Lidocaine patch as noninvasive alternative treatment option in children with anterior cutaneous nerve entrapment syndrome: A retrospective case series

Chronic abdominal pain in children is occasionally caused by anterior cutaneous nerve entrapment syndrome (ACNES). Diagnosing and treating this typical peripheral abdominal wall neuropathy is challenging. Management usually starts with minimally invasive tender point injections. Nevertheless, these injections can be burdensome and might even be refused by children or their parents. However, a surgical neurectomy is far more invasive. Treatment with a Lidocaine 5% medicated patch is successfully used in a variety of peripheral neuropathies.


| INTRODUC TI ON
The anterior cutaneous nerve entrapment syndrome (ACNES) can be the origin of chronic abdominal pain (CAP) in children.
Interestingly, this often neglected abdominal wall pain syndrome appeared the cause of CAP in 3% of 426 children. 1 At the pediatric department of our hospital, some 13% of 95 children with CAP were diagnosed with ACNES. 2 However, diagnosing the cause of CAP in children is challenging, as it often depends on multiple physiological and psychological factors. 3Therefore, these children are usually screened and treated by their pediatricians, often in a multidisciplinary approach.If the treatment by pediatricians and other (para-) medical specialists is not successful, referral is considered to our outpatient department of SolviMáx, center of excellence for abdominal wall and groin pain syndromes, which is a subdivision of the surgical department.
In our center, children with ACNES currently receive a treatment regimen that is largely comparable to the adult approach.
Treatment begins with tender point injections using an anesthetic agent, typically 5-10 mL lidocaine 1% (depending on age and physique), with a success rate of approximately 40% in our center. 2,4wever, a 87% success rate was reported by a different center. 5 this conservative treatment fails, a neurectomy of the anterior branches of the intercostal nerve may be considered, with reported success rates up to 100% in small sample sizes. 2,5,6The largest study, conducted in our center and including 60 children, reported a success rate of 78%. 7en though a regimen of tender point injections is considered minimally invasive, an injection at an already painful spot may be burdensome for children.In fact, some children (or their parents) refuse this treatment or are uncooperative.In adults, a minimally invasive pulsed radiofrequency treatment is considered as a next step, but studies in children are lacking. 8Moreover, pulsed radiofrequency treatment requires a needle insertion at the tender point as well.Therefore, at present, the only alternative local intervention in children with ACNES is a far more invasive neurectomy.
Lidocaine 5% patches are an accepted treatment for postherpetic neuralgia.In addition, this approach was also effective in various other peripheral neuropathies in both adults and children. 9-14A pilot study in adult carpal tunnel syndrome showed similar pain relief following lidocaine patch application or injection with a combination of lidocaine and a corticosteroid. 15Lidocaine patches are usually well tolerated.14]16 Several studies showed that lidocaine plasma concentrations during patch treatment remained well below systemic therapeutic and toxic ranges in both adults and children. 13,17,18us, lidocaine patches may be a potential safe and noninvasive treatment option in childhood ACNES.The present retrospective case series is the first to assess the effects of lidocaine patches in a pediatric population with ACNES.

| ME THODS
All patients aged <18 years who were diagnosed with ACNES and treated with lidocaine 5% patches between December 2021 and December 2022 were included in the current case series.ACNES was diagnosed by the treating physician at the outpatient department of SolviMáx, center of excellence for abdominal wall and groin pain syndromes, a subdivision of the surgical department of Máxima Medical Center, Eindhoven/Veldhoven, the Netherlands.
The Daily Board of the Medical Ethics Committee (METC) Máxima Medical Center confirmed that no ethical approval was required for this retrospective study (METC number: N23.063).Due to the retrospective design of the study, which only involved the analysis of existing medical records, informed consent was not required.

| Diagnosis ACNES
Objective tests or a diagnostic gold standard for ACNES are lacking.
For that reason, visceral causes of abdominal pain must be excluded before referral to our outpatient clinic.The diagnosis ACNES was based on previously published major criteria identified in patient's history and physical examination. 19Children are supposed to experience an ongoing pain at a fixed small area of the anterior abdominal wall (present in 97% of children with ACNES) that worsens during exercise (present in 91%). 20During physical examination, findings include a circumscript pain area (tender point) within the lateral boundaries of the rectus abdominis muscles.Palpation of this tender point evokes the recognizable pain (present in 100%), which increases when tensing the rectus abdominis muscle (positive Carnett's sign, present in 97%).
When testing the sensibility of the skin overlaying the tender point, patients report hypoesthesia or hyperesthesia (present in 87%).Pinching the skin in this area is disproportionately painful (hyperalgesia, present in 89%). 19,20In this study, children had to fulfill all criteria to ensure the highest diagnostic accuracy.

| Lidocaine patch treatment
A lidocaine 5% patch (10 × 14 cm) contains 700 mg of lidocaine that was used according to the manufacturer's instructions.Specifically, patients should not have an allergy related to any substance in the patch and the affected skin must be intact.The skin area of interest should not exceed the patch' circumference.The patch should be applied over the affected skin including the tender point.It should be applied in the morning and removed just prior to bedtime, with a maximum of 12 consecutive hours per day.The next day, a new patch is applied.
After extensive counseling patients and their parents/guardians and completing the informed consent procedure, the patch was cut in the proper size as per the manufacturer's instructions (Figure 1).
Parents were advised to picture the patch location prior to removal and focus on landmarks such as the umbilicus for unaltered patch application during the treatment period.A total of 10 patches were provided.
After 5 days of treatment, the effect was evaluated during a telephone consultation with patient and parents.If no pain relief was experienced, the treatment was discontinued and an appointment was made to discuss further management.If patients experienced some degree of pain relief, the treatment was continued.
The patch treatment was standardly stopped after 10 days followed by a consultation at day 14.If pain relief was not sufficient at this time point, additional treatment options including patch continuation, tender point injections, or surgery were discussed.A 10 days initial treatment period was selected to limit further treatment delay.
Contrary to tender point injections, lidocaine patches are not reimbursed by the Dutch health insurance.Therefore, they were provided by SolviMáx Research Foundation.

| Data accrual
Patient characteristics (age, body mass index (BMI), gender, and medical history), pain related variables (duration, pain score, findings during physical examination), treatment outcome, and complications were extracted from electronic patient files of all eligible patients during the 12 month study period.The Numeric Rating Scale (NRS) scored pain intensity (0, no pain to 10, worst possible pain) before and after treatment.Clinically significant pain relief was defined as at least 30% pain reduction or a minimal reduction of two NRS points.Treatment success was defined as a >50% reduction in pain score without need for additional treatment. 21Treatment outcome was scored as temporary pain reduction (defined as significant pain reduction only during patch application) or lasting pain reduction (persistent significant pain reduction during the 4 days after treatment discontinuation).

| Data analysis
All analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 22 for Windows.No statistical test was performed as the current effort is a retrospective descriptive pilot study.

| RE SULTS
Between December 2021 and December 2022, 16 children were diagnosed with ACNES by the SolviMáx physician.Following counseling, 12 children chose to undergo lidocaine 5% patch treatment.
Patient and pain characteristics are shown in Table 1.Half of the patients were referred by a pediatrician, while others were referred by general practitioners, surgeons, or pain specialists.However, all children previously consulted a pediatrician who excluded a visceral cause of the abdominal pain.

| Treatment outcomes
The lidocaine patch treatment resulted in a significant pain relief in eight patients, of which two were pain free after patch treatment.The remaining four patients experienced no pain reduction after 5 days, and therefore, treatment was discontinued as per protocol.Outcome of individual patients and additional treatments are presented in Table 2.
All nine successfully treated children (patch or other treatments) reported a normal return to school and resumption of previous physical activities, some with temporary support of a manual therapist.

| Pain free after lidocaine patch treatment (n = 2)
Two children experienced a steadily decrease in pain since start of the treatment, resulting in a completely pain free situation.The first child reported that the pain had disappeared after 8 days, but continued treatment up to the 10th day.This patient remained pain free during the 4 months of follow-up.The second child reported a decrease in NRS from 8 to 5 after 10 days.The decision was made to continue lidocaine patch treatment and the patient became pain free after four more weeks of treatment.This child remained pain free during the 7 months of follow-up.

| Lasting pain reduction (n = 1)
One patient reported a 50% decrease in pain at the 2 weeks followup, despite treatment discontinuation at day seven (due to skin rash at the application site).Fortunately, the rash disappeared within a few days, and the pain remained alleviated.Since the patient was not completely pain free, tender point injections and an anterior neurectomy were performed with temporary success.Ultimately, a posterior neurectomy was successful, and the child remained free of pain after 8 months of follow-up.

| Temporary pain reduction (n = 5)
Five patients reported significant pain reduction during patch application only.At the 2 weeks follow-up, tender point injections were initiated in 4 patients.One patient became long-term pain free whereas the remaining three experienced only temporary relief.
Therefore, these three patients underwent an anterior neurectomy that was successful in all.At 15 months follow-up, all were pain free.
The fifth patient still reported abdominal pain although physical examination showed normal sensory testing without hyperalgesia or a tender point.Consequently, the patient was referred back to the pediatrician.b Discontinued patch treatment at Day 7 due to adverse effects.
c Became pain free after four more weeks of patch treatment.

| No pain reduction (n = 4)
Four patients experienced no pain relief during 5 days of patch application, and treatment was discontinued as per protocol.
Subsequently, all four underwent tender point injections.One patient experienced significant pain relief but preferred additional treatment.A pulsed radiofrequency treatment resulted in a 10 month pain free period, after which the treatment was repeated, now completely resolving the pain.The remaining three patients experienced no pain relief following injections and opted for a neurectomy.The neurectomy was long-term successful in one.However, the other two patients had persistent pain after both the anterior and posterior neurectomy and were classified as unsuccessful treatment outcome.

| Tolerability
Except for the one patient who discontinued the patch treatment due to a skin rash, no other adverse events were reported.patient noted that the patch did not always adhere for the full 12 h.

| DISCUSS ION
In the ongoing search for an optimal ACNES treatment regimen, this single center retrospective case series is the first to assess the effectiveness of noninvasive lidocaine patches in 12 children.Significant pain reduction during the lidocaine patch treatment was reported by 4 of the 12 patients, whereas two patients achieved a pain free status rendering more invasive treatments superfluous.Although these success rates are lower compared to tender point injections or a neurectomy, one may consider the patches use as a preferential first treatment option, considering a step up approach in a pediatric setting.
13]16 Varying success rates are related to differences in neuropathic pain conditions, treatment duration, and definition of outcome.A large study in 115 children reported that 69% benefitted from the use of lidocaine patches (on multiple outcomes). 12Another cohort found a significant pain reduction over two consecutive days in nearly half of the 39 included children. 16Two smaller case series reported that 2 of 5, and 11 of 12 children were pain free after 3 months of lidocaine patch treatment.The remaining patients experienced significant pain relief in all but one. 11,13It may be concluded from the literature and the present study that most children experience (temporary) significant pain reduction during treatment.Occasionally, a persistent pain free status after treatment discontinuation may be attained.
It is theoretically possible that pain reduction in a portion of patients is caused by a placebo effect.For instance, some adult ACNES patients benefitted from a saline tender point injection or sham surgery. 22,23wever, these studies reported only a short-lived effect in the placebo groups, in contrast to the pain free patients in the present study. 22,23ficacy of patch treatment may in part be determined by length of application.For instance, studies reporting on several months of topical treatment reported high success rates. 11,13In the present pilot study, patches were discontinued if patients experienced no pain relief at all after 5 days.It may be argued that these patients could have benefitted from a longer treatment duration.In fact, one of the children continued topical treatment for an additional 4 weeks and finally became pain free.However, in contrast to other studies in peripheral neuropathies, alternative local treatment options such as injections are available for ACNES.Therefore, it was often decided to not to continue patch treatment to avoid treatment delay and to engage in the next phase of the treatment regimen.
Our current step-up regimen of ACNES starts with a low-invasive treatment option and may progress towards surgery.While other noninvasive treatment modalities such as oral (neuropathic) pain agents, psychotherapy, or manual therapy could be initiated before invasive treatments, most of our children previously received these treatments without success prior to referral.For that reason, we focus on local treatment rather than systemic therapy.Our current protocol starts with tender point injections once every 2-3 weeks, up to 3 or 4 repetitions.In childhood ACNES, success rates following this approach range from 38% to 87%. 2,4,5In adults, if tender point injection treatment is unsuccessful, pulsed radiofrequency is the next treatment of choice.However, this treatment is not standard practice in children. 8[7] Even though the success rate of lidocaine patches is much lower, its non-invasive nature is an important advantage.A regimen of lidocaine 5% patches could be considered as a first treatment option, possibly as an adjunct for injection therapy in a pediatric setting.
The potential adverse effects of chronic patch treatment in childhood ACNES are unknown.Luckily, lidocaine patches were in general well-tolerated although one child developed a skin rash.
Following discontinuation, the rash dissolved within a few days.A second patient reported that the patch did not adhere for the full 12 h but was able to continue treatment.These findings are in line with reported 6-8% adverse event rates in two large cohorts of children. 12,16As the largest patch in the current study was just half the size of a standard 10 × 14 cm patch, systemic effects were neither expected nor reported.For instance, the use of three patches was considered safe as suggested by other studies. 12,18e present pilot study has limitations associated with its retrospective character and small sample size lacking a control group.Nonetheless, our findings are in line with the existing literature on lidocaine patch treatment in children with various other peripheral neuropathies.
Questions on optimal treatment duration as well as the role of potential

F I G U R E 1
Example of a patient diagnosed with a right-sided ACNES T10.(A) Marked area of the skin with hypoesthesia and positive pinch test, the 'X' indicates the tender point.(B) A halved lidocaine patch is applied over the marked area.TA B L E 1 Characteristics of children receiving lidocaine patch treatment for ACNES.Pharmacotherapy covers both oral nociceptive, and neuropathic agents.Abbreviations: BMI, body mass index; MT, manuel therapy; NRS, Numeric Rating Scale; PT, pharmacotherapy.

TA B L E 2
Abbreviations: AN, anterior neurectomy; FU, follow-up; PN, posterior neurectomy; PRF, pulsed radiofrequency; TPI, tender point injections.a Physical examination did not reveal any characteristics of ACNES, thus treatment was stopped.
adverse factors such as long duration of pain, young age, substantial subcutaneous thickness, and numerous previous (local) treatments require answering.A randomized controlled trial may compare efficacy of patches with subfascial anesthetic injections.A cost-effectiveness analysis is required as lidocaine patches are more expensive than lidocaine injections.In the Netherlands, 10 patches cost approximately 40 euros, and costs are not covered by the Dutch health insurance.Additionally, it