In a patient with active Lyme disease (positive IgG serology, fatigue, and knee pain), can serum ferritin be elevated?

Can Ferritin Be Elevated in Active Lyme Disease?

Ferritin elevation is not a recognized feature of active Lyme disease itself, but can occur if there is a co-infection with Anaplasma (human granulocytic anaplasmosis) or if the patient develops hemophagocytic lymphohistiocytosis as a complication of tick-borne illness.

Primary Consideration: Lyme Disease Alone Does Not Typically Elevate Ferritin

The major clinical practice guidelines for Lyme disease 1, 2 do not identify ferritin elevation as a characteristic laboratory finding in active Lyme borreliosis. The typical laboratory abnormalities in Lyme disease are limited to:

• Elevated inflammatory markers (ESR, CRP) in some cases
• CSF pleocytosis in neuroborreliosis
• Positive Borrelia-specific serology (IgM and/or IgG)

Your patient's presentation with positive IgG serology, fatigue, and knee pain is consistent with Lyme arthritis 1, but this would not explain ferritin elevation.

Critical Differential: Co-infection with Anaplasma

If ferritin is markedly elevated (>1000-5000 μg/L), strongly consider co-infection with Anaplasma phagocytophilum (human granulocytic anaplasmosis/HGA). This is transmitted by the same Ixodes tick that carries Borrelia and can present with:

• Fever, malaise, myalgia
• Profound hyperferritinemia (levels >5000 ng/mL documented) 3
• Elevated liver transaminases
• Acute kidney injury in severe cases
• Risk of progression to hemophagocytic lymphohistiocytosis if untreated 3

Algorithmic Approach to Elevated Ferritin in This Context

If ferritin >1000 μg/L:

1. Check for tick-borne co-infections - Order Anaplasma serology immediately
2. Assess for HLH criteria - Check CBC with differential, triglycerides, fibrinogen, liver enzymes
3. Consider other causes - Malignancy (most common cause overall) and iron overload syndromes are more frequent than rheumatologic causes 4

If ferritin 500-1000 μg/L:

• Consider chronic inflammation from the Lyme arthritis itself (though uncommon)
• Evaluate for concurrent conditions (infection, malignancy, chronic disease)

If ferritin <500 μg/L:

• Likely unrelated to the Lyme disease

Important Caveats

• Extremely elevated ferritin (>10,000 μg/L) suggests adult-onset Still's disease, systemic JIA, or HLH 4, not typical Lyme disease
• Doxycycline treats both Lyme disease and Anaplasma - If co-infection is suspected, this is the preferred antibiotic 3
• The average ferritin in inflammatory rheumatologic conditions is 14,242 μg/L, far higher than typical infectious causes 4
• In a large study of 627 patients with ferritin >1000 μg/L, malignancy and iron overload were most common; only 7 had anemia of chronic inflammation 4

Clinical Bottom Line

Do not attribute ferritin elevation to Lyme disease alone. Investigate for Anaplasma co-infection if the ferritin is significantly elevated (>1000 μg/L), especially if there are systemic symptoms beyond arthritis. If Anaplasma testing is positive or highly suspected clinically, ensure doxycycline is part of the treatment regimen, as it covers both pathogens effectively.