Extravertebral low back pain: a scoping review

Abstract

Background

Low back pain (LBP) is one of the most common reasons for consultation in general practice. Currently, LBP is categorised into specific and non-specific causes. However, extravertebral causes, such as abdominal aortic aneurysm or pancreatitis, are not being considered.

Methods

A systematic literature search was performed across MEDLINE, Embase, and the Cochrane library, complemented by a handsearch. Studies conducted between 1 January 2001 and 31 December 2020, where LBP was the main symptom, were included.

Results

The literature search identified 6040 studies, from which duplicates were removed, leaving 4105 studies for title and abstract screening. Subsequently, 265 publications were selected for inclusion, with an additional 197 publications identified through the handsearch. The majority of the studies were case reports and case series, predominantly originating from specialised care settings. A clear distinction between vertebral or rare causes of LBP was not always possible. A range of diseases were identified as potential extravertebral causes of LBP, encompassing gynaecological, urological, vascular, systemic, and gastrointestinal diseases. Notably, guidelines exhibited inconsistencies in addressing extravertebral causes.

Discussion

Prior to this review, there has been no systematic investigation into extravertebral causes of LBP. Although these causes are rare, the absence of robust and reliable epidemiological data hinders a comprehensive understanding, as well as the lack of standardised protocols, which contributes to a lack of accurate description of indicative symptoms. While there are certain disease-specific characteristics, such as non-mechanical or cyclical LBP, and atypical accompanying symptoms like fever, abdominal pain, or leg swelling, that may suggest extravertebral causes, it is important to recognise that these features are not universally present in every patient.

Conclusion

The differential diagnosis of extravertebral LBP is extensive with relatively low prevalence rates dependent on the clinical setting. Clinicians should maintain a high index of suspicion for extravertebral aetiologies, especially in patients presenting with atypical accompanying symptoms.

Background

Fundamentally, low back pain (LBP) represents a symptom rather than an aetiological diagnosis per se. Since establishing a definite pathophysiological diagnosis is often neither necessary nor possible, most clinical guidelines pragmatically distinguish between non-specific LBP, specific LBP, and sciatica/radiculopathy [1]. Furthermore, extravertebral or non-spinal medical disorders may mimic or present clinically as LBP. Consequently, some guidelines recommend considering extravertebral or non-spinal diseases in the differential diagnosis. Recognising extravertebral causes is crucial to avoid misdiagnosis and inappropriate management of potentially life-threatening diseases. In settings where patients have direct access to specialised care, such as orthopaedics and physiotherapy, the likelihood of considering non-musculoskeletal disease may be lower [2]. Deyo and Weinstein once estimated that approximately 2% of patients presenting with LBP in primary care have what they referred to as “visceral” disease. However, this percentage lacks a specific data source [3], yet it has been consistently cited in subsequent literature [4,5,6,7,8,9,10,11,12,13,14,15,16]. Within a specialist setting, it has been estimated that up to 10-25% of patients presenting with back pain do not have a vertebral pathology [17].

While LBP caused by conditions such as abdominal aortic aneurysm, peripheral arterial disease [18,19,20], or renal calculus can unambiguously be classified as extravertebral or non-spinal diseases, in many instances, categorisation remains challenging. For example, determining whether conditions involving intramedullary tumours, metabolic diseases (e.g., spinal gout), or hip pathology [21] mimicking radiculopathy should be attributed to spinal or extravertebral causes of pain remains debatable (Fig. 1). At times, these conditions are collectively referred to as unusual or rare causes for LBP [22,23,24,25,26,27,28,29,30,31,32,33,34]. The term “extravertebral” or “non-spinal” LBP is anatomically incorrect since it refers only to the bony structures of the back. Currently, there is no consensus on a definition or terminology to classify serious LBP not typically covered by “red flags”. Red flags are warning signs related to pathologies like tumours, fractures, inflammations or infections of the spine [35,36,37].

Fig. 1

Overlap of definitions with bubble sizes approximately representing epidemiology. LBP = low back pain

The aim of this scoping review is to summarise what is known on the epidemiology and presentation of extravertebral or non-spinal LBP, in order to help clinicians assessing patients with LBP to recognise when it is appropriate to include this in the differential diagnosis.

Methods

This is a scoping review conducted according to the PRISMA extension for scoping reviews (Appendix 1) [38]. Since PROSPERO does not register scoping reviews, a protocol was not registered. A scoping review was chosen due to several factors, including the absence of a universally accepted definition, the broad spectrum of diseases, and the limited existing literature on the topic. Furthermore, this methodology was selected to facilitate a comprehensive overview of the field, identify current research gaps, and provide recommendations for future research.

Search strategy

The authors searched three electronic databases (MEDLINE, Embase, and the Cochrane Library). In 2001, Deyo and Weinstein published the first major narrative review of extravertebral causes of LBP [3]. Therefore, the search scope was limited to publications from 1 January 2001 to 31 December 2020. The detailed search strategy is outlined in Fig. 2, and the specific search terms used are available in Appendix 2. Where required, search terms were amalgamated using Boolean logic and database-specific filters. All publications available in either German or English languages were included.

Fig. 2

Search flow diagram of the literature review process for studies on extravertebral low back pain according to the PRISMA2020 Statement [39]. LBP = low back pain

Study selection

There is no universally accepted definition allowing to separate “extravertebral” unambiguously from “vertebral” LBP (Fig. 1). Furthermore, the terminologies are not formulated clearly and are insufficient for classifying both included and excluded diseases. Alternatively, the terms “extraspinal” or “non-spinal” back pain are also used. During the review process, the authors encountered difficulties in finding an accurate definition due to overlapping terms and classification systems. Nevertheless, an attempt was made to classify the diseases related to low back pain.

Inclusion criteria comprised publications of case reports, case series, case-control studies, cohort studies, randomised controlled trials, observational studies, and reviews reporting low back pain as a symptom of non-primary vertebral/musculoskeletal disease in adults, including systemic diseases. The MeSH-terms are available in Appendix 2.

Exclusion criteria comprised publications with patients under the age of 18 and pain primarily reported in thoracic and cervical spine. Furthermore, “red flags” indicating pathologies, such as infections, rheumatic diseases, tumours, and fractures were excluded. A complete summary of excluded pathologies can be seen in Appendix 3.

After the removal of duplicates, two authors screened the titles and abstracts independently. The included articles were discussed among the authors according to relevance, data extraction, and quality. Dissents were solved by consensus. This was followed by a handsearch.

Clinical guideline selection

All clinical guidelines listed in the most recent review of LBP guidelines [1] written in English or German language were reviewed to find recommendations regarding extravertebral LBP.

Data extraction

Descriptive characteristics were extracted from each manuscript, including, author’s name(s), year of publication, country, study design and setting. Depending on the type of publication, further data was extracted.

For case reports and case series, extracted data included participant characteristics (sample size, sex, age, and co-morbidities), pain characteristics (acute vs chronic LBP, pain description, neurological and other symptoms), diagnostic characteristics (laboratory results, imaging, biopsy/other diagnostic, diagnostic confirmation, and physical examination) and differential diagnosis.

For case-control or cohort studies, the following data were extracted: data collection (retrospective/prospective), inclusion criteria, baseline, follow-up, LBP (acute/chronic), other symptoms, pain description, differential diagnosis and other information (e.g., epidemiological information, risk factors, and physical examination findings).

For reviews encompassing LBP in general, the following data points were extracted: classification, terminology, causes, estimated prevalence, symptoms pointing toward a non-spinal pathology, diagnostic values (e.g., patient history, physical examination, laboratory results, and imaging) and whether Weinstein and Deyo 2001 was cited or not. If specific pathologies were mentioned, only unique information about LBP associated with those diseases were extracted.

Results

After elimination of duplicates and resolving disagreement between the reviewers, a total of 4105 manuscripts were screened. Additionally, a handsearch was carried out and a further 197 manuscripts were included in the review (Fig. 2), thereby bring the total number of manuscripts included in this review to 462. Various extravertebral causes of LBP were identified and are illustrated in Fig. 3.

Fig. 3

Overview: causes of extravertebral low back pain organised by pathologies. AAA = abdominal aortic aneurysm. LBP = low back pain. UTI = urinary tract infection

Description of studies

Case reports and case series

Various case reports mentioned LBP as part of the clinical presentation, but it often remained unclear, if LBP was the chief complaint. Case reports, where back pain was mentioned but no connection to the final diagnosis could be made or it seemed that back pain was a coincidence, were excluded. None of the case reports claimed adherence to the standards of reporting from CARE [40].

Case control and cohort studies

Only a few case-control or cohort studies were included. In these studies, various diseases, their therapies, and diagnostic methods were examined. If LBP was reported, comparisons were often made between pre- and post-interventional symptoms to draw conclusions regarding the association between pathology and LBP.

Narrative and systematic reviews

The content of narrative or systematic reviews often dealt with low back pain in general or in association with other pathologies, where LBP was a reported symptom. Reviews of other pathologies often omitted information regarding duration or localisation of LBP, while frequently including associated symptoms.

Guidelines

The included guidelines were examined with regards to the recommendations for dealing with extravertebral low back pain.

Results of the guideline review

Guidelines featured in the latest review of clinical practice guidelines on LBP were examined by Oliveira et al. 2018 [41]. They presented a total of 15 guidelines across various countries, of which 11 guidelines available in German or English were reviewed. Four guidelines mentioned extravertebral, non-vertebral, or systemic causes of LBP. One guideline reported that an “alternative diagnosis” should be considered [42]. The rest did not mention the possibility of an extravertebral origin of low back pain.

Results organised by pathology

Systemic diseases

Spinal gout

Gout is a systemic disease where monosodium urate crystal deposit in various joints, such as, facet, sacroiliac or interverbal joints as well as discs. Rheumatic diseases are pathologies indicated by red flags and usually refer to axial spondyloarthropathies excluding gout. Spinal or axial gout was first described in 1950 [43]. Since then, several case reports and case series have been published (Table 1). Toprover et al. published a review of 131 cases of spinal gout. We decided to disregard all case reports featured in their review in Table 1 [30, 44,45,46,47,48,49,50,51,52]. Furthermore, many of them were not within the time frame of this review. The majority (roughly 75%) had a history of gout. It is frequently concluded that axial gout is more common than assumed. However, no conclusions about the prevalence of axial gout can be drawn from the case reports and case series. The case series reveal a prevailing trend wherein a significant number of patients with axial gout have a confirmed diagnosis of gout, frequently accompanied by the presence of peripheral tophi. In most cases, the diagnosis was confirmed through intraoperative biopsies or fluoroscopy [43]. The case series conducted by de Mello et al. [53], stands out due to its investigation of spinal computed tomography (CT) scans in individuals who had a confirmed diagnosis of gout. Possible evidence of axial gout was found in 12/42 (29%) and peripheral tophi were associated with CT-findings suggestive for gout. The findings were not associated with current pain. Therefore, the claim that spinal gout is more frequent than assumed is weak, assuming that despite radiological findings, many patients with urate deposition in the spine are asymptomatic.

Table 1 Case reports of gout presenting with low back pain

Pseudogout

Pseudogout is a rare disease with calcium-pyrophosphate deposition, which can affect any joint, including facet joints, causing inflammatory arthritis. Five case reports and case series of pseudogout presenting with low back pain (Table 2) were included. Symptoms are non-specific and diagnosis is usually made incidentally due to suspicious findings leading to operative exploration with biopsies. Only one patient had a history of pseudogout.

Table 2 Case reports or case series of pseudogout presenting with low back pain

Skeletal fluorosis

Two case reports were identified where the diagnosis of skeletal fluorosis, contributing to the onset of chronic metabolic bone disease, was associated with chronic LBP (Table 3). Skeletal fluorosis is a rare disease caused by increased ingestion of fluoride. It is endemic in some parts of Asia (e.g., China, India), where elevated fluoride concentrations are found in soil and water. Industrial exposure, accidental ingestion of fluoride containing medication or toothpaste and substance abuse are other possible causes. Mottling of teeth is a clinical sign of excessive exposure to fluoride as an infant. The condition is typically diagnosed incidentally based on osteosclerosis and ligamentous calcification on X-ray. There is no established treatment.

Table 3 Case reports of skeletal fluorosis presenting with low back pain

Spinal sarcoidosis

Sarcoidosis is a multisystem granulomatous disease, which most commonly affects the lung. It is estimated that 1-3% of patients with sarcoidosis have some form of osseous disease, which is mostly asymptomatic. A total of 6 case reports highlighting spinal sarcoidosis associated with LBP were included (Table 4). Back pain can be caused by either spinal osseous involvement or medullary disease. Improvement following treatment, e.g., with corticosteroids, has been reported. In some patients, the diagnosis of sarcoidosis was pre-existing, while in other cases, suspicious findings on magnetic resonance imaging (MRI) prompted bone biopsies that lead to diagnosis [68, 69]. The radiological findings, however, lack specificity. Given the array of potential differential diagnoses encompassing osseous metastasis, myeloma, lymphoma, tuberculosis, and osteomyelitis, the verification of the diagnosis primarily relied on bone biopsy. No discernible clinical clue beyond a pre-existing diagnosis of sarcoidosis were evident.

Table 4 Case reports of sarcoidosis presenting with low back pain

Hyperparathyroidism

Hyperparathyroidism is another rare condition that can arise from either primary origin, such as, adenomas (and rarely carcinomas), or as a secondary manifestation of end stage kidney disease (ESKD). Presenting complaints typically include general and non-specific symptoms such as weakness, thirst, polyuria, weight loss, and musculoskeletal pain. Only five case reports describing hyperparathyroidism as a cause of LBP were found and included (Table 5). Up to 3% of individuals with hyperparathyroidism will develop brown tumours (osteitis fibrosa cystica), which are neoplastic and can cause LPB and neurological symptoms due to compression if located in the spine. The presence of the mass lesion is typically identified through imaging as a consequence of neurological symptoms [74]. Symptoms suggesting the need to consider hyperparathyroidism in the differential diagnosis include a patient’s previous history of urolithiasis and ESKD in the context of chronic LBP. The diagnosis is likely with elevated serum calcium and alkaline phosphatase, low serum level of phosphate and confirmed by measuring serum hyperparathyroid hormone.

Table 5 Case reports and reviews of hyperparathyroidism presenting with low back pain

Vitamin D deficiency / insufficiency

Osteomalacia arises from a deficiency in vitamin D, an essential substance for maintaining bone health, consequently leading to the manifestation of LBP [79]. However, most people with low 25-hydroxyvitamin (25-OH) D3 (calcidiol) level do not develop osteomalacia. A connection between low calcidiol and LBP was initially made by Al Faraj et al. [80], in an observational study, which subsequently resulted in numerous studies (Table 6). The documented deficiency of calcidiol in 83% of individuals experiencing lower back pain (LBP), along with the observed cessation of LBP in all patients with low levels following supplementation within an unspecified time frame, prompted the initiation of cross-sectional and case-control studies into the potential correlation between LBP and vitamin D insufficiency or deficiency. (Table 6). Most studies, except one [81], concluded that vitamin D deficiency was contributing to LBP and even recommended screening patients with chronic LBP. However, no specific symptoms, which could help to identify patients with vitamin D deficiency, were described. Additionally, the definitions of vitamin D deficiency or insufficiency were heterogenous. A Cochrane review on the effectiveness of vitamin D for chronic pain, including LBP, found no consistent evidence for the effectiveness of vitamin D substitution [82].

Table 6 Studies reporting on vitamin D and low back pain

Ochronosis / Alkaptonuria

Ochronosis, also known as alkaptonuria, is a rare autosomal recessive genetic disorder leading to accumulation of homogentisic acid in the body. Ochronotic arthritis gives rise to chronic back pain typically occurring during the fourth and fifth decade of life, mimicking ankylosing spondylitis including the marked spine stiffness. However, this condition commonly extends its involvement to other joints as well. A total of 12 case reports were found, all focussing on chronic LBP (Table 7). Diagnostic signs, such as pigmentation of the sclera and ear, and darkening of morning urine, were not always present. Intervertebral disc calcification on imaging can be considered pathognomonic and was observed in all case reports. The diagnosis was confirmed with measurement of homogentisic acid in the urine or sometimes from specimens obtained during surgery [87,88,89]. Only a few patients had been previously diagnosed during childhood, and one patient received a diagnosis during prior surgery.

Table 7 Case reports^a of ochronosis presenting with chronic low back pain

Vascular diseases - arterial

Abdominal aortic aneurysm

An aneurysm is an outward bulging of the vessel wall usually caused by wall weakness. Most aneurysms develop slowly and are initially asymptomatic. Symptoms of abdominal aortic aneurysm (AAA), such as LBP and abdominal pain, can vary depending on the location and type, i.e., acute versus chronic contained ruptured. Several case reports, three cohort studies and nine narrative reviews were identified documenting AAA featuring LBP within the clinical manifestation (Table 8). Mainly middle-aged to older male individuals were affected. Initially 8-18 % of non-inflammatory AAA are symptomatic, while patients with inflammatory AAA exhibit symptoms in 65 to 90% of cases [97]. The majority of symptomatic patients report chronic LBP, occasionally characterised by a progressive exacerbation. Acute or subacute back pain presentations are also possible. The presence of LBP as part of the clinical presentation of an AAA ranged from 32% [98] to 72% [99]. The co-occurrence of LBP and abdominal pain was 29.4% [100]. Furthermore, abdominal pain and a pulsatile abdominal mass in patients with LBP were indicative of the presence of an abdominal aortic aneurysm [97, 99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123]. The presence of the complete triad of LBP or abdominal pain with hypotension and a pulsatile abdominal mass is rather low at 21% [100] and usually observed during rupture [117, 118, 124]. In some cases, history of smoking was reported [97, 102,103,104, 106, 108, 110, 111, 115, 117, 119, 121,122,123, 125,126,127,128,129,130,131,132]. Other common risk factors are atherosclerotic disease, hypertension, positive family history for AAA and other aneurysms, collagen vascular disease and Marfan and Ehlers-Danlos-syndromes [106, 117, 119, 121,122,123, 133].

Table 8 Abdominal aortic aneurysm presenting with back pain

In summary, in middle-aged and elderly males with chronic back pain and a pulsatile mass, abdominal pain, or other present risk factors, an AAA should be considered. The median time to diagnosis of an AAA is 7.3 years [99], with imaging studies (CT, MRI) typically used to confirm the diagnosis. In patients presenting with LBP as chief complaint and without other accompanying symptoms, an AAA is usually an incidental finding in lumbar radiographs [124]. Subsequent differential diagnoses include spinal tumours, metastasis, retroperitoneal tumours, iliopsoas muscle abscess, rheumatoid arthritis, osteoporosis and osteomalacia [103], especially when AAA leads to vertebral erosion.

Other aneurysms

A total of twelve case reports and a cohort study revealed instances of patients with aneurysms in locations other than the abdominal artery experiencing LBP as part of their clinical presentation (Table 9). Visceral artery aneurysms, for example, account for 1-2 % of non-aortic aneurysms. Of these, 60% affect the splenic artery [152]. Here, LBP was mostly described as acute pain [25, 153,154,155,156,157,158,159]. Extraspinal symptoms varied depending on the location of the aneurysm. For example, a splenic artery aneurysm showed gastrointestinal symptoms [152], while an aneurysm of the artery of Adamkiewicz showed neurological/vegetative symptoms [153]. The aetiology of non-aortic aneurysms is diverse and also includes infections, such as Takayasu arteritis, albeit rarely [154]. Moreover, additional underlying diseases can further contribute. For example, the majority of intercostal artery aneurysms arise in association with neurofibromatosis.

Table 9 Other aneurysms presenting with back pain

Acute aortic syndrome

The acute aortic syndrome includes pathologies, such as aortic dissection (AD), intramural haematoma (IMH), and penetrating aortic ulcer (PAU). An aortic dissection is a tear in the inner wall of the aorta, which is potentially life-threatening and often occurs in patients with underlying diseases that weaken the aortic wall, e.g., hypertension, atherosclerosis, and AAA. A distinction is made between type A und type B dissection. Type A is a proximal aortic dissection involving the ascending aorta, while type B affects the descending aorta. The IMH is an atypical aortic dissection and characterised by bleeding into the aortic wall without an intimal tear. A PAU is an ulcerative defect of the intima of the aorta, which breaks through the internal membrane into the tunica media. Acute aortic syndromes usually present with sudden onset of symptoms, like devastating chest pain, which can radiate into the back, including the lower back, and mainly affect middle-aged men. Eleven case reports, two case series, ten cohort studies, nine register studies, a chart review study, an interventional study, thirteen narrative and one systematic review have documented acute aortic syndrome concomitant with LBP (Table 10). Wu et al. published a systematic review and meta-analysis which examines various studies on acute aortic syndrome (partly included in Table 10), where the incidence of back pain varies greatly between 10 % and 75% [164]. Most patients present with a sudden onset of acute severe LBP (pain scale: 7/10, [165]). Possible accompanying symptoms are chest discomfort, abdominal pain, nausea/vomiting, and dyspnoea [9, 166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204]. To confirm the diagnosis, imaging studies, such as computed tomography angiography (CTA), are used [167, 170, 189, 194, 205,206,207,208].

Table 10 Acute aortic syndrome presenting with back pain

Fistula

A fistula is an uncommon connection between two structures, such as organs or vessels. A total of twelve case reports, five case series, seven cohort studies, a chart review, and nine narrative reviews describing different fistulas (e.g., aorto-enteric, aorto-caval, aorto-venous) presenting with LBP (Table 11) were found. Middle-aged and elderly men were most commonly affected. The aetiology varies greatly depending on the localisation, for example, aorto-enteric fistulas are often (up to 80% [213]) caused by AAAs. LBP is described as a frequently accompanying symptom of fistulas, ranging from 1.7% [214] to 93% [215] of affected patients. Accompanying symptoms depend on the structures affected and can include abdominal pain or vomiting [118, 120, 213, 216,217,218,219]. Neurological symptoms like paraplegia and sensory disorders can also occur, especially when it is an aorto-venous fistula affecting the spine. The diagnosis is made incidentally during imaging studies especially when patients present with marked symptoms. CT is often used initially [118, 120, 216, 217, 219,220,221,222,223,224,225,226,227,228], followed by other possible imaging methods such as duplex sonography, MRI, and digital subtraction angiography (DSA). In some cases, surgery was necessary for diagnosis [215, 221, 229].

Table 11 Vascular fistulas presenting with back pain

Miscellaneous

Six case reports, one cohort study and two narrative reviews reporting miscellaneous vascular disorders presenting with LBP, e.g., aortic thrombosis or coronary artery dissection, were found (Table 12). These disorders commonly present with acute LBP [168, 246,247,248,249,250] with accompanying symptoms like chest discomfort and weakness of lower extremities [227, 247, 251, 252].

Table 12 Miscellaneous vascular disorders presenting with back pain

Vascular diseases – venous

Pathologies within the venous system, such as deep venous thrombosis (DVT) involving the lower extremities or the inferior vena cava (IVC) [253], may present with LBP. Numerous case reports were found, where acute LBP formed a component of the clinical manifestation, frequently co-occurring with symptoms suggestive of DVT like leg swelling and oedema (Table 13). Some patients exhibited a history of DVT or factors that predispose them to venous thrombosis. Within many of the documented case reports, there was an additional observation of stenosis, aplasia, and hypoplasia affecting the IVC. Malformation of the IVC can contribute to LBP through two distinct mechanisms. Firstly, they directly elevate the risk of DVT. Secondly, they might induce engorgement (varicosis) of the epi- and intradural veins surrounding the spinal cord, thereby causing neural compression that results in radicular symptoms even in the absence of a DVT. Despite the identification of a compressing mass prior to surgery in patients with radicular symptoms, the definitive diagnosis of thrombosed or non-thrombosed spinal varices exerting pressure on nerve roots was established intraoperatively. It is estimated that between 1-4% of radicular symptoms are due to vascular compression [254, 255]. Most patients experienced clinical improvement after surgical decompression confirming the cause-and-effect relationship with LBP.

Table 13 Venous diseases associated with low back pain

Ikeda et al. [264], documented a case of pulmonary embolism originating from an IVC calcification, which manifested with symptoms of back and chest pain. However, the specific anatomical site of the back pain was not provided in their report.

Ovarian vein syndrome (OVS) is a rare condition caused by varicose, dilated ovarian veins inducing chronic ureteral obstruction. In one case series, the majority (12/13) of women reported back pain; however, the clinical presentation was dominated by urological symptoms [275].

A completely different venous pathology was described by Kalender et al. [276], who reported the rupture of an iliac vein leading to a retroperitoneal haematoma. The patient presented with LBP associated with abdominal pain [276].

Paraspinal haematoma

Spinal subdural, epidural, or subarachnoid haematomas are infrequent occurrences that can lead to acute spinal cord compression, giving rise to symptoms like radicular syndromes, paraparesis, or cauda equina syndrome (characterised by urinary and faecal incontinence or constipation). A total of 17 case reports or case series depicting paraspinal haematoma-induced LBP were identified (Table 14). They are mostly caused by trauma, lumbar puncture, and spinal surgery, which are beyond the scope of this review. However, they can also manifest spontaneously in individuals with coagulating disorders, oral anticoagulation, underlying vascular malformations (e.g., aneurysms or arteriovenous fistulas), neoplasms, and other vulnerabilities of the vessel walls. It can be assumed that a diagnosis is seldom missed due to the severity of symptoms, which usually prompt the utilisation of advanced imaging techniques that ultimately facilitate accurate diagnosis.

Table 14 Case reports or case series of paraspinal haematoma presenting as back pain

Chronic periaortitis

Retroperitoneal fibrosis

Chronic periaortitis is a term used to describe a group of rare inflammatory diseases, such as retroperitoneal fibrosis (RPF) and inflammatory abdominal aortic aneurysm (IAAA). RPF is characterised by benign proliferation of fibrotic tissue in the retroperitoneal space, which can result in compression of the aorta, sometimes called periaortitis, and the ureters. It is nowadays classified as immunoglobulin G4 (IgG4)-related autoimmune disorder [294]. Multiple case reports or case series and narrative reviews, six cohort studies, one case-control study, one register study, and one randomised controlled trial related to LBP in the context of retroperitoneal fibrosis were identified (Table 15). Due to the location of the fibrotic tissue, certain characteristic symptoms and complications manifest. The predominant initial presenting symptoms typically include LBP accompanied with abdominal pain, with flank pain occasionally reported [294,295,296,297,298,299,300,301,302,303,304,305,306,307,308]. RPF predominantly presents with subacute or chronic back pain, with acute LBP being a rare occurrence. The nature of the pain is typically described as dull [303, 309, 310], but can also be colicky, if complications such as unilateral or bilateral ureteral stenosis develop [303]. The occurrence of LBP in the presence of RPF varies greatly between 10% [311] and 100% [312]. Other accompanying symptoms are malaise, fever, anorexia, weight loss, unilateral or bilateral lower limb oedema, and scrotal swelling [27, 294,295,296,297,298,299,300,301,302,303, 305,306,307,308,309,310,311, 313,314,315,316,317,318,319,320,321,322,323,324,325,326,327,328,329,330,331,332,333,334,335,336,337,338,339,340,341,342,343,344,345,346,347,348,349,350,351,352]. The patients in the case reports and case series were mostly men aged 40 to 60 years. Confirmation of the diagnosis primarily relied upon biopsies or imaging studies with a reported diagnostic delay between 7 weeks and 16 months [300, 353].

Table 15 Retroperitoneal fibrosis presenting with back pain

Inflammatory abdominal aortic aneurysm

Inflammatory abdominal aortic aneurysms represent a subtype of aortic aneurysm characterised by the thickening of the aortic wall and periaortic tissue, occasionally involving fibrotic remodelling. A total of two case reports, one case-control study, one cohort study, and two narrative reviews pertaining to IAAA linked with LBP were identified (Table 16). The incidence of LBP varies between 58% [364] and 80% [365]. Predominantly, it presents as chronic LBP, often accompanied by typical symptoms such as anorexia, fatigue, night sweats, nausea and vomiting [97, 111, 121, 365, 366] or lower abdominal pain [111, 121, 365, 366]. While the two case reports centred around female individuals, findings from the case control and case cohort studies indicated a higher prevalence among males. The typical age of onset ranged from 50 to 70 years. Notably, the narrative review highlighted that IAAAs constitute 2-10% of all AAAs [366]. This review further underscored the tendency for IAAA patients to exhibit a younger age profile compared to those with an AAA [121].

Table 16 Inflammatory abdominal aortic aneurysms presenting with back pain

Myocardial infarction

One case report, two case series, one chart review study, and two observational studies documenting instances of myocardial infarction presenting with back pain were identified (Table 17). The exact location of back pain was often not reported. In one case report, one of the patients presented with increasing back pain over a two-day period. Despite being in shock at admission, the initial presenting symptom was back pain [367]. An observational study indicated a higher prevalence of back pain as a symptom of myocardial infarction in women compared to men, whereas men typically presented more frequently with chest pain. Other accompanying symptoms were, for example, chest pain or discomfort, shoulder pain, cold sweat, or nausea [368,369,370,371,372].

Table 17 Myocardial infarction presenting with back pain

Gastrointestinal diseases

Gallstone disease / cholecystitis

Gallstone disease and cholecystitis usually present with colicky upper abdominal pain. Two case reports and one randomised controlled trial (RCT) investigating LBP as an initial complaint associated with gallstone disease or cholecystitis were identified (Table 18). The RCT compared two treatment strategies for managing gallstone disease and reported baseline symptoms encompassing pain radiating to the back. Among the case reports, one focussed on cholecystitis [373], while the other delved into symptomatic cholecystolithiasis [374], both involving female patients. LBP can present both acutely (particularly with inflammation) [373] as well as chronically (with symptomatic cholecystolithiasis without inflammation) [374]. Accompanying symptoms often comprise abdominal pain [373, 374], predominantly localised in the right upper quadrant or epigastric region [375]. Other symptoms include gastrointestinal symptoms such as fat intolerance, nausea and vomiting, diarrhoea, and difficulty in defecation [375].

Table 18 Gallstone disease / cholecystitis presenting with back pain

Pancreatitis

Pancreatitis, an inflammatory condition of the pancreas, can either manifest acutely or chronically. Two case reports, one narrative review and one guideline were found detailing LBP as presenting symptom attributed to pancreatitis (Table 19). Accompanying symptoms were abdominal pain, loss of appetite and weight, or jaundice [376,377,378,379]. Furthermore, one narrative review [378] was identified, outlining back pain as radiating pain originating from the epigastric region.

Table 19 Pancreatitis presenting with back pain

Miscellaneous

Five case reports featuring different gastrointestinal diseases as the primary presentation of LBP were identified (Table 20). These include intussusception [23], coeliac disease [380], pyeloduodenal fistula [381], liver abscess [34], and acute appendicitis [382]. While LBP predominantly presents acutely [34, 381, 382], it could also manifest chronically, as observed in coeliac disease [380]. Depending on the disease, accompanying symptoms such as occasional fever with nausea and diarrhoea (intussusception) [23] or weight loss (coeliac disease) [380, 382] indicated an extravertebral origin of LBP. However, the patient with the liver abscess presented solely with acute LBP [34]. Diagnosis was confirmed either by imaging [23, 34, 381, 382] or biopsy [380, 382].

Table 20 Miscellaneous gastrointestinal diseases presenting with back pain

Paraspinal compartment syndrome

Compartment syndrome, marked by fluid accumulation in a muscle compartment leading to increased pressure and compromised blood supply, predominantly affects the lower leg but can involve other muscle groups, including paraspinal muscles. Identified were ten case reports and one narrative review reporting instances of paraspinal compartment syndrome in individuals presenting with acute LBP (Table 21). Across all case reports, only males were affected. The pain was described as abrupt, severe, sharp, throbbing, constant, or exacerbated by movement [22, 29, 383,384,385,386,387,388,389,390]. Typical accompanying symptoms were pain radiating into the leg and groin, numbness, and sensory deficits [22, 29, 256, 383,384,385, 389, 390]. Other extravertebral signs and symptoms were generally absent, aside from occurrences of dark urine due to myoglobinuria [22, 385] or fatigue [389]. Notably, all case reports described symptoms that started after weightlifting or heavy exercising. The review also reported aetiologies such as downhill skiing, surfboarding, or weightlifting, as well as iatrogenic causes like aortic or gastric bypass. An elevated creatine kinase (CK) in patients with LBP is a diagnostic clue for paraspinal compartment syndrome. Diagnosis was confirmed by imaging studies or measurement of intramuscular pressure. Compartment syndrome is an emergency which requires immediate referral when suspected.

Table 21 Paraspinal compartment syndrome presenting with low back pain

Gynaecological diseases

Endometriosis

Endometriosis, a gynaecological disease characterised by the presence of endometrial tissue outside the uterus, predominantly affects women in their childbearing years. Given the varying locations of the endometriosis foci, a range of non-specific symptoms, including LBP, can arise. A total of ten case reports, two case series, ten cohort studies, one case-control-study, one cross-sectional study, four narrative and one systematic review were identified (Table 22). The incidence of LBP associated with endometriosis varied greatly from 14.48% [392] to 93.4% [393]. An observational study by Darai et al. [392] suggested a causal relationship between LBP and endometriosis, noting LBP improvement in 55% of women following intervention. However, 18% reported worsening or no change of LBP, indicating that not all reported LBP among endometriosis patients can be directly attributed to endometriosis. Symptoms pointing towards endometriosis were chronic LBP, cyclical LBP, and increasing pain intensity [394,395,396,397,398,399,400]. Furthermore, patients with endometriosis commonly complain of dysmenorrhoea (up to 90% [401]) and dyspareunia (up to 85% [401]). Other accompanying symptoms depend on the localisation of the endometriosis foci and include urological symptoms like dysuria [395, 402,403,404] or gastrointestinal symptoms like rectal bleeding [396], cyclic and non-cyclic dyschezia [402,403,404], and alterations in bowel habits (constipation, diarrhoea) [405,406,407,408,409]. Due to the delay between the onset of symptoms and the diagnosis of endometriosis [399, 400, 410], endometriosis should be considered, especially in young women with chronic low back pain.

Table 22 Endometriosis presenting with back pain

Miscellaneous

Six case reports and one narrative review encompassing various gynaecological diseases, such as benign cystadenoma [422], endosalpingiosis [423, 424], uterine fibroid [425], uterus-like structure of Müllerian origin [426], spinal intradural Müllerianosis [41], retroverted uterus, and tuboovarian abscess [399] associated with LBP, were identified (Table 23). The patients frequently presented with chronic radicular LBP, especially concurrent with the presence of tumorous tissue. Across all identified studies, notable findings during physical examinations included various neurological signs, e.g., decreasing muscular strength [426], tenderness on palpation [423], positive straight leg test [425], or sensory loss [426]. Therefore, when taking a patient’s history, more attention should be directed toward the presence of chronic LBP [41, 422,423,424, 426], occasionally exhibiting cyclical patterns [41, 426], primarily among pre-menopausal women [423, 425, 426]. Ahmad et al. [422] also reported abdominal swelling and pain, indicating that these aspects should also be included in history taking and physical examination as potential accompanying symptoms.

Table 23 Miscellaneous gynaecological diseases presenting with low back pain

The inclusion of ovarian cancer invading the spine within the context of red flags remains uncertain. The Cochrane review addressing screening for malignancy in patients with LBP does not refer to ovarian cancer [36]. While this review omits all forms of cancers, it is important to note that LBP has been documented as a symptom in 23% of ovarian cancer cases [427].

Urological diseases

Urinary tract infection and pyelonephritis

Urinary tract infection (UTI) can cause inflammation in any part of the urogenital tract, such as in the kidney, bladder, ureters, or urethra. It commonly presents with symptoms like painful urination, urinary frequency, and sometimes fever [428]. While cystitis usually presents with exactly these symptoms, pyelonephritis is an inflammatory disease of the kidney, which can also present with LBP. It commonly occurs in middle aged and older women. Three case reports, and one case series describing acute LBP as initial clinical presentation of pyelonephritis were included. Additionally, one case report, one cross-sectional study, and two reviews have expanded upon UTI as a potential cause of LBP (Table 24). Notably, 23.3% of patients diagnosed with pyelonephritis report LBP [428], indicating it as a reliable predictor [429]. In a majority of cases, the LBP can be localised as either left- or right-sided [430]. While UTI can be a cause of LBP, it lacks a significant association [431]. On the other hand, LBP has been identified as a symptom associated with an increased probability of urinary tract infection [432]. This connection is especially pertinent in patients with neurogenic bladder and sensory deficits, where LBP can manifest as a non-specific symptom of UTI [433]. In women presenting with acute LBP alongside accompanying symptoms such as general fatigue, signs of poor health or fever, UTI should be considered as differential diagnosis. Other clinical indicators encompass prior sexual intercourse, recent utilisation of spermicidal products, asymptomatic bacteriuria, or previous history of cystitis [433].

Table 24 Urinary tract infections and pyelonephritis presenting with low back pain

Urinary kidney stone and hydronephrosis

Urinary kidney stones can develop due to various factors, potentially resulting in complications like ureteral obstructions, which can lead to colic and subsequent hydronephrosis. Only one case report was identified, where acute LBP was the leading presenting complaint (Table 25). The individual had a history of urolithiasis a few years ago. Laboratory tests and pyelography were used for definitive diagnosis. The presence of urinary tract symptoms or a history of urolithiasis may serve as clinical clues in patients with acute LBP [437].

Table 25 Urinary kidney stones and hydronephrosis causing low back pain

Hydronephrosis is a disease characterised by renal pelvis expansion resulting from obstructed urinary outflow and subsequent retention. In most cases, it is caused by urinary kidney stones. Two case reports were identified, showing an association between LBP and hydronephrosis (Table 25). The reports detailed exacerbated and chronic LBP, accompanied by neurological symptoms like radicular pain, paraesthesia, and mild limping [33]. Otherwise, there were no other clinical signs or symptoms implicating hydronephrosis as an underlying cause of LBP. Diagnosis frequently occurs incidentally, prompted by imaging studies ordered for evaluation of neurological symptoms.

Prostatic diseases

Prostatic diseases (including prostatitis, prostatic calculi, and cysts) can also present with acute LBP. Five relevant case reports (Table 26) on the subject were identified. Prostatitis can manifest in young males, while prostatic calculi predominantly occur in older male individuals. Clinical clues that point to prostatic pathology as underlying cause for acute LBP are symptoms of urinary tract infections [438], fever, and occasional incontinence [439].

Table 26 Prostatic diseases presenting with low back pain

Renal infarction

Renal infarction can result from an embolism entering the renal vein or artery. A case report documenting LBP as part of the clinical presentation was found (Table 27). Accompanying symptoms were vomiting and chest discomfort. There may be abnormalities seen in the blood test, such as elevated troponin I levels [443, 444].

Table 27 Low back pain in association with renal infarction

Renal ischaemia

Renal ischaemia is a rare condition that can result from various causes, for example, exercising. A case report outlining acute LBP within the context of renal ischaemia was identified (Table 28). Additional symptoms encompassed nausea, vomiting, and abdominal pain [443, 444].

Table 28 Low back pain in association with renal ischaemia

Infected kidney cysts

Kidney cysts, fluid-filled sacs found in kidneys, can vary in size and can be solitary or multiple. In total, three case reports documented instances of acute LBP associated with infected kidney cysts (Table 29). In patients presenting with acute LBP along with symptoms like fever and vomiting [445], kidney cysts should be considered as differential diagnosis. Furthermore, if the patient’s past medical history includes previous kidney diseases, this could serve as a valuable clinical clue.

Table 29 Infected kidney cysts presenting with low back pain

Low back pain

Multiple narrative reviews and one systematic review were identified (Table 30). Major differences emerged regarding the classification of LBP causes and terminology. The most commonly proposed classification systems are based on either mechanical/non-mechanical [3,4,5,6, 8, 10, 12, 448,449,450] or specific/non-specific [37, 451,452,453,454] causes of LBP. In certain instances, degenerative diseases [455, 456] or radiculopathy [12, 13, 16, 449, 453,454,455, 457,458,459] were also designated as major categories. Several classification systems further isolate extravertebral diseases as a distinct class [3,4,5,6, 8, 10, 12, 13, 16, 37, 448,449,450, 454,455,456,457,458,459,460,461]. Various terms have emerged to describe these extravertebral causes, such as visceral diseases, non-spinal diagnoses or aetiologies, medical causes, and referred pain. The lack of a clear definition of extravertebral LBP was also reflected in the listing of various diseases according to the classification system. For example, intestinal infections were included in non-mechanical LBP [4] despite explicit classification of them as an extravertebral cause. Many classification systems adopt the concept of red flags as indications of specific LBP, which generally do not explicitly cover extravertebral pathologies. The most frequently referenced publication regarding extravertebral pathologies was the work by Deyo and Weinstein in 2001 [3]. They estimated a prevalence of 2% for extravertebral LBP without specifying the clinical setting, such as ambulatory care versus emergency room, or providing a data source for this assumption. However, recent research studies have found disparities from this estimate with prevalences ranging from <1% [458] to 10% [8], which can be explained by the assortment of pathologies grouped within the extravertebral LBP category.

Table 30 Publications of low back pain in general

Solely a singular case series involving 95 patients (34.7% female) from Japan presenting themselves at an emergency department (ED) with LBP [469] was identified. Within this group, a total of 66.2% were diagnosed to have a urological disease. Other reported disorders were vascular diseases like AAA or aortic dissection and pancreatitis. In most cases the diagnosis was confirmed by using a CT. However, given that primary care services in Japan are frequently attached to hospitals, the generalisability of this finding is limited.

Miscellaneous

Spinal epidural lipomatosis

Spinal epidural lipomatosis is a rare condition characterised by excessive proliferation of adipose tissue within the epidural space leading to spinal canal stenosis. In total, nine case reports, one case series, one cohort study and one narrative review reporting LBP associated with spinal epidural lipomatosis were identified (Table 31). Predominantly, this condition manifested in middle-aged and older male individuals. An association with elevated body mass index (BMI), previous treatment with corticosteroids or other endocrinological disorders, e.g., Cushing syndrome, is postulated [470]. Due to neurological symptoms, such as limb weakness or numbness [470,471,472,473], an MRI was usually performed, ultimately confirming the diagnosis.

Table 31 Spinal epidural lipomatosis presenting with low back pain^a

Episacral lipoma – Back mice

Back mice are subfascial fat herniations in the back. They are often accompanied by painful swellings, but one case report showed that they can also cause LBP (Table 32). Ultrasound examination is used to confirm the diagnosis.

Table 32 Case reports of back mice presenting with low back pain

Hip pathology

Hip and lumbar spine pathologies often occur in combination and may be difficult to separate [482,483,484]. Pathologies of the lower back, e.g. in the iliosacral joint, or radicular symptoms can present predominantly with hip pain or pain in the thigh. Hip pain was frequently reported in the case reports reviewed, e.g. in systemic diseases affecting the hip and facet joints [88, 91, 92], but it was also part of the presentation in cases involving other organs [23, 380]. On the other hand, hip pathology can lead to LBP. An observational study of 25 patients (32-84 years) with hip and spinal pain showed improvement of back pain following total hip replacement [482]. Limited range of motion of the hip has been observed in patients with chronic LBP compared to healthy individuals, with improvement noted following hip exercise [485]. This is in line with other studies and a recent systematic review, despite low certainty evidence that hip strenghtening can improve LBP [486]. Examination of the hip (forced internal rotation) should be part of the clinical examination in patients presenting with pain radiating into the thigh.

Summary of clinical clues for the diagnosis of extravertebral LBP (Table 33)

Table 33 Summary of clinical clues for the diagnosis of extravertebral low back pain

Discussion

Summary of evidence

It can be difficult to distinguish clinically between vertebral and extravertebral causes of LBP and there is limited research to date. This is further complicated by the wide range of differential diagnoses and the rare incidence of extravertebral disorders that mimic LBP. This scoping review attempts to provide a comprehensive overview of the aetiologies underlying extravertebral LBP, with a particular focus on identifying symptoms indicative of extravertebral pathology. The available body of evidence, largely derived from case reports and retrospective cohort studies, does not allow epidemiological conclusions to be drawn regarding the prevalence of extravertebral LBP. The diagnosis of extravertebral pathology is frequently made incidentally by imaging or intraoperatively. However, as summarised in Table 33, this review has identified clinical signs and symptoms that may facilitate the identification of specific aetiologies of extravertebral LBP.

Interpretation of the results

The large number of case reports highlights the clinical relevance of individuals presenting with LBP ultimately attributed to extravertebral causes. However, the clinical relevance of these reports varies widely, ranging from life-threatening conditions to those of lesser clinical consequence. This variability is not surprising, given the diverse range of extravertebral causes for LBP. Accurately estimating the prevalence of extravertebral LBP proves challenging and most likely depends on the clinical setting. It is reasonable to hypothesise that the prevalence is lower in the primary care setting. Deyo, without providing a specific source, estimated the prevalence at 2 % in primary care [3], a figure that has subsequently been cited in numerous LBP reviews [4, 7,8,9,10,11, 13, 14, 16, 449, 451, 458, 460, 487], albeit this has never been confirmed in an epidemiological study.

Many case reports lack details regarding the clinical setting, but it is reasonable to assume that they predominantly originate from specialist clinics or hospitals, as these comprise the majority of reports. Unfortunately, only a limited number of reports indicated whether patients were referred from primary care and the specific reasons for their referral [54, 137, 211, 229, 263, 274, 279, 297, 374]. It has been suggested that non-mechanical back pain may indicate the possibility of extravertebral LBP [3, 464]. Although this assumption seems plausible, there is currently a lack of empirical evidence to substantiate it. This is consistent with the situation of the “red flags” for specific low back pain, which similarly also lack a solid epidemiological foundation [77, 468, 488].

Retrospective case series focussing on specific pathologies often demonstrate LBP as part of the clinical presentation, as seen, for example, in endometriosis [416, 417] or retroperitoneal fibrosis [294, 300, 304, 320, 322, 323, 326, 327, 330, 333, 334, 353, 361, 362]. The practical utility of these observational studies for the clinician, who frequently encounter LBP, is limited due to the relative rarity of these pathologies in patients presenting with LBP as leading symptom. However, the definitive causal relationship with LBP remains uncertain, and the possibility of coincidence must be considered. Nonetheless, when patients present with an unusual combination of symptoms that deviate from the usual clinical picture, consideration of extravertebral pathologies becomes important. Certain extravertebral pathologies are less likely overlooked, as they present with symptoms such as paraplegia [171, 183, 188, 230, 247, 281], and always warrant advanced imaging or surgical exploration, ultimately leading to the correct diagnosis.

Case reports frequently conclude that especially primary care providers should remain vigilant for specific pathologies in patients presenting with LBP. However, given that LBP is a common reason for consultation and the majority of patients with low back pain do not exhibit serious underlying vertebral or extravertebral pathology, this approach appears impractical. The extensive examinations and test required to cover all potential differentials would exceed what is feasible and reasonable. Therefore, a primary care strategy of watchful waiting seems appropriate in the absence of serious symptoms necessitating urgent investigation.

This scoping review identified two categories of extravertebral back pain, classifying them based on symptoms that led to incidental diagnoses or cases with symptoms prompting clinical suspicion of non-vertebral pathology, such as a pulsatile swelling and AAA [101, 102, 104, 106,107,108,109,110, 115, 127, 131, 147, 149]. This differentiation holds forensic implications when patients litigate against health professional for misdiagnosis. Negligence can only be assumed if the clinical presentation rendered an extravertebral cause of LBP reasonably probable.

The majority of clinical guidelines [1] did not explicitly recommend considering extravertebral causes in the evaluation of low back pain. Based on the findings of this scoping review, it is recommended that the clinical assessment of LBP should incorporate a brief consideration of possible extravertebral causes as a measure to improve patient safety.

Comparison with existing literature

There is limited comprehensive literature on the topic, with the majority of reviews on red flags focussing on spinal pathologies, neglecting extraspinal pathologies [36, 468, 487, 488]. Reviews addressing extravertebral causes tend to be narrative in nature, lacking a systematic literature search dedicated to extravertebral causes [3, 7,8,9,10,11, 13, 14, 37, 449, 451, 458, 460]. Siddiq et al. conducted a focused systematic review on differential diagnosis of sciatica, emphasising musculoskeletal causes, which incidentally identified a few extraspinal causes of sciatica [489]. Maselli et al. provided a more targeted review of red flags in thoracolumbar pain, highlighting myocardial infarction, reflux, and pulmonary disease as important differential diagnosis [35]. Our review, focused on lumbar pain, excluded thoracic pain and treatment complications. The clinical clues for extravertebral LBP identified in our review (Table 33) exhibit limited reliability, akin to “red flags” for spinal pathologies [35, 36, 468, 487, 488].

Strength and limitations

To the best of current knowledge, this scoping review is the first attempt to comprehensively evaluate extravertebral LBP and provide an overview of associated clinical clues (Table 33). A detailed review addressing extravertebral causes that mimic radicular pain, encompassing infectious pathologies and post-injection complications, has already been published and was consequently excluded from this scoping review [489].

Limitations of the review

Clear decisions regarding the inclusion or exclusion of case reports often presented challenges, particularly in distinguishing between “red flag” pathologies and extravertebral diseases. Furthermore, the pragmatic decision to exclude cancers, metastases, and benign tumours from this review was made due to the extensive spectrum of pathologies involved.

Determining whether LBP was the primary complaint in the clinical presentation and differentiating it from related neurological diseases and leg pain was often impossible based on the publications. Despite the focus on low back pain, precise descriptions of the localisation of back pain were frequently absent. Furthermore, given low back pain’s high prevalence and chronic nature, it was not always feasible to differentiate between LBP as an independent condition or as part of the clinical manifestation of an underlying disease. As a result, some of the exclusion decisions may seem arbitrary. Moreover, not all reports provided details on the outcomes following specific interventions.

Complications from prior surgeries, pharmaceutical treatments, invasive or local procedures associated with LBP were excluded, as it was assumed that clinicians assessing the presenting complaint would consider these aspects. It is worth noting that this review’s search was limited to English and German only, therefore potentially introducing language bias. However, we assume that missing some case reports or case series published in other languages would have minimal impact on the scope of the review. Including those case reports and case series would not allow for a better inference on the epidemiology of extravertebral LBP.

Limitations of the studies

In numerous studies, LBP was mentioned as part of the clinical presentation; however, it was not consistently stated how the reported presence of LBP related to accompanying symptoms. The description of back pain was often inadequate in terms of location (lumbar versus thoracic or cervical pain), duration, and other important clinical circumstances, such as movement-related (mechanical) pain. Although a standard for reporting case reports has been issued [490], we did not attempt a formal quality assessment of the case reports or case series, since the majority of them did not meet the standard set and many of them where published before the CARE guidelines where established.

Some retrospective cohort studies examined the presence of LBP in patients with an established diagnosis, e.g., aortic dissection. From the perspective of clinicians evaluating patients with LBP, this information is of limited value given the epidemiological aspects of LBP. No prospective studies investigating the epidemiology of extra-vertebral pathologies presenting with LBP were found.

Conclusion

The differential diagnosis of extravertebral LBP is extensive. However, it is reasonable to assume that the prevalence is relatively low and varies depending on the clinical setting. It is essential that a distinction is made between two categories of extravertebral LBP: cases where clinical presentation indicates a likely extravertebral cause, and those where extravertebral LBP is diagnosed incidentally, such as through advanced imaging or intraoperatively.

Implication for practice

Extravertebral LBP is often diagnosed incidentally in the absence of symptoms indicative of extravertebral pathologies. However, this review identified symptoms suggestive of possible extravertebral LBP, yet the association is predominantly weak and lacks reliable quantification. Clinicians should therefore consider potential extravertebral causes when evaluating patients with LBP, particularly in instances where LBP appears in combination with atypical symptoms such as abdominal pain or leg swelling, or in patients with demographic characteristics (age and sex) predisposing to specific pathologies.

Implication for research

Given the diverse aetiology and rarity of extravertebral LBP, it is unlikely that more reliable data on its prevalence and presentation will emerge, particularly in primary care settings. In such settings, the prevalence of serious spinal pathologies is already low, and that of extravertebral ones is likely even lower. Therefore, specific settings within specialist care may be more conducive to systematic evaluations for extravertebral LBP. Prospective studies should prioritise reporting on non-spinal pathologies presenting with low back pain. Additionally, case reports and case series should offer a more comprehensive basis for investigating LBP. Moreover, more focused reviews targeting specific pathologies could enhance guidance for clinicians in identifying when to suspect a particular pathology.

Implication for clinical guideline makers

Guidelines on low back pain should address extravertebral causes of LBP beyond the conventional spinal pathologies typically highlighted by “red flags”. Moreover, achieving consensus on the terminology used to denote such causes is imperative. The integration of an evaluative step within the treatment algorithm of LBP guidelines, tailored to assess the potential for extravertebral LBP, could help to improve recognition and management for these conditions.

Appendices

Appendix 1

Table 34 Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist

Appendix 2

Table 35 MeSH-terms for MEDLINE, Embase and Cochrane Library

Appendix 3

Table 36 Excluded pathologies