Allergic reaction to hyaluronidase in cataract surgery

EDITOR: Thiomucase® injectable is a pharmaceutical product containing hyaluronidase, a mucopolysaccharidase obtained from bovine testicles. Hyaluronidase breaks down hyaluronic acid, a key component of connective tissue, reducing viscosity and facilitating drug absorption [1]. Hyaluronidase has many clinically proven indications [2]: plastic surgery, ophthalmology and in dental anaesthesia as a spreading agent to facilitate local anaesthetic block. In paediatric oncology it facilitates drug penetration in chemotherapy [3]. Only a few cases of allergic reactions associated with hyaluronidase have been reported. In our hospital we have had only one case in 3285 ophthalmological surgical operations in 2 yr. We report a case of allergic reaction to hyaluronidase in a patient scheduled for cataract surgery. A 71-yr-old male was admitted for cataract surgery. His surgical history included an uneventful transurethral removal of the prostate under spinal anaesthesia 5 yr before. He had no history of atopy or drug allergy. After intravenous (i.v.) administration of alfentanil 150 μg and propofol 25 mg a peribulbar block was performed using bupivacaine 0.5% 5 mL and mepivacaine 2% 5 mL with the addition of hyaluronidase 1 mL (100 IU). The patient developed a generalized rash, pruritus and periorbital oedema immediately after the injection. The operation was cancelled and hydrocortisone 100 mg and deschlorpheniramine 5 mg were administered i.v. All the symptoms disappeared within 6 h. Two hours after the reaction only the urinary methylhistamine level was positive: 215 μg mL−1 (normal range up to 115 μg mL−1). All other tests for allergy (complement factors C3, C4, C3a, latex specific IgE and serum tryptase level) were negative. Six weeks after the reaction allergic skin tests (prick test) to hyaluronidase were positive. Hyaluronidase SDS-PAGE immunoblotting revealed two IgE-binding bands of 35 and 36.4 kDa, respectively. Skin tests to bupivacaine, mepivacaine, alfentanil and propofol were negative. Peribulbar block with the association of hyaluronidase and local anaesthetics is a common practice in ophthalmic surgery. In ophthalmic surgery, allergic reactions to hyaluronidase are uncommon. In spite of this, four cases of early and local reactions in which symptoms disappeared rapidly after i.v. administration of antihistamines and corticosteroids [4-7] and one of the delayed reactions 28 h after hyaluronidase administration have been also reported [8]. Szepfalusi and colleagues [3] described five cases of serious systemic reactions after i.v. administration of hyaluronidase for treating central nervous system tumours. Apart from ours, this is the only other study which has described the molecular mass of the protein fraction involved: two IgE-binding bands of 73 and 41-43 kDa. Allergic sensitization by previous exposure is an essential event to suffer from an IgE-mediated reaction after drug administration, but unlike other published cases [5,7] our patient had not been previously treated with hyaluronidase. We conclude that allergic reactions to hyaluronidase in ophthalmic surgery are rare and difficult to diagnose. Anaesthetists and ophthalmologists should be aware of the potential complications of this drug. Anaphylaxis to hyaluronidase in ophthalmic anaesthesia is usually IgE-mediated; nevertheless, it could produce a dangerous increase in intraocular pressure. Serious anaphylactic reactions have only been reported when hyaluronidase was administered i.v. F. Escolano N. Parés I. Gonzalez J. Castillo A. Valero B. Bartolomé 1Department of Anaesthesiology, Hospital Universitario del Mar-Esperança (IMAS), Barcelona, Spain 2Department of Allergy, Hospital Clinico Universitario, Barcelona, Spain 3Laboratory Bial-Arístegui, Bilbao, Spain