ACTAS Dermo-Sifiliográficas 112 (2021) 389---391

OPINION ARTICLE

Skin Reactions to Glucose Sensors: Present and

Servicio de Dermatología Médico-Quirúrgica y Venereología, Departamento de Eczema de Contacto e Inmunoalergia, Hospital

Received 24 May 2020; accepted 17 September 2020

The increase in the number of diabetic patients who used glucose sensor is occluded for 14 days has 2 major implica-
glucose sensors has led to more frequent findings of local tions. First, the sensor remains occluded for a long period,
skin reactions caused by these devices. Affected patients are and, second, it is necessary to apply a material that enables
evaluated by dermatologists, endocrinologists, and pediatri- the device to be used for such a long period. This is exactly
cians. Since not all hospitals have cutaneous immunoallergy where the main allergen to date, isobornyl acrylate (IBOA;
units, the specialist must be aware of the peculiarities of CAS 5888-33-5), comes into play. Many published articles
this new contact dermatitis ‘‘epidemic’’. Recent years have show that IBOA is the main culprit behind allergic contact
seen the publication of numerous articles on skin reactions dermatitis to FreeStyle Libre® .3 A positive reaction to IBOA
caused by glucose sensors. was observed in 83.3% of pediatric patients studied because
The first sensor marketed (not funded at the time) was of cutaneous reactions to the device.4 Some authors have
FreeStyle Libre (Abbot Laboratories). Subsequent funding proposed changing the glucose sensor to Eversense (Roche)5
of the device led to a considerable increase in its use or Dexcom (Medtronic)6 in order to resolve the problem of
by patients with type 1 diabetes mellitus (DM). Through skin reactions. However, this proposal is ‘‘problematic’’ for
enhanced control of blood glucose, the device changed a number of reasons. First, to date, these glucose sensors are
the lives of many patients with diabetes mellitus, enabling not publicly funded in Spain and are very expensive. As an
them to lead an almost normal life, in terms of both their example, Dexcom G5 costs around D 200 every 7 days, which
social setting and sporting activities. However, cutaneous is when the sensor is changed, thus preventing the device
inflammatory reactions at the application site have not from being universally affordable. Second, the use of these
gone unnoticed, and their prevalence has been estimated at devices is not exempt from skin reactions, which are initially
between 3.8%1 and 8.4%.2 The fact that the FreeStyle Libre irritant, although for now, we do not know whether they
contain a potentially sensitizing allergen. However, patients
who come to my eczema clinic (diagnosed with contact
夽 Please cite this article as: Navarro-Triviño FJ. Reacciones dermatitis to IBOA) mentioned that they had received a
cutáneas a sensores de glucosa: presente y futuro. Actas Dermosi- new version of the FreeStyle Libre device. Tolerance to the
filiogr. 2021;112:389---391. device was good for the first 14 days, and it seems that the
E-mail address: fntmed@gmail.com

1578-2190/© 2020 AEDV. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
 F.J. Navarro-Triviño

Figure 1 A, Vesicular reaction in the area of contact with the adhesive of the FreeStyle glucose sensor, with sparing of the area
in contact with the plastic. B, Positive reaction to isobornyl acrylate 0.1% pet at 96 hours. C, Positive reaction to the adhesive of
the FreeStyle sensor.

composition of the adhesive has been modified to eliminate Insulin pumps, which constitute another medical device
IBOA, since the patients were unable to tolerate the sensor directly related to glucose sensors,11 can also cause allergic
for more than 48 hours owing to allergic contact dermati- contact dermatitis, with the main culprit allergens being
tis. Oppel et al.7 recently published an interesting article in IBOA, N,N-dimethylacrylate, and 2-ethyl-cyanoacrylate.
which they analyze the new FreeStyle Libre 2 sensor, which Patients who use glucose sensors clearly require special
does not contain IBOA. The allergens that could be asso- care of the skin where the device is applied. In this sense,
ciated with sensitization include 2,6-di-tert-butyl-4-cresol there have been reports of various materials with a bar-
(butylated hydroxytoluene), which is now included in the rier function, such as hydrocolloid patches12 and Tegaderm
new adhesive. Therefore, it should form part of the specific Advanced dressings.13 While these approaches work for some
allergen series that we use for patch testing in patients who patients, my experience indicates that they are not a long-
develop contact dermatitis after using FreeStyle Libre 2. term solution.
Other allergens associated with glucose sensors are Patch testing is crucial for confirming allergic contact
colophony and Abitol,8 sesquiterpene lactone mix,9 and N,N- dermatitis in patients who use these devices. Adhesive as
dimethylacrylamide.10 N,N-dimethylacrylamide has been is, in addition to testing IBOA 0.1% pet (allergen marketed
shown to be present in the adhesive of FreeStyle Libre, by Chemotechnique Diagnostics), makes it possible to cor-
and after IBOA, it is the second most frequent allergen rectly identify patients with true allergic contact dermatitis.
associated with contact dermatitis to this device. N,N- Local reactions are usually vesicular and severe (Fig. 1). It is
dimethylacrylamide is not currently commercially available also important to take into account that IBOA does not seem
for patch testing, although it may be in the future. It to cross-react with other acrylates. In my department, all
can therefore form part of the group of allergens to be patients were assessed using the acrylate series and reacted
assessed in patients with contact dermatitis to glucose only to IBOA. In clinical terms, contact dermatitis to glucose
sensors. N,N-dimethylacrylamide can be purchased directly sensors usually manifests as acquired leukoderma (Fig. 2A),
from Sigma-Aldrich, where it is prepared in the labora- which has received attention in the literature,14 reactions
tory (or hospital pharmacy) in an appropriate vehicle, with purpuric areas (Fig. 2B), and papulovesicular reactions
such as petrolatum. It must be borne in mind that N,N- (Fig. 2C).
dimethylacrylamide is combined with another substance, The development of new devices for control of glycemia
hydroquinone; therefore, when assessing this allergen, is essential if we are to improve the quality of life of
hydroquinone should be tested individually in order to pre- patients with diabetes mellitus. Also key for the manage-
vent diagnostic errors. ment of this condition are adhesives with less sensitizing
The fact that some patients who are sensitized to IBOA potency in order to prevent allergic contact dermatitis. In
experience positive reactions to sesquiterpene lactone mix this sense, I believe that avoiding long occlusions (e.g.,
could be explained by the isomerization of ␣-pinene to 14 days for FreeStyle Libre) could play a major role in
camphene; binding to a methylene group, a hydrogen, and preventing sensitization, although this has not been demon-
2-dioxygens leads to the structure of IBOA. strated.

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 ACTAS Dermo-Sifiliográficas 112 (2021) 389---391

Figure 2 A, Leukoderma acquired after application of the FreeStyle glucose sensor. B, Vesicular and purpuric eczema after
application of the FreeStyle glucose sensor. C, Papulovesicular eczema after application of the FreeStyle sensor.

The future seems promising, given that new noninva- 3. Kamann S, Oppel E, Liu F, Reichl FX, Heinemann L, Högg C.
sive devices could replace current glucose sensors. These Evaluation of isobornyl acrylate content in medical devices for
include GlucoWise (Medical Expo), which is applied on the diabetes treatment. Diabetes Technol Ther. 2019;21:533---7.
finger and can detect glucose levels by means of 65-Hz 4. Herman A, Darrigade AS, de Montjoye L, Baeck M. Contact der-
matitis caused by glucose sensors in diabetic children. Contact
radiofrequencies. Senseonics Eversense (Senseonics, Inc) is
Dermatitis. 2020;82:105---11.
a subcutaneous invasive device that lasts 90 days and will be 5. Oppel E, Kamann S, Heinemann L, Reichl FX, Högg C. The
yet another option in the future. Both models could repre- implanted glucose monitoring system Eversense: an alternative
sent a solution for patients with allergic contact dermatitis for diabetes patients with isobornyl acrylate allergy. Contact
caused by currently available glucose sensors. However, in Dermatitis. 2020;82:101---4.
real terms, the high price of the devices, which will probably 6. Oppel E, Kamann S, Reichl FX, Högg C. The Dexcom glucose
not be covered, will limit patients’ access to these modern monitoring system---an isobornyl acrylate-free alternative for
glucose sensors. diabetic patients. Contact Dermatitis. 2019;81:32---6.
I think that, for now, given the gradual increase in the fre- 7. Oppel E, Kamann S, Heinemann L, Klein A, Reichl FX,
Högg C. Freestyle libre 2: the new isobornyl acrylate
quency of cases, all dermatology reference centers treating
free generation. Contact Dermatitis. 2020, http://dx.doi.org/
patients with contact dermatitis, including those associated
10.1111/cod.13638.
with medical devices used in diabetes mellitus, should have 8. Ahrensbøll-Friis U, Simonsen AB, Zachariae C, Thyssen JP,
access to the most common allergens, namely, IBOA, Abitol, Johansen JD. Contact dermatitis caused by glucose sensors,
the specific cyanoacrylate series, and, in the best case insulin pumps, and tapes: results from a 5-year period. Contact
scenario, N,N-dimethylacrylamide (which can be purchased Dermatitis. 2020, http://dx.doi.org/10.1111/cod.13664.
from Sigma-Aldrich), even though it must be prepared in 9. Herman A, Mowitz M, Aerts O, Pyl J, de Montjoye L, Goossens A,
a laboratory or hospital pharmacy. A meticulous study of et al. Unexpected positive patch test reactions to sesquiterpene
patients with suspected contact dermatitis should enable lactones in patients sensitized to the glucose sensor FreeStyle
us to detect the culprit allergens; therefore, it is necessary Libre. Contact Dermatitis. 2019;81:354---67.
10. Mowitz M, Herman A, Baeck M, Isaksson M, Antelmi A, Ham-
to have access to those mentioned here. In special situa-
nerius N, et al. N,N-dimethylacrylamide---a new sensitizer
tions, cooperation with the endocrinology and pediatrics
in the FreeStyle Libre glucose sensor. Contact Dermatitis.
departments can enable us to draw up a detailed clinical 2019;81:27---31.
history and provide the patient with the option of request- 11. Wagner N, Kamann S, Oppel E. Kontaktallergie auf
ing a change of sensor (to one that is not funded), without Glukosemesssysteme und Insulinpumpen [Contact allergy
having to pay for it. due to insulin pumps and glucose sensor systems]. Hautarzt.
2020;71:205---10.
12. Kamann S, Heinemann L, Oppel E. Usage of hydrocolloid-based
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