IVIG for Refractory Clostridium difficile Colitis in an Immunosuppressed Patient

Abstract

Purpose: Background: Clostridium difficile-associated diarrhea (CDAD) is increasing in incidence and severity, with recent outbreaks due to more virulent strains.1 Metronidazole is still considered the first-line therapy, with oral Vancomycin reserved for severe cases.2 CDAD is, however, becoming increasingly refractory to these two therapies. Intravenous immunoglobulin (IVIG) has been reported as an alternative treatment for refractory cases in several case reports and three uncontrolled studies.3 Case Report: A 56 year-old female with a history of multiple sclerosis (MS) presented with sudden bilateral lower extremity weakness, bloody diarrhea, and diffuse abdominal pain. Home medications included monthly Natalizumab and a recent 7 day course of Ciprofloxacin. She was diagnosed with CDAD by positive stool toxin and treated with Metronidazole 500 mg orally three times daily. She also received intravenous Methylprednisolone 1 gram daily for 5 days for MS exacerbation. The diarrhea initially improved, but became increasingly severe and associated with abdominal pain and distention one week after initiating Metronidazole therapy. Oral Vancomycin was added to the regimen, but the patient failed to improve. Stool toxin remained positive at 10 days. Leukocyte count remained persistently high at 35.000-40.000/dl. Abdominal computerized tomography revealed diffuse colonic wall thickening and ileus. On day 11, the patient was transferred to the intensive care unit. Vancomycin enemas were considered, but the patient could not tolerate them due to profuse diarrhea. Serum levels of total IgG, and of IgG1, IgG2, and IgG4 were low. The patient was administered two doses of IVIG 400 mg/kg on days 13 and 14. She had a significant clinical improvement after the IVIG and colectomy was thereby avoided. Discussion: Patients with severe CDAD may have a defective humoral response to toxin A as suggested by finding lower levels of IgG antitoxin A antibodies in these patients4,5. Correction of hypogammaglobulinemia by IVIG administration in the post-transplant period has been shown to decrease the incidence of CDAD6. The currently reported patient was on Natalizumab maintenance therapy, and received high-dose steroids synchronous with treatment for CDAD. Both factors are associated with CDAD development and relapse7,8. She failed both Metronidazole and oral Vancomycin therapy, but improved promptly with administration of IVIG. Colectomy was thereby averted. IVIG therapy may be considered as salvage therapy in immunosuppressed patients with refractory CDAD, especially if they have hypogammaglobulinemia.