Acute Human Parvovirus B19 Infection and Nephrotic Syndrome in Patients with Sickle Cell Disease
Authors: Quek Lynn , Sharpe Claire , Dutt Neelanjana , Rees David , Height Sue , Zuckerman Mark , Thein Swee Lay 
Published: April 2020

Abstract
Human Parvovirus B19 (HPV B19) infection has previously been thought to be a trigger of nephrotic syndrome. The virus is associated with significant morbidity in patients with sickle cell disease (SCD) and a major cause of transient red cell aplasia (TRCA). We report three patients with SCD who presented with TRCA secondary to acute HPV B19 infection who subsequently developed significant proteinuria and nephrotic syndrome (NS) on outpatient follow up. There were 37 cases of acute HPV B19 infection in SCD patients admitted to King’s College Hospital between November 2002 and July 2008. 29 cases were in children below the age of 16 years, eight in patients over the age of 16 years. The average age of the cohort was just over 11 years at diagnosis. Three patients developed NS within 4 months of acute HPV B19 infection and TRCA. Two of these patients were aged 17 and 26 years at diagnosis (patient 1 and 2 respectively), whereas the third was a child aged 11 (patient 3). Renal histology demonstrated the collapsing variant of focal segmental glomerulosclerosis (FSGS) in the acute phase of NS in patient 1, a characteristic finding associated with HPV B19-associated nephrotic syndrome. A subsequent biopsy in the same patient two years later demonstrated non-collapsing FSGS and marked interstitial fibrosis. Patient 2 had a renal biopsy performed 4 months after the onset of NS. This demonstrated non-collapsing FSGS, acute sickle nephropathy and significant chronic tubular atrophy. Patient 3 also had a renal biopsy 1 year after her acute HPV B19 infection which demonstrated the cellular variant of FSGS. Patient 1 was treated with immunosuppression and although the NS has improved slowly he continues to have significant proteinuria and progressive renal impairment. Patient 2 has not received immunosuppressive therapy and has also slowly improved from her NS but continues to have significant proteinuria; her estimated GFR has fallen from 169 ml/min to 104 ml/min six months after the acute HPV B19 infection. Patient 3 was treated with corticosteroids with subsequent improvement in serum albumin and symptoms but proteinuria persists with normal renal function. Consistent with previous reports, we observe that NS is a relatively rare complication of HPV B19 infection in young children with SCD (one case in 29 in our cohort). However, two out of eight patients older than 16 years developed this complication. Proteinuria in patients with SCD is common and gradual in onset, and eventually may progress to NS. Nephrotic syndrome of acute onset in adults with SCD is rare, only two cases were observed during a 6-year period among our cohort of over 400 adult patients with SCD. In both cases, they were associated with recent HPV B19 infection. It has previously been noted that acute HPV B19 infection in older patients with HbSC SCD have a more severe clinical course than younger children (Smith-Whitley et al., 2004). Our data, though limited by small numbers in the cohort, suggest that older SCD patients with acute HPV B19 infection may be more susceptible to chronic complications including the development of NS and progressive renal fibrosis. A correct diagnosis of the aetiology of NS is vitally important as the HPV B19-associated condition may not be responsive to corticosteroids, unlike other aetiologies of NS in this age group. It is possible that antiviral therapy may be of benefit in the acute setting but this needs further investigation. Furthermore, immunisation of older children and young adults who are HPV B19-naïve may be effective in preventing an important contributor of chronic renal disease in SCD patients.