What labs should I order for an adult with suspected inflammatory disease such as autoimmune arthritis, vasculitis, inflammatory bowel disease, connective‑tissue disease, or unexplained chronic pain/fever?

Laboratory Workup for Suspected Inflammatory Disease

For adults with suspected inflammatory disease, order high-sensitivity C-reactive protein (hs-CRP) as your primary inflammatory marker, along with a complete blood count (CBC), and add disease-specific tests based on clinical presentation—including ESR, autoimmune panel (ANA, RF, anti-CCP), and organ-specific markers like fecal calprotectin for suspected IBD. 1

Core Inflammatory Markers

Primary Test: High-Sensitivity CRP

• Obtain hs-CRP as your first-line inflammatory marker due to superior analytic characteristics including stability, precision, accuracy, and standardization 1
• Measure twice (optimally 2 weeks apart) and average the results to reduce within-individual variability 1
• Interpret as: low risk (<1.0 mg/L), average risk (1.0-3.0 mg/L), high risk (>3.0 mg/L) 1
• Test only metabolically stable patients without obvious acute infection 1
• CRP is more reliable than ESR in hospital practice because ESR has slow variation and frequent confounding factors that make it misleading in unselected patients 2

Complete Blood Count

• Order CBC for white blood cell count as a general inflammatory indicator, though recognize that up to 75% of patients with prolonged inflammatory conditions have normal WBC counts 1
• Normal WBC with thrombocytopenia and elevated liver enzymes suggests specific infections like Q fever in prolonged fever cases 1

ESR: Use Selectively

• ESR and CRP show poor agreement (kappa=0.38) in hospital practice, with disagreement in 33% of cases 2
• Prioritize CRP over ESR when inflammatory disorder is suspected, as ESR is frequently misleading due to slow variation and confounding factors 2
• ESR remains useful for specific conditions: highly elevated in immune checkpoint inhibitor-induced arthritis and helpful in bone/joint inflammation assessment 3, 1

Disease-Specific Laboratory Panels

For Suspected Autoimmune Arthritis or Connective Tissue Disease

• Order autoimmune panel including ANA, RF, and anti-CCP antibodies along with inflammatory markers (ESR and CRP) 4
• Highly elevated ESR and CRP indicate inflammatory/autoimmune arthritis, while normal or mildly elevated markers suggest non-inflammatory causes 4
• Screen for viral hepatitis B, C, and latent/active TB before initiating DMARD treatment if severe disease requires immunosuppression 4

For Suspected Inflammatory Bowel Disease

• Order fecal calprotectin (preferred over serum markers) as it has higher sensitivity and specificity for detecting intestinal inflammation 3, 1, 5
• Interpret calprotectin levels: <100 μg/g suggests IBS (manage in primary care), 100-250 μg/g requires repeat testing or routine referral, >250 μg/g warrants urgent gastroenterology referral 3, 5
• Avoid testing within 6 weeks of NSAID use, as this falsely elevates calprotectin 5
• Use first morning stool, stored no more than 3 days at room temperature 5
• Add full blood count, urea & electrolytes, CRP, coeliac screen, and stool culture 3
• Recognize that patients may have normal CRP despite active intestinal disease, so fecal calprotectin is essential 1

For Suspected Chronic Non-Bacterial Osteitis or Bone Inflammation

• Order routine labs: full blood count with differential, inflammatory markers (CRP/ESR), renal function, alkaline phosphatase, calcium, 25-hydroxy-vitamin D, parathyroid hormone, and phosphate 3, 1
• Consider on case-by-case basis for differential diagnosis: bone turnover markers, anti-CCP, RF, HLA-B27 3
• Most laboratory markers lack specificity for CNO but help investigate differential diagnoses 3

For Suspected Adult-Onset Still's Disease or Systemic JIA

• Order ferritin and IL-18 levels, which show excellent diagnostic performance 3
• Ferritin cut-offs: 684 ng/mL (sensitivity 80.6%, specificity 71.5%) for AOSD versus various controls 3
• IL-18 cut-offs: 148.7-20,000 ng/mL depending on control group, with sensitivities 61-95.8% and specificities 82.9-100% 3
• IL-18 >18,550 ng/mL distinguishes AOSD from adult HLH (sensitivity 90.3%, specificity 93.5%) 3

For Suspected Vasculitis

• Order ANCA testing if AAV (granulomatosis with polyangiitis, EGPA, MPA) is suspected 6
• Recognize that vasculitis diagnosis often precedes IBD diagnosis in 12/13 LVV cases and 8/8 AAV cases 6
• Consider that patients with IBD have increased risk of vasculitis, especially Takayasu arteritis 6

Critical Diagnostic Pitfalls

• Do not rely on autoantibody positivity alone—clinical context is paramount, as positivity does not make a diagnosis 4
• Avoid joint measurement of ESR and CRP in routine hospital practice, as this is unwarranted given poor agreement and CRP's superiority 2
• Do not use calprotectin to exclude colorectal cancer in patients with alarm features (rectal bleeding, weight loss, iron-deficiency anemia)—these require cancer pathway referral regardless of calprotectin level 5
• Recognize that fecal calprotectin cannot discriminate between IBD and gastroenteritis in acute diarrhea—use stool culture and/or endoscopy instead 5
• Exclude other causes before diagnosing autoinflammatory syndromes, evaluating for primary immunodeficiency, malignancy, or autoimmune disease 4

Monitoring After Initial Workup

• Conduct serial inflammatory marker measurements every 4-6 weeks after treatment initiation 4
• For patients on biologic therapy (infliximab, adalimumab), consider proactive therapeutic drug monitoring with serum drug levels and anti-drug antibody measurements, particularly in those with high baseline disease activity, obesity, or persistently elevated fecal calprotectin in IBD 3