Allergic reaction to hypoglossal nerve stimulator: a case report

Abstract

Little is documented about the frequency and management of allergic reactions to hypoglossal nerve stimulator implants. This case report describes a 69-year-old female with obstructive sleep apnea who received a hypoglossal nerve stimulator device and had an adverse reaction concerning for an allergic reaction to the medical device. The complication was managed via topical steroids, and although the patient’s symptoms initially resolved she experiences continued intermittent maculopapular pruritic rashes approximately once per week. This case report details the patient’s presentation, including progression and management, while also highlighting the diagnostic challenges in identifying allergic reactions to medical implants and offering considerations for future management.

Citation:

Gouldman KP, Yu JL. Allergic reaction to hypoglossal nerve stimulator: a case report. J Clin Sleep Med. 2025;21(1):211–213.

INTRODUCTION

Hypoglossal nerve stimulation (HGNS) is a novel surgical therapy for treating obstructive sleep apnea that uses neurostimulation to protrude the tongue during sleep. The Inspire neurostimulator implant (Inspire Medical Systems, Inc., Minneapolis, Minnesota) is currently the only Food and Drug Administration–approved device that uses this treatment modality. Inspire consists of an implantable pulse generator, a stimulation electrode lead, and a respiratory sensing lead that are surgically placed in the chest and submental neck.¹

Allergic reactions to medical device components are a known but rare risk. There is minimal reported literature documenting allergy to HGNS devices; however, the incidence may rise as more patients receive them. Significant allergic reactions could necessitate removal of the device, but limited alternative treatments are available. We present the case of a patient who likely experienced an allergic reaction to an HGNS implant, along with a discussion of its evaluation and management.

REPORT OF CASE

A 69-year-old female with a history of obstructive sleep apnea and intolerance to continuous positive airway pressure therapy underwent Inspire neurostimulation implantation. On postoperative day 1, she developed a pruritic maculopapular rash extending from her chest to her upper abdomen and right neck. She recalled a similar rash on her chest and left arm after pacemaker implantation 2 years previously, which resolved within a week, and an erythematous rash after receiving a titanium wrist plate 7 years previously. Interestingly, she had a cobalt knee replacement 12 years previously and reported no rashes associated with that implant. The patient attempted to alleviate the itching with over-the-counter antihistamines and steroid creams, which partially helped alleviate the itching. On postoperative day 5 she presented to the office for routine follow-up, where we were first made aware of her pruritic rash (Figure 1). The incisions appeared to be healing well without evidence of breakdown or drainage. She had already switched her soap and laundry detergent to fragrance-free alternatives without improvement. A 14-day course of twice-daily 2.5% hydrocortisone cream for her facial rash and twice-daily 0.1% triamcinolone cream for her chest rash were prescribed for management. She remained otherwise asymptomatic and afebrile, but a 7-day course of 800–160 mg of Bactrim DS twice daily was also prescribed as a precaution in case of infection as well as to prevent incisional infection from her itching. Results of complete blood count and differential laboratory tests were normal. The rash gradually improved, and at her 1-month device activation visit only mild erythema remained over the chest incision. The device was activated without issue. By her 3-month follow-up she reported intermittent pruritic rash flare-ups over the HGNS, pacemaker, and wrist plate sites, which she found tolerable given the improvement in sleep quality from the HGNS. She saw an allergist, who conducted patch testing for titanium, cobalt, iridium, and platinum based on the composition of the device, all of which were negative. She continues to experience mild but persistent erythema and itching at the 3 implant sites.

Figure 1. Photographs of the rash.

(A) A maculopapular rash was present on the patient’s chest 5 days after surgery. (B) The rash site only appeared to have mild erythema 14 days after surgery following a course of steroid treatment.

DISCUSSION

Allergic reactions to HGNS are minimally reported in the literature, with no detailed case reports or series regarding these events. We searched the Food and Drug Administration’s Manufacturer and User Device Facility Experience (MAUDE) database to identify any reported allergy-related adverse events associated with HGNS therapy. Of the 1,068 reported adverse events between July 11, 2014, and September 30, 2023, 5 were allergy-related events and 3 required removal of the device, with none having confirmed positive allergen testing to components of the device. Regarding other adverse events, the most common was infection, followed by neuropraxia of the nerve and migration or extrusion of the device.² In terms of the differential diagnosis relevant to the patient’s presentation, infection is the most significant alternative diagnosis, which prompted us to prescribe antibiotics.

Contact dermatitis resulting from changes in home skincare or cleaning products, or related to surgery such as adhesives, bandages, or skin preparations, should also be considered in the differential. The patient tried modifying her skincare products to fragrance-free products but received no benefit. The persistence of the reaction months after surgery also makes contact dermatitis from the surgery less likely. Finally, the commonality of having a reaction at 2 other implant sites suggested a localized reaction to a common exposure material.

Allergies to medical devices in general remain a diagnostic dilemma. Reviews of cardiac literature regarding allergy to pacemakers, which contain components similar to those of HGNS devices, show it is also rare, with only 57 patients reported in 43 case reports³ over the past 50 years. Commonly discussed are symptoms of allergy that are misdiagnosed as infection and sometimes realized only after multiple failed revision implantations.⁴ Significant reactions typically can only be managed by removal of the device.^4–6

Per the manufacturer, Inspire’s tissue-contacting materials include titanium, silicone, polyurethane, platinum, iridium, and polyether urethane. Interestingly, our patient had multiple metal implants including a titanium cardiac pacemaker and titanium wrist plate, which also had reported erythema, whereas her cobalt knee replacement never did. Given that titanium was a component in the affected areas, our primary suspicion is that she has a titanium allergy. Our patient did receive skin-patch testing for the metals contained in the device, and the results were all negative. Unfortunately, testing for titanium allergy is often unreliable. Titanium skin-patch tests infrequently yield positive results, and even negative results do not guarantee that the patient is not allergic to titanium.⁷ Memory Lymphocyte Immunostimulation Assay is a newer method for testing titanium hypersensitivity that may be an option for ruling out suspected titanium allergy, but its availability is currently limited.⁶ Our patient had only a mild reaction to the device that did not require removal; however, more significant reactions may require the device to be explanted. One possible future solution for patients allergic to the implant would be to use a gold-coated implantable pulse generator, which has been reported in pacemaker literature and successfully placed in patients with titanium allergy.^4,5

CONCLUSIONS

When managing a potential allergy to the HGNS implant, it is crucial to first consider other diagnoses in the differential, particularly postoperative infection and contact dermatitis. A thorough patient history can provide valuable insights to support the diagnosis of allergy over other possibilities, though confirming an allergy remains challenging due to limitations in diagnostic testing, especially related to titanium allergy testing. Antibiotic treatment should always be considered, because erythema and itching may also indicate a surgical infection. In this case, the suspicion of allergy was heightened by the patient’s history of erythema around her pacemaker and recurrent localized erythema at both pacemaker and titanium wrist implant sites, which coincided with erythema at the HGNS implant site, suggesting titanium as the common underlying factor. If a device is removed for concern of allergy, reimplanting a new device should be approached with caution owing to the risk of repeating the allergic reaction. Further study is needed regarding this rare complication, including modification of device materials for patients who may benefit from this treatment modality.

DISCLOSURE STATEMENT

All authors have seen and approved the manuscript. Dr. Yu has received consulting payments and research support from Deerfield Catalyst LLC and Lunair Medical, Inc. Katherine Gouldman reports no conflicts of interest.

ABBREVIATIONS

HGNS

hypoglossal nerve stimulation