Can I Get Rituxan Again if I Had Reaction

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• Published: 26 June 2020

Type I allergic reaction to rituximab upon first lifetime exposure: a case report

Allergy, Asthma & Clinical Immunology volume 16, Commodity number:56 (2020) Cite this article

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Background

While drug reactions to rituximab accept been commonly reported in the literature, a type I allergic reaction to rituximab after offset lifetime exposure has never been reported.

Case presentation

Nosotros depict a case of a 58-twelvemonth-erstwhile female patient who received rituximab for the first fourth dimension for treatment of rheumatoid arthritis. She developed symptoms immediately after infusion, even so presented eleven days later on drug exposure with cyclical anaphylaxis-similar reaction requiring multiple doses of epinephrine. On second exposure, she experienced immediate anaphylaxis 30 min into infusion.

Determination

Our instance illustrates the importance of heightened awareness by physicians that type I IgE-mediated reactions later first exposure to monoclonal antibodies such every bit rituximab are possible, and if unrecognized, could be potentially life-threatening.

Background

Rituximab is a chimeric monoclonal antibody (MAB), which is approximately 65% human being, the residual existence mouse epitope. Information technology binds to the CD20 antigen on B cells and is primarily used in the handling of autoimmune disorders and malignancies [1]. We describe an unusual presentation of rituximab hypersensitivity.

Case presentation

Our patient is a 58-year-erstwhile woman known for rheumatoid arthritis, depression, and migraines. Her medications include bupropion and low-dose prednisone (5–ten mg [mg] daily). She has no personal or family history of allergy or urticaria. She previously failed handling for her rheumatoid arthritis with methotrexate, tocilizumab, and tofacitinib. During her get-go infusion of rituximab (administered over 4 h), she adult fatigue and a migraine which persisted for four days mail service-infusion. On day two post-rituximab, she too developed 1 day of pharynx pain. On 24-hour interval 10, the patient had transient lengthened scalp pruritus. On mean solar day 11, she adult pruritus which adult into urticaria followed past face and tongue angioedema and throat tightening. On presentation to the emergency room (ER), she was tachycardic (at 123) with otherwise normal vital signs and normal physical test. She was given famotidine twenty mg and methylprednisolone 80 mg intravenously (IV), and diphenhydramine 50 mg orally (PO). Despite initial comeback of her symptoms, the patient's urticaria, angioedema, and chest tightness with wheezing re-occurred. She was given a dose of epinephrine 0.5 mg IM. The patient remained in the ER for over 48 h with recurrences of her symptoms necessitating IM epinephrine a total of three times. Repeated vital signs were normal other than intermittent tachycardia (100–125). Bloodwork showed a C-reactive poly peptide (CRP) of 144.14 mg/L (liter), a tryptase of 11.9 μg (microgram)/50 done 15 h after arrival, and a white blood prison cell count of 15.sixty. One time stable, she was discharged domicile with cetirizine ten mg PO daily as needed.

20-four hours afterward belch, the patient returned with subjective symptoms of pruritus and trunk aches. She had received epinephrine IM in ambulance. Bloodwork showed a CRP of 52.96 mg/L and a tryptase of 3.4 μg/L. There was no objective evidence of ongoing reaction. She was discharged home with a PO prednisone taper. She was subsequently seen in the allergy clinic and at that time, the reaction was thought to be unlikely secondary to Rituximab.

On day 26, she received her second dose of Rituximab in an outpatient clinic. She was pre-medicated with acetaminophen 650 mg PO, diphenhydramine fifty mg IV and methylprednisolone 125 mg 4. Thirty minutes after initiation of the infusion, the patient developed symptoms of chest hurting and throat tightness. Objectively, she was found to have urticaria at the infusion site and became hypotensive with a systolic blood force per unit area of 94 from 140, along with hypoxia requiring 5 L/min oxygen via nasal prong to maintain a saturation of 95%. The rest of her vital signs were normal. She was given epinephrine IM equally well as diphenhydramine 25 mg IV and transferred to ER. In the ambulance, her oxygen requirement and hypotension quickly resolved post-assistants of epinephrine. Upon arrival she was asymptomatic, with normal vital signs. Her CRP was 3.11 mg/L and tryptase was 5.two μg/L. After ascertainment for 12 h, she was discharged on PO prednisone with a slower taper to home dose, and was referred back to the allergy dispensary.

Rituximab peel prick examination was negative at a concentration of 10 mg/mL. Intradermal skin testing was started at 1:1000 dilution (0.01 mg/mL) and apace became positive with a wheal of half-dozen mm and flare of 20 mm. Saline command was negative. Histamine control showed a wheal of five mm.

Word and determination

Reports of mild infusion reactions with rituximab are mutual, particularly during outset infusions. Molecular studies seem to propose a primal role for complement organization activation for infusion reaction [2]. Mutual symptoms include flushing, fever, rigors, and malaise. They improve with symptomatic treatment (anti-pyretic, anti-emetic medications, steroids) or slower infusion, and tend not to recur. Cytokine-mediated reactions tin can present with similar symptoms, however different infusion reactions, they can persist many days post-infusion, exercise not respond to symptomatic treatment, and will recur with subsequent infusions [3, four]. Blazon I reactions to Rituximab are frequent and both IgE and non-IgE mediated. Symptoms may involve multiple organ systems. Pare-testing to Rituximab is i manner to aid confirm IgE-mediated allergy [5, 6].

In this instance, since the patient's symptoms persisted more than than 24 h mail service-infusion, we question a potential cytokine-release reaction initially. On 24-hour interval 11 subsequently initial exposure to rituximab, the patient presented with urticaria and angioedema which can be consistent with Type I reaction versus other unrelated status such every bit spontaneous urticaria/angioedema. Even so, nosotros hypothesize that, given the half-life of rituximab in the blood for rheumatoid arthritis is approximately 18–23 days [7], circulating antigens in the bloodstream acquired the patient to develop antibodies to rituximab and convert from a cytokine-mediated reaction to a Type I reaction. In hindsight, this theory was supported by her elevated tryptase level of 11.9 μg/L (from baseline tryptase of 3.4 μg/L, using formula i.two × baseline tryptase + two μg/50) [viii]. The persistence of circulating antigens in her bloodstream may too explicate why the patient had a cyclical nature to her symptoms requiring multiple doses of epinephrine. Given it was the first exposure to rituximab, and given culling possible explanations to her first presentation (for example, spontaneous urticaria/angioedema), the allergy clinic initially thought her first reaction was unrelated to rituximab. However, her symptoms after second exposure along with subsequent evidence of positive peel testing confirmed a true type I hypersensitivity to rituximab. Too, in that location was no history and no recurrence of urticaria/angioedema outside of exposure to rituximab.

Another potential question may be cross-reactivity between rituximab and the patient's previous MAB treatment with tocilizumab due to the mouse epitope in both. Nosotros practise not think this was the case since the patient received doses of tocilizumab on multiple occasions in the past without any reaction. The literature also supports that cross-reactivity is unlikely, given that in that location are no reported cases of proven anaphylaxis after first exposure due to cross-reactivity between MABs [ix]. In fact, there are reports of safe administration of rituximab after anaphylaxis to obinutuzumab, which belongs to the same grade of MAB as tocilizumab and is over 95% humanized [one, ten].

Nosotros have described an unusual example of cytokine-mediated reaction to rituximab subsequently a first infusion, which afterward converted to a type I IgE-mediated reaction subsequently only one infusion of rituximab. To our knowledge, this is the first reported case of this blazon of reaction to rituximab. The patient and her treating squad were fabricated aware that desensitization for future infusions could be pursued, however, they decided to opt for an alternative treatment regimen.

Availability of data and materials

Non applicable.

Abbreviations

MAB:

Monoclonal antibiotic

mg:

Milligram

IM:

Intramuscularly

IV:

Intravenously

PO:

Orally

CRP:

C-reactive protein

50:

Liter

μg:

Microgram

ER:

Emergency room

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Affiliations

1. McGill Academy, Montreal, QC, Canada

   Five. Polito & A. Barbacki

2. Division of Allergy and Clinical Immunology, Department of Medicine, McGill University Health Centre, McGill University, Montreal, QC, Canada

   G. Isabwe

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All authors contributed to the writing, editing the manuscript. All authors read and approved the final manuscript.

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Correspondence to G. Isabwe.

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Polito, V., Barbacki, A. & Isabwe, G. Type I allergic reaction to rituximab upon first lifetime exposure: a instance written report. Allergy Asthma Clin Immunol 16, 56 (2020). https://doi.org/10.1186/s13223-020-00448-8

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• Received: 04 April 2020

• Accustomed: 04 June 2020

• Published: 26 June 2020

• DOI : https://doi.org/x.1186/s13223-020-00448-8

Keywords

• Rituximab
• Monoclonal antibiotic
• MAB
• Hypersensitivity
• IgE
• Anaphylaxis
• Drug allergy
• Infusion reaction
• Cytokine reaction
• Type I reaction

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