OFFICE of RESEARCH & DEVELOPMENT

Chronic Multisymptom Illness: Insights from a Population Based Health Evaluation

National Academy of Sciences

Seth Eisen, MD, MSc VA Office of Research and Development (ORD)

Seth.Eisen@va.gov

June 26, 2013

Illnesses Among United States Veterans of the Gulf War: A Population-Based Survey of 30,000 Veterans
Kang HK, Mahan CM, Lee KY et al. Journal of Occupational & Environmental Medicine. 2000:42; 491-501.

In a population based sample of 15,000 deployed and 15,000 non-deployed Gulf War era Veterans, Gulf War Veterans reported a higher prevalence of: Functional impairment Health care utilization Medical symptoms and conditions Low general health
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Medical Evaluation of a Gulf War Veteran Cohort

Eisen SA et al. Ann Intern Med 2005:142:881 VETERANS HEALTH ADMINISTRATION

Medical Evaluation of a Gulf War Veteran Cohort

Standardized evaluations (12 hours, 2 days) at 16 VA medical centers o Physical exam and laboratory tests o Dermatologic exam o Neurologic exam by a neurologist, and nerve conduction study (NCS) o Pulmonary function tests o Psychiatric assessment with CIDI1; PTSD with CAPS2 o Fibromyalgia syndrome exam o Chronic fatigue syndrome
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CIDI: Composite International Diagnostic Interview CAPS: Clinician Administered PTSD Scale
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Results: Self-Reported Illnesses

Self-Reported Illnesses No Differences in: o past year health visits, gastritis, HBP, hepatitis, arthritis, bronchitis, asthma, diabetes, neuropathic symptoms, thyroid abnormalities Differences: o Chronic fatigue syndrome (2.3% vs 0.4%; OR = 8.5, p<.004) o Skin rash (40% vs 28%; OR = 1.74, p<.001)

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Results: Comprehensive Examination

Clinical Evaluation No Differences In: o HBP, hepatitis, chronic obstructive lung disease (PE and PFT), DM, peripheral neuropathy (PE and NCS), hypo/hyperthyroidism Differences: o Self Reported physical health (SF-36) (49.3 vs 50.8); p<.001 o Dyspepsia1 9% vs 6%; OR 1.4, OR 1.9, p.01 o Fibromyalgia Syndrome (2.0% vs 1.2%); OR 2.3, p=.04 o Chronic fatigue syndrome (1.6% vs 0.1%); OR 40.6, p<001) o Group 22 skin conditions (35% vs 27%); OR 1.3, p=.02
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Dyspepsia: frequent heartburn, recurrent abdominal pain, and use of antacids or H2blockers Group 2 Skin = conditions other than moles, freckles, scars, hemangiomas, skin tags, seborrheic keratoses

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Results: Psychiatric Disorders With Onset During Gulf War Era

Prevalence (%) Disease PTSD Panic Major Depression One or more mental disorders Deployed 6.2 1.2 7.1 18.1 Non-Deployed 1.1 0.1 4.1 8.9

Odds Ratio 5.8 10.5 1.8 2.1

95% CI 2.6, 12.7 2.0, 56 1.03, 3.2 1.4, 3.1

P-Value <.0001 .006 .04 .0001

No Differences Between Deployed & Non-Deployed In: generalized anxiety disorder; nicotine, alcohol, illicit substance use; somatization; schizophrenia, anorexia, bulemia

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CDC Symptom Criteria for Chronic Multisymptom Illness

Cluster Self-Reported Symptoms

Cluster A
Cluster B

Persistent fatigue for > 24 hours following exertion

Feeling depressed Feeling irritable Feeling worried, tense or anxious Problems finding words Problems getting to sleep

Cluster C

Joint pain Muscle pain

Case Definition: One or more symptoms for > 6 months from at least 2 separate Clusters Case Severity: Cases classified as severe if at least one symptom from each case-defining Cluster was rated as severe.

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Results: Chronic Multisymptom Illness Based on CDC Symptom Criteria

Prevalence (%) CMI Deployed (n=1,035) Non-Deployed (n=1,116)

Odds Ratio

95 CI

All Cases Severe Only

29 7

16 1.6

2.2 4.7

1.6, 2.9 2.3, 9.5

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Summary
The following medical conditions were more common among deployed than non-deployed:
Disease CFS1
FMS2 Group 2 Skin3 Dyspepsia4
1 Chronic

Odds Ratio 41
2.3 1.9 1.9

95% CI 10.2, 161

1.02, 5.3 1.06, 1.8 1.2, 2.0

P Value <.001
.04 .02 .01

Fatigue Syndrome Syndrome 3 Conditions other than moles, freckles, scars, hemangiomas, skin tags, seborrheic keratoses 4 Frequent heartburn, recurrent abdominal pain, and use of antacids or H blockers 2
2 Fibromyalgia

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Study Limitations

Cross sectional Doesnt provide information on health status from deployment to study, or subsequent to study Participation bias - May have obscured differences Lack of Theoretical Model Without a clear theoretical model, the most informative research design may not have been selected Test Selection - May not have performed the best tests to identify disease Non-Blinded Interviewers interviewers knew deployment status Sample size - Insufficient to identify low prevalence illnesses

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Study Strengths

Sample Selection - Independent of medical or psychiatric disease, or disability o Over sampling for women, Reserves, and National Guard permitted subgroup analyses Non-Participation Bias Availability of 1995 data permitted addressing participation bias Diagnoses Made with computer algorithms, reducing observer bias

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What is Chronic Fatigue Syndrome?

Unexplained, persistent or relapsing fatigue of definite onset not explained by exertion, not relieved by rest, and substantially interferes with activity Concurrence of 4 or more of the following symptoms: o Substantial memory impairment o Sore throat o Tender lymph nodes o Muscle pain o Multi-joint pain without inflammation o Headaches o Unrefreshing sleep o Post exertional malaise, lasting > 24 hours Excluded Psychiatric Disorders - bipolar affective, schizophrenia, any delusional disorder, any dementia, anorexia or bulemia, alcohol or substance abuse within 2 years Non-Exclusionary FMS, anxiety disorders, somatoform disorder, non-psychotic depression, neurasthenia, multiple chemical sensitivity disorder
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What is Fibromyalgia Syndrome?

Widespread Pain - Pain above and below the waist, on the left and right side of the body, and along the axial skeleton Tender Points 11 or more of 18 specified points of the body are tender Exclusions none (FMS subdivided into primary and secondary)

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Our Studies Support Including the Following in the Research Definition of Chronic Multisymptom Illness

Fatigue - Unexplained Malaise - Post-exertional Pain - Widespread, joint and/or soft tissue Cognition - Memory impairment Gastro-intestinal symptoms

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Citations

Kang HK, Mahan CM, Lee KY, Magee CA, Murphy FM. Illnesses Among United States Veterans of the Gulf War: A Population-Based Survey of 30,000 Veteran. J Occupa & Environ Med 2000:42; 491-501. Eisen SA, Kang HK, Murphy FM, Blanchard M, Reda DJ, Henderson WG, Toomey R, Jackson LW, Alpern R, Parks BJ, Klimas N, Hall C, Pak HS, Hunter J, Karlinsky J, Battistone MJ, Lyons MJ. Gulf War veterans health: a comprehensive clinical evaluation of a population based sample of 2189 Gulf War Era veterans. Annals Internal Medicine 2005;142:881-890. Blanchard MS, Eisen SA, Alpern R, Karlinsky J, Toomey R, Reda D, Murphy FM, Jackson LW, Kang HK. Chronic multisymptom illness complex in Gulf War Era veterans 10 years later. American Journal of Epidemiology 2006; 163:66-75. Toomey R, Kang HK, Karlinsky JK, Baker DG, Vasterling JJ, Alpern R, Reda DJ, Henderson WG, Murphy FM, Eisen SA. Mental health of US Gulf War veterans: psychological evaluation 10 years after the war. British Journal of Psychiatry 2007;190:385-93. Eisen SA, Karlinsky J, Jackson LW, Blanchard M, Kang HK, Murphy FM, Alpern R, Reda DJ, Toomey R, Battistone MJ, Parks BJ, Klimas N, Pak HS, Hunter J, Lyons MJ, Henderson WG. Spouses of Gulf War I Veterans: Medical Evaluation of a Population Based Cohort. Military Medicine 2006;171:613-18. Karlinsky JB, Blanchard M, Alpern R, Eisen SA, Kang H, Murphy FM, Reda DJ. Late prevalence of respiratory symptoms and pulmonary function abnormalities in Gulf War veterans. Arch Int Med 2004;164:2488-2491 Davis LE, Eisen SA, Murphy FM, Alpern R, Parks BJ, Blanchard M, Reda DJ, King MK, Mithen FA, Kang HK. Clinical and laboratory assessment of distal peripheral nerves in Gulf War veterans and spouses. Neurology, 2004;63:1070-1077

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