EDITORIAL

• Published in: Immunity, Inflammation and Disease Vol. 8; no. 4; pp. 847 - 853
• Main Authors: Röseler, Stefani, Leufgens, Friederike, Merk, Hans F, Baron, Jens M, Silke Moll‐Slodowy, Wurpts, Gerda, Balakirski, Galina
• Format: Journal Article
• Language: English
• Published: Bognor Regis John Wiley & Sons, Inc 01.12.2020
• Subjects: Cardiac arrhythmia; Dyspnea; Multiple sclerosis; Patients; Urticaria
• ISSN: 2050-4527
• DOI: 10.1002/iid3.357

1 While some mechanisms of action of GA are still not completely understood, it has been shown to bind to major histocompatibility complex molecules and to induce an in vivo change of the cytokine secretion pattern of CD4+ and CD8+ T cells. 1 Injection site reactions and immediate post‐injection systemic reactions (IPISR) are adverse events caused by GA that are most frequently described in the literature. 2 The latter are characterized by flushing, chest tightness, palpitations, and shortness of breath, and may occur several minutes after the injection, but resolve spontaneously, usually within 1 h. IPISR can take the form of a single episode or recurrent event. The mechanism of this reaction is still unclear. 2 Moreover, as the use of GA became more common in clinical practice, a number of reports on possible type I hypersensitivity reactions to this drug were released. 3‐13 In most cases, a positive skin prick test, an intradermal test, or the basophil activation test (BAT) led to the diagnosis of an immediate‐type hypersensitivity reaction to GA and to a subsequent cessation of the therapy. 5,7,8,12,13 At the present time, there are no generally accepted recommendations on how allergy diagnostic testing should be carried out to evaluate these reactions to GA. [...]angioedema of the lips, tongue, and genital area occurred twice. Since cutaneous reactions have been described as possible side effects of GA, the therapy was discontinued. [...]the patient was being followed up at the neurological clinic and did not require treatment for multiple sclerosis. 1 TableResults of the systematic review: a summary of all available scientific literature on immediate‐type hypersensitivity reactions to glatiramer acetate Literature/reference Number of patients Clinical symptoms Time to onset of symptoms after injection Emergency treatment required Skin prick test (SPT), dilution, and results Intradermal test (IDT), dilution, and results In vitro diagnostics Control persons Outcome/drug provocation test (DPT) Amsler E et al., 2017 (3) 18 10/18: urticaria only; 3/8: facial erythema and edema, dizziness; 4/8: chest tightness; 3/8: heat sensations; 2/8: abdominal pain; 2/8: tachycardia or palpitations; 3/8 itching or rash 8/18: immediately to a few minutes; 1/18: 30 min; 5/18: 1 to a few hours; 4/18: unknown 14/18: none; 2/18: emergency consultation, no treatment; 2/18: emergency consultation, corticosteroid with/without antihistamines 16/18: negative with undiluted GA; 2/18: not performed 1/18: positive with undiluted GA; 2/18: positive and 1/18: inconclusive at dilution of 1:10; 7/18: positive and 1/18: inconclusive at dilution of 1:100; 4/18: positive at dilution of 1:1000; 1/18: positive at dilution of 1:10,000; 1/18: negative at all tested dilutions Not performed Two controls (who had never received GA) had a positive IDT (at dilution 1:100 or 1:10) 16/18: tolerated DPT without reaction; 1/18: reoccurrence of IPISR; 1/18: not performed Syrigou E et al., 2015 (4) 1 Injection site redness and swelling followed by generalized urticaria Unknown Levocetirizine 5 mg × 4/24 h and corticosteroid therapy (methyl‐prednisolone 60 mg/24 h) Borderline reaction to undiluted GA Positive at dilution of 1:10,000 Not performed Not performed Successful desensitization and continuation of the drug Corominas M et al., 2014 (5) 3 Patients 1 and 2: generalized urticaria, nausea, and hypotension; Patient 3: facial angioedema Patients 1 and 2: upon the first administration of GA (exact time after injection not specified); Patient 3: 20 min after injection Not reported 3/3 patients tested positive with undiluted GA Not performed Specific IgE to GA was determined in the serum of patients and controls using ImmunoCAP Technology, Thermo Fisher Scientific; 3/3 patients had elevated sIgE to GA 10/10 control subjects tested negative in SPT with undiluted GA; 6 patients with MS treated with GA and 10 healthy controls had negative sIgE to GA Not specified, possibly discontinuation of the drug Crestani E et al., 2014 (6) 1 Severe shortness of breath, dizziness with shivering, tachycardia, flushing, perioral cyanosis, and brief loss of consciousness Immediately after injection By the time of arrival of emergency personnel, the symptoms subsided, and no treatment was needed Negative with undiluted GA Positive at dilution of 1:100,000 Not performed 1/1 negative at dilution of 1:100000 Successful desensitization and continuation of the drug Soriano Gomis V et al., 2012 (7) 3 Patient 1: generalized itching, weals, facial angioedema, dyspnea, and near unconsciousness; Patient 2: facial angioedema, dyspnea, abdominal cramps, and vomiting; Patient 3: generalized itching Immediately or a few minutes after injection All patients received epinephrine, dexchlorpheniramine, and methylprednisolone Patient 1 tested positive in SPT (dilution not specified) Positive in all three patients at dilution of 1:100 Specific IgE to GA were determined using ELISA, Patients 1 and 2 had elevated levels compared to 10 controls; Patients 2 and 3 tested positive in BAT at 1:100 and 1:400, respectively 3/3 control persons had negative IDT results (dilution