NDT Advance Access originally published online on July 19, 2007
Nephrology Dialysis Transplantation 2007 22(12):3672-3673; doi:10.1093/ndt/gfm483
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Goodpasture's syndrome associated with autoimmune thrombotic thrombocytopenic purpura—an unusual case
Email: wim.terryn{at}yperman.net
Sir,
Goodpasture's syndrome is a rare autoimmune disease caused by anti-glomerular basal membrane antibodies (anti-GBM), presenting with rapidly progressive renal failure, associated or not with pulmonary haemorrhage [1]. We report a case of Goodpasture's syndrome limited to the kidneys, combined with thrombotic thrombocytopenic purpura (TTP).
A 37-year-old man without significant medical history presented with macroscopic haematuria since 4 weeks. He had no other complaints and denied substance abuse. He worked in a concrete factory, where he nebulized a mixture of hydrocarbons for the construction of concrete pillars. He mentioned that urinary stick analysis 6 months earlier had already revealed the presence of haematuria without proteinuria.
Clinical investigation was normal, except for arterial hypertension of 180/110 mmHg. Microscopic examination of a fresh urinary sample revealed large amounts of dysmorfic erythrocytes (>100 per high power field), together with erythrocyte casts. There was also proteinuria at 2.3 g/l. Serum creatinine was 5.9 mg/dl, and the patient was scheduled for renal biopsy after the weekend. At the moment of his admission for biopsy, he presented with anuria and a serum creatinine of 14 mg/day; he was feeling ill with nausea and vomitus. Chest X-ray was normal. He had been treated with amlodipine and blood pressure was 140/80 mmHg. The renal biopsy showed a diffuse crescentic glomerulonephritis involving all glomeruli with disruption of the glomerular basal membrane; immunofluorescence and immunohistochemical staining demonstrated pathognomonic linear basement membrane IgG deposition (Figure 1). There were no signs of vasculitis or TTP. Antineutrophilic cytoplasmatic antibodies (ANCA) and anti-nuclear antibodies (ANA) were absent and hepatitis serology was negative. Anti-GBM antibodies were detected in the serum. Haemodialysis was started, but without immunosuppressive therapy or plasmapheresis, because of the lack of any proven benefit in anuric patients with Goodpasture's syndrome [1]. A few days later, he developed spiking fever (39.5°C) with diarrhoea and progressive anaemia (Hb 7.7 g/dl) and thrombopenia (87.000/µl). Blood cultures remained negative and a faeces culture was negative for enteric pathogens or Escherichia coli 0157. Serum LDH was elevated (1500 U/ml) as was indirect bilirubin (1.46 mg/dl), with a negative direct Coombs test and an unmeasurable haptoglobin. Schistocytes were detected (5%). All these parameters had been normal at the time of the renal biopsy. Steroids (80 mg/day methylprednisolone) combined with daily plasma-exchange were started because of a high probability of TTP. After 5 days fever disappeared, but a lower grade of microangiopathic haemolysis persisted. Three weeks after the onset of microangiopathic haemolysis, the patient developed a generalized complex epileptic insult with severe agitation. A CT-scan of the brain was normal, and funduscopy revealed no signs of malignant hypertension. This epileptic insult could not be attributed to hypertension or medication and was considered secondary to his TTP. Daily plasma exchange was continued, and vincristine 1 mg weekly was added for a total of 3 mg, with progressive improvement and normalization of thrombopenia, disappearance of neurological symptoms and schistocytes. At that time, anti-GBM was negative. Plasma-exchange and steroids were then tapered, and 6 months after a final plasma-exchange, in the absence of anti-GBM antibodies, he was transplanted with a kidney from his wife. Three months after transplantation, creatinine clearance was 80 ml/min, and a protocol renal biopsy disclosed no pathologic abnormalities.
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Patients with anti-glomerular basement membrane antibodies in which glomerulonephritis and lung haemorrhage develop have Goodpasture's syndrome [1]. Our patient, who had no pulmonary symptoms, suffered from the so-called ‘renal limited’ variant of Goodpasture's syndrome.
The anti-glomerular antibodies are very specific and directed against the alpha3(IV) NC1 epitope of collagen [1]. Since the alpha3(IV) NC1 epitope is hidden within the alpha3.alpha4.alpha5(IV) protomer, it is presumed that an environmental factor [1], such as exposure to hydrocarbons as in our patient, or tobacco smoke, is required in order to reveal cryptic epitopes to the immune system. The microscopic isolated haematuria noted 6 months earlier could have been an early symptom of the disease, warranting early nephrologic assessment of haematuria in patients exposed to hydrocarbons.
The cornerstone of treatment of Goodpasture's syndrome consists of plasmapheresis, but this was not started because of anuria at the time of diagnosis, which predicts an infaust renal prognosis [1].
After a few days, our patient presented with fever and micro-angiopathic haemolytic anaemia, without obvious cause. Because TTP was suspected, treatment with steroids and plasma-exchange (1.5 times the plasma volume daily) was started, with only partial remission. After 20 days, this was furthermore complicated with an epileptic insult, further confirming the diagnosis of TTP. To the best of our knowledge, the association of autoimmune TTP with Goodpasture has only been reported in one article from 1984, which reports on 12 cases of Goodpasture's syndrome, of which six showed clinical as well as pathological signs of microangiopathic haemolytic anaemia [2]. Our present report confirms these data, and underscores the fact that the latter findings were neither incorrect nor coincidental. Because of the risk of recurrence of anti-GBM disease in a transplant kidney [3], transplantation with a kidney from his spouse was postponed until 6 months after disappearance of anti-GBM antibodies. Patient was advised to seek other employment, because in our opinion it is mandatory to avoid future exposition to hydrocarbons or other toxins.
In conclusion, we report for the first time since 1984 the association between Goodpasture and TTP, corroborating the existence of such an association.
Conflict of interest statement. None declared.
1Department of Nephrology
Regionaal Ziekenhuis Jan Yperman
Ypres
2Ghent University Hospital
3Department of Intensive Care
Ghent University Hospital
4Department of Nephrology
Heilig Hartziekenhuis
Roeselare
5Department of Pathology
Regionaal Ziekenuis Jan Yperman
Ypres, Belgium
Notes
See http://www.oxfordjournals.org/our_journals/ndtplus/
References
- Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport's Syndrome, Goodpasture's Syndrome, and Type IV Collagen. N Engl J Med (2003) 348:2543–2556.
[Free Full Text] - Stave GM, Croker BP. Thrombotic microangiopathy in anti-glomerular basement membrane glomerulonephritis. Arch Pathol Lab Med (1984) 9:747–751.
- Netzer KO, Merkel F, Weber M. Goodpasture syndrome and end-stage renal failure–to transplant or not to transplant? Nephrol Dial Transplant (1998) 13:1346–1348.[Web of Science][Medline]
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