Preserving Skin Integrity with Chronic Device Use in Diabetes

Although use of CSII and CGM can lead to similar skin integrity and adhesive problems, the literature bodies are largely discrete, as routine CSII use preceded CGM use by 20 years. A recent study in 143 pediatric patients showed that 90% of individuals using CSII >4 months experienced dermatological complications from insulin infusion sets (IIS), including pruritus (77%), wounds (50%), and nonspecific eczema (46%).¹¹ It also found that individuals with a history of atopic disease were 3.7 times more likely to experience dermatological complications compared to those without an atopic history (P < 0.01). Barrier cream use was also associated with higher risk for skin reactions (OR 7.3, P < 0.01), although this may be due to patient attempts to reduce reactions and not the cause of reactivity.¹¹ Another pediatric study reported scars <3 mm as the most common dermatologic complication from IIS (94%), followed by erythema (66%), lipohypertrophy (LH) (44%), subcutaneous nodules (erythematous 42% and nonerythematous 20%), scars ≥3 mm (12%), and less than 10% each from epidermal abrasions, hyperpigmentation, lipoatrophy, and bruising.¹² Binder et al. conducted a cross-sectional observational study with CSII users (3–20 years old) and found that 43% experienced scarring (24%), LH (20%), eczema-like lesions (11%), pigmentation changes (6%), and lipoatrophy (6%).¹³ The study also showed that steel catheter use was not associated with a lower prevalence of skin complications compared to Teflon sets (37% steel vs. 53% Teflon, P = 0.39).¹³ LH has further been reported as one of the most common issue associated with CSII use.¹⁴

CGM use has also been shown to cause dermatological issues. The earliest indication of CGM adhesive irritation and hypersensitivity appeared in the literature in 2007,¹⁵ with the DirecNet study group subsequently reporting skin irritation and rashes in a pediatric study popluatuon.¹⁶ This was more commonly found in individuals who had never used an insulin pump or CGM before.¹⁷ Ives et al. reported similar findings in a clinical pediatric population using CGM, reporting skin irritation and poor adhesion exacerbated by sweating and activity.¹⁸ A more recent randomized controlled trial of CGM in pregnancy reported that 48% of pregnant women and 44% of women planning pregnancy experienced adverse skin reactions with CGM, including erythema (31%), chronic dry skin (11%), and hyperpigmentation (7%), but “other” was the reason for 23% of the total cohort's skin reactions.¹⁹ Of particular concern, 18% of participants cited skin irritation/pain/discomfort as the reason for discontinuing CGM use.¹⁹ Finally, a recent report from 83 pediatric patients using CGM showed 80% experiencing skin issues, including pruritus (70%), eczema (46%), and wounds (33%).¹¹ There was no difference in risk for dermatological issues by age or history of atopy, although individuals who used CGM for less than 1 year did report fewer complications.¹¹

Few reports compare skin complications across devices. CSII and CGM have slightly different complications due to unique concerns with insulin infusion (e.g., LH) and the longer duration of CGM sensors. In both CGM and CSII use, dermatological complications typically appear within 4 to 6 months of initiation, although pediatric subjects in one recent study reported the CGM skin issues to be more problematic than IIS skin issues.¹¹ This same study further reported more dermatological issues with the Medtronic Enlite and Dexcom G5 sensor compared to Freestyle Libre.¹¹ Since the Libre has not been on the market as long as other sensors, there is less data on its use. During the IMPACT trial using the Libre in 328 adults,²¹ there were 13 cutaneous adverse events in 10 participants, with 6 being classified as severe.²² Since completion of the trial, Abbott made changes to the commercial Libre device to improve breathability of the skin and reduce the occurrence of trapped moisture between the sensor and skin.²⁴

As the literature has shown, CGM and CSII device usage can lead to skin injury and irritation (hypersensitivity reactions, contact dermatitis), scarring, and lipodystrophy. Hypersensitivity reactions are typically classified as one of four types.²⁵ Type 1 hypersensitivity is termed immediate type hypersensitivity, is IgE mediated, and is the form most common in atopic-type skin reactions. Reactions typically occur within minutes. Type 2 hypersensitivity (cytotoxic) and type 3 hypersensitivity (immune complex) are not typical to diabetes device wear, and are not covered in this study. Type 4 hypersensitivity is termed delayed-type or cell-mediated hypersensitivity, and is the most common form of hypersensitivity reaction. It is T-cell mediated, and occurs in response to sensitization to the offending agent in susceptible individuals. Reactions typically take a long period of exposure to induce initially, but may occur more rapidly after repeated exposure due to reactivation of memory Th1 cells. These reactions may occur in response to chemicals in CGM and IIS adhesives.

Contact dermatitis is a broader term describing both type 4 hypersensitivity reaction described above (also known as allergic contact dermatitis), as well as irritant contact dermatitis.^26,27 Irritant contact dermatitis occurs as a result of direct damage to the skin by chemical or physical agents resulting in a nonimmune inflammatory reaction. Irritant and allergic contact dermatitis are not mutually exclusive, however, destruction of the skin barrier by irritant contact dermatitis may play a role in increasing antigenic exposure and exacerbate or accelerate allergic contact dermatitis.¹⁰ The type of adhesive used in a device also plays a key role in development of allergic contact dermatitis. While the exact composition and preparation of adhesives used by various manufacturers remain a trade secret, most contain acrylate monomers, which are known to be a potent source of contact dermatitis.^10,20 There is one published case report detailing sensitization to ethyl cyanoacrylates in a Dexcom G4 sensor adhesive in a 2-year-old girl.²⁰ Another study reported on 15 patients with allergic contact dermatitis caused by the Freestyle Libre, and patch testing revealed that all patients had been sensitized to isobornyl acrylate in the adhesive.²³

Scarring is another dermatological complication from CGM and IIS and appears to be more common with IIS. Scarring manifests as small hypo- or hyperpigmented lesions of fibrous tissue.^12,28 Although it is unclear whether scarring affects sensor accuracy or insulin absorption, it may disrupt the insertion process of sensors or cannulas, and scarred areas should therefore be avoided when selecting new insertion sites.

Finally, CSII alone can lead to lipodystrophy—both lipoatrophy (localized loss of subcutaneous adipose tissue) and LH (abnormal growth of subcutaneous adipose tissue). Lipoatrophy is caused by an adverse immunological response to insulin therapy.^29,30 It is less common than LH, but can nonetheless be caused by CSII therapy. It should be noted, however, that CSII can also be helpful for treating severe cases of lipoatrophy caused by MDIs.³⁰ CGM use is not thought to contribute to lipodystrophy.

Incidence of LH, although still common,¹⁴ decreased when highly purified insulins came to the market. The mainstay of management remains avoidance of lipohypertrophic areas with careful rotation of CGM and CSII.²⁸ Interestingly, recent studies have reported that LH does not appear to adversely affect CSII delivery or CGM sensor accuracy. Karlin et al. reported no difference in infusion set survival or set failure rate due to hyperglycemia between IIS placed in LH and non-LH tissue.³ Likewise, DeSalvo et al. placed CGM sensors in LH and non-LH tissue, and found slightly better accuracy in LH tissue compared to non-LH tissue, indicating that CGM accuracy is not compromised in LH.² Overall, rotating sites still plays a critical role in the prevention (and possible treatment) of LH and lipoatrophy, but once these conditions develop, there does not appear to be a significant difference in the performance of CSII therapy or CGM, although more studies are needed in this area.

There are few resources that detail practical recommendations for optimal skin management with diabetes devices.^16,18,31 The earliest publication on practical CGM use (including dermatological issues) came from an academic children's diabetes center, which described their “toolbox of tapes” to handle poor adhesion, sweating, and skin irritation,¹⁸ many of which are listed below in Tables 1–4. The authors emphasized the importance of appropriately cleaning the skin and drying it completely before attempting to place CGM sensors, and also described possible uses for overbandages/films and tackifying agents. Sweating could be mitigated by applying antiperspirant to the skin before insertion.

The DirecNet Study Group educators likewise published practical considerations for CGM adhesion.¹⁶ Sensors were less likely to be accidentally dislodged if they were placed on a flat plane such as upper buttocks, upper arm, upper abdomen, or upper thigh. A useful list of commercial adhesives, barriers, and wraps were presented, stressing that individuals often required a combination of products. Bandages placed over the entire sensor and transmitter were not recommended due to buildup of moisture and further loosening of adhesive.

The non-peer reviewed “Pink Panther” series of books written for patients with T1D offer similar suggestions for CGM and CSII usage related to taping, placement, and skin care.³¹ Skin preparation suggestions include exfoliation, trimming hair, and removing oil before adhesive placement to maximize adhesion and minimize irritation. Also discussed is the occurrence of Pressure Induced Sensor Attenuation (PISA), or “compression lows.” PISA refers to artificially low sensor glucose readings that occur when sensors abut muscle tissue. This is common with sleeping, laying, or sitting on a sensor, and can be resolved with strategic placement and changing positions.

Important guidance related to skin care also come from the nursing literature, specifically wound care. It has been clearly shown that medical grade adhesive use can lead to preventable skin irritation concerns when used incorrectly.^32,33 Examples of incorrect use include selecting tapes with excessive adhesive properties (causing skin injury upon removal), improper application of adhesives, applying to wet/moist skin, not allowing skin preps or barriers to dry (causing irritant contact dermatitis), excessive use of tackifiers/bonding agents, leaving occlusive dressings on too long, not trimming hair under adhesive dressings, removing dressings too quickly or from a high angle, and repeated taping in the same area.³³ Although these examples are related to generic wound care, they can all be directly applied to clinical diabetes care.

An expert panel of 23 wound care nurses and specialists published recommendations for maintaining optimal skin integrity with medical adhesives.³³ First step is proper assessment: Skin should be routinely assessed for evidence of damage with every adhesive change. A medical history of allergies/sensitivities should be obtained to minimize risk of reaction to medical adhesive. Next step is taking preventative measures: Nutrition, hydration, and topical skin care measures should be used for optimal skin integrity. Strategically placing adhesive can reduce disruptions from joints or skin movement. Appropriate barrier/adhesive products should be selected based on minimal amount of product necessary, breathability, and gentleness of product. Carefully remove adhesives by including use of removal agents and techniques to minimize tissue damage. The final step is infection prevention: Monitoring sites for pain, edema, erythema, warmth, or suppuration. Nonsterile adhesive products should be stored in closed containers with minimal handling.

Device placement is the first consideration in anticipating skin issues with use of CGM sensors and IIS for insulin pumps. Common areas for insertion include the upper buttocks, abdomen, upper hip (flank), upper thigh (inner and outer areas), upper arm, and occasionally forearm (Table 1). Regardless of location, when subcutaneous tissue is insufficient, individuals may feel persistent discomfort when the cannula/sensor abuts underlying musculature. Furthermore, compression on the tissue may cause PISA in CGM users. PISA can occur and resolve quickly when pressure is applied and then released from tissue, often leading to characteristic “stalactite” sensor tracings with a precipitous drop in CGM values followed by an abrupt climb back to baseline.

Diabetes providers should elicit a thorough history of known or suspected allergies, as well as any previous history of contact dermatitis before recommending use and type of IIS or CGM.³³ Skin should be visually inspected for color, texture, previous lesions, and scarring to determine appropriateness for device insertion and adhesive mount. Identifying multiple sites for device insertion allows the wearer to rotate insertion sites, maximizing time for skin to heal in-between insertions.

Table 1 contains general considerations for device placement as well as specific considerations for commonly used device locations.

Once an appropriate location has been identified, a variety of techniques and barrier agents may be used to minimize risk of hypersensitivity reactions and irritant contact dermatitis (Table 2). Good skin care practices such as thorough cleansing, gentle exfoliation (if needed), and omitting oil containing moisturizer on the candidate area are essential.

A common solution to previously known hypersensitivity reactions has been the off-label use of nasal steroid sprays (e.g., fluticasone) being applied topically to the skin. Although there are no studies about long-term use of nasal steroids applied topically, it has been anecdotally endorsed as a way to prolong sensor use and protect skin from adverse reactions.^31,35 Many of our clinical patients use this technique, prompting ongoing surveillance by diabetes care providers to assess the skin for changes. Although topical antihistamines have also been suggested as a prophylactic agent, we typically discourage use due to possible local and systemic adverse effects.³⁷

For some individuals, liquid barriers may offer sufficient protection from adhesive agents. Solid barrier bandages are a more robust solution for blocking adhesive tapes from contacting skin. Solid barriers can be used in conjunction with liquid barriers or used alone. Many of the products listed in Table 2 provide a combination of barrier protection and adhesive enhancement, maximizing potential device use.

Enhancing adhesion is important for a variety of device wearers, especially children (due to curvy surfaces and high activity levels), swimmers, individuals who live in high humidity, and athletes (due to increased perspiration and movement). Similar to barrier methods, adhesive agents and tackifiers come in both liquid and solid forms (Table 3).

Adhesive patches or supplemental tapes are usually applied over the CGM/IIS adhesive patch and are used to maintain adhesion throughout device life. The two primary types of adhesive patches are the transparent hypoallergenic films (also used as barrier film above) and kinesiology tape-like products. These come in a variety of precut sizes and shapes, as well as rolls for custom cutting. Adhesive tapes can be used to reinforce tape that is prematurely peeling (Table 3).

Careful removal techniques can greatly reduce the likelihood of contact dermatitis and mechanical injury from device use. In general, adhesive tapes should be removed slowly and with low energy, reducing risk of injury. McNichol et al. recommends several excellent approaches that have been incorporated into Table 4.³³ Diabetes providers can educate individuals about the importance of “low and slow” removals to preserve long-term skin health.

There are a variety of removal aids on the market, which are especially useful when tackifying agents and tapes, that have been used (Table 4). Overall, it is important that the skin is cleansed thoroughly after device removal, as these agents leave oily (and often unpleasantly scented) residues.

After device removal, skin should be gently cleansed and assessed for mechanical injury or contact dermatitis (Table 4). If skin is intact and not bothersome, moisturizing lotion may be applied to sooth and protect skin. If skin is intact but irritated, additional anti-inflammatory or anti-itch compounds may be applied to the skin. Skin that is broken but not obviously infected can be treated with over-the-counter antimicrobial agents, topical corticosteroids, or liquid antacid to address pain and itching. However, broken skin should be frequently monitored for development of infection. Diabetes providers can educate individuals to assess the skin for worsening of pain and itching, spreading redness, heat, pus, formation of pustules, or a burning sensation. If infection is suspected, individuals should contact their diabetes provider for assessment and prescription of antibiotics if needed. Ongoing monitoring and careful skin care postdevice use can preserve skin for future use.

Generally, when managing contact dermatitis, avoidance of the offending antigen or agent is the mainstay of the therapy. In the case of allergy to materials in a CGM or IIS, this can be challenging. First and foremost, one must identify the sensitized antigen. This is typically done with the aid of a dermatologist via patch testing.^23,33 Once the agent has been identified, it can only be avoided if patients are able to determine where it is present. Greater transparency from manufacturers, stating known antigens in the sensors or infusion sets (either on packaging or online), could help in this regard. Additional benefit would be seen if various products offered a variety of adhesives, which may allow patients to avoid a certain antigen without changing device brand. While cross-reactions between similar antigens may still be possible, removing the initial offending agent as early as possible should help to decrease this risk.