Rheumatology Advance Access published online on November 6, 2008
Rheumatology, doi:10.1093/rheumatology/ken402
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Cyclophosphamide-associated complications: we need to be aware of SIADH and central pontine myelinolysis
1Department of Rheumatology, Nizam's Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India
Correspondence to:
G. Narsimulu, Department of Rheumatology, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad 500 082, Andhra Pradesh, India. E-mail: narsimulunims{at}hotmail.com
SIR, We report a case highlighting a rare complication that rheumatologists might come across while using cyclophosphamide.
A 49-yr-old lady with dcSSc for 2 yrs, presented with cough and dyspnoea on exertion of 4 months duration. Clinical examination, HRCT-thorax and pulmonary function test revealed interstitial lung disease with severe restrictive abnormality. She was started on monthly pulses of intravenous cyclophosphamide (500 mg) and oral prednisolone (20 mg/day).
A day after the second pulse, she presented with extreme fatigue and restlessness. There was no history of fever, chest pain or headache. Investigations revealed hyponatraemia (serum Na 106 meq/l) and she was started on 0.9% normal saline. Over the next 12 h her consciousness deteriorated. She had two episodes of generalized tonic–clonic seizures and became comatose. Serum sodium did not improve.
At this time, the urine osmolality was found to be high (620 mOsmol/kg) with low-plasma osmolality (248 mOsmol/kg) and normovolaemia. These features were consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH) possibly related to cyclophosphamide infusion since no other underlying cause could be identified. Fluids were restricted. As she had altered consciousness and seizures, we tried to correct hyponatraemia with hypertonic saline. Sodium deficit was calculated and 3% saline initiated at 15 ml/h. The consciousness improved 24 h after initiating hypertonic saline, but again deteriorated over the next 24 h. CSF examination was normal. Blood and urine cultures were negative. MRI-brain at this stage was normal. She remained in coma despite the serum sodium becoming normal. There were no further seizures. A repeat MRI done after a week showed typical features of central pontine myelinolysis (CPM) (Fig. 1). The patient continues to be comatose till the time of writing this report which is about 3 months after the event.
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SIADH is the most frequent cause of normovolaemic hyponatraemia [1]. Cyclophosphamide can also produce SIADH [2]. This is, however, usually known with higher doses used in oncology practice [3]. In the present case, this complication was seen at a relatively lower dose (500 mg). There are only a few reports of low-dose intravenous cyclophosphamide causing SIADH [4, 5].
CPM is a well-known complication encountered while correcting hyponatraemia [6]. Both prolonged hyponatraemia as well as rapid correction of it can cause CPM [7]. In this case, both might have contributed to this complication. But what this case highlights is that SIADH, although uncommon with low-dose cyclophosphamide, is nevertheless an important complication one should keep in mind while using this drug irrespective of the dosage.
Disclosure statement: The authors have declared no conflicts of interest.
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