Interstitial pneumonitis during lamotrigine therapy

Abstract

A 57 year-old female with a previous history of eczema was admitted with sudden onset of severe headache in November 2003. A CT of brain showed subarachnoid haemorrhage and left subdural haematoma with mass effect. The patient transferred to a regional neurosurgical unit where she underwent removal of subdural haematoma with insertion of ventriculoperitoneal shunt in November 2003. During the postoperative period, she had left focal seizures and methicillin resistant staphylococcus aureus (MRSA) infection of wound site. In view of left focal seizures during the postoperative period, phenytoin was initially commenced at 300 mg once daily increasing to 425 mg once daily. Since seizures were not well controlled, sodium valproate 700 mg twice daily and 1 g nocte along with clobazam 10 mg nocte were added later as add-on therapy. Baclofen 20 mg three times daily was added to control spasticity. The patient was transferred from the neurosurgical unit to the local hospital for further rehabilitation in February 2004. Her seizures were well controlled at the time of transfer. Chest radiograph was within normal limits. Her anticonvulsant therapy optimized during the stay. On 19th February 2004, baclofen was discontinued and phenytoin gradually withdrawn by 30 mg weekly. During the same period, lamotrigine was introduced commencing at a dose of 25 mg once daily on alternate days for first 2 weeks. The dose of lamotrigine increased to 25 mg once daily after 2 weeks with further increments of 25 mg every 2 weeks. By 19th April 2004, she was off phenytoin completely and the dose of lamotrigine increased to 75 mg once daily. She encountered no problems during the withdrawal of phenytoin and tolerated the slow build-up of lamotrigine. On 26th April 2004, she became acutely unwell with shortness of breath and oxygen saturation dropping to 69% on air. On clinical examination, she was apyrexial, cyanosed, dyspnoeic, tachycardia (112 min−1), and on auscultation chest was clear. Chest radiograph performed at the time showed evidence of infiltrates, both lung fields consistent with pneumonitis (Figure 1). Figure 1 Chest radiograph showing alveolar infiltrates both lung fields The full biochemistry and haematology were normal. Both ESR and CRP were normal. ECG was normal with no evidence of ischaemia. Microbiology (blood cultures and urine cultures) sent at the time came back negative. Medications at the time were lamotrigine 75 mg once daily, clobazam 10 mg once daily, valproate 700 mg twice daily and 1 g nocte, paracetamol 1 g four times daily, loperamide 2 mg prn and emollients for eczema. The clinical picture was that of interstitial pneumonitis [1, 2]. Since there was no laboratory or historical evidence of any other interstitial lung disease, drug-induced pneumonitis was considered most likely. Anticonvulsants were examined and lamotrigine selected as the most likely candidate as the dose had been recently increased. A decision was made to withdraw the drug immediately and her clinical condition improved in a few days. She improved dramatically on withdrawal of lamotrigine with no other treatments like steroids and diuretics. She only had oxygen during this time. Symptomatically she became better and the chest radiograph showed resolution of lung appearances within 1 week. The resolution of radiological changes within 10 days after stopping lamotrigine confirmed our initial diagnosis. A detailed drug information search revealed no previous documented reports of such an adverse event with lamotrigine. We did not perform computed tomography of thorax [4] and bronchoalveolar lavage [3, 4] in view of poor mobility and as she improved clinically on withdrawal of lamotrigine. The pharmacodynamic interaction between sodium valproate and lamotrigine might have increased the drug concentrations of lamotrigine triggering the abnormality in the lung [5–7]. She did not have other side-effects from lamotrigine during the period of therapy or immediately after withdrawal. The resolution of radiological changes following withdrawal of lamotrigine, with no other treatments confirms the possibility of lamotrigine-induced interstitial pneumonitis.