Headache After Treatment with Intravenous Immunoglobulin (IVIG)

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

A 34-year-old Caucasian female is followed by the allergy clinic for common variable immunodeficiency (CVID) and a treatment with intravenous immune globulin (IVIG) was started 4 months ago. She started to have headaches after the second infusion which are progressively getting worse. Her last dose of IVIG was given 2 days ago and since then she had a persistent pounding headache not relieved by Percocet. She denies any symptoms of aseptic meningitis including photophobia, neck stiffness, nausea, or fever. She rates the pain as 8/10.

Past medical history (PMH)

Common variable immunodeficiency (CVID).


Intravenous immune globulin (IVIG) 400 mg/kg every 4 weeks, Percocet (oxycodone and acetaminophen)

Social history and family history

Not contributory.

Physical examination

Vital signs stable. Normal nose and throat exam. Respiratory system: Clear to auscultation bilaterally. Cardiovascular system: Clear S1, S2. Abdomen: Soft, non-tender, non-distended. Extremities: no edema. Skin: no rashes.Neurological examination: non focal.

What is the most likely diagnosis?

- Headache associated with intravenous immunoglobulin.
- Migraine.
- Aseptic meningitis is in the differential diagnosis but she did not have features of meningitis.

What tests would you suggest?

No additional tests are needed at this time.

What treatment would you suggest?

After verifying that the patient was not pregnant, she was prescribed zolmitriptan (Zomig) 5 mg po x 1, the dose may be repeated 2 hours later. The headache resolved after the second dose.

How to prevent IVIG-related headache?

Post-infusion headaches may be prevented by the following treatments for as long as 72 hours after the infusion is completed
- NSAIDs such as naproxen or ibuprofen
- Prednisone 30 to 60 mg
- cyproheptadine (an antihistamine and serotonin receptor antagonist)
- migraine medications

In this patient, we recommended prednisone 30 mg po x 1 and zolmitriptan (Zomig) 5 mg po x 1 before the infusion.

Other options that may be considered include "splitting" the dose to every 2 weeks and using subcutaneous immunoglobulin rather than IVIG.

Final diagnosis

Headache associated with intravenous immunoglobulin (IVIG) treatment.


Headache is a common side effect of intravenous immunoglobulin (IVIG) treatment; it usually resolves shortly after completing or slowing the infusion. Aseptic meningitis occurs in up to 17% of patients afterIVIG treatment, with more than 30 cases described in the literature. Aseptic meningitis usually presents with crescendo headache that also causes changes in sensorium or behavioral changes.

Headaches associated with intravenous immunoglobulin may have features of migraine and may be successfully prevented and/or treated with 5-HT1D receptor agonists.

Many patients develop mild headaches during IVIG infusions, which can be prevented or treated with acetaminophen, aspirin, or NSAIDs; and/or by administering the IGIV at a slower rate.

In some cases, the onset may be delayed until 24 to 48 hours after the infusion is completed. The duration of symptoms is generally less than 48 hours, but occasionally, severe headaches lasting as long as 72 hours have been reported.

Anaphylaxis may occur in patients treated with IVIG who have IgE antibodies against IgA, for example patients with selective IgA deficiency (incidence 1 in 500). Preventive measures include using products with the lowest IgA content and pre-medication with antihistamines or corticosteroids.

Mnemonic: Dose of IVIG in PIDD

400-600 mg/kg/month
4 letter words:


Management of the Acute Migraine Headache. AFP, 2002.

Successful Treatment of Headache Related to Intravenous Immunoglobulin With Antimigraine Medications. Alan G. Finkel, MD ; James F. Howard Jr., MD ; J. Douglas Mann, MD. Headache: The Journal of Head and Face Pain, Volume 38 Issue 4, Pages 317 - 321, 2003.

What Can Be Used to Treat Persistent Headache Caused by Aseptic Meningitis? Randolph Warren Evans, MD. eMedicine, 2000.

Published: 04/19/2009
Updated: 08/18/2010

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