Are we numb to the facts? Our experience of local anaesthetic allergy testing in a tertiary hospital immunology department

This study reinforces the rarity of true IgE-mediated hypersensitivity to LAs. Among the 37 patients referred to our tertiary allergy service with suspected LA allergy between December 2021 and June 2024, none were found to have a confirmed IgE-mediated reaction on formal testing. A significant proportion of patients (25/37; 67.6%) experienced symptoms consistent with non-IgE-mediated mechanisms, including vasovagal syncope, sympathetic stimulation (such as palpitations and tachycardia), systemic toxic effects, psychomotor response (e.g., perioral tingling, dizziness), and procedural trauma. These presentations often lacked objective allergic features and were self-limited in nature. Nevertheless, they frequently resulted in emergency intervention and all received specialist referral, particularly when the cardiovascular or neurologic symptoms were interpreted as early anaphylaxis.

Even among the seven patients (18.9%) whose symptoms initially suggested IgE-mediated hypersensitivity, alternative diagnoses were established following detailed workup. Four patients (10.8%) had positive skin testing to substances co-administered with the LA, specifically, PEG, polysorbate 80, and chlorhexidine. Two patients (5.4%) were diagnosed with chronic spontaneous urticaria, and one additional case was highly suggestive of anaphylaxis related to ibuprofen administered post-procedure, though formal testing was not performed. These findings underscore the importance of testing all agents administered during the reaction episode, not just the LA, as failure to do so risks misattributing causality.¹¹ Diagnosis was excluded using a combination of detailed clinical history, negative skin testing, and negative DPT in 36 of 37 patients (97.3%), with one patient declining challenge.

A notable feature of our cohort was the high proportion of referrals originating from dental practice (64.8%; 24/37). This likely reflects the increased use of LAs in dental procedures, where they are a mainstay in both routine and surgical care. In addition, LA use in dentistry is more complex than in many other settings. Injections are frequently delivered into highly vascular oral tissues, and adrenaline-containing formulations are often used to prolong anaesthesia and control bleeding. These factors increase the risk of rapid systemic absorption or inadvertent intravascular administration, leading to acute symptoms such as palpitations, flushing, tremor, or dizziness.¹ Although these effects are pharmacological and typically self-limiting, they may be mistaken for early signs of anaphylaxis in the moment, especially in time-pressured clinical environments. This misinterpretation can result in emergency management, labelling of allergy, unnecessary avoidance, and referral for specialist assessment, even in the absence of objective allergic features.

None of the patients referred in this cohort had serum tryptase measured at the time of their reaction, despite several being treated for suspected anaphylaxis. Although serum tryptase is not diagnostic on its own and a normal level does not exclude anaphylaxis, a post-event elevation can support the diagnosis when interpreted alongside clinical features and timing.¹² Its absence represents a missed opportunity to strengthen diagnostic certainty, particularly when patients undergo escalation of care such as adrenaline administration. Wider awareness and accessibility of tryptase testing in dental and general practice settings may help reduce misclassification in future cases.

A total of 17 patients (45.9%) in our study recovered from their adverse reaction without receiving any treatment, suggesting that a substantial proportion of suspected allergic reactions are in fact transient, non-allergic events that resolve spontaneously. These cases reinforce the need for careful consideration of acute management, particularly when there are no objective signs of systemic involvement. Conversely, adrenaline was administered in five patients (13.5%), sometimes in repeated doses, despite the lack of confirmatory evidence of anaphylaxis. While adrenaline is the mainstay of anaphylaxis treatment, the absence of clinical improvement following appropriate dosing should prompt reconsideration of the working diagnosis.¹³ Vasovagal syncope, anxiety, and sympathomimetic side effects from adrenaline itself may explain persistent symptoms in such cases. Escalating treatment without reassessment risks reinforcing misdiagnosis, potentially leading to long-term avoidance of safe and effective medications.¹⁴

Demographically, our patient cohort had a female predominance (3.1:1) and a mean age of 50.5 years (range 19–85). A total of 11 patients (29.7%) reported a history of atopy, and 20 patients (54.0%) reported previous adverse reactions to other drug classes, including antibiotics, non-steroidal anti-inflammatory drugs, opioids, general anaesthetics, and radiocontrast agents. However, these historical features were not associated with an increased likelihood of confirmed LA allergy in our analysis. In fact, the tendency to accumulate multiple suspected drug allergies may reflect heightened symptom vigilance or past misinterpretations, reinforcing the value of formal allergy assessment before applying long-term diagnostic labels.¹⁵

These findings have important implications for daily clinical practice, particularly in dentistry and minor surgical specialties where LAs are frequently used. Dentists and general practitioners should be aware that most acute reactions to LAs are not true allergies, and in the absence of clear signs such as urticaria, angioedema, bronchospasm, or hypotension, the likelihood of anaphylaxis is low.¹⁶ Improved understanding of the pharmacological effects of adrenaline and the expected physiological responses following local injection can help clinicians better assess these events in real time. Strengthening this clinical awareness is key to avoiding misdiagnosis, inappropriate treatment, and unnecessary avoidance.¹⁷

In the event of acute symptoms following LA administration in a private or outpatient setting, clinicians should assess the clinical context thoroughly before assuming an allergic cause. Key features that support an allergic diagnosis include sudden-onset skin involvement, respiratory compromise, or cardiovascular instability. If anaphylaxis is strongly suspected, intramuscular adrenaline should be administered promptly, and emergency services contacted. However, in milder or ambiguous cases, supportive care, patient reassurance, and careful monitoring may be more appropriate.¹⁸ Clinicians should also document the reaction in detail and consider timely referral for allergy testing where uncertainty persists.^19,20

To reduce unnecessary referrals, dental professionals should be trained to distinguish between pharmacological side effects and true allergic reactions. Taking a detailed history at the time of the event, including timing, symptoms, drugs administered, and response to treatment, can help stratify risk. Recording the specific LA product, along with any co-administered substances (e.g., chlorhexidine, topical anaesthetics), is essential. When in doubt, non-urgent referral to an allergy clinic is preferred over avoidance without evaluation, as structured testing is the only reliable way to confirm or exclude LA allergy.¹¹

Access to allergy services remains limited in many regions. This systemic limitation contributes to delays in definitive diagnosis and extended uncertainty for both patients and clinicians. Expanding clinician education, particularly in dentistry and primary care, may help reduce unnecessary referrals and unwarranted LA avoidance, while improving patient safety and resource use.

Our findings are reinforced by recent international literature confirming the rarity of true IgE-mediated LA allergy. A national Danish study by Kvisselgaard et al. (2017) evaluated 162 patients referred for suspected LA allergy over a 10-year period and found no confirmed cases of IgE-mediated hypersensitivity.⁹ Similarly, the UK-based DALES study (Thomas et al., 2021), a prospective multicentre review of over 5,000 elective surgery patients, reported that 86% of recorded drug allergy labels, including many related to anaesthetics, were incorrect.¹¹ From France, Hascoët et al. (2022) retrospectively reviewed LA-related reactions in dental procedures and identified only nine confirmed cases of anaphylaxis among tens of thousands of procedures, estimating an incidence below 0.01%.²¹ These large-scale, geographically diverse studies align closely with our own findings and emphasise the importance of structured diagnostic evaluation in reducing misdiagnosis, unnecessary avoidance, and unwarranted referral.

Our study has several limitations. It was retrospective and conducted at a single tertiary allergy centre, which may limit generalisability to broader clinical contexts. The relatively small sample size (n = 37) reduces statistical power and increases sensitivity to selection bias. As a specialist centre, our patient population is likely enriched for complex or ambiguous presentations, potentially skewing referral patterns and diagnostic yield. Tryptase testing was not performed at the time of reaction in any patient, limiting our ability to corroborate or refute mast cell activation in cases managed as anaphylaxis. Additionally, while many alternative diagnoses were identified with high clinical confidence, objective confirmation (e.g., via challenge testing for co-administered drugs) was not always feasible. Regional differences in LA formulations, administration practices, and access to dental anaesthesia protocols may also affect generalisability.