P081 Unravelling SLE in a young male child

Background Juvenile-onset systemic lupus erythematosus (jSLE)) is a rare but severe multisystem autoimmune, inflammatory disease that can affect any organ system and cause significant morbidity and mortality. The disease onset occurs before the age of 18, however the peak age of onset is between 12 and 14 years and it affects ∼15–20% of all SLE patients. Patients with disease onset before 5 years of age are very uncommon and may be referred to as early-onset SLE. They commonly present with fever and general malaise, rash and arthritis. In addition, cases of jSLE, tend to have more severe organ manifestations and greater damage at the time of diagnosis as well as a higher incidence of renal, cardiovascular and neuropsychiatric involvement. Compared with adult-onset SLE, it is more aggressive, with higher medication burden including corticosteroids and other immunosuppressive drugs. Method and results This case report reviews the journey of a 5-year-old boy, who developed recurrent skin rashes, fever and generalised lymphadenopathy in his second year of life. After multiple hospital admissions and various investigations at different facilities spanning a year, he was admitted to the paediatric emergency unit at a tertiary hospital on account of an acute infection. On presentation, he was pyrexial. There were hypo- and hyperpigmented lesions extending over his scalp, face and upper arms as well as vasculitic lesions in his palms and soles; lip ulcers, sparse brown hair and multiple, non-tender lymph nodes in the cervical, supraclavicular and axillary regions. Respiratory examination revealed a right lobar pneumonia. Heart rate was 112 bpm and heart sounds were normal, however an echocardiogram showed a moderate pericardial effusion with no signs of tamponade. His abdomen was distended with a non-tender hepatomegaly. There was no synovitis. He was lethargic, but had no focal neurological signs. Laboratory results were as follows: normocytic anaemia (8.5 g/dl); ESR (120 mm/h); deranged transaminases; albumin (32 g/dl); Creatinine (12umol/l); urinalysis was normal, positive antinuclear antibody (1:320); positive double-stranded DNA (1:40); positive anti-smith, anti-Ro and anti-RNP antibodies; low C3, C4. A lymph node biopsy showed reactive changes only, with no evidence of haematological malignancy. The diagnosis of jSLE was confirmed at age 3yrs. The acute illness due to pneumonia was treated with antibiotics. Prednisolone 10 mg, Hydroxychloroquine (HCQ) 80 mg daily, Azathioprine 25 mg daily, calcium supplementation and gastric protection were added to manage the jSLE. He made an initial recovery and was managed in the outpatient clinic for months. However, his illness flared up again around age 4 years when he developed generalized seizures, facial and pedal oedema, low urine output, proteinuria 3+, low albumin (25 g/dl), creatinine (252umol/l) and high urine albumin-creatinine ratio (278.62 mg/mmol) reflecting new renal and CNS involvement. A renal biopsy was not available. He received pulse iv methylprednisolone 250 mg daily for 3 days followed by monthly iv cyclophosphamide therapy 500 mg (NIH Regime) which was discontinued after the 5th cycle due to haemorrhagic cystitis. He eventually continued treatment with mycophenolate mofetil 125 mg daily, HCQ 80 mg daily, Prednisolone 10 mg daily, Nifedipine and Enalapril and a year later, has low activity from the cutaneous, renal and CNS manifestations. There is renal damage (creatinine 180 μmol/l) and hypertension, as well as treatment complications from prednisolone causing bilateral cataracts. Conclusion Early diagnosis of jSLE is still a challenge and a high index of suspicion is required especially in the very young. Severe presentation and aggressive clinical course is associated with tissue damage, as in the case presented. Management is complex and we were challenged by the choice and availability of treatment suitable for the severity of his disease, bearing in mind that damage can occur early especially in a male child. In addition, it is important to consider his young age and long-term exposure to drug toxicity and complications.

Pretransplant BK Virus-Specific T-Cell-Mediated Immunity and Serotype Specific Antibodies May Have Utility in Identifying Patients at Risk of BK Virus-Associated Haemorrhagic Cystitis after Allogeneic HSCT

BK polyomavirus (BKPyV) persists lifelong in renal and urothelial cells with asymptomatic urinary shedding in healthy individuals. In some immunocompromised persons after transplantation of hematopoietic stem cells (HSCT), the BKPyV high-rate replication is associated with haemorrhagic cystitis (HC). We tested whether the status of BKPyV immunity prior to HSCT could provide evidence for the BKPyV tendency to reactivate. We have shown that measurement of pretransplant anti-BKPyV 1 and 4 IgG levels can be used to evaluate the HC risk. Patients with anti-BKPyV IgG in the range of the 1st–2nd quartile of positive values and with positive clinical risk markers have a significantly increased HC risk, in comparison to the reference group of patients with “non-reactive” anti-BKPyV IgG levels and with low clinical risk (LCR) (p = 0.0009). The predictive value of pretransplant BKPyV-specific IgG was confirmed by determination of genotypes of the shed virus. A positive predictive value was also found for pretransplant T-cell immunity to the BKPyV antigen VP1 because the magnitude of IFN-γ T-cell response inversely correlated with posttransplant DNAuria and with HC. Our novel data suggest that specific T-cells control BKPyV latency before HSCT, and in this way may influence BKPyV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of HSCT recipients at high risk of BKPyV disease.

Renal Failure Associated with Human Polyomavirus BK and Human Adenovirus in a Child with Acute Lymphoblastic Leukaemia

Immunocompromised patients are susceptible to multiple severe viral infections. This paper describes a 4-year-old boy with newly diagnosed B-cell precursor acute lymphoblastic leukaemia. The 4-year-old patient developed haemorrhagic cystitis, obstructive nephropathy and renal failure due to human polyomavirus BK and human adenovirus co-infection. Cidofovir should be used only in life-threatening cases.

BK Polyomavirus—Biology, Genomic Variation and Diagnosis

The BK polyomavirus (BKPyV), a representative of the family Polyomaviridae, is widespread in the human population. While the virus does not cause significant clinical symptoms in immunocompetent individuals, it is activated in cases of immune deficiency, both pharmacological and pathological. Infection with the BKPyV is of particular importance in recipients of kidney transplants or HSC transplantation, in which it can lead to the loss of the transplanted kidney or to haemorrhagic cystitis, respectively. Four main genotypes of the virus are distinguished on the basis of molecular differentiation. The most common genotype worldwide is genotype I, with a frequency of about 80%, followed by genotype IV (about 15%), while genotypes II and III are isolated only sporadically. The distribution of the molecular variants of the virus is associated with the region of origin. BKPyV subtype Ia is most common in Africa, Ib-1 in Southeast Asia, and Ib-2 in Europe, while Ic is the most common variant in Northeast Asia. The development of molecular methods has enabled significant improvement not only in BKPyV diagnostics, but in monitoring the effectiveness of treatment as well. Amplification of viral DNA from urine by PCR (Polymerase Chain Reaction) and qPCR Quantitative Polymerase Chain Reaction) is a non-invasive method that can be used to confirm the presence of the genetic material of the virus and to determine the viral load. Sequencing techniques together with bioinformatics tools and databases can be used to determine variants of the virus, analyse their circulation in populations, identify relationships between them, and investigate the directions of evolution of the virus.

Pretransplant BK virus-specific T-cell-mediated immunity and serotype specific antibodies may have utility in identifying patients at risk for BK virus associated haemorrhagic cystitis after allogeneic HSCT

BK polyomavirus (BKV) persists lifelong in the urinary tract with asymptomatic urinary shedding in healthy individuals. In immunocompromised persons after transplantation of hematopoietic stem cells (HSCT) the BKV high-rate replication is associated with haemorrhagic cystitis (HC) with a reported incidence of 17 %. Numerous studies of reconstitution of the immune system after HSCT have established the principal role of T cell effectors in the control of viral replication and reactivation. The value of pretransplant BKV-specific antibodies in transplanted patients for the protection from viral disease was long considered insignificant. We hypothesized that the status of BKV immunity prior to HSCT could provide evidence for the BKV tendency to reactivate and that examining the level of subtype-specific antibodies and T-cell response in individual patients could help to predict the risk of BKV reactivation and HC. Evaluation of the risk of HC in relation to pretransplant anti-BKV1,2,4 IgG levels together with clinical factors known before transplantation revealed that patients with medium anti-BKV IgG and significant clinical risk (SR) have a very significantly increased HC risk in comparison with the reference group of low anti-BKV IgG level and low clinical risk (LR) (P=0.0009). Analysis of pretransplant T cell immunity to BKV antigens VP1 and LTag has shown that magnitude of IFN-gamma T cell response inversely corelated with posttransplant DNAuria. We hypothesize that the control of BKV latency by BKV specific T cells before HSCT would be one of the factors that influence BKV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of patients who are at risk of developing BKV disease after HSCT.