Guillain–Barré syndrome after rituximab in a patient with idiopathic thombocytopenic purpura: a causal association?

Abstract

Guillain–Barre syndrome (GBS) is an acute demyelinating inflammatory polyradiculoneuropathy characterised by rapidly progressing predominantly motor impairment and areflexia. Studies in patients and animals have provided convincing evidence that GBS is caused by an aberrant autoimmune response that damages peripheral nerves [1]. GBS rarely develops in patients who suffer from other autoimmune conditions, such as idiopathic thrombocytopenic purpura (ITP), which suggests a shared immune response [2–11]. Rituximab is a monoclonal antibody particularly efficacious in the treatment of several haematological cancers, which has also been used for the treatment of some autoimmune conditions [12]. Here we report on a patient with ITP who developed a typical GBS after treatment with rituximab. This 86-year-old man, with the antecedents of arterial hypertension, chronic obstructive lung disease and atrial fibrillation, consulted in December, 2008, due to purpuric lesions in the lower limbs. He was diagnosed as ITP. His platelet count was 5,000/mm. He received intravenous immunoglobulins (ivIG) 1 mg/kg/day for 2 days plus a descending treatment with oral prednisone (beginning with 1 mg/kg/day) for 1 month. His platelet count after this treatment was 250,000. In January, 2009, he was admitted again because his blood sample showed 10,000 platelets. He was treated with oral prednisone 1 mg/kg/day for 16 consecutive days. This treatment was stopped due to persistent thrombocytopenia (20,000 platelets). IvIG 1 g/kg/day for 2 days and intravenous rituximab (750 mg once a week for 4 weeks) were administered. His platelet count before the last rituximab dose (27 February 2009) was 121,000. Thirty-nine days after the last dose of rituximab (8 April 2009) he developed an acutely ascending progressive tetraparesis. On admission, two days after the beginning of the clinical picture, symmetric weakness, 4/5 in the upper extremities and 3/5 in lower extremities, and universal arreflexia were found. Plantar responses were flexor. Sensory examination was normal and sphincters were not affected. Platelet count was 192,000/mm. A lumbar tap was performed on admission. Glucose levels were normal, there were no cells and protein concentration was 57 mg/dl. The remaining routine laboratory determinations, including tumor markers and a complete autoimmune profile, were normal. With the presumptive diagnosis of Guillain–Barre syndrome, treatment with ivIG 0.4 g/kg/day for 5 days was given. An electrophysiological study, performed six days after the beginning of the symptoms, disclosed slowing of motor conduction velocities (MCV) in all studied nerves. MCV were markedly delayed (\32 m/s) in peroneal and tibial nerves, and slightly slowed in median and ulnar nerves (46 and 49 m/s, respectively). Motor distal latencies (MDL) were clearly prolonged in tibial and medial nerves and within normal limits in peroneal and ulnar nerves. F waves could not be obtained in right peroneal nerve, right posterior tibial nerve and right median nerve, and were delayed in right ulnar nerve. There was attenuation of distal compound muscle R. Jaso C. Valero Services of Internal Medicine, University Hospital Marques de Valdecilla, Santander, Spain