Case Presentation: A 53-year-old female with chronic small fiber polyneuropathy and erythromelalgia presented with severe headaches, nausea, vomiting, diarrhea, body aches, photophobia, and neck stiffness for two days. Symptoms started one week after receiving intravenous immunoglobulin (IVIG) for an erythromelalgia flare. On presentation to the ER, she was afebrile and physical examination was unremarkable. Respiratory pathogen panel was negative. Cerebrospinal fluid showed an elevated protein and white blood cell count with normal glucose leading to a diagnosis of acute meningitis. She was started on empiric antibiotics including, ampicillin, ceftriaxone, vancomycin, and acyclovir. Further infectious work-up was negative including a negative CSF culture and gram stain and CSF viral panel. A CT head without contrast, MRI and MRA of the brain were normal. The acute meningitis was determined to be aseptic in etiology, the antibiotic regimen was deescalated, her symptoms resolved, and she was discharged home.
Discussion: Erythromelalgia (EM) is a rare disorder characterized by episodes of intense burning pain with erythema of the extremities and an estimated prevalence of 0.01% in the United States. First-line treatment includes lifestyle changes and trials of aspirin, anticonvulsants, or SSRI’s. Second-line therapies include steroids, antihistamines, beta-blockers, and IVIG (4). IVIG consists of IgG pooled from healthy blood donors and is used to treat many inflammatory diseases through various immunomodulatory mechanisms (1). The most common adverse effects of IVIG include headache, anaphylaxis, nausea, and vomiting. Aseptic meningitis (AM) can be a rare adverse effect of IVIG (3). The inflammation of the meninges is thought to occur through a type III/IV hypersensitivity reaction (8). It has been documented to occur in 1% of patients treated with IVIG (7). We report a case of a patient with erythromelalgia who developed AM after receiving IVIG therapy.As of April 2022, there are 44 cases described of IVIG-induced AM (3). AM is associated with higher IVIG doses such as 1-2 g/kg. Of the described cases of IVIG induced AM, onset ranged from 24h after first infusion-10 days after the last infusion (6). In this case, the patient was administered 5 days of IVIG at a dose of 2g/kg. Her symptoms developed six days after her last infusion. Based on the timing of our patient’s treatment, high dosage, and lack of an infectious cause, her AM was determined to be associated with IVIG administration. In patients who develop adverse side effects to IVIG therapy, pretreatment with adequate hydration, antihistamines, NSAIDs, or decreasing infusion rate can minimize side effects without compromising symptomatic relief (5). Smaller and more frequent subcutaneous immunoglobulin administration is also an option that may present with fewer systemic side effects (2).
Conclusions: Aseptic meningitis associated with IVIG is uncommon. This case highlights a rare but significant adverse effect of IVIG. For patients who have developed side effects in response to IVIG therapy, modifications to the protocol can be considered, such as decreasing the infusion rate, pretreatment with hydration, antihistamines, NSAIDs, or changing the route of administration to subcutaneous. This case supports the need to further investigate the adverse effects of IVIG therapy.