A 47-year-old woman with history of immunoglobulin G (IgG) deficiency presented with severe headache, fever, vomiting, neck pain and photophobia. On the day prior to admission, she received first dose of Intravenous immunoglobulin (IVIG) infusion for recurrent bacterial infections refractory to antibiotic prophylaxis. On examination, her temperature was 100 °F and vital signs were stable. She had neck stiffness but no other signs of meningeal irritation. Fundus examination was normal and there was no focal neurological deficit. Other systems were normal and a diagnosis of meningitis was considered. Investigations revealed leukocytosis with a white blood cell (WBC) count of 14000 cells/mm3. Computed tomographic (CT) scan of brain showed no abnormalities. Cerebrospinal fluid (CSF) was clear and showed leukocytic pleocytosis (723/ mm3) with neutrophilic predominance (89%); normal glucose (43 mg/dl) and elevated protein (71 mg/dl). CSF gram stain, acid-fast bacillus stain (AFB) stain, KOH (potassium hydroxide) preparation and India ink were negative. Treatment with intravenous antibiotics (vancomycin, ceftriaxone, ampicillin, and acyclovir) and dexamethasone was administered in the meantime. Bacterial and fungal cultures of CSF and blood cultures remained sterile. Polymerized chain reaction of CSF was also negative for herpes simplex virus, epstein barr virus, cytomegalovirus and tuberculosis. A diagnosis of aseptic meningitis possibly due to immune reaction of IVIG therapy was made and antibiotics were stopped. Her symptoms and signs of meningitis completely regressed within a week of hospitalization.
Discussion:
IVIG is a lifesaving therapeutic agent, increasingly used to treat various hematological and immunological disorders. Majority of adverse reactions of IVIG therapy are mild, transient and self-limiting with potentially serious complications occurring only in <5% of patients. The various postulated mechanisms of IVIG-associated aseptic meningitis include direct toxic effect, immunological drug hypersensitive reaction, allogenic immune reaction, hypersensitivity reaction to various stabilizing agents and cytokine release triggered by the therapy. The risk factors include rapid, high-dose infusion of IVIG and previous history of migraine. Secondary preventative measures are controversial, and research is lacking. Slower infusion rate, proper hydration and antihistamines may help to prevent mild adverse reactions to IVIG therapy. Systemic steroid may be required in severe cases.
Conclusions:
Aseptic meningitis is a rare but significant complication of IVIG therapy . Recognition of this condition is important as it may be treated effectively in many patients, allowing the continuation of IVIG infusion. A high index of clinical suspicion should be kept for IVIG-induced aseptic meningitis and should be confirmed by careful neurological examination and CSF analysis as it is potentially manageable.