What is the appropriate diagnosis and treatment for a patient with joint pains and anemia?

Diagnostic Approach to Joint Pains and Anemia

The combination of joint pains and anemia should prompt immediate evaluation for inflammatory rheumatic diseases, particularly rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) with extra-intestinal manifestations, as anemia in these conditions reflects disease severity and predicts worse outcomes including accelerated joint damage.

Initial Clinical Assessment

History and Physical Examination

• Document fever patterns: High-spiking quotidian fevers (>39°C) peaking in late afternoon/evening suggest Adult-Onset Still's Disease (AOSD) 1
• Examine all peripheral joints systematically for tenderness, swelling, and range of motion, plus spine and entheseal sites 1
• Identify joint pattern: Pauci-articular (<5 large joints, asymmetric) versus polyarticular (>5 small joints, symmetric) helps differentiate peripheral arthropathy types 2
• Look for characteristic rashes: Evanescent salmon-pink maculopapular eruption on proximal limbs/trunk suggests AOSD 1; erythema nodosum on anterior tibial areas suggests IBD-associated arthropathy 2
• Screen for extra-articular features: Sore throat (68-92% in AOSD), lymphadenopathy, splenomegaly, serositis 1; gastrointestinal symptoms suggesting ulcerative colitis 2

Mandatory Laboratory Workup

Complete Blood Count and Inflammatory Markers

• Define anemia severity: Hemoglobin <12 g/dL in women, <13 g/dL in men per WHO criteria 2
• Check leukocyte count: Leukocytosis >15×10⁹/L (especially >20×10⁹/L) strongly suggests infection or AOSD; pancytopenia suggests hemophagocytic syndrome requiring urgent immunosuppression 1
• Measure ESR and CRP: Elevated in virtually all AOSD patients and correlates with disease activity in inflammatory arthritis 1, 3
• Obtain reticulocyte count, MCV, and RDW to classify anemia type 2

Iron Studies and Anemia Classification

The diagnostic criteria for iron deficiency depend critically on inflammatory status 2:

• Without inflammation (normal CRP, no clinical/endoscopic disease activity): Serum ferritin <30 μg/L indicates iron deficiency 2
• With inflammation present: Ferritin up to 100 μg/L may still represent iron deficiency 2
• Anemia of chronic disease: Ferritin >100 μg/L AND transferrin saturation <20% 2
• Mixed picture: Ferritin 30-100 μg/L suggests combination of iron deficiency and anemia of chronic disease 2
• Add transferrin receptor (sTfR) if available: High in iron deficiency, normal/low in anemia of chronic disease 2

Autoimmune Serologies

• Rheumatoid factor (RF) and anti-CCP antibodies if rheumatoid arthritis suspected 1
• Antinuclear antibody (ANA) for connective tissue disease screening 1
• HLA-B27 if spondyloarthritis suspected (axial involvement, reactive arthritis pattern) 1

Additional Testing

• Blood cultures if fever present or acute onset to identify bacteremia 1
• Vitamin B12 and folate if macrocytosis present or cause unclear 2
• Haptoglobin and lactate dehydrogenase if hemolysis suspected 2

Imaging Studies

• Plain radiographs of affected joints at baseline to evaluate joint damage, erosions, and exclude alternative diagnoses 1
• Chest radiograph if systemic symptoms present or tuberculosis suspected 1
• Ultrasound or MRI for persistent arthritis unresponsive to treatment, suspected septic arthritis, or equivocal clinical findings 1

Pre-Treatment Screening

Before initiating any DMARD or immunosuppressive therapy, test for 1:

• Viral hepatitis B and C
• Latent/active tuberculosis

Treatment Approach

Treat the Underlying Inflammatory Disease First

Treating the underlying inflammatory condition is the first step in managing anemia, though this alone rarely normalizes hemoglobin levels 2. The likelihood of anemia increases with disease severity, and anemia independently predicts accelerated radiographic joint damage even after adjusting for clinical disease activity measures 4, 3.

Iron Supplementation

Iron supplementation is recommended in all patients when iron deficiency anemia is present 2:

• Mild anemia (Hb >10 g/dL): Oral iron sulfate 100 mg/day may be adequate 2
• Moderate to severe anemia or active inflammation: Intravenous iron is preferred as it is more effective and avoids gastrointestinal side effects that can exacerbate IBD 2
• Dosing for IV iron (if IBD-associated):
  • Hb 10-12 g/dL (women) or 10-13 g/dL (men): 1000 mg if <70 kg, 1500 mg if ≥70 kg 2
  • Hb 7-10 g/dL: 1500 mg if <70 kg, 2000 mg if ≥70 kg 2

Monitoring Strategy

• Serial rheumatologic examinations with inflammatory markers every 4-6 weeks after treatment initiation 1
• UC patients in remission: Monitor every 12 months; mild disease every 6 months 2
• Repeat radiographs within 1 year to assess disease progression 1
• Recurrence of anemia is common (>50% after 1 year) and often indicates ongoing intestinal inflammation 2

Critical Pitfalls to Avoid

• Do not rely on ferritin alone in inflammatory states: Ferritin is an acute-phase reactant and can be falsely elevated despite true iron deficiency 2
• Do not ignore anemia as merely a symptom: Anemia independently predicts worse joint outcomes and quality of life, warranting specific diagnosis and treatment 5, 4, 3
• Do not use intramuscular iron: No evidence it is less toxic or more effective than oral or IV routes 2
• Avoid oral iron in active IBD when possible: Unabsorbed iron generates reactive oxygen species that can exacerbate inflammatory bowel disease 2