allow and available literature provides support for efficacy, consideration should be given to greater use of PIVC.

AB0606 Lupus Myocarditis in the Western Cape, South Africa: Analysis of Clinical and Echocardiographic Features

Background Lupus myocarditis (LM) is a serious manifestation of systemic lupus erythematosus (SLE). LM in patients of African American ethnicity has an increased prevalence and higher mortality compared to other ethnic groups. In the mixed racial population of the Western Cape, South Africa, no data exists on the clinical features and outcome of LM. Echocardiography is frequently used to support the diagnosis of LM. Speckle tracking (ST) is more sensitive than standard imaging in the detection of left ventricular (LV) dysfunction. Literature on the use of ST in patients with clinically evident LM is limited. Objectives To give a comprehensive description of the clinical and echocardiographic features of acute LM in a mixed racial population. Methods Clinical records (over 6 years) of adult SLE patients at a tertiary referral centre were retrospectively screened for a clinical and echocardiographic diagnosis of LM. Clinical features, laboratory results, management and outcome were described. Echocardiographic images stored in a digital archive were reanalysed (where views allowed), including LV regional wall motion abnormalities (RWMA) and longitudinal strain through ST. Results 28 patients (6.1%) met inclusion criteria: 92.9% were female and 89% were of mixed racial origin. 54% of patients presented with LM within 3 months after being diagnosed with SLE. Median SLE disease activity index was 17.5 (IQR:12.3-24) and 50% of patients had concomitant lupus nephritis. Laboratory results included: low complement (92.3%); urinary protein >0.5g/day (83%); increased aRNP (62%). Initial (at time of diagnosis) and most recent echocardiographic data are summarised in table 1. Treatment included corticosteroids (96%) and cyclophosphamide (75%); 14% of patients required additional immunosuppression. Clinical improvement occurred in 67% of patients (563 days, median); 2 patients relapsed. Though the median LV ejection fraction (LVEF) improved from 35 to 47%, reduced longitudinal strain and RWMA persisted in most patients (Table 1). Overall mortality was high (12/28): 5/28 (17.9%) died due to LM compared to 2/24 (8.3%) in another case series. Mortality due to LM and/or treatment related complications were 35.7% (10/28).Table 1 Initial echocardiogram (n=28) Most recent echocardiogram (n=19) Median Ratio of test done Median Ratio of test done (IQR) (%) (IQR) (%) Time (days) 0 390 (93–799) Increased LVIDa (cm) 5.2 (4.4–5.6) 11/28 (39) 4.8 (4–5.6) 5/19 (26) LVEFb 35% (26–46) 47% (37–50) RWMA present 24/24 (100) 16/18 (89) Decreased longitudinal strain 13/13 (100) 8/8 (100) IQR: interquartile range; LVID: left ventricular internal diameter; LVEF: left ventricular ejection fraction; RWMA: regional wall motion abnormalities.a Increased LVID >5.3cm;b LVEF: Mild impairment: 45–54%; moderate: 36–44%; severe: ≤35%. Conclusions This is the largest reported case series on LM. The mixed racial population had a similar prevalence, but higher mortality compared to other ethnic groups (published literature). An increased awareness towards an early diagnosis is essential, especially in recently diagnosed SLE patients with concomitant lupus nephritis. ST (not previously described in acute LM) and RWMA showed persistent LV dysfunction despite an improved LVEF and could be utilised as a sensitive diagnostic tool in LM. Disclosure of Interest None declared