ANA testing should not be used to screen subjects without specific symptoms (e.g., photosensitivity, malar rash, symmetrical polyarthritis, etc.) or without a clinical evaluation that may lead to a presumptive diagnosis of SLE or other CTD, since ANA reactivity is present in many non-rheumatic conditions and even in “healthy” control subjects (up to 20%). In a patient with low pre-test probability for ANA-associated rheumatic disease, positive ANA results can be misleading and may precipitate further unnecessary testing, erroneous diagnosis or even inappropriate therapy.
BC Guidelines. Antinuclear antibody (ANA) testing protocol [Internet]. 2013 Jun [cited 2017 May 5].
Kavanaugh A, et al. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med. 2000 Jan;124(1):71-81. PMID: 10629135.
Solomon DH, et al. Evidence-based guidelines for the use of immunologic tests: Antinuclear antibody testing. Arthritis Rheum. 2002 Aug;47(4):434-44. PMID: 12209492.
Tozzoli R, et al. Guidelines for the laboratory use of autoantibody tests in the diagnosis and monitoring of autoimmune rheumatic diseases. Am J Clin Pathol. 2002 Feb;117(2):316-24. PMID: 11863229.
HLA-B27 testing is not useful as a single diagnostic test in a patient with low back pain without further spondyloarthropathy (SpA) signs or symptoms (e.g., inflammatory back pain ≥3 months duration with age of onset <45 years, peripheral synovitis, enthesitis, dactylitis, psoriasis or uveitis) because the diagnosis of spondyloarthropathy in these patients is of low probability. If HLA-B27 is used, at least two SpA signs or symptoms, or the presence of positive imaging findings, need to be present to classify a patient as having axial SpA. There is no clinical utility to ordering an HLA-B27 in the absence of positive imaging or the minimally required SpA signs or symptoms.
Rostom S, et al. New tools for diagnosing spondyloarthropathy. Joint Bone Spine. 2010 Mar;77(2):108-14. PMID: 20153677.
Rudwaleit M, et al. How to diagnose axial spondyloarthritis early. Ann Rheum Dis. 2004 May;63(5):535-43. PMID: 15082484.
Rudwaleit M, et al. The development of assessment of SpondyloArthritis international society classification criteria for axial spondyloarthritis (part II): Validation and final selection. Ann Rheum Dis. 2009 Jun;68(6):777-83. PMID: 19297344.
Sidiropoulos PI, et al. Evidence-based recommendations for the management of ankylosing spondylitis: Systematic literature search of the 3E initiative in rheumatology involving a broad panel of experts and practising rheumatologists. Rheumatology (Oxford). 2008 Mar;47(3):355-61. PMID: 18276738.
The use of repeat DEXA scans at intervals of every 2 years is appropriate in most clinical settings, and is supported by several current osteoporosis guidelines. Because of limitations in the precision of testing, a minimum of 2 years may be needed to reliably measure a change in BMD. If bone mineral densities are stable and/or individuals are at low risk of fracture, then less frequent monitoring up to an interval of 5-10 years can be considered. Shorter or longer intervals between repeat DEXA scans may be appropriate based on expected rate of change in bone mineral density and fracture risk.
Papaioannou A, et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: Summary. CMAJ. 2010 Nov 23;182(17):1864-73. PMID: 20940232.
Schousboe JT, et al. Executive summary of the 2013 international society for clinical densitometry position development conference on bone densitometry. J Clin Densitom. 2013 Oct-Dec;16(4):455-66. PMID: 24183638.
U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med. 2011 Mar 1;154(5):356-64. PMID: 21242341.
Patient Pamphlet: Bone Density Tests: When you need them and when you don’t
There is no convincing evidence that anti-osteoporotic therapy in patients with osteopenia alone reduces fracture risk. The 2008 Cochrane Reviews for three bisphosphonates (Alendronate, Etidronate, Risedronate) found no statistically significant reductions for primary prevention of fracture in postmenopausal women. Fracture risk is determined using either the Canadian Association of Radiologists and Osteoporosis Canada risk assessment tool (CAROC) or FRAX®, a World Health Organization fracture risk assessment tool. Both are available as online calculators of fracture risk. Given the lack of proven efficacy, widespread use of bisphosphonates in patients at low risk of fracture is not currently recommended.
FRAX®. WHO fracture risk assessment tool [Internet]. 2011 Jun [cited 20177 May 5].
Osteoporosis Canada. Assessment of 10-year fracture risk – women and men [Internet]. 2010 [cited 2017 May 5].
Roux C. Osteopenia: Is it a problem?. Int J Clin Rheumtol. 2009 Dec;4(6):651-5.
Wells GA, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD001155. PMID: 18253985.
Wells GA, et al. Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003376. PMID: 18254018.
Wells G, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD004523. PMID: 18254053.
Patient Decision Aid: Mayo Clinic’s Bone Health Choice Decision Aid
The diagnosis of peripheral and axial inflammatory arthritis can usually be made on the basis of an appropriate history, physical exam and basic investigations. Whole body bone scans, such as the Tc-99m MDP scintigraphy, lack specificity to diagnose inflammatory polyarthritis or spondyloarthritis and have limited clinical utility. This approach is cost-effective and reduces radiation exposure.
Fisher BA, et al. Do tc-99m-diphosphonate bone scans have any place in the investigation of polyarthralgia? Rheumatology (Oxford). 2007 Jun;46(6):1036-7. PMID: 17449485.
Picano E, et al. Unnecessary radiation exposure from medical imaging in the rheumatology patient. Rheumatology (Oxford). 2011 Sep;50(9):1537-9. PMID: 21183451.
Song IH, et al. The diagnostic value of scintigraphy in assessing sacroiliitis in ankylosing spondylitis: A systematic literature research. Ann Rheum Dis. 2008 Nov;67(11):1535-40. PMID: 18230629.
Whallett A, et al. Isotope bone scans: An assessment of their diagnostic use in polyarticular pain of uncertain origin. Ann Rheum Dis. 2003 Aug;62(8):784-5. PMID: 12860741.
Opioids in chronic non-cancer pain are associated with substantial risks. Optimize non-opioid pharmacotherapy and non-pharmacologic therapy. Opioids are not superior to non-opioid medications for pain-related function over 12 months in moderate to severe hip or knee osteoarthritis, or mechanical back pain. Opioids should only be prescribed by physicians skilled in their use.
Busse JW, et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ. 2017 May 8;189(18):E659-E666. PMID: 28483845.
Krebs EE, et al. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients with Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial. JAMA. 2018; 319(9):872–882. PMID: 29509867.
A palliative approach to care alongside disease-specific treatment should be part of the continuum of care for patients with advanced rheumatic disease toward the end of life. This approach aims to improve quality of life for patients with life-limiting illnesses, through the prevention and relief of suffering, the control of symptoms, and the management of physical, psychosocial and spiritual distress. Such an approach is supported by a growing body of evidence that demonstrates improved patient satisfaction with care, decreased symptom burden and, in some cases, better survival, when a palliative approach to care is integrated early in a patient’s disease trajectory.
Crosby V, Wilcock A. End-of-life care in rheumatolog: room for improvement. Rheumatology (Oxford). 2011 Jul;50(7):1187-8. PMID: 21097447.
Karpoff M, et al. 2019, November. Palliative Care Curriculum in Rheumatology: Teaching Serious Illness Conversations. Paper presented at the meeting of American College of Rheumatology, USA. Abstract retrieved from
Saltman A. Palliative Care for the Rheumatologist: When Does the End Begin…And Why Does It Matter? CRAJ. 2019;29(2).
Saltman A, et al. (2020, November). Rheumatologists’ Attitudes Toward Palliative Care and Medical Assistance in Dying. [Poster presentation]. American College of Rheumatology, Online (ACR Convergence).
Simon S, Schwarz-Eywill M, Bausewein C. Palliative care in rheumatic diseases: a first approach. J Palliat Care. Winter 2008;24(4):270-3. PMID: 19227019.
Patients on stable doses of non-biologic DMARDs (e.g., methotrexate, sulfasalazine) without specific comorbidities (e.g., obesity, diabetes mellitus, renal disease, liver disease, alcohol use, concomitant use of hepatotoxic or myelosuppressive medications) are at a low overall risk of toxicity. More frequent blood draws pose an unnecessary burden to patients. Patients new to treatment, on escalating doses, or with abnormal baseline labs typically require more frequent monitoring.
Hideto Kameda, Takao Fujii, Ayako Nakajima, Ryuji Koike, Akira Sagawa, Katsuaki Kanbe, Tetsuya Tomita, Masayoshi Harigai, Yasuo Suzuki & Japan College of Rheumatology subcommittee on the guideline for the use of methotrexate in patients with rheumatoid arthritis (2019) Japan College of Rheumatology guideline for the use of methotrexate in patients with rheumatoid arthritis, Modern Rheumatology, 29:1, 31-40, DOI: 10.1080/14397595.2018.1472358. PMID: 29718746.
Jo Ledingham, Nicola Gullick, Katherine Irving, Rachel Gorodkin, Melissa Aris, Jean Burke, Patrick Gordon, Dimitrios Christidis, Sarah Galloway, Eranga Hayes, Andrew Jeffries, Scott Mercer, Janice Mooney, Sander van Leuven, James Galloway, on behalf of the BSR and BHPR Standards, Guidelines and Audit Working Group, BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs, Rheumatology, Volume 56, Issue 6, June 2017, Pages 865–868, https://doi.org/10.1093/rheumatology/kew479. PMID: 28339817.
Nakafero G, Grainge MJ, Card T, Mallen CD, Zhang W, Doherty M, Taal MW, Aithal GP, Abhishek A. What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline? Rheumatology (Oxford). 2021 Dec 1;60(12):5785-5794. doi: 10.1093/rheumatology/keab254. PMID: 33725120.
Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O’Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016 Jan;68(1):1-26. doi: 10.1002/art.39480. Epub 2015 Nov 6. PMID: 26545940.
Yazici, Y et al. “Long term safety of methotrexate in routine clinical care: discontinuation is unusual and rarely the result of laboratory abnormalities.” Annals of the rheumatic diseases vol. 64,2 (2005): 207-11. doi:10.1136/ard.2004.023408. PMID: 15208176.
Avoid ordering these autoantibodies in patients with arthralgia (joint pain) but who do not meet the CSA criteria or have arthritis (>one swollen joint) on physical exam. EULAR defines CSA at risk for developing Rheumatoid Arthritis (RA) as having 3 or more parameters including new joint symptoms <1 year, symptoms located in metacarpophalangeal (MCP) joints, morning stiffness >60 min, most severe symptoms in the morning, 1st degree relative with RA, and difficulty making a fist and positive MCP squeeze test on physical exam. Even in CSA with positive RF and ACPA, more than 30%-60% of patients will not develop RA over the next two years. Most musculoskeletal pain causing global disability is not related to rheumatoid arthritis. Inappropriate testing of RF serology in patients with low likelihood of RA is associated with low positive predictive value (PPV) and increased cost.
Ahrari A, Barrett SS, Basharat P, Rohekar S, Pope JE: Appropriateness of laboratory tests in the diagnosis of inflammatory rheumatic diseases among patients newly referred to rheumatologists. Joint Bone Spine 2020, 87(6):588-595. PMID: 32522598.
Bos WH, Wolbink GJ, Boers M, Tijhuis GJ, de Vries N, van der Horst-Bruinsma IE, Tak PP, van de Stadt RJ, van der Laken CJ, Dijkmans BA et al: Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study. Ann Rheum Dis 2010, 69(3):490-494. PMID: 19363023.
Briggs AM, Woolf AD, Dreinhöfer K, Homb N, Hoy DG, Kopansky-Giles D, Åkesson K, March L: Reducing the global burden of musculoskeletal conditions. Bull World Health Organ 2018, 96(5):366-368. PMID: 29875522.
Ruta S, Prado ES, Chichande JT, Ruta A, Salvatori F, Magri S, Salinas RG: EULAR definition of “arthralgia suspicious for progression to rheumatoid arthritis” in a large cohort of patients included in a program for rapid diagnosis: role of auto-antibodies and ultrasound. Clinical Rheumatology 2020, 39(5):1493-1499. PMID: 31933033.
Ten Brinck RM, van Steenbergen HW, van Delft MAM, Verheul MK, Toes REM, Trouw LA, van der Helm-van Mil AHM: The risk of individual autoantibodies, autoantibody combinations and levels for arthritis development in clinically suspect arthralgia. Rheumatology (Oxford) 2017, 56(12):2145-2153. PMID: 28968865.
Anti-nuclear antibody (ANA) should not be used as a screening test in patients without specific signs or symptoms of systemic lupus erythematosus or other systemic autoimmune rheumatic disease (e.g. inflammatory arthritis, malar rash, photosensitivity, etc.) since ANA positivity may occur in non-rheumatic conditions and in “healthy” populations (up to 20%). In consideration of juvenile idiopathic arthritis (JIA), a positive ANA indicates increased risk of uveitis, but is not a useful screening test for the diagnosis of JIA. Inappropriate ANA testing may be misleading, precipitate further unnecessary testing, and lead to patient anxiety.
Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med 2000;124:71-81. PMID: 10629135.
Solomon DH, Kavanaugh AJ, Schur PH. American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum 2002;47:434-44. PMID: 12209492.
Tozzoli R, Bizzaro N, Tonutti E, et al. Guidelines for the laboratory use of autoantibody tests in the diagnosis and monitoring of autoimmune rheumatic diseases. Am J Clin Pathol 2002;117:316-24. PMID: 11863229.
Pediatric patients on stable doses of non-biologic disease modifying anti-rheumatic drugs (DMARDs) (e.g. methotrexate, sulfasalazine) without specific risk factors (e.g. obesity, diabetes mellitus, renal disease, alcohol use, concomitant use of hepatotoxic or myelosuppressive medications) are at a low overall risk of toxicity. More frequent blood draws pose an unnecessary burden to pediatric patients and the health-care system. Patients new to treatment, on escalating doses, or with abnormal baseline labs typically require more frequent monitoring.
Karlsson Sundbaum J, Eriksson N, Hallberg P, Lehto N, Wadelius M, Baecklund E. Methotrexate treatment in rheumatoid arthritis and elevated liver enzymes: A long-term follow-up of predictors, surveillance, and outcome in clinical practice. Int J Rheum Dis. 2019 Jul;22(7):1226-1232. PMID: 31012257.
Ledingham J, Gullick N, Irving K, et al. BSR and BHPR Standards, Guidelines and Audit Working Group. Rheumatology (Oxford). 2017 Jun 1;56(6):865-868. PMID: 28339817.
Zajc Avramovič M, Dolžan V, Toplak N, Accetto M, Lusa L, Avčin T. Relationship Between Polymorphisms in Methotrexate Pathway Genes and Outcome of Methotrexate Treatment in a Cohort of 119 Patients with Juvenile Idiopathic Arthritis. J Rheumatol. 2017 Aug;44(8):1216-1223. PMID: 28572465.
Back pain is a common symptom relative to the incidence of spondyloarthropathy (SpA) in children. In addition, the prevalence of HLA-B27 is 2-8% in the general population, and individuals with a positive HLA-B27 have a low probability of developing SpA. As such, HLA-B27 testing is not useful as a single diagnostic test in a patient with low back pain without specific signs or symptoms of SpA (e.g., inflammatory back pain, peripheral arthritis, enthesitis, or acute anterior uveitis) or suggestive findings on MRI. Of note, patients with confirmed Juvenile Idiopathic Arthritis (JIA) may have HLA-B27 testing in order to classify their JIA subtype.
Gran JT, Husby G. HLA-B27 and spondyloarthropathy: value for early diagnosis? J Med Genet. 1995;32(7):497-501. PMID: 7562959.
Reveille JD. Epidemiology of spondyloarthritis in North America. Am J Med Sci. 2011;341(4):284-6. PMID: 21430444.
Reveille JD, Hirsch R, Dillon CF, Carroll MD, Weisman MH. The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum. 2012;64(5):1407-11. PMID: 22139851.
In children, the vast majority of musculoskeletal (MSK) pain is non-inflammatory (97%) and is rarely secondary to a rheumatic disease. For patients with arthralgia (joint pain) but no arthritis on physical exam (defined as presence of joint effusion or ≥2 of warmth, tenderness, stress pain, reduced range of motion), testing rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) is not clinically useful and has low diagnostic utility. For example, a positive RF may result from various infections. Performing such tests without clinical relevance may result in unnecessary additional testing and anxiety.
Hermosillo-Villafranca, J.A., et al., Role of rheumatoid factor isotypes and anti-citrullinated peptide antibodies in the differential diagnosis of non-selected patients with inflammatory arthralgia. Reumatol Clin. 2021. 17(1): p. 12-15. PMID: 31399351.
Wang, Y., et al., Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody for juvenile idiopathic arthritis. J Immunol Res. 2015. 2015: p. 915276. PMID: 25789331.
Wong, K.O., et al., Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Peptide Tests for Evaluating Musculoskeletal Complaints in Children. Comparative Effectiveness Review No. 50 (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. HHSA 290 2007 10021 I). 2012, Agency for Healthcare Research and Quality: Rockville (MD). PMID: 22514802.
Lyme disease is most likely to occur if an individual resides in or visits an endemic area. The most common musculoskeletal (MSK) manifestation of Lyme disease is persistent or intermittent arthritis in at least one joint (typically the knee) which develops within weeks to months after a tick bite. Chronic diffuse arthralgias, myalgias or fibromyalgia alone are not criteria for MSK Lyme disease. Testing for Lyme disease should be limited to children with characteristic clinical signs and risk of exposure to Lyme to avoid false positive tests and unnecessary treatment.
Government of Canada, Surveillance of Lyme Disease. [Internet].
Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease. Arthritis Rheum. 2021;73(1):12-20. PMID: 33251700.
Lipsett SC, Nigrovic LE. Diagnosis of Lyme disease in the pediatric acute care setting. Curr Opin Pediatr. 2016;28(3):287-293. PMID: 27138805.
Pediatric patients with juvenile idiopathic arthritis (JIA) often benefit from treatment with intra-articular corticosteroid injections, especially when arthritis is impacting activities of daily living. However, in patients with polyarticular JIA (≥5 affected joints) the probability of a short-lived or poor response to corticosteroid injections is increased when compared to those with oligoarticular JIA (≤4 affected joints). Lack of concomitant initiation of a disease modifying anti-rheumatic drug (DMARD) in polyarticular disease is also a risk factor for suboptimal response to joint injections. In addition, repeating joint injections in the same joint (e.g. >2-3 times/year) has a lower probability of achieving disease control compared to initiating a DMARD and may be a risk factor for the development of osteochondritis dissecans. Multiple or recurrent intra-articular corticosteroid injections may be considered as an adjunctive therapy while awaiting the effect of an escalation in systemic therapy.
Heidt C, Grueberger N, Grisch D, Righini-Grunder F, Rueger M, Ramseier L. The assessment of steroid injections as a potential risk factor for osteochondral lesions in children with juvenile idiopathic arthritis. Cartilage. 2020 Sep:1947603520961173. PMID: 32985233.
Lanni S, Bertamino M, Consolaro A, et al. Outcome and predicting factors of single and multiple intra-articular corticosteroid injections in children with juvenile idiopathic arthritis. Rheumatology (Oxford). 2011 Sep;50(9):1627-1634. PMID: 21561981.
Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for non-systemic polyarthritis, sacroiliitis, and enthesitis. Arthritis Care Res (Hoboken). 2019 Jun;71(6):717-734. PMID: 31021516.
Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome is a clinical diagnosis, and currently, no genetic mutations have been identified for this condition. Periodic fever genetic panel in patients with classic features of PFAPA—without any features of another periodic fever syndrome—rarely yields an alternate diagnosis and as such is costly and has no clinical benefit. However, genetic testing may be warranted if patients have atypical features at presentation, don’t respond to treatment as expected, or develop concerning features over time.
Berkun Y, Levy R, Hurwitz A, et al. The familial Mediterranean fever gene as a modifier of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome. Semin Arthritis Rheum. 2011 Apr;40(5):467-72. PMID: 20828792.
Dagan E, Gershoni-Baruch R, Khatib I, Mori A, Brik R. MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA. Rheumatol Int. 2010 Mar;30(5):633-6. PMID: 19579027.
Gattorno M, Caorsi R, Meini A, et al. Differentiating PFAPA syndrome from monogenic periodic fevers. Pediatrics. 2009 Oct;124(4):e721-8. PMID: 19786432.