Assessment of seronegative arthritis

Sacroiliitis may be unilateral or bilateral and is graded from 1-4 depending on the severity.[Figure caption and citation for the preceding image starts]: Plain radiograph showing bilateral sacroiliitis in a patient with ankylosing spondylitisBMJ 2006;333:581-585. Copyright@2009 by the BMJ Publishing Group [Citation ends].

Radiographically apparent sacroiliitis may take many years to develop, and therefore a normal pelvic x-ray does not exclude the diagnosis.

HLA-B27 is not diagnostic and should not be tested in all patients with back pain. HLA-B27 is present in about 90% of patients who have AS.[52]Arévalo M, Gratacós Masmitjà J, Moreno M, et al. Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: results from the REGISPONSER database. Arthritis Res Ther. 2018 Oct 3;20(1):221. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235234 http://www.ncbi.nlm.nih.gov/pubmed/30285828?tool=bestpractice.com

In a patient with classic inflammatory back pain and normal radiographs, a positive HLA-B27 in the presence of 1 or 2 associated features of AS should prompt the request of an MRI.

Instrumental in allowing clinicians to diagnose AS early.

MRI scans may demonstrate abnormality in the presence of normal radiographs.[Figure caption and citation for the preceding image starts]: Coronal STIR (short tau inversion recovery) magnetic resonance image showing unilateral (right) sacroiliitisBMJ 2006 Sep 16;333(7568):581-5. © BMJ Publishing Group Ltd 2009 [Citation ends].

A highly specific test for rheumatoid arthritis (RA). However, it may be present in a small number of patients with established polyarticular psoriatic arthritis. In patients presenting with oligoarticular disease, a negative anti-CCP antibody test is useful for excluding RA.

These findings are unlikely to appear in the acute stage and are more commonly seen in chronic reactive arthritis. Sensitivity and specificity of imaging are low.[85]Expert Panel on Musculoskeletal Imaging, Subhas N, Wu F, et al. ACR appropriateness criteria® chronic extremity joint pain-suspected inflammatory arthritis, crystalline arthritis, or erosive osteoarthritis: 2022 update. J Am Coll Radiol. 2023 May;20(5s):S20-32. http://www.ncbi.nlm.nih.gov/pubmed/37236743?tool=bestpractice.com

In asymptomatic men or in men with suspected sexually acquired reactive arthritis (i.e., with urethritis, urethral discharge, and/or dysuria).[89]Carlin E, Marzo-Ortega H, Flew S. British Association of Sexual Health and HIV national guideline on the management of sexually acquired reactive arthritis 2021. Int J STD AIDS. 2021 May 20;:9564624211020266. http://www.ncbi.nlm.nih.gov/pubmed/34014782?tool=bestpractice.com

In asymptomatic women or in women with suspected sexually acquired reactive arthritis (i.e., with purulent vaginal discharge, dysuria, and/or post-coital or intermenstrual bleeding).[89]Carlin E, Marzo-Ortega H, Flew S. British Association of Sexual Health and HIV national guideline on the management of sexually acquired reactive arthritis 2021. Int J STD AIDS. 2021 May 20;:9564624211020266. http://www.ncbi.nlm.nih.gov/pubmed/34014782?tool=bestpractice.com

In asymptomatic men and in women with suspected sexually acquired reactive arthritis.[89]Carlin E, Marzo-Ortega H, Flew S. British Association of Sexual Health and HIV national guideline on the management of sexually acquired reactive arthritis 2021. Int J STD AIDS. 2021 May 20;:9564624211020266. http://www.ncbi.nlm.nih.gov/pubmed/34014782?tool=bestpractice.com

In early disease, radiological studies are likely to be negative.

Synovial fluid should be aspirated and intracellular CPPD crystals demonstrated.[84]Bencardino JT, Hassankhani A. Calcium pyrophosphate dihydrate crystal deposition disease. Semin Musculoskelet Radiol. 2003;7:175-185. http://www.ncbi.nlm.nih.gov/pubmed/14593559?tool=bestpractice.com It should be sent for Gram stain and culture. Synovial fluid exam under plane-polarised microscopy is required to confirm the diagnosis.[86]Choi MH, MacKenzie JD, Dalinka MK. Imaging features of crystal-induced arthropathy. Rheum Dis Clin North Am. 2006;32:427-446. http://www.ncbi.nlm.nih.gov/pubmed/16716888?tool=bestpractice.com [Figure caption and citation for the preceding image starts]: Image of intracellular calcium pyrophosphate crystals under compensated polarising light microscopyFrom the collection of Ann K. Rosenthal, MD; used with permission [Citation ends].

Radiograph.[Figure caption and citation for the preceding image starts]: Knee radiograph with linear calcific deposits of cartilage calcificationFrom the collection of Ann K. Rosenthal, MD; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Wrist radiograph from a patient with chronic calcium pyrophosphate arthritis showing severe degenerative changesFrom the collection of Ann K. Rosenthal, MD; used with permission [Citation ends].

Important to confirm the diagnosis, exclude septic arthritis, and differentiate gout from calcium pyrophosphate deposition disease (pseudogout).

Uric acid level by itself is not diagnostic of gout. During an acute attack, it may be falsely normal.

The hands are an optimal place to look for gouty erosions.

Elevated in 91.5% of patients at diagnosis but is not as sensitive as a CRP. An elevated ESR at diagnosis is associated with a higher risk of >1 relapse.[90]Helfgott SM, Kieval RI. Polymyalgia rheumatica in patients with a normal erythrocyte sedimentation rate. Arthritis Rheum. 1996 Feb;39(2):304-7. http://www.ncbi.nlm.nih.gov/pubmed/8849384?tool=bestpractice.com

A sensitive indicator of disease activity, which is elevated in 98.9% of patients diagnosed with polymyalgia rheumatica.[90]Helfgott SM, Kieval RI. Polymyalgia rheumatica in patients with a normal erythrocyte sedimentation rate. Arthritis Rheum. 1996 Feb;39(2):304-7. http://www.ncbi.nlm.nih.gov/pubmed/8849384?tool=bestpractice.com ​ Unlike ESR, the pre-treatment levels of CRP are not prognostic.

These findings may increase suspicion of polymyalgia rheumatica but may not distinguish it from older-onset rheumatoid arthritis.[5]Dasgupta B, Cimmino MA, Maradit-Kremers H, et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012;71:484-492. http://ard.bmj.com/content/71/4/484.long http://www.ncbi.nlm.nih.gov/pubmed/22388996?tool=bestpractice.com

More sensitive than ultrasound, but not routinely done.

OA is essentially a clinical diagnosis. Guidelines recommend a clinical diagnosis of OA based on symptoms, patient age, and examination findings.[91]Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. http://www.ncbi.nlm.nih.gov/pubmed/3741515?tool=bestpractice.com [92]National Institute for Health and Care Excellence. Osteoarthritis in over 16s: diagnosis and management. Oct 2022 [internet publication]. https://www.nice.org.uk/guidance/ng226

OA is essentially a clinical diagnosis, but inflammatory markers should be ordered if inflammatory arthritis is a possible differential: for example, in an older patient who presents with a knee effusion.

OA is essentially a clinical diagnosis, but inflammatory markers should be ordered if inflammatory arthritis is a possible differential: for example, in an older patient who presents with a knee effusion.

OA is essentially a clinical diagnosis. Imaging studies are not routinely recommended, they should only be considered if the diagnosis is unclear or an alternative/additional diagnosis is suspected subsequent to initial investigations.[85]Expert Panel on Musculoskeletal Imaging, Subhas N, Wu F, et al. ACR appropriateness criteria® chronic extremity joint pain-suspected inflammatory arthritis, crystalline arthritis, or erosive osteoarthritis: 2022 update. J Am Coll Radiol. 2023 May;20(5s):S20-32. http://www.ncbi.nlm.nih.gov/pubmed/37236743?tool=bestpractice.com

RF may be negative in 37% or less of patients with RA.[2]Sokka T, Pincus T. Erythrocyte sedimentation rate, C-reactive protein, or rheumatoid factor are normal at presentation in 35%-45% of patients with rheumatoid arthritis seen between 1980 and 2004: analyses from Finland and the United States. J Rheumatol. 2009;36:1387-1390. http://www.ncbi.nlm.nih.gov/pubmed/19411389?tool=bestpractice.com

High specificity for RA, with about 70% of RA patients testing positive.[93]Goldbach-Mansky R, Lee J, McCoy A, et al. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res. 2000;2(3):236-43. https://pmc.ncbi.nlm.nih.gov/articles/PMC17811 http://www.ncbi.nlm.nih.gov/pubmed/11056669?tool=bestpractice.com

X-rays are done at baseline and then repeated as needed if clinically indicated. Erosions are seldom useful for treatment decisions because they are seen in late disease; most of the benefit of treatment of RA is seen when treatment is started before erosions develop.

May complement x-ray in the evaluation of suspected RA.

May be associated with renal insufficiency. Anti-dsDNA and anti-Smith antibodies are highly specific for SLE.

Synovial fluid specimen should be sent for cell count and differential, Gram stain, culture, and crystals.

Staphylococcus aureus infection and streptococci infection is most common in non-gonococcal bacterial arthritis; gram-negative bacteria or anaerobes in intravenous drug users or immunocompromised patients.[15]Margaretten ME, Kohlwes J, Moore D, et al. Does this adult patient have septic arthritis? JAMA. 2007;297:1478-88. http://www.ncbi.nlm.nih.gov/pubmed/17405973?tool=bestpractice.com

Typically elevated, but normal result does not exclude diagnosis if clinical picture suggestive.

Viral testing is determined by the clinical context and risk factors for the respective viral infection.

Diagnosis is based on clinical presentation along with an elevated erythrocyte sedimentation rate and a prompt and dramatic response to corticosteroids.

CXR.[Figure caption and citation for the preceding image starts]: Bilateral hilar adenopathyFrom the collection of Muthiah P. Muthiah, MD, FCCP; used with permission [Citation ends].

Elevated in many patients, but correlation with disease activity is inconsistent. Poor sensitivity and specificity, not used as a diagnostic tool.

Common but not specific.

Common but not specific.

Often abnormal early in the course of disease. Useful in identifying joints for corticosteroid injection in oligoarthritis. Can be an important positive or negative finding if the diagnosis is questionable.

Has demonstrated higher sensitivity in assessing synovitis than clinical examination.

MRI may be indicated in patients with monoarticular disease to rule out other diagnoses such as pigmented villonodular synovitis or synovial haemangiomas. It can also be used to monitor cartilage injury.

ANA is positive in >90% of patients.

Elevated serum urea and creatinine with scleroderma renal crisis.

Mild proteinuria with few cells or casts occurs with scleroderma renal crisis.

A decrease in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) plus an overall restrictive pattern may be present in interstitial lung disease.

A disproportionate drop in DLCO compared with FVC is seen in pulmonary hypertension.

A rise in right ventricular systolic pressure; pericardial effusion, right ventricle, or left ventricle diastolic dysfunction may be present.

ANCA may be positive in granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. It is not diagnostic of these conditions. If ANCA is positive, anti-proteinase 3 and anti-myeloperoxidase antibodies should also be ordered.

To suggest differentials of granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), microscopic polyangiitis.

Elevated transaminases may suggest presence of viral hepatitis. Alkaline phosphatase may be elevated in giant cell arteritis.

Urethral, endocervical, rectal, pharyngeal, blood, synovial fluid, cerebrospinal fluid, or conjunctival specimen can be used.

Recurrent gonococcal infection should prompt a search for early complement deficiencies.[21]Rice PA. Gonococcal arthritis (disseminated gonococcal infection). Infect Dis Clin North Am. 2005;19:853-861. http://www.ncbi.nlm.nih.gov/pubmed/16297736?tool=bestpractice.com

A throat culture should be sent in all patients with suspected acute rheumatic fever. However, <10% of throat cultures are positive for group A streptococci, reflecting the post-infectious nature of the disease; group A streptococci have usually been eradicated before onset of the disease.[94]Martin DR, Voss LM, Walker SJ, et al. Acute rheumatic fever in Auckland, New Zealand: spectrum of associated group A streptococci different from expected. Pediatr Infect Dis J. 1994 Apr;13(4):264-9. http://www.ncbi.nlm.nih.gov/pubmed/8036041?tool=bestpractice.com

If available, rapid polymerase chain reaction assays can be used at the point-of-care. Sensitivity and specificity is comparable to throat culture.

Associated with prolonged PR interval. Can help eliminate other causes of cardiac symptoms.

Used to confirm the diagnosis if the IFA or ELISA are positive or equivocal.

In late stage, joint destruction may be seen.