Standardized Definition of Red Flags in Musculoskeletal Care: A Comprehensive Review of Clinical Practice Guidelines
Abstract
1. Background
2. Methods
2.1. Protocol and Registration
2.2. Inclusion Criteria
- Population: individuals of any age with MSK disorders.
- Concept: systematic reviews of clinical practice guidelines and clinical practice guidelines that explicitly reported a definition of RFs.
- Context: musculoskeletal healthcare settings.
2.3. Exclusion Criteria
2.4. Search Strategy
2.5. Study Selection
2.6. Data Extraction
- Author and year of publication;
- Study design;
- Definitions and application of RFs;
- Any other pertinent information for the analysis.
2.7. Agreement
2.8. Data Synthesis
3. Results
4. Discussion
Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A. String Research Strategies
Appendix A.1. PubMed
Appendix A.2. Web of Science
References
- Andreoletti, F.; Maselli, F.; Storari, L.; Vongher, A.; Erbesato, M.; Testa, M.; Turolla, A. Screening for referral of serious pathology by physical examination tests in patients with back or chest pain: A systematic review. Int. J. Environ. Res. Public Health 2022, 19, 16418. [Google Scholar] [CrossRef] [PubMed]
- Ferrari, A.J.; Santomauro, D.F.; Aali, A.; Abate, Y.H.; Abbafati, C.; Abbastabar, H.; Samar Abd ElHafeez, S.A.; Abdelmasseh, M.; Sherief Abd-Elsalam, S.; Abdollahi, A.; et al. Global burden of disease study 2021: Systematic analysis for 371 diseases and injuries. Lancet 2024, 403, 2133–2161. [Google Scholar] [CrossRef] [PubMed]
- Peterson, S.; Heick, J. Referral decision-making and care continuity in physical therapist practice. Phys. Ther. 2023, 103, pzad030. [Google Scholar] [CrossRef]
- Taylor, A.; Mourad, F.; Kerry, R.; Hutting, N. A guide to cranial nerve testing for musculoskeletal clinicians. J. Man Manip. Ther. 2021, 29, 376–389. [Google Scholar] [CrossRef]
- Babatunde, O.O.; Bishop, A.; Cottrell, E.; Jordan, J.L.; Corp, N.; Humphries, K.; Hadley-Barrows, T.; Huntley, A.L.; van der Windt, D.A. A systematic review and evidence synthesis of non-medical triage, self-referral and direct access services for patients with musculoskeletal pain. PLoS ONE 2020, 15, e0235364. [Google Scholar] [CrossRef]
- Deyo, R.A.; Rainville, J.; Kent, D.L. What can the history and physical examination tell us about low back pain? JAMA 1992, 268, 760–765. [Google Scholar] [CrossRef]
- Bury, T.J.; Stokes, E.K. A global view of direct access and patient self-referral to physical therapy: Implications for the profession. Phys. Ther. 2013, 93, 449–459. [Google Scholar] [CrossRef] [PubMed]
- Finucane, L.M.; Downie, A.; Mercer, C.; Greenhalgh, S.M.; Boissonnault, W.G.; Pool-Goudzwaard, A.L.; Beneciuk, J.M.; Leech, R.L.; Selfe, J. International framework for red flags for potential serious spinal pathologies. J. Orthop. Sports Phys. Ther. 2020, 50, 350–372. [Google Scholar] [CrossRef]
- Maselli, F.; Palladino, M.; Barbari, V.; Storari, L.; Rossettini, G.; Testa, M. The diagnostic value of red flags in thoracolumbar pain: A systematic review. Disabil. Rehabil. 2022, 44, 1190–1206. [Google Scholar] [CrossRef]
- Chartan, C.; Singh, H.; Krishnamurthy, P.; Sur, M.; Meyer, A.; Lutfi, R.; Stark, J.; Thammasitboon, S. Isolating red flags to enhance diagnosis (I-RED): An experimental vignette study. Int. J. Qual. Health Care 2019, 31, G97–G102. [Google Scholar] [CrossRef]
- Cook, C.E.; George, S.Z.; Reiman, M.P. Red flag screening for low back pain: Nothing to see here, move along: A narrative review. Br. J. Sports Med. 2018, 52, 493–496. [Google Scholar] [CrossRef] [PubMed]
- Feller, D.; Chiarotto, A.; Koes, B.; Maselli, F.; Mourad, F. Red flags for potential serious pathologies in people with neck pain: A systematic review of clinical practice guidelines. Arch. Physiother. 2024, 14, 105–115. [Google Scholar] [CrossRef] [PubMed]
- Gallotti, M.; Campagnola, B.; Cocchieri, A.; Mourad, F.; Heick, J.D.; Maselli, F. Effectiveness and consequences of direct access in physiotherapy: A systematic review. J. Clin. Med. 2023, 12, 5832. [Google Scholar] [CrossRef] [PubMed]
- Aromataris, E.; Lockwood, C.; Porritt, K.; Pilla, B.; Jordan, Z. (Eds.) JBI Manual for Evidence Synthesis; JBI: Adelaide, Australia, 2024. [Google Scholar] [CrossRef]
- Ouzzani, M.; Hammady, H.; Fedorowicz, Z.; Elmagarmid, A. Rayyan-a web and mobile app for systematic reviews. Syst. Rev. 2016, 5, 210. [Google Scholar] [CrossRef]
- Altman, D.G. Practical Statistics for Medical Research, 1st ed.; Chapman and Hall: London, UK, 1991. [Google Scholar]
- Ladeira, C.E. Evidence based practice guidelines for management of low back pain: Physical therapy implications. Braz. J. Phys. Ther. 2011, 15, 190–199. [Google Scholar] [CrossRef]
- Côté, P.; Wong, J.J.; Sutton, D.; Shearer, H.M.; Mior, S.; Randhawa, K.; Ameis, A.; Carroll, L.J.; Nordin, M.; Yu, H.; et al. Management of neck pain and associated disorders: A clinical practice guideline from the OPTIMa Collaboration. Eur. Spine J. 2016, 25, 2000–2022. [Google Scholar] [CrossRef]
- Dowson, A.J.; Lipscombe, S.; Sender, J.; Rees, T.; Watson, D. New guidelines for the management of migraine in primary care. Curr. Med. Res. Opin. 2002, 18, 414–439. [Google Scholar] [CrossRef]
- Enseki, K.; Harris-Hayes, M.; White, D.M.; Cibulka, M.T.; Woehrle, J.; Fagerson, T.L.; Clohisy, J.C. Nonarthritic hip joint pain: Clinical practice guidelines linked to the ICF from the Orthopaedic Section of the APTA. J. Orthop. Sports Phys. Ther. 2014, 44, A1–A32. [Google Scholar] [CrossRef]
- Peter, W.F.H.; van der Wees, P.J.; Huisstede, B.M.A.; Nijhuis-van der Sanden, M.W.G.; Dekker, J. Physiotherapy in hip and knee osteoarthritis: Development of a practice guideline. Acta Reumatol. Port. 2011, 36, 268–281. [Google Scholar]
- Hurkmans, E.J.; van der Giesen, F.J.; Vliet Vlieland, T.P.M.; Schoones, J.W.; Van den Ende, C.H.M. Physiotherapy in rheumatoid arthritis: Development of a practice guideline. Acta Reumatol. Port. 2011, 36, 146–158. [Google Scholar]
- Van Wambeke, P.; Desomer, A.; Jonckheer, P.; Depreitere, B. Belgian national guideline on low back pain and radicular pain. Eur. J. Phys. Rehabil. Med. 2020, 56, 220–227. [Google Scholar] [CrossRef] [PubMed]
- Verhagen, A.P.; Downie, A.; Popal, N.; Maher, C.; Koes, B.W. Red flags presented in current low back pain guidelines: A review. Eur. Spine J. 2016, 25, 2788–2802. [Google Scholar] [CrossRef] [PubMed]
- Verhagen, A.P.; Downie, A.; Maher, C.G.; Koes, B.W. Most red flags for malignancy in low back pain guidelines lack empirical support: A systematic review. Pain 2017, 158, 1860–1868. [Google Scholar] [CrossRef]
- O’Connell, N.E.; Cook, C.E.; Wand, B.M.; Ward, S.P. Clinical guidelines for low back pain: Inconsistencies across major guidelines. Best Pract. Res. Clin. Rheumatol. 2016, 30, 968–980. [Google Scholar] [CrossRef]
- Bier, J.D.; Scholten-Peeters, W.G.; Staal, J.B.; Pool, J.; van Tulder, M.W.; Beekman, E.; Knoop, J.; Meerhoff, G.; Verhagen, A.P. Clinical practice guideline for physical therapy assessment and treatment in patients with nonspecific neck pain. Phys. Ther. 2018, 98, 162. [Google Scholar] [CrossRef] [PubMed]
- Parreira, P.C.S.; Maher, C.G.; Traeger, A.C.; Hancock, M.J.; Downie, A.; Koes, B.W.; Ferreira, M.L. Evaluation of guideline-endorsed red flags to screen for fracture in patients with low back pain. Br. J. Sports Med. 2019, 53, 488–493. [Google Scholar] [CrossRef]
- Bussières, A.E.; Stewart, G.; Al-Zoubi, F.; Decina, P.; Descarreaux, M.; Haskett, D.; Hincapié, C.; Pagé, I.; Passmore, S.; Srbely, J.; et al. Spinal manipulative therapy and other conservative treatments for low back pain: A guideline from the Canadian Chiropractic Guideline Initiative. J. Manip. Physiol. Ther. 2018, 41, 265–293. [Google Scholar] [CrossRef]
- Standards of Physical Therapy Practice. 2011. Available online: www.world.physio (accessed on 3 December 2024).
- Murad, M.H.; Asi, N.; Alsawas, M.; Alahdab, F. New evidence pyramid. Evid. Based Med. 2016, 21, 125–127. [Google Scholar] [CrossRef]
- Rushton, A.; Carlesso, L.C.; Flynn, T.; Hing, W.A.; Rubinstein, S.M.; Vogel, S.; Kerry, R. Position Statement: International Framework for Examination of the Cervical Region for potential of vascular pathologies of the neck prior to Musculoskeletal Intervention: International IFOMPT Cervical Framework. J. Orthop. Sports Phys. Ther. 2022, 53, 1–62. [Google Scholar]
- Henschke, N.; Maher, C.G.; Ostelo, R.W.J.G.; de Vet, H.C.W.; Macaskill, P.; Irwig, L. Red flags to screen for malignancy in patients with low-back pain. Cochrane Database Syst. Rev. 2013, 2013, CD008686. [Google Scholar] [CrossRef]
- Han, C.S.; Hancock, M.J.; Downie, A.; Jarvik, J.G.; Koes, B.W.; Machado, G.C.; Verhagen, A.P.; Williams, C.M.; Chen, Q.; Maher, C.G. Red flags to screen for vertebral fracture in people presenting with low back pain. In Cochrane Database of Systematic Reviews; John Wiley and Sons Ltd.: Hoboken, NJ, USA, 2023; Volume 2023. [Google Scholar] [CrossRef]
- Williams, C.M.; Henschke, N.; Maher, C.G.; van Tulder, M.W.; Koes, B.W.; Macaskill, P.; Irwig, L. Red flags to screen for vertebral fracture in patients with low-back pain. Cochrane Database Syst. Rev. 2013, 2013, CD008643. [Google Scholar] [CrossRef] [PubMed]
- Maselli, F.; Testa, M. Superficial peroneal nerve schwannoma presenting as lumbar radicular syndrome in a non-competitive runner. J. Back Musculoskelet. Rehabil. 2019, 32, 361–365. [Google Scholar] [CrossRef] [PubMed]
- Ramanayake, R.P.J.; Basnayake, B.M.T.K. Evaluation of red flags minimizes missing serious diseases in primary care. J. Family Med. Prim Care. 2018, 7, 315. [Google Scholar] [CrossRef]
- Ross, M.D.; Boissonnault, W.G. Red flags: To screen or not to screen? J. Orthop. Sports Phys. Ther. 2010, 40, 682–684. [Google Scholar] [CrossRef] [PubMed]
- Mourad, F.; Giudice, A.; Maritati, G.; Maselli, F.; Kranenburg, R.; Taylor, A.; Kerry, R.; Hutting, N. A guide to identify cervical autonomic dysfunctions (and associated conditions) in patients with musculoskeletal disorders in physical therapy practice. Braz. J. Phys. Ther. 2023, 27, 100495. [Google Scholar] [CrossRef]
- Feller, D.; Giudice, A.; Faletra, A.; Salomon, M.; Galeno, E.; Rossettini, G.; Brindisino, F.; Maselli, F.; Hutting, N.; Mourad, F. Identifying peripheral arterial diseases or flow limitations of the lower limb: Important aspects for cardiovascular screening for referral in physiotherapy. Musculoskelet Sci. Pract. 2022, 61, 102611. [Google Scholar] [CrossRef]
Title | Year | Authors | Journal | Study Design | RF Definition |
---|---|---|---|---|---|
Clinical guidelines for low back pain: A critical review of consensus and inconsistencies across three major guidelines | 2016 | O’Connell, N.E. and Cook, C.E. and Wand, B.M. and Ward, S.P. [26] | Best Practice and Research: Clinical Rheumatology | Review of clinical practice guidelines | “All three guidelines recommended consideration of potential alternative diagnoses such as specific spinal pathologies…” “…none of the guidelines provide notable detail on the best methods for screening. This reflects a broader inconsistency in the specific detail for red flag screening advocated across guidelines for LBP” “…the Canadian guideline specifies a list of specific indications for MRI including major or progressive neurologic deficit, suspected cauda equina syndrome, progressive severe pain and debility despite non-interventional therapy, severe or incapacitating back or leg pain, and clinical or radiological suspicion of neoplasm or infection”. |
Clinical practice guideline for physical therapy assessment and treatment in patients with nonspecific neck pain | 2018 | Bier, J.D. and Scholten-Peeters, W.G.M. and Staal, J.B. and Pool, J. and van Tulder, M.W. and Beekman, E. and Knoop, J. and Meerhoff, G. and Verhagen, A.P. [27] | Physical Therapy | Clinical practice guideline | “Red flags are patterns of sign or symptoms (warning signs) that may indicate serious pathology requiring further medical diagnostics. Red flags may indicate a specific pathology, such as neck pain grade IV” “If RFs are present and not explicable by a known pattern of neck pain, then the patient must be refered” “The evidence supporting the RF for neck is weak and inconsistent because many RF are rather generic (such as enexplained weight loss) and have high false positivity rates”. “RFs are indicators for serious pathological conditions. These conditions include fracture, vertebral artery dissection, spinal cord injury, carvical myelopathy, infection, neoplasm and systemic disease”. |
Evaluation of guideline-endorsed red flags to screen for fracture in patients presenting with low back pain | 2019 | Parreira, P.C.S. and Maher, C.G. and Traeger, A.C. and Hancock, M.J. and Downie, A. and Koes, B.W. and Ferreira, M.L. [28] | British Journal of Sports Medicine | Systematic review of guidelines | The authors describe the use of red flags to identify fractures in LBP citing several examples in the text “Red flags are clinical indicators—signs, symptoms, or patient history factors—that raise suspicion of a serious underlying pathology in patients presenting with low back pain, such as vertebral fracture, malignancy, infection, or inflammatory disease. Their primary purpose is to assist clinicians in identifying individuals who may require further diagnostic evaluation or referral for medical assessment. Commonly endorsed red flags for vertebral fracture include older age, history of significant trauma, prolonged corticosteroid use, and osteoporosis. However, many red flags—such as night pain or female gender—lack robust diagnostic evidence and may lead to unnecessary imaging or false positives when used in isolation. The authors emphasize that combinations of red flags are more diagnostically useful than individual indicators, as the presence of multiple red flags significantly increases the likelihood of serious pathology”. |
Evidence based practice guidelines for management of low back pain: Physical Therapy implications | 2011 | Ladeira, C.E. [17] | Revista Brasileira de Fisioterapia | Systematic Review of guidelines | Red flags were designed to identify patients with LBP associated with specific spine pathologies that require physician specialist referral. Any patient who presented with red flags indicating suspicion of cancer, infection, cauda equina syndrome, spondyloarthritis, spinal fracture, visceral (gastrointestinal and genitourinary) referred pain, and abdominal aortic aneurism need to be sent to a specialist. Red flags for patients with low back pain: cauda equina syndrome: saddle anesthesia or paresthesia, perianal/perineal sensory loss; positive straight leg raise testing, multiple motor deficits; bowel/bladder dysfunction, fecal/urinary incontinence; severe (paralysis rather than paresis) or bilateral neurological compromise. Spinal fracture recent violent trauma (fall from great height, car accident); minor trauma in patients with a history of osteoporosis, older age; structural bone deformity, prolonged corticosteroid use; severe central back pain relieved by lying down. Cancer or infection age above 50 and below 20 years old; constitutional symptoms (e.g., fever, weight loss, chills, malaise); history of cancer (malignancies), thoracic spine pain; recent bacterial infection (e.g., urinary tract, respiratory tract); immune depression (e.g., HIV *, chemotherapy), intravenous drug abuse; prolonged use of corticosteroids, recent puncture wound or surgery, diabetes, spinal tenderness to percussion; recent or fast developing spine deformity (e.g., scoliosis); non-mechanical (e.g., not better when lying down) or progressive pain, failure to improve with treatment in 4 to 6 weeks, unremitting night time pain. Abdominal aortic aneurysm age over 60, history of cardiovascular disease (e.g., myocardial infarct or stroke); pulsating mass on the abdomen, leg pain, thoracic pain; absence of aggravating features; spondyloarthritis age less than 45 years old, morning stiffness improved with exercise; alternating buttock pain, significant and persistent lumbar flexion restriction (positive Schober’s test); awakening because of back pain during second part of night; oligoarthritis or polyarthritis, skin rashes, diarrhea, hypersensitivity to NSAIDs *. Gastrointestinal or genitourinary abdominal or flank pain/tenderness, rebound tenderness, costo-vertebral angle tenderness; reduced urine stream, reduced stool caliper, burning during urination, abnormal urine or stool coloration/smell; diarrhea, constipation, anuria, oliguria, polyuria; abnormal menses, dyspareunia, painful erection; patients presenting with cauda equina syndrome and abdominal aortic aneurism required immediate referral and possibly emergency care. Patients with high fever (>38 °C or 100.4 °F) lasting longer than 48 h, progressive neurological signs and symptoms (i.e., paresis to paralysis, peripheralization of pain), or unrelenting night pain not relieved by postural changes required urgent consultation within 24 h. A single red flag (e.g., age over 50) was not enough to indicate specialist referral, but a patient presenting with a cluster of red flags (e.g., age over 50, non-mechanical pain, thoracic spine pain) should definitely be referred for medical consultation. |
Management of neck pain and associated disorders: A clinical practice guideline from the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration | 2016 | Cote, P. et al. [18] | European Spine Journal | Guideline | “Recommendation 1: Clinicians should rule out major structural or other pathologies as the cause of NAD. Evaluation Clinicians should conduct a clinical evaluation to rule out major structural or other pathologies (NAD grade IV) as the cause of signs and symptoms. The Canadian C-spine Rule should be used to rule out cervical spine fractures and dislocations associated with acute trauma. The presence of risk factors for serious pathologies (also termed ‘red flags’) identified during the history/examination warrants further investigation and referral to the appropriate healthcare professional. Clinicians should assess for neurological signs (decreased deep tendon reflexes, muscle weakness, sensory deficits). NAD III refers to neck pain associated with clear clinical evidence of neurologic signs (decreased deep tendon reflexes, weakness, or sensory deficits) on physical examination. Once major pathology has been ruled out, clinicians should classify the grade of NAD as grade I, II, or III; as recent or persistent; and the patient should receive the appropriate evidence-based interventions. Figures 1 and 2 (rule out risk factors for serious pathologies—red flags) and Table 4 (risk factors for serious pathology—red flags) for neck pain): Cancer (history of cancer, unexplained weight loss, nocturnal pain, age > 50 years), vertebral infection (fever, intravenous drug use, recent infection), osteoporotic fractures (history of osteoporosis, use of corticosteroid, older age), traumatic fractures (positive Canadian C-Spine Rule), myelopaty-severe/progressive neurological deficits (painful stiff neck, arm pain and weakness sensory changes in lower extremities, motor weakness and atrophy, hyper-reflexia, spastic gait), carotid/vertebral artery dissection (sudden and intense onset of headache or neck pain), brain hemorrage/mass lesion (sudden and intense onset of headache), inflammatory arthritis (morning stiffness, swelling in multiple joints)”. |
Most red flags for malignancy in low back pain guidelines lack empirical support: A systematic review | 2017 | Verhagen, A.P. and Downie, A. and Maher, C.G. and Koes, B.W. [25] | Pain | Systematic Review of guidelines | We defined red flags as signs or symptoms collected in the clinical assessment signaling underlying serious pathology that requires attention (Merriam-Webster dictionary); Table 1 (number of guidelines endorsing red flag for malignancy for the management of low back pain in primary care): history of malignancy/cancer; unexplained/unintentional) weight loss; atypical pain either increasing at night or at rest or pain at night that is not eased by a prone position (or increasing in supine position); older age; either just older age or more specifically over 50 years; malaise; failure to improve with treatment (>4–6 weeks)/seeking medical care last month; strong clinical suspicion; fever; reduced appetite; rapid fatigue; progressive symptoms; multiple cancer risk factors; paraparesis. Red flags not endorsed in guidelines: duration of the complaint > 1 month; disturbed balance, weakness of limbs. |
New guidelines for the management of migraine in primary care | 2002 | Dowson, A.J. and Lipscombe, S. and Sender, J. and Rees, T. and Watson, D. [19] | Current Medical Research and Opinion | Guideline | “Sinister headache: Primary care physicians need a means of identifying patients with rare or secondary (sinister) headaches who are best referred to a specialist. Has the pattern of your headache changed over the last 6 months? (This is designed to alert the physician to sinister headache conditions. A new or different headache mandates a thorough diagnostic approach, while a stable headache pattern provides reassurance to the physician and patient). Table 1: The exclusion of secondary headaches, by a search for ‘headache alarms’, by history taking or physical examination. Table 2: Sinister headache should be excluded. Sinister headaches tend to appear de novo in young children or mature adults, or present as a change in character compared with older patients’ usual headache attacks. They are new-onset, acute headaches that are associated with a range of other symptoms (e.g., rash, neurological deficit, vomiting and pain or tenderness). Signs of neurological change or deficit do not disappear when the patient is pain-free between headache attacks. They may also be associated with an accident or head injury, infection or hypertension. A full neurological examination is essential if sinister headache is suspected”. |
Nonarthritic hip joint pain: Clinical practice guidelines linked to the international classification of functioning disability and health from the orthopaedic section of the american physical therapy association | 2014 | Enseki, K. and Harris-Hayes, M. and White, D.M. and Cibulka, M.T. and Woehrle, J. and Fagerson, T.L. and Clohisy, J.C. and Godges, J. [20] | Journal of Orthopaedic and Sports Physical Therapy | Clinical Practice Guideline | In the context of clinical practice guidelines for nonarthritic hip joint conditions, the information provided suggests that the authors define a red flag as follows: “Red flag is a clinical indicator suggesting the potential presence of a condition more serious or unrelated to nonarthritic hip joint pain. It should be suspected when the patient’s history, reported activity limitations, or impairments in body function and structure are inconsistent with the typical presentation of nonarthritic hip disorders, or when symptoms do not improve with interventions aimed at normalizing identified impairments. In such cases, clinicians should broaden their diagnostic approach to consider alternative or serious pathologies such as infection, neoplasm, gynecological disorders, stress fractures, or systemic diseases, which require different diagnostic and therapeutic strategies”. |
Physiotherapy in hip and knee osteoarthritis: Development of a practice guideline concerning initial assessment treatment and evaluation | 2011 | Peter, W.F.H. et al. [21] | Acta Reumatologica Portuguesa | Clinical Practice Guideline | In this context, the authors state that a “red flag” “is a clinical sign or symptom that indicates a potentially serious underlying condition requiring immediate attention or referral to a specialist. These signs or symptoms suggest the need for further investigation beyond typical musculoskeletal issues, such as infections, malignancies, or severe joint conditions. Specifically, in the case of hip and knee osteoarthritis patients, red flags include: A warm, swollen (red) knee joint (potential bacterial infection) Swelling in the groin (possible malignancy) Severe blocking of the knee joint (indicating significant joint dysfunction) Physiotherapists are responsible for identifying these red flags during their assessment and referring patients for further medical evaluation as needed”. |
Physiotherapy in rheumatoid arthritis: development of a practice guideline | 2011 | Hurkmans EJ et al. [22] | Acta Reumatologica Portuguesa | Clinical Practice Guideline | In the context of rheumatoid arthritis, the authors defined “red flags” as specific signs and symptoms that indicate a serious underlying condition or complication, potentially requiring urgent medical attention or referral to a specialist. These red flags may signal acute or worsening health issues that go beyond typical RA symptoms, suggesting the need for further evaluation. |
Red flags presented in current low back pain guidelines: a review | 2016 | Verhagen, A.P. and Downie, A. and Popal, N. and Maher, C. and Koes, B.W. [24] | European Spine Journal | Systematic Review of clinical practice guidelines | “To identify and compare the red flag recommendations in current guidelines for the detection of medically serious pathology in patients presenting with low back pain. The authors included 16 discrete guidelines for the management of patients with low back pain in the primary care setting presenting 46 different red flags for the four main categories of serious underlying pathologies (malignancy, fracture, infection and cauda equina syndrome) [1]. Malignancy = History of malignancies/cancer, (Unexplained/unintentional) Weight loss, (Increasing) Pain at night, (Continuous) Pain at rest, Pain at multiple sites, Pain over 1 month (duration), Pain at night that is not eased by a prone position (or increasing in supine position), Failure to improve with treatment (4–6 weeks), Age over 50 years/Old age, Elevated erythrocyte sedimentation (ESR), General malaise, Multiple cancer risk factors, Strong clinical suspicion, Reduced appetite, Rapid fatigue, Progressive symptoms, Fever, Paraparesis, Age over 50 (over 65), first episode of severe back pain and history of cancer/carcinoma in the last 15 years, unexplained weight loss, failure of conservative care (4 weeks) [2]. Fracture = (History of) Major/significant trauma, (Systemic) Use of steroids, Osteoporosis, Female gender, Age over 50/Age over 60/Older age (over 70), Sudden onset (of pain), Loading pain, Minor trauma, Fracture in history/previous fractures, Low body weight, Increased thoracic kyphosis, Structural deformity, Minor trauma (if age over 50, history of osteoporosis and taking corticosteroids), Severe onset of pain (with minor trauma, age over 50, prolonged steroid intake or structural deformity) [3]. Infection = Fever ?38 °C, Use of corticosteroids or immunosuppressant therapy, Intravenous drug abuse/drug addiction, Immunodeficiency/AIDS, Urinary tract infection, Pain with recrudescence at night, Intense night pain (and rest pain), Bone tenderness over the lumbar spinous process, Previous back surgery, Previous bacterial infections, Penetrating wound, Reduced appetite, Rapid fatigue, Impaired immune system, Underlying disease process [4]. Cauda Equina Syndrome (CES) = Saddle anesthesia/perineal numbness, (Sudden onset) Bladder dysfunction (e.g., urinary retention, overflow incontinence), Sphincter disturbance/reduced tonus, Progressive weakness in lower limbs/lower motor neuron weakness (Wide) Spread sensory deficit (in lower limbs), Gait disturbance/abnormality, Fecal incontinence, Pain (radiating) in both legs, Sciatica Red flags unrelated to specific diseases: Pain: Onset of pain <20 or >50 years old, Constant progressive non-mechanical pain, No pain relief with bed rest, Thoracic or abdominal pain, (Continuous) Pain at rest, (Increasing) Pain at night, Pain increase in flexion, Increasing pain despite treatment, Pain at night that is not eased by a prone position (or increasing in supine position); Malignancy: History of malignancies/cancer, (Unexplained/unintentional) Weight loss, General malaise, Elevated erythrocyte sedimentation (ESR), Age over 50 years; Fracture: (History of) Major/significant trauma, (Structural spinal) deformity, (Systemic) Use of steroids, Osteoporosis; Infection: Fever ?38 °C, Intravenous drug abuse/drug addiction, Use of corticosteroids or immunosuppressant therapy, Immunodeficiency/HIV/AIDS; Cauda Equina Syndrome (CES): Saddle anesthesia/perineal numbness, (Sudden onset) Bladder dysfunction (e.g., urinary retention, overflow incontinence), (Wide) Spread sensory deficit (in lower limbs), Progressive weakness in lower limbs/lower motor neuron weakness, Gait disturbance/abnormality; Other: Significant limitation of lumbar flexion, Not flexion of 5th lumbar spine, Morning stiffness”. |
Spinal Manipulative Therapy and Other Conservative Treatments for Low Back Pain: A Guideline From the Canadian Chiropractic Guideline Initiative | 2018 | Bussières, A. E., Stewart, G., Al-Zoubi, F., Decina, P., Descarreaux, M., Haskett, D., Hincapié, C., Pagé, I., Passmore, S., Srbely, J., Stupar, M., Weisberg, J., & Ornelas, J. [29] | Journal of Manipulative and Physiological Therapeutics | Guideline | Signs of serious structural or systemic pathologies: history of malignancy and strong clinical suspicion; older age; Prolonged corticosteroid use (increased risk of vertebral fractures); major or significant trauma (high-impact events); presence of contusion or abrasion. |
The Belgian national guideline on low back pain and radicular pain: Key roles for rehabilitation, assessment of rehabilitation potential and the PRM specialist | 2020 | Van Wambeke, P. and Desomer, A. and Jonckheer, P. and Depreitere, B. [23] | European Journal of Physical and Rehabilitation Medicine | Clinical practice guideline | It is of outmost importance to perform a thorough evaluation of the complaints of the patient each time and exclude signs and/or symptoms of possible serious underlying pathology (identified as red flags) and to focus hereby on clusters of red flags. The actual guideline does not address the further management of these pathologies. |
Red flags for potential serious pathologies in people with neck pain: a systematic review of clinical practice guidelines | 2024 | Feller, D. et al. [12] | Archives of Physiotherapy | Systematic Review of clinical practice guidelines | “Authors identified 29 guidelines in which they found 114 red flags: Fracture (Canadian C-Spine Rule [a clinical decision rule used to determine the need for radiography in patients with neck trauma], history of trauma, history of osteoporosis, use of corticosteroids, older age >50/60); Cancer (history of cancer, unexplained weight loss, age >50/60, failure to improve after one month of conservative care, pain that worsens at night, unrelenting pain, not relieved by rest); Spinal Infection (fever, history of recent infection, immunosuppression, drug use, HIV positivity, night sweats or chills); Myelopathy (spasticity, gait disturbances, clumsiness of hands, hyperreflexia, bowel or bladder dysfunction); Spinal Cord Injury (neurological deficits following trauma); Cervical Artery Dissection (recent neck trauma or sudden neck movement, severe unilateral headache or neck pain, signs of stroke or transient ischemic attack, visual disturbances, dizziness or vertigo, horner’s syndrome); Intracranial Pathology (severe, sudden-onset headache, loss of consciousness, neurological signs like visual loss, diplopia, or cranial nerve dysfunction); Inflammatory Arthritis (swelling in multiple joints, morning stiffness lasting more than 30 min); Other Systemic Diseases (fatigue, general malaise, unexplained fever, skin changes, history of autoimmune disease); Non-specific (General) Red Flag (fever, night pain, pain not mechanical in nature, rapidly progressive symptoms, failure to improve with treatment)”. |
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Storari, L.; Piai, J.; Zitti, M.; Raffaele, G.; Fiorentino, F.; Paciotti, R.; Garzonio, F.; Ganassin, G.; Dunning, J.; Rossettini, G.; et al. Standardized Definition of Red Flags in Musculoskeletal Care: A Comprehensive Review of Clinical Practice Guidelines. Medicina 2025, 61, 1002. https://doi.org/10.3390/medicina61061002
Storari L, Piai J, Zitti M, Raffaele G, Fiorentino F, Paciotti R, Garzonio F, Ganassin G, Dunning J, Rossettini G, et al. Standardized Definition of Red Flags in Musculoskeletal Care: A Comprehensive Review of Clinical Practice Guidelines. Medicina. 2025; 61(6):1002. https://doi.org/10.3390/medicina61061002
Chicago/Turabian StyleStorari, Lorenzo, Jennifer Piai, Mirko Zitti, Graziano Raffaele, Fabio Fiorentino, Rachele Paciotti, Fabiola Garzonio, Giulia Ganassin, James Dunning, Giacomo Rossettini, and et al. 2025. "Standardized Definition of Red Flags in Musculoskeletal Care: A Comprehensive Review of Clinical Practice Guidelines" Medicina 61, no. 6: 1002. https://doi.org/10.3390/medicina61061002
APA StyleStorari, L., Piai, J., Zitti, M., Raffaele, G., Fiorentino, F., Paciotti, R., Garzonio, F., Ganassin, G., Dunning, J., Rossettini, G., Feller, D., Heick, J. D., Mourad, F., & Maselli, F. (2025). Standardized Definition of Red Flags in Musculoskeletal Care: A Comprehensive Review of Clinical Practice Guidelines. Medicina, 61(6), 1002. https://doi.org/10.3390/medicina61061002