How to approach a 25-year-old male presenting with chronic neck pain, low back pain, and mild joint involvement of the elbows, wrists, and ankles, without rash, inflammatory bowel disease (IBD) symptoms, or uveitis?

Diagnostic Approach to Young Male with Chronic Axial and Peripheral Joint Pain

This patient should be evaluated for axial spondyloarthritis (axSpA), with initial plain radiographs of the sacroiliac joints and spine, followed by MRI if radiographs are negative or equivocal, and referral to rheumatology for definitive diagnosis and management. 1

Initial Clinical Assessment

Key Historical Features to Elicit

Inflammatory back pain characteristics that distinguish axSpA from mechanical pain include: 1

• Age of onset before 45 years (patient is 25 years old—highly consistent) 1
• Duration greater than 3 months (patient has 2.5 years—meets criteria) 1
• Insidious onset
• Morning stiffness lasting more than 30 minutes 1
• Improvement with exercise but not with rest 1
• Pain worse in the latter part of the night 1
• Response to NSAIDs (good response suggests inflammatory etiology) 1

Critical Extra-Articular Features to Document

The absence of uveitis, IBD symptoms, and rash does not exclude axSpA, but their presence would strengthen the diagnosis: 1, 2, 3

• Approximately 40% of AS patients develop acute anterior uveitis during disease course 2, 3
• Uveitis occurs in 33% of AS cases, but its absence is common early in disease 3
• IBD and psoriasis are associated but not required for diagnosis 1, 4

Physical Examination Priorities

• Assess spinal mobility (Schober's test, chest expansion, cervical rotation)
• Examine peripheral joints (elbows, wrists, ankles) for synovitis versus enthesitis
• Palpate entheseal sites (Achilles insertion, plantar fascia, greater trochanter)
• Evaluate sacroiliac joint tenderness with provocative maneuvers

Diagnostic Testing Algorithm

Step 1: Laboratory Evaluation

Order the following tests: 1

• HLA-B27: Positive in approximately 90% of AS patients, though 25% of HLA-B27-positive first-degree relatives develop axSpA over 35 years 1
• CRP and ESR: Elevated in many but not all cases; normal values do not exclude axSpA 1
• Complete blood count, liver function tests, creatinine: Baseline before treatment
• Rheumatoid factor and anti-CCP antibodies: To exclude rheumatoid arthritis 1

Important caveat: HLA-B27 negativity does not exclude axSpA—approximately 10% of AS patients are HLA-B27 negative, and HLA-B27 carriage does not adversely impact survival 1

Step 2: Initial Imaging

Plain radiographs are the appropriate first imaging study: 1

• X-ray sacroiliac joints (rating 9/9 "usually appropriate") 1
• X-ray spine as complementary examination (rating 9/9 "usually appropriate") 1

Radiographic findings to assess:

• Sacroiliitis (erosions, sclerosis, joint space narrowing, ankylosis)
• Vertebral squaring, syndesmophytes, bamboo spine (late findings)

Step 3: Advanced Imaging if Radiographs Negative/Equivocal

If plain radiographs are negative or equivocal but clinical suspicion remains high, proceed to MRI: 1, 5

• MRI sacroiliac joints and spine (without contrast initially) 1
• MRI detects bone marrow edema and active inflammation before radiographic changes develop 1, 5
• Sagittal images of cervicothoracic and thoracolumbar spine with T1 and STIR sequences 1
• Coronal/oblique sacroiliac joints with T1 and STIR sequences 1

Critical point: MRI in all patients with suspected axSpA enhances diagnostic accuracy by 25% compared to on-demand imaging, particularly in HLA-B27-negative patients 5

CT and nuclear imaging are NOT recommended (rating 1/9 "usually not appropriate") for initial evaluation 1

Diagnostic Classification

Distinguishing Radiographic from Non-Radiographic axSpA

• Radiographic axSpA (r-axSpA): Definite sacroiliitis on plain radiographs by modified New York criteria 1
• Non-radiographic axSpA (nr-axSpA): Clinical features of axSpA with positive MRI but negative radiographs 1

Prognostic consideration: After 35-year follow-up, r-axSpA patients have increased mortality (SMR 1.4) compared to general population, while nr-axSpA patients do not (SMR 0.4), suggesting radiographic damage reflects disease severity 1

Peripheral Arthritis Pattern Recognition

The mild elbow, wrist, and ankle involvement suggests:

• Type 2 peripheral arthropathy (more than 5 joints, symmetrical, upper and lower limbs) if truly polyarticular 1
• This pattern is usually independent of gut inflammation and more persistent 1
• Alternatively, could represent enthesitis rather than true synovitis—critical to distinguish clinically

Differential Diagnosis to Exclude

Key conditions to differentiate: 1

• Psoriatic arthritis: Look for nail dystrophy, dactylitis, family history of psoriasis 1
• Rheumatoid arthritis: Symmetrical small joint polyarthritis, anti-CCP/RF positivity 1
• Chronic non-bacterial osteitis (CNO): Consider if bone pain with sclerosis on imaging 1
• Mechanical low back pain: No inflammatory features, older age, degenerative changes 1

Rheumatology Referral

Refer to rheumatology for: 1, 5

• Definitive diagnosis and classification
• Initiation of disease-modifying therapy
• Long-term disease monitoring

Approximately 30-40% of patients with chronic back pain and extra-articular manifestations (like this patient's peripheral joint involvement) will have undiagnosed axSpA 5

Initial Management Pending Rheumatology Evaluation

First-Line Pharmacologic Therapy

NSAIDs are the cornerstone of initial treatment: 1, 6

• Continuous NSAID therapy at full anti-inflammatory dose is recommended over on-demand use 1
• Good response to NSAIDs supports inflammatory etiology 1

Important safety consideration: Higher NSAID doses associated with increased cardiovascular risk (HR 1.1) in large Korean database of r-axSpA patients, though this analysis has confounding limitations 1

Therapies NOT Recommended at This Stage

• Methotrexate: Not effective for axial disease; only indicated for persistent peripheral arthritis when TNF inhibitors contraindicated 1
• Sulfasalazine: Only for persistent peripheral arthritis, not axial symptoms 1
• Systemic corticosteroids: Not routinely used for axSpA 1

Non-Pharmacologic Interventions

• Physiotherapy: Essential component of management 1
• Exercise programs: Improve symptoms and function
• Patient education: About disease course and treatment options

Red Flags Requiring Urgent Evaluation

Immediately evaluate for: 1

• Progressive neurologic deficits
• Cauda equina syndrome (urinary retention, fecal incontinence, saddle anesthesia)
• Unexplained weight loss or fever (malignancy, infection)
• History of cancer (increases post-test probability of spinal malignancy to 9%) 1

Follow-Up and Monitoring

• Do NOT routinely monitor with serial spine radiographs for radiographic progression 1
• MRI may aid assessment if disease activity unclear after initial evaluation 1
• Monitor treatment response clinically with validated outcome measures
• Screen periodically for development of uveitis, IBD, psoriasis

The absence of uveitis at presentation does not predict future risk—acute anterior uveitis can develop at any point and is a significant predictor of axSpA development (OR 4.7) in at-risk individuals 1