Background/Purpose: Infusion-related reactions have been reported with rituximab, a monoclonal antibody targeting the CD20 antigen on B cells, and may result in discontinuation of the medication and/or changing to a potentially less effective alternative agent.  A positive skin testing with a non- irritating dose of a medication is thought to predict an IgE mediated reaction which includes life-threatening anaphylaxis. Furthermore, rituximab skin testing in lymphoma patients may correlate with the severity of IgE hypersensitivity[1].

To our knowledge, there is no data establishing the value of rituximab skin testing in patients with rheumatological conditions who have a presumed IgE mediated hypersensitivity reaction. We present our observational analysis on skin testing results in rheumatology patients who previously developed presumed IgE hypersensitivity reactions to rituximab, and whether the skin testing results correlated to the severity of the clinical reaction.

Methods: We present the skin testing results from a retrospective review of 8 patients followed from January 2000 through September 2019 with systemic rheumatologic conditions who developed presumed IgE mediated hypersensitivity reactions while receiving rituximab.  Patients previously underwent epi-cutaneous prick testing using rituximab at a concentration of 10 mg/mL. If negative testing resulted at 10mg/ml concentration (defined as a wheal diameter measured less than 3mm), testing proceeded to intradermal injections of 1:1000, 1:100, and 1:10 dilutions of the full strength.  Testing was discontinued and defined as a positive with a wheal 3mm or greater than the histamine control. We defined a “mild” IgE mediated reaction as that involving one organ system which did not require epinephrine. A “severe” IgE reaction has two or more organ system involvement which required epinephrine administration.

Results: Regardless of background immunosuppressive agents, all patients except one mounted an appropriate histamine response.  Patients 1-5 and 7 developed “mild” IgE reactions and had negative skin testing. Patient 8 had severe IgE reactions requiring epinephrine IM and on testing mounted a positive intradermal test.  A summary of patient characteristics and skin testing results are provided in Table 1.

Conclusion: Rituximab skin testing has not been studied in patients with underlying rheumatic and inflammatory diseases.  Our preliminary analysis demonstrates mild presumed IgE reactions can possibly predict negative skin testing. A negative test may then allow clinicians to have discussions with patients on the possibility of re-challenging the medication if no alternative medications are suitable. Additionally, our analysis demonstrates that patients are able to mount an adequate histamine response despite immunosuppression by their disease and current medications.

Further studies will be needed to evaluate the utility in the evaluation of skin testing in rheumatic and inflammatory conditions.

Table 1

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rituximab-hypersensitivity-in-rheumatic-and-inflammatory-diseases-role-of-skin-testing/