An Occlusive Hydrocolloid-Based Patch Is Effective,Feasible,and Safe As a Treatment of Irritant Contact Dermatitis Due to Diabetes Devices in Children and Adolescents with Type 1 Diabetes

Abstract

Irritant contact dermatitis (ICD) occurs frequently with the use of diabetes devices, but no guidelines for treatment exist. Since subsequent devices need intact skin for intended use, quick healing is crucial. Normal wound healing is expected to be 7–10 days. This was a single-center cross-over study that investigated the effectiveness of an occlusive hydrocolloid-based patch versus nonocclusive treatment of ICD. Participants were aged 6–20 years with active ICD caused by using diabetes device. First study period was patch treatment for 3 days. A control arm was initiated if a new ICD occurred within 30 days. ICD healed completely in 21% of the patch group but none in the controls. Itching was reported as an adverse event (AE) in both arms, but only one additional AE was noted in the patch arm: an infection at a different site from investigated. The hydrocolloid-based patch showed signs of faster healing of ICD with no additional AEs, but larger studies are needed.

Introduction

Children and adolescents with type 1 diabetes (T1D) are increasingly treated with diabetes devices, such as insulin infusion pumps and continuous glucose monitoring, as standard of care. These devices require a needle/catheter/filament insertion that is fixated to the skin by an adhesive patch.¹ The patches require a fast tack and strong adhesion, and use potentially irritant materials, such as acrylic adhesives.² Our previous research has shown that 90% of patients using diabetes devices have experienced skin irritation, with two-thirds experiencing active irritation at the time of the questionnaire-based research.³ The research showed several different subcategories of skin irritation prevalent in the studied population, with the largest being irritant contact dermatitis (ICD).

There is currently no consensus or standard of care guidelines on optimal treatment of ICD in these patients.⁴ In general, device manufacturers discourage the use of topical steroid treatments as this may impact the use of the devices applied to the same area. Indeed, patients are dissuaded from using any type of treatment that limits, or potentially interferes with, the direct contact of the device and skin. Furthermore, dermatologists are cautious of continuously using steroid treatment for >4 weeks due to the hypothesized skin barrier impairment.⁵

However, steroid creams are often used to continue the use of diabetes devices in recognition of the multiple other benefits they confer.³ Occlusion is known to improve healing through moist wound healing⁶ and may also speed up recovery when caused by irritant materials in the diabetes devices.

Therefore, the explorative objective of this study is to investigate the efficacy and safety of an investigational occlusive hydrocolloid-based patch as therapy of ICD compared with standard nonocclusive care.

Materials and Methods

This study was a single-center cross-over study investigating the response of ICD on active treatment with an occlusive hydrocolloid-based polymer patch versus nonocclusive standard of care therapy. Study participants were patients aged 6–20 years with active and evaluable ICD caused by a diabetes device. The first study period examined the occlusive patch with an intended wear time of 3 days used from days 1 to 4 equivalent to next infusions set shift. Clinical assessment of the skin site was performed by the investigator on days 1, 4, and 8 through (1) visual examination, (2) measurement of transepidermal water loss (TEWL) with Aquaflux AF200 from Biox Systems, (3) dimensions of ICD, and (4) photography of the site.

Follow-up photography was performed on days 5, 6, and 7 as well as from home. Dermatology life quality index (DLQI) was answered on days 1, 4, and 8, and a satisfaction questionnaire was answered on day 8. If a new ICD was observed in the 30 days that followed, a control arm was initiated with the same measurements and follow-up but with standard care therapy without any occlusion. The same participant could participate more than one time but only if it was a new skin site located at least 5 cm from the previously treated skin site.

The primary endpoint was ICD response, defined as the proportion of patients having a partial or complete reduction in ICD based on the 5-point scale of eczema assessment on days 4 and 8. To detect differences in ICD response, the chi-squared or Fisher's test was used. Other endpoints were evaluated with descriptive methods and unpaired t-tests for TEWL and DLQI. All analyses were based on the intention-to-treat principle. P-values of <0.1 were regarded as significant in this explorative study.

The research ethical committee (H-20072095) and the unit of medical devices at Danish Medicines Agency also (Ref: 2020122086) approved the study. Before study participation, oral and written consent was obtained from either the participant or their caregivers, depending on age, in accordance with Danish legislation. The Data Agency approved the study (P-2020-858), and it was preregistered at ClinicalTrials.gov (NCT04909983). REDCap was used for data collection and study management.^7,8

Results

The patch was investigated in a total of 14 individuals. Seventeen treatment periods were included in the patch arm, of which five became the control arm. In both groups, study participants had a median age of 13.5 years, ranging from 6 to 18 years made up of predominately males. Median duration of T1D was 6 years (range 3–13 years) and Hemoglobin A1c was 50–52 mmol/mol (equal to 6.7%–6.9%). Half of the participants had an atopic disease, and one had a history of atopic dermatitis. In the patch arm, 47% of treated ICD reactions were caused by infusion sets, 17% from pump patches, and 35% from glucose sensors.

In the control arm, 80% were caused by infusion sets and 20% by glucose sensors. All baseline characteristics are given in Supplementary Table S1. The control arm consisted of nonocclusive treatment according to standard of care, that is, lipid moisturizer and/or steroid lotion. Lipid moisturizer was used in all five control periods and steroid lotion in two of the five control periods.

As shown in Figure 1, 21% and 24% had complete remission of ICD at days 4 and 8, respectively, in the patch arm, whereas none was logged in the control arm. Partial remission was seen in 93% of patch arm at day 4 compared with 75% in control arm. Though Fisher's test failed to discern significance, the mean odds ratio of partial remission was 3.9 in favor of patch over control arm. At day 8, 100% had partial remission in control arm compared with 88% in patch arm. Supplementary Figure S1, panel A, shows how the severity of ICD changed over time.

FIG. 1.

Bar plots of control and patch arm for the frequency of, respectively, complete remission of ICD, partial remission of ICD, and improvement of QoL at, respectively, days 4 and 8. Complete remission of ICD was defined as “Clear” in ICD severity and partial remission was any improvement in ICD severity score. ICD, irritant contact dermatitis; QoL, quality of life.

There was a steep decrease in the severity of ICD in the patch arm from days 1 to 4, which stabilized thereafter, whereas the control arm seemed to show a more linear decrease. When comparing the two types of control arm with use of steroid lotion or only lipid lotion, there was a trend toward a steeper decline in severity of ICD in the steroid group, although statistically insignificant due to small group sizes (Supplementary Fig. S2). The patch adhered for the full 3-day period in 12 out of 17 treatment periods. Reasons for performance failure were itching and the resulting scratching. Table 1 summarizes TEWL value, severity of ICD, score and group of DLQI, and types of reported adverse events (AEs) at time of baseline (T1), day 4 (T4), and day 8 (T8).

Table 1.

Results of Patch and Control Arm

	Patch arm, n (%)			Control arm, n (%)
	T1 ^a (N = 17)	T4 ^a (N = 17)	T8 ^a (N = 17)	T1 ^a (N = 5)	T4 ^a (N = 5)	T8 ^a (N = 5)
TEWL at ICD site
Median [Min, Max]	32.5 [19.9, 116]	33.4 [25.0, 49.0]	33.1 [19.7, 86.9]	33.8 [33.2, 133]	74.4 [74.4, 74.4]	37.9 [21.6, 54.2]
Missing	1 (5.9)	14 (82.4)	2 (11.8)	2 (40.0)	4 (80.0)	3 (60.0)
Severity of ICD
Clear	0 (0)	3 (17.6)	4 (23.5)	0 (0)	0 (0)	0 (0)
Almost clear	1 (5.9)	6 (35.3)	6 (35.3)	0 (0)	1 (20.0)	3 (60.0)
Mild	5 (29.4)	3 (17.6)	7 (41.2)	0 (0)	0 (0)	2 (40.0)
Moderate	7 (41.2)	2 (11.8)	0 (0)	2 (40.0)	3 (60.0)	0 (0)
Severe	4 (23.5)	0 (0)	0 (0)	3 (60.0)	0 (0)	0 (0)
Missing	0 (0)	3 (17.6)	0 (0)	0 (0)	1 (20.0)	0 (0)
Score of DLQI
Median [Min, Max]	2.00 [2.00, 19.0]	2.00 [0, 15.0]	2.00 [0, 13.0]	2.00 [2.00, 19.0]	2.00 [2.00, 15.0]	2.00 [2.00, 13.0]
Group of DLQI
Big effect	2 (11.8)	2 (11.8)	2 (11.8)	2 (40.0)	2 (40.0)	2 (40.0)
Little effect	13 (76.5)	9 (52.9)	13 (76.5)	3 (60.0)	3 (60.0)	3 (60.0)
Moderate effect	2 (11.8)	2 (11.8)	1 (5.9)	0 (0)	0 (0)	0 (0)
No effect	0 (0)	4 (23.5)	1 (5.9)	0 (0)	0 (0)	0 (0)
Types of AE reported
Itching	0 (0)	8 (47.1)	1 (5.9)	0 (0)	1 (20.0)	2 (40.0)
Infection	0 (0)	0 (0)	1 (5.9)	0 (0)	0 (0)	0 (0)
None	17 (100)	9 (52.9)	15 (88.2)	5 (100)	4 (80.0)	3 (60.0)

T1, T4, and T8 represent three different time points where T1 represents day 1 (baseline) before initiation of either patch or control arm, T4 represents day 4 after removal of patch, and T8 represents day 8.

AEs, adverse events; DLQI, dermatological life quality index; ICD, irritant contact dermatitis; Max, maximum; Min, minimum; TEWL, transepidermal water loss measured at the ICD site.

Lack of data points due to large proportion of virtual visits at day 4 made it impossible to calculate reasonable descriptive statistics for TEWL. However, for days 1 and 8, TEWL was comparable in the patch arm and although there was a slight increase in the control arm, the change did not reach significance.

Skin-specific quality of life with DLQI improved by day 4 for most participants independent of treatment arms; Supplementary Figure S1, panel B. The number of AEs other than itching was low with only one AE (infection at day 8) in the patch arm, although in a different site from the site treated with the patch. Itching was described at days 4 and 8 for both arms, but to a higher extent at day 4 for patch arm compared with control arm, whereas it seemed opposite at day 8.

The satisfaction questionnaire (shown with results in Supplementary Appendix SA1) revealed only significant differences between patch and control arm for question 2 on perception of the effect of treatment, which was in favor of patch. The effect of treatment with a patch was underexpected or as expected in most cases. Patch treatment had a positive influence on the life of some of the children or adolescents, but none in most cases. Most children or adolescents had not noticed the treatment or positively noticed the treatment. The skin after use of the patch was mostly described with “no difference” or “better” compared with “no influence” for the control group only.

Discussion

This explorative study revealed that treatment with the investigated hydrocolloid-based patch was as safe, effective, and feasible as the standard of care lipid or steroid lotion treatment.

Safety was established based on the low number of AEs. Though itching was reported in both arms, it is recognized as part of the natural skin recovery pattern.⁹ Hence, it could be taken as a positive, rather than negative, AE in this instance. The only non-itching AE was an infection reported in accordance with protocol and regulatory units. However, the site of infection was separate from the site of the patch and was, therefore, determined unlikely to be related to the use of the patch. The intended efficacy of the patch was a faster healing of the ICD, enabling the skin area to be used for a new device placement compared with standard of care.

Even though only five patients were included in the control arm, it is still an intriguing finding that >20% of the skin sites in the patch arm after 3 days of patch treatment had complete remission of ICD compared with none in the control arm. The result hints at a steeper decline in severity of ICD during use of patch followed by a flatter stable severity decline after removal as compared with the normal linear recovery of ICD areas in the control arm.

This was supported by the findings of more itching AEs in patch arm on day 4 compared with that on day 8 in control arm, which again may be interpreted as a sign of recovery. The ability of the Patch to shorten the recovery period for at least 20% of the ICDs is particularly clinically relevant in a pediatric population due to limited skin sites suitable for diabetes devices.

Admittedly, the control arm was small thereby limiting the ability to detect differences in efficacy. However, the study was exploratory in nature, and considering the clinical relevance of the message, the identification of a potentially safe and effective patch treatment in a field with an unmet need is valuable. The cross-over design with intervention in first period was chosen to avoid limiting the ability to evaluate the patch, but since no studies have determined the natural recovery course of ICD by diabetes devices, the control arm was also important and warrants further investigation. Like our data, others have also found that the use of hydrocolloid-based therapies in treating other types of ICD is feasible.¹⁰

The quality of life improved in most cases irrespective of treatment arm per se. The differences were small, emphasizing that the dermatitis seen in relation to diabetes device treatment is often chronic, with short-term treatment unlikely to result in significant and sustainable improvement. Satisfaction with the patch treatment was good, although high expectations indicating the burden of the dermatitis could not be fulfilled in all cases.

This study is the first to evaluate a treatment method for ICD caused by diabetes devices. Future perspectives include the need for larger studies and repeated treatment if eczema persists after 3 days resulting in sustained effect. The material in current diabetes devices causing ICD should also be questioned with a view toward developing significantly more skin-friendly diabetes devices for the future. Still, quick, and strong adhesion of diabetes devices to the skin will bear a risk of ICD. Hence, there remains a need for treatment opportunities with few or no side effects that avoid/minimize topical steroid use to secure healthy skin barrier and encourage long-term treatment compliance.

In conclusion, we have shown how a hydrocolloid-based patch appears to be safe and effective for treatment of ICD in children and adolescents with ICD caused by diabetes devices. Nevertheless, larger studies are needed to confirm these findings.

Footnotes

Acknowledgments

We acknowledge the children, adolescents, and their parents who voluntarily participated in, and thereby made, this study possible. We also thank the nurses and doctors who helped by recruitment of participants, and Annemarie Cecilie Grauslund and Fiona Marie Wiborg Sørensen for helping with some of the visits. Lastly, we thank Olivia McCarthy for language editing.

Authors' Contributions

Conceptualization of the study was contributed by A.K.B. and J.S.; methodology was done by M.H.S. and H.S.K.; investigation was carried out by A.K.B.; data curation was by A.K.B.; formal analysis was done by A.K.B.; project administration was carried out by A.K.B. and J.S.; resources were taken care by M.H.S. and H.S.K.; supervision was done by J.S.; writing–original draft was by A.K.B.; and writing–review and editing was by M.H.S., H.S.K., and J.S.

Author Disclosure Statement

A.K.B. had for this study received study materials in terms of the patch from Dapplix Medical Aps, besides Dapplix Medical Aps had paid 1000 DKK per subject in this investigator-initiated study but all decisions on study design, data analysis, and reporting were made by A.K.B. and J.S. A.K.B. had besides received economical support for research from Medtronic, consulting fees from Convatec, and lecture fees from Rubin Medical. M.H.S. and H.S.K. are cofounders and have personal ownership of Dapplix Medical Aps.

J.S. had for this study received study materials in terms of the patch from Dapplix Medical Aps, besides Dapplix Medical Aps had paid 1000 DKK per subject in this investigator-initiated study, but all decisions on study design, data analysis, and reporting were made by A.K.B. and J.S. J.S. had besides received economical support for research from Medtronic and lecture fees from Rubin Medical.

Funding Information

This study was financially supported by a research grant from the Danish Diabetes Academy, funded by the Novo Nordisk Foundation (grant ID NNF17SA0031406) and by Dapplix Medical ApS who invented the patch that was investigated in this study by 1000 DKK per study participant.

Supplementary Material

Supplementary Figure S1

Supplementary Figure S2

Supplementary Table S1

Supplementary Appendix SA1

References

Sherr

, Schoelwer

, Dos Santos

, et al. ISPAD Clinical Practice Consensus Guidelines 2022: Diabetes technologies: Insulin delivery. Pediatr Diabetes, 2022; 23(8):1406–1431; doi: 10.1111/pedi.13421.

Cameli

, Silvestri

, Mariano

, et al. Allergic contact dermatitis, an important skin reaction in diabetes device users: A systematic review. Dermatitis, 2022; 33(2):110–115; doi: 10.1097/DER.0000000000000861.

Berg

, Olsen

, Thyssen

, et al. High frequencies of dermatological complications in children using insulin pumps or sensors. Pediatr Diabetes, 2018; 19(4):733–740.

Saary

, Qureshi

, Palda

, et al. A systematic review of contact dermatitis treatment and prevention. J Am Acad Dermatol, 2005; 53(5):845.

Hashim

, Nia

, Terrano

, et al. A comparative study to evaluate epidermal barrier integrity of psoriasis patients treated with calcipotriene/betamethasone topical suspension versus betamethasone dipropionate 0.05% lotion. J Drugs Dermatol, 2017; 16(8):747–752.

Eaglstein

. Moist wound healing with occlusive dressings: A clinical focus. Dermatol Surg Off Publ Am Soc Dermatol Surg Al, 2001; 27(2):175–181.

Harris

, Taylor

, Thielke

, et al. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform, 2009; 42(2):377–381.

Harris

, Taylor

, Minor

, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform, 2019; 95:103208.

, Zanvit

, Hu

, et al. The cytokine TGF-β induces interleukin-31 expression from dermal dendritic cells to activate sensory neurons and stimulate wound itching. Immunity, 2020; 53(2):371.e5–383.e5.

10.

Gunasegaran

, Ang

, Ng

, et al. The effectiveness of a hydrocolloid crusting method versus standard care in the treatment of incontinence-associated dermatitis among adult patients in an acute care setting: A randomised controlled trial. J Tissue Viability, 2023; 32(2):171–178.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

1.27 MB

0.71 MB

0.01 MB

0.41 MB