What is the best course of action for a patient potentially exposed to Per- and Polyfluoroalkyl Substances (PFAS)?

PFAS Blood Testing and Clinical Management

For patients with potential PFAS exposure, blood testing should be performed to measure serum PFAS levels, with clinical action focused on monitoring immune function—particularly vaccine antibody responses—and screening for metabolic complications, as these represent the most sensitive and well-documented health impacts. 1

Who Should Be Tested

• Individuals with known exposure to contaminated water supplies (particularly when PFAS levels exceed 20 ng/mL in community water sources) 2
• Residents of communities near AFFF (aqueous film-forming foam) contamination sites, including military bases and firefighting training facilities 1
• Occupationally exposed workers in industries using PFAS-containing products 3
• Individuals consuming contaminated seafood from affected regions, as seafood represents a major dietary exposure source 4

What to Test

Initial Blood Testing

• Serum PFAS panel including at minimum: PFOA, PFOS, PFHxS, PFNA, and PFDA 1, 3
• These five compounds represent the most studied and frequently detected PFAS in human populations 3, 5

Follow-up Testing Based on Results

For PFAS levels >20 ng/mL (highest exposure category): 2

• Vaccine antibody titers, specifically tetanus and diphtheria antibodies, as reduced antibody response represents the strongest evidence of PFAS immunotoxicity 2, 1, 6
• Lipid panel (total cholesterol, LDL, HDL, triglycerides) due to established associations with dyslipidemia and cardiovascular risk 2, 3
• Liver function tests (ALT, AST, GGT) to assess hepatotoxicity 1
• Screen for ulcerative colitis symptoms at routine well-visits 2

Clinical Management Algorithm

Step 1: Risk Stratification by Serum PFAS Level

• Low exposure (<20 ng/mL): Annual monitoring with lipid panels 2
• High exposure (≥20 ng/mL): Implement comprehensive immune and metabolic monitoring 2

Step 2: Immune Function Assessment

• Check tetanus and diphtheria antibody titers 4-6 weeks after routine vaccination 2, 1
• If antibody response is inadequate: Administer additional booster doses not normally required 2, 1
• Monitor for increased susceptibility to infections, including respiratory and gastrointestinal infections 1, 6

Step 3: Implement Protective Measures

Treat PFAS-exposed patients similarly to immunocompromised individuals: 2, 1

• During infectious disease outbreaks (influenza, COVID-19), recommend enhanced precautions including masking, social distancing, and prioritization for vaccination 2
• Counsel on avoiding additional PFAS exposure through contaminated water, food packaging, and consumer products 4, 5
• For pregnant women: Close monitoring as PFAS affects placental function through immune-mediated mechanisms 1

Step 4: Metabolic Monitoring

• Lipid panels every 6-12 months for patients with elevated PFAS levels 2, 3
• Screen for hypertension at each visit, as evidence supports association with PFAS mixtures 3
• Monitor for adiposity changes and metabolic syndrome development 3

Critical Caveats and Pitfalls

Testing Limitations

• Most PFAS lack comprehensive toxicity data—only PFOA and PFOS have been extensively studied, yet thousands of PFAS compounds exist 2, 3
• Standard panels may miss emerging PFAS of concern, but testing for the five main compounds (PFOA, PFOS, PFHxS, PFNA, PFDA) captures the majority of documented health risks 3, 5

Interpretation Challenges

• PFAS levels vary by age and sex—older individuals and males typically show higher serum concentrations due to differences in elimination rates 4, 7
• Pregnancy and breastfeeding alter PFAS kinetics, requiring adjusted reference ranges 1
• Compare results to population norms: In the 2013-2014 NHANES, median PFNA was significantly lower than in contaminated communities (285% difference documented in Paulsboro, NJ) 7

Clinical Guidance Gaps

The 2022 NASEM guidance paradoxically recommends screening for ulcerative colitis (limited evidence) but not for vaccine antibody responses (sufficient evidence), creating an inconsistency that clinicians should recognize. 2 The National Research Council's 1992 recommendations to check immune function 1-2 times yearly for all immunotoxicant-exposed individuals remain more comprehensive 2.

Vulnerable Populations

• Children are particularly susceptible to PFAS immunotoxicity during immune system development 1, 6
• Individuals with pre-existing immune compromise face compounded risks 1

When to Refer

• Persistently inadequate vaccine responses despite additional boosters warrant referral to immunology 1
• Development of autoimmune conditions (ulcerative colitis, thyroid disease) in highly exposed individuals 2
• Occupational exposure cases may benefit from occupational medicine consultation 3