ModifiedMolina HealthcarePolicy G2155

General Inflammation Testing (CRP and ESR)

Policy G2155 defines coverage criteria and limitations for measurement of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as inflammatory biomarkers across multiple diagnosed or suspected inflammatory conditions, including test preferences and recommended testing frequency for specific conditions.

Policy Summary

PayerMolina Healthcare

PolicyGeneral Inflammation Testing (CRP and ESR)

Policy CodePolicy G2155

Change TypeClarification + operational enforcement

Effective Date

Next Review Date

Key ActionDo not order ESR for individuals without a diagnosed inflammatory condition; follow Note 1 indications and when both are ordered for a condition that allows only one, expect only CRP to be approved.

POLICY UPDATE CHANGES

Revision Date listed as 10/15/2025 in header.

Removed the word 'inflammatory' from CC1 to reflect that some conditions in Note 1 are noninflammatory and CRP/ESR are used to differentiate between noninflammatory and inflammatory conditions.

Added enforcement statement: 'If CRP and ESR are ordered at the same time for a condition where CRP or ESR are allowed, only CRP will be approved.'

Within the table of Note 1, added '(e.g., inflammatory bowel disease)' in the 'Frequency of Testing' column for IBS to clarify rationale for including a noninflammatory condition.

16+Conditions listed with test preferences

1Policy number

4Primary CPT codes listed

1Material Enforcement Change(s)

1MIS-C numeric thresholds cited

Coverage Summary

Policy G2155 addresses coverage for measurement of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as biomarkers for inflammation across a range of diagnosed or suspected inflammatory conditions. The policy stance is mixed: CRP and/or ESR meet coverage criteria for the specific conditions listed in Note 1, but ESR testing is not covered for individuals without a diagnosed inflammatory condition and routine testing during a general exam without abnormal findings is not covered. The policy includes test preferences and frequency guidance for specific conditions and an operational enforcement that when both CRP and ESR are ordered concurrently for a condition that allows only one, only CRP will be approved. Last reviewed: 2025-10-15.

Key facts

Policy numberG2155

SubjectGeneral inflammation testing (CRP and ESR)

Coverage stanceMixed

Last review2025-10-15

Medical-Necessity Criteria

Coverage Determination

Covered when the diagnostic or monitoring condition meets the specified indications:

Measurement of C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) MEETS COVERAGE CRITERIA for the conditions specified in Note 1.

Not Covered

For individuals without a diagnosed inflammatory condition, measurement of ESR DOES NOT MEET COVERAGE CRITERIA.

Measurement of CRP and/or ESR during general exam without abnormal findings DOES NOT MEET COVERAGE CRITERIA.

Coverage Criteria and Note 1 Clarification

Modifications for clarity without changing coverage criteria; specific operational enforcement added for CRP vs ESR:

Guideline-based Indications and Monitoring

Guideline-based indications and monitoring recommendations (multiple organizations)

Coverage/clinical appropriateness guidance summarized from professional society guidelines:

EULAR (large vessel vasculitis, 2009 & 2018): recommend clinical monitoring supported by ESR and CRP; schedule follow-up visits every 1-3 months during first year and 3-6 months thereafter (2018 update).

No specific preference of ESR vs CRP stated.

EULAR (early arthritis, 2016): monitor disease activity including ESR and CRP, usually using composite measures, assess every 1-3 months until treatment target reached, then less frequently.

Recommends composite measures; frequency depends on activity.

EULAR/ACR (PMR, 2015): baseline labs before therapy to exclude mimics and establish monitoring baseline; include RF/ACPA, CRP and/or ESR, CBC, CMP, bone profile, UA.

No specific frequency stated.

Provider Actions and Operational Rules

Documentation Required

Order tests only for diagnosed/suspected inflammatory conditions

Do not order ESR for individuals without a diagnosed inflammatory condition; ordering ESR or CRP during a general exam without abnormal findings does not meet coverage criteria.

Billing Rule

CRP preferred when both are allowed

When either CRP or ESR are allowed, CRP is the preferred biomarker; if both CRP and ESR are ordered for a condition where CRP or ESR are allowed, only CRP will be approved (payer will approve only CRP).

Coding

Applicable CPT/HCPCS procedure codes (other/neutral)mixed

No codes listed

Covered CPT/HCPCS Procedure CodesCPTCovered

85651	Sedimentation rate, erythrocyte; non-automated.
85652	Sedimentation rate, erythrocyte; automated.
86140	C-reactive protein.
86141	C-reactive protein; high sensitivity (hsCRP).

Providers should order CRP or ESR only according to the conditions and frequencies specified in Note 1 and document indications when ordering ESR given its lower specificity and method variability. CRP is the preferred biomarker when either test is allowed; operationally, if both tests are ordered for a condition where only one is permitted, only CRP will be approved. Applicable CPT codes include 85651, 85652, 86140 (and 86141 for hsCRP). Per regional operational rules (for example, British Columbia guidance), outpatient laboratories may perform only CRP and will perform ESR only if a written indication is provided on the requisition; ESR may not be payable if not justified, risking non-payment when ESR is not indicated.

Evidence and Clinical Thresholds

Study/Source	Key result
Watson et al. (2019)	CRP had higher overall diagnostic AUC (0.682) vs ESR (0.589); adding a second test minimally increased AUC to 0.688 — authors conclude multiple markers rarely improve diagnostic accuracy and CRP should generally be first-line.
Berbari et al. (2010) meta-analysis	CRP diagnostic odds ratio 13.1 vs ESR diagnostic odds ratio 7.2 for prosthetic joint infection (23 studies included CRP in 23/30, ESR in 25/30).
Bingham et al. (2019)	Identified lower cutoffs to achieve ≥95% sensitivity for PJI screening: ESR 10 mm/h and CRP 5 mg/L; combined thresholds yielded 100% sensitivity in their cohort; standard MSIS cutoffs (ESR 30 mm/h, CRP 10 mg/L) had lower sensitivity.
Guideline references (multiple societies)	Numerous professional guidelines cited (EULAR, ACR, BSR, NICE, AAFP, AAOS, AGA, WHO, PIDS/IDSA, Government of British Columbia) providing condition-specific recommendations and monitoring guidance, generally favoring CRP for acute inflammation and noting settings where ESR is specifically informative (e.g., Hodgkin lymphoma, some SLE/low-grade infections).

Numeric thresholds

MIS-C triggerCRP ≥5 mg/L or ESR ≥40 mm/hr

Hodgkin lymphoma (unfavorable)ESR ≥50 mm/hr

AAOS/MSIS common PJI cutoffs (discussed)ESR 30 mm/hr and CRP 10 mg/L (alternative study: ESR 10 mm/hr and CRP 5 mg/L for ≥95% sensitivity)

Early-onset neonatal sepsis (study)CRP ≥10 mg/L

ESR/CRP ratio to differentiate PJI acuity (study)ESR/CRP ratio cutoff = 0.96 (chronic >0.96; acute <0.96)

AAFP PMR/GCA ESR elevation referenceESR >30 to 40 mm/hr (approximate) associated with PMR/GCA

Revision History

10/15/2025revisedLatest

Revision Date listed as 10/15/2025 in header.

revised

Removed the word 'inflammatory' from CC1 to reflect that some conditions in Note 1 are noninflammatory and CRP/ESR are used to differentiate between noninflammatory and inflammatory conditions.

added

Added enforcement statement: 'If CRP and ESR are ordered at the same time for a condition where CRP or ESR are allowed, only CRP will be approved.' (MATERIAL ENFORCEMENT CHANGE)

Policy Summary

PayerMolina Healthcare

PolicyGeneral Inflammation Testing (CRP and ESR)

Policy CodePolicy G2155

Change TypeClarification + operational enforcement

Effective Date

Next Review Date

On This Page

Measurement of C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) MEETS COVERAGE CRITERIA for the conditions specified in Note 1.

If CRP and ESR are ordered at the same time for a condition where CRP or ESR are allowed, only CRP will be approved.

Operational enforcement: simultaneous orders for both tests when only one is allowed will result in approval of CRP alone.

ACR (RA activity measures, 2012 & 2019): endorse DAS28, SDAI, CDAI, RAPID3; DAS28 can use CRP or ESR (both validated).

No frequency specified in 2012; 2015 ACR suggests functional status at least annually.

ACR (GCA, 2021): do not recommend CRP/ESR for diagnosis alone; recommend inflammation marker monitoring as part of long-term clinical monitoring; for isolated rises in markers without other signs, recommend observation and increased clinical/radiographic assessment rather than automatic escalation of immunosuppression.

Optimal frequency not established; monitoring recommended long-term.

AAFP (PMR/GCA, 2013 & 2022): recommend testing ESR or CRP at each clinic visit; baseline and monitoring labs at presentation and during management; consider IL-6 when ESR/CRP not elevated but suspicion high.

AAFP recommends routine testing at each visit.

ACR (MIS-C): tier one testing includes ESR and CRP; proceed to tier two if CRP ≥5 mg/L or ESR ≥40 mm/hr with other suggestive lab features.CRP ≥5 mg/L or ESR ≥40 mm/hr

Triggers further cardiac evaluation in children.

AAOS (PJI): strong evidence supports ESR and CRP to aid preoperative diagnosis of prosthetic joint infection but neither is perfect; should not be sole diagnostic test.

Used as part of diagnostic evaluation; adjunctive tests required.

WHO: recommends CRP as preferred test for detecting inflammation; ESR may be used where CRP unavailable and may be informative in SLE and low-grade bone/joint infections.

WHO prefers CRP except in some conditions.

Bingham et al. / MSIS-related PJI thresholds: ESR 10 mm/h and CRP 5 mg/L achieved ≥95% sensitivity in one study; commonly used cutoffs cited include ESR 30 mm/h and CRP 10 mg/L.ESR 10 mm/h; CRP 5 mg/L

AAOS/MSIS common PJI cutoffs discussed.

BSR/ BHPR and BSR guidance (GCA/PMR, SLE): recommend baseline CRP/ESR and monitoring; BSR notes CRP for all suspected GCA and ESR/plasma viscosity optional; BSR (SLE) recommends CRP at diagnosis and every 1-3 months during active disease then every 6-12 months once stabilized.

BSR advises CRP for all suspected GCA and ESR/plasma viscosity optional; CRP testing advised during pregnancy for mothers with SLE.

CRP and ESR are nonspecific inflammatory biomarkers used across many conditions (for example, RA, PMR, GCA, SLE, cardiovascular disease, Hodgkin lymphoma, and periprosthetic joint infection). CRP is generally more sensitive and specific for acute inflammation, rises rapidly after tissue injury or infection, and is preferred in many settings (WHO and multiple specialty guidelines recommend CRP as the first-line test). ESR is a simple sedimentation method (Westergren and alternate automated methods exist) but is influenced by noninflammatory factors (age, anemia, renal disease, obesity, ambient conditions) and by methodology variability between Westergren and other methods, which can produce substantial measurement differences. Guidelines therefore generally prefer CRP except in certain conditions (for example, SLE, low-grade bone/joint infections, and Hodgkin lymphoma) where ESR can provide additional or specific information.

Documentation Required

Because ESR has lower specificity and is influenced by noninflammatory factors and methodology, ensure documentation ties ESR orders to conditions where ESR is specifically allowed (e.g., Hodgkin lymphoma, certain SLE and low-grade bone/joint infections).

Documentation Required

Indication documentation for ESR when CRP elevated (BC guideline operational rule)

If ordering ESR when CRP is elevated, provide a written indication on the laboratory requisition in jurisdictions following British Columbia guidance; outpatient labs may only perform CRP unless ESR indication is stated.

Affected codes: 85651, 85652, 86140

Documentation Required

Baseline labs prior to initiating therapy for PMR and GCA

Obtain baseline labs including CRP and/or ESR, CBC, CMP, bone profile, and relevant serologies prior to starting long-term steroid/immunosuppressive therapy for PMR/GCA or document reason if immediate treatment given.

Include CRP/ESR, CBC, CMP, bone profile, serologies

Prior Authorization

Laboratory-developed tests (LDTs) validation note

Recognize that LDTs are regulated under CLIA as high-complexity tests and may have local lab validation requirements; FDA clearance is not required for clinical use.

Denial Risk

Potential non-payment when ESR not indicated

Outpatient laboratories may perform only CRP and not ESR unless a written indication is provided; ESR may not be payable per local outpatient payment schedules if not justified.

Affected codes: 85651, 85652

Documentation Required

Use of CRP/ESR with disease activity scores

When using composite disease activity scores (e.g., DAS28, SDAI), document which acute phase reactant (CRP or ESR) is used as either is acceptable per guidelines; timing/logistics of measurements should align with composite score requirements.

Codes referenced where applicable: 85651, 85652, 86140

Documentation Required

Follow Note 1 indications and frequency guidance

Providers must order CRP or ESR according to the conditions and frequency specified in Note 1; when both are ordered concurrently for a condition that allows only one, only CRP will be approved.

revised

Within the table of Note 1, added '(e.g., inflammatory bowel disease)' in the 'Frequency of Testing' column for IBS to clarify rationale for including a noninflammatory condition.