The study was approved by the Ethics Committee of Hannover Medical School (number 2987-2017) and was conducted under the Declaration of Helsinki. All patients provided written informed consent after they were informed about the purpose of the study.

Our study population consisted of patients from the emergency department of Hannover Medical School who were referred to internal medicine physicians between March 2017 and October 2017. Eligible patients were adults (age ≥18 years in Germany), presenting with an acute medical problem and with the ability to provide written informed consent. Furthermore, patients needed to be oriented as to place, time, and person. Exclusion criteria comprised refusal or inability to provide written consent, previously known or acutely diagnosed spinal cord injury, pregnancy, acute or past ocular illnesses, acute or past central or peripheral nervous disease, uncooperative patients, and patients who only presented to the emergency room for educational purposes or to receive a prescription. For a flowchart, see Figure 1.

We recruited 208 patients (85, 40.9% women) for participation in our study. Nine drawings were lost due to technical failure of a tablet PC during the physical examination. The characteristics of the final study population can be found in Table 2, and their final diagnoses can be found in Multimedia Appendix 1.

All clinical data were collected by 2 of the authors (AA and NS), henceforth called examiners. AA is an internal medicine specialist, and NS is a physician with 4 years of training for an internal medicine specialization. The examiners were fully informed about the study purpose and trained to do the physical examination for segmental signs and symptoms according to the protocol described below. Prior to the study, the examiners trained intensively together to ensure their physical examinations were standardized. This was also necessary to ensure that all procedures could be completed in a very limited timeframe.

During recruitment, the examiners screened the emergency dashboard to identify patients who were referred to internal medicine specialists. They approached all eligible patients, informed them about the study, and obtained written informed consent.

The examination took place directly after triage and before any medical intervention, diagnosis, or treatment. The examination lasted between 7 and 15 minutes, depending on the patient’s compliance (ie, general motivation to be examined, speed of undressing and answering the examiner’s questions, precision of the answers given, unrelated conversation, etc) and interruptions by nurses and physicians (as routine diagnostics and medical interventions had priority over the scientific investigation). Directly after the physical examination, all findings were recorded on a tablet computer running the app “SymptomMapper” (described in the section “Tablet Computer and Software Application”).

The clinical findings we were interested in can be divided into 3 groups, according to the ways they were recorded in the tablet: (1) distributed findings (ie, those with a bodily pattern), (2) lateralized findings (ie, those without a bodily pattern but with clear lateralization), and (3) other findings.

First, distributed findings were spontaneous pain, allodynia, superficial hyperalgesia, deep hyperalgesia, superficial skin resistance, muscle resistance, defense, asymmetric hyperhidrosis, piloerection, vasomotor changes, herpes zoster, and resistance to passive movement of the limbs. Distributed findings were recorded by the examiners in the form of electronic drawings on a body template, thus capturing their exact location and extent.

Second, lateralized findings were anisocoria, glossy eye, eyelid separation, tense facial muscles, asymmetric posture, and reduced respiration movements. These findings were recorded by choosing from a list of the abovementioned findings in conjunction with a side label (eg, “glossy eye right,” “mydriasis left,” etc).

Third, other findings were symptoms potentially related to viscero-visceral reflexes, namely, nausea, vomiting, constipation, diarrhea, meteorism, and urinary retention. These findings were recorded by choosing from a simple list of the abovementioned symptoms.

All findings were recorded on Galaxy Note 10.1 (2014) tablet PCs with an electronic stylus based on inductive digitizing technology (Samsung, Seoul, South Korea). The tablets had a 10.1-inch touch screen with a resolution of 800×1280 pixels and were running Android 5.1.1 (Open Handset Alliance, Mountain View, CA, United States). The stylus was used for all data entry, hence allowing for a higher resolution while eliminating unwanted activation of the screen, for example, by the palm. The tablet and stylus were disinfected after every patient using disinfectant wipes.

We used a modified version of the SymptomMapper app developed by our group (Somatosensory and Autonomic Therapy Research, Institute for Neuroradiology, Hannover Medical School, Hannover, Germany) to acquire electronic pain drawings [35]. Its usability for doctors and the reliability of its symptom-drawing approach have recently been shown [35]. The app allowed the examiners to enter all findings from the bodily examination quickly. They could either draw distributed findings on a body template or choose from a list of lateralized or other findings. For the electronic drawings, examiners had a front and back view of the body available, and each newly added sign or symptom was displayed in a semitransparent way and in a different color.

Medical reports of all recruited patients were followed up through Hannover Medical Schools’ electronic health records by 3 of the authors (NS, AA, and MM), to identify those patients with a definite diagnosis of visceral disease. All information regarding the acute complaint, previous diagnoses, and diagnostic procedures (electrocardiogram, laboratory, radiology, etc) were reviewed, and the most likely etiology for each patient was discussed. Patients without a definite visceral diagnosis were excluded from further analysis (n=50). The remaining cases were divided into those where a single organ was affected (n=110) and those with multi-organ problems (n=39). Only the single-organ cases were included in the final analysis, and only organs with at least 4 patients in the sample were included in any organ-specific analyses (Figure 1).

Of the 110 patients in our final sample, 85 (77.3%) had spontaneous pain, 81 (73.6%) showed at least 1 segmental sign, and 52 (47.3%) showed at least 1 segmental symptom. On average, each patient had a mean of 1.80 (SD 1.86) segmental signs and 0.77 (SD 1.00) segmental symptoms. The most frequent signs and symptoms are shown in Table 3.

All lateralization of signs and segmental symptoms are shown in Multimedia Appendix 2. As predicted by the side rule (see [33] and Table 1), the majority of lateralization signs were ipsilateral to the affected organ for the unpaired organs heart, stomach, and liver/gallbladder. The most striking finding was the high number of patients showing ipsilateral mydriasis as a potential sign of unilateral sympathetic activation. This lateralization was 100% ipsilateral for diseases of the liver/gallbladder (5 right vs 0 left), 100% ipsilateral for stomach diseases (1 left vs 0 right), and 83% ipsilateral for heart diseases (15 left vs 3 right).

Bodily maps of segmental signs and spontaneous pain for a representative selection of individual patients are shown in Figure 2. The cases shown in Figure 2 reflect the entire bandwidth of segmental signs encountered in patients presenting to the emergency room. It ranges from “textbook cases” (eg, patients 2, 3, 6, 9, 13, 18, and 19), where segmental signs alone allow for a preliminary diagnosis, to those where segmental signs are hardly helpful or even misleading (eg, patients 7, 12, and 15). Their primary diagnoses and demographic information are summarized in Multimedia Appendix 3.

Bodily maps of all distributed segmental signs are shown in Figure 3, while Figure 4 contains detailed segmental information concerning the distribution of the individual signs and spontaneous pain. In general, the observed distributions of segmental signs were largely consistent with those reported by Hansen and Schliack [33]. The lungs were the only exception, which showed a more widespread distribution than predicted. Concerning lateralization, segmental signs from the unpaired organs showed a clear side difference, with more signs appearing ipsilateral to the affected organ, thus supporting the “side rule” represented in Table 1. For the lungs and kidneys/ureters, however, this rule could not be tested, since results for these organs reflected a mixture of left, right, and bilateral affections.

Within-organ comparison showed that the different segmental signs but also spontaneous pain had a similar segmental distribution (Figure 4). Between organs, these distributions showed considerable overlap. Superficial hyperalgesia (Head zone) exhibited the greatest spread in terms of segments. Regarding lateralization, segmental signs for the unpaired organs mostly obeyed the side rule, according to which signs should appear on the body half where the organ is located. Pain differed markedly in that respect and, instead, showed a rather symmetric pattern.

For cardiac-related conditions, segmental signs were mostly located in the thoracic segments and, to a lesser extent, in cervical segments. Superficial hyperalgesia (Head zone) was also detected in the trigeminal segments. The maximum of the averaged signs was in the T3-T5 region (Figure 3B), as predicted by Hansen and Schliack [33]. In terms of lateralization, all distributed signs were strongly left-dominated with deep hyperalgesia (Mackenzie zone), showing complete left-lateralization (Figure 4). In heart patients, defense and allodynia were rare and nonexistent, respectively.

For diseases of the lungs, segmental signs were very widespread and covered a range from V2 to L2. Signs were generally less focused than for the heart, and no clear maximum was discernible. In this, the distribution deviated from Hansen and Schliack’s [33], who reported T9 as the lower margin of segmental signs in lung diseases. As was to be expected due to the mixture of left, right, and bilateral organ diseases, no lateralization could be seen.

For the stomach, the segmental distribution was almost strictly thoracic, from T2 to T12, with a maximum at T6-9 on the front and on the back. Similar to the heart, superficial hyperalgesia for the stomach was lateralized to the left, as predicted by the side rule. The comparison with Hansen and Schliack [33] showed that the maximum of signs in T6-9 fell in the expected range in the front view. On the back, however, there was only a partial overlap, with Hansen and Schliack [33] predicting higher thoracic segments than were found in our study.

The similarity with Hansen and Schliack’s [33] results was much higher for patients with liver/gallbladder diseases. Here, segmental signs showed a largely thoracic distribution but with the characteristic shoulder presentation in segments C3-C5 [33]. In terms of lateralization, muscle resistance, defense, and superficial and deep hyperalgesia were predominantly right-lateralized, with superficial hyperalgesia (Head zone) showing almost complete right-lateralization.

Finally, segmental signs of the kidneys had the narrowest distribution, starting at T6 and extending down to L2, once again, showing a rather high similarity with the predicted distribution by Hansen and Schliack [33].

The segmental distributions of spontaneous pain and segmental signs are shown in Figure 5. It is evident that spontaneous pain differed markedly from segmental signs. It spanned fewer segments but extended to the head region (V1) in cardiac, respiratory, and liver/gallbladder affections. Furthermore, spontaneous pain was much less lateralized than segmental signs and, instead, rather localized in the body midline. In general, the pain was less widespread and showed much weaker lateralization than segmental signs in the unpaired organs (ie, heart, stomach, and liver/gallbladder).

In this study, we investigated bodily patterns and lateralization of segmental signs and spontaneous pain in acute visceral diseases. We derived mean distributions of spontaneous pain and segmental signs for the heart, lungs, stomach, liver/gallbladder, and kidneys/ureters by combining digital pain drawing technology and a structured 10-minute bodily examination in patients presenting to the emergency room. We extracted precise information on the segmental content and lateralization and compared the results with the slightly outdated but authoritative German work of Hansen and Schliack [33]. Although purely descriptive by design, our study is the first in the English language to provide a detailed account of simultaneously collected segmental signs and symptoms for visceral diseases in the clinical setting.

The lateralization of segmental signs is important, as it allows one to quickly identify the affected body side (ie, the side hosting the affected organ; Table 1). This side rule may be useful in the differential diagnosis, such as in differentiating gastritis from hepatitis or pancreatitis, or acute coronary syndrome from a pulmonary embolism or esophagitis. Due to our study design and the very mixed patient sample, our results regarding lateralization were limited to the heart, stomach, and liver/gallbladder. Although segmental signs of the lungs and kidneys/ureters are also expected to be found ipsilateral to the affected side, a separate analysis for the individual sides was not possible for these organs due to the limited number of cases, many of which showed bilateral affections.

Although our data were not analyzed prospectively, it appears, for the heart, stomach, and liver/gallbladder, that they may support the findings of Hansen and Schliack [33] that segmental signs appear ipsilateral to the affected organ. While this was evident for the mean bodily distributions of segmental signs, we also found an ipsilateral occurrence of mydriasis, a finding rarely raised outside the neurological setting. It results from a reflex mediated by the ciliospinal center, which conducts impulses from the entire body to the sympathetically innervated dilator pupillae muscle (p271) [28] and, more than 100 years ago, was first described to occur in affections of the lungs [36] and the heart [37]. More recently, Rosenberg [38] has shown that anisocoria (ie, unequal pupil size) under physiological conditions is a manifestation of sympathetic asymmetry.

We found ipsilateral (ie, right-sided) mydriasis in 42% of our liver/gallbladder patients and not a single case of contralateral mydriasis. For the heart, mydriasis was less frequent (24% ipsilateral vs 5% contralateral), yet this means that patients showing the sign had it on the ipsilateral side in almost 83% of the cases. Hansen and Schliack [33] reported qualitatively similar but generally higher numbers for mydriasis. In their sample of 28 heart patients, 27 (96%) had mydriasis, and this was ipsilateral in 26 patients (96%). In 56 liver/gallbladder patients, 54 (96%) had mydriasis, of which 50 cases (93%) were ipsilateral (ie, right-sided).

The generally higher numbers of mydriasis in heart diseases found in Hansen and Schliack’s [33] work may be explained by the fact that these authors used dark adaptation and infrared photographs in many of their patients, which made their examination less subjective, while our examiners were restricted to visual inspection under normal light. Clinicians interested in this phenomenon should consider using a portable infrared pupilometer.

A subset of the findings collected in our study was further analyzed to extract detailed segmental information. We called this group of findings “distributed signs.” It comprised a number of somatosensory (ie, superficial and deep hyperalgesia and allodynia), somatomotor (ie, superficial skin resistance, muscle resistance, and defense), and visceromotor signs (ie, vasomotor changes, piloerection, and asymmetric hyperhidrosis). Of these, superficial hyperalgesia (ie, Head zones), muscle resistance, defense, and deep hyperalgesia (ie, Mackenzie zones) were the most frequently observed in our sample of patients, while others, such as allodynia, piloerection, asymmetric hyperhidrosis, or zoster, were exceedingly rare.

There was a close similarity between the original maps of segmental signs by Hansen and Schliack [33] and our mean distributions of all signs (Figure 3). For a prospective evaluation, however, future studies should aim to quantify this similarity (eg, by using spatial similarity measures).

Several groups have studied individual segmental signs or groups of signs since the days of Hansen and Schliack. For example, Nicholas and colleagues [39] found that patients with myocardial infarction showed characteristic paravertebral soft tissue changes readily detected by palpation. Compared with patients without diagnosed cardiovascular diseases, patients with myocardial infarction had a significantly higher incidence of increased firmness, warmth, ropiness, oedematous changes, and heavy musculature, almost entirely confined to cardiac segments T1-4. In a follow-up 3 years after the infarction, these signs had regressed in the majority of patients [40]. Vecchiet and colleagues [41] found ipsilateral superficial and deep hyperalgesia of the first lumbar (L1) segment in patients after renal/ureteral calculosis.

For the gallbladder, Stawowy and colleagues [42] found that all patients with acute cholecystitis reported referred pain in the epigastrium and under the right curvature. Segmental signs inside this area were quantitatively evaluated using von Frey hairs, warm and cold metal rollers, and a constant current stimulator to test for the different forms of hypersensitivity or allodynia. The authors reported that 20% of the patients showed hypersensitivity or allodynia to mechanical, 53% to cold, 40% to warmth, and 63% to electrical stimulation [42]. The same authors reported that 50% to 56% of patients with acute appendicitis showed segmental signs over the right abdominal quadrant, with the maximum located approximately at McBurney point [43]. These findings were recently confirmed by Roumen and colleagues [44], who reported that 39% of patients with acute appendicitis demonstrated at least one segmental sign (ie, hyperalgesia, hypoesthesia, altered cool perception, or positive pinch test) over the lower right abdomen. Finally, a large number of smaller studies and case reports have been published, which have been reviewed by Beal [45].

The majority of our patients with visceral diseases reported spontaneous pain (Table 3). In 85% of the cases, it was, by far, the most frequent finding, followed by superficial hyperalgesia (46%), nausea (45%), and muscle resistance (39%).

Many textbooks assign pain location a discriminative role in the differential diagnosis (eg, retrosternal chest pain that radiates to the left arm or lower jaw usually refers to acute coronary heart disease. However, such predictive power of pain location has been a matter of debate for decades [11-13]. Here, we found, by direct comparison of spontaneous pain and segmental signs, that the two were rather dissimilar in their bodily patterns and segmental distributions (Figure 5). Irrespective of the affected organ, spontaneous pain was less widespread than segmental signs (ie, it included fewer segments). Furthermore, spontaneous pain appeared mostly in the body midline, thus lacking the diagnostically relevant ipsilateral distribution seen in the majority of segmental signs. As Figure 5 shows, patients with lung, stomach, and liver/gallbladder diseases all showed spontaneous pain in the epigastric region (T5-9), thus rendering this symptom unsuitable for differential diagnosis.

The substantial differences found between pain and segmental signs regarding their location and lateralization underline the importance of making a clear distinction between visceral pain, (referred) hyperalgesia, and other segmental signs.

Despite the purely descriptive design of this study, our results (Figures 4 and 5) regarding the benefit of using spontaneous pain or segmental signs seem to favor the latter over the former. Future studies should test this in a prospective way (eg, by letting a blinded assessors predict the affected organ from the distribution of spontaneous pain or from that of segmental signs).

Our study had several limitations that need to be discussed. Firstly, our patient sample was relatively small, as we could only analyze approximately half of the included patients. There were two reasons for this. On the one hand, approximately one-quarter of our patients had to be excluded from the analysis, since they left the hospital without a confirmed final diagnosis. This is due to the unique situation in the emergency room, where the vital role of the specialist is to rule out life-threatening conditions. A further one-quarter of the remaining patients had to be excluded from the analysis because they suffered from diseases affecting multiple organs. Secondly, while we took great care to include only patients with single-organ problems, it is likely that affections of other organs were present but overlooked in some of the patients. This means that some patients who seemed to only present with cardiac disease may have had another underlying disease affecting other organs. Thirdly, findings collected by means of palpation are naturally more subjective than, for example, laboratory results. While there are ways to measure segmental signs more quantitatively, we did not do so to keep the examination time to an absolute minimum, as required by the clinical setting. Finally, we did not differentiate explicitly between signs and symptoms that patients had only during their acute problem from patient symptoms that occurred usually. This may have introduced some bias.

This study underlines the usefulness of including segmental signs in the bodily examination of patients with acute medical problems. As we have shown, capturing the location of segmental signs on a digital body map may assist in the clinical decision-making process in some acute visceral conditions. Segmental information and lateralization from the 3 most-frequent signs (superficial hyperalgesia, muscle resistance, and mydriasis) can be quickly acquired and may help physicians narrow the differential diagnosis.