Diagnostics and Clinical Diagnostics and Clinical Markers in CRPSMarkers in CRPS

Edwin Perez, MDEdwin Perez, MDPain FellowPain Fellow

University of Washington University of Washington

PreamblePreamble

““Whatever the Thinker thinks, the Whatever the Thinker thinks, the Prover provesProver proves””

-Robert Anton Wilson-Robert Anton WilsonPrometheus Rising,1983Prometheus Rising,1983

GoalsGoalsMedical History of DiseasesMedical History of DiseasesCurrent Diagnostic Criteria in CRPSCurrent Diagnostic Criteria in CRPSCurrent Surrogate Markers in CRPSCurrent Surrogate Markers in CRPSRationale for Non-Practitioner Based Rationale for Non-Practitioner Based

Diagnostic and Prognostic ToolsDiagnostic and Prognostic ToolsOverview of Recently Used ToolsOverview of Recently Used ToolsFuture DirectionsFuture Directions

What Disease Process is This?What Disease Process is This?

Gay Related Immunodeficiency Gay Related Immunodeficiency SyndromeSyndrome

Identified in 1982Identified in 1982Diagnostic CriteriaDiagnostic Criteria

1)1) Homosexual PromiscuityHomosexual Promiscuity2)2) Heterosexual living in proximityHeterosexual living in proximity

3)3) Use of Amyl NitrateUse of Amyl Nitrate4)4) Haitian DescentHaitian Descent

2008 Diagnosis-AIDS2008 Diagnosis-AIDS

1986 Diagnostic Criteria1986 Diagnostic Criteria

Presence of HIV-1 or HIV-2 by Presence of HIV-1 or HIV-2 by ELISA/Western BlotELISA/Western Blot

What Disease Process is This?What Disease Process is This?

Multiple SclerosisMultiple Sclerosis1960 Diagnostic Criteria1960 Diagnostic Criteria

Age 10-50Age 10-50History of Neurologic AbnormalitiesHistory of Neurologic AbnormalitiesEvidence of changes over time and spaceEvidence of changes over time and spaceExam with Neurological AbnormalitiesExam with Neurological AbnormalitiesNeurologic Attacks lasting 24hrs and Spaced 1 Neurologic Attacks lasting 24hrs and Spaced 1

month apartmonth apartNo better explanationNo better explanationDiagnosis made by competent physician-Diagnosis made by competent physician-

neurologistneurologist

MRI invented 1977MRI invented 1977

Now Routinely used in Diagnosis of MSNow Routinely used in Diagnosis of MS

AlsoAlso

Now Routinely used as a Marker of MS Now Routinely used as a Marker of MS progression and Serial MRIs are part of progression and Serial MRIs are part of Standard of CareStandard of Care

MRI as a Marker of MSMRI as a Marker of MS

““Unfortunately, however, changes in MRI Unfortunately, however, changes in MRI behavior have not yet been convincingly behavior have not yet been convincingly shown to be sufficiently specific or shown to be sufficiently specific or predictive of disease progression to allow predictive of disease progression to allow clinicians to feel confident that a short-clinicians to feel confident that a short-term change in MRI behavior will term change in MRI behavior will accurately predict and important later accurately predict and important later change in clinically identifiable disease change in clinically identifiable disease progression”progression”

Complex Regional Pain Syndrome Complex Regional Pain Syndrome (CRPS)(CRPS)

Circa 1947Circa 1947 Evans coined the term “reflex sympathetic dystrophy”Evans coined the term “reflex sympathetic dystrophy”

1994 IASP Criteria For CRPS1994 IASP Criteria For CRPSType 1Type 1

1)1) Presence of a noxious event (not necessary)Presence of a noxious event (not necessary)2)2) Continuing pain, allodynia, hyperalgesia, with which Continuing pain, allodynia, hyperalgesia, with which

the pain is disproportionate to any inciting eventthe pain is disproportionate to any inciting event3)3) Evidence at some time of edema, changes in skin Evidence at some time of edema, changes in skin

blood flow, or abnormal sudomotor activity in the blood flow, or abnormal sudomotor activity in the region of the painregion of the pain

4)4) This diagnosis is excluded by the existence of This diagnosis is excluded by the existence of conditions that would otherwise account for the degree conditions that would otherwise account for the degree of pain and dysfunctionof pain and dysfunction

1994 IASP Criteria For CRPS1994 IASP Criteria For CRPSType 2Type 21)1) The presence of continuing pain, allodynia, or The presence of continuing pain, allodynia, or

hyperalgesia after a nerve injury, not hyperalgesia after a nerve injury, not necessarily limited to the distribution of the necessarily limited to the distribution of the injured nerveinjured nerve

2)2) Evidence at some time of edema, changes in Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity skin blood flow, or abnormal sudomotor activity in the region of the painin the region of the pain

3)3) This diagnosis is excluded by the existence of This diagnosis is excluded by the existence of conditions that would otherwise account for the conditions that would otherwise account for the degree of pain and dysfunctiondegree of pain and dysfunction

(All three criteria must be satisfied)(All three criteria must be satisfied)

2007 Proposed Diagnostic Criteria 2007 Proposed Diagnostic Criteria for CRPS for CRPS (sensitivity 0.76/specificty 0.83)(sensitivity 0.76/specificty 0.83)

1)Continuing pain, which is disproportionate to any 1)Continuing pain, which is disproportionate to any inciting eventinciting event

2) Must report at least 1 symptom in ¾ categories-2) Must report at least 1 symptom in ¾ categories-sensory, vasomotor, sudomotor, motor/trophicsensory, vasomotor, sudomotor, motor/trophic

3) One sign at evaluation in 2 or more categories-3) One sign at evaluation in 2 or more categories-sensory,vasomotor,sudomotor, motor/trophicsensory,vasomotor,sudomotor, motor/trophic

4) There is no other diagnosis that better explains 4) There is no other diagnosis that better explains the signs and symptomsthe signs and symptoms

Currently Used MarkersCurrently Used Markers

NONENONE

Rationale for CRPS TestsRationale for CRPS TestsStigma associated with diagnosis of CRPSStigma associated with diagnosis of CRPSMay lead to new modalities of treatmentMay lead to new modalities of treatmentPrognosticationPrognosticationPossible increased patient satisfactionPossible increased patient satisfactionMay lead to new treatment algorithmMay lead to new treatment algorithmPatient ValidationPatient Validation

StigmaStigma “Many CRPS patients are mentally anguished

because physicians misdiagnose their condition or disregard it as imaginary.”

“Few physicians are familiar with the disease

and some maintain that the disease is a psychiatric condition where “patients with this were often dismissed as being ‘neurotic,’ ‘self-serving,’ or ‘somatizing”

Modalities of TreatmentModalities of Treatment

Designer TreatmentDesigner TreatmentGerman 5 Day Ketamine Coma-30,000 EuroGerman 5 Day Ketamine Coma-30,000 Euro

Common TreatmentCommon TreatmentPhysical Therapy-238,808 USPhysical Therapy-238,808 US

Physical Therapy + Spinal Cord Stimulator-Physical Therapy + Spinal Cord Stimulator-177,999 US177,999 US

Stellate Ganglion Block Total Cost-1,400 USStellate Ganglion Block Total Cost-1,400 USLyrica-1,920 US Lyrica-1,920 US

Patient Satisfaction And ValidationPatient Satisfaction And Validation

The average CRPS patient sees eight to ten doctors before a diagnosis is made.

Medical testing is not available to diagnose CRPS thus the lack of certainty for diagnosis “raises doubts in the eyes of doctors and the people that are looking for hard lab evidence or good imaging confirmation.”

ImagingImagingStudies have looked at:Studies have looked at:

1)1) Thermography-8 weeks?Thermography-8 weeks?2)2) Plain XR-maybe laterPlain XR-maybe later3)3) MRI with contrast-consequence of trauma or operationsMRI with contrast-consequence of trauma or operations4)4) Triple phase bone scan-maybe laterTriple phase bone scan-maybe later

One study from 2007 had the following conclusion:One study from 2007 had the following conclusion:

““The poor sensitivity of all tested procedures combined with a The poor sensitivity of all tested procedures combined with a reasonable specificity produced a low positive predictive value reasonable specificity produced a low positive predictive value (17% to 60%) and a moderate negative predictive value (79% to (17% to 60%) and a moderate negative predictive value (79% to 86%). These results suggest, that these procedures cannot be used 86%). These results suggest, that these procedures cannot be used as screening tests. Clinical findings remain the gold standard for the as screening tests. Clinical findings remain the gold standard for the diagnosis of CRPS I”diagnosis of CRPS I”

Laboratory DataLaboratory DataSystemic markers-CRP and IL-6 found to Systemic markers-CRP and IL-6 found to

be not elevated in CRPSbe not elevated in CRPS IL-8 was found elevated in one study but IL-8 was found elevated in one study but

not in another studynot in another studyCSF studies for IL-6 and TNF are CSF studies for IL-6 and TNF are

inconclusiveinconclusiveBlister analysis shows some increase in Blister analysis shows some increase in

IL-6 and TNF as in CRPS patients IL-6 and TNF as in CRPS patients compared to non-CRPS patientscompared to non-CRPS patients

Future DirectionsFuture Directions

1) Genetics?1) Genetics?-Angiotensin gene is not correlated-Angiotensin gene is not correlated-Twin studies-Twin studies2) Quantitative sensory pointing to 2) Quantitative sensory pointing to

Thalamus?Thalamus?-like ballism-like ballism3) Economic Analysis?3) Economic Analysis?

In ConclusionIn Conclusion

““-and somewhere within him, a drop of pain -and somewhere within him, a drop of pain moving briefly and vanishing, like a moving briefly and vanishing, like a raindrop on the glass of a window, its raindrop on the glass of a window, its course in the shape of a question mark”course in the shape of a question mark”

Ayn RandAyn RandAtlas ShruggedAtlas Shrugged

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