When should a lacrimal level be checked in patients with symptoms of excessive tearing or suspected lacrimal apparatus dysfunction, including infants, postmenopausal women, and those with a history of autoimmune diseases or facial trauma?

When to Check Lactoferrin Levels

Lactoferrin levels should be checked when evaluating patients with clinically significant dry eye and suspected Sjögren syndrome, particularly when there is concurrent dry mouth, systemic symptoms, or viral infections such as hepatitis C that may affect tear composition.

Primary Indications for Lactoferrin Testing

Suspected Sjögren Syndrome

• Ophthalmologists should maintain a high index of suspicion for Sjögren syndrome and have a low threshold for serological work-up in patients with clinically significant dry eye, as approximately 10% of these patients have underlying primary Sjögren syndrome 1
• Lactoferrin testing is particularly relevant when dry eye occurs in younger patients or males, despite the strong female predominance (20:1 ratio), as this should raise suspicion for systemic or local associated conditions 1, 2
• Decreased tear concentrations of lactoferrin have been specifically reported in patients with hepatitis C virus infection, making this a key scenario for testing 1

High-Risk Clinical Scenarios Warranting Lactoferrin Assessment

Postmenopausal women with dry eye symptoms should be evaluated more thoroughly, as dry eye is most common in this population and may indicate underlying autoimmune disease 1

Patients with concurrent systemic symptoms including:

• Dry mouth (xerostomia) requiring frequent water sipping or liquids to swallow dry foods 2
• Joint pain (arthralgias) and muscle pain (myalgias) 2
• Extreme fatigue 2
• Peripheral neuropathy (numbness or burning pain in extremities) 2

Viral infection contexts where lactoferrin may be reduced:

• Hepatitis C infection (specifically documented to reduce tear lactoferrin) 1
• HIV/AIDS (dry eye diagnosed in 21% of AIDS patients) 1
• Epstein-Barr virus infections associated with lacrimal gland swelling 1

Diagnostic Algorithm for Lactoferrin Testing

Initial Clinical Assessment

• Perform slit-lamp biomicroscopy evaluating tear meniscus height, tear break-up time, and ocular surface staining with fluorescein or lissamine green 2
• Assess for lacrimal gland enlargement on external examination 2
• Document presence of both dry eye AND dry mouth symptoms, as this combination significantly increases Sjögren syndrome probability 2

When to Proceed with Lactoferrin Testing

Order lactoferrin levels when:

1. Schirmer test shows ≤5 mm/5 minutes without anesthesia (scores 1 point toward Sjögren diagnosis) 2
2. Patient has known hepatitis C infection with ocular symptoms 1
3. Clinically significant aqueous deficient dry eye is present with systemic inflammatory symptoms 1
4. Initial serological testing (Anti-SSA/Ro antibody) is negative but clinical suspicion remains high 2

Integration with Comprehensive Serological Work-Up

• Lactoferrin testing should be part of a broader evaluation including rheumatoid factor, Anti-SSA/Ro antibodies, and potentially point-of-care testing for salivary protein 1, carbonic anhydrase 6, and parotid secretory protein 2
• Co-management with rheumatology is mandatory given that approximately 5% of Sjögren syndrome patients develop lymphoid malignancy, representing an increased incidence of 320 cases per 100,000 patient-years 1, 2

Critical Pitfalls to Avoid

• Do not delay lactoferrin testing in patients with both dry eye and systemic viral infections, particularly hepatitis C, as this is a documented cause of reduced tear lactoferrin 1
• Do not dismiss the possibility of Sjögren syndrome based solely on negative Anti-SSA antibody results, as diagnosis can still be made with a total score of ≥4 points using other objective criteria including tear composition abnormalities 2
• Do not overlook the need for lactoferrin assessment in patients with graft-versus-host disease following hematopoietic stem cell transplants, as severe dry eye with lacrimal gland infiltration and fibrosis commonly occurs 1

Special Populations Requiring Consideration

Infants and Children

• While lactoferrin testing is less commonly performed in pediatric populations, consider evaluation in children with HIV infection and diffuse infiltrative lymphadenopathy syndrome 1

Post-Surgical or Post-Radiation Patients

• Patients with history of orbital/eyelid surgery or radiation may develop dry eye, though lactoferrin testing is more relevant when autoimmune etiology is suspected rather than mechanical causes 1

Patients with Facial Trauma

• Lactoferrin testing is not typically indicated for epiphora related to nasolacrimal duct obstruction from trauma, as this represents a mechanical rather than secretory problem 3