Rituximab in c-ANCA associated vasculitic polyneuropathy complicated by local peritonitis

Abstract

A 70-year-old woman presented with progressive weakness over 3 weeks and paresthesia of the lower extremities. Except for a recent history of recurrent respiratory tract infections, she had been healthy previously. Within hours after hospital admission, paresis progressed markedly, and she required intensive care. Physical examination showed sensory-motor polyneuropathy with tetraplegia and symmetrical distal sensory impairment of all extremities, no cranial nerve abnormalities nor autonomous dysregulation. Because of involvement of the diaphragm the patient was intubated and ventilated. The clinical presentation was suggestive of Guillain–Barre syndrome (GBS). CSF examination revealed 92 WBC/ll, 33,700 erythrocytes/ll, glucose 69 mg/dl, lactate 35.4 mg/dl and protein 181 mg/dl. Electrophysiology was consistent with a sensorymotor polyneuropathy with axonal affection. A cranial MRI demonstrated central nervous system involvement (Fig. 1g–i). Laboratory testings showed an elevated c-antineutrophil cytoplasmic antibodies (c-ANCA)-titer (168 U/ml) and slightly elevated creatinine. In synopsis with the patient’s history of recurrent respiratory infections, Wegener’s granulomatosis with vasculitic polyneuropathy and central nervous system involvement was suspected and confirmed by sural nerve biopsy (Fig. 1a–f), as well as skin , and nasopharyngeal mucosa biopsy (not shown). High-dose steroids, plasmapheresis, and intravenous immunoglobulins were sequentially administered without improving the patient’s symptoms. Then a severe lower gastro-intestinal bleeding, which eventually required surgical removal of the ileocecum complicated the clinical course. Histology, it revealed no signs of vasculitis, but a disseminated cryptitis of the colon. Subsequently, the patient developed a localized peritonitis due to abdominal wound healing disturbance and dehiscence, warranting multiple surgical revisions. Meanwhile, the patient’s neurological and pulmonary status remained unchanged. Because therapy-escalation seemed mandatory, administration of rituximab (dose: 375 mg/m in 4 weekly courses) was preferred to cyclophosphamide, which is described to worsen wound healing [1]. Remarkably, under rituximab, the abdominal infection did not recur and the patient’s condition improved substantially. Ten weeks after admission, the patient could be weaned off the ventilator and transferred to the general ward. Within the following weeks, muscle strength in the upper, and later on in the lower extremities, recurred and the patient was transferred to rehabilitation. The patient was able to touch her nose with the left hand and to lift up her right hand against gravity. Both legs could be elevated against gravity but she was still unable to walk. The neurological improvement was quantified using the Wegener’s J. Witsch (&) J. Braun G. Trendelenburg Department of Neurology, Charite University Medicine, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany e-mail: Jens.Witsch@charite.de