Rheumatologic Clinical Assessment and Diagnostic Testing

Pediatric Musculoskeletal History

Asking the right questions during the pediatric musculoskeletal history will help differentiate between inflammatory and mechanical pain, identify red flags, and guide the differential diagnosis.

• Determine whether joint pain is inflammatory or mechanical: Joint pain is one of the most common chief complaints of new patients presenting to the rheumatology clinic.

  • Inflammatory pain: If the pain is inflammatory (see features in table below), the process is more suggestive of an inflammatory arthritis such as juvenile idiopathic arthritis (JIA) or systemic lupus erythematosus (SLE)-associated arthritis.

  • Mechanical pain: If the pain is mechanical (see features in table below), consider etiologies of noninflammatory musculoskeletal pain.

• Consider broadening the differential diagnosis if the following red-flag symptoms suggest other conditions (e.g., malignancy, infection, severe multisystem illness)

• Always evaluate further (versus watchful waiting) when the following musculoskeletal symptoms are present:

  • limping and/or abnormal gait (even if intermittent)

  • joint swelling

  • falling more than peers and/or more than the patient’s baseline

  • difficulty climbing stairs

• Ask about preceding trauma/injury and consider nonaccidental trauma:

  • Minor falls are common in children with underlying joint or muscle pathology (e.g., JIA, juvenile dermatomyositis [JDM])

• Incorporate developmental milestones into your assessment:

  • Consider muscle disease such as congenital myopathy with gross motor delay or regression of motor milestones

• Ask about stressors (school, family, peer groups) and mental health concerns:

  • Stressors can contribute to amplified musculoskeletal pain syndromes and indicate difficulty coping with chronic illness

• Ask about the family’s and patient’s main concerns:

  • Often patients and families are worried about a certain disease based on family history of autoimmune disease (e.g., lupus) or prior blood tests (e.g., positive antinuclear antibodies [ANA]).

Physical Examination

The following tools are used for screening and assessment of the musculoskeletal system:

• pGALS (pediatric Gait Arms Legs Spine) is a fast (<3 minutes) and sensitive screening tool used for musculoskeletal examination and identification of abnormal joints or anatomical regions in school-age children. A free app is available for download on the app store.

  • Remember that inflammatory joint disease in children is often asymptomatic.

• pREMS (pediatric Regional Examination of the Musculoskeletal System) is a more-detailed examination of relevant regions based on history and screening. The pREMS exam focuses on the following components:

  • LOOK for asymmetry (atrophy, leg length, appearance), swelling, joint contractures, and erythema

  • FEEL for warmth, effusions, and enthesitis

  • MOVE for range of motion and pain

  • FUNCTION to assess strength and gait

Laboratory Testing

No single diagnostic test exists for any rheumatologic condition. However, laboratory tests are used for the following purposes:

• To support or exclude potential diagnoses:

  • Diagnosis is based on a combination of history, examination, and (in some, but not all, cases) lab testing.

  • Labs are often ordered to rule out non-rheumatologic causes (e.g., infection, malignancy).

  • JIA is a diagnosis of exclusion, and lab results are often normal. Rheumatoid factor (RF) is not a diagnostic test for JIA and is rarely (<5%) positive in patients with JIA

• For prognostication and risk stratification (for certain disease-specific complications and prognosis after a diagnosis of a rheumatologic condition has been made):

  • Positive antinuclear antibodies (ANA) in JIA suggest increased risk of uveitis.

  • Positive rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody in polyarticular JIA is associated with increased risk of persistent and aggressive disease course.

  • Positive anti-MDA-5 antibody in JDM is associated with increased risk of interstitial lung disease (ILD).

  • Positive anti-Jo-1 antibody in JDM is associated with higher mortality and risk of ILD.

• To monitor medication toxicity:

  • Methotrexate

    • Check complete blood count (CBC) and/or comprehensive metabolic panel (CMP) before initiation of medication, 1 month after starting, and every 3 months thereafter.

  • Tumor necrosis factor (TNF)-alpha inhibitors

    • Before initiation, test for latent tuberculosis (TB) with purified protein derivative (PPD) skin test/interferon-gamma release assay (IGRA).

    • Monitor CBC and/or CMP for cytopenias and transaminitis prior to initiation of therapy, one month after starting, and every 6 months thereafter.

• To monitor disease activity:

  • See disease-specific rotation guides for specific monitoring lab tests.

  • JIA disease activity is primarily based on the exam with the exception of systemic JIA, which is also monitored with labs (e.g., inflammatory markers and ferritin level).

  • The ANA test is not a useful marker of disease activity in any rheumatologic condition.

ANA Antibodies

Approximately 10% to 20% of healthy children have positive ANA titers. Therefore, ANA is a poor screening test for rheumatologic disease (poor sensitivity and even worse specificity).

ANA antibodies are measured for the following reasons:

• To stratify risk of uveitis after a diagnosis of JIA

  • Indirect immunofluorescence is the preferred modality because enzyme-linked immunosorbent assay (ELISA) can be falsely negative in JIA

• To evaluate signs and symptoms suggestive of SLE, Sjögren syndrome, systemic sclerosis, or mixed connective tissue disease

  • Example: New-onset Raynaud’s phenomenon should prompt ANA testing, and if positive, additional testing can be considered based on titer and additional review of symptoms.

Muscle Enzymes

Measure the following muscle enzymes to screen for inflammatory myopathies such as juvenile dermatomyositis or mixed connective tissue disease.

• Creatine kinase [CK] - can be normal so the others are needed too

• Aldolase

• Alanine aminotransferase [ALT]

• Aspartate aminotransferase [AST]

• Lactate dehydrogenase [LDH]

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are the most common inflammatory markers measured.

• Inflammatory markers are usually normal or mildly elevated in JIA.

  • Exceptions include systemic JIA, severe polyarticular JIA, and enthesitis-related arthritis with axial involvement

• Discordant elevation of ESR compared to CRP is common in SLE, Sjogren syndrome, scleroderma, and mixed connective tissue disease.

• Falling ESR with rising CRP in a sick patient with persistent fevers should raise concern for macrophage activation syndrome (MAS) because ESR is based on fibrinogen, which gets consumed in MAS.

  • Markedly elevated ferritin levels (typically in the thousands) can be seen in patients with MAS.

Imaging

Indications for imaging include:

• to rule out other causes of joint swelling in atypical cases of JIA

  • Examples: trauma, infection, malignancy, pigmented villonodular synovitis [PVNS])

• to confirm arthritis in joints where exam has low sensitivity and specificity

  • Examples: temporomandibular joint (TMJ) arthritis or sacroiliitis

Imaging selection considerations:

• MRI with contrast is preferred to confirm an inflammatory arthropathy, particularly based on presence of synovial enhancement.

• Bedside ultrasound is a quick method for confirming exam findings.

• Radiographs are sometimes obtained to monitor erosive disease or to rule out infectious (osteomyelitis) and oncologic processes.

• Echocardiogram is used when there is concern for acute rheumatic fever or Kawasaki disease, or in patients with new diagnosis of SLE, mixed connective tissue disease, or systemic sclerosis to check for cardiac involvement.

• Chest CT is indicated for a new diagnosis of systemic sclerosis or ANCA-associated vasculitis, or abnormal pulmonary function tests (PFTs) in patients with JDM, mixed connective tissue disease, or overlap syndrome.

• CT angiography or magnetic resonance angiography are first-line vessel-imaging studies for systemic vasculitis; conventional angiography may be needed for small-to-medium vessel disease (i.e., polyarteritis nodosa).

Healthcare Maintenance

Patients on immunosuppressive medications should receive annual flu shots and all recommended vaccinations except for live vaccines.