Beyond the Norm: Managing Reactions to Immunoglobulin Replacement

Immunoglobulin replacement is frequently associated with adverse reactions which are commonly managed by changing the route or rate of administration, premedication, or changing products. Some patients with life-threatening reactions to replacement do not respond to these interventions. We present two cases where alternative methods are used to prevent life-threatening reactions to immunoglobulin replacement. Patient 1 is a 36-year-old female with a humoral immunodeficiency and a history of chronic spontaneous urticaria but no history of anaphylaxis. She was started on IVIG 600 mg/kg every 4 weeks, which she initially tolerated for multiple months. She then developed urticaria, dyspnea, and chest tightness within 60 minutes of starting an infusion. Pretreatment with IV corticosteroids, antihistamines, infusion rate reduction, IVIG brand changes, and switching to subcutaneous replacement did not prevent anaphylaxis. Based on her history of chronic urticaria and now immunoglobulin replacement induced anaphylaxis, she was initiated on omalizumab 300 mg monthly. After three months of therapy, IVIG was restarted which has been tolerated without further reactions. Patient 2 is a 49-year-old male with a humoral immunodeficiency. IVIG 600 mg/kg every 4 weeks was initiated and initially tolerated but multiple months into therapy he developed urticaria, chest pain, dyspnea, and mental status changes near the end of his infusions with one reaction requiring mechanical ventilation. He had no benefit with the management changes previously noted or with increasing the frequency of IVIG administration to decrease the amount of IVIG administered per infusion. Because the reactions appeared to be dose-dependent as he did not react until the end of infusions, he was switched to daily dosing of SCIG with 1/28 of the monthly dose administered daily and has tolerated this with no reactions. Our findings showcase that adverse reactions to immunoglobulin replacement therapy that are not responsive to conventional management may be effectively treated by considering specific patient features and possible pathophysiologic mechanisms; reactions that are consistent with mast cell–mediated processes may respond best to anti-IgE therapy, while those with dose-dependent mechanisms may benefit from low-dose daily dosing to avoid dose thresholds triggering a reaction.