a b s t r a c t

Background: The emergency department evaluation of patients with abdominal pain is most appropriately di- rected at identifying acute inflammation, infection, obstruction, or surgical disease. Doing so commonly involves “routine” (and often extensive) diagnostic imaging and laboratory testing. Benign mimics of serious visceral ab- dominal pain that can be diagnosed by physical exam and confirmed with local anesthetic injections have been identified over the last century. These syndromes derive from painful irritation of the intercostal nerves by a mo- bile rib below, or from impingement of the cutaneous branches of those same intercostal nerves as they penetrate the abdominal wall. These peripheral neuropathic mimics of visceral abdominal pain continue to go unrecog- nized and underdiagnosed.

Methods: Our purpose is to review the affirmative diagnosis of non-visceral abdominal pain by physical examina- tion.

Results: The consequences of failure to identify these conditions are considerable. In the search for a diagnosis that is literally at the provider’s fingertips, patients frequently undergo months to years of fruitless and often in- vasive diagnostic tests, not uncommonly including unsuccessful surgeries.

Conclusions: With proper consideration of and appropriate testing for visceral etiologies, a carefully directed physical examination may yield an affirmative diagnosis in a percentage of these common emergency depart- ment patients.

Introduction: Neuropathic mimics of visceral pain

Background

Clinical scenario: A 46-year-old woman presented to the emergency department (ED) with 2 months of abdominal pain localized to the right anterior axillary line, radiating to the right upper quadrant (RUQ) and right back. Initial examination found RUQ tenderness without a Murphy’s sign. Laboratory evaluation and RUQ ultrasound were nega- tive. A second examiner exactly reproduced her pain with meticulous palpation of the right 11th rib. Over the next year her outpatient records documented recurrent primary care visits for the same pain, negative Abdominal computed tomography (CT), normal upper and lower en- doscopy and no explanation for her ongoing symptoms. No further ex- amination in the area of the 11th rib was specifically recorded. This patient exemplifies a very common ED scenario of recurrent visits for undiagnosed flank or abdominal pain. The finding of discrete tenderness

* Corresponding author at: Emergency Medicine Department, Naval Medical Center, 620 John Paul Jones Circle, Portsmouth, VA 23708, USA.

E-mail address: [email protected] (K. Frumkin).

of the 11th rib, reproducing the patient’s pain, was noteworthy. This case prompted an informal effort to identify similar findings in subse- quent patients and a literature search for benign mimics of serious vis- ceral pains that might be identified by physical examination.

We identified and discuss two similar clinical syndromes of Flank and abdominal pain of suspected visceral origin, for which no organ- based pathology is found, and which can be reproduced by simple phys- ical examination maneuvers. These are intercostal neuralgias, first de- scribed in 1919 [1], and abdominal wall neuralgias from cutaneous nerve entrapment, identified in 1926 [2]. The goal of this paper is to re- view the literature describing neuropathic mimics of visceral abdominal and flank pain, and to discuss the clinical diagnosis and management of these conditions.

Abdominal pain tops the list of daily Emergency Department (ED) complaints [3]. Emergency physicians routinely evaluate for life threats and seek a definitive diagnosis, yet no specific explanation is found in up to 40% of these ED patients [4-7]. To those without a diagnosis we offer symptomatic relief, a discussion of the likely possibilities, return precau- tions, and referral for ongoing evaluation. The consequences of failing to consider these easily diagnosed mimics of visceral pain can be as severe as those conditions ruled out. In an often-futile search for a diagnosis that is literally at the provider’s fingertips, patients frequently undergo

https://doi.org/10.1016/j.ajem.2018.08.042 0735-6757/

months or years of diagnostic testing, and even unsuccessful surgeries. They are at risk for chronic pain, Iatrogenic injury, Opioid dependence, and depression.

Clinical features

Sufferers from both entities present with acute, subacute, or chronic abdominal or flank pains, generally unilateral. As in our clinical scenario, the initial history and physical examination often raise concerns for vis- ceral disease (hepato-biliary, gastrointestinal, genitourinary, or pelvic). When appropriate diagnostic tests reveal no acute abnormalities and symptoms are controlled, patients are discharged and referred for fur- ther evaluation.

There are no studies of prevalence in the general population [8,9]. In the single published emergency department series, 2% of ED patients with acute abdominal pain were diagnosed with Anterior Cutaneous Nerve Entrapment Syndrome [10]. That study came from a 543-bed Dutch hospital which operates a “Surgical Center of Excellence for Ab- dominal Wall and Groin Pain”. The remainder of the literature consists of case series culled from various practice settings, with a wide range of occurrence frequency. From 3 to 30% of patients with chronic abdom- inal pain have had their symptoms attributed to the abdominal wall [8,9,11-16]. Intercostal neuralgias were found in nearly 5% of gastroenterology-clinic patients, with a higher incidence in those with prior negative evaluations [17-19]. While more than a few studies of in- tercostal neuralgias show equivalence between the sexes [17,20,21], 70% of one larger series were women [18]. Female predominance is more consistently present in the abdominal wall neuralgias [12,14,22,23]. While “middle age” (40’s to early 50’s) was the median in adults [14,17,18,23-27], both syndromes occur in children and ado- lescents [16,28-33]. With intercostal neuralgias, at diagnosis, symptoms had been present for 2-25 years in half of 46 patients [17]. The mean du- ration of pain at presentation was 32 months in the largest series [18], shorter in children (9-20 months) [29,30]. Most patients had been sub- jected to multiple evaluations prior to diagnosis, including contrast studies, Cross-sectional imaging, endoscopies, laparotomies, and “non-

curative cholecystectomy”, without diagnosis or symptom resolution [17,18,22,34-36]. Psychiatric referrals often added to delays [11,17,32,36-41], and costs incurred prior to diagnosis were consider- able [11,22,34].

Anatomy and pathophysiology

Neuralgia is defined as “pain in the distribution of a nerve or nerves” [42]. The conditions discussed fall into that category and derive from ir- ritation of the intercostal nerves, or impingement of their cutaneous branches. Both can mimic serious pathology in underlying organs. Col- lectively they can be considered “peripheral neuropathic mimics of vis- ceral abdominal pain”.

Pain related to the ribs and their intercostal nerves (“Intercostal neu- ralgias”): Innervation of the lower chest and upper abdominal wall is supplied by the intercostal nerves, located along the inferior borders of the ribs (Fig. 1). Since ribs 8-10 are not connected to the sternum, they are more mobile and susceptible to trauma [43]. Connected to each other with a fibro-cartilaginous band, they join and articulate with the costal cartilage. Disruption of these articulations results in in- creased mobility of the ends of the ribs leading to contact with the inter- costal nerve above [20], the presumed source of pain [39]. Increased mobility gave rise to the first of many names for this syndrome, “slip- ping rib” [44]. Such slipping, reproducing pain, has been visualized by ultrasound in symptomatic patients during Valsalva maneuvers [45]. Hypermobility and intercostal nerve irritation by the lower “floating” ribs (11-12) are associated with flank pains, the “12^th Rib Syndrome” [46].

Pain related to fibromuscular entrapment of cutaneous branches of the intercostal nerves (“Abdominal wall neuralgias”): The intercostal nerves (T7-12) supply sensation to the abdominal wall and flank through their anterior, lateral, and posterior cutaneous branches (Fig. 1). These cutaneous nerves are susceptible to painful entrapment as they penetrate the muscular fascia at the lateral borders of the rectus muscle anteriorly [9,12,13,37,48], the serratus anterior or Intercostal muscles laterally [27], or the paravertebral muscles posteriorly [49]

Fig. 1. Diagram of the course and branches of a typical intercostal nerve [47].

Fig. 2. Intercostal nerves, the superficial muscles having been removed [47].

(Fig. 2). Infra-umbilical pain from entrapment of the lower nerves adds appendicitis, diverticulitis, other intestinal etiologies, and pelvic pathol- ogy to the visceral differential diagnosis [50].

Diagnosis

Complete replication of the patient’s pain by physical examination is fundamental to the diagnosis. From the earliest series, authors explicitly recognized that, for some patients, a physical examination with atten- tion to the key features of these syndromes may be all that is needed for identification and safe disposition [18,20,34,51].

Intercostal neuralgias: “Tenderness on pressure over the rib” was the

original diagnostic criterion [21]. Rib-related upper abdominal pain originating from the intercostal nerves is also easily reproduced with the “hooking maneuver” (Fig. 3) [52]. The fingers of both hands are hooked under the costal margin and the rib cage is pulled anteriorly,

Fig. 3. The “Hooking Maneuver” [52]. The examiner’s curved fingers are hooked under the costal margin and the rib cage is pulled anteriorly, reproducing the patient’s pain on the affected side.

reproducing the patient’s pain on the affected side. In some, a “click” or “pop” may be heard or felt during this maneuver, coinciding with production or exacerbation of the patient’s symptoms. Similar painful rib motion has been induced by the Valsalva maneuver. Rib “slip” during Valsalva (repetitively triggering painful rib pain) has been observed with ultrasound [45].

Flank pains originating from the “floating” 11th and 12th ribs may not be as easily provoked by the hooking maneuver applied at the costal margin. In the authors’ experience, localized and reproducible tender- ness in the areas of the two lowest ribs is often overlooked on physical examination unless specifically sought. Examination of the back in pa- tients with flank pain is often limited to a search for renal tenderness to percussion at the costovertebral angle (CVA). That exam is classically performed with the patient sitting. The examiner is to “make a fist and gently hit the area overlying the costovertebral angle on each side” [53]. While often able to identify kidney pain, CVA percussion can be un- remarkable in patients with symptoms referable to the lower two ribs.

[36] The authors find that with the patient supine, careful and gentle proximal-to-distal palpation and manipulation of the 11th and 12th ribs with one finger often easily elicits the exactly-reproducible tender- ness that defines an intercostal neuralgia, even in the obese. Tenderness on CVA percussion can, of course, also reflect rib-related pain.

Abdominal wall neuralgias: Specific physical examination character- istics of painful cutaneous nerve entrapment in the abdominal wall in- clude a “trigger point” (b2 cm²) of maximum pain and tenderness. Carnett’s original sign [12] is present: persistence of pain at the point of maximum tenderness with “vigorous palpation made while the pa- tient balloons out his abdomen [raises their head and shoulders] and voluntarily holds his [sic] abdominal muscles so tense that the examiner’s fingers cannot possibly come in contact with the abdominal

viscera [51].” Tenderness of visceral intraabdominal origin diminishes during this maneuver. A well-localized trigger point may be surrounded by a larger region of altered skin sensation (not necessarily correspond- ing to a specific dermatome) where simple somatosensory testing with an alcohol swab or light touch demonstrates hypoesthesia, hyperesthe- sia or altered temperature perception [10,27,32,48,49,54,55]. “Patients are often so preoccupied with the large area of pain spread that they do not realize the area of tenderness is extremely localized and superfi- cial” [56]. A positive pinch test may be present: “using thumb and index finger to ‘pinch’ and lift the skin around the tender point eliciting a pain- ful response in comparison to the contralateral side” [27,48,51].

confirmatory testing is via local anesthetic infiltration. While the physical examination features described above are often adequate to defer further evaluation, additional confirmation in patients with both intercostal and abdominal wall neuralgias can be provided by pain relief from local anesthetic infiltration at the point of maximum tenderness [9,11,22,26,32,46,48,51,57], and by Intercostal nerve blocks [30,58]. The diagnostic value of abdominal trigger point infiltration was sup- ported by a randomized sham-controlled study [26].

Differential diagnosis

Abdominal pain

As in the case presented, all patients merit thoughtful evaluation for acute intra-abdominal inflammation, infection, obstruction, or surgical disease before diagnosing of one of these peripheral Neuropathic pain syndromes [9,48,56]. Even when visceral disease is ruled out, there are a number of other non-surgical, Benign conditions to be considered. These include irritation or entrapment by scars, postoperative adhe- sions, hernias, diabetic radiculopathy, herpes zoster, myofascial tears, Abdominal wall hematomas, or thoracic spine lesions [9,12,48,56,59- 61].

Chest pain

Pains from intercostal nerves and their cutaneous branches occur in the lower chest as well as the abdomen [18,21,31,62-67]. While, chest pain arising from these mechanisms can sometimes be dismissed after history and physical examination alone, a lower threshold for cardiac evaluation in patients with suspected chest wall pains is commonly ad- vocated [68].

Ranking second to abdominal pain in frequency of ED visits [3], chest pain complaints are additionally burdened by their attachment to scary lists of “can’t miss” ED diagnoses and by the status of this complaint as number one in ED closed malpractice claims [69]. Findings of chest wall tenderness can fail to exclude coronary etiology with a satisfactory negative predictive value. In their study of ED chest pain patients, Disla et al. diagnosed myocardial infarction in 6% of patients with pain reproduced by chest wall palpation [70]. In nearly 2000 ED chest-pain patients, those discharged with a “clear-cut alternative noncardiac diag- nosis” still had a 4% event rate (death, acute myocardial infarction, or re- vascularization) at 30 days [71].

Musculoskeletal pain is still the most common discharge diagnosis in chest pain patients. While the same physical examination maneuvers may be utilized in their diagnosis, neuralgias represent a smaller pro- portion of the non-visceral causes of chest pain than they do of abdom- inal or flank pain. The larger list includes thoracic muscle strains, dorsal spine radiculitis, rib fractures, bone metastases, herpes zoster, thoracic disc herniation, precordial catch, Myofascial pain, chest wall muscle in- jury, xiphodynia, fibromyalgia, costochondritis, and Tietze syndrome, all sharing the broader benign differential with intercostal neuralgias [72]. Given that chest wall tenderness may be present in an unacceptable percentage of patients with acute coronary syndromes, combined with the much larger list of non-cardiac causes, the literature reviewed does

not support changes in the evaluation of chest pain.

Other pain syndromes and systemic illnesses

Patients with the more generalized non-visceral pains of fibromyal- gia or Myofascial pain syndromes additionally have Trigger points and referred pain [27]. Diagnostic criteria for fibromyalgia include wide- spread pain with tenderness at eleven or more specific sites [73]. The muscular trigger points of the myofascial pain syndromes are located throughout the body and arise without connection to specific peripheral nerves [74,75].

Complex regional pain syndrome (CRPS) is a chronic painful condi- tion, often post-traumatic. CRPS is characterized by severe and continu- ous extremity pain in a non-dermatomal distribution, disproportionate to any inciting event, and accompanied by sensory, autonomic, and motor abnormalities [76-78].

Metabolic causes of chronic non-visceral abdominal pain include chronic renal failure, Addison’s disease, porphyria, etc., are well- recognized [60]. Functional abdominal pain remains in the differential for many chronic-pain patients [16].

Treatment

Management of these syndromes has included all the common ther- apies for musculoskeletal pains: compression, stretching, weight loss, modifications of physical activity, exercises, heat, cold, transdermal li- docaine, nonsteroidal anti-inflammatories, acetaminophen, manual manipulation and Physical therapy. For some patients, the presence of a named diagnosis, reassurance, and explanation may be all that is nec- essary [37,50].

The prompt relief obtained from local anesthetic injection (with or without steroids) has been both diagnostic and therapeutic [9,11- 13,22,26,32,37,38,48,49,51,57,62,79-81]. Intercostal nerve blocks are ef- fective and often curative [29,30,38,39,46,54,58,67,82]. Pirali et al. re- port success with Botulinum toxin injection into the intercostal muscles [35].

For cases refractory to standard measures or injections, surgical re- section of portions of the involved rib or costal cartilage has been suc- cessful [20,28,30,31,36,44,83-87]. For refractory cutaneous nerve entrapment, neurectomy of the involved nerve branch has been advo- cated [48,81,88-90], and supported by a sham-controlled study [25]. Spinal cord stimulation has been used after failed neurectomy [90].

Limitations

The bulk of the supporting literature is anecdotal, without the rigor of evidence-based medicine (EBM). However, in the absence of con- trolled studies, case reports and series have always contributed to clin- ical practice [91] and continue to merit publication in emergency medicine journals. EBM sources “suggest using evidence derived from case reports and case series to inform decision-making when no other higher Level of evidence is available.” [92] It is worth considering the conclusions shared by authors from nearly a dozen specialties, reporting more than 2000 cases in the 56 references cited here:

applying specific simple physical examination maneuvers has the potential to identify benign mimics of visceral abdominal pain in some patients, and

failure to recognize these mimics leads to unnecessary testing and the morbidity that can follow a diagnosis of unspecified ab- dominal pain.

The nature of the underlying literature makes an accurate determi- nation of the prevalence of such patients difficult. With over 12 million yearly US ED visits for abdominal pain [3], even the most conservative estimates (2-3%) do not negate the value of an affirmative diagnosis of non-visceral abdominal pain to hundreds of thousands of individual patients.

The sensitivity and specificity of the physical examination features described have not been quantified. However, even for a problem as widely studied as evaluation for appendicitis, any one diagnostic ele- ment is of weak discriminatory and Predictive capacity. [93] As with any single data point, readers are cautioned to place the results of these suggested maneuvers in context. Adding these two entities to the 40-item textbook differential diagnosis of abdominal pain [7] does not define the nature and extent of the work-up for an individual pa- tient, but hopefully informs the discussion and disposition when no emergent diagnosis is found.

Discussion

The intercostal and abdominal wall neuralgias have been identi- fied and re-identified as sources of non-visceral abdominal pain for nearly one hundred years [1,2]. Over the intervening decades, multiple authors from various specialties reported series of patients and reiterated the value of specific physical examination features in excluding underlying visceral pathology [8,9,11- 13,15,17,18,20,21,27,32,43,48,49,51,65,82,89,94,95]. Yet, a Na-

tional Library of Medicine search in November 2017 that retrieved over 500 references for “cutaneous nerve entrapment syndrome”, found only one citation with “Emergency” in either the article title or journal name [10]. We repeat concerns raised in nearly every report since 1922: “Unfortunately, this syndrome is not widely recognized but it is hoped that this article will bring it to the attention of those most likely to encounter it … and so save nu- merous unnecessary investigations and consultations” [96].

As the most common ED complaint, the evaluation and management of abdominal pain can, of necessity, become protocolized and routine. Testing and treatment often begin well before a comprehensive history and exam, even at triage or in the waiting room [97]. More testing equates to higher costs and longer lengths of stay [98].

It is encouraging to note that physical examination alone can some- times point to a quick affirmative diagnosis of the cutaneous neuralgias. Diagnostic maneuvers can take less than a minute. For the intercostal neuralgias one can assess for reproduction of the patient’s pain with careful direct palpation of the ribs, the “hooking maneuver”, or Valsalva. There may be an associated “click” with these, or by history. For the ab- dominal wall neuralgias, a trigger point with surrounding skin dysesthesia, Carnett’s sign, and the “pinch test”, are strongly suggestive. Confirmation with relief from local anesthesia and an explanation of one’s findings and their significance in ruling out visceral pathology may take a few minutes more.

It is, however, discouraging to note the lack of impact of the nearly 100-year cycle of discovery and rediscovery of these syndromes on the day-to-day evaluations of patients with abdominal pain. The conse- quences of failure to identify these conditions is clear from the pub- lished case series: progressively more invasive testing with potential for Iatrogenic complications, chronic pain with the associated risk of opioid dependence, and depression. Emergency physicians have all seen patients like ours, with recurrent right upper quadrant pain, whose course has covered years, and often included a nontherapeutic cholecystectomy. Did anyone tug on a rib? In the largest series of inter- costal neuralgia patients, 87% became chronic AFter 3 months [18].

In the age of cost containment, “choosing wisely” [99], “first-pre- scription” risk for chronic opioid use [100], and what has been called out as an unhealthy reliance on imaging [101], there is value to adding specific consideration for these peripheral neuropathic mimics of vis- ceral pain earlier to the differential diagnosis and discharge planning for patients with abdominal pain. Examples like our patient with the negative hepato-biliary ultrasound and laboratory evaluation, or the 43% of “renal colic” patients with no CT finding to explain their pain [102], are seen every day.

Limiting ED testing will hinge on the rest of the history and exam, age and comorbidities, availability of follow-up, the history of prior

episodes and evaluations, patient and provider risk tolerance, and “ge- stalt”. It is not uncommon for busy providers to jump reflexively into the lab/CT abdominal pain work-up, even in the well-appearing, com- fortable, young patient. We suggest taking a minute or two to make a re- alistic assessment of the pretest probability of surgical disease, and to examine for one of these Alternative diagnoses. If one can make an affir- mative diagnosis with physical examination, improve pain with simple means or local anesthetic infiltration, relieve anxiety with an explana- tion and shared decision-making, offer good return precautions and diagnosis-appropriate follow-up suggestions, an H&P may be all that is needed in a reasonable number of these most common ED patients.

The same diagnostic process may be even more important to our chronic pain patients. Examples include those frequently-returning pa- tients with years of recurrent flank pain, microhematuria, and a known non-obstructing Kidney stone. Keoghane et al. note “A history of stone formation or indeed a confirmed urinary tract calculus should not dis- tract the examining clinician from considering ’12th rib syndrome’ as a possible diagnosis” [79]. Examining such patients for a painful rib or nerve entrapment has the potential to provide a treatable diagnosis, an appropriate referral for targeted therapy, and a chance to break the cycle of ED visits, negative labs, imaging and invasive studies, suspicions of drug seeking, iatrogenic injury, opioid overuse, chronic pain, and depression.

Conclusions

Emergency physicians see more patients with abdominal pain than any other complaint. Almost all abdominal pain patients will need some workup. In spite of an appropriate evaluation, there may still be some (up to 40%) with “abdominal pain” and no obvious etiology [4,6,7]. There are few situations in emergency medicine when just a minute or two added to the physical examination and discharge discus- sion can ease diagnostic uncertainty in a reasonable percentage of such a large volume of patients. Emergency-physician consideration of these peripheral neuropathic mimics of visceral pain can interrupt the century-long cycle of discovery, rediscovery, and renaming of these conditions. The answer to their pain is at your fingertips.

Sources of support

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

Conflicts of interest

None.

Presentations

None.

Required disclaimer

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense or the United States Government.

Copyright constraints

Authors of this work are an employee of the U.S. Government at the time of its creation, and a military service member. This work was pre- pared as part of their official duties. Title 17 U.S.C. 105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service

member or employee of the United States Government as part of that person’s official duties.

Acknowledgements

The authors gratefully acknowledge the able assistance and exten- sive support provided by Tracy Shields, MSIS, AHIP and the rest of the staff of the Health Sciences Library, Naval Medical Center Portsmouth, VA. Valuable technical assistance was provided by Katharine Yamulla and her staff at the Clinical Skills and Simulation Center, New York Med- ical College School of Medicine.

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