Type 1 hypersensitivity reaction with elosulfase alpha treated with desensitisation

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Ahmet KAN1, Aslı İNCİ2, Büşra TOPUZ3, İlyas OKUR2, Arzu BAKIRTAŞ1
Departments of 1Pediatric Allergy and Asthma, 2Pediatric Metabolic Disorders and 3Pediatrics, Gazi University Faculty of Medicine, Ankara
Article Type
Case Reports
Mucopolysaccharidosis type 4A, elosulfase alpha, hypersensitivity reaction, desensitisation


Elosulfase alpha is an recombinant enzyme used to treat patients withmucopolysaccharidosis type 4A (MPS 4A). A patient diagnosed with mucopolysaccharidosis type 4A had 13 doses of elosulfase alpha with 2 mg/kg per dose weekly. Thepatient developed urticaria, angioedema of the lips and dyspnea, maculopapular andurticarial rash over the foot and also he had fever. The patient then was consulted topediatric allergy and intradermal test with elosulfase alpha 1/100 dilution was foundpositive with 6x6 mm enduration surrounding erythema. Total enzyme amount was calculated and desensitisation with dilutions of 1/100, 1/10 and whole concentration wereperformed within six hours. No complications or reactions were seen. The patient hastaken 40 doses of enzyme within about 10 months with desensitisation protocol. Elosulfase is currently the only approved medication to be used in mucopolysaccharidosistype 4A patients. Desensitisation seems to be an effective method to overcome type Ihypersensitivity reaction.


Elosulfase alfa is the first and the only treatmentfor MPS type 4A today. In the literature, there isonly one study about safety of elosulfase alfa treatment which is a a placebo-controlled randomized,double-blinded phase 3 study that was conductedat 33 centers from 17 countries between 2011-2012. One hundred and seventy-six patients diagnosed as Morquio A syndrome with mean age11.9 years were included. Immunogenicity profileof elosulfase alfa besides efficacy and safety wereinvestigated. All patients developed elosulfase alfaanti-drug antibodies, majority of which were neutralizing antibodies capable of interfering with cation-independent mannose-6- phosphate receptorbinding in vitro. Less than 10 % of patients testedpositive for drug-specific IgE during the study. Serious drug-related adverse events were observedin 9 of patients treated with elosulfase alfa 2 mg/kg/week and 4 of patients treated with 2 mg/kgelosulfase alfa every other week. Three patients developed serious drug-related hypersensitivitywith anaphylaxis. No correlations were detectedbetween elosulfase alfa- specific IgE type antibodypositivity or total antibody titers and increased incidence of drug-related hypersensitivity reactionslike anaphylaxis and angioedema (9). Desensitisation remains one of the choices for elosulfase alfarelated severe allergic hypersensitivity. This caseis the first MPS type IVA patient who underwentelosulfase alfa desensitisation in the literature.In 2010, the European Network of Drug Allergy(ENDA) and the European Academy of Allergy andClinical Immunology (EAACI) research groups declared a consensus report compromising generalconsiderations about desensitisation for drug hypersensitivity reactions (1). The desensitisationmethod by castells et al. can be one of the choicesused for rapid desensitisation (10). We applied thisgeneral protocol to our patient who received elosulfase alfa desensitisation for 40 infusions withoutany complications for 10 months. As a result, dataabout drug-specific Ig E mediated hypersensitivity reactions to elosulfase alfa in the treatment ofMPS type IV A is limited and ours is the first casewith successful desensitisation.


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