Maculopapular rash after intravitreal injection of an antivascular endothelial growth factor, aflibercept, for treating age-related macular degeneration

Nagai, Norihiro; Ibuki, Mari; Shinoda, Hajime; Kameyama, Kaori; Ohta, Michio; Ozawa, Yoko

doi:10.1097/md.0000000000006965

Cited by 12 publications

(8 citation statements)

References 15 publications

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“…In all cases, no concomitant intraocular inflammation or vasculitis was associated with these cutaneous manifestations. Previous anecdotal reports have reported similar reactions to all of these three drugs [12][13][14][15][16][17]. However, so far no similar event is known after brolucizumab, the most recent anti-VEGF drug for intraocular use.…”

Section: Discussionmentioning

confidence: 98%

“…Aflibercept is composed from the fusion of domains of VEGF-receptor 1 and 2 to an IgG1 Fc-portion. Brolucizumab is a single-chain antibody fragment (scFv) composed of two complementarity-determining regions of the anti-VEGF molecule grafted to a human scFv scaffold itchy diffuse rash [12][13][14][15][16][17]. The initial pivotal trials did not report cutaneous eruptions as anti-VEGF related side effects.…”

Section: Introductionmentioning

confidence: 99%

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Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors

Moret

Ambresin

Gianniou

et al. 2021

Graefes Arch Clin Exp Ophthalmol

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Purpose To describe a series of non-immediate drug hypersensitivity reactions after intravitreal anti-vascular endothelial growth factors (anti-VEGFs). Patients and methods Retrospective report of 6 patients with cutaneous non-immediate drug hypersensitivity reactions following intravitreal anti-VEGF injections, 4 after ranibizumab, 1 after bevacizumab and 1 after aflibercept. Results Clinical manifestations ranged from mild maculopapular rash, purpura to severe generalized erythroderma, with or without systemic involvement such as microscopic hematuria and proteinuria or fever. In two out of the six patients, reintroduction of either the same or an alternative anti-VEGF drug did induce a recurrence of the drug hypersensitivity reaction, while 4 patients showed no recurrence. Conclusion Cutaneous non-immediate drug hypersensitivity reactions secondary to intravitreal anti-VEGF may occur. Continuation of the same drug or switch to another anti-VEGF may either induce recurrence or be well supported by the patient. The decision of drug discontinuation should be guided by the severity of the disease.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors

Moret

Ambresin

Gianniou

et al. 2021

Graefes Arch Clin Exp Ophthalmol

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“…1 Nagai et al report a case of a patient who developed a maculopapular rash 10 hr after injection with aflibercept and was presumed to have a type IV hypersensitivity reaction to this biologic. 2 In addition, a case report detailed a series of patients who were found to have type IV hypersensitivity reactions after intravitreal injections; however, these reactions were most commonly found to be secondary to phenylephrine used during the procedures and not the anti-VEGF medications. 3 A practicing allergist needs to remain aware of hypersensitivity reactions to biologics but also consider other medications used in each procedure so as to not overlook other possible culprits.…”

Section: Discussionmentioning

confidence: 99%

The Eyes Have It: Eyelid Swelling and Rash in a 79-year-old Woman With Macular Degeneration

Kleris

Keswani

Lugar

2018

Allergy�Rhinol (Providence)

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IntroductionA 79-year-old woman with macular degeneration was referred to the Allergy/Immunology clinic for the evaluation of a potential allergy to anti-vascular endothelial growth factor (anti-VEGF) treatments. The patient developed urticaria and eyelid swelling immediately following a retinal injection of aflibercept, which she had previously tolerated. She previously had allergic reactions following ranibizumab and bevacizumab injections. Injections of anti-VEGF treatments were discontinued given concern for allergy with progression of the patient’s disease.ObjectiveTo assess the culprit medication(s) responsible for hypersensitivity reactions following anti-VEGF injections for macular degeneration.MethodsMedication records were reviewed for each retinal injection. All medications used in each procedure, including the anti-VEGF therapy (aflibercept), topical anesthetics (tetracaine and proparacaine hydrochloride), and antiseptic (povidine), were evaluated with skin testing. She was additionally tested for alternative anti-VEGF therapies (ranibizumab and bevacizumab) as she was thought to have allergies to these agents by prior history. A test dose challenge was completed for aflibercept, ranibizumab, and bevacizumab.ResultsSkin prick and intradermal testing were negative to aflibercept, ranibizumab, bevacizumab, and povidine. Intradermal testing was positive to tetracaine and proparacaine hydrochloride. The patient passed test dose challenges to aflibercept, ranibizumab, and bevacizumab. Due to her positive hypersensitivity testing to 2 ester anesthetics, the patient underwent skin prick and intradermal testing to the amide anesthetic, lidocaine. This was negative and the patient tolerated a graded challenge to lidocaine. She was deemed to have an immunoglobulin E (IgE)-mediated hypersensitivity to ester-type local anesthetics. She successfully resumed anti-VEGF therapy with an amide local anesthetic.ConclusionsThe reason for this consult was the concern for hypersensitivity to a biologic anti-VEGF medication. The culprit allergen, the local anesthetic, could have been overlooked without an assessment of all medications used during the procedure. This case highlights the importance of a thorough allergy evaluation of all medications used during procedures to determine the causative agent.Chief Complaint: Eyelid swelling and rash after ophthalmic procedures for macular degeneration.

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“…In addition, ADA have been reported to develop in 1.4-3.1 % of patients, and the clinical significance of their neutrali zation has not been assessed due to limited data [50]. Maculopapular rash may develop after intravitrael administration of this drug in retinal diseases [51].…”

Section: Afliberceptmentioning

confidence: 99%

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events*

Gülşen¹,

Wedi²,

Jappe³

2020

Allergo J

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Purpose: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. Methods: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. Results: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). Conclusion: There is an urgent need for a simpler symptom-or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future. Cite this as Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events.

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Maculopapular rash after intravitreal injection of an antivascular endothelial growth factor, aflibercept, for treating age-related macular degeneration

Cited by 12 publications

References 15 publications

Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors

Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors

The Eyes Have It: Eyelid Swelling and Rash in a 79-year-old Woman With Macular Degeneration

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events*

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