This is a case study of a male patient with Fabry disease who presented with severe anaphylaxis following re-initiation of full-strength treatment with intravenous agalsidase beta (Fabrazyme).
A recent case study discusses a 38-year-old man with adult-onset Fabry disease who thrice presented with severe anaphylaxis following re-initiation of full-strength treatment with intravenous (IV) agalsidase beta (Fabrazyme).
He was able to tolerate treatment with Fabrazyme again only after pretreatment with omalizumab.
Fabry disease, a rare lysosomal storage X-linked genetic disorder, has 2 phenotypes that men present with: severe disease and mild disease. Severe disease is characterized by reduced activity in the α-galactosidase A (α-Gal A) gene leading to multi-organ failure and death and typically presents in early life, and mild disease often presents later in life with varying levels of α-Gal A activity.
“For both phenotypes, severe localized and systemic inflammation occurs after glycolipids bind to the toll-like receptor 4, are processed, and then presented to the T-cell receptors on invariant natural killer T cells (CD1d-restricted T cells) capable of rapidly responding to the lipid antigenic stimulation with release of proinflammatory cytokines (interleukin-1b, tumor necrosis factor- α, and interleukin-6),” the authors noted in Annals of Allergy, Asthma and Immunology
In addition to Fabrazyme, agalsidase alfa (Replagal) is available as enzyme replacement therapy for patients with Fabry disease. The twice-weekly treatments are meant to slow disease progression and improve patient outcomes.
Due to a nationwide Fabrazyme shortage, the patient’s previous regimen of biweekly 75-mg Fabrazyme injections had been drastically reduced to either missed or halved doses for a 3-month period. To this point, he had 5 years of uninterrupted treatment.
Full-strength treatment resumed on May 8, 2012. Six weeks later, after developing hives, lip numbness, scratchy throat, itching, and shortness of breath halfway through his infusion, he had to stop treatment and required epinephrine, diphenhydramine, and oral prednisone. When treatment resumed again on July 18, 2012, the patient’s reaction was similar, necessitating a second stoppage and treatment.
When full-strength treatment commenced a third time, the patient had another inflammatory reaction despite being pretreated with IV diphenhydramine, oral acetaminophen, and a decreased infusion rate.
These inflammatory reactions all progressed in severity.
Following an allergy consultation on August 8, 2012, the following results were obtained:
Especially important was the patient’s reaction to a Fabrazyme skin-prick test. That resulted in a 3 mm wheal/9 mm flare reaction. In addition, “an enzyme-linked immunosorbent assay, performed following the manufacturer (Sanofi-Genzyme, Cambridge, Massachusetts), for Fabrazyme serums IgE (no titers provided) and Fabrazyme sIgG (at a 1:6400 titer) was reported to be positive,” the authors noted.
Several 3-bag Fabrazyme desensitization protocols were attempted following these pretreatment regimens:
The Fabrazyme dose was subsequently increased to 90 mg after 6 months of biweekly Fabrazyme infusions plus monthly omalizumab, with the patient doing well to this day.
“Omalizumab has previously been reported effective for suppressing anaphylactic reactions during aeroallergen, venom, or food immunotherapy, among others,” the authors concluded. “This case adds to the existing literature by supporting omalizumab use as a pretreatment strategy for the management of severe allergic drug or biologic reactions.”
However, they still recommend additional study on the exact mechanisms that enable pretreatment with omalizumab to ward off, or lessen, severe allergic drug reactions.
DuBuske I, Schmidlin K, Bernsteain JA. Successful desensitization of a patient with Fabry disease with agalsidase beta (Fabrazyme) anaphylaxis after omalizumab pretreatment. Ann Allergy Asthma Immunol. 2021;126(1):96-98. doi:10.1016/j.anai.2020.08.026