D1.372 - Transition to SCIG as an Alternative in Patients with Cytokine Storm from IVIG

Introduction: Replacement therapy with normal human immunoglobulin is the treatment of choice for primary humoral immunodeficiencies, such as common variable immunodeficiency (CVID). Administration by the intravenous (IVIG) or subcutaneous (SCIG) route allows restoration of adequate IgG levels and reduces the incidence of severe infections. However, IVIG may be associated with potentially serious systemic reactions such as cytokine storm.

Materials and Methods: A 58-year-old man with CVID associated with protein-losing enteropathy had been treated with weight-adjusted IVIG (Flebogamma®, 45 g every 21 days) since 2015, with persistently low IgG levels. After IVIG administration in February 2023, he developed intense chills, sudden low back pain, facial flushing, and general malaise, a clinical picture compatible with cytokine storm. Elevated IL-6 levels were documented (123.5 pg/mL; baseline 36.9 pg/mL), with no significant increase in serum tryptase. From that time on, IVIG was administered using a desensitization protocol, completing 12 cycles without incidents but with persistently suboptimal IgG levels. Transition to SCIG with recombinant hyaluronidase (HyQvia®) was decided in June 2025.

Results: A controlled exposure protocol with progressive dose escalation was performed:

- 1st dose (June 2): 10 g in both abdominal flanks.

- 2nd dose (June 12): 20 g in the thighs.

- 3rd dose (June 26): 30 g in the thighs.

- 4th dose (July 17): 40 g in the thighs, with partial self-administration initiated.

All doses were administered with oral premedication 1 hour before each infusion: paracetamol 1 g, montelukast 10 mg, famotidine 40 mg, and bilastine 20 mg. Initially, administration was performed under supervision in the day hospital.The patient tolerated all phases of subcutaneous escalation. He only developed mild, self-limited local erythema after the second dose. The slow progression allowed tissue and immunological adaptation, preventing systemic immunoglobulin peaks. Since starting subcutaneous maintenance therapy, he has remained clinically stable, without infections or relevant adverse effects, and is undergoing reevaluation of serum IgG levels.

Conclusions: We report a case of SCIG challenge in a patient with a previous diagnosis of moderate cytokine storm related to IVIG. Subcutaneous administration, especially when introduced through a progressive and stepwise schedule, is characterized by slow and controlled absorption that prevents systemic peaks and abrupt immune activation, thereby hindering the development of cytokine storm. In patients who have experienced cytokine storm with IVIG, gradual transition to the subcutaneous route is a safe alternative that maintains therapeutic efficacy and improves adherence through home self-administration.