1 Department of Renal Medicine 2 Department of Histopathology, Royal Preston Hospital Preston, UK Email: john.anderton{at}ithtr.nhs.uk
Sir,
In the February 2002 issue of Nephrology Dialysis Transplantation, Kingdon et al. [1] reported a case of ANCA +ve vasculitis following autologous stem cell transplantation. Their literature review revealed only three other cases of small vessel vasculitis following bone marrow or stem cell transplantation [24]. We wish to report a case of double positive (i.e. ANCA and anti-GBM +ve) vasculitis presenting with severe acute renal failure 20 months after successful bone marrow transplantation.
The patient, a 42-year-old female, was treated for adenocarcinoma of the cervix in 1996 with hysterectomy and radiotherapy. Two years later, she presented with acute myeloid leukaemia (AML type M2), presumed secondary to her previous radiotherapy. She relapsed following initial Clarkson's chemotherapy (i.e. daunorubicin and cytosine). Consequently, she received further chemotherapy with cytosine arabinoside-cytarabine, mitoxantrone and etoposide and underwent matched unrelated bone marrow transplantation in April 2000. Her post-transplant progress was smooth, aside from mild graft vs host disease. At the time of review in October 2001, haematology profile and renal function were normal (creatinine 109 µmol/l).
She presented again in January 2002, having been unwell for 3 weeks with malaise and dyspnoea. She was afebrile and euvolaemic with no evidence of sepsis. The following results were obtained: potassium 7.0 mmol/l, urea 92.8 mmol/l, creatine 1667 µmol/l, C-reactive protein 182 mg/l. Anti-myeloperoxidase antibody (pANCA)-positive 31.6 ELISA units (normal range 04), anti-glomerular basement membrane antibody (anti-GBM)-positive 42 ELISA units (normal range 02.5). The above two laboratory results were confirmed at a different reference laboratory, anti-GBM was positive at 149 U/ml (normal range 020) and pANCA was positive at 38 U/ml (normal range 06). Her other auto antibody screen was negative. Haematology profile was normal and all cultures were sterile. Chest X-ray and carbon monoxide transfer factor were normal, excluding pulmonary haemorrhage.
Urgent renal biopsy showed 74 glomeruli, 30 globally sclerosed, with 40 having crescents; these were predominantly cellular with a few showing fibrosis. Focal necroses were seen in occasional glomerular tufts and crescents. There were several areas of tubular atrophy with only 60% of the cortex being viable. Immunohistochemistry was negative with no glomerular deposits.
A diagnosis of double positive (ANCA/anti-GBM +ve) systemic vasculitis was made. She received haemodialysis, high-dose steroids, cyclophosphamide and five plasma exchange treatments. Dialysis-independence was achieved after five sessions and now, 3 months following presentation, her vasculitis is in remission with stable renal function (creatinine 200 µmol/l). A recent blood test showed absence of anti-GBM and pANCA antibodies.
In our case the negative immunohistochemistry could be explained by the fact that our laboratory used immunoperoxidase rather than immunofluroscence. It is well documented that linear anti-IgG deposits are often impossible to detect by immunoperoxidase [5,6]. The good recovery of renal function favours the renal lesion being predominantly ANCA-associated glomerulonephritis rather than anti-GBM disease, which only exceptionally recovers when treated late in the course of the disease.
Viral and bacterial infections are postulated triggers for post-transplant vasculitis, but no infection was documented in this case. As noted by Sanmarco et al. [7], a variety of auto antibodies may be detected following bone marrow transplantation. Furthermore, they are more likely to be of multiple specificity and may be more persistent in allogenic than autologous transplants. However, the development of systemic vasculitis is clearly very rare, and potential triggers to this remain speculative. To our knowledge this is the first report of double positive disease in this context: we urge both nephrologists and haematologists to be aware of this rare association.
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