Progressive dyspnoea and chest X-ray shadows in a patient with focal segmental glomerulosclerosis on haemodialysis
Johnson T. Samuel1,,
Shahedlal Bari2,
Michael J. Kumwenda2,
Keith J. Taylor1,
Mark W. Atkinson3 and
Alistair F. Douglas2
1 Department of Respiratory Medicine,
2 Department of Nephrology and
3 Department of Pathology, Glan Clwyd Hospital, Rhyl, Denbighshire, UK
Keywords: cryptogenic organizing pneumonia; focal segmental glomerulosclerosis
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Introduction
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Focal segmental glomerulosclerosis (FSGS) is frequently treated with immunosuppressant drugs to influence progression of the disease [1]. In the immunosuppressed state, infections are common and respiratory infections when diagnosed on the basis of chest X-ray changes are often treated with antibiotics empirically before microbiological confirmation. Cryptogenic organizing pneumonia (COP) is an uncommon condition presenting with progressive dyspnoea and alveolar shadows on the chest X-ray and responds dramatically to corticosteroids [2]. Diagnosis of COP is by histology and early diagnosis and treatment result in clinical and radiological improvement. As infection is a common cause for a similar clinical picture in the immunocompromised, the use of corticosteroids may be detrimental if inappropriately used and creates a therapeutic dilemma. Hence the need for early histological diagnosis if this condition is suspected.
We report the first case of COP occurring in a patient with FSGS on regular haemodialysis.
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Case
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A 49-year-old Caucasian man first presented with uncontrolled hypertension, proteinuria and renal impairment. There was no history of heroin or other recreational drug use and he was negative for HIV. A renal biopsy showed FSGS and he was commenced on immunosuppressant therapy (prednisolone 1 mg/kg and cyclophosphamide 2 mg/kg). As his renal function continued to deteriorate, cyclophosphamide was withdrawn after 8 weeks and the dose of prednisolone was tapered gradually. He progressed rapidly to end-stage renal failure and was commenced on haemodialysis via a right internal jugular vein tunnelled catheter 10 weeks after starting immunosuppression. Six weeks later while on prednisolone (10 mg/day), he developed progressive dyspnoea and haemoptysis and was admitted to hospital.
On admission, he was dyspnoeic at rest, apyrexial and had a sinus tachycardia with a blood pressure of 180/90 mmHg. His respiratory rate was 30/min and his oxygen saturation was 85% on air. He had peripheral oedema but his jugular venous pressure was not elevated. Chest auscultation revealed bilateral inspiratory and expiratory crackles at the bases and mid-zones.
Initial investigations showed: haemoglobin 8.7 g/dl, white cell count 10.7x109, C-reactive protein 33 mg/l, plasma viscosity 1.5 mPas, serum sodium 132 mmol/l, serum potassium 4.7 mmol/l, urea 25 mmol/l, creatinine 1184 µmol/l, bilirubin 5 µmol/l, alkaline phosphatase 64 IU/l, aspartate aminotransferase 16 IU/l, alanine aminotransferase 16 IU/l, total serum protein 59 g/l, albumin 29 g/l, globulin 30 g/l, calcium 2.26 mmol/l, phosphate 1.3 mmol/l. Arterial PO2 (PaO2) on room air was 6.4 kPa, PCO2 4.2 kPa, pH 7.45 and oxygen saturation 85%. Initial chest X-ray showed air space consolidation in the right lower zone.
Serial blood, sputum, urine and catheter tip cultures were sterile and serological tests for mycoplasma and legionella infections were negative. Full-lung function tests showed a restrictive defect and the transfer factor by single breath CO method (TLCO) was 50% predicted. Echocardiogram showed moderate left ventricular hypertrophy, normal sized right ventricle and a small pericardial effusion. Autoantibody tests (anti-nuclear antibody, anti-double-stranded DNA, anti-neutrophil cytoplasmic antibody, anti-glomerular basement membrane antibody and rheumatoid factor) were negative. Serum complement was normal and there was a non-specific inflammatory pattern on serum protein electrophoresis. Initial bronchoscopic washings were sterile and at this stage he was unfit for trans-bronchial biopsy. He was treated with intravenous antibiotics (cefotaxime, clarithromycin and metronidazole), high flow oxygen and continuous positive pressure ventilation (CPAP). Serial chest radiographs showed the air space consolidation gradually progressing to involve the right and left lower and mid-zones in addition to cardiomegaly (Figure 1
).

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Fig. 1. Chest X-ray postero-anterior view showing patchy air space consolidation in both mid and lower zones of the lungs.
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At this stage, in the absence of an infectious agent, cryptogenic organizing pneumonia was considered and prednisolone (10 mg/day) was changed to high dose intravenous methyl prednisolone (500 mg twice daily). Forty-eight hours after the steroid dose was increased, the patient improved dramatically both clinically and radiologically and no longer required CPAP. Repeat bronchoscopy and trans-bronchial biopsy a week after steroids were started showed a non-specific inflammatory infiltrate in the alveolar walls with adjacent alveoli showing obliteration by a proliferation of organizing fibroblastic tissue typical of organizing interstitial pneumonia (Figure 2
). The steroids were tapered and the patient continued to improve clinically and the radiological changes resolved.

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Fig. 2. Trans-bronchial biopsy (haematoxylin & eosin x100) with focus of organizing interstitial fibrosis (arrow).
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Discussion
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Organizing pneumonia has now been recognized as a distinct clinicopathological entity defined by the presence in the distal air spaces of granulation tissue progressing from fibrin exudates to loose collagen-containing fibroblasts [3]. Organizing pneumonia has a number of associations including infections, drugs and connective tissue disorders but may remain cryptogenic in many cases [2]. There is no previous report of COP in association with FSGS and the only report of COP in association with glomerular diseases was in a patient with mesangiocapillary glomerulonephritis [4]. Patients present with subacute symptoms of non-productive cough, malaise, weight loss and dyspnoea, which can be severe and life threatening. Chest X-ray features are not specific and comprise of multiple alveolar shadows. Lung function tests show mild to moderate restrictive defects with reduced transfer factor to carbon monoxide. The diagnosis relies on the typical histological features mentioned and video-assisted thoracoscopic lung biopsy is preferred to trans-bronchial biopsy [5]. Corticosteroids are the standard treatment and symptoms resolve in as early as 48 h. The prognosis is usually excellent following treatment with corticosteroids [6].
We postulate that the organizing pneumonia was cryptogenic in this case as no immune or infective cause was found. The presence of new X-ray findings in a patient on tapering doses of steroids posed a diagnostic dilemma, as infections are common in this clinical situation. The diagnosis of COP was made after excluding an infective cause and on tissue biopsy. We report this case because organizing pneumonia is rare but eminently treatable and should be considered in patients with dyspnoea and progressive chest X-ray findings when infective and oedematous states are ruled out.
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Notes
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Correspondence and offprint requests to: Johnson T. Samuel, Department of Respiratory Medicine, Glan Clwyd Hospital, Rhyl, Denbighshire LL18 5UJ, UK. Email: abethamarathu{at}aol.com 
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References
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Received for publication: 7. 4.02
Accepted in revised form: 14. 8.02