Systemic Allergic Dermatitis to Cyanoacrylate Used for Embolisation

We describe a systemic allergic dermatitis mimicking a DRESS syndrome to butyl- cyanoacrylate from a surgical glue, in a patient with a history of contact dermatitis to octyl- cyanoacrylate. Radiologists, surgeons, dermatologists and allergists should be aware of this potential severe reaction with the use of this medical device. A 36-year-old female patient with pelvic congestion syndrome underwent embolisation of pelvic varices using GLUBRAN-2 (GEM Srl, Viareggio, Italy) containing a mix of N-butyl-2-cyanoacrylate and methacryloxysulfolane, the radio contrast media VISIPAQUE (iodixanol) and LIPIODOL ULTRA FLUID ethiodized oil in interventional radiology. Two days later, she developed a pruritic maculopapular rash starting on the lower limbs then spreading to the trunk and upper limbs (Figure 1), with fever, fatigue, abdominal and joint pain, anorexia, and headache. Biological tests performed on day (D)12 of the rash showed hypereosinophilia at 1.510 G/L (normal count 0.01–0.4 G/L), a C-reactive protein level of 42 mg/L, while on D16, ALT levels were twice the normal limit (92 UI/L). The rash, treated with oral and topical corticosteroids, and antihistamines, resolved in 4 weeks. The patient had a history of allergic contact dermatitis (ACD) on laparoscopic incisions, 6 years ago, due to DERMABOND surgical glue, containing 2-octyl-cyanoacrylate. She worked as a nurse and reported no use of this kind of medical device nor domestic or cosmetic cyanoacrylates. Patch tests were performed with the European baseline, acrylates series (Chemotechnique Diagnostics, Vellinge, Sweden), octyl and butyl-cyanoacrylate (BLD Pharmatech GmbH, Reinbek, Germany) 10% petrolatum (pet). GLUBRAN-2 glue was tested 30% pet and 'as is' with an open test. DERMABOND was tested with an open test 'as is', Readings were performed on D2, D3 and D7 according to ESCD guidelines [1] (Figure S1). Results are given in Table 1. Intradermal tests (IDT) to VISIPAQUE diluted 1/10 and pure and to LIPIODOL ULTRA FLUID 1/10 were negative on immediate and delayed readings (D1 and D7). EGDMA 2% pet ++ on D2, D3 and D7 Ethyl-cyanoacrylate 10% pet — Butyl-cyanoacrylate 10% pet +++ on D2, D3 and D7 Octyl-cyanoacrylate +++ on D2, D3 and D7 2-HEMA 2% pet ++ on D2, D3 and D7 Nickel sulphate + on D3 (without relevance) GLUBRAN Open test—30% pet +++ on D2, D3 and D7 DERMABOND Open test +++ on D2, D3 and D7 GLUBRAN-2 is a medical device Class III CE marked for internal and external use. It is a synthetic biodegradable ready-for-use cyanoacrylate-based glue, modified by the addition of a monomer, with high adhesive and hemostatic properties [2]. Liquid in its monomeric state, it polymerises very rapidly upon contact with moist tissues. It is indicated in open and laparoscopic surgery and in digestive tract endoscopy as a sclerosant agent but also as an embolising agent in radiology and vascular radiology [2]. The main complications of the use of GLUBRAN-2 are local moderate inflammation and the migration of glue fragments after ovarian vein embolisation [3]. We suppose that the open test with GLUBRAN-2 was negative because a fine superficial film was detached from the skin after a few hours. The patch test with GLUBRAN-2 30% pet showed strong positive results at D2, still present at D7, against an irritative test. Cyanoacrylate-based surgical glues such as DERMABOND and LEUKOSAN are known to cause ACD at application sites sometimes with extension of the lesions at distance [4, 5]. Indeed, an ACD due to surgical glue was reported with secondary diffusion at distance from the application but incorrectly referred to as systemic contact dermatitis (SCD) [6]. ACD have been reported with all three types ethyl, octyl, and butyl-cyanoacrylates with possible cross-reactions [4, 6]. Our patient shows dual sensitisation to butyl and octyl-cyanoacrylate, with clinical relevance linked to both episodes. DERMABOND glue contains octyl cyano-acrylate and GLUBRAN-2 glue contains butyl-cyanoacrylate. Ethyl-cyanoacrylate, the only cyanoacrylate in the acrylates series, can be negative such as in our case [5]. Cyanoacrylate glues are also used in cosmetics for extensive eyelashes or, less commonly, for artificial nails. They are also used as fast-setting super glue. Our patient had also a strong positive patch test to 2-HEMA and EGDMA without known ACD to adhesives or artificial nails. GLUBRAN-2contains another monomer, methacryloxysulfolane, and cross reactions with these methacrylates cannot be excluded [7]. The nature of the lesions, with blood hypereosinophilia, hepatic cytolysis and extracutaneous symptoms initially led us to consider drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) but no medication use outside of the radio contrast media and ethiodized oil was found, with negative IDT. The patient's history of a previous ACD to a surgical cyanoacrylate glue led to the consideration of a diagnosis of systemic allergic dermatitis (SAD) also known as SCD to another cyanoacrylate glue, then introduced systemically, with cross-reaction between the 2 cyanoacrylates. SAD is an inflammatory skin disease occurring in contact-sensitised individuals secondarily exposed to the hapten (i.e., metals, balsam of Peru) by another route of administration [8]. A maculopapular rash may be observed, sometimes accompanied by fever, malaise, nausea, vomiting, diarrhoea, or arthralgias [9]. Our hypothesis is that the patient probably reacted to residues of cyanoacrylate monomers which are known to be the haptens because of an incomplete polymerisation. An alternative for embolisation with an ethylene vinyl alcohol copolymer was offered to the patient [10]. To conclude, our case report suggested a SAD mimicking DRESS syndrome to butyl-cyanoacrylate in a patient with a history of ACD to octyl-cyanoacrylate. The use of these medical devices via non-cutaneous routes should warrant prior investigation of any previous contact allergies to surgical glues or other glues containing cyanoacrylates. Salomé Allichon: conceptualisation, investigation, visualisation, writing – original draft preparation, writing – review and editing. Xavier Stefanovic: investigation, writing – review and editing. Nadia Raison-Peyron: conceptualisation, investigation, methodology, project administration, supervision, visualisation, writing – original draft preparation, writing – review and editing. Marie Lagreula: conceptualisation, investigation, methodology, project administration, supervision, visualisation, writing – original draft preparation, writing – review and editing. The patient gave written consent to publish her case and photographs. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Figure S1: A&B: Results of patch tests and open test at D2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.