Localised Hypersensitivity Reaction to Polysorbate 80 During Secukinumab Treatment: A Case of Injection‐Site Contact Urticaria

The advent of biologic drugs in the past decade has significantly improved the treatment of several dermatological diseases. While these drugs are highly effective and generally safe, hypersensitivity reactions have been reported. These are commonly attributed to the active ingredient; however, the real culprit is often not disclosed. Patch testing, skin prick testing (SPT), and intradermal testing (IDT) have focused not only on the active ingredient but also on key excipients, such as polysorbate 80‐present in the vehicle of many biologics, including secukinumab‐. The study of such excipients can help clarify the origin of these reactions.

Case Report

A 40‐year‐old woman with a history of hidradenitis suppurativa, who developed a paradoxical palmo‐plantar psoriasis due to adalimumab, presented with a 4‐month history of injection‐site reactions to secukinumab 300 mg (Cosentyx). From the first administration, she developed extensive, well‐defined erythematous‐edematous itchy hives at the injection site, which started within an hour of administration and spontaneously resolved within 6 h. The study using the European and Spanish baseline series patch tests, along with polysorbate 80 5% pet., were negative. However, SPT with polysorbate 80 at 1:100 and 1:1000 dilutions, along with IDT using the same dilutions of polysorbate 80, and undiluted Cosentyx, yielded positive results at 60 min (Figure 1). Induced wheals spontaneously resolved within 2 h. Five control subjects tested negative with polysorbate 80 at the same dilutions. With reactivity to such high dilutions, a diagnosis of immediate reaction type contact urticaria due to polysorbate 80 was established. The drug was maintained, as all available biologics contain polysorbates, with the administration of 2 mg of oral dexchlorpheniramine the night before and 1 h prior to drug injection. A second‐generation anti‐H1 was considered, but dexchlorpheniramine was maintained due to good tolerance and patient's preferences. This anti‐H1 therapy was partially effective, reducing the size and duration of the injection‐site wheals, and preventing the appearance of generalised wheals.

FIGURE 1.

Clinical picture of skin prick test (SPT), the results of which are shown on the left, and intradermal test (IDT), which are shown on the right. A black line separates the two types of skin test used. The photography was taken 60 min after testing.

Discussion

Polysorbate 80, also known as Tween 80, is a nonionic surfactant, stabiliser and emulsifier widely employed in foods, cosmetics and topical, oral, and subcutaneous/parenteral drugs, including biologic therapies for hidradenitis suppurativa, psoriasis, and atopic dermatitis [1]. Polysorbate 80 contained in adalimumab and ustekinumab has been reported to induce generalised acute urticaria in a woman with psoriasis [2]. Another case documented generalised urticaria secondary to polysorbate 20 in a psoriasis patient treated with brodalumab, who had previously experienced urticaria and/or anaphylactoid reactions with infliximab, ustekinumab, adalimumab, and secukinumab [3]. Given the aforementioned biologics contain polysorbate 80, which is analogous to polysorbate 20, a cross‐reaction could be hypothesized.

Polysorbate 80's role as a contact sensitizer is mostly reported in type IV eczematous reactions [4]. Contact urticaria from this excipient is rare [1], and this form of localised urticaria due to polysorbate 80 in relation to biologics has not been previously reported. In this case, however, polysorbate 80 was injected rather than applied topically, which deviates from the classical definition of contact urticaria. Nonetheless, the clinical presentation featured well‐defined, localised, itchy wheals, hallmark characteristics of this condition. It is plausible that injecting the substance directly into the dermis, bypassing the epidermal barrier, could facilitate such reactions, potentially involving the same mechanism as in classical contact urticaria. Injection‐site reactions are frequent but rarely studied, which may underscore the potential underdiagnosis of these localised immediate hypersensitivity reactions to excipients contained in subcutaneous drugs.

The mechanism behind polysorbate hypersensitivity is unclear, but some studies suggest a non‐immunological basis [5], consistent with the delayed reaction observed in our case. Interestingly, the patient did not experience similar reactions with adalimumab, which also contains this excipient. These differences in reaction timing and severity [3] may further support a non‐immunological mechanism. When facing hypersensitivity reactions to biologics, excipients should be carefully considered, especially in cases of unclear origin and atypical clinical presentation. Since stages 3 and 4 of contact urticaria syndrome involve extracutaneous manifestations [6], and potentially fatal anaphylactoid reactions to polysorbate 80 have been documented [5], it may be necessary to identify hypersensitivity to this ubiquitous component.

Author Contributions

Emilio Berna‐Rico: conceptualization, investigation, writing – original draft. David Pesqué: conceptualization, investigation, writing – original draft, supervision. Gemma Martin‐Ezquerra: writing – review and editing, conceptualization, investigation. Nidia Planella‐Fontanillas: conceptualization, investigation. Ramon Pujol Vallverdu: writing – review and editing, supervision. Fernando Gallardo: writing – review and editing, supervision. Ana M. Giménez‐Arnau: conceptualization, investigation, writing – review and editing, supervision.

Consent

The patient in this manuscript has given written informed consent to publication of her case details.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.