Childhood Systemic Lupus Erythematosus: Presentation, management and long-term outcomes in an Australian cohort.

OBJECTIVES: Systemic Lupus Erythematosus (SLE) is a serious autoimmune disease often resulting in major end-organ damage and increased mortality. Currently, no data exists focussing on the presentation, long-term management and progression of SLE in the Australian paediatric population. We conducted the first Australian longitudinal review of childhood SLE, focussing on response to treatment and outcomes. METHODS: Detailed clinical and laboratory data of 42 children diagnosed with SLE before 16 years from 1998 to 2018 resident in Western Australia was collected. Data was collected at diagnosis and key clinical review time points and compared using the Systemic Lupus Collaborating Clinics (SLICC) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) criteria. End organ damage was assessed against Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Incidence rates of disease complications and end organ damage were determined. RESULTS: Of the 42 children, 88% were female with average age at diagnosis of 12.5 years. Indigenous Australians were over represented with an incidence rate 18-fold higher than non-Indigenous, although most children were Caucasian, reflecting the demographics of the Australian population. Median duration of follow-up was 4.25 years. On final review, 28.6% had developed cumulative organ damage as described by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (incidence rate: 0.08/PY (95% CI 0.04-0.14)), and one child died. Twenty-nine children had renal involvement (incidence rate: 0.38/PY (95% CI 0.26-0.56)). Of the 27 patients with biopsy proven lupus nephritis, 70% had Class III or IV disease. Average length of prednisolone use from diagnosis was 32.5 months. Hydroxychloroquine (n = 36) and mycophenolate mofetil (n =21) were the most widely used steroid sparing agents. 61.9% received rituximab and/or cyclophosphamide. CONCLUSION: This is the first longitudinal retrospective review of Australian children with SLE, with a markedly higher incidence in Indigenous children. Although improving, rates of end organ complications remain high, similar to international cohort outcomes. Longitudinal multi-centre research is crucial to elucidate risk factors for poor outcomes, and identifying those warranting early more aggressive therapy.

Invasive fungal disease in children with acute myeloid leukaemia: An Australian multicentre 10-year review.

BACKGROUND: Invasive fungal disease (IFD) is a common and important complication in children with acute myeloid leukaemia (AML). We describe the epidemiology of IFD in a large multicentre cohort of children with AML. METHODS: As part of the retrospective multicentre cohort TERIFIC (The Epidemiology and Risk factors for Invasive Fungal Infections in immunocompromised Children) study, proven/probable/possible IFD episodes occurring in children with primary or relapsed/refractory AML from 2003 to 2014 were analysed. Crude IFD prevalence, clinical characteristics, microbiology and treatment were assessed. Kaplan-Meier survival analysis was used to estimate 6-month survival. RESULTS: There were 66 IFD episodes diagnosed in 63 children with AML. The majority (75.8%) of episodes occurred in the context of primary AML therapy. During primary AML therapy, the overall prevalence was 20.7% (95% CI 15.7%-26.5%) for proven/probable/possible IFD and 10.3% (95% CI 6.7%-15.0%) for proven/probable IFD. Of primary AML patients, 8.2% had IFD diagnosed during the first cycle of chemotherapy. Amongst pathogens implicated in proven/probable IFD episodes, 74.4% were moulds, over a third (37.9%) of which were non-Aspergillus spp. Antifungal prophylaxis preceded 89.4% of IFD episodes, most commonly using fluconazole (50% of IFD episodes). All-cause mortality at 6 months from IFD diagnosis was 16.7% with IFD-related mortality of 7.6% (all in cases of proven IFD). CONCLUSIONS: IFD is a common and serious complication during paediatric AML therapy. Mould infections, including non-Aspergillus spp. predominated in this cohort. A systematic approach to the identification of patients at risk, and a targeted prevention strategy for IFD is needed.

Invasive fungal infections in children with acute lymphoblastic leukaemia: Results from four Australian centres, 2003-2013.

BACKGROUND: Invasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL. METHODS: IFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria with a 'modified-possible' category included. RESULTS: A total of 123 IFI episodes in 119 patients with ALL were included. A proven, probable, possible and modified-possible IFI was diagnosed in 56 (45.5%), 22 (17.9%), 39 (31.7%) and six (4.9%) episodes, respectively. The prevalence was 9.7% (95% confidence interval [CI] 8-11.4%) overall and 23.5% (95% CI 14.5-32.5%) for relapsed/refractory ALL. For non-relapsed ALL, the IFI prevalence was significantly higher for children with high-risk compared to standard-risk ALL (14.5% vs 7.3%, P = .009), and IFI were more common during induction, consolidation and delayed intensification phases. Mould infections occurred more frequently than non-mould infections. Thirteen children (10.9%) died within 6 months of IFI diagnosis with five deaths (4.2%) attributable to an IFI. CONCLUSIONS: IFI is more common in children with high-risk ALL and in relapsed disease. Overall survival was encouraging, with IFI contributing to very few deaths.

Epidemiology of invasive fungal infections in immunocompromised children; an Australian national 10-year review.

BACKGROUND: A thorough understanding of local and contemporary invasive fungal infection (IFI) epidemiology in immunocompromised children is required to provide a rationale for targeted prevention and treatment strategies. METHODS: Retrospective data over 10 years from four tertiary pediatric oncology and hematopoietic stem cell transplant (HSCT) units across Australia were analyzed to report demographic, clinical, and mycological characteristics of IFI episodes, and crude IFI prevalence in select oncology/HSCT groups. Kaplan-Meier survival analyses were used to calculate 180-day overall survival. RESULTS: A total of 337 IFI episodes occurred in 320 children, of which 149 (44.2%), 51 (15.1%), and 110 (32.6%) met a modified European Organization for Research and Treatment of Cancer (mEORTC) criteria for proven, probable, and possible IFI, respectively. There were a further 27 (8.0%) that met a "modified possible IFI" criteria. Median age at IFI diagnosis was 8.4 years. Crude mEORTC IFI prevalence in acute lymphoblastic leukemia, acute myeloid leukemia, solid tumor, and allogeneic HSCT cohorts was 10.6%, 28.2%, 4.4%, and 11.7%, respectively. Non-Aspergillus species represented 48/102 (47.1%) molds identified, and non-albicans Candida represented 66/93 (71.0%) yeasts identified. There were 56 deaths among 297 children who met mEORTC criteria, with 180-day overall survival for proven, probable, and possible IFIs of 79.7%, 76.2%, and 84.4%, respectively. CONCLUSION: Non-Aspergillus molds and non-albicans Candida contributed substantially to pediatric IFI in our study, with high IFI prevalence in leukemia and allogeneic HSCT cohorts. Inclusion of IFIs outside of European Organization for Research and Treatment of Cancer criteria revealed an IFI burden that would go otherwise unrecognized in published reports.

Clinical presentation of rheumatic fever in an endemic area.

This study documented whether patients diagnosed with acute rheumatic fever (ARF) in North Queensland, Australia, conformed to the 1992 Revised Jones Criteria (RJC). The authors aimed to determine whether inclusion of subclinical carditis (SCC) and monarthritis as major manifestations and a low-grade temperature as a minor manifestation in the RJC are justified in this population. A retrospective review of patients in whom the diagnosis of ARF relied on the experience of clinicians and who were admitted to the Townsville and Cairns Base Hospitals between 1997 and 2007 was undertaken. Of the 98 cases reviewed, 71.4% satisfied the RJC. Modification of the RJC increased the rate of criteria satisfaction to 91.8%. On presentation, 27 patients had SCC. Of the patients with SCC followed up, 70.5% had long-term valvular consequences. In populations endemic for ARF, monarthritis, SCC and a low-grade temperature should be included in the RJC.